August 2018

You'll never flush your toilet again without thinking about this newsletter!

Steatorrhea and Pancreatic Enzymes

Why is fat content of the stool most important:
Healthy people, excrete less than 6 grams of fat per day even if intake is increased to 100 to 125 g of fat/day. Most patients experiencing steatorrhea excrete more than 20 gram of fat per day in their stool. The pancreas normally responds with between 700,000 and 1,000,000 lipase units (USP) per meal.

The activity of the lipase in patients with EPI (exocrine pancreatic insufficiency) is generally 10% of that of healthy individuals. Since all three enzymes (amylase, protease and lipase) are excreted parallel, lipase is used to determine the appropriate dose of pancreatic enzyme supplements.

Absorption: Of all the macronutrients (fat, carbohydrates, and protein), the absorption process of fat is the most complex and tends to be the most sensitive to interference from disease processes.

Calories: Fat is the most calorically dense macronutrient and, therefore, its malabsorption is a critical factor in the weight loss that often accompanies malabsorptive disorders. Protein and carbohydrates contain 4 kcal per gram, while fat contains 9 kcal per gram.

Patients should be followed up in two weeks to assess and titrate PERT (pancreatic enzyme replacement therapy) dose if needed. The dosage should be individualized and adjusted based on:
  • Clinical symptoms
  • Degree of steatorrhea present
  • Fat content of the diet
As unpleasant as this may sound patients need to report the frequency and consistency of their stools, along with the following symptoms:

Clinical Symptom tracker
  • Frequency of diarrhea or loose stoolst
  • Bloating
  • Excessive gas
  • Abdominal pain
  • Rush to bathroom during the night
Stool appearance indicating steatorrhea:
  • Stool color- pale yellow
  • Foul smelling stool
  • Stool floats on top of water, rather than sinking
  • Hard to flush stool
  • Greasy appearance
  • Droplets of oil in your toilet
Degree of steatorrhea present
  • Foul smelling stools (we are aware than no one’s stools smell good, but have your patients report on foul smelling stools)
  • Do their stools float on the top of the water in the toilet bowl?
Fat content of the diet:
Restriction of the fat content to 20gm per day is recommended. If this is unsuccessful, pancreatic enzymes need to be taken. Remember though that fat is an important macronutrient. Medium chain triglycerides (MCTs) can be supplemented to provide extra calories in patients with weight loss and a poor response to diet and pancreatic enzyme therapy

Adherence Of course, before we make any adjustments to therapy, we need to ask the patient about adherence and measure their understanding about the pancreatic enzymes.
  • Remind the patient that PERT should be taken with meals and snacks to aid in digestion
  • Confirm that the total daily dose of PERT is divided among approximately 3 meals and 2 to 3 snacks a day
  • Ensure the patient understands that half of the prescribed enzyme dose for an individualized full meal should be taken with each snack
Self-Care Strategies:
  • Vitamin supplementation, including fat-soluble vitamins A, D, E, and K
  • A nutritionally well-balanced diety
  • Abstaining from alcohol
  • Smoking cessation
Follow up care:
  • After 12 months, 61% of PERT patients are still on their starting dose
  • 67% of patients are under dosed on their PERT
Most of us did it today, and if not, will be doing it tomorrow. Yet most of us feel very uncomfortable discussing our bowel movements let alone listening to someone else’s vivid description of theirs.

As unpleasant as these discussions are, stool consistency is about the only gauge our patients have to assist with appropriate dosing of pancreatic enzymes.

Most of us cringe when we head out to our laxative section, where we often get excruciating descriptions of patient’s bowel movements. When we are monitoring the efficacy of pancreatic enzyme replacement therapy, such descriptions are necessary for clinicians to gauge the success of the therapy.

I'd recommend discussing the contents of this column with all of your patients within the two weeks suggested after a new start. For pharmacists, at the first refill it would be worth discussing specifically adherence, as well as stool appearance. Hey, we're accustomed to hearing such descriptions anyway!

I remember one of my first lower GI consults, after I was recently licensed in 1981. A rough old gent walked into the store and asked me for a “physic” after asking him what he meant, as I’ve never heard that term before. He said “listen buddy I can’t s----” , using the four letter work my Mom would wash our mouths out with soap if she caught us saying that!

The available pancreatic enzymes: Creon® (Abbvie), Zenpep® (Allergan), Pancreaze® (Janssen), Viokace® (Allergan), and Pertzye® (Digestive Care) are currently the only FDA-approved PEPs that are marketed in the United States. They have excellent websites, that have savings programs for our patients. The sales representatives are a wealth of information as well.

Have a great day on the bench!!

Patient information to help our patients get the most benefit from their pancreatic enzymes

When Our Patients Pancreas Fails--

Your six-inch pancreas is quite a busy organ, producing close to 2000ml (2 quarts) of pancreatic juices that aid in digestion. As discussed last week when the pancreas fails to produce adequate enzymes we see several symptoms of inappropriate digestion such as diarrhea, gas, unexplained weight loss and steatorrhea.

SOURCE: The digestive enzymes lipase, protease and amylase are extracted from the pancreas of pigs. Both Muslim and Jewish leaders approve these pork derived enzymes if there are no other alternatives for treatment of the patient’s condition.

HISTORY: In July 1991, FDA announced that all pancreas enzyme products (PEPs) must be approved, and the companies were required to submit a New Drug Application, even though these drugs have been around a long time. This was done to assure the safety, effectiveness, and product quality, due to variations between the actual enzyme content in the product and the amount indicated on the label. Some companies began the application process soon after that announcement. The FDA required approval of all marketed PEPs by April 28, 2008. Because the manufacturers struggled with this time frame the FDA extended the approval deadline to April 28,2010 The FDA provided technical assistance to all manufacturers of PEPs and extension of the approval deadline, however some of the products failed to get FDA approval for marketing prior to the April 28, 2010 deadline.

DOSING: The initial dose of pancreatic enzyme replacement therapy (PERT) can be calculated, based on the weight of the patient. Dosage adjustments thereafter are based on the following 3 parameters:
  • degree of steatorrhea present
  • content of dietary fat in the ingested meal
  • clinical symptoms of the disease
The recommended dosage of all pancreatic enzyme replacement products is 500 lipase units/kg/meal. These patients based on symptoms can be titrated to a maximum of 2,500 lipase units per kg/meal.

Starting dose: Looking at the math a 180-pound patient (80kg) patient should be taking around 40,000 units per meal as a starting dose. Think Creon® 36,000 one capsule at each meal.

Maximum dose: The above patient would be able to take a maximum dose of 200,000 lipase units per meal. (after titration of course). Think a maximum of Creon® 36,000 at a dose 5 capsules per meal. Most patients should be on 2 capsules per meal (72,000 units)

Observing these calculations, most patients (estimated 2/3) are under dosed. Unfortunately, after 12 months at least 60% of the patients are on their initial starting dose and have not been upwardly titrated. Tell patients it may take 1-2 weeks for a patient to adjust their dose of the new PEP. Patients usually take half of a mealtime dose for each substantial snack.

Approved Products include: Creon® (Abbvie), Zenpep® (Allergan), Pancreaze® (Janssen), Viokace® (Allergan), and Pertzye® (Digestive Care) are currently the only FDA-approved PEPs that are marketed in the United States Viokace is the only pancreas enzyme product (PEP) without an enteric coating. Viokace must be taken with a proton pump inhibitor (PPI). The PPI decreases stomach acid to help prevent the drug from breaking down in the stomach and delays the release of the drug until it reaches the lower digestive tract.

  • Take with every meal or snack or the symptoms of malabsorption may return if doses are missed.
  • Heat labile: Capsules must be swallowed with a cold drink, as a hot drink might weaken the enzymatic activity. Also, enzymes should not be carried in trouser pockets, due to body radiating heat.
  • The capsules should be swallowed whole and must not be crushed or chewed. If opened and sprinkled it should be on an acidic food (such as applesauce). Do not retain in the mouth, due to potential irritation of oral mucosa.
  • If you are having a large extended meal more than 2 courses, divide dose during the meal.
Since use of PEPs preceded the Federal Food, Drug and Cosmetic Act of 1938, they had been marketed without formal FDA approval, and major differences were reported between the actual enzyme content in the product and the amount indicated on the label.

After reading this letter it is obvious that we pharmacists at each refill should be questioning our patients as to the level of improvement of their gastrointestinal symptoms, especially steatorrhea. Although these enzymes are expensive, the biggest waste of money comes if the patients are not deriving benefit due to improper dosing or adherence.

Next week we will discuss follow up care.

Have a great day on the bench!!

We think a lot about insulin and the pancreas... let's explore the other function of our pancreas.

Digestive enzymes and your "tired" pancreas...

Digestive enzymes are available in the front of our stores, but most often are prescribed and dispensed from the pharmacy. With all the Type-2 diabetics we care for, we realize the function of the pancreas is to produce insulin from the beta cells, and glucagon from the alpha cells in the islet of Langerhans. Another extremely important, and often forgotten function of the pancreas is to produce the digestive enzymes to process the foods we eat.

Just as the endocrine function (insulin and glucagon production) may fail, the effectiveness of the exocrine function (production of digestive enzymes) may fail as well. When the exocrine function becomes impaired, this condition is referred to as EPI (Exocrine Pancreatic Insufficiency)

In people with EPI, it is the exocrine function of the pancreas that is affected. EPI occurs when prandial enzyme output is ≤10% of normal. The undigested food moving through the intestines that causes the unpleasant symptoms of EPI.

EPI is a condition that can be managed with prescription medication called PERT (pancreatic enzyme replacement therapy). PERTs replace the enzymes the pancreas is no longer making. The capsules/tablets are taken with every meal to help break down food into nutrients that can be absorbed. They contain the enzymes lipase which breaks down fats, protease which breaks down proteins, and amylase which breaks down carbohydrates.

  • Frequent diarrhea (usually characterized by frequent, soft bowel movements that appear pale)
  • Unexplained weight loss
  • Steatorrhea (due to excess fat content, stools are loose, floating, oily, foul smelling, and hard to flush)
  • Flatulence and bloating
  • Abdominal pain
  • Conditions associated with EPI:
    • Chronic pancreatitis (CP)
    • Cystic fibrosis (CF
    • Pancreatic cancer
    • Partial resection or total pancreatectomy
    • Diabetes mellitus
  • Fecal Elastase-1 Concentration (done with a single stool sample)
  • Fecal Fat Collection (done over a 72-hour time period)
  • Secretin and/or cholecystokinin (CCK) stimulation tests (available in specialized pancreatic centers- not done routinely)
Along with the pancreatic enzyme replacement therapy (which we will “digest” next week) the following should be recommended:
  • A nutritionally well-balanced diet
  • Vitamin and mineral supplements, including fat-soluble vitamins A, D, E, and K
  • Lifestyle modifications such as abstaining from alcohol and smoking cessation
  • Check the med list: Most drugs report diarrhea as a side effect, but especially watch out for:
    • Selective Serotonin Reuptake Inhibitors (Citalopram, fluoxetine, sertraline and others)
    • Other antidepressants such as bupropion and trazodone
    • Lithium
    • Metformin- frequently prescribed for our Type-2 diabetics, who are also at risk for EPI
    • Proton pump inhibitors (omeprazole, esomeprazole) along with H2RA’s like ranitidine and famotidine (very rare)
    • Bisphosphonates (alendronate, ibandronate, risedronate)
    • Colchicine
    • NSAIDS- (ibuprofen, naproxen and others)
    • ACE inhibitors
    • Chemotherapeutic drugs
Our pancreas is an important organ to keep us going metabolically. We quickly think of insulin from the beta cells, maybe glucagon from the alpha cells, but equally important is the digestion of our foods from the exocrine function of the pancreas. After the next couple weeks of discussion with relationship of digestive enzymes we will come to appreciate this six inch organ, that weighs only 2 to 3 ounces even more!

Have a great day on the bench!!

JULY 2018

I take a statin and my legs hurt... will Co-Q -10 help??

Statin Induced Myopathy Treatment and Prevention:

Coenzyme Q-10 has been touted for everything from eye disease, heart disease to HIV. Most of the time we are using it for people who complain about muscle pain while on a statin for cholesterol management. Many of our patients complain about muscle aches, some of them are not even on statins. Here are the terms used to describe muscle pain. First recommendation is to have a creatine kinase (CK) level done.

  • Myopathy - a general term related to any muscle complaint. Muscle weakness (not due to pain), with or without an elevation in Creatine Kinase (CK) level.
  • Myalgia - muscle complaints (i.e., ache, weakness) without elevations in CK. This is the most common myopathy reported with statins
  • Myositis – inflammation of the muscles
  • Myonecrosis – Elevation in muscle enzymes compared with either baseline CK levels (while not on statin therapy) or the upper limit of normal that has been adjusted for age, race, and sex:
    • Mild – Threefold to 10-fold elevation in CK.
    • Moderate – 10-fold to 50-fold elevation in CK.
    • Severe – 50-fold or greater elevation in CK.
  • Rhabdomyolysis - markedly elevated levels of CK, usually greater than ten times the upper limit of normal; usually accompanied by creatinine elevation, acute renal failure including brown urine, and urinary myoglobin. Defined as myonecrosis with myoglobinuria or acute renal failure (an increase in serum creatinine of least 0.5 mg/dL).
Many of the elevations in CK are due to statin therapy but is not usually a concern until it is over 10 times the upper limits of normal. This is very rare, and occurs in less than 0.5% of patients. Unfortunately, many patient’s statin therapy is discontinued due to perceived side effects of muscle pain. Hypothyroidism, acute or chronic renal failure, and obstructive liver disease can also enhance to statin induced muscle pain.
  • If the patient has muscle pain my first approach would be to recommend switching to a hydrophilic statin. Pravastatin (Pravachol®) -a lightweight- and rosuvastatin (Crestor®) -a powerhouse- are both available generically and are hydrophilic. Those two are least likely to cause muscle pain.
  • A lot of the elevations of CK might be due to statin drug interactions with CYP450-3A4, and rosuvastatin and pravastatin are not metabolized by this enzyme system, and are safer.
  • I am not a huge fan of Zetia (ezetimibe), which blocks the absorption of cholesterol. Most clinicians feel the liver “up-regulates” cholesterol production in response to decreased absorption. Most want a statin on board with ezetimibe therapy, which now is rather cheap to use.
  • Always avoid gemfibrozil (Lopid®) with statin therapy.
  • Never prescribe Simvastatin (Zocor®) 80mg due to increased risk of rhabdomyolysis.
CoQ10 for myopathy prevention: The link to statin therapy-
Statins inhibit CoQ10 formation many theorize low CoQ10 levels might lead to myopathy. There's no conclusive proof that CoQ10 works for statin induced myopathy but some anecdotal reports suggest it might be helpful.

Dosage: If patients want to try CoQ10, suggest starting low and dividing doses over 100 mg. Take two to three times daily to minimize nausea and diarrhea.

Adverse effects: Most studies have not reported serious side effects related to CoQ10 use. The most common side effects of CoQ10 include insomnia, increased liver enzymes, rashes, nausea, upper abdominal pain, dizziness, sensitivity to light, irritability, headaches, heartburn, and fatigue.
  • CoQ10 should not be used by women who are pregnant or breastfeeding.
  • Statins may lower the levels of CoQ10 in the blood. However, it is unclear what type of health effect this may have on an individual.
  • CoQ10 may make warfarin, an anticoagulant (blood thinner), less effective.
The only way I recommend Co-Q10 if that is the only thing that will keep a patient on their statin. I think of it as an expensive placebo! We struggle to find cheaper prescription prices for our statins, and it is counter-intuitive to recommend a very expensive supplement. A few case reports have noted benefit with doses of 30 to 250 mg daily. There is currently inadequate evidence to recommend CoQ10 supplementation for prevention of statin-induced muscle toxicity.

Have a great day on the bench!!

Another benefit of this don't have to check the PDMP!!!

Melatonin-- a good night sleep might be in our supplement section!

Melatonin is classified as a “dietary supplement by the FDA.
Endogenous melatonin, secreted by the pineal gland is a neurohormone used to regulate sleep-wake cycles or circadian rhythms. Melatonin is synthesized from the amino acid tryptophan. Melatonin secretion begins around the third or fourth month of life, peaks in pediatric years, and lessens as we age. This decline in melatonin secretion seems to be due to calcification of the pineal gland. A 70-year-old has about ¼ of the melatonin secretion as young adults do. Supplementation of melatonin seems to be a reasonable option for sleep induction.

  • USE: May be useful may help to regulate sleep disturbances that occur with insomnia, jet lag, rotating shift-work, depression, chronic kidney disease.
  • Jet lag: Melatonin can improve some symptoms of jet lag, such as alertness and psychomotor performance, may also be useful for daytime sleepiness and fatigue.
Might not be effective for decreasing sleep latency.
  • DOSE: 0.3—1 mg produce physiological melatonin levels in the circulation; Suggest higher doses of (2—6 mg) which are needed to obtain beneficial effects. Maximum: 10 mg/day. Doses over 10mg may produce supraphysiologic concentrations of melatonin which can produce numerous biological effects. Daytime sleepiness, impaired mental and physical performance, hypothermia , and hyperprolactinemia can be caused by excessive melatonin doses. These effects are not observed with physiologic concentrations of melatonin.
Novel uses for melatonin:
  • is an orphan drug for blind people who have no light dark cycle, and cant synchronize sleep.
  • is being studied for relief of perioperative anxiety (3-5mg) – causes less respiratory depression, sedation and delirium than the benzos.
Ramelteon (Rozerem®) available as 8mg tablets ($490.00/month) Mechanism: selectively binds to the MT1 and MT2 receptors in the suprachiasmatic nucleus , inhibiting the neuronal firing that maintains wakefulness. Rozerem® shows no evidence of abuse, dependence or withdrawal, or rebound insomnia and can be prescribed long term.

Tasimelteon (Hetlioz®) is approved for non-24 sleep-wake disorder, where patients can't synchronize their internal clock to the 24-hour light-dark cycle. It occurs in over half of blind people, rarely in sighted people. Hetlioz increases nighttime sleep in blind patients about same as melatonin (28 minutes) at a cost of $10,000/MONTH. Do not recommend Hetlioz for sighted or blind patients who don't have non-24.

Melatonin warnings:
  • Asthma: melatonin may play role in the expression of asthma symptoms- patients should seek advice before starting this therapy.
  • Drowsiness precautions, driving, dangerous tasks that require alertness.
  • Avoid during pregnancy and breast feeding.

We all see a lot of issues using the traditional sleep aids in our patients, especially the elderly. We often hear of reports of “sleep driving” on zolpidem (Ambien), not to mention the risk of falls. Many of our patients seeing that their benzodiazepines, like temazepam (Restoril), and the “Z” hypnotics like zolpidem are not covered for sleep and look in the over the counter aisle for relief. Keep in mind that due to their anticholinergic effects the antihistamines are not recommended for the elderly due to exacerbation of prostate symptoms and increase fall risk. That rules out all the “PM” products that contain diphenhydramine. Melatonin seems to be an option worth exploration.

Sleep hygiene is also worthy of discussion. Use of laptops, tablets, smartphones before bedtime can have a negative impact on melatonin secretion, circadian rhythms, and sleep. Any device with a “gray screen” all which are low light emitting, and dilates the pupils can cause this effect. One study compared the effects of reading an “e-book” versus a printed book for four hours prior to bedtime for five consecutive nights. The e-book readers had suppressed melatonin concentrations in the early part of the night, a delayed endogenous circadian melatonin phase, felt less sleepy before bed, took longer to fall asleep, and reported feeling sleepier the following morning, than the “paper book” readers. Looks like this gray haired pharmacist needs to create these columns in the morning, and NOT before bedtime.

Have a great day on the bench!!

Milk thistle-- should we get out the "weedeater" or the mortar and pestle?

Milk Thistle—this invasive weed might have health benefits for your liver.

Latin Name: Silybum marianum also called “Mary thistle” or “holy thistle”

Milk thistle grows in North and South America, and throughout most of the world, as it is native to the Mediterranean region. This plant is considered by most to be an invasive species. Silymarin is the main component of milk thistle seeds.

People have used milk thistle for liver disorders, such as hepatitis and cirrhosis, and gallbladder problems. Silymarin is the most commonly used herbal supplement in the United States for liver problems. Silymarin has chemo preventive effects on hepato-cellular carcinoma, according to in vivo and in vitro studies. The silymarin exerts antioxidant activity, stabilizes liver cell membranes, promotes regeneration of the hepatocytes, and inhibits fibrogenesis in the liver, which drives the progression of chronic liver disease. Silymarin also increases survival time in patients with alcoholic cirrhosis.

Milk thistle products are available as capsules, powders, and extracts. Capsules are available in 175mg, 250mg and 1000mg strengths.

The 2008 Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) study, sponsored by the National Institutes of Health (NIH), found that hepatitis C patients who used silymarin had fewer and milder symptoms of liver disease and somewhat better quality of life but no change in virus activity or liver inflammation. A 2012 clinical trial, higher-than-usual doses of silymarin were no better than placebo for chronic hepatitis C in people who had not responded to standard antiviral treatment.

Milk thistle might lower blood sugar in people who have type 2 diabetes

NonAlcoholic SteatoHepatitis (NASH) is a more severe form of liver disease with inflammation and sometimes fibrosis, which is becoming one of the most frequent causes for liver transplants. Weight loss, statins and pioglitazone (Actos) may reduce liver fat, fibrosis and inflammation. Use pioglitazone (Actos) whether patient has diabetes or not. Milk thistle seems to be of minimal value.

In clinical trials, milk thistle appears to be well tolerated in recommended doses. Occasionally, people report various gastrointestinal side effects.

CYP2C9 interactions:
milk thistle is an inhibitor of CYP450-2C9 and might potentially produce clinically significant increases in warfarin (Coumadin and diazepam (Valium). Other references discount any CYP family interactions with milk thistle.

Milk thistle may produce allergic reactions, which tend to be more common among people who are allergic to plants in the daisy family (for example, ragweed, chrysanthemum, marigold, and daisy).

Compounds in milk thistle may lower blood sugar levels in people with type 2 diabetes. Some of the compounds in milk thistle have peroxisome proliferator-activated receptor (p-par) agonist properties similar to the TZD’s like Actos (pioglitazone) People with diabetes should use caution, and monitor for hypoglycemia.

Next I'm walking around the fields and forests of Central Pennsylvania, and my shoelaces get untied by this noxious week, I will have a greater respect for milk thistle! Milk thistle, although originally from the Mediterranean area can easily be spotted along hedgerows and in the farmers fields of most areas of our country.
This herbal might have a place in therapy, although not useful for NASH, it might benefit certain populations suffering from liver disease. With its low incidence of drug interactions, and minimal adverse reactions I'm OK with my patients trying this herbal product. Although it doesn't lower viral load in our hepatitis patients, the HALT-C study showed a better "quality of life." Isn't that after all what healthcare is all about?

Have a great day on the bench!!

Is ginger effective for treatment of nausea and vomiting?

Ginger snaps and ginger ale... good for snacks, not so for vomiting!

Latin Name: Zingiber officinale

Ginger can be found in our kitchens as spice for “ginger snaps” and in “ginger ale”. Ginger which is found in the tropics has green-purple flowers and a rhizome (a bulky underground stem) that is the basis for its use in the kitchen. Ginger has been used since antiquity, especially in Asian medicine, dried ginger has been used for thousands of years to treat stomach ache, diarrhea, and nausea.

Dramamine offers as a brand extension an all-natural product with ginger root (2 capsules=1000mg), along with its dimenhydrinate 50mg and meclizine 25mg versions! Foods containing ginger as a flavoring agent, like ginger ale or ginger snaps are not effective in treatment of nausea.

Ginger has been studied for nausea for a variety of situations, such as motion sickness, post op nausea, and chemotherapy. It is more effective than placebo, however prescription medications are more effective for treatment of vomiting. Ginger provided little benefit in treatment of nausea and vomiting due to chemotherapy. Ginger’s most common strengths are 250mg and 550mg per capsule.

Nausea of Pregnancy: the usual dose of ginger is 250mg four times daily. This supplement might bring adequate relief, but for hyperemesis gravidarum using metoclopramide (Reglan) or ondansetron (Zofran) would provide greater benefit. According to a meta-analysis by the American Board of Family Medicine, ginger (Z. officinale) was better than placebo in improving nausea of early pregnancy when given at doses of 1 gram/day for a duration of at least 4 days. The ACOG (American College of Obstetricians and Gynecologists) list ginger as a treatment option for nausea of pregnancy. Safety in pregnancy has not been adequately proven.

Side Effects

Heartburn: For non-pregnant patients, GI reflux has been commonly reported with ginger. In a study of the prevention of postoperative nausea and vomiting, 8% of subjects had heartburn after taking 1 gram of ginger.

Bleeding risk: advise caution if the patient is currently taking any anti-platelet drugs (aspirin, clopidogrel) or anticoagulants as ginger could possibly increase bleeding risk.
As with all herbal supplements in the United States there is variation between products due to lack of standardization.

Back when Zofran® (ondansetron) came to market in 1992 it was extremely expensive costing around $40.00 per tablet. Its unique mechanism of action is that it blocks serotonin, a natural substance that causes nausea and vomiting. This was a godsend to oncologists who struggled with the vomiting caused by chemotherapy regimens, especially cisplatin.

Family practice physicians were using other alternatives such as prochlorperazine (Compazine) promethazine (Phenergan) and metoclopramide (Reglan). The extrapyramidal side effects of these "dopamine blockers" could make treatment of nausea and vomiting a challenge.

Ginger was frequently recommended for the simple nausea of "the flu", or due to motion sickness. Ginger is better than placebo, but is not as effective as the serotonin or dopamine blockers.

Today ondansetron tablets are very inexpensive, and are frequently prescribed for treatment of all forms of nausea and vomiting. However in September 2011, the FDA warned "Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm"

Have a great day on the bench!!

JUNE 2018

Urinary Tract infections: prevention with cranberry juice or tablets are of no value. Save your cranberries for your next turkey dinner!

When the first urinary tract infection is caused by Escherichia coli, women appear to be more likely to develop a second UTI within six months than those with a first UTI due to another organism. A study done in Finland showed 44 percent of women with an E.coli urinary tract infection had a recurrence within one year. This is indeed a very common complaint with our female patients and the go to our supplement aisle looking for a “natural” product to prevent these bothersome infections.

Cranberry (Vaccinium macrocarpon) is an evergreen bush that grows in North America. For years it has been touted for its use in prevention of urinary tract infections. Here is what you need to share with your patients.

Cranberry therapy is not worth trying: Any of the oral cranberry products to date have no data to support its use, and causes significant GI upset and heartburn. Withdrawal rates have been quite high (up to 55%), suggesting that these products may not be acceptable over long periods. Adverse events include gastrointestinal intolerance, weight gain (due to the excessive calorie load) and drug-cranberry interactions (due to the inhibitory effect of flavonoids on cytochrome P450-mediated drug metabolism).
  • Drinking cranberry juice appears to be safe, although large amounts can cause stomach upset and may over time increase the risk of kidney stones.
  • Large doses of cranberry may alter levels of warfarin (Coumadin).
Approaches to Urinary Tract infection prophylaxis that are worth trying:
  • Post coital antibiotic treatment: antibiotic treatment after each act of sex using: trimeth/sulfa SS; Nitrofurantoin 50mg or 100mg capsules (not MacroBID), cephalexin 250mg or ciprofloxacin 125mg
  • Continuous antibiotic prophylaxis: daily antibiotic treatment with trimethoprim 100mg (watch for resistance), trimeth/sulfa SS, nitrofurantoin 50mg or 100mg (not MacroBID), cephalexin 250 or ciprofloxacin 125mg
  • Self-treatment: women who can self-diagnose and who are compliant can be given a course of therapy with Trimeth/Sulfa DS or Ciprofloxacin or Levofloxacin. Women should call provider if symptoms are not resolved in 48 hours
Patient counseling tips that work to prevent recurrent urinary tract infections:
  • Urinate immediately after having sexual intercourse. Urinating flushes out bacteria that may have entered the urethra during intercourse.
  • Use proper hygiene. Wipe front to back.
  • Rinse the vulva after sex.
  • Keep well hydrated with water and avoid “holding it” throughout the day
  • Wear regular cotton underwear. Thong underwear can lead to UTI’s by tracking bacteria from the rectal area into the urethra via the vagina.
  • Don’t smoke, it lowers your immunity.
  • Avoid condoms coated with nonoxynol-9

We see a lot of patients coming to our pharmacies getting Trimeth/Sulfa DS, Nitrofurantoin, Levofloxacin and Ciprofloxacin for urinary tract infections. Of course, some of us gray haired pharmacists remember Mandelamine®(Methenamine mandelate) and Hiprex® (methanamine hippurate), which became available in 1967, are seldom used today.

Females, due to their own special structural anatomy have a shorter urethra and the E.coli more easily “climb” through this shorter urethra and colonize in the bladder.

Another challenge becomes finding appropriate therapy for treatment of urinary tract infections. The Sanford Antibiotic Guide recommends avoiding Trimeth/Sulfs DS (Bactrim-DS) if local E. coli resistance rates are over 20%. The same reference recommends avoiding fluoroquinolone (levofloxacin/ciprofloxacin) therapy if local resistance rates are over 10%. The latest antibiogram from our local hospital calculates a 27% resistance rate for Trimeth Sulfa and a whopping 35% resistant rate for the fluoroquinolones against E. coli.

Fortunately our nitrofurantoin resistance rate is just 6% for E. coli. Bacterial resistance is becoming a bigger challenge for our female patients suffering from urinary tract infections.

Have a great day on the bench!!

What about all natural Red Yeast Rice for management of cholesterol?

Red yeast rice (RYR) (Monascus purpureus) is a nutraceutical that lowers LDL-C levels by 20 to 30 percent. Red yeast rice is a fermented rice product that has been used in Chinese cuisine (like Peking duck) and medicinally to promote "blood circulation”. Because it is a “natural product “patients assume it is a safer alternative to the prescription statins.

Red yeast rice may also induce muscle complaints because of its statin-like content. The product contains varying amounts of a family of naturally occurring substances called monacolins that have HMG CoA reductase inhibitor activity. The LDL-C lowering effect of red yeast rice is due to the presence of monacolin K, a compound like lovastatin (Mevacor®).

According to a meta-analysis it will:
  • lower LDL-C by 19-62 mg/dL
  • increase HDL by 3mg/dL
  • lowers triglycerides by 23mg/dL
When we directly compare it to lovastatin, the daily lovastatin content of red yeast rice was 0.2 percent of the total product, which at the recommended dose of red yeast rice of 2.4 g/day translates into a daily lovastatin dose of 4.8 mg, compared to lovastatin (Mevacor®) that we have available in the pharmacy. The capsules are available as 600mg and can be dosed as two capsules twice daily.

My concerns:
  • Wide variability exists in the amount of lovastatin-like compounds in commercially available RYR products. In a study that evaluated the content of twelve preparations of commercially available red yeast rice, the total monacolin content ranged from 0.31 to 11.15 mg/capsule and monacolin K (similar to lovastatin) ranged from .1mg to 10 mg per capsule. This study also showed that four of the preparations had elevated levels (1.6mcg/day) of citrinin, a potentially kidney damaging mycotoxin.
  • Although red yeast rice lowers LDL-C like a mild potency statin, and may be tolerated by some patients who have discontinued statin therapy for muscle side effects, this therapy is not recommended due to lack of clinical outcomes data, variable drug bioavailability, and possible toxic effects from contaminants.
  • In 1998, the FDA determined that a red yeast rice product that contained a substantial amount of monacolin K was an unapproved new drug, not a dietary supplement. On several occasions since then, the FDA has acted against companies selling red yeast rice products that contain more than trace amounts of monacolin K, warning them that it is against the law to market these products as dietary supplements. Truth be known our patients and we pharmacists have no idea what is in these products, as the labels state only the amount of red yeast rice that they contain, not the amounts of monacolin K or other monacolins.
  • Lack of standardization, nephrotoxicity, as well as the costs of these products do not allow me to recommend this product. Most products are well over $18.00/month.

Before recommending Red yeast rice, think about the active compound in this natural product, that being lovastatin or Mevacor®. Lovastatin is considered a sensitive CYP3A4 substrate, since its levels may be increased five-fold or higher by CYP3A4 inhibitors. Lovastatin was a game changer in the world of hyperlipidemia management. Up until Mevacor® became available in 1987 clinicians managed cholesterol levels with diet, exercise and bile acid sequestrants, such as cholestyramine (Questran) and colestipol (Colestid).

Simvastatin (Zocor®) and Pravastatin (Pravachol®) became available in 1991. Fluvastatin (Lescol®) followed in 1993, to be joined by the blockbuster atorvastatin (Lipitor) in 1996.

Cerivastatin (Baycol®) came to the market in 1997, only to be withdrawn after four years in 2001, because of 52 deaths attributed to drug-related rhabdomyolysis that lead to kidney failure.

Rosuvastatin (Crestor®) came to the market in 2003, and the last one to join the HmgCo-A reductase family was pitavastatin (Livalo®) in 2009. Except for pitavastatin, all of the statins are now available generically.

When we recommend statins, we think of drug interactions, cost and potency and of course insurance coverage. Most clinicians when selecting a statin today gravitate toward rosuvastatin because it meets the parameters of minimal drug interactions and potency.

Most would agree that the active ingredient in red yeast rice (lovastatin) would be our last choice. Red yeast rice with the potential for contamination with citrinin, along with the lack of standardization between products, should be our last choice in the management of hyperlipidemia.

Have a great day on the bench!!

Ceiling fans and dry tee shirts might be your patients best treatment option for hot flashes!

Black Cohosh:
  • Cimicifuga racemose- rhizomes and roots are used. It is a member of the buttercup family.
  • USE: extracts seem to modestly reduce symptoms of menopause, such as hot flashes. However, there is considerable variability in the preparations used in clinical trials, and in the results obtained. Historically was one of the ingredients in Lydia Pinkham’s Vegetable Compound
  • Remifemin® contains only black cohosh, and has been one of Germany's top proprietary herbs since the 1960's. It is not recommended to be used over 6 months.
  • Germany's Commission E has found this extract of black cohosh effective for the treatment of dysmenorrhea, PMS, and climacteric ailments since 1989. Remifemin is the only formulation approved by Commission E.
What the US studies show: With a daily dose of 40 mg, for a mean duration of 23 weeks, compared to placebo, hormone therapy, red clover and fluoxetine. Reported outcomes included vasomotor symptoms, vulvovaginal symptoms, menopausal symptom scores and adverse effects. There was no significant difference between black cohosh and placebo. Source: Results for evening primrose oil and flaxseed have also been disappointing.

Adverse effects: Stomach upset, headache are common side effects. There have been reports of liver damage in patients, one patient needing a liver transplant.

Drug interactions: because of the potential (not yet proven) estrogenic effects of black cohosh, do not recommend in patients taking tamoxifen (Nolvadex). No other drug interactions have been reported.

Non-Hormonal alternatives for hot flashes:
  • most references recommend venlafaxine (Effexor), desvenlafaxine (Pristiq), paroxetine (Paxil, Brisdelle), citalopram (Celexa), and escitalopram (Lexapro) have a similar modest benefit for hot flashes. Most sources seem to favor citalopram as the favorite at a 20mg dose for hot flashes.
  • Gabapentin (Neurontin) is a good option for women who have their hot flashes at night. It is effective when the hot flashes occur in the first four hours of sleep, especially if the hot flashes wake up the woman.
So, as with so many of the herbal preparations there just isn’t a lot of evidence for use of black cohosh. This drug seems to be safer than most herbal supplements for most of our middle aged women, and for some it might be worth a try. Share this information that there isn’t a lot of evidence for use of black cohosh. Might be best to save the money and turn on the ceiling fan in the bedroom!

I remember back in the day in the 1980’s when we bought our Premarin 0.625 and Premarin 1.25mg in bottles of 1000! We would sell 100 Premarin for around $15.00. Then the HERS trial came out at the turn of the millennium, and we have all but stopped dispensing this drug. Back in the 1980’s we were using it for everything from osteoporosis, hot flashes, prevention of colon cancer and even cardiac protection. After the results of the HERS trial, estrogen was to be used for relief of vasomotor symptoms, at the lowest possible dose for the shortest period of time. Estrogen is no longer recommended for prevention of chronic heart disease, osteoporosis, or prevention of dementia. That same bottle of 100 Premarin® costs the pharmacy almost $550.00 !!

“Hot flashes” are the most common complaint during the menopausal transition, occurring in up to 80 percent of women. However, only about 20 to 30 percent of women seek medical attention for treatment. Indeed, estrogen has fallen out of favor, and our female patients (including our wives!) are looking for relief of hot flashes and turn to the over the counter supplements such as black cohosh, the active ingredient in Remifemin®.

Have a great day on the bench!!

Valerian root might be an option for our anxious patients... and you don't have to check the PDMP!!

Valerian... seems good for insomnia--- and unlike Zolpidem, you can "tweet" !!

Valerian (Valeriana officinalis) is a perennial plant native to North America, Europe and Asia. For hundreds of years it has been used in Europe as a sedative and an antispasmolytic to relieve insomnia, anxiety, muscle spasms and stress induced palpitations. Native Americans boiled the roots into a tea for calming the nerves. The roots contain essential oil with monoterpenes and sesquiterpenes (valerenic acids).

Various compounds have been detected in valerian, including alkaloids, flavonoids, and GABA, which seem to have some affinity for the GABA receptor. Remember from our basic pharmacology when the GABA receptor is activated by benzodiazepines we will see sedative, hypnotic, anxiolytic, anticonvulsant, and muscle relaxant effects. Could we then expect the same from valerian?

Source: Valerian products are made from its roots, rhizomes (underground stems), and horizontal stems. Dried roots are prepared as teas or tinctures, and dried plant materials and extracts are put into capsules.

Efficacy: Some studies suggest that valerian may be useful for insomnia and other sleep disorders; results of other studies do not. Some of these studies had small sample sizes, used different amounts and sources of valerian, measured different outcomes, or did not consider potential bias resulting from high participant withdrawal rates. Overall, the evidence from these trials for the sleep-promoting effects of valerian is inconclusive.

Numerous trials have not shown it to be better than placebo, while some other trials showed it had less side effects than placebo! One study showed a decrease in slow-wave sleep onset (13.5 minutes) compared with placebo (21.3 minutes). Another study enlisting 75 patients comparing Valerian 600mg to oxazepam (Serax®) 10mg. Both groups had the same improvement in sleep quality but the valerian group reported fewer side effects than did the oxazepam group. Those patients experienced less morning drowsiness. NCBI

Adverse effects: Few adverse events have been reported because of valerian. As we would expect from its sedative properties, valerian can cause drowsiness or dizziness. The risk of respiratory depression should be considered if valerian is used with multiple sedating drugs (like benzos) and/or significant alcohol consumption. Valerian can cause abdominal pain in large doses.

Worth recommending? Valerian is a seems to be a safe herbal choice for the treatment of mild insomnia and has good tolerability. Valerian seems to be more effective when used continuously rather than as an acute sleep aid. Most references recommend using 400mg-900mg one hour before bedtime. Best results occur when a person takes it for at least 28 days. A potential advantage of valerian over benzodiazepines is the lack of sleepiness on awakening when used at the recommended dosages. Valerian also may be helpful in weaning patients with insomnia from benzodiazepines.

In 1960 the first benzodiazepine, chlordiazepoxide (Librium) hit the market, introduced by Roche Labs. In 1963 diazepam (Valium) was released and the market really took off. All the benzodiazepines work on the GABA receptor to allow chloride to rush into the neuron. Chloride is the major suppressing ion in the CNS. The Z-hypnotics zolpidem (Ambien®), zaleplon (Sonata®) and eszopiclone (Lunesta®) work at the same receptor, causing influx of chloride and causing the same net effect.

When combined with opioids, benzodiazepines can cause an increase in opioid deaths. More than 30 percent of overdoses involving opioids also involve benzodiazepines. According to Psychiatry-Online (18March2016) between 1996 and 2013, the number of adults filling a benzodiazepine prescription increased 67 percent, from 8.1 million to 13.5 million. Among those filling benzodiazepine prescriptions, the median cumulative quantity filled over the year increased by 140 percent, from 86.8 mg to 208.0 mg lorazepam equivalents. Meanwhile in this time frame deaths involving benzodiazepine increased fivefold.

Pharmacists and prescribers are feeling the heat when it comes to prescribing benzodiazepines and opioids, especially in combination. Valerian root might be an option, rather than another new start on a benzo!

In recent news actor Roseann Barr blamed her controversial tweet on "Ambien tweeting". Sanofi quickly responded: "People of all races, religions and nationalities work at Sanofi every day to improve the lives of people around the world. While all pharmaceutical treatments have side effects, racism is not a known side effect of any Sanofi medication."

My take on valerian: If it works for a particular patient, that is one less benzo we have to check the PDMP for!

Have a great day on the bench!!

May 2018

Since I turned 60 last weekend, these men's health issues have become more important!

Saw Palmetto, how effective is it for BPH?

Common Names: saw palmetto, American dwarf palm tree, cabbage palm, is a tree native to South Eastern United States.

Latin Name: Serenoa repens, Sabal serrulata
  • USE: urinary symptoms associated with benign prostatic hyperplasia (BPH), as well as for chronic pelvic pain, bladder disorders, decreased sex drive, hair loss, hormone imbalances, and prostate cancer.
  • Medicinal part: The ripe fruit of saw palmetto is used in several forms, including ground and dried fruit or whole berries. It is available as liquid extracts, tablets, capsules, and as an infusion or a tea. The saw palmetto berry contains over 100 different compounds, mostly fatty acids, long chain alcohols and sterols.
EVIDENCE: (or lack thereof) Some studies compare saw palmetto’s efficacy to that of finasteride (Proscar), which “shrinks” the prostate gland allowing for better emptying of the bladder.
  • Placebo-controlled, double-blind studies of its use in benign prostatic hyperplasia (BPH) have been carried out in > 2000 patients in Germany. A 1998 meta-analysis of published trials concluded that compared to finasteride, saw palmetto appears to produce similar improvements (28%) in urinary tract symptoms and flow measures. Some studies suggest that it's comparable to finasteride, less effective than alpha-blockers.
  • 2011 NCCIH-cofunded study in 369 older men demonstrated that saw palmetto extract administered at up to three times the standard daily dose (320 mg) was no more effective than placebo. The supplement should be a fat soluble saw palmetto extract that contains 85 to 95% fatty acids and sterols.
  • A 2012 study in JAMA concluded that increasing doses of a saw palmetto fruit extract did not reduce lower urinary tract symptoms more than placebo. This study reached the same conclusion as the New England Journal of Medicine in 2006, of the lack of efficacy of saw palmetto.
  • UP-To-Date® does not recommend any herbals for BPH until herbals are further studied. Given the body of evidence against herbal products, efficacy is likely tied to the placebo effect.
  • Saw Palmetto does have anti-coagulant properties, do not recommend if patient takes any blood thinning drugs such as warfarin, aspirin, Plavix, Xarelto, or NSAIDS.
  • Because of saw palmetto’s mechanism of action being anti-estrogenic and anti-androgenic, it may decrease the efficacy of oral estrogen and oral contraceptives. It is recommended that a condom be used to prevent pregnancy if partner is using birth control pills.
  • Speaking of drug interactions, certain medications need to be avoided in men of my age group, especially if they have BPH:
MEDICATIONS to Avoid with BPH:
  • Testosterone: causes prostate enlargement and growth
  • Sympathomimetic agents: may cause or worsen urinary difficulty in patients with prostate enlargement due to smooth muscle contraction in the bladder neck via stimulation of alpha-1 adrenergic receptors. Therapy with sympathomimetic agents should be administered cautiously in patients with hypertrophy or neoplasm of the prostate. Avoid amphetamines, pseudoephedrine and phenylephrine.
  • Drugs with significant anticholinergic (antimuscarinic) adverse effects: decrease urinary bladder detrusor muscle contractility, resulting in urinary retention (antihistamines, TCA, phenothiazines). However, drugs like Detrol® (tolterodine) poses little risk of urinary retention, IF there is good flow. Antimuscarinics work during storage, rather than voiding.
  • Anticholinergics: same as above (benztropine, hyoscyamine)
  • Diuretics: polyuria secondary to high dose therapy may present as urinary frequency.
CAUTION: Be sure that prostate cancer has been ruled out before recommending saw palmetto.

According to the May 2016 fact sheet from the Department of Professional Employees, more than 26.2 percent of pharmacists were 55 years or over in age. As this gray haired 60-year-old pharmacist approaches senior citizen status let’s talk about saw palmetto and its use in treatment for BPH.

Benign Prostatic Hypertrophy (BPH) is characterized by too frequent urination, having trouble starting or maintaining urination, and needing to urinate during the night. The urethra, the tube that “drains” urine from the body, runs through the prostate gland in men. When the prostate gland is enlarged, obstruction of the urethra occurs and men may have trouble urinating.

At the Empower-3 clinic where I practice two days a week, we have changed three men from Flomax (tamsulosin) to alfuzosin (Uroxatrol) which both drugs have generic formulations that are inexpensive. According to Up-To-Date®, tamsulosin decreased the volume of ejaculate in more than 90 percent of patients, with 35% had no ejaculate.

Silodosin (Rapaflo) produces retrograde ejaculation (semen gets rerouted into the bladder) in 28 percent of patients. There are no reports of Alfuzosin (Uroxatrol) causing these ejaculatory difficulties. Have that conversation with your sexually active males on alpha-1 blockers!

Have a great day on the bench!!

Ginkgo biloba for memory, circulation, tinnitus?? Depends what side of the ocean you are on. Germans consider it first line.

When is the last time you wrote or filled a prescription for Ginkgo biloba?

Ginkgo biloba “maiden hair tree” said to be the world's oldest living tree species. The leaves are used with the highest concentrations occurring in the autumn when the leaves begin to change color. Even so, the compounds need to be extracted. Dried leaves, and teas are probably ineffective. Dose 120-240mg daily in 2-3 doses. USE: dementia, including Alzheimer's, vascular, and mixed dementia. Also used for cerebral vascular insufficiency. Ginkgo has also been used for peripheral occlusive vascular disease (intermittent claudication). It has also been tried for sexual dysfunction, multiple sclerosis and tinnitus.

if taking oral anticoagulant therapy. Ginkgo inhibits the binding of platelet-activation factor (PAF) to platelets; this action may increase bleeding time and can augment effects of anti-coagulant therapy. Stop 2-3 weeks before elective procedure. Also use caution if given with other NSAIDS and herbals like turmeric.

headache, nausea, gastrointestinal upset, diarrhea, dizziness, or allergic skin reactions. More severe allergic reactions have occasionally been reported.

According to a study done on rats and mice by the National Toxicology Program, Ginkgo biloba extract caused cancers of the thyroid gland in male and female rats and male mice and cancers of the liver in male and female mice.

German Commission E:
monograph states that Ginkgo Biloba Extract formulation (which is the dry leaf extract and is standardized) is effective for symptomatic treatment of organic brain syndrome caused by cerebral insufficiency or dementia syndromes. This is dated 1994, and whether these results can be extrapolated to other ginkgo products is uncertain. German physicians still consider Ginkgo extract to be the first choice for their dementia patients; it is also used for depression, Raynaud’s disease and tinnitus.

Here is what the studies say: (and it is all bad news for gingko)
GEM Study (Gingko Evaluation of Memory study) which enrolled 3,000 volunteers over the age of 75, were taking 240mg of standardized gingko daily. They were followed for an average of 6 years. Analysis of the data was disappointing, showing that ginkgo was ineffective in slowing cognitive decline, lowering blood pressure, or reducing the incidence of hypertension. This study was funded by NCCIH (National Center for Complementary and Integrative Health)
National Institute on Aging did a trial of more than 200 healthy adults over age 60 found similar results in that ginkgo taken for 6 weeks showed no improvement in memory.

Alzheimer’s disease, which is the most common cause of dementia and affects as many as 5.1 million Americans age 65 and older in the U.S., may triple in the next 40 years. (With my 60th birthday coming this Friday, I now pay attention to these statistics!!)

We all dispense a lot of Donepezil, Rivastigmine and Galantamine. Only 1 in 12 patients on these cholinesterase inhibitors show any improvement. Not to mention that 1 in 12 patients have significant side effects, usually GI upset (due to increased GI secretions), as well as bradycardia and fainting.

These cholinesterase inhibitors are first line for mild to moderate Alzheimer's if the patient or family wants to try drug therapy. Cholinesterase inhibitors increase the levels of acetylcholine, which may cause increase in increase in urinary incontinence, which is usually treated with an anti-cholinergic. The two opposing drugs may lead to a pharmacological stalemate.

Many of our caregivers, sometimes out of desperation will turn to herbals or over the counter supplements to help their loved ones. Gingko biloba and DHA, a component of fish oil are touted as being beneficial for “memory support”.

Have a great day on the bench!!

We dispense a lot of generic antidepressants to our patients. Are there any over-the counter treatment options??

St. John's Wort and treatment of depression

Common Names: St. John’s wort, hypericum, Klamath weed, goatweed.
Latin Name: Hypericum perforatum: flowering tops of St. John's wort are used to prepare teas, tablets, and capsules containing concentrated extracts. St. John's wort consists of the dried, above ground parts of H. perforatum gathered during flowering season near the end of June around the Feast of St. John the Baptist (June 24th). Antidepressant activity of SJW is attribute to its hyperforin content, which is highest in the plant during its flowering season. Hyperforin has strong reuptake inhibitor effects on all four of the mood neurochemicals (serotonin, norepinephrine, dopamine and GABA)

USE: depression, dysthymia, and sleep disturbances.
DOSE: most common regimen is 300mg up to 3 times daily up to 6 weeks Before we even discuss all the ramifications of using this drug, consider the following:
  • Should we even be considering the treatment of depression as “treatable” condition for our patients? Do we have the clinical skills necessary to manage treatment of depression? This pharmacist certainly does not.
  • Before recommending this herbal, remember that inadequately treated depression may become severe and, in some cases, may be associated with suicide.
  • The German Commission E has recognized St. John's wort as a "modestly effective" antidepressant. Some sources say it is comparable to low dose SSRI’s (like Prozac) or Tri Cyclic Antidepressants (like Elavil)
  • Doubtful efficacy for the treatment of moderate to severe major depressive disorder
  • Remember: Some studies highlight the ongoing concerns with placebo response rates in antidepressant studies which have recently been estimated to be as high as 35—45%. Almost ½ of your patients will get a positive effect from taking a placebo.
  • Usual dose: The usual dose for mild depression and mood disorders is 300 mg (standardized to 0.3% hypericin extract), 3 times per day, with meals. As with all antidepressants expect about three weeks for benefit.
  • Topical use: some value for treating Herpes labialis. Dynamiclear is a single application product for cold sore treatment. He topical oil may have some value in treatment of psoriasis lesions.
  • potent photosensitizer- make sure patients are using sunscreen. Risk increases when patients take 2-4 grams of St. John’s Wort extract (contains 5-10mg hypericin)
  • may precipitate manic attack if a patient is bipolar
  • Combining St. John’s wort with certain antidepressants can lead to a potentially life-threatening increase of serotonin, thus precipitating “serotonin syndrome”. Serotonin syndrome symptoms range from tremor and diarrhea, confusion, muscle stiffness, tachycardia (rapid heartbeat), seizures, hyperthermia (high fever), and even death. Dextromethorphan may also precipitate serotonin syndrome when given with antidepressants.
  • Avoid if pregnant or nursing
DRUG: DRUG INTERACTIONS: CYP450-3A4 inducer (expect to decrease levels of interacting drugs), avoid using St. John’s Wort with any drug metabolized by the CYP450-3A4 pathway especially:
  • Warfarin and anticoagulants
  • Phenobarbital and phenytoin
  • Digoxin
  • Other antidepressants
  • Birth control pills
  • Some HIV drugs (NNRTI and Protease inhibitors)
  • Monamine oxidase inhibitors (MAOI)
  • Alprazolam (Xanax) will speed up its metabolism and decrease efficacy by half.
We can tell that by our purchases of generic Zoloft, Prozac, Celexa and Lexapro in bottles of 500 or 1000 that depression is one of the most common conditions we treat in our pharmacies. Although this herb is in the “Top 10” of herbs used in the United States it also made the “Top 4 Herbal Supplements Your Doctor Hates” list by US News and World Report (2/22/12).

If our patient's would insist on counseling or the appropriateness of St. John's Wort the minimum "screening questions" we could ask are: (source:
  • "During the past month, have you often been bothered by feeling down, depressed, or hopeless?"
  • "During the past month, have you often been bothered by having little interest or pleasure in doing things?"
Given the facts of the drug interactions, the placebo effect of treating depression, the potential for serotonin syndrome and even suicide, self-management of depression for our patients is not recommended. Let’s leave the treatment of this condition to clinicians with some level of experience. I'm not recommending that we become amateur psychiatrists!

Have a great day on the bench!!

Most of our migraine patients will do anything to alleviate the severity or frequency of their headaches. This herbal product might be of benefit.

Feverfew... neurologist recommended!

Petasites is a genus of flowering plants in the sunflower family, that are commonly referred to as butterburs and coltsfoots. Tanacetum parthenium, Chrysanthemum parthenium (feverfew, bachelor’s buttons, featherfew) is ranked #19 as the most often used herb in the US. The leaves or flowers, which can be fresh or dried, as well as a tincture are available. The active ingredient parthenolide, has been studied to prevent menstrual cramps, cancer, as well as treat rheumatoid arthritis and migraine headaches. Petasin appears to be a major active compound of petasites hybridus extract. It has inhibitory activities on leukotriene generation in eosinophils and neutrophils. This indicates that it may have anti-inflammatory and anti-allergy properties.

  • MIGRAINE HEADACHES: Some research suggests that feverfew may be helpful in preventing migraine headaches; however, results have been mixed and more evidence is needed from well-designed studies. Five trials (total 343 patients) were unable to establish that feverfew is efficacious for preventing migraine. There is insufficient evidence from some controlled clinical trials that feverfew was better than placebo for migraine treatment. Side effects were minimal with only mild and transient adverse events were reported in the included trials. Some of the trials used an alcoholic extract, while trials that used the dried leaves seemed to show more efficacy for migraine treatment.
  • Some studies showed patients reported a decrease in severity and frequents of headaches, as well as a decrease in nausea. American Academy of Neurology and the American Headache Society suggest that a feverfew extract may be effective and should be considered for migraine prevention. Petadolex® is the brand most studied.
  • RHEUMATOID ARTHRITIS: One study found that feverfew did not reduce rheumatoid arthritis symptoms in women whose symptoms did not respond to conventional medicines. It has been suggested that feverfew could help those with milder symptoms. It was found to no more effective than placebo for the treatment of rheumatoid arthritis.
  • CANCER: Did show some anti-cancer effects in lab studies. Human studies are needed.
  • If allergic to other members of the daisy family (which includes ragweed and chrysanthemums) are more likely to be allergic to feverfew.
  • Pregnancy and nursing: NOT recommended during pregnancy, because of its abortifacient properties in early pregnancy.
  • People taking anticoagulants should use feverfew with caution because feverfew may potentiate the activity of anticoagulants such as warfarin
  • Side effects: Common: Minor gastrointestinal distress; oral ulcerations from chewing fresh feverfew leaves; airborne contact dermatitis; exacerbated dermatitis following use of a moisturizer containing feverfew.
Feverfew got its name from the Greeks, who thought it reduced fever, but is of minimal value. In the 1980’s it was frequently recommended along with magnesium and Riboflavin (B2) for the prevention of migraine headaches. Many of our local neurologists start patients with Magnexium Oxide and Riboflavin (B-2) as initial prophylactic therapy.

As we journey through the many herbals that are available to our patients, we wont seen many that are endorsed by traditional medical societies. Feverfew is one exception to that notion. After reading that the American Academy of Neurology and the American Headache Society recommend it's use, I'd feel comfortable recommending it to my patients.

The challenge, as always in the United States, is the lack of standardization of these herbal products. Petadolex® seems to be the product with the most support for efficacy. It is available through our pharmacy warehouses, and retails around $45.00 per month. Most references, particular in Canada require feverfew supplements should be standardized to contain at least 0.2% parthenolide.

Have a great day on the bench!!

Echinacea... might be better for our patients than a Z-pak!

Our next herbal product...Echinacea

Echinacea is one of the top five herbs that our patients have questions about. Many have their own notions on this herbs efficacy. Like all products we sell it does come with a few warnings that might not make it appropriate therapy for a select group of patients. Efficacy seems to be another issue.

Ecinacea comes from the Echinacea angustifolia, or E.purpurea, or E.pallida (American cone flower, Kansas snake root). It is found widely throughout North America and was used by the Native Americans both topically and orally for the treatment of burns, snakebites, pain, cough, and sore throat. All nine species are native to North America. The fresh or dried roots or above-ground parts that are collected at the time of flowering of the Echinacea angustifolia, is what is used in medicinal preparations.

Echinacea is used today in the prevention and treatment of the common cold to decrease both the duration and severity. According to most current literature, prevention and treatment of common cold is modest at best. Well-designed clinical trials have not proven its benefit in treatment/prevention of upper respiratory infections, including the common cold.

  • Allergy to related plants in the daisy family: ragweed, chrysanthemums, marigolds, and daisies.
  • The immune stimulating effects of Echinacea have led to concerns regarding the use of Echinacea in patients with autoimmune disorders. It isn’t known whether Echinacea may exacerbate autoimmune disorders, such as Lupus, Sjogrens syndrome or rheumatoid arthritis. I wouldn’t recommend Echinacea in any of these patients. Patients that have atopic dermatitis have increase likelihood of allergic reactions and should also avoid echinacea.
  • According to one study the authors noted that there were small trends in the direction of a benefit from echinacea—an average half-day reduction in duration, or an approximate 10 percent decrease in severity—the researchers concluded that echinacea, at this dose formulation, does not significantly change the course of the common cold.
  • A 2001 study of 80 adult male and female subjects showed a reduction of duration of cold symptoms from 9 days for the placebo group versus 6 days for the echinacea group.
  • Dose most frequently studied: (The echinacea tablets contained the equivalent of 675 mg of E. purpurea root and 600 mg of E. angustifolia root.) Most common strength available OTC is 400mg capsules.
  • Commission E monographs from Germany: Only two preparations have been approved by the German Commission E. These include the root extract of Echinacea pallida used to support and promote natural powers of resistance of the body, especially infectious conditions (influenza and colds), and the expressed juice of Echinacea purpurea, as a supplemental treatment for upper respiratory and urinary tract infection.
So it seems like Echinacea doesn’t have the evidence that supports our recommendation for treatment or prevention of the common cold. As we with Vitamin C, patients need to be on it chronically to reduce the duration or intensity of the common cold. Antibiotic prescriptions that many prescribers send our way, actually do more harm.

The latest antibiograms from Central Pennsylvania hospitals are showing resistance to Azithromycin (Z-pak) of 50%. Thanks to the indiscriminate use of antibiotics, Azithromycin is ineffective against the most common bacterial pathogen half of the time! All of a sudden now using echinacea for the common cold doesn’t seem like such a bad idea!

Just make sure it is for the right patient. With the lack of standardization of herbal products in the United States, and the fact there are 9 different species of coneflower makes consistency of Echinacea very challenging.

Remember if you treat the common cold it lasts 7 days; if untreated it lasts one week!

Have a great day on the bench!!

April 2018

We have insulin, sulfonylureas, SGLT2 inhibitors, gliptins, alpha glucosidase inhibitors, DPP4 inhibitors and biguanides... how about a sprinkle of cinnamon?

Instead of all those pills, can I take a natural product for my Type-2 diabetes?

Cinnamon fits into both the food and medicinal herb categories. We have our “Cinnamon Toast Crunch” (my kids favorite) cereal for breakfast, and we sell cinnamon in our herbal section to improve glycemic control for our diabetics. Because of the lack of standardization in the United States, and the very conflicting data, I am hesitant to recommend this herbal product. Cinnamon contains coumarins, which in high doses can lead to liver toxicity, when doses exceed 7grams. Here is some background information:

From Cinnamomum aromaticum, a small evergreen tree native to Southern India and Sri Lanka, Malaysia and Madagascar. Cinnamon bark (Cinnamomum verum) is the most common type used in the Western world, as a cooking spice. Bark most commonly used and occasionally, leaves and buds.

Use: Treatment of Type-2 Diabetes. Cassia cinnamon (“Chinese cinnamon”) is believed to be most effective. This type of cinnamon is commonly found in herbal products in pharmacies and health food stores. As of now most believe it is to be used as “adjunctive” therapy, when added to sulfonylurea therapy (8.22% to 7.86% after 12 weeks) in a well-designed study. Seemed to be of some benefit in those with poor glycemic control, by increasing sensitivity at the insulin receptor.

ADA journal article: 60 DM Type-2 patients studied for 60 days: After 40 days, all three levels of cinnamon reduced the mean fasting serum glucose (18–29%), triglyceride (23–30%), LDL cholesterol (7–27%), and total cholesterol (12–26%) levels; no significant changes were noted in the placebo groups. Dose used was 1g, 3g, 6g of cinnamon. (2004 article). Patients took 1, 3 and 6 grams of cinnamon in the study arm. This study was done in Pakistan.

National Institutes of Health: “High-quality clinical evidence (i.e., studies in people) to support the use of cinnamon for any medical condition is generally lacking”

University of Connecticut School of Pharmacy: Diabetes Care. 2008;31(1):41. PRECAUTIONS/CONTRAINDICATIONS:
  • RESULTS: Five prospective randomized controlled trials were identified. Upon meta-analysis, the use of cinnamon did not significantly alter A1C, Fasting Blood Glucose, or lipid parameters. Subgroup and sensitivity analyses did not significantly change the results.
  • CONCLUSIONS: Cinnamon does not appear to improve A1C, FBG, or lipid parameters in patients with type 1 or type 2 diabetes.
CAUTION: Cassia cinnamon contains coumarin, consuming large amounts my lead to liver toxicity.
DRUG/FOOD INTERACTIONS: Cinnamon may reduce the effectiveness of tetracycline antibiotics. PREGNANCY: Use of cinnamon in amounts greatly exceeding those found in foods is not recommended during pregnancy

In 1958 the rate of Type-2 diabetes in the United States was 1%, sixty years later we are approaching the 10% mark. Many of our patients want to take "natural" products to manage their Type-2 diabetes. Most often they inquire about cinnamon, and the results are variable indeed.

Depending on what the patients want to believe they can find evidence supporting claims that cinnamon is useful for Type-2 diabetes management.

There is a plant called goats rue (Latin: Galega officinalis) that is endemic to the temperate climates of Europe and the United States. By studying some of the compounds in this plant the biguanide class was discovered which includes phenformin (D.B.I) which was removed from the market in the 1970's due to lactic acidosis, as well a metformin (Glucophage). Goat's rue was considered an agricultural pest and placed on the "Federal Noxious Weed List" in the United States. Think of that next time you prescribe or dispense metformin!

The newest class of diabetes drugs, the "flozins" or SGLT-2 inhibitors like canaglaflozin (Invokana) also came from a natural product. Phlorizin, a naturally occurring compound extracted from the root bark of an apple tree in 1835 and later identified as a SGLT1 and SGLT2 dual inhibitor, was the precursor to this category of drugs.

Maybe there is an active compound in cassia cinnamon that will be elucidated as a treatment for Type-2 diabetes, but for now tell your patients that it is best to sprinkle their cinnamon on a fresh apple!

Have a great day on the bench!!

Bright yellow and in our spice cabinet, this Indian herb may be beneficial to our arthritis patients.

Turmeric---not just for cooking!

Latin name: Curcuma longa

Common Name: Indian saffron or curcuma which is related to ginger, is grown throughout India, other parts of Asia, and Central America. Turmeric is a major ingredient in curry powder. The medicinal part of the plant used is the dried rhizome.

Primary active ingredients: curcuminoids, which are bright yellow and used to color foods and cosmetics. Turmeric is what gives curry it’s bright yellow color in cooking. The German Drug Codex monograph requires turmeric to contain not less than 3.0% curcuminoids, calculated as curcumin, and not less than 3.0% volatile oil.

Possible uses: osteoarthritis, digestive disorders, and potentially stroke prevention by quelling inflammation in blood vessels,

Possibly effective: Osteoarthritis-- Some turmeric extracts can improve symptoms of osteoarthritis. Taking a specific turmeric extract (Meriva by Indena) 500 mg twice daily seems to reduce pain and improve functionality in patients with osteoarthritis of the knee after 2-3 months of treatment. Patients using this product saw decreased use of NSAIDS.

The University of Arizona Health Sciences secured an NIH grant to conduct studies of turmeric (CLaRA study), where they found turmeric to be effective as an anti-inflammatory, in rheumatoid arthritis patients. Researchers also found that turmeric blocks a protein that causes bone breakdown in these patients.

The rhizome contains an anti-inflammatory and choleretic volatile oil. Anti-inflammatory actions may be due to leukotriene inhibition, as well as COX-2 inhibition. Turmeric has been used as a “digestive aid”; as a choleretic it increases release of bile, therefore it is contraindicated if the patient has gallstones.

  • High doses of turmeric can act as a blood thinner, and also cause stomach upset. Avoid turmeric/curcumin in patients that take blood thinners such as warfarin (Coumadin).
  • Are about to have surgery
  • Pregnant
  • Have gallstones or any gallbladder disease
  • Osteoarthritis: In capsule form use 400 mg to 600 mg, three times per day.
  • Rheumatoid Arthritis: 500 mg twice daily.
In last week’s column, I invited all my readers to feel free to e-mail me their request for whatever herb they would like covered. My first response was from one of my pharmacist colleagues who is 87 years old, and still practicing part time. He is a voracious reader, and is a self-proclaimed “nerd” as I am. To respond to this very seasoned pharmacist’s request the first herb we will cover is Turmeric or Tumeric.

Our warehouse has at least 12 different brands of turmeric capsules available, and most cost less than $10.00 per month. This is one herb I will feel comfortable recommending to our arthritis patients, as long as they do not have any contraindications as listed in this newsletter. There seems to be a fair amount of efficacy for this herb, and our questions about its use will be answered when the CLaRA study is completed.

Have a great day on the bench!!

Herbal Therapy-- pharmacists are expected to have some degree of proficiency!

Herbal Pharmacy --- what a challenge!

So often it is difficult to substantiate any benefit from Herbal therapy, while side effects seem to appear rapidly. I find these products to be particularly challenging, given the fact we seem to have better pharmacotherapeutic choices in the prescription department.

Herbals: Challenges for pharmacists
  • our training is very limited- including mine
  • the prescribing community knows even less!
  • consistency of products between distributors and manufacturers
  • At best supporting literature is weak. Frequently we see conflicting studies and results.
Best website I’ve found: National Center for Complementary and Integrative Health.
  • For this project I’ve joined the American Botanical Council (ABC) for access to the Commission-E monographs. The cost is $50 per year, which allows you access to this herbal website. You can read about each herb individually, or can look up therapeutic categories, and the herbs that are associated with treatment of that disease state.
Herbal Regulations
  • The FDA loosely regulates dietary supplements, under the Dietary Supplement Health and Education Act of 1994 (DSHEA ’94)
  • Dietary supplementary are considered to be: vitamins, minerals, other botanicals, amino acids, enzymes, organ tissues, glandular, and metabolites. These dietary supplements fall under the category of "foods" and not "drugs".
  • Consequently, scientific data supporting claimed benefit are not always available as for traditional pharmaceuticals. The burden of proof for safety and adulteration of products lays on the Food and Drug Administration (FDA)
  • Consumers should also note that rigid quality control standards are not required for nutraceuticals and substantial variability can occur in both the potency and the purity of these products.
  • Given the regulatory structure for herbal medicines, there is substantial variation in the quality of commercially available products in the United States and elsewhere. Variability in product quality can impact the product's efficacy, safety, and therefore clinical usefulness.
What Germany does so well:
  • Commission-E is Germany’s equivalent to the FDA in the United States.
  • There are 380 monographs evaluating the safety and efficacy of herbs for licensed medical prescribing in Germany. Published in 1998.
  • Official monographs that give the approved uses, contraindications, side effects, dosage, drug interactions and other therapeutic information essential for the responsible use of herbs and phyto-medicines.
  • Up to 70% of German doctors prescribe "phytomedicines"
SAFETY of Herbals: Despite ephedra products comprising only 0.8 percent of all dietary supplement sales in 2001, they were responsible for 64 percent of all herb-related adverse events reported to United States Poison Control Centers during the same year. Fortunately, the FDA banned all products containing ephedra in April 2004. Then the manufacturers substituted bitter orange (citrus aurantium) which contains “synephrine” for ephedra in weight loss products. Synephrine has been associated with serious cardiovascular and neurological side effects.

I think most of us pharmacists would feel better about recommending these herbal products if we had the guidance of the FDA, as do our pharmacists in Germany have with the Commission-E monographs. Until that happens, I will continue to proceed with caution. Patients seem to equate safety with natural products. I always remind my patients that one of our favorite botanicals is “digoxin” from the foxglove plant, knowing that 1mg can stop a person’s heart. Natural does not equate to safety!

Feel free to send me an email, so we can explore in depth herbals you might have questions about.

Have a great day on the bench!!

Fresh fruits and vegetables might be adequate to prevent constipation, but when it comes to opioid induced constipation, a pharmacist recommendation is critical.

Management of Opioid Induced Constipation

Numerous side effects are commonly seen with opioid use such as euphoria, respiratory depression, sedation, GI upset and constipation. Of all the common side effects associated with opioid use, the patient never develops a tolerance to constipation. Opioid induced constipation (OIC) occurs in approximately 40% of patients treated with opioids.
  • Use Rome III criteria (less than 3 BM per week)
  • OIC is dose related. As doses escalate, OIC becomes more prevalent
  • Mechanism: opioids bind to mu receptors in the GI tract inhibiting peristalsis.
Over The Counter:
  • Stool softeners can result in "all mush, no push" simply because there's not enough GI motility. Stool softeners are of little value for OIC.
  • For patients on opioids (hydrocodone, oxycodone, codeine etc.) recommend a stimulant laxative (senna or bisacodyl) to increase GI motility plus docusate if the stool is too hard to pass.
  • OTC Polyethylene Glycol 3350 (MiraLAX) is another excellent choice.
Peripherally Acting Mu-Opioid Receptor Antagonists (PAMORAs)
How they work: preferentially block mu-opioid receptors in the GI tract and do not interfere with the pain-relieving effects of opiates on the mu receptor in the central nervous system.

Methylnaltrexone: (Relistor®)
  • Mechanism: Methylnaltrexone is a PAMORA with a quaternary amine structure, blocking the ability of methylnaltrexone to cross the blood-brain barrier.
  • Indication: Treatment of opioid-induced constipation in patients with advanced illness who are receiving palliative care, when response to laxative therapy has not been sufficient.
  • Warnings/Precautions/Adverse Effects:
    • Contraindicated if known or suspected mechanical gastrointestinal obstruction
    • Discontinue therapy if severe or persistent diarrhea occurs
    • Use with caution in patients with known or suspected lesions of the GI tract
    • May cause gastrointestinal perforation (serious adverse effect)
    • Pregnancy category: B
    • May cause diaphoresis, abdominal pain, flatulence, nausea, dizziness (common adverse effects)
  • Effects can be seen within 4 hours of administration
Relistor® (methylnaltrexone) injection dosage:
cost around $125 for 12mg vial

Injection is based on body weight. Typical dose is 12mg SC once a day for chronic non-cancer pain.
Relistor 150mg (ORAL) tablets cost: $1635.00/month
Dose: 3 x150mg tablets (450mg) daily in the morning half hour before first meal of day

Naloxegol (Movantik®) cost: $314/month
opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain.
Dose: 25mg once daily; if not tolerated reduce to 12.5mg daily. If renal impairment less than 60ml/min, use 12.5mg daily. Take on empty stomach, one hour before a meal or 2-3 hours after a meal.
Drug interactions: Avoid CYP450-3A4 inhibitors (diltiazem, verapamil, erythromycin), or reduce to 12.5mg daily. Avoid grapefruit juice.
STOP all maintenance laxatives before starting Naloxegol, may restart in 3 days if not effective.
  • effective in people who have taken opioid pain medicines for at least 4 weeks
  • if opioid is stopped, stop Movantik®
Naldemedine (Symproic®) cost: $314/month
opioid antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic non-cancer pain. Is a derivative of opioid antagonist naltrexone. It has a large polar side chain to prevent penetration into the CNS. Works by blocking opioid receptors in the GI tract.
Dose: 0.2mg tablet once daily, any time of day, with or without food.
Drug interactions: is a substrate of CYP 450 3A4 watch for drug interactions with rifampin (induce). CYP-450 3A4 blockers can cause excessive levels of naldemedine.
Prescription medications for treatment of OIC
  • Methylnaltrexone (Relistor) 12mg SC daily (chronic non-cancer pain)
    • Relistor 150mg tablets 3 tablets in the morning
  • Naloxegol (Movantik) 25mg orally in the morning
  • Naldemedine (Symproic) 0.2mg tablet orally daily in the morning
  • Lubiprostone (Amitiza) 24mcg orally twice daily (see last week’s newsletter)
Opioid induced constipation can be a challenge to treat. So often a clinician will recommend docusate for prevention which for most cases is not adequate to treat OIC. Addition of fiber like Metamucil or Citrucel is a worse choice as lack of peristaltic activity can lead to impaction.

Fresh fruits and vegetables might be adequate for a teenager who has their wisdom teeth extracted to prevent constipation for their acute hydrocodone prescription. However for our patients taking chronic opioids, this newsletter will be of great benefit helping clinicians select appropriate treatment. Stimulant laxatives over the counter are the most economical ways to handle OIC, however for patients receiving higher doses of opioids, prescription treatment might be indicated.

Have a great day on the bench!!

March 2018

We'll explore some of the most expensive treatment options for constipation...of course they are prescription!!


Let’s look at the prescription options for treatment of chronic idiopathic constipation (CIC) and Irritable bowel syndrome constipation predominant (IBS-C)


AMITIZA® (Lubiprostone) : 8mcg and
First approved 2006

Mechanism: Lubiprostone is a locally acting chloride channel activator that enhances a chloride-rich intestinal fluid secretion without altering sodium and potassium concentrations in the serum. By increasing intestinal fluid secretion, lubiprostone increases motility in the intestine, thereby increasing the passage of stool and alleviating symptoms associated with chronic idiopathic constipation. Indication

  • Treatment of chronic idiopathic constipation (CIC) in adults.
  • Treatment of irritable bowel syndrome with constipation (IBS-C) in women over 18 years old
  • Also indicated for opioid induced constipation.
Warnings/precautions/adverse effects
Potential to cause miscarriage (have negative pregnancy test, use contraceptive measures) Pregnancy category: C
May cause nausea, diarrhea, abdominal distention, loose stools, flatulence and vomiting
May also cause headache, dizziness and peripheral edema

Amitiza® (lubiprostone) 24mcg and 8mcg CIC: Dosage: 1 capsule (24mcg) BID with food IBS-C: 8mcg BID for women age 18 and over.

LINZESS® (linaclotide) 72mcg, 145cg and 290mcg caps
First approved:2012

Indication: irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC).

Dose: one capsule each day on an empty stomach, at least 30 minutes before your first meal of the day. Swallow LINZESS capsules whole. Do not break or chew the capsules
Mechanism: guanylate cyclase-C agonist. By increasing the concentration of cyclic guanosine monophosphate (cGMP), linaclotide leads to secretion of chloride and bicarbonate into the intestinal lumen which causes an increase in fluid and GI transit time.
  • For IBS-C, linaclotide should be dosed as 290 mcg once daily on an empty stomach. For IBS-C, Linzess decreases PAIN from IBS-C
  • For CIC, the approved dose is 145 mcg or 72mcg once daily on an empty stomach
  • Do not use in patients less than 18 years of age
TRULANCE® (plecanatide) 3mg tablets ($466.16)
First approved-2017

Trulance (plecanatide) 3 mg tablets is indicated in adults for the treatment of
  • Chronic Idiopathic Constipation (CIC) and
  • Irritable Bowel Syndrome with Constipation (IBS-C).
Mechanism: Except for a single amino acid substitution, Trulance is structurally identical to human uroguanylin. Uroguanylin activity modulates within the changing pH environment of the intestines, coinciding with areas of fluid secretion, and decreases pain sensation.
Dose: 3mg once a day, taken with or without food.

Next week we will discuss the prescription treatment options for opioid induced constipation.

TFiber supplements and stimulant laxatives have been around for a very long time. Many of us “seasoned” pharmacists remember “if not nature---Metamucil” and “Doxidan in the PM for a BM and the AM.” We cant forget to mention "Natural and Gentle Fletcher's Castoria".

And of course every Saturday night Lawrence Welk would be promoting "Serutan--that is Natures spelled backward." There have always been a lot of advertising for laxatives in the media, but our patients always asked for our recommendations.

Since 2006, we have had three new laxatives on the prescription shelves that are indeed effective and very expensive. We've seen ads on TV for Amitiza "move to your own beat" as well as Linzess "ease the pain"-- just ask your doctor!! Just be sure to have enough in your health savings accounts!

Have a great day on the bench!!

When fiber and softeners are not quite enough, we have to "get things moving" with a stimulant laxative.

Sometimes our patient's boels need a little "push"

Laxatives that Result in Soft or Loose stool in 6-12 hours

Bisacodyl (oral) Dulcolax® 5mg 5-15mg daily HS
Senna Senokot® 8.6mg 2HS, max=4 daily
Magnesium hydroxide Milk of Magnesia (400/5) 30-60ml HS

Stimulant agents

Indication: Are effective as initial therapy to treat constipation but should not be used for more than 1 week. Chronic use was believed to lead to cathartic colon, which results in poorly functioning colon, resembling ulcerative colitis. However, most of these cases are reported before 1960 when toxic cathartics were used (podophyllin). Still a subject of controversy whether mild laxatives can be used long term.

Mechanism: Increases propulsive contractions by local irritation or action on the intramural nerve plexus of the intestinal smooth muscle, stimulate secretion of water and electrolytes.

Patient information:
  • Causes discoloration of urine
  • Temporary measure, do not use for longer than one week, without consultation.
  • These agents are often abused.
  • Are excreted in breast milk.
  • May cause harmless melanotic pigmentation of colon
  • May color the urine from pink to brown.
Senokot® (senna) 8.6mg/ tablet.
Dosage: start 2 tablets at bedtime; do not exceed 2 tablets twice a day. Senna is often combined with docusate.

Dulcolax® (bisacodyl) 5mg tablets Dosage: start with 1 tablet at bedtime. Usual adult dose is 2 tablets at bedtime. NOTE: this product is enteric coated do not crush or chew. Do not take within 1 hour of antacids, milk or any product that raises gastric pH.

Magnesium hydroxide

Indication: can be used as an antacid for temporary relief of heartburn, or occasionally as a laxative.

Mechanism: Highly osmotic ions draw water into the intestine and cause an increase in the intraluminal pressure, thereby exerting a mechanical stimulus that increases intestinal motility. Increase cholecystokinin – pancreozymin which is an enzyme that increases the secretion of fluids into the GI tract.

Drug interactions: Oral anticoagulants, Digoxin, Tetracyclines, Quinolones

Patient information:
  • May lead to hypermagnesemia (as much as 20% Mg may be absorbed)—problem if renal impaired. Patients with a CrCl <30 mL/minute should be monitored by serum magnesium levels.
  • Sodium: hypertensive or CHF patients should not receive these on a long term basis due to fluid retention from sodium absorption.
  • May see abdominal cramping, excessive diuresis, Nausea, vomiting, dehydration electrolyte disturbances, incontinence.
  • Milk of Magnesia 400mg/5ml
Is an 8% suspension of magnesium hydroxide Antacid: For the temporary relief of heartburn, upset stomach, sour stomach, or acid indigestion. Laxative: For relief of occasional constipation. Expect results within 30 minutes to 6 hours. Dose: 1 to 2 ounces at bedtime. Shake well before using and follow dose with 8 oz of water.

Thanks to the frequent practice of "cross-branding" we pharmacists should always be consulted before our patients make a laxative purchase. Some companies use their Proprietary name to enhance a whole line of products. I feel Dulcolax is the worst offender as they have the "Dulcolax" name blasted across their softener which actually contains docusate sodium.

Among us older practitioners Dulcolax has always meant bisacodyl. Clinicians should encourage patients to consult the pharmacist before purchasing laxative products. Better yet it is prudent for clinicians to write a prescription for the patient to decrease confusion.

However, I once received a prescription from a physicians office that was computer generated. It said "Dulcolax" (docusate) - take 4 capsules at bedtime the night before the test. I called the physician's office and told them this was the same as "Colace" . The nurse told me, that was the first thing that came up under "Dulcolax". She authorized me to switch it to the bisacodyl product.

You can only imagine how confused our patients can get with this very foolish practice. As I tell my students---"when I become head of the FDA...this is the first thing I will change!"

Have a great day on the bench!!

Sometimes we need more than prunes and psyllium!

Laxatives that cause softening of feces in 1-3 days

Generic Representative Brand Dosage
Docusate sodium Colace® 50, 100 50-360mg/day
Docusate calcium Surfak 240mg 50-360mg/day
MINERAL OIL Kondremul® 15-30ml
LACTULOSE Chronulac®, Constulose® 15-30ml
SORBITOL 30-50gm
PEG 3350 soln Miralax® 1 cap 17gm in 8oz water

Stool softeners

Indication: Beneficial in anorectal conditions in which passage of a firm stool is painful. Generally used for prevention of constipation.

Mechanism: Anionic surfactants increase the wetting efficiency of intestinal fluid, thereby softening fecal mass. Facilitates admixture of fat and water to soften stool.
FYI: Docusate is a “soap” and bridges the barrier between the lipid stool, and water. Cut open a capsule, add to a small prescription vial, add water and shake. Looks like dish-washing soap.

Patient information:
  • Take with fill glass of water.
  • Do not take with any mineral oil containing laxatives, as this will lead to the oil’s absorption and cause hepatotoxicity.
Available as:
  • Colace® (docusate sodium) 50mg (rarely used) 100mg (common) 50- 300mg daily in divided doses.AKA : “DOSS”or “DSS””: dioctyl sodium sulfosuccinate
  • Surfak® (Docusate calcium) 240mg dose: one capsule daily.
Emollients (lubricants)
Indication: prophylactically in patients who should not strain (anorectal surgery, MI)

Mechanism: Softens fecal contents by coating them, thereby preventing the colonic absorption of water.

Patient Information:
  • Do NOT give with stool softeners (Colace, Surfak)
  • Avoid in any patient with the potential to aspirate such as GI reflux, as this could cause lipid pneumonia
  • May cause anal leakage leading to anal pruritis. May stain clothes/furniture.
  • If used long term, supplement with fat soluble vitamins (ADEK) as this will impair their absorption.
  • Take on an empty stomach.
Available as:
  • Mineral oil: dose 15-45ml HS
  • Kondremul® (mineral oil emulsion) dose: 30-75 ml at bedtime. This product is a pleasantly flavored marshmallow liquid, and is much more palatable than straight mineral oil.
Chronulac® (Rx only) Indication: useful particularly in elderly patients. Not usually first line. Takes at least 24-48 hours for action.
  • Also used for hepatic encephalopathy to decrease blood ammonia levels.Because colon contents are now more acidic than blood, ammonia migrates from blood to colon, acid colon contents convert NH3 to the ammonium ion (NH4+) trapping it and preventing its reabsorption.Also because of the laxative effect of lactulose, the ammonia spends less time in the colon, decreasing time for absorption to occur.
Mechanism: disaccharide used orally or rectally. Metabolized by colonic bacteria to form lactic acid, formic acid, acetic acid and carbon dioxide. Increase osmotic pressure and acidify the colonic contents, thus increasing stool water content and softening.

Patient information:
  • Give with fruit juice, water or milk to increase palatability.
  • Will cause significant gas, leading to -flatulence, abdominal pain and cramping.
  • May also cause diarrhea and electrolyte imbalances.
  • Because it contains galactose & lactose, use with caution in diabetics.
  • If used over 6 months in elderly measure: electrolytes (K & Cl) & carbon dioxide periodically.
Available as: Chronulac® (lactulose) 10gm / 15ml available in pints and quarts Dosage 15-30ml daily. Increase to 60ml if necessary.

Not available as a laxative but is available as a sweetening agent for prescription compounding. Along with mannitol, these are alcohol sugars that are used as sweeteners. If your patients are ingesting excessive sugar free candy or gum diarrhea can occur.
Mechanism: similar to lactulose.

Polyethylene glycol laxatives
Indication: Used for colon cleansing before diagnostic procedures or colorectal operations. Can also be used in lower doses for chronic constipation.

Mechanism: is an osmotic laxative that large molecules draw water into the gut, and increased volume results in distention of the intestines, increasing peristalsis and bowel motility, and softening stools.
FYI: the number 3350 is the molecular weight of this particular polyethylene glycol.

Patient information
  • May cause abdominal cramping, flatulence, rectal irritation and incontinence.
Miralax® contains PEG 3350 (this product for long term management of constipation)

Dosage: 1 capful (17gm) in 8 oz of water once daily.
  • Available prescription sizes: 255gm (2 weeks supply) and 527gm as (1 month supply).
  • Caution: some generic caps are “oversized” and have a fill line inside. May cause over dosage—more than 17 grams.17gm= 1 heaping tablespoonful
  • Also available over the counter in 7-day, 14-day and 28-day packaging.
GoLytely, CoLyte, Nu-Lytely: contains PEG 3350, in a 4 liter jug, (approximately 230-240Gm)

The 4L jug should be reconstituted to the fill line early in the morning, then refrigerated. Do not add flavors (unless provided by manufacturer) or colors to the solution. Follow prescribers protocol.
  • Some prescribers give Metoclopramide (Reglan®) to decrease nausea
There is always a lot of opportunities for us to discuss laxative use with our patients. Often the intake of water, fiber supplements, fresh fruits and vegetables on't produce the desired results.

Of all the products we discuss today, docusate (Colace®) and PEG3350 (Miralax®) are the most common we use in the pharmacy. PEG3350 falls nicely into the "softener" category when taken as a 17gm dose once a day. I remember as a much younger pharmacist we had a patient who had multiple sclerosis. She battled constipation for many years.

Her very astute neurologist would have me break down a bottle of the bowel preparation, and she would mix a portion with water and drink it over a 2 day period. In 1999, Miralax was finally released as a single daily dose of 17 grams. In 2006 the Bayer company got FDA approval to sell this product over-the-counter. In 2012 the product became available as a generic.

This laxative is the "go to" for pediatric patients (with a doctors recommendation).

Have a great day on the bench!!

Less than 10% of our patients ingest enough fiber for bowel regularity. What can we do to help them...

An apple a day is a good start!!

The traditional classification of laxatives by mechanism of action is not very useful. Many mechanisms have not been elucidated. Most work by promotion of mechanisms associated with diarrhea, such as electrolyte secretion, decreased water & electrolyte secretion, increased intraluminal osmolarity, and increased hydrostatic pressure in the gut.

Classification is best accomplished by dividing the drugs into categories based on their time to onset of action. for the next couple newsletters we will focus on laxatives that cause soften of feces in 1-3 days

Generic Representative Brand Dosage
Methylcellulose Citrucel® 4-6 gm per day
Wheat Dextrin Benefiber® 2 teaspoon up to 3 times daily
Psyllium Metamucil®, Konsyl® Varies
Polycarbophil FiberLax®, Fibercon® 4-6gm per day

Bulk Forming Agents:

Fiber are natural or synthetic polysaccharide derivatives that absorb water to soften stool and increase bulk, which stimulates peristalsis. Because dietary fiber works in both small and large intestines the onset of action is slow (12-24 hours—up to 72 hours.). Fiber supplements are used to prevent rather than treat constipation. Insoluble fiber does not absorb water; while soluble fiber does. Both help material move through your digestive tract, but soluble fiber can help give stool a softer, bulkier consistency that’s easier to pass.

Metamucil®: is made from ground psyllium husks, from the plantago ovata plant. Adult dose is 1-2 rounded teaspoonful in 8oz of water 1 to 3 times daily. If using the “Orange Smooth-Real Sugar” product the dose is 1 tablespoonful.

Fun Fact: Metamucil website has dosages for
  • For helping feel less hungry between meals
  • For promoting and maintaining digestive health
  • For helping lower cholesterol to promote heart health- (psyllium traps bile acids)
  • For helping maintain healthy blood sugar levels as part of your diet
Patient counseling points:
  • There are Metamucil capsules available, if patients complain of grittiness especially if they wear dentures
  • Make sure patients mix with adequate water
  • Because of fermentation it may cause abdominal cramping, bloating, flatulence, distention, esophageal obstruction, intestinal obstruction, allergic reactions
  • Drug interactions: oral anticoagulants, digitalis, salicylates, tetracycliness
is a synthetic bulk laxative containing methylcellulose. Methylcellulose is derived from cellulose which comes from the cell walls of green plants. It is less likely to cause fermentation leading to bloating and flatulence.
Dose: 1 tablespoonful 1 to 3 times daily.

Patient counseling points:
  • Available as orange flavor, sugar free and caplets.
  • Be sure to mix with adequate fluids to prevent esophageal obstruction.
  • Mix with cold fluids, avoiding carbonated beverages and milk.
ingredient: wheat dextrin, which is extracted from wheat starch. Wheat dextrin is a soluble fiber which absorbs water in the intestine to form a viscous liquid which promotes peristalsis and reduces transit time. Helps lower cholesterol (LDL and total cholesterol), reduces risks of coronary heart disease and type 2 diabetes. May be beneficial lowering blood sugar and reducing risk for heart disease.
Dose 2 teaspoonfuls daily, up to 3 times daily. Benefiber® promotes wheat dextrin as a "prebiotic" which are carbohydrates that act as food for beneficial bacteria in the gut. These carbs (or starches) travel undigested to the colon, where they ferment and produce small chain fatty acids that feed the gut flora. Prebiotics encourage growth of good flora and crowd out the "bad flora"

Patient counseling points:
  • Will not thicken in liquid, no taste, no gritty texture.
  • Will not alter taste of food or beverages.
  • May mix with water, juice, coffee, baked goods
  • Patients should avoid if they are gluten sensitive
Calcium polycarbophil (FiberLax®, FiberCon & Equilactin): can be used for both diarrhea and constipation. Is a “stool normalizer”. Polycarbophil absorbs about ten times its own weight of water under acidic conditions, but the swells to 70 times its weight in the neutral pH of the small and large intestines.
Each caplet contains 625mg calcium polycarbophil=500mg polycarbophil
Dose: 2 caplet 1 to 4 times daily.

We discuss another common problem that presents in our clinics, that in many cases can be ameliorated by adequate diet, exercise and hydration. The recommended levels for dietary fiber is 25 grams/day for adult women, 38 grams/day for adult men (consisting of fruits, vegetables, legumes, whole grains)

About 90% of the US population does not consume this level of dietary fiber, averaging only 15 grams/day.

"An apple a day keeps the doctor away" with its 4.4 gm of fiber. You will do better with a pear (5.5gm), or half of an avocado (6.75gm) or best of all 1 cup of navy beans at 19.1 grams! Adequate dietary intake as well as exercise and hydration might be all our patients need.

Have a great day on the bench!!

We do this every morning! You'll see things in a different way next time you flush!

There are different types of constipation!!

We clinicians have a real opportunity to bring comfort to our patients that present to us with constipation. We’ve been all trained to ask about stool frequency, consistency, remitting factors, diet, and exercise but we also need to inquire about the presence of pain. Pain in the belly seems to be the determining factor between Chronic Idiopathic Constipation(CIC) and Irritable Bowel Syndrome Constipation Predominant (IBS-C).

But as always before we act on any such symptom we need to check the medication list for DRUGS frequently causing constipation:
Medications that can affect the color of our stools (feces)

Opioids Calcium channel blockers
Anticholinergics Calcium carbonate
Aluminum antacids Iron supplements
Antidepressants Clonidine
Antipsychotics Sucralfate
Diuretics Cholestyramine


Chronic idiopathic constipation is frequently referred to as “functional constipation”. It is estimated that 14% (as many as 35 million) patients may suffer from this condition.
  • Chronic constipation was more common in females, in older subjects, and those of lower socioeconomic status. 58% of patients suffering from CIC are female
  • Chronic constipation has also been linked to impaired quality of life, especially among the elderly.
  • 72% of CIC patients self-treat with OTC medications, while 13% receive prescription therapy.
IRRITABLE BOWEL SYNDROME-Constipation predominant (IBS-C)
Irritable bowel syndrome is defined as abdominal pain or discomfort associated with constipation. This condition is long-lasting and keeps recurring. Patients will have hard or lumpy stools at least 25% of the time, and loose or watery stools less than 25% of the time. It is estimated that 5% (as many as 13 million) patients may suffer from IBS-C. 64% of IBS-C patients are female, and 66% are under the age of 50, therefore this seems to be a “younger woman” problem.
  • Pain is what separates IBS-C from CIC, patients will complain “it feels like a knot in my guts”. 62% will experience abdominal pain.
  • 72% of the patients are constipated, and 59% will have incomplete evacuation on bowel movements
  • 57% of IBS- C patients will self-treat with OTC medications, while 15% will receive prescription medications.
  • OTC meds most often recommended by physicians
    • 52% fiber supplements: psyllium, methylcellulose, wheat dextrin etc.
    • 32% OTC laxatives: senna, docusate, bisacodyl etc.
Next week we will begin discussions of the pharmacological treatment of constipation.

We pharmacists are frequently asked what to recommend for constipation. We all have shelves full of laxatives. For the next couple of weeks we will discuss all of the treatment options for constipation, but first we need to know if we should even recommend a self-care product.

Simply getting the bowels to move might not be adequate treatment for our IBS-C patients. Referral to a gastroenterologist is prudent when there is any type of belly pain or any appearance of blood in the stool.

Have a great day on the bench!!

February 2018

We do this every morning! You'll see things in a different way next time you flush!

The consistency of our patients stools depend on a lot of factors!!

Getting to know your innards:
How long does it take my food to digest? That depends on a lot of factors, depending on the food types we eat, and medications we might be taking to decrease our stomach acid. The pH of your stomach is 1.5 to 3.5, because your stomach excretes about 1.5 liters of gastric acid daily. Fat takes longer to leave the stomach than other foods, sometimes remaining in the stomach for up to six hours. Remember a big meal of a double burger and fries? You feel full for a very long time. Liquids take around 20-30 minutes to exit the stomach. Water and liquids do fill you up, but that effect doesn’t last very long. Complex carbohydrates break down at a slower rate than simple carbohydrates. Proteins take about 1.5 hours to leave the stomach.

Usually, most of a regular-sized meal empties from the stomach within two hours. After that it takes about 6 hours to pass through the small intestine, where bicarbonate is added to the mix to bring the pH to a more neutral 7. Your small intestine as around 22.5 feet long and about 1.5 inches wide. Food enters the large intestine, which is around 5 feet long, for more digestion and absorption of water and essential vitamins. Undigested material gets pushed toward the anus for elimination. It takes an average of 33 hours (almost 1.5 days) for foods to reach from the mouth to the anus.
Once it gets to the end, for elimination our stools can be graded for texture and even color depending on medications being taken: Bristol Stool Scale: is a scale that gastroenterologists use to “classify” our feces. Feel free to see the Bristol Stool Scale charts on-line!
  • Type 1: Separate hard lumps, nut-like in appearance
  • Type 2: Sausage-shaped, but lumpy
  • Type 3: Like a sausage but with cracks on its surface
  • Type 4: Like a sausage or snake, smooth and soft. (most normal stool)e
  • Type 5: Soft blobs with clear cut edge
  • Type 6: Fluffy pieces with ragged edges, a mushy stool
  • Type 7: Watery, no solid pieces, entirely liquid
Medications that can affect the color of our stools (feces)

Color Agents
black Iron, charcoal, bismuth (PeptoBismol)
Red or orange phenazopyridine, rifabutin, rifampin, or antacids with aluminum. Cefdinir interacts with iron in baby formulas, and breast milk
White speckled Antacids with aluminum
Yellow Alli (orlistat) or anything that inhibits fat absorption
Green Chlorophyll, iron or drugs causing diarrhea (antibiotics, laxatives)
Red or black tarry stools GI bleeding due to aspirin, NSAIDs, antiplatelet drugs, or anticoagulants
Pale stools Liver injury from hepatoxic drugs

Most of us seasoned practitioners have our own favorite stories about patients and their vivid descriptions of their bowel movements! Most often when they need a laxative they go to great lengths to describe their consistency of their stools.

When I was first licensed an elderly gentleman came to the pharmacy and asked for a good "physic". He got a blank stare from this newly minted pharmacist. I asked him what he meant, and he said "Kid I need to take a good s---t" What a lesson in vocabulary building!

I have also had patients on wax matrix potassium supplements bring in a "ghost tablet" from their stool to prove to me that the potassium I dispensed wasn't working because it did not dissolve!

For the past 36 years I remember to tell all of my potassium patients about the ghost tablets and this is a normal sighting. My question is why don't the makers of potassium wax matrix tablets make them brown in color, rather than orange (Klotrix®) or bright yellow (K-tabs®) !

Tomorrow morning when you flush the toilet, you will have a greater appreciation for your gastrointestinal tract! Next week we will start covering laxatives.

Have a great day on the bench!!

Not exactly billion dollar GI drugs... but they are still used!

Miscellaneous GI drugs to treat GERD and Ulcers.

We’ll wrap the last of the stomach drugs of the 1980’s three drugs with unique mechanisms of actions.
SUCRALFATE (Carafate®) approved Oct- 1981 Indications: indicated in the short-term (up to 8 weeks) treatment of active duodenal ulcer. Because it does not suppress acid formation or release it is minimally effective for GERD.

Mechanism: a mucosal protectant, nonabsorbable disaccharide containing sucrose and aluminum. It heals chronic ulcers without altering gastric acid or pepsin secretion or significantly buffering acid. It stimulates small-vessel formation, and granulation tissue. It binds to the injured tissue and protects it from pepsin and acid.

Warnings/precautions/adverse effects
  • Constipation, metallic taste, hypophosphatemia (with long term)
  • Compliance problems with QID administration
  • Pregnancy Category: B
Drug interactions – the aluminum salt is responsible for the impairment in the absorption of several drugs:
  • Bind tetracyclines & fluoroquinolones decreasing their absorption
  • Decreases warfarin absorption
  • Decreases digoxin & quinidine absorption
  • Decreases phenytoin absorption
  • Decrease levothyroxine absorption
Counseling points:

Sucralfate should be given on an empty stomach about half hour before meals to “coat” the lining of the stomach.

Reglan® (metoclopramide) approved Dec-1980

Indications: short term use (4-12 weeks) for GERD who fail to respond to conventional therapy. Also, used for diabetic gastroparesis. Metoclopramide (Reglan®) also used off label for improved lactation, by increasing serum prolactin. Generally used in patients with motility disorders, or if patients fail on high dose Proton Pump Inhibitors.

Mechanism: is a dopamine antagonist (blocker) that stimulates motility of upper GI tract, without stimulating gastric, biliary or pancreatic secretions. Appears to sensitize tissues to acetylcholine.

Warnings/precautions/adverse effects (Major)
  • Depression, restlessness, gynecomastia
  • Tardive dyskinesia
  • Extrapyramidal effects--Parkinson like symptoms
  • May cause drowsiness.
  • Pregnancy Category: B
Drug interactions: increases alcohol absorption rapidly absorbed in small intestine. Decreases absorption of: cimetidine, digoxin.

Patient counseling
  • Do not use for more than 12 weeks.
  • Dosed 5mg-10mg four times daily 30 minutes before meals and bedtime
  • Report any signs of tremor. A local neurologist tole me “Pete, before I check a suspected patient for Parkinson’s disease I always check the med list and look for metoclopramide”
MISOPROSTOL (Cytotec® )Approved Dec-1988 Indications: prevention of NSAID gastric ulceration, in patients at high risk for complications (over 60, debilitating disease, history of ulcers) relief of GERD, reduced gastric acid secretions.
Mechanism: has anti-secretory (inhibits gastric acid secretion) and mucosal protective properties. NSAIDs inhibit prostaglandin synthesis, a deficiency of prostaglandins within gastric mucosa may lead to diminished bicarbonate and mucus secretion, contributing to damage of gastric mucosa by NSAIDs. Misoprostol is a prostaglandin that increases bicarbonate, and mucus production, and maintains mucosal blood flow. Is also available combined with diclofenac as a single tablet (Arthrotec®)

Warnings/precautions/adverse effects
  • Abortifacient: black box warning
  • Pregnancy Category-X
  • Diarrhea, abdominal pain up to 40% (usually dose related-take with food)
  • Use Contraceptives in female patients
  • Must have negative pregnancy test in the past 2 weeks.
  • Oral and written warnings.
Drug interactions: none

Back in November we talked about the fact that Tagamet was the first billion-dollar drug. The second drug to reach the billion-dollar drug rank was Zantac.

By 1990 Zantac hit the two-billion-dollar mark. In the 1980’s there was a lot of interest in developing drugs for peptic ulcers, along with gastroesophageal reflux disease.

A lot of us believe that the proliferation of these “stomach drugs” parallels the exponential increase in restaurants and fast food! Think about that the next time you pull the omeprazole, pantoprazole, esomeprazole, lansoprazole, rabeprazole, dexlansoprazole, ranitidine, cimetidine, famotidine and others off the shelf.

Have a great day on the bench!!

Flu season is in full swing... does oseltamivir make your cash register ring???

$100.00 or more for one day of benefit... at best!

Oseltamivir (Tamiflu) has been available for treatment of the flu since 1999. It works by inhibition of neuraminidase. By binding to neuraminidase proteins, oseltamivir prevents flu viruses from spreading from infected cells to other healthy cells. Oseltamivir is a prodrug and is pharmacologically similar to zanamivir. After oral administration, oseltamivir is readily absorbed from the gastrointestinal tract and extensively converted to the active metabolite.

So far this flu season of 2018, influenza viruses have been susceptible to the neuraminidase inhibitor antiviral medications, which also includes zanamivir (Relenza®), and peramivir (Rapivab®).

Indications for use:
  • Patients two weeks of age and older, who have had flu symptoms for 2 days (48 hours) or less. Oseltamivir is effective against both influenza type A and B. Therapy should begin within 48 hours of the onset of symptoms. Oseltamivir may reduce symptoms by 1 day.
  • Prevention of influenza A and B in patients one year of age and older
Warnings/Precautions/ Adverse effects:
  • Nausea, vomiting, headache and pain.
  • Drug interactions: probenecid causes a 2-fold increase due to decreased tubular secretion.
  • CDC warning: November 13, 2006: The FDA approved a labeling supplement to include a precaution about neuropsychiatric events for Oseltamivir (Tamiflu®). Self-injury and delirium has been observed in Japan primarily among pediatric patients. Monitor pediatric patients for signs of unusual behavior.
Representative Products:

Tamiflu® (oseltamivir) 30mg, 45mg, 75mg capsules, (generics are available)
and powder for suspension 6mg/ml: 60 ml per bottle Adults: 75mg twice daily for 5 days. Children: based on body weight If younger than 1 year old: 3 mg/kg/dose twice daily If 1 year or older, dose varies by child’s weight:
  • 15 kg or less, the dose is 30 mg twice a day (suspension: 5ml BID)
  • >15.1 to 23 kg, the dose is 45 mg twice a day (susp: 7.5ml BID)
  • >23.1 to 40 kg, the dose is 60 mg twice a day (susp: 10ml BID)
  • >40 kg, the dose is 75 mg twice a day (susp: 12.5ml BID)
Patients should start the 5-day regimen as soon as possible. Take two doses the first day, no matter when the prescription is received.

The prophylaxis dose is the same as above EXCEPT all doses are given ONCE daily for 10 days. Patients need to be over 1 year of age to receive prophylaxis.

What oseltamivir doesn’t do:
  • It does not prevent bacterial infections
  • It is NOT a substitute for the annual flu vaccine
  • Of no value if started later than 48 hours after onset of symptoms.
APPROACH WHEN TAMIFLU (oseltamivir) liquid is not available: (from the Tamiflu® website) For patients who cannot swallow capsules, TAMIFLU for oral suspension is the preferred formulation.
  • When TAMIFLU for oral suspension is not available from wholesaler or the manufacturer, TAMIFLU capsules may be opened and mixed with sweetened liquids such as regular or sugar-free chocolate syrup, corn syrup, caramel topping, or light brown sugar (dissolved in water).
  • During emergency situations and when neither the oral suspension or the age-appropriate strengths of TAMIFLU capsules to mix with sweetened liquids are available, then a pharmacist may prepare an emergency supply of oral suspension from TAMIFLU 75 mg capsules.
The following chart shows how to make Tamiflu in an oral suspension of 6mg/ml

Total Volume of Prepared Oral Suspension 37.5ml 75ml 100ml 125ml 150ml
Number of Tamiflu 75mg strength
capsules (total strength)
3 capsules (225mg oseltamivir) 6 capsules (450mg oseltamivir) 8 capsules (600mg oseltamivir) 10 capsules (750mg oseltamivir) 12 capsules (900mg oseltamivir)
Amount of water 2.5ml 5ml 7ml 8ml 10ml
Volume of vehicle (Cherry Syrup (Humco);
OR Ora-sweet SF (Paddock Laboratories) OR simple syrup
34.5ml 69ml 91ml 115ml 137ml

  1. Place specific amount of water in PET or Glass bottle
  2. Separate capsules and pour powder from those capsules into bottle
  3. Gently swirl suspension to ensure adequate wetting of powder
  4. Slowly add specified amount of vehicle. Use only the vehicles listed above. Cap the bottle.
  5. Shake well for 30 seconds. Add shake well label to bottle.
  6. Stability
    1. Refrigeration: Stable for 5 weeks (35 days) when stored in a refrigerator at 2° to 8°C (36° to 46°F).
    2. Room temperature: : Stable for five days (5 days) when stored at room temperature, 25°C
  7. Counsel patient on storage, instruct to shake well, discuss dosing regimen, provide a liquid measuring device.

Remember rimantadine (Flumadine®) and amantadine (Symmetrel®)? High levels of resistance to amantadine and rimantadine persisted among circulating influenza A viruses. Adamantanes are not effective against influenza B viruses. They have not been recommended for treatment of the flu for at least 10 years.

All we have in the prescription department to combat influenza are the neuraminidase inhibitors. I have not dispensed Relenza® (zanamivir) in years. When I see many copays crashing the $100.00 mark, as many of elderly have not met their Medicare-D deductibles, we often put the medication back in stock.

When we see that oseltamavir only shortens the duration by a little over one day, and has to be started within 48 hours of onset, we can see how important influenza vaccines are!

Frequent hand washing, avoiding sick people, covering mouth and nose when sneezing are all practical tips for staying healthy this time of the year. Remember the flu virus can “live” on some surfaces for up to 24 hours. Routine cleaning of surfaces may reduce the spread of flu.

Oseltamivir with its high cost over $100 for many, the narrow window of opportunity, and limited efficacy fo shortening flu by one day, make those flu shots in October very important indeed!

Have a great day on the bench!!

Hand Holding and dry crackers can only go so far in treating hyperemesis gravidarum. Prescription treatment might be warranted

Help for Mom, when she needs it the most! Rx treatment of hyperemesis gravidarum

Last week we discussed using two rather common over the counter medications (with physician’s approval) Vitamin B-6 and Doxylamine. As discussed, this combo could be used instead of the very expensive Diclegis®. However, Diclegis is the only FDA approved drug for treatment of nausea of pregnancy.

The other prescription drugs listed below are being used off label for treatment of nausea and vomiting of pregnancy. This week we can discuss the prescription treatment of nausea of pregnancy, and the more intensive form: hyperemesis gravidarum.

I’m well aware that the FDA is phasing out the traditional pregnancy categories, but they still serve as a guide for many clinicians

Pregnancy Category Comments
Doxylamine (Unisom®) A Very safe combined with B-6
Pyridoxine (Vitamin-B6®) A First line. Alone or in combo with Doxylamine
Diclegis® 10mg/10mg (doxylamine succinate and
pyridoxine hydrochloride delayed-release tablets)
A Only FDA approved treatment for nausea of pregnancy; not for hyperemesis gravidarum
Dramamine (Dimenhydrinate)
Diphenhydramine (Benadryl)
Meclizine (Antivert/Bonine/Dramamine-II)
B Generally safe- may cause drowsiness. None are considered to be teratogenic
Dolasetron (Anzemet®)
Granisetron (Kytril®)
Ondansetron (Zofran)
B Limited human data- animal data suggests low risk. Zofran –most studied-
Metoclopramide (Reglan®) B Watch Mom for drug induced movement disorder. Monitor baby for extrapyramidal symptoms at birth.
Hydroxyzine (Atarax & Vistaril®) C Caused 5.8% rate major birth defects
Chlorpromazine (Thorazine®)
Perphenazine (Trilafon®)
Prochlorperazine (Compazine®)
Promethazine (Phenergan®)
C All considered as 3rd line agents. Watch for QT prolongation and extrapyramidal effects, and movement disorders.
Corticosteroids C
D-1st trim
Oral clefting first trimester exposure. Last resort.

Ondansetron (Zofran) can be dosed at 4mg every 8 hours, up to a maximum dose of 16mg/dose. Ondansetron can cause QT prolongation, and serotonin syndrome in susceptible patients. As far as the baby goes there is a slight increase in heart defects and cleft palates, but most obstetricians feel the very small risk of these side effects are superseded by all of the well-known problems of prolonged dehydration caused by nausea and vomiting.

According to the American College of Obstetrics and Gynecology (ACOG) prenatal vitamins in the preconception period may reduce the severity of nausea and vomiting in early pregnancy. Most clinicians do not recommend ginger supplements, due to lack of standardization, but will recommend ginger containing food such as lollipops, candy, and tea.

Hyperemesis may lead to dehydration, vitamin deficiency, and weight loss, therefore, adequate hydration, vitamin replacement, nutrition, and antiemetic therapy is critical to avoid maternal morbidity. Most physicians feel the risk of ondansetron therapy is worth the benefit.

So often with our pregnant population when they complain of nausea, reassuaance and dietary modifications may be all that is necessary. Basic recommendations include avoiding stimuli that trigger nausea and vomiting such as sensory stimuli to strong odors, and other sensory stimuli such. Dietary counseling about frequent small meals and avoidance of spicy or fatty foods is appropriate even though the evidence is lacking for such a recommendation.

Most obstetricians are quite comfortable using ondansetron for nausea and vomiting of pregnancy. Now that the generics are so inexpensive obstreticians seldom hesitate to use it if needed. Remember back in 2012, when Zofran 4mg was $22.00 per tablet! We have a lot of reasonable priced medications to treat these women with very safe drugs to insure a happy and healthy pregnancy.

Have a great day on the bench!!

January 2018

Help share the joy with the new mother, and make her tummy feel better too!

Treatment and Prevention of Nausea of Pregnancy

Often referred to as “morning sickness” 75-80% of pregnant patients complain of morning or evening nausea. The peak time for morning sickness is in the first trimester between weeks 5-12 of pregnancy. Most women experience this discomfort, and by adjusting diet or routines, have minimal difficulty as resolution occurs at the beginning of the second trimester.

Hyperemesis gravidarum – the worst kind of morning sickness: 15% of pregnancies experience nausea and vomiting until delivery. Persistent vomiting may cause weight loss, dehydration, starvation ketosis, hypochloremic alkalosis and hypokalemia. This severe vomiting might also lead to transient elevation of liver enzymes.

The exact cause of nausea and vomiting during pregnancy is unknown. However, it is believed to be caused by a rapidly rising blood level of human chorionic gonadotropin (HCG), which is produced in the placenta. High levels of HCG is most common with multiple gestations. High-fat diets and Helicobacter pylori infection also contributes to the incidence and severity of hyperemesis gravidarum. Helicobacter pylori, the bacteria that causes stomach ulcers in the general population, is seen in 90% of the patients with hyperemesis gravidarum.

  • Reassurance and dietary advice is all that is required in most instances.
  • Best to hospitalize patient in private room with bed rest.
  • The hospitalized patient should not eat or drink (NPO) for 48 hours, electrolyte balance and hydration should be maintained by parenteral nutrition.
  • Place patient on “dry diet” plus clear liquids 1 hour after eating.
  • Get plenty of rest.
  • Avoid smells that are bothersome.
  • Eat five or six small meals each day instead of three large meals.
  • Eat small snacks high in protein (such as a glass of milk or a cup of yogurt) throughout the day.
  • Avoid spicy foods and fatty foods.
First line (always weigh risks versus benefits). Most over-the counter products do carry pregnancy warnings, so it is safest to use these products on a physician’s recommendation.

  • Vitamin-B-6 (pyridoxine) 10-25mg every six hours. Most often dosed at night before bed, then additional doses in the morning and in the late afternoon, IF NEEDED
  • Doxylamine (Unisom®) since 25mg is the lowest dose available in the United States, it is reasonable to use 12.5 to 25mg along with the dose of pyridoxine at bedtime, then in the morning and late afternoon if needed. Just make sure the patient is buying the “Sleep-tabs®” which contain doxylamine, and not SleepGels® which contain diphenhydramine.
DICLEGIS: fixed dose combination drug product (Delayed-release tablets containing 10mg doxylamine succinate and 10 mg pyridoxine hydrochloride) direct cost is nearly $700 per 100 tablets Dosage: Take two tablets daily at bedtime. The dose can be increased to a maximum recommended dose of four tablets daily one in the morning, one mid-afternoon and two at bedtime. (cost: $600.00/ 100 tablets). BONJESTA is the same combination, but each tablet contains 20mg of pyridoxine and doxylamine.

Writing this column takes me back 32 years ago, when my wife Denise was pregnant with our second daughter Elizabeth. She was the textbook case for hyperemesis gravidarum. She lost so much weight during her pregnancy, she weighed less after delivery than before she got pregnant!

Of course back in 1986, we didn't have the medications we do today to help control the nausea and vomiting, on an outpatient basis. At her check-up her obstetrician was so disturbed by her weight loss, he admitted her to the hospital, for IV fluids to re-hydrate her. After spending a few days in the hospital she came home, and was able to eat small meals. She never fully got back her appetite until delivery.

Next week we will discuss the prescription therapy for hyperemesis gravidarum. For simple cases of nausea, the pyridoxine and doxylamine may be of great benefit. Many of us seasoned pharmacists remember Bendectin® which was withdrawn by the manufacturer, as they got tired of defending this product in court.

The ingredients in Bendectin, are the same as in Diclegis, which are rated as Pregnancy Category-A: " Controlled studies show no risk or find no evidence of harm" With the physician’s approval we can easily save our patients over $500.00 per month by substituting these over-the-counter recommendations.

Have a great day on the bench!!

We'll have lots of educating to do with our patients. FDA labeling changes on fat soluble vitamins are sure to cause lots of confusion.

Hey, are you out of Vitamin D-2000? All I see out here is Vitamin-D 50!!

I was dumbfounded when our OTC manager brought back a bottle of Vitamin-D and asked what this microgram stuff is about? Don't they make Vitamin D-2000 any more??

In May 2016, the U.S. Food and Drug Administration (FDA) announced regulations that require amendments to the existing supplement facts label, which uses units and conversions based on the Recommended Daily Allowances that were established back in 1968. The new regulations will be mandatory in 2019-2020. On Sept. 29, 2017, the FDA released its proposed rule to extend the compliance dates for Supplement and Nutrition Facts Labeling. The agency said it wanted to give manufacturers more time to comply, citing concerns from stakeholders that the current deadlines would not give them enough time to do so. Some of the vitamin companies have made the labeling change, which I’m sure will cause a lot of confusion, both for patients and prescribers. Let’s hope EPIC and other electronic medical records convert soon, as the new nomenclature is appearing on our shelves!

To convert Vitamin A as retinol:
From IU to mcg: IU/3.33 = mcg

(old labeling)
(new labeling)
5000iu 1500mcg (1.5mg)
8000iu 2400mcg (2.4mg)
10,000iu 3000mcg (3mg)

To convert Vitamin A as beta-carotene:
From IU to mcg: IU/1.66 = mcg

(old labeling)
(new labeling)
25,000iu 15,000mcg (15mg)

To convert Vitamin D:
From IU to mcg: IU/40 = mcg

(old labeling)
(new labeling)
400iu 10mcg
800iu 20mcg
1000iu 25mcg
2000iu 50mcg
5000iu 125mcg
50,000iu 1250mcg= 1.25mg

To convert Vitamin E if the product label has dl-Alpha-tocopherol (blended) as the ingredient:
From IU to mg: IU * 0.9 = mg

(old labeling)
(new labeling)
30iu 27mg
100iu 90mg
200iu 180mg
400iu 360mg
800iu 720mg
1000iu 900mg

To convert Vitamin E if the product label has d-Alpha-tocopherol (pure d-alpha) as the ingredient:
From IU to mg: IU * 0.67 = mg

(old labeling)
(new labeling)
30iu 20.1mg
100iu 67mg
200iu 134mg
400iu 268mg
800iu 536mg
1000iu 670mg

I called our primary vitamin vendor, and asked why they made these label changes. She assured me those changes are being made by the FDA's insistence. I asked her if they are providing conversion charts for the pharmacies, and prescribers. She answered, "not