I have discussed Tamiflu (oseltamivir) and Relenza (zanamivir) previously – see Bird Flu: Tamiflu and Relenza for Prevention and Treatment in the Articles section on our Web site, http://www.AvoidBirdFlu.com. This current article adds important information about making your supply of Tamiflu go farther in an emergency situation.

First, as I noted in my previous article, it is important to be aware of the fact that the effectiveness of Tamiflu and Relenza has been studied against circulating strains of human influenza (so called seasonal influenza), not against the bird flu virus. In a study reported in the August 2005 issue of the Journal of Infectious Diseases, Dr. Yen and others from St. Jude Children’s Research Hospital in Memphis, Tennessee found that in animal experiments eight-day regimens of Tamiflu were more effective than the suggested five-day regimen for treating infections with the H5N1 bird-flu virus.

The authors concluded that a prolonged and higher-dose oseltamivir regimen may be required for the most beneficial antiviral effect. This possibility was recently underscored when two Vietnamese (one a 13 year old girl) died of bird flu—as reported in a December 2005 issue of the New England Journal of Medicine—even after receiving treatment within the required 48 hours after the start of infection with standard doses of Tamiflu.

Let’s assume that you have one treatment course of Tamiflu (one 75 mg tablet taken twice a day for five days, for a total of 10 pills), that you either acquired on your own or that was given to you by your healthcare provider or by the government. Unfortunately you are still not home free yet, so to speak. You now may face one of two problems:

Problem # 1: If preliminary scientific studies indicating that a course of treatment of bird flu using higher doses than those currently recommended by the FDA, for more than the current recommended five days of treatment are correct—as indicated by Dr. Yen’s research—you will need more that one dose pack. In fact, the best treatment might mean taking two pills (150 mg) twice a day for eight or even ten days. That would mean that you should have FOUR dose packs (40 pills) for the treatment of one person, not just one!

Problem # 2: You have a dose pack—officially the amount need to treatment one person—but there are two people who just became infected with bird flu in your family. If you combine this problem with problem number one, you now actually need EIGHT dose packs, not just two!

What can you do? There are two possible solutions:

SOLUTION # 1: Take PROBENECID, a medicine approved for the treatment of gout, along with the Tamiflu. Probenecid interferes with the normal metabolism of Tamiflu, increasing the blood level of Tamiflu and keeping it in circulation longer—effectively doubling the amount of Tamiflu “exposure.” The precise dose is unclear. Until more scientific information becomes available, in an emergency situation, for otherwise healthy adults, I would recommend taking one 500 mg table twice daily. Probenecid is generally very safe. Nevertheless, I have included detailed information about it below.

According to information about probenecid from the National Library of Medicine’s and the National Institutes of Health’s Web site Medline Plus (available at http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202480.html):

Probenecid (proe-BEN-e-sid) is used in the treatment of chronic gout or gouty arthritis. These conditions are caused by too much uric acid in the blood. The medicine works by removing the extra uric acid from the body. Probenecid does not cure gout, but after you have been taking it for a few months it will help prevent gout attacks. This medicine will help prevent gout attacks only as long as you continue to take it.

Probenecid is also used to prevent or treat other medical problems that may occur if too much uric acid is present in the body.

Probenecid is sometimes used with certain kinds of antibiotics to make them more effective in the treatment of infections.

Probenecid is available only with your doctor's prescription, in the following dosage form (tablets):

a. Before Using This Medicine

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For probenecid, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to probenecid. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Probenecid has not been shown to cause birth defects or other problems in humans.

Breast-feeding—Probenecid has not been reported to cause problems in nursing babies.

Children—Probenecid has been tested in children 2 to 14 years of age for use together with antibiotics. It has not been shown to cause different side effects or problems than it does in adults. Studies on the effects of probenecid in patients with gout have been done only in adults. Gout is very rare in children.

Older adults—Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults. There is no specific information comparing use of probenecid in the elderly with use in other age groups.

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking probenecid, it is especially important that your health care professional know if you are taking any of the following:

• Antineoplastics (cancer medicine)—The chance of serious side effects may be increased

• Aspirin or other salicylates—These medicines may keep probenecid from working properly for treating gout, depending on the amount of aspirin or other salicylate that you take and how often you take it

• Heparin—Probenecid may increase the effects of heparin, which increases the chance of side effects

• Indomethacin (e.g., Indocin)

• Ketoprofen (e.g., Orudis)

• Methotrexate (e.g., Mexate)—Probenecid may increase the blood levels of these medicines, which increases the chance of side effects

• Medicine for infection, including tuberculosis or virus infection—Probenecid may increase the blood levels of many of these medicines. In some cases, this is a desired effect and probenecid may be used to help the other medicine work better. However, the chance of side effects is sometimes also increased

• Nitrofurantoin (e.g., Furadantin)—Probenecid may keep nitrofurantoin from working properly

• Zidovudine (e.g., AZT, Retrovir)—Probenecid increases the blood level of zidovudine and may allow lower doses of zidovudine to be used. However, the chance of side effects is also increased

Other medical problems—The presence of other medical problems may affect the use of probenecid. Make sure you tell your doctor if you have any other medical problems, especially:

• Blood disease or

• Cancer being treated by antineoplastics (cancer medicine) or radiation (x-rays) or

• Kidney disease or stones (or history of) or

• Stomach ulcer (history of)—The chance of side effects may be increased

b. Proper Use of This Medicine If probenecid upsets your stomach, it may be taken with food. If this does not work, an antacid may be taken. If stomach upset (nausea, vomiting, or loss of appetite) continues, check with your doctor.

For patients taking probenecid for gout:

• After you begin to take probenecid, gout attacks may continue to occur for a while. However, if you take this medicine regularly as directed by your doctor, the attacks will gradually become less frequent and less painful than before. After you have been taking probenecid for several months, they may stop completely.

• This medicine will help prevent gout attacks but it will not relieve an attack that has already started. Even if you take another medicine for gout attacks, continue to take this medicine also. If you have any questions about this, check with your doctor.

For patients taking probenecid for gout or to help remove uric acid from the body:

• When you first begin taking probenecid, the amount of uric acid in the kidneys is greatly increased. This may cause kidney stones or other kidney problems in some people. To help prevent this, your doctor may want you to drink at least 10 to 12 full glasses (8 ounces each) of fluids each day, or to take another medicine to make your urine less acid. It is important that you follow your doctor's instructions very carefully.

Dosing—

The dose of probenecid will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of probenecid. If your dose is different, do not change it unless your doctor tells you to do so.

• For treating gout or removing uric acid from the body:

 Adults: 250 mg (one-half of a 500-mg tablet) two times a day for about one week, then 500 mg (one tablet) two times a day for a few weeks. After this, the dose will depend on the amount of uric acid in your blood or urine. Most people need 2, 3, or 4 tablets a day, but some people may need higher doses.

 Children: It is not likely that probenecid will be needed to treat gout or to remove uric acid from the body in children. If a child needs this medicine, however, the dose would have to be determined by the doctor.

• For helping antibiotics work better:

 Adults: The amount of probenecid will depend on the condition being treated. Sometimes, only one dose of 2 tablets is needed. Other times, the dose will be 1 tablet four times a day.

 Children: The dose will have to be determined by the doctor. It depends on the child's weight, as well as on the condition being treated. Older children and teenagers may need the same amount as adults.

Missed dose—

If you are taking probenecid regularly and you miss a dose, take the missed dose as soon as possible. However, if you do not remember until it is almost time for the next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage—

To store this medicine:

• Keep out of the reach of children.

• Store away from heat and direct light.

• Do not store this medicine in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.

• Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

c. Precautions While Using This Medicine

• If you will be taking probenecid for more than a few weeks, your doctor should check your progress at regular visits.

Before you have any medical tests, tell the person in charge that you are taking this medicine. The results of some tests may be affected by probenecid.

For diabetic patients:

• Probenecid may cause false test results with copper sulfate urine sugar tests (Clinitest®), but not with glucose enzymatic urine sugar tests (Clinistix®). If you have any questions about this, check with your health care professional.

For patients taking probenecid for gout or to help remove uric acid from the body:

• Taking aspirin or other salicylates may lessen the effects of probenecid. This will depend on the dose of aspirin or other salicylate that you take, and on how often you take it. Also, drinking too much alcohol may increase the amount of uric acid in the blood and lessen the effects of this medicine. Therefore, do not take aspirin or other salicylates or drink alcoholic beverages while taking this medicine, unless you have first checked with your doctor.

d. Side Effects of This Medicine

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

The following side effects may mean that you are having an allergic reaction to this medicine. Check with your doctor immediately if any of the following side effects occur:

• Rare

Fast or irregular breathing; puffiness or swellings of the eyelids or around the eyes; shortness of breath, troubled breathing, tightness in chest, or wheezing; changes in the skin color of the face occurring together with any of the other side effects listed here; or skin rash, hives, or itching occurring together with any of the other side effects listed here

Also, check with your doctor as soon as possible if any of the following side effects occur:

• Less common

Bloody urine; difficult or painful urination ; lower back or side pain (especially if severe or sharp); skin rash, hives, or itching (occurring without other signs of an allergic reaction)

• Rare

Cloudy urine; cough or hoarseness; fast or irregular breathing; fever; pain in back and/or ribs; sores, ulcers, or white spots on lips or in mouth; sore throat and fever with or without chills; sudden decrease in the amount of urine; swelling of face, fingers, feet, and/or lower legs; swollen and/or painful glands ; unusual bleeding or bruising; unusual tiredness or weakness; yellow eyes or skin ; weight gain

Other side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, check with your doctor if any of the following side effects continue or are bothersome:

• More common

Headache; joint pain, redness, or swelling ; loss of appetite; nausea or vomiting (mild)

• Less common

Dizziness; flushing or redness of face (occurring without any signs of an allergic reaction); frequent urge to urinate; sore gums

Other side effects not listed above may also occur in some patients. If you notice any other effects, check with your doctor.

SOLUTION # 2: Unless you are a divine follower of the late Mahatma Gandhi, who used to drink his urine daily, this solution is not nearly as appealing as taking probenecid. However, it apparently would be very effective. Dr. Grattan Woodson, a specialist in internal medicine at the Druid Oaks Health Center in Decatur, Georgia, offers the following advice for emergency treatment of bird flu:* This is an advanced, potentially life-saving emergency strategy, that should only be done under medical supervision—unless none is available.

Tamiflu Re-Administration Strategy: Tamiflu is excreted unchanged almost entirely in the urine. If Tamiflu supplies are limited, as they most certainly will be [during a bird-flu pandemic], consider giving the patient two Tamiflu tablets at the same time, collect the patient’s urine and re-administer it to the patient via naso-gastric (NG) tube or orally. If managed carefully, this approach means that you can completely treat a patient with only 2 Tamiflu tablets [by re-administering the patient’s urine daily for five to 10 days].

*Woodson G: Preparing for The Coming Influenza Pandemic. Fluwikie.com. Available at: http://fluwikie.com/annex/WoodsonMonograph.htm#_Toc116746508.

About The Author

Bradford Frank M.D., M.P.H., M.B.A.

Dr. Bradford Frank graduated from the University of Colorado with a B.A. in chemistry and his M.D. degree. He completed two residencies, one in family practice and one in psychiatry. He is a clinical assistant professor at the University of Buffalo School of Medicine and Biomedical Sciences, Buffalo, New York. He has a master’s degree in public health (M.P.H.) from Yale (1992), where he studied infectious diseases, and a master’s in business administration (M.B.A.) from Northwestern University’s Kellogg School of Management (2003).

Dr. Frank has expertise in the areas of business continuity and strategic planning, emerging infectious diseases, severe acute respiratory syndrome (SARS), avian influenza (bird flu), weapons of mass destruction, terrorism, epidemiology, various public health issues, health and wellness, and wealth.

He is president of The Frank Group, a diverse group of businesses, and executive director and host of The Health and Wealth Show, an Internet radio talk show (www.TheHealthandWealthShow.com), which will be starting in February 2006.

He is the author of numerous scientific articles and several books. His latest article is A Review of Antioxidants and Alzheimer’s Disease, published in the October-December 2005 issue of Annals of Clinical Psychiatry. He is the author of Bird Flu: Overview and Economic Considerations - Special Report, and a series of DVDs about bird flu. He is the author of a series of DVDs about the 2003 SARS (severe acute respiratory syndrome) pandemic in Toronto, which includes in-depth on-camera interviews with seven doctors involved in the outbreak, and which has direct relevance to the coming bird-flu pandemic. His new book is Bird Flu: Expert Advice to Help You and Your Family Stay Safe (see www.AvoidBirdFlu.com for details).

Dr. Frank is married and has three children. He lives in upper state New York where he enjoys hiking, sailing, and skiing. He is a black belt in Tae Kwon Do. (For further information visit http://www.BradFrankMD.com.)