September 2018

Wanna sleep tight? Make sure these little guys don't hitch a ride from the hotel to your bedroom! View this email in your browser


BEDBUGS (Cimex lectularius) are wingless insects about the size of an apple seed that feed on warm blooded animals. Bedbugs are nocturnal and hide during the day. Bedbugs are associated with unsanitary conditions but may be found in the cleanest of homes, hotels, or other buildings and have occurred in all social and economic classes. Infestations most often occur where there is a high turnover of occupants, such as hotels, motels, cruise ships, dormitories, apartment complexes, and shelters.

The Care and feeding of bedbugs:
  • Bedbugs feed on a blood meal for about 10 minutes, injecting an anticoagulant. Females need a blood meal at least every 14 days to produce eggs. Females lay one to three eggs per day, and up to 500 eggs in a lifetime. Males also need a blood meal every 14 days to mate.
  • Unlike fleas or ticks, they do not live on their food source. They hide near their host, and bite during the night.
  • Adult bedbugs can live without feeding for 2 or 3 months which makes getting rid of them such a challenge. (Not like lice that are dead in 10 days without a human host)
  • Presentation: The bite reaction usually presents as a red bump (wheal) ranging in size from a few millimeters to 1 centimeter and does not usually have a red puncture mark in the middle. The bites can occur in lines or clusters of three or four.
Where to look:
Around the bed, they can be found near the piping, seams and tags of the mattress and box spring, and in cracks on the bed frame and headboard. If the room is heavily infested, you may find bed bugs:
  • In the seams of chairs and couches, between cushions, in the folds of curtains.
  • In drawer joints.
  • In electrical receptacles and appliances.
  • Under loose wall paper and wall hangings.
  • At the junction where the wall and the ceiling meet.
  • Even in the head of a screw.
The role of DDT

DDT’s history parallels closely the presence of bedbugs. DDT (dichloro-diphenyl-trichloroethane) was developed as the first of the modern synthetic insecticides in the 1940s. Initially used effectively to combat malaria, typhus, and the other insect-borne human diseases among both military and civilian populations. DDT was also effective for insect control in crop and livestock production, institutions, homes, and gardens. DDT was banned in 1972, was considered to be the first victory for the environmentalist movement.

DDT is still present in the environment
  • will accumulate in fatty tissues, and
  • can travel long distances in the upper atmosphere
  • DDT is one of 12 pesticides recommended by the World Health Organization for indoor residual spray programs.
Because of DDT use in the 1940’s, bedbugs were virtually eliminated. After the year 2001, they have made a resurgence, as the DDT has “worked out” of the environment.

Next week we will discuss Treatment and Prevention of Bedbugs.

I, Peter Kreckel of sound mind and body, bequeath this box of DDT to...

When my father-in-law passed away back in 2012, I helped my wife Denise and her sisters clean out his garage. The garage was full of "treasures" like jars of nails, nuts, bolts, tools and even a bumper off of a Corvair! I left with the grand prize that I have pictured here, a box of unopened DDT, that back in the day retailed for $1.99 for a one pound box!

I keep it in my garage, and my wife insists if a bedbug ever finds its way from a hotel into our house, she will be more than prepared to bring it to it's demise! I'm sure it will remain unopened, and when the day comes that Gretchen and her siblings clean out my garage, this family heirloom will move to the next generation!

Good night, sleep tight and thanks to the DDT in my garage, the bedbugs won't bite!!

Have a great day on the bench!!

This should be the last column that leaves you scratching!


Caused by the mite: Sarcoptes scabei . Mostly affects the interdigital & popliteal folds, axillary folds, umbilicus & scrotum. Spread by direct, prolonged, skin-to-skin contact with a person who has scabies. Transmitted through direct contact, and frequently sexual contact. Can survive off a human host 24-36 hours under normal conditions of heat and humidity. Increased humidity prolongs survival off the host.

Clinical presentation:
  • Severe itching and an inability to sleep.
  • Excoriations in the interdigital web spaces, wrists, buttocks, elbows groin & scalp.
  • Look for burrows made by the mite, and skin scrapings. Short irregular mark, 2-3 cm long and the width of a hair.
  • The diagnosis of scabies is confirmed by detecting scabies mites, eggs, or feces with microscopic examination.
Permethrin 5% (Elimite) DRUG of CHOICE available in 60 gm tubes

Warnings/Precautions / Adverse Effects
  • Pregnancy category-B
  • Not recommended if nursing.
  • Can be used in children over age 2 months.
  • Caution with asthmatics.
Patient Education
  • Thoroughly massage cream from the head to the soles of the feet. Rarely do scabies affect the heads of adults. They may infest the infants or geriatrics around the hairline.
  • Remove cream by washing off in bathtub or shower after 8 to 14 hours.
  • One application is generally curative. (30gm is sufficient for 1 adult)
  • Patients may experience itching after treatment, rarely a sign of treatment failure. Living mites after 14 days would indicate that re-treatment is necessary
Crotamiton lotion 10% and Crotamiton cream 10%
10% (Eurax®); Crotan® approved by the FDA for treatment of scabies, but due to frequent treatment failures is seldom used.

Ivermectin (Stromectol®) may be a safe and effective treatment for scabies, although not FDA-approved for scabies. Consider for patients who have failed treatment with or who cannot tolerate FDA-approved topical medications for the treatment of scabies. If used for classic scabies, two doses of oral ivermectin (200µg/kg/dose) should be taken with food, each approximately one to two weeks apart.

A patient weighing 75kg (165lbs) would take 15,000mcg or 15 mg. Dose would be five tablets as a single dose.
(SHORTCUT: weight in pounds divided by 33 equals the number of 3mg tablets of ivermectin)

Might be a good option for nursing homes, where head to toe treatment of each patient is impractical. After successful treatment, patients may continue to itch for several weeks.
  • A steroidal cream like Triamcinolone 0,1% cream will help resolve the dermatitis.
  • Short course of corticosteroids, like prednisone will also decrease itching.
  • Oral antihistamines like diphenhydramine (Benadryl) or hydroxyzine (Atarax) might be of some benefit to relieve itching.
  • If no relief of itching, recheck for reinfestation.
Worst of the worst: Crusted scabies or “Norwegian scabies” — occurs only in people with a weakened immune system (such as HIV infection, lymphoma, or other conditions). This condition may also affect older adults or those with Down syndrome. Ivermectin or permethrin 5% are used to treat this condition. Lesions appear as large, crusty red patches or bumps on the skin.

Scabies is another one of those dreaded skin conditions, that after reading this article will leave you scratching. A patient with ordinary scabies may have an average of 12 mites; however, those with crusted scabies (Norwegian scabies) may have thousands of mites. The infestation occurs at all ages, but particularly in children. It is a common public health problem in poor communities and is widespread in many underdeveloped countries.

It can spend a maximum of only 2 weeks without a human host to live upon and when doing so hides out in clothing, bed linens and sleeping bags. Called the “seven year itch” because it used to wax and wane in about seven year epidemic cycles, the little critters are no longer sticking to that schedule and have become more difficult and resistant to former treatments.

I love the shortcut for dosing the ivermectin. I can see that being very helpful if you had a large population to dose such as in a nursing home or large family.

Vince, one of the excellent Physician Assistants I work with at Dr. Gates office, tells me he is a scabies expert because of his time serving in the U.S Army. When we see that scabies thrive in close quarters and can live in sleeping bags without a human host for 14 days, our servicemen are definitely at risk.

Have a great day on the bench!!

Those sneaky little head lice are becoming resistant to over-the- counter products!

Prescription Products for Pediculosis

OVIDE® (malathion)
Mechanism: is an organophosphate cholinesterase inhibitor. Widely used as a lawn and garden insecticide. Has been on, and off the market for the past several years. Has “high” Ovicidal activity. This seems to be the “go to” product when concern of resistance to permethrins. Malathion was first registered as an insecticide in 1956. Became prescription product (Ovide®) in 1982.

Warnings/Precautions /Adverse Effects
  • Flammable!! 78% alcohol. Do not expose to flame or hairdryers or electric curlers.
  • Don’t use if under age 6. May use down to 24 months if resistance is a problem. (AAP) The safety and effectiveness of malathion lotion has not been established by well controlled trials in children less than 6 years old. Malathion is contraindicated in children younger than 2 years of age.
  • Unpleasant odor, due to sulfhydryl groups
Application Information:
  1. Avoid any open flames.
  2. Apply to dry hair, especially back of head and behind ears.
  3. Wash hands after application.
  4. Allow hair to air dry (no hairdryers!)
  5. After 8-12 hours wash hair with non-medicated shampoo
  6. Reapply in 7-9 days only if required.
ULESFIA® (benzyl alcohol lotion)

Mechanism: does not have ovicidal activity. It inhibits lice from closing their respiratory spiracles which allows the product to penetrate lice, causing them to asphyxiate. Can be used on age 6 months and older.

Application Information: As with the other topical agents, two applications of Ulesfia, separated by at least seven days are necessary to eradicate lice. May be a good choice for parents concerned with “pediculicides” NOTE: because it suffocates the lice (a physical action), less likely to develop resistance to this product. I tell my students it is like an ant becoming resistant to a sledge hammer!

NATROBA® (spinosad)

One treatment is usually needed with Natroba ® Repeat in 7 days only if live lice are seen again.

Mechanism: Spinosad causes neuronal excitation and involuntary muscle contractions in lice. After periods of excitation, the lice become paralyzed and die. Use in patients at least 6 months of age.

Dosage: Apply to dry hair. Leave on 10 minutes. Rinse thoroughly. Combing not required.

STROMECTOL (ivermectin) 3mg tablets (usual dose 200mcg/kg)

Ivermectin binds to glutamate chloride channels in nerve and muscle cells of lice. This leads to an increased permeability to chloride ions resulting in paralysis and death. Based on this mechanism, it would appear that ivermectin is not ovicidal.

Dosage: used for certain parasitic infections (off-label for scabies or lice) use 400mcg/kg. a 15kg child would take about 2 tablets. Repeat dose in 7 days to eradicate any newly hatched lice.

SKLICE (Ivermectin topical)
Can be used in patients 6 months of age and older.
Completely coat hair. Leave on 10 minutes, then rinse well. No combing needed

old brand name was Kwell®, now only as a generic. Second-line treatment.

Mechanism: neurotoxic to head lice and their eggs.
Indications: has fallen into disfavor because of potential toxicities, and its efficacy is LESS than other agents available. 45-70% ovicidal

Warnings/Precautions /Adverse Effects/Drug Interactions
  • Patient MUST weigh at least 110 pounds.
  • Do not prescribe more than 2 oz. of product
  • Do not retreat.
  • Black box warning: neurological toxicity. Has caused seizures and deaths.
  • Avoid using in infants, children, and elderly. Must weigh over 110lbs.
  • Pregnancy category-C
  • Caution if using with drugs that lower seizure threshold (theophylline, Wellbutrin, quinolones, antidepressants, meperidine, methocarbamol)
Trimethoprim-sulfamethoxazole —
Combination therapy with topical permethrin (Nix) and oral trimethoprim-sulfamethoxazole (Bactrim) may be more effective than treatment with permethrin alone. The mechanism of action of trimethoprim-sulfamethoxazole may involve the death of symbiotic bacteria in the louse gut that produce B vitamins necessary for louse survival. This combo is 92% effective compared with only 72% efficacy with permethrin alone. By itself Trimeth/sulfa was shown to be 78% effective. With risks of Stevens-John Syndrome, and allergic reactions it is best to reserve this combo for resistant cases.

Head Lice Chart

Brand name Generic Name Minimum treatment age Ovicidal? (kills nits?) Major warnings/precautions
Nix crème rinse Permethrin 1% 2 months of age and older Good activity resistance is becoming a problem
RID/ A-200 Pyrethrins/pipronyl butoxide Over 2 years of age NO Retreat in 7-9 days. Avoid if allergic to chrysanthemums or ragweed.
Ovide Malathion 0.5% Over 6 years of age.
Contraindicated if under age-2 yrs
Partially ovicidal Flammable. No hair dryers
Ulesfia Benzyl alcohol 5% Over 6 months of age NO, it suffocates live lice Retreat in 7 days
Sklice Ivermectin lotion 0.5% Over 6 months of age Prevents newly hatched nymphs from surviving. Single treatment only. No combing needed.
Natroba Spinosad 0.9% Over 6 months of age Kills live lice and unhatched eggs Nit combing not required
Lindane (Kwell) Lindane Must weigh over 110 lbs About 50% ovicidal Second line. Potent neurotoxin. (AVOID!)

Last week we covered the OTC options for Head Lice Control. Although safe and effective, resistance is becoming a problem and sometimes the need to bring out the “big guns” to take care of those pesky bugs.

Keep in mind though, a lot of treatment failures are due to inadequate environmental controls and are not so much as resistance as re-infestation. Other causes might be improper use of the products dispensed be it not completely covering the hair or not leaving the product on long enough.

I was also amazed to learn about using trimethoprim/sulfamethoxazole (Bactrim) for head lice. I have not seen it used as a treatment for head lice, but after reading the literature, it might be an option as resistance keeps popping up. When DDT was banned in the 70's there was a scramble for insecticides to replace that very potent bug killer. My favorite extreme example of drug pricing going crazy is malathion. Malathion is frequently used as an insecticide around the home and garden, in a 50% strength, while the prescription strength is 1/100% as whet we can buy in a hardware store! Of course we cant recommend the lawn/garden product for human use, but this yet another example of how ridiculous the drug prices can be!!

Have a great day on the bench!!

Same ingredient, but when dispensed as a prescription the price goes up exponentially.

August 2018

We can treat those pesky head lice without a prescription!

The first line therapy for head lice is over-the-counter...

Permethrin 1% Crème rinse (NIX®):
Made from a natural chrysanthemum extract, pyrethrins are neurotoxic to lice. Permethrin is a synthetic pyrethroid. Was first approved in 1986 by prescription and in 1990 was moved to over the counter. Is available as a 1% crème rinse, which is considered to be first line treatment for head lice. Mechanism: acts on the parasites nerve cell membrane. Resulting in paralysis of the pest. Remains on hair shaft for 14 days, despite normal shampooing. Can be used prophylactically, in “epidemics” where over 25% of the population (family, daycare, or classroom) is affected. Is 70-80% ovicidal. We are seeing an increase of resistance to permethrin. May be used for a child as young as 2 months.

Directions for Permethrin creme rinse:
  1. Wash hair first, with regular shampoo.
  2. Towel dry briskly
  3. Apply a sufficient amount of permethrin crème rinse to saturate hair and scalp (especially problem areas)
  4. Let on hair for NO longer than 10 minutes.
  5. Rinse with water
  6. May reapply in 7 days if necessary. One application is generally curative. However, Permethrin’s adherence to the hair shaft can be affected by conditioners and silicone-based additives present in almost all currently available shampoos. This may impair efficacy of the crème rinse. Many experts routinely advise re-treatment on day-9.
Piperonyl Butoxide (4%), Pyrethrum Extract (Equivalent to 0.33% Pyrethrins) (Rid®

Brand: RID® and other generics are available over the counter
Pyrethrins are naturally occurring pyrethroid extracts from the chrysanthemum flower. Pyrethrins are safe and effective when used as directed. Pyrethrins can only kill live lice, not unhatched eggs (nits). Piperonyl Butoxide/pyrethrin Lice Killing Shampoo is designed to be used on DAY ONE and then again 7 to 10 days later, but not before. To apply the shampoo, follow the directions on the package, including:
  1. Protect child's eyes—Use towels to protect child's eyes from treatment and prevent clothes from getting wet.
  2. Apply Piperonyl Butoxide/pyrethrin Lice Killing Shampoo—Apply thoroughly to DRY HAIR or other affected area. Wetting the hair dilutes the treatment making it less effective.
  3. Let set for 10 minutes—first apply behind the ears and to the back of the neck. Lice can crawl up and down the shaft of the hair very quickly, so it is important to apply the treatment from the roots to the ends of the hair. Allow product to remain on the hair (or other affected area) for 10 minutes, but no longer.
  4. PRECAUTION: A second treatment is recommended 9 to 10 days after the first treatment to kill any newly hatched lice before they can produce new eggs. Pyrethrins generally should not be used by persons who are allergic to chrysanthemums or ragweed. Piperonyl Butoxide/pyrethrin is approved for use on children 2 years of age and older.
For all lice killing shampoos: All topical pediculicides should be rinsed from the hair over a sink rather than in the shower or bath to limit skin exposure and with warm rather than hot water to minimize absorption attributable to vasodilation. Removal of nits immediately after treatment with a pediculicide is not necessary to prevent spread, because only live lice cause an infestation. Individuals may want to remove nits for aesthetic reasons or to decrease diagnostic confusion. Because none of the pediculicides are 100% ovicidal, manual removal of nits (especially the ones within ½ inch of the scalp) after treatment with any product is recommended by some.

RID LICE CONTROL SPRAY (permethrin 0.5%)
Contains permethrin 0.5% (just like the tick repellant for clothing). Spray only those garments and parts of bedding, including mattresses and furniture that cannot be either laundered or dry cleaned. Most agree that this treatment is no more effective than a thorough vacuuming with a Shop-vac. Some sources recommend against using these insecticides at all. Viable nits are unlikely to incubate and hatch at room temperatures which are cooler than a human host; if they did, the nymphs would need to find a source of blood for feeding within hours of hatching. Next week we will discuss the prescription treatment of head lice infestations, and I’ll provide a summary treatment chart.

Last week we covered the topic of head lice, and patient consultation points. This week's discussion focuses on the OTC recommendations we can use for the treatment of head lice. In this week's column are the directions, and counseling points to share with those “slightly” upset caregivers.

Probably our first step is to always reassure the very upset parent, then provide all of the counseling points to insure a successful treatment. Be sure to share last week's column with those parents who seem to be full of misinformation.

Help educate parents and schools that there's no medical reason to keep kids out of school after treatment. Explain that remaining nits or itching doesn't indicate treatment failure, only live lice do.

Have a great day on the bench!!

School opens soon--- time to "brush up" on our lice treatments!


With school around the corner, one of the biggest concerns parents have is if their child brings home some unwanted friends, those being of the six-legged variety… head lice! This week we will cover the basics of head lice and next week we can cover the pharmacological treatment.

PEDICULOSIS (LICE): Pediculosis is a skin infection caused by blood sucking lice. They are small flat wingless insects with stubby antennae and 3 pairs of legs that end in sharp curved claws.

There are 3 major types of lice:
  • Head Lice : Pediculus humanus capitis
  • Body Lice : Pediculus humanus corporis
  • Pubic Lice: Pthirus pubis (note: different species than above)
Life cycles of the human louse:
  • All lice need human warmth to survive.
  • Head and pubic lice spend their entire life cycle on the skin of human host.
  • Head & pubic lice deposit their eggs (known as nits) on hair strands, about 1/4th of an inch from the skin. Each louse develops from eggs (nits) that incubate 1 week. When the eggs hatch the nymphs appear the eggs are small and gray white.
  • Each louse survives about 1 month as a mature adult.
  • The female head louse can produce 3-6 eggs per day. Head lice nits can survive 10 days off a body.
  • Nits are easier to find than the live adults. Check around the back of the ears, and the nape of the neck (warmest parts of the body). Nits are cemented to hair shaft, unlike dandruff that can be brushed away.
Non-Pharmacological treatment of lice:
  • Change clothing daily
  • All household contacts should be inspected and treat if necessary
  • Bed linens and clothes should be washed in hottest water (130degrees or hotter), and dried on heated air cycle for at least 20 minutes to kill both the lice and nits. Dry cleaning also kills head lice and nits. Only items that have been in contact with the head of the infested person in the 48 hours before treatment should be considered for cleaning.
  • Wash hairbrushes, combs, toys in hot water (130degrees) for at least 10 minutes.
  • Stuffed animals, pillows and articles that can’t be laundered. Stuff into large trash bag, seal the bag, and hold for 2 weeks.
  • All household items, carpets, chairs & couches should be thoroughly vacuumed. OTC sprays such as A-200 or R&C spray are no more effective than vacuuming
HEAD LICE MYTHS are numerous! The following FACTS should reassure and inform patients and parents!
  • No significant difference in incidence between various socioeconomic classes or races.
  • Hygiene & hair length are NOT contributing factors.
  • Head lice do not fly or jump. They can crawl about 3 feet.
  • Head lice do NOT carry other disease. (Body lice can)
  • Head lice cannot be contracted from pets.
  • Head does NOT have to be shaved to get rid of the lice.
  • Washing head with brown soap is not effective.
  • Head lice are not related to ticks
  • Hair does NOT fall out because of infestation
  • Head lice can occur at any time of the year.
  • Females are more susceptible to head lice infestations.
  • White children are more susceptible that black children in the United States
  • Pruritus occurs as an allergic reaction to lice saliva injected during feeding
No Nit Policy…. NO WAY!!!
From the CDC website---Here’s why “no-nit” policies should be discontinued” Both the American Academy of Pediatrics (AAP) and the National Association of School Nurses (NASN) are in favor of stopping the common practice of “no-nit” policies for the following reasons:
  • Many nits are more than ¼ inch from the scalp. Such nits are usually not viable and very unlikely to hatch to become crawling lice, or may in fact be empty shells, also known as ‘casings’.
  • Nits are cemented to hair shafts and are very unlikely to be transferred successfully to other people.
  • The burden of unnecessary absenteeism to the students, families and communities far outweighs the risks associated with head lice.
  • Misdiagnosis of nits is very common during nit checks conducted by nonmedical personnel.
As we approach the end of August the school buildings that have been quiet for nearly three months are coming back to life. In Central Pennsylvania where we live, the sports page, full of football stories is the harbinger to the first day of school. Kids are getting their backpacks ready, and the first day of school of outfits are hanging in the closet.

The kids are excited, and the parents are looking forward to the first day as well. However one facet of the beginning of school is the return of the six legged critters, head lice.

Nothing upsets and frustrates parents more than when their kids bring home these unwanted inhabitants of the kids hair! I made sure that the generic permethrin creme rinse is stacked up in the front shelves of the store. I sure it wont be there for long!

In the next two weeks we will cover the over the counter lice treatments, followed by the prescription treatments for pediculosis capitis.

Have a great day on the bench!! (you can stop scratching now!)

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.