Taking Thalidomide for HIV-Related Oral Ulcers and Weight Loss
A Guidebook for People With AIDS
The People With AIDS Health Group
Healing Alternatives Foundation 1748 Market Street San Francisco, California 94102
(415) 626-2316 Fax: (415) 626-0451
Note: All the words in italics are explained in the glossary at the end of this page.
Thalidomide can cause serious side effects. It causes severe birth defects if taken during pregnancy. Since the drug is useful for treating ulcers in the mouth and throat, the FDA makes it available on an emergency basis for those in need. Small studies suggest that thalidomide may also help weight loss in AIDS and TB. The FDA refuses to make it available for people with AIDS fighting severe weight loss. They are afraid that the more people who take the drug, the greater the chance that someone may give birth to a baby with serious birth defects.
The PWA Health Group and Healing Alternatives believe that people with AIDS under a doctor's care can take thalidomide safely, and that the real danger is keeping a possible life-saving treatment from people who need it. People with AIDS should not be denied a drug under a doctor's care because of a 30 year-old corporate scandal. However, due to the real possibility of serious side-effects, we ask that you read this booklet carefully BEFORE deciding to take thalidomide.
Taking thalidomide during pregnancy causes severe birth defects or death to the baby. The most common birth defect caused by thalidomide is when the hands of the newborn are attached to the shoulder, and the feet are attached to the hips, a condition known as phocomelia. If you get pregnant while you are taking thalidomide, stop taking the drug and let your doctor know immediately. We know how dangerous thalidomide is, because in the 50's the drug was falsely sold as safe for pregnancy. Most women who took thalidomide when pregnant had miscarriages or stillbirths, meaning that their babies were born dead.
How thalidomide causes birth defects has only been understood recently. It appears that the drug stops blood vessels from growing into the arms or legs. The most dangerous time to take thalidomide is between the 29th and the 40th day of pregnancy. Thalidomide can hurt a baby even if you take it only once during this period. This is the first month of pregnancy -- when many women don't know for sure if they're pregnant yet.
Clearly, the plan is to not get pregnant in the first place. If there is any chance of your getting pregnant, use reliable birth control, such as the birth control pill, a diaphragm, IUD, Norplant, double up the condoms, the works -- to make sure that pregnancy does not happen while you are taking thalidomide. MEN taking thalidomide should also use condoms every time they have sex with women for the same reason.
If you do have sex without birth control, forced or otherwise, stop taking the drug immediately, and talk with your doctor.
No one knows. In fact, this has never been studied. Thalidomide breaks down into two chemicals in your blood. These chemicals cause the birth defects. They don't stay active in blood very long, so maybe thalidomide won't hurt future pregnancies. Talk about this with your doctor.
FOR INFORMATION ABOUT FREE OR CHEAP BIRTH CONTROL ANYWHERE IN THE COUNTRY,
In San Francisco call: Planned Parenthood (415) 441-5454
Thalidomide is used all over the world (including the USA) for leprosy. Its usefulness for mouth and throat sores (aphthous ulcers) has been reported for some time. Otherwise it has not been studied very much. This is now changing, because thalidomide may help:
Thalidomide may turn out to be a surprisingly useful and even life-saving drug.
Although thalidomide has been known to help with leprosy, for years no one understood why. Recent research has shown that thalidomide can lower a common inflammatory chemical in the body. This chemical is called TNF-alpha. TNF-alpha is made by your body any time something causes inflammation inside you. You need some TNF-alpha, but high amounts have been shown to make many diseases worse (see above list) and can cause rapid, uncontrollable weight loss. Thalidomide is extremely important, because it can lower TNF-alpha, without wiping it out altogether.
For years, researchers paid little attention to the fact that many people with AIDS have a hard time keeping weight on. As with later stage cancer, it was seen as a natural part of the disease. Some doctors argued differently, and argued that being skinny made the disease worse. Many researchers now agree that many (but not all) PWAs have high levels of TNF-alpha, and that this can lead to severe weight loss. By lowering TNF-alpha safely, thalidomide offers great promise for AIDS and many diseases.
What follows next is a description of the latest research about thalidomide. Share it with your doctor. We also have a list of research references. If you want to skip this data part, that's okay -- talk with us instead. But you must read: Side Effects, Dosing and How to Order Thalidomide -- in order to get thalidomide from us.
Aphthous (ap-thuss) ulcers are open sores that can happen on mucous membranes, in the mouth, throat, vagina and rectum. They are not caused by herpes or CMV. They can be large and very painful. Thalidomide has been used successfully to treat chronic aphthous ulcers for some time.
Study #1: In a small controlled study of 10 people with AIDS, 5 men took 100 mg of thalidomide a day, plus a steroid cream. Five other men used just the steroid. Results on steroid cream: 3 men didn't get better, and two men did, although slowly. The one who responded best had 350 T cells, many more than anyone else. The 3 PWAs who didn't get better switched to thalidomide. Results of taking thalidomide + steroid: 7 of the 8 men got better within 2 to 4 weeks. The 8th man stopped because of side effects. One also developed a rash after his ulcers went away. Five of the 7 who responded on thalidomide also gained 5 to 9 pounds.
Study #2: Another placebo-controlled study of 73 people (HIV status unknown) were randomly given either thalidomide (100 mg/day) or a placebo. Results: 32 of 38 people on thalidomide got better. Six of 35 people on placebo got better. Almost half of the people on thalidomide had their sores completely heal, and the rest improved, with their sores getting significantly smaller and fewer. In many cases, the ulcers came back within 20 days after stopping the drug. 50 mg twice a week was the best dose to keep the ulcers from coming back (maintenance dose). Side effects: sleepiness and constipation.
Case studies: A recent review of 25 case reports of people with AIDS suggests that thalidomide is useful, but can cause serious side effects. Doses ranged from 50 mg to 400 mg/day. In this review, 22 men and 3 women got rid of oral ulcers in two weeks. Half got rid of the ulcers permanently. Others got their ulcers back one to five months after stopping the drug. In several reports, PWAs were able to prevent the ulcers from returning with a dose of 50 mg twice a week, or 100 mg every five days. Side effects: sleepiness, neuropathy (2 people), and hypersensitivity, all of which stopped with lower doses or stopping the drug.
Case study #1: One PWA took 300 mg of thalidomide a day, and his ulcers cleared up in 3 days. After three weeks, he got a rash, and stopped taking thalidomide.
Case study #2: A PWA took 300 mg/day, and his ulcers got better quickly. He stopped taking the drug because of stomach-aches and nausea. His ulcers came back, and thalidomide again worked very well for him (300 mg/day). He switched to 100 mg/day, but then stopped because of peripheral neuropathy
Vaginal ulcers: Thalidomide has also been used to treat genital ulcers in people without AIDS, and should be useful for non-specific (not herpes or chrancroid) vaginal ulcers. Unfortunately, there are no plans to study thalidomide for vaginal ulcers.
Note: see following section for other treatments for apthous ulcers.
III -- Thalidomide for HIV-Related Weight Loss
Three small placebo-controlled studies suggest that thalidomide can help people with AIDS and tuberculosis gain weight, without adding to immune suppression. As mentioned above on page 4-5, it may do this by lowering levels of TNF-alpha, without wiping it out altogether. Also, case studies and reports from doctors treating PWAs with ulcers suggest it may reverse weight loss.
Weight loss in AIDS is not well understood, and can have many causes. There are many ways to fight weight loss, depending on the reason you're losing weight, or not gaining it back. Weight loss can be caused by: fighting an opportunistic infection, like pneumonia; an infection in your gut causing diarrhea; not eating enough; a sped up metabolism (so that even if you eat enough, your body burns it up too fast); depression; or poor absorption in your gut (so that what you eat doesn't get digested, and used by your body). There are different things to try. Work with a doctor and a nutritionist or dietician to find out what's going on in your body. Weight loss is not inevitable -- get help, and fight it.
Study #1: 30 PWAs with a six-month history of weight loss took 300 mg of thalidomide or placebo. Those taking thalidomide gained 4.5% in body weight after three weeks. (For example, if they weighed 100 pounds, they gained back 4-5 pounds in a few weeks.) The 15 PWAs on placebo gained back only 0.9% of their weight. Side effects: skin rash in a third of the PWAs on thalidomide.
Study #2: 18 PWAs who had lost 10% or more of their weight, took 400 mg of thalidomide or a placebo daily. After 12 weeks, 8 out of 9 people taking thalidomide gained weight or stabilized, compared to 2 of the 9 PWAs on placebo, a statistically significant difference. Side effects: sleepiness and skin rash.
Study #3: 30 people with tuberculosis (13 were HIV+) took 300 mg of thalidomide or placebo daily for two weeks. Taking thalidomide was significantly associated with weight gain. After that, a smaller group of participants took three more cycles of thalidomide and/or placebo, with a seven day washout period between cycles. In all cases, taking thalidomide caused significant weight gain compared to placebo.
Case studies: Only one case study of thalidomide to treat weight loss in PWAs has been published. Three PWAs with AIDS-related wasting took 100 mg of thalidomide a day, and each gained about ten pounds in three weeks. Also, weight gain in PWAs has been reported in other studies and case reports, as noted in the above section on aphthous ulcers. See following section for other treatments for weight loss.
IV -- Treating diarrhea from microsporidiosis
In a recent case study, twelve PWAs who each had diarrhea for over a year took 100 mg of thalidomide a day for three weeks. In all cases, their diarrhea got better, from an average of 6 movements to 2.8 a day. This improvement often happened within 3 days. All had been diagnosed only with microsporidiosis,and all had tried albendazole with no success. Side effects: One person developed a skin rash after 3 days, and stopped taking thalidomide. The diarrhea came back. Three others got too drowsy during the day. Two of them dropped to 50 mg per day, which still controlled the diarrhea. Another person's diarrhea came back after a week. The average weight loss before taking thalidomide was 18.5 lbs, and the average weight gain after 3 weeks was 2.6 pounds.
The authors note that they do not know why thalidomide would be such a good treatment for microsporidiosis. Not everyone with microsporidiosis in their stool gets diarrhea. TNF-alpha has recently been found in the stools of some PWAs with microsporidiosis. Perhaps high TNF-alpha is part of why microsporidiosis sometimes causes such severe diarrhea. Clearly, more research is needed.
V -- What's the best dose?
We don't know yet. Clinical trials are underway now to figure this out. For both aphthous ulcers and weight loss, most doctors are prescribing either 100 mg or 200 mg per day, to avoid allergic reactions. Current AIDS trials for ulcers and weight loss offer 200 mg/day. They used to offer 300 or 400 mg/day. At those doses, many PWAs have allergic reactions, like bad skin rashes.
VI -- Side Effects
Read this section carefully -- thalidomide can cause serious side effects in the nervous system, and can cause severe allergic reactions. You know your body best. Stop taking thalidomide if you feel like you're having a reaction, and speak to a doctor.
Most studies report that the side effects are temporary and go away when people stop taking the drug. They happen more often in people who take high doses for a long period of time. A letter to Lancet describes hypersensitivity to thalidomide by two men with AIDS who took 200 mg/day to treat ulcers. One patient became hypersensitive and required colloid infusion and hydrocortisone. Allergic reactions resolved within 24 hours. Neither patient had their ulcers come back.
Peripheral neuropathy: In the '50s, many people reported neurological effects, and some people developed permanent neuropathy. One PWA took 100 mg of thalidomide daily for 18 months, and developed permanent peripheral neuropathy. There are other case reports of temporary neuropathy in PWAs. Most doctors report that neuropathy gets better when people stop taking the drug. The good news is that so far, no one in AIDS clinical trials has gotten neuropathy. Also, there have been no cases of neuropathy among people taking thalidomide for leprosy, even among people taking it for 20 years. If you feel any tingling or numbness in your feet and hands -- stop taking the drug, and see your doctor.
Thalidomide may be a good drug to treat TB symptoms. But active TB and MAC are usually diagnosed by those same symptoms (night sweats, fever, cough, weight loss). The drug might cover up that you are developing an active case, and you could suddenly break out into a very bad case. GET CHECKED for TB and MAC BEFORE you start taking thalidomide.
VII -- Before you order thalidomide
Step A -- Make plans for birth control before taking thalidomide. If you are going to have sex while you take thalidomide, consider using another birth control method and a condom. For more information on options and where to get birth control in your area call the national Planned Parenthood at 1-800-230-PLAN, in San Francisco, call (415) 441-5454 or in New York, call 230-1111.
Step B -- Talk to your doctor if you have mouth or throat ulcers, or if you are losing weight. We can provide you with research and information about other treatments. For ulcers, consider the free FDA program. For women it may be hard to have this discussion with medical professionals. Many people link the drug's use to its early history of birth defects. It will be important to explain that the drug can only cause such problems in women who are pregnant and that pregnancy can be avoided or delayed.
Step C -- Make plans as to where you can safely store this drug. This drug must not be mistakenly taken by anyone else. If you no longer want to take it, or have to go into the hospital -- whatever- please call and we will arrange to pick it up. Keep it out of reach of children, in a safe, secure place.
Step D -- Additional counseling about birth control and side effects will be provided at the buyers' clubs. This is a chance to learn more about what to expect if you choose to take thalidomide and to discuss any worries about pregnancy or toxicities. Everyone will be counseled to use birth control, since it causes serious birth defects.
To order thalidomide from Healing Alternatives or the PWA Health Group:
Read this booklet and sign the front, indicating that you have talked over your decision to take thalidomide with a doctor, and that you promise to return any unused drug to us; Provide us with a doctor's prescription for a ten-day supply; Read and sign our standard release form, if you haven't ordered from us before. Take this drug at night before going to sleep (it's a sedative!). Let us know of any side effects, or reactions. To get another ten day supply, you will need to provide another prescription. YOU MUST RETURN ANY UNUSED DRUG TO US. Call us if it's difficult to get it back to us, and we'll make arrangements to pick it up. Thank you for your carefulness. After four weeks, please call us to discuss your experience with taking thalidomide. A detailed report will be kept on file and updated every four weeks. If side-effects occur or you think you may be pregnant, call your doctor immediately and STOP taking the drug.
Note: This is one of the most conservative drug distribution programs we have ever set up. We have done this because of public and FDA concern that this drug will lead to someone having a baby with awful birth defects. Since the problem is well known, and easily prevented, we do not think this is the case, especially if these guidelines are followed. Thank for your patience and flexibility and responsibility. You are fabulous.
The history of thalidomide has been one of the most painful experiences ever for women, parents, doctors, children and many governments. As a result, thalidomide has probably the worst reputation of any drug known. So, doctors, nurses, family members, friends, and others may be uncomfortable if you decide to take thalidomide. Aphthous ulcers and weight loss in HIV are serious conditions that must be addressed. We at the PWA Health Group and Healing Alternatives believe that women have just as much right to survive AIDS as anyone else. We know that women are not pregnant every minute of their lives, and we believe that all people with HIV and AIDS have the undeniable right to decide upon their own treatment strategies. You should be aware that you may have to explain, advocate -- and, at times, even defend -- your right to use the drug. Reading about the history of thalidomide may help with this. For women who are having sex with men taking the drug, unfortunately nothing is known about the effect of thalidomide on sperm. No birth defects have been reported in children fathered by the thousands of men who took thalidomide in the 1950s and '60s. But they have hardly been looked for. Other drugs that men have taken have caused birth defects, so using condoms makes sense.
Current medications for aphthous ulcers include treatments put directly on the sores, such as tetracycline and corticosteroids; injections of steroids into the ulcers; or taking oral steroids, like prednisone (also a corticosteroid).
Many PWAs respond well to these options. Corticosteroids are powerful. Generally, they are avoided as much as possible in AIDS. Some research suggests that they may radically speed up HIV growth. This means that you might have less T-cells in a year than if you hadn't taken the drug. BUT these drugs are powerful anti-inflammatory medicines, and can save your life in some situations. In general, be careful, even with over-the-counter creams, like hydrocortisone. Also, corticosteroids do not help with the pain of ulcers. Lidocaine can be used. One benefit of thalidomide is that the pain usually goes away very quickly. NOTE: if your ulcers are caused by herpes, prednisone can make the herpes much worse. Only a biopsy can tell if it's herpes.
Although thalidomide seems to work well for aphthous ulcers, not all researchers feel it should be the first treatment choice. A small French study found that while it worked well for ulcers in PWAs, the drug should be used sparingly due to neurological side-effects. Dr. Mike Youle, one of the researchers, wrote in Lancet that: "in view of the possibility of peripheral neuropathy and the difficulty of obtaining thalidomide, we suggest that steroids may be a first line treatment and that thalidomide should be reserved for patients who do not respond."(Lancet, 335:1591,1990)
There are many treatments for AIDS-related weight loss. The first step is trying to figure out why you are losing weight. Find a doctor and a nutritionist or dietician with a lot of experience with AIDS-related weight loss, and push them for answers. There are different causes of weight loss, and different choices to make accordingly. Some treatments work to help build muscles, such as nandrolone (decadurabolin), oxandrolone, and human growth hormone. One of these, rHGH (by Serono) has shown significant weight gain in PWAs. Other drugs lower TNF-alpha, such as ketotifen, which has also shown muscle gain in PWAs. PWAs have also benefitted from appetite boosters, like Marinol or Megace. There are treatments to help with diarrhea and poor absorption. Finally, there are new food supplements designed for PWAs, with special oils to help you gain weight, like Advera and Peptamen.
Like thalidomide, all of these have good points and possible side effects. Some may be safer for women than men, like Megace. Megace can also cause serious birth defects, and should be avoided if you're pregnant. And like most drugs, some treatments work better in some people than others.
This article was provided by PWA Health Group.