December 2018

Getting nauseated from pregnancy? Getting headache from kung pao chichen? Got kidney stones? Vitamin B-6 might be the answer!

Pyridoxine (B6)

Sources:
meat, fish, legume, dry yeast, potatoes and other starchy vegetables and non-citrus fruits. Function: as a coenzyme for a variety of essential reactions in the metabolism of certain amino & fatty acids. Vitamin B6 in coenzyme forms performs a wide variety of functions in the body and is extremely versatile, with involvement in more than 100 enzyme reactions, mostly concerned with protein metabolism

Deficiency States:
may lead to anemia, convulsions in infants, cheilosis (cracked lips), seborrhea like skin reactions and neuropathy. As with riboflavin, the deficiency state consists of rather diffuse symptoms, probably no wonder that Casimir Funk didn’t discover this B vitamin. Dialysis patients, and those deficient in other B-vitamins are more likely to express symptoms of Vitamin-B-6 deficiency. Health benefits conferred by ODA: may alleviate PMS symptoms, improves mood, decreases risk of heart disease, and stimulates immune system. Possibly decrease nausea of pregnancy.

Treatment of Nausea of Pregnancy:
Remember Bendectin? It was that combination of pyridoxine/doxylamine that was pulled from the market in the early 1980’s. Both drugs are Pregnancy Category-A, but Merrill Dow grew tired of defending claims in court. The same formulation is available as DICLEGIS: a fixed dose combination drug product (Delayed-release tablets containing 10mg doxylamine succinate and 10 mg pyridoxine hydrochloride. Diclegis 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: almost $600.00/ 100 tablets). The American Congress of Obstetrics and Gynecology (ACOG) recommends monotherapy with 10–25 mg of vitamin B6 three or four times a day to treat nausea and vomiting in pregnancy. If the patient’s condition does not improve, ACOG recommends adding doxylamine. Patients can find doxylamine under the brand name of Unisom SLEEPTABS 25mg, and have patients split in half. Make sure they are the SLEEPTABS, and not other Unisom formulations that contain diphenhydramine.

Supplement B-6 with the following drugs that DEPLETE Vitamin B-6:
  • Isoniazid- to decrease peripheral neuropathy
  • Birth Control pills
  • Long Term corticosteroid use
  • Loop diuretics
  • Phenytoin, carbamazepine
B-6 and Chinese Restaurant Syndrome:
Proper metabolism of Monosodium Glutamate (MSG) requires sufficient vitamin B6. Supplementation may eliminate symptoms which often include headache, skin flushing, and sweating.

Kidney stones:
Vitamin B6 and magnesium supplementation can prevent calcium oxalate kidney stones in patients predisposed to forming these stones

Early on in my career, we would dispense LAROBEC, which was a combination vitamin that did not contain Vitamin-B-6 due to the interaction of B-6 with oral Levodopa. It is suggested that pyridoxine accelerates systemic metabolism of levodopa, thereby decreasing availability of the amino acid to pass the blood brain barrier. Pyridoxine reduced the levels of plasma levodopa by two thirds. The combination of levodopa and carbidopa (Sinemet, Rytary) prevents the loss of levodopa effect produced by exogenous pyridoxine, so this interaction is no longer clinically significant.

When we examine the cost savings of over $600 between Diclegis® versus Vitamin B-6 and Unisom SLEEPTABS, pharmacists and prescribers can really impact the costs of health care. We do it every day behind the counter; expertise in the vitamin aisle can also present opportunities for us as well.

Have a great day on the bench!!

November 2018

Another one of Casimir Funk's vitamins... NIACIN

Niacin (Vitamin B-3)

Dietary sources: meat, fish, legumes, whole grains. Grains are supplemented with micronutrients such as thiamin, riboflavin, niacin, iron and folic acid.

Function: oxidation reduction reactions it is an essential co-enzyme for many dehydrogenases in Krebs cycle. Lipid & protein metabolism.

Deficiency states are rare, due to the presence in most of the foods we ear. Niacin deficiency causes Pellagra “translation: rough skin”. Primary symptoms involve the 3 D’s of Pellagra: Dermatitis, Diarrhea, Dementia.

Health benefits conferred by Optimal Daily Allowance (ODA) : decreases cholesterol & triglycerides. Decreases risk of heart disease (?)

Adverse effects: flushing, GI upset, and may increase blood sugar levels. The “flushing” is similar to a hot flash, and is driven by prostaglandins. This flushing can be blocked by taking an Aspirin 325mg tablet one hour before the dose of niacin. Acetaminophen (Tylenol) does NOT work.

Supplemental doses: 50mg, 100mg, 250mg & 500 mg (immediate release release)
  • No Flush niacin (inositol hexaniacinate) not as effective for hyperlipidemia
  • At doses over 1 gram per day, Niacin will increase the chances of rhabdomyolisis, if a patient is currently taking a statin. Use only if benefits outweigh the risks
  • OTC-Niacin: The immediate-release niacin formulations are more likely to cause flushing, especially first dose. Long-acting niacin Slo-Niacin (long acting niacin) is more likely to cause liver problems. Don’t recommend it for hyperlipidemia.
Let’s discuss prescription Niacin extended release:
  • Niaspan® (Rx only) is an extended release prescription product that is used for hyperlipidemia, with minimal risk for liver dysfunction. Has fallen out of favor since September 2014. AIM-HIGH study: was stopped 18 months early because interim analysis showed lack of benefit of simvastatin/niacin vs simvastatin alone.
Niacin does NOT improve cardiovascular outcomes more than a statin alone when LDL is around 70 mg/dL. Adding niacin to bump up HDL makes number look better, but does not improve outcomes.

Patient Education for niacin therapy:
  • Cutaneous flushing- may be managed with Aspirin 325mg 1 hour before dose.
  • Take with food or light snack to decrease GI upset.
  • Swallow whole, with cold water.
  • Avoid sudden changes in posture. May cause dizziness.
  • Avoid alcohol and hot drinks during administration.
  • Increase blood glucose monitoring if diabetic.
  • Watch niacin content in multivitamin.
SAFETY: For every 1000 patients treated for about 4 years with a statin plus niacin ( + aspirin), about 18 more will develop diabetes and 37 more diabetics will have worse glycemic control, compared to patients on a statin alone. Knowing that hyperlipidemia and diabetes go hand-in hand, this hardly seems a good trade-off.

RECOMMENDATION: Niacin is associated with stomach upset, diarrhea, rash, muscle pain, and flushing with possibly more infections and GI bleeding. If they have low LDL and stable cardiovascular disease recommend stopping the Niacin

The latest on Niacin: Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) study showed a form of vitamin B3 (niacinamide) showed a reduction in the risk of skin cancer of 23%. The though is that niacinamide may help repair sun-damaged skin and prevent immune suppression in the skin after sun exposure.
  • Dose is 500mg BID if they have non-melanoma skin cancer. Reduces risk by 1 lesion per year. No proof of efficacy if patient does NOT have skin cancer.
  • Keep recommending proper application of sunscreen and protective clothing.
“Urban Legend”:
No scientific evidence indicates that taking niacin can alter a urine drug test result. However, readily accessible information on the Internet lists ingestion of niacin as a way to prevent detection of tetrahydracannabinol (THC), the main psychoactive ingredient of marijuana. High dose niacin, may cause liver toxicity.

As we journey through the water-soluble vitamins, lets focus on Niacin (Vitamin B-3) which is available both as an extended release prescription product, as well as over the counter in our vitamin aisles. Niacin (B-3) is one of the vitamins discovered by Casimir Funk. In the early 1900’s this condition was common in the southern United States due to diets being heavy in corn-based products. United States Surgeon General Joseph Goldberger observed the link in pellagra and orphanages and mental hospitals. In 1926 he established a diet that supplemented Brewers yeast to correct this deficiency. Pellagra can also occur in populations that are homeless, alcoholic or psychiatric patients who refuse food.

Here's a word that we don't use in our daily conversation: NIXTAMALIZATION: which is a process the ancient Aztecs and Mayans used when processing corn (maize). By cooking the corn in a lime solution, it would free up the bound niacin in the corn kernel, and allow it to be absorbed. This is how the Central America Indian populations ate a corn based diet, but didn't suffer from pellagra. Over 90% of the niacin in corn is bound up, and is not absorbed unless the corn is nixtamalized.

Have a great day on the bench!!

Riboflavin does more than turn your pee neon yellow!

Vitamin B-2 (Riboflavin)

Function of riboflavin:
Function: central component in a number of enzyme systems. Acts as a cofactor for various respiratory flavoproteins.

Dietary sources: milk and eggs, meats, fish, green vegetables, yeast, and enriched foods such as fortified cereals and breads. Grains have been fortified with B vitamins since the 1950’s. Folic acid was added to the grain fortification program in 1998 to prevent neural tube defects. Because riboflavin is light sensitive, milk is usually commercially sold in an opaque container.

Deficiency States: Riboflavin deficiency is extremely rare in the United States. In addition to inadequate intake, causes of riboflavin deficiency can include endocrine abnormalities (such as thyroid hormone insufficiency) and some diseases.
  • Cheilosis: (inflamed lips) cracks and sores at corners of the mouth
  • Stomatitis (inflammation of oral mucosa)
  • Ophthalmologic: Corneal Vascularization, amblyopia, dimness of vision without detectable lesions of eye
  • Sebaceous dermatosis
Potential riboflavin deficiency states:
  • Patients with anorexia nervosa
  • Very rarely, inborn errors in metabolism of riboflavin dependent enzymes
  • Maladaptive syndromes including celiac disease
  • Long term phenobarbital use may speed up oxidation of riboflavin
  • Lactose intolerant patients who avoid dairy products.
Migraine Prophylaxis:
Many neurologists will try first line for migraine prophylaxis. A few small studies found evidence of a beneficial effect of riboflavin supplements on migraine headaches in adults and children. In a randomized trial in 55 adults with migraine, 400 mg/day riboflavin reduced the frequency of migraine attacks by two per month compared to placebo. Riboflavin is available over the counter in 100mg tablets.

Drug interactions/Adverse effects: minimal. Not toxic due to limited GI absorption. This is the vitamin that turns your urine a bright yellow a couple hours after ingestion.

Riboflavin (Vitamin-B-2) was not one of Casimir Funk's discoveries, probably because of it's non-specific symptoms in a state of deficiency. Although most of our patients get adequate riboflavin intake from their diet, we dispense a fair amount or riboflavin.

Most of our neurologists will start a patient on riboflavin (200mg-400mg/day) along with magnesium oxide 400mg twice a day. In high doses the magnesium can cause diarrhea. Due to limited gastrointestinal absorption of riboflavin excessive doses rarely cause harm.

Have a great day on the bench!!

Thiamine: necessary for select groups of patients.

Vitamin B-1 (Thiamine) (also spelled “thiamin”)

Function of Thiamine:
Function: precursor for thiamine pyrophosphate, which is a coenzyme required for carbohydrate oxidation. Thiamine plays a role in nerve conduction.

Deficiency States:
Also associated with malabsorption, dialysis, and protein-calorie under nutrition. In addition to insufficient intakes of thiamine from the diet, the causes of thiamine deficiency include lower absorption or higher excretion rates than normal due, for example, to certain conditions (such as alcohol dependence or HIV/AIDS) or use of some medications
  • Dry beriberi: nervous system deficiency resulting in a degenerating neuropathy characterized by neuritis, paralysis, and atrophy of muscle. Some patients develop “Wrist drop” and marked wasting of lower extremities. Accompanied by low calorie intake and inactivity. Heavy alcohol intake may cause Wernicke’ encephalopathy & Korsakoff’s psychosis.
  • Wet beriberi: involves cardiovascular system, resulting in edema, partly due to myocardial insufficiency, palpitations, tachycardia, and abnormal EKG. Accompanied by severe physical exertion, and high carbohydrate intake. Has marked peripheral vasodilation.
Alcoholics:
Most thiamine deficiencies in the US are due to alcoholism. Chronic alcohol use disorders appear to be the most common cause of thiamine deficiency. Up to 80% of people with chronic alcoholism develop thiamine deficiency because ethanol reduces gastrointestinal absorption of thiamine, thiamine stores in the liver, and thiamine phosphorylation.

People with alcoholism tend to have poor nutritional intake and therefore inadequate intakes of essential nutrients, including thiamine. Wernicke-Korsakoff syndrome is one of the most severe neuropsychiatric sequelae of alcohol abuse. The “triad of Wernicke” symptoms are: encephalopathy, oculomotor dysfunction and gait ataxia. All patients with alcohol abuse should be supplemented with thiamine.

Other patient groups prone to thiamine deficiency:
  • Patients with HIV/AIDS
  • People with Type-1 and Type-2 diabetes have 75% less thiamine levels (increase renal clearance)
  • People with gastric bypass surgery
  • Furosemide (Lasix®) increases the clearance of thiamine from the kidneys leading to deficiency.
  • Other intake deficiencies: dieting, starvation hyperemesis of pregnancy
How much Thiamine should I recommend?
Dosing of Thiamine (Vitamin B-1):
  • Dietary requirements for thiamine are only 1 to 2 mg daily, absorption and utilization of thiamine are incomplete, and some patients have genetically determined requirements for much larger dose. Most over the counter once daily vitamins contain 1.5 mg of thiamine.
  • Most patients are started on IV thiamine in the hospital.
  • After discharge daily oral administration of 100 mg of thiamine (Vitamin B-1), is recommended until the patient is no longer at risk.


Thiamine is the first vitamin we will study that Casimir Funk discovered. Funk experimented with extracts made from the dark outer coating of rice that was removed during polishing. He found that there was a substance within that coating that cured beriberi.

He experimented with pigeons by feeding them polished rice (rice without the hulls). The pigeons got sick and showed signs of beri-beri. When Funk fed them an extract from the rice hulls, he reversed the beri-beri. Knowing that the pigeons were given adequate protein he knew it was not a protein deficiency. In 1936 Dr Funk was able to elucidate the structure of thiamine.

Three more of Funk's vitamins left to study!

Have a great day on the bench!!

Out in the vitamin aisle are a LOT of questions, and our patients are counting on our expertise!

Last week we covered the regulation of vitamins, this week as we continue “Vitamin Boot camp” we will do an overview of these amazing compounds that sit out front on the shelves of our stores. The first question we will answer is “what does a vitamin do?” Vitamins in general work in the body by 3 different mechanisms:

Who takes them:
  1. Coenzymes: Most water soluble vitamins are co¬enzymes. Remember in biology we learned that an enzyme is a catalyst for biochemical reactions. Co-enzymes are non-protein compounds that are necessary for the functioning of an enzyme.
  2. Antioxidants (Vitamin A, C & E)- are enzymes or other organic substances, that are capable of counteracting the damaging effects of oxidation in animal tissue. They protect tissues from damage by “free radicals”
  3. Hormones (Vitamin A, D, K are hormones) A hormone by definition is internally secreted compound, that affect the functions of specifically receptive organs or tissues when transported to them by the body fluids.
The next question becomes; how much should I recommend for a patient?
  1. RDA: (Recommended Daily Allowance) is the level of intake of essential nutrients that are considered adequate to meet the known nutritional needs of practically all healthy patients.
  2. The DRI (Dietary Reference Intake) also include other reference values such as the Estimated Average Requirement (EAR) , and Adequate Intake (AI). The RDA, EAR, and AI all define nutritional intake adequacy. These are all for healthy individuals.
  3. The Dietary Reference Intakes (DRI) also includes the tolerable upper intake level of vitamins (UL). The UL is defined as the highest level of intake of a nutrient that will not pose risk of adverse health effects to most individuals in the general population.
Vitamin deficiencies… not so much in America, in the USA will see syndromes of vitamin excess rather than deficiency, especially with vitamins A, D, B-6. Vitamin deficiency is usually insidious in nature, with rather non-specific symptoms. Therefore, a physical exam is rarely helpful in diagnosis. Most characteristic physical findings are seen late in the course of the syndrome. For example, swelling of the tongue (glossitis) and dry scaling and cracking of the lips (cheilosis) are seen with deficiencies in many of the “B” vitamins. These abnormalities suggest a nutritional deficiency, but NOT for a specific nutrient.

The following chart is the MDR and dietary sources for the vitamins.

VITAMIN MDR-adults Dietary Sources
Thiamine (vitamin B1) 1.2mg/day Peas, pork, legumes, whole grains
Riboflavin (vitamin B2) 1.1-1.3mg/day Liver, eggs, dark greens, whole grains
Niacin (vitamin B3) 14-16mg/day Liver, fish, poultry, meat, whole grains
Pantothenic acid (vitamin B5) 5mg/day liver, kidney, meats, egg yolk, whole grains, and legumes.
Pyridoxine (vitamin B6) 1.3mg/day Pork, meats, whole grains, greens.
Biotin (vitamin B7) 30mg/day liver, kidney, egg yolk, milk, most fresh vegetables, grains
Folic acid (vitamin B9) 400mcg/day Liver, meats, fish, whole grains, legumes citrus
Cobalamin (vitamin B12) 2.4mcg/day meats, liver, kidney, fish, eggs, milk and milk products, oysters, shellfish
Ascorbic acid (vitamin C) 75-90mg/day Plant foods; citrus is highest
Vitamin-A 3000iu (men)
2300iu (women)
fish liver oils, egg yolks, green leafy & yellow vegetables
Vitamin-D 600iu fish liver oils, egg yolk, fortified milk, synthesized in skin exposed to UV light
Vitamin-E 22.5iu Vegetable oils, wheat germ, leafy vegetables, egg yolk, margarine, legumes
Vitamin K 120mcg leafy vegetables, vegetable oils, liver, & synthesis by intestinal flora


Casimir Funk (1884-1967), a Polish biochemist who is credited with formulating the concept of vital amines, which today we call “vitamins”, and matching them to their deficiency disorders. In 1912 Dr. Funk wrote a book postulating that the diseases of beriberi, scurvy, pellagra, and rickets could be prevented with “vitamines”. He realized that poor nutrition, specifically white rice, lead to disease states which could be manage with appropriate nutrition, such as brown rice.

He is considered the Godfather of the vitamin movement. We have sections in our drug stores that are there due to the efforts of this little recognized researcher, who never received the Nobel prize. Dr Funk elucidated the causes, and therefore the management of four disease states, and was never appropriately honored for his efforts.

Have a great day on the bench!!

Hey doc? Which one of these vitamins should I take??

Vitamins--does everyone need them?

Who takes them:
  • More than one-half of Americans take multiple vitamins either single entity or multivitamins
  • 70% of adults over the age of 65 report taking a vitamin or mineral supplement.
  • Total spent is $12 billion per year.
  • About one in four young children takes an MVM.
  • Adolescents are least likely to take them.
Who regulates them:
The FDA loosely regulates dietary supplements, under the Dietary Supplement Health and Education Act of 1994 (DSHEA ’94).
In June 2007, FDA established dietary supplement "current Good Manufacturing Practice" (cGMP) regulations requiring that manufacturers evaluate their products through testing identity, purity, strength, and composition. Dietary supplementary are: vitamins, minerals, other botanicals, amino acids, enzymes, organ tissues, glandular, and metabolites. These dietary supplements fall under the category of "foods" and not "drugs".

They do NOT need FDA approval before marketing nor do they need to be registered with the FDA before being produced or sold. The manufacturer does not have to prove that the supplement is effective, unlike for drugs. The manufacturer can say that the product addresses a nutrient deficiency, supports health, or reduces the risk of developing a health problem, if that is true. If the manufacturer does make a claim, it must be followed by the statement “This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.”

FDA regulates the label content and health claims. Claims that can be used on food and dietary supplement labels fall into three categories: health claims, nutrient content claims, and structure/function claims. Here are some examples of permissible supplement claims:
  • “Supports a healthy immune system”
  • “Builds strong bones”
  • “Maintains bowel regularity”
  • “Decreases blood platelet stickiness”
  • “A good source of Vitamin-C”
Notice no disease state is mentioned, such as “prevents osteoporosis”, or “prevents stroke”. Burden of proof is on the FDA to prove that a supplement is Unsafe, before that product can be removed from the market. It is the responsibility of the manufacturer to ensure product safety and product efficacy.

Reporting by patients and manufacturers:
Starting December 22, 2007, any serious adverse events reported to a dietary supplement manufacturer must be reported to FDA within 15 days of the manufacturer receiving the adverse event report. Adverse drug events can also be reported directly to the FDA via the MedWatch program. https://www.fda.gov/Safety/MedWatch/default.htm

For the next couple of months, we will journey through our vitamin aisle. We are expected to have a high level of expertise with vitamins. Unfortunately, our level of training with respect to over the counter therapies taught in pharmacy school is minimal. I’ll be providing you with the therapeutic uses of each vitamins, as well as uses for vitamins as therapeutic agents. We will also focus on vitamin depletion caused by the prescription products we commonly dispense. I’m not a “vitamin nut” I believe appropriately recommended vitamins are of great value to our patients. Next week we can discuss “at risk” populations and therapeutic dosing of vitamins and supplements.

Good resource to read:
https://www.hopkinsmedicine.org/health/healthy_aging/healthy_body/is-there-really-any-benefit-to-multivitamins

Have a great day on the bench!!

October 2018

SERMS- very specific targets in the woman's body.

As we move through the month of October, we are discussing women’s health issues. The first three units we discussed breast cancer. Last week we discussed raloxifene and tamoxifen, which are SERMS (selective estrogen receptor modifiers). Estrogen receptors are present throughout the body. SERMs act as agonists or antagonists on various estrogen tissue receptors, including breast, bone, endometrium, hypothalamus and coagulation system. We will discuss in detail the three other SERMS, not associated with breast cancer prevention.
  • Nolvadex® (tamoxifen): (BREAST CANCER PREVENTION)is considered first line therapy of estrogen receptor positive breast cancer. Both for pre-menopausal and post-menopausal women. (No effect on vaginal tissue)
  • Evista® (raloxifene): (BREAST CANCER PREVENTION/OSTEOPOROSIS) is for reduction in risk of invasive breast cancer in postmenopausal women with osteoporosis OR if at high risk for invasive breast cancer. (No effect on vaginal tissue)
Osphena (ospemifene) (DYSPAREUNIA) 60mg tablets
Dose: take (1) tablet daily
Mechanism: estrogen agonist on vaginal tissue. Minimal effect in uterine tissue and serves as an estrogen antagonist in breast tissue. Ospemifene may have a positive effect on bone tissue. Up to 45% of postmenopausal women can experience vulvovaginal atrophy due to estrogen loss.
Indications: approved by the FDA to treat moderate to severe dyspareunia (painful intercourse), due to estrogen deficiency of menopause.
Watch for: May make hot flashes worse. Scan for CYP4503A4 interactions
NOTES: expect about 45% of postmenopausal women to experience vulvovaginal atrophy (VVA) due to declining estrogen levels. Symptoms of VVA may include dryness, itching, irritation, and dyspareunia. Diagnosis of VVA is based on symptoms as well as various laboratory findings. Vaginal lubrication decreases and vaginal pH increases. One of the best indicators of VVA is a pH of 5 or higher. On a cellular level, increases in the number of parabasal cells are seen as well as a decrease in the superficial cell layer.
USE: being promoted for its estrogenic effect on vaginal symptoms.

Duavee®: (conjugated estrogens/ bazedoxifene) (MENOPAUSAL SYMPTOMS)
Use: moderate to severe hot flashes and preventing osteoporosis. Estrogen is used for menopausal symptoms & osteoporosis. Bazedoxifene (SERM) is added to inhibit estrogen's endometrial effects (instead a progestin). Must have intact uterus, because SERM reduces risk of endometrial hyperplasia.
BEST USE: women who want to use estrogen for menopausal symptoms but need an alternative to a progestin.

Clomifene (Clomid):
(FERTILITY) is a nonsteroidal estrogen receptor modulator (SERM). It inhibits the negative feedback response on the hypothalamus by bonding to estrogen receptors. This causes an increase in release of FSH (follicle stimulating hormone) and LH (luteinizing hormone). This promotes follicular growth and maturation. Enhancement of the natural hypothalmic-pituitary-ovarian axis is the primary mechanism of action.
Dosage: 50mg daily beginning day 5 of the cycle.

The first SERM available was (Clomid (Clomifene) which was first approved in 1967. Clomid was the first ever drug to "enhance" fertility. It increases the odds of pregnancy from 1.3% to 5.5% per cycle.

Nolvadex (tamoxifen) was released in 1977 for prevention of breast cancer. It wasn't until 1997 when another SERM became available, Evista (Raloxifene) for osteoporosis. Both Duavee (bazedoxifene) and Osphena (ospemifene) were released in 2013.

Have a great day on the bench!!

Breast Cancer Prevention medications available in the community pharmacy

For the month of October our focus is on breast cancer its diagnosis and prevention. This week we discuss our role as community pharmacists in the treatment with drug therapy. Here is a brief review of the two main classes of drug therapy, along with counseling points for those therapies.

Role of Anti-Estrogens: (SELECTIVE ESTROGEN RECEPTOR MODULATORS)

For breast cancer that is estrogen receptor positive, ANTI-Estrogens are the mainstay of treatment. Antiestrogens bind to estrogen receptors and prevent receptor mediated gene transcription, and are therefore used to block the effect of estrogen on the end target. 70-75% of Breast cancer tumors are estrogen receptor positive.

Nolvadex® (tamoxifen): available as tablets 10 & 20mg is an estrogen antagonist, structurally related to the synthetic estrogen diethylstilbestrol (DES) and is considered first line therapy of estrogen receptor positive breast cancer. Tamoxifen is the only “anti-estrogen” that can be used for BOTH pre-menopausal and post-menopausal women.

Side effects include: hot flashes, nausea, skin rash, vaginal bleeding, hypercalcemia, increased bone pain if tumor has metastasized to the bone. Thrombotic events (PE and DVT) cataract formation, uterine cancer.

Dosage: Breast cancer patients: 20-40mg daily (divide dose if more than 20mg) High risk women: use 20mg daily for 5 years.

Evista® (raloxifene) Available as tablets: 60mg
Dosage: 60mg once daily
Indications: Reduction in risk of invasive breast cancer in postmenopausal women with Osteoporosis OR if at high risk for invasive breast cancer.

Adverse effects: Venous thromboembolic potential. (PE, DVT, stroke). May cause hot flashes, muscle aches & pains.

Mechanism: binds to estrogen receptors. Binding results in activating some and blocking other pathways. Effects on bone similar to estrogen therapy. However, it acts as an antagonist on receptors in the breast and endometrium.

Efficacy: seems to be less effective than Tamoxifen for breast cancer treatment.

ROLE of Aromatase Inhibitors for prevention of Breast Cancer
In postmenopausal women and women whose ovaries have been removed, the main source of estrogen is derived from the peripheral conversion of androstenedione produced by the adrenal gland into the female hormones estrone and estradiol. This conversion requires the aromatase enzyme, which also catalyzes the conversion of androgens to estrogens in the ovary of pre-menopausal women and in extra-glandular tissue, including the breast itself, in post-menopausal women. Aromatase inhibitors effectively reduce the levels of circulating estrogens. Indicated only for post-menopausal women.

Side effects: hot flashes, infrequent vaginal bleeding, do not predispose to endometrial cancer. All these drugs are available generically and are rather inexpensive therapies.
  • Arimidex® (anastrozole) available as 1mg tablets dosed once daily.
  • Femara® (letrozole) available as 2.5mg tables dosed once daily.
  • Aromasin® (exemestane) available as 25mg tablets dosed once daily after a meal
Counseling points for breast cancer during drug treament:
  • Drug therapy is used following “adjuvant therapy” which consists of surgery & radiation to “clean up” cancer cells that may have spread beyond breast
  • Goal of hormonal therapy is block estrogen’s growth promoting effect. Continue anti-estrogen therapy for 5 years—patient adherence is paramount!
  • Tamoxifen and aromatase inhibitors are first line. Remember that only tamoxifen can be used in pre-menopausal women.
  • Hot flashes are most common side effect.
Aromatase inhibitors cause less hot flashes that Tamoxifen. SSRI/SNRI’s may be of benefit: Effexor® (venlafaxine) & Celexa® (citalopram) are best choices.

Avoid Prozac® (fluoxetine), Cymbalta® (duloxetine), Wellbutrin® (bupropion) & especially Paxil® (paroxetine) because they decrease formation of active metabolite of tamoxifen, decreasing efficacy of tamoxifen.
  • Teach patients symptoms of venous thromboembolism (tamoxifen side effect):
    • Shortness of breath
    • Chest pains worsen with breathing or coughing.
    • Coughing up blood
    • Pain, tenderness, swelling, warmth, redness in one leg
  • Aromatase inhibitors may cause significant bone loss. Osteoporosis and fractures have been reported. Treat accordingly- drugs like Alendronate (Fosamax®) are a good choice.
We pharmacists should always be preaching adherence for all medications, be it for an antibiotic for a urinary tract infection, or for Type-2 diabetes medications.Adherence for these drugs for the prevention of breast cancer are critical indeed. According to a study women on tamoxifen with an adherence rate of less than 80% (determined by prescription records) had an increased risk of mortality at a median duration of 2.4 years. Adherence makes a huge difference for the breast cancer prevention with tamoxifen or the aromatase inhibitors.

Missing just 6 doses a month can be cause a significant rise in mortality. Recommend any of the adherence apps on a patients phone, set an alarm, and recommend using a plastic pill box to improve adherence. I also recommend enrolling any of these breast cancer patients in your pharmacy's medication synchronization program.

Have a great day on the bench!!

More than wearing a pink ribbon... share this information with your patients (guys too!)

Prevention--Mammograms save lives The newest recommendations from the American Cancer Society recommends all women should begin having yearly mammograms at age 45 and can change to having mammograms every other year beginning at age 55. Women should talk to their health professional if they have any symptoms or changes in their breasts, or if breast cancer runs in their family. Some patients as young as 40 years of age can begin annual mammograms.

Breast Self-Exams- a smaller role in decection
Breast self-exam (BSE) is an option for women starting in their 20s. Women should be told about the benefits and limitations of BSE. Women should report any breast changes to their health professional right away. Benefits of breast exam is minimal whether performed by a health care provider or the patient. Research has shown that BSE plays a small role in finding breast cancer compared with finding a breast lump by chance or simply being aware of what is normal for each woman. Some women feel very comfortable doing BSE regularly (usually monthly after their period) which involves a systematic step-by-step approach to examining the look and feel of one’s breasts. Other women are more comfortable simply feeling their breasts in a less systematic approach, such as while showering or getting dressed or doing an occasional thorough exam. Sometimes, women are so concerned about “doing it right” that they become stressed over the technique. Doing BSE regularly is one way for women to know how their breasts normally look and feel and to notice any changes. The goal, with or without BSE, is to report any breast changes to a doctor or nurse right away. Bottom line: The American Cancer Society does not recommend clinical breast examination (CBE) for breast cancer screening among average-risk women at any age. (source JAMA)

Common Types of Breast Cancer
Ductal carcinoma. The most common kind of breast cancer. It begins in the cells that line the milk ducts in the breast, also called the lining of the breast ducts. Ductal carcinoma in situ (DCIS). The abnormal cancer cells are only in the lining of the milk ducts and have not spread to other tissues in the breast. Has a higher risk of subsequent invasive cancer. Invasive ductal carcinoma. The abnormal cancer cells break through the ducts and spread into other parts of the breast tissue. Invasive cancer cells can also spread to other parts of the body. Lobular carcinoma. In this kind of breast cancer, the cancer cells begin in the lobes, or lobules, of the breast. Lobules are the glands that make milk. Lobular carcinoma in situ (LCIS). The cancer cells are found only in the breast lobules. Lobular carcinoma in situ, or LCIS, does not spread to other tissues. Invasive lobular carcinoma. Cancer cells spread from the lobules to the breast tissues that are close by. These invasive cancer cells can also spread to other parts of the body

Reducing Risk of Breast Cancer
  • Keep a healthy weight and exercise regularly (at least four hours a week).
  • Get enough sleep.
  • Don’t drink alcohol, or limit alcoholic drinks to no more than one per day.
  • Avoid exposure to chemicals that are carcinogenic
  • Reduce exposure to radiation during medical tests like mammograms, X-rays, CT scans, and PET scans.
  • Discuss with prescriber about hormone replacement therapy or oral contraceptives and the risks associated with therapy. Remember for estrogen replacement… lowest possible dose for shortest period of time.
  • Breastfeeding may be protective
What about the guys? (source: American Cancer Society)
  • About 2,550 new cases of invasive breast cancer will be diagnosed in men in 2018
  • Treatment: mastectomy is indicated but follow-up with radiation or chemotherapy is not as definitive as it is for women. Most breast cancer in men is treated the same as in women.
  • About 480 men will die from breast cancer in 2018
  • Overall odds of a male getting breast cancer is 1:833
  • Overall odds of a woman getting breast cancer are 1:8
  • White males are 1/100th as likely to die of breast cancer compared to white women, while black men are 1/70th as likely as black women to die from breast cancer.
Breast cancer treatment including surgery, radiation and chemotherapy have indeed become more specialized in the 37 years I've been practicing. At one time it was the realm of the general surgeon, while today there are surgeons who specialize in breast cancer surgery and reconstruction.

Even the rural hospital in the small town of Tyrone where I live has its own breast cancer treatment center, with outstanding surgeons and radiologists. There are plenty of resources for our female (and male!) population in detection, prevention and treatment of breast cancers. It is our job as health care professionals to see that our patients are encouraged to use these available resources.

Have a great day on the bench!!

We need to do more for our female patients than just wear a pink ribbon!

Breast Cancer Basics

After skin cancer, breast cancer is most common cancer in women, causing more deaths than any malignancy other than lung cancer. The lifetime risk of developing breast cancer in women is 1 in 8 (13%). There was a 7% drop in breast cancer incidence in 2003, probably due to drop in Hormone Replacement Therapy due to publication of the Women’s Health Initiative (WHI) study in 2002. This study established that HRT increases risk of breast cancer.

Breast cancer warning signs and symptoms
  • Breast lumps: Single painless mass that feels solid. Breast pain is not usually a symptom of malignancy, but it can occur.
  • Skin changes: areas of thickening, swelling, depression, dimpling, redness, irritation or unusual appearance on the breast or underarm.
  • Veins on surface of one breast have become more prominent.
  • Nipple discharge: bloody or watery from one nipple only is cause for most concern
  • Nipple changes: turning inward, rash, changes in nipple skin texture.
  • Breast cancer develops in the breast tissue, usually in the milk ducts (ductal carcinoma) or glands (lobular carcinoma)
Factors that increase risk for breast cancer Risk factors for a 2-5 fold increase:
  • Age: 78% of women with invasive breast cancer are 50 or older
  • Inherited genetic mutations: Genes BRCA-1, BRCA-2 have a 60-85% chance of developing breast cancer.
  • Personal history: previous breast biopsy result of atypical hyperplasia increases risk 4 to 5 times
  • Women with breast cancer in one breast have a 3-4 times greater risk of developing a new cancer in the other breast, or the same breast..
  • High dose radiation the chest (Hodgkin’s disease treatment)
  • Family history: 1 first degree relative (mom, sister, and daughter) doubles risk. First degree relatives is 5 times the risk
Risk Factors for a 1.1 to 2 fold increase
  • Race (white women are more susceptible)
  • Use of estrogen
Current or recent use of HRT- risk returns to normal in 5 years after stopping hormone replacement.

Use of oral contraceptives: no increase risk if stopped greater than 10 years ago Prolonged estrogen stimulation
  • Early menstruation (less than age 12)
  • Late menopause (over age 55)
  • Pregnancy: no children, or first pregnancy after age 30.
  • Lifestyle: alcohol consumption: greater than 3 drinks per day.
  • Obesity
Breast cancer receptors:
  1. Estrogen: About 80% of breast cancers are estrogen receptor positive. Cancers grow in response to estrogen. Known as ER positive.
  2. Progesterone: About 65% of the estrogen receptor positive receptor positive breast cancers are progesterone receptor positive. Cancer grows in response to progesterone. Known as PR positive.
  3. Human epidermal growth factor receptor-2: (HER2) – is a protein which promotes the growth of cancer cells. Is not inherited from a parent. It accounts for about 20% of all breast cancers,and are the most rapid growing and aggressive cancers.
Any of these three cancers are treatable, with specific therapy directed at the receptor to help destroy the rapid growing cells.

And now for the really bad news:
Triple-Negative Breast Cancer
Between 10% and 20% of breast cancers are known as “triple negative” because they don’t have estrogen and progesterone receptors and don’t express the HER2 protein. Many breast cancers associated with the gene BRCA1 are triple negative.
  • There are currently no “targeted therapies”, so treatment includes surgery either lumpectomy or mastectomy, followed by chemotherapy or radiation. Chemotherapy is considered to be the “backbone” for TNBC therapy.
  • TNBC is more commonly diagnosed in women younger than 40 years compared with hormone-positive breast cancer. (twice the incidence in some studies versus hormone receptor positive)
  • African American women have a higher incidence than non-African American women.
  • Pre-menopausal women have a higher incidence than that of post-menopausal women
  • One study demonstrated that breast feeding women were at a lower risk for TNBC, however this study has not been duplicated.
  • Prognosis is poorer than women with other receptor positive cancers.
With October being breast cancer awareness month, let's focus on our female patients, and provide them with sound, clinical information concerning breast cancer. Breast cancer awareness should be more than just using those "Breast Cancer Awareness" prescription bags, or wearing a pink ribbon.

Let's pledge to provide our female patients with good information about breast cancer, and encourage them to get their mammograms. As pharmacists we can also do our part to encourage adherence to the medications prescribed for the treatment of the hormone positive breast cancers.

Have a great day on the bench!!

September 2018

Is it time to get out the DDT? What to do when exposed to bedbug infestation!

Bedbugs---what to do when they show up!

Treatment of a bitten patient:
  • Treatment might not be necessary, as the bites usually resolve without any intervention.
  • Oral antihistamines to relieve itching
  • Prednisone, at doses of 40-60mg per day seem to be of little value.
  • Topical corticosteroids seem to be effective Use mild potency such as triamcinolone 0.1% cream on the bites.
  • May have to treat secondary infections.
Prevention:
  • using a hair dryer on end seams of mattress will “chase” the bed bugs out of hiding for detection.
  • Check out hotel/motel rooms and look for bedbugs or their feces before climbing into bed. Be sure to check out the mattress cords and crevices in box springs.
  • Placement of luggage on a luggage rack or away from the bed or upholstered furniture while traveling. Some sources recommend placing luggage in the bathtub, as bedbugs can’t crawl up that slippery surface.
  • Placement of worn garments in a sealed plastic bag to minimize bedbug attraction to worn clothing.
  • It’s no bargain mattress even if the bedbugs are free! Examine carefully garage sales or resale shops (especially bedding items), for bedbugs or bedbug feces prior to bringing them inside the home
  • Rid Home Lice, Bedbug and Dust mite Spray: contains Permethrin 0.5% - might be of benefit to spray areas that are not directly slept on.
Eradication of Bedbugs:
Insecticides and heat treatment are the best options. Combinations of insecticides are generally used to avoid failure due to resistance. Long-lasting residual insecticides may be necessary for heavy infestations. Heat treatment involves use of equipment to heat rooms to a lethal temperature. All stages of bedbugs can be killed at 50°C (122°F) Cold treatment can be successful in the home environment if the freezer is set to 0- degrees F. You must leave the items in the freezer at that temperature for four days

Your Friendly Exterminator says:
(January 2011) We are using Pyrethrins; Also using heat—over 120 degrees will kill bedbugs. Bedbugs are attracted to carbon dioxide (CO2). We have CO2 machines that attract bedbugs, and then get trapped in plastic traps. Note: The EPA says Some bed bug populations have become resistant to pyrethrins and pyrethroids

(August 2018):
use Alpine WSG (Dinotefuran) to treat. This is a broad spectrum insecticide. The exterminator described a huge problem in Altoona Housing projects. He spends more time in the housing projects combating infestation than in hotels. Hotels deal immediately with the problem, and keep things cleaned up afterward. Such is not the case with the residents in the housing projects. Alpine WSG (dinotefuran) is a neonicotinoids are synthetic forms of nicotine and act on the nicotinic receptors of the nervous system by causing nerves to fire continually until they fail. Because neonicotinoids use this different mechanism of action, bed bugs that are resistant to other pesticides will remain susceptible to the neonicotinoid. (source: EPA)

Permethrin spray that we use as a mosquito and tick repellent is designed for clothing and gear and lasts up to 6 weeks. We spray our hiking and gardening clothes every 6 weeks to keep the deer ticks off. Repellent should be applied outdoors and before clothing is worn; hang clothing, spray and let dry two hours (four hours in humid conditions).

We also spray our suit cases with permethrin 0.5% before packing for a trip. Make sure they are closed. Package reads “for clothing and gear” , so it is appropriate to use on our suitcases. Seems like a good idea to keep these critters from hi-jacking a ride back to Tyrone, PA ! That hotel room you just checked into is only as clean as the last guests who left!

Have a great day on the bench!!