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Diarrhea ... Again?

Treatment Options for Medication-Induced Diarrhea

July/August 2002

Let's face it. Diarrhea is not a glamorous subject to talk about. But it does occur, especially in HIV infection. It affects as many as 30-50 percent of HIV positive individuals at some point in time. Diarrhea is defined by the Centers for Disease Control and Prevention (CDC) as an average of greater than or equal to two loose or watery stools per day for one month or longer.


Why Is This Happening?

Diarrhea has many causes, including opportunistic infections (OI), diet, traditional herbs, stress, and infectious pathogens (bacteria, virus, parasite). Additionally, several medications may cause diarrhea. These include antibiotics, immunosuppressives (corticosteroids), antacids and H2 blockers (cimetidine, ranitidine, famotidine), excessive antidiarrheals, and highly active antiretroviral therapy (HAART), particularly protease inhibitors (PIs).

It is useful to find out the cause of diarrhea in order to provide effective treatment. One of the most important tests is the CD4 count, as this value shows the strength of the immune system. Generally, the lower the CD4 count (below 200 cells/mm3) the higher the chance of developing an OI. Microbiological evaluation of a stool specimen is necessary to rule out infectious pathogens (e.g., salmonella, shigella, campylobacter, C. Difficile toxin, ova and parasite, cryptosporidia, Isospora, cyclospora, microsporidia, Giardia, etc.) and fat malabsorption. This is done by providing the medical provider with a stool sample, which is then sent to a laboratory for analysis. Routine blood tests are also helpful to objectively check the severity of the diarrhea, such as electrolyte abnormalities and state of hydration. Finally, a thorough medical check-up is necessary to document diet history, medications and herbal products used currently or in the recent past.


What if I Don't Treat the Diarrhea?

It is well known that diarrhea left untreated can result in a significant increase in morbidity and mortality, reduced quality of life (QOL), and higher health care costs. Many HIV-infected individuals may have to remain indoors or near a bathroom because of the unpredictability of the diarrhea. A fear of eating may result as the diarrhea progresses, causing malnutrition, weight loss, further weakening of the immune system, infections, and depression. Diarrhea may also have a big impact on adherence to HAART, especially if the PIs are thought to cause the diarrhea.

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Treatment Options

The treatment options range from over the counter (OTC) and prescription medications to dietary changes. It is important to note that some of the remedies may work better than others and often more than one agent is necessary for maximum relief. The following information comes mainly from studies performed on small numbers of subjects and from retrospective data.

What are these agents and where can they be found?


Glutamine

Glutamine is a non-essential amino acid that is used as an energy source for certain cells. It is reduced with conditions of metabolic stress, long-lasting illness, gastrointestinal tract diseases and surgery. Reliable sources of glutamine include Baxter Healthcare and Novartis Nutrition Corporation.


Calcium

Calcium is known to act as a constipating agent, and therefore may reduce diarrhea. Calcium can be purchased OTC in various formulations, including calcium carbonate and calcium citrate.


Psyllium

Psyllium is a concentrated vegetable powder that acts as a stool bulking agent on one hand, and a laxative on the other. Side-effects include bloating and flatulence (gas). The taste of psyllium is often a complaint, so it is also available in the form of fiber bars. Psyllium is available at many grocery stores and pharmacies, in products such as Metamucil.


Oat Bran

A good source of soluble fiber, oat bran adds bulk to stool and moves the digested food quickly through the intestines. Like psyllium, it can cause bloating and flatulence. Oat bran can be purchased OTC in tablet form.


SP-303

SP-303 is found in the South American Croton lechleri plant. It has been shown to decrease stool weight and stool frequency. For many years it has been used by the people of South America for the relief of diarrhea and has been more recently studied in the treatment of HIV-associated diarrhea. An herbal product, SB Normal Stool Formula contains SP-303 and can be purchased from the website of Shaman Botanicals, San Francisco, CA (www.shamanbotanicals.com).


Pancrealipase

The combination of lipase, amylase, and protrease are the pancreatic enzymes known as pancrealipase. They reduce the fat content of stool; increasing stool consistency and decreasing stool frequency. Patients may also report a reduction in bloating, flatulence, and stomach cramps. Pancrealipase is sold both OTC and by prescription. It is important to note that the products have different amounts of enzymes and various formulations (enteric coating preferred). The products available by prescription include Ultrase MT-20, Viokase and Pancrecarb (studies of the first two are included in the table below). Side-effects of pancreatic enzymes include nausea and stomach cramps.


Medical Nutrition Therapy

Changing the diet is another way to reduce diarrhea. Certain foods and drinks may cause diarrhea and may need to be avoided. The following tips may be helpful:
  • Try peeled fresh fruit, steamed skinless vegetables, enriched white rice and bread (less insoluble fiber).

  • Try lactose-reduced milk, soy milk or rice milk. The lactose in milk and milk containing products may not be well tolerated.

  • Drink decaffeinated beverages (decaffeinated coffee and soda, herbal or decaffeinated teas).

  • Avoid fried and high fat foods (such as butter, margarine, cream sauces and cream soups).

  • Avoid alcoholic beverages.

  • Take less than 2,000 mg vitamin C per day.

  • Drink more fluids (water, sport drinks).

  • Tell your medical provider about any supplements, vitamins and minerals, or herbal products that you may be taking.

  • Meet with a Registered Dietitian.

Severe diarrhea may be linked with malnutrition. It is important that foods and beverages that are tolerable be consumed on a daily basis. For people who do not absorb food well, nutritional supplements may also be helpful to reach better nutritional status. Included in this category are "elemental" products such as Peptamen and Subdue. These products may be ordered via a prescription from your medical provider, although keep in mind that such products may or may not be covered by the health insurance carrier. For severe cases of diarrhea and associated malnutrition, alternate nutrition support may be indicated. Delivery of nutrients via tube feeding or total parenteral nutrition are such options.


Other

Preventive measures such as good hygiene (hand washing) and good food safety are important. The phrase "keep hot foods hot and cold foods cold" is a good tip to keep in mind. It is also important to check expiration dates on food labels to make sure the food is fresh (especially meat, poultry, fish and dairy products). It is best to drink bottled, boiled or filtered water and to make sure fluids are replaced in cases of severe diarrhea. Psychosocial support may also be helpful for both the affected individual and/or the caregiver. Anxiety as a result of the diarrhea may be reduced with appropriate counseling.


Final Words

Diarrhea is a common problem that occurs in many individuals with HIV. Many reasons exist for the cause of diarrhea, including OIs, diet, herbs, stress, infectious pathogens and medications. Whatever the cause, it is important to talk to your medical provider to make sure the correct steps are taken to treat the diarrhea. This article has suggested many agents that have been studied, each leading to less diarrhea. Glutamine, calcium, psyllium, oat bran, SP-303, and pancreatic enzymes may be useful to try in cases of medication-induced diarrhea. A review of diet and lifestyle behaviors by an HIV savvy registered dietitian is also crucial in the management of diarrhea. It is important to note that each tip may work differently for each person and often more than one option may need to be used for the diarrhea to go away. The main goals remain -- to maximize nutritional status, reduce weight loss, and improve quality of life while maintaining strict adherence to antiretroviral medication to effectively manage HIV.


Review of Studies Regarding the Management of PI-Induced Diarrhea
MedicationOver-the-Counter (OTC) or PrescriptionStudy DesignDoseNumber of Subjects (PI Used)Study Results
GlutamineOTCRandomized, double-blind, placebo-controlled crossover study10 gm three times daily25 (nelfinavir)Significant decrease in diarrheal severity and improved QOL (quality of life) in both treatment groups
CalciumOTCOpen-label, prospective trial500 mg twice daily15 (nelfinavir)13 (87%) reported normal stools; 15 (100%) reported decrease in symptoms
PsylliumOTCSurvey1-2 Tbsp, 1-3 times daily77 (nelfinavir)20 patients tried psyllium; 55% reported less frequent stools, 40% reported improved stool quality
Oat BranOTCOpen-label, prospective trial1,500 mg with each dose of PI medication51 (43% nelfinavir, 27% ritonavir/ saquinavir, 30% other)Frequency of diarrhea decreased from a mean grading score of two (4-7 loose stools/day) to 1.04 (<3 loose stools/day); 84% had improved symptoms
SP-303OTCRandomized, double-blind, placebo-controlled trial500 mg every six hours for four days51 (PI not specified)Reduction in stool weight and frequency compared with placebo group
Ultrase MT 20PrescriptionRetrospective trial1-2 tablets with meals and snacks26 (nelfinavir)25 patients (96%) had a decrease in # of stools per day
ViokasePrescriptionOpen-label, prospective trial325 mg55 (19 saquinavir, 36 nelfinavir)87% reported bowel control with no further diarrhea, most had relief within 12 hours


Susan Basinger, R.D. works at the Owen Clinic, University of California San Diego Healthcare. Address correspondence to smbasinger@ucsd.edu or phone (619) 543-6763. References are available upon request. (Thanks to Moira Mar-Tang for her assistance with editing this article.) This article is supported by an unrestricted educational grant from Agouron Pharmaceuticals, Inc.


Got a comment on this article? Write to us at publications@tpan.com.


  
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This article was provided by Positively Aware. It is a part of the publication Positively Aware. Visit Positively Aware's website to find out more about the publication.
 
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