Thioacetazone

Thioacetazone (also known as thiacetazone, thiosemicarbazone, benzothiozane and amithiozone) has been used for TB treatment since the 1960s. Thioacetazone is never used alone to treat TB, because by itself it is weak and ineffective against the bacteria. It is only used as a combination with first-line TB medications, such as isoniazid and rifampicin. It is used primarily to prevent the development of bacteria that are resistant to first-line drugs, and to treat patients infected with drug-resistant TB. Thioacetazone is extremely cheap. However, it is associated with adverse patient reactions. These reactions are more severe, sometimes leading to death, in individuals co-infected with HIV. As a result, Thioacetazone is used rarely. It is prescribed for TB treatment in certain countries in Asia, Africa, and Latin America, where access to other TB medications is limited. It is unavailable for use in South Africa. Dosage (as a medication administered in combination with isoniazid) ------------------------------------------------------------------- _Adults:_ 150 mg thioacetazone + 300 mg isoniazid daily. _Children:_ - Children up to 10 kg: 50 mg of isoniazid and 25 mg of thiacetazone once a day. - Children 10 to 20 kg: 100 mg of isoniazid and 50 mg of thiacetazone once a day. - Children 20 to 30 kg: 200 mg of isoniazid and 100 mg of thiacetazone once a day. - Children 30 to 40 kg: 250 mg of isoniazid and 125 mg of thiacetazone once a day. _Notes on dosing:_ - Thioacetazone is most often administered as a combination with isoniazid, particularly during the continuation phase of long-term regimens. - A major benefit is its ability to prevent failure and relapse in patients with initially isoniazid-resistant strains. - Thioacetazone is generally used as a replacement for ethambutol in countries where access to ethambutol is restricted. There is no advantage to using thioacetazone as a replacement for ethambutol. How it works ------------ Thioacetazone is referred to as a bacteriostatic medication. A medication that is bacteriostatic does not kill bacteria, but rather stops them from reproducing. Thioacetazone is bacteriostatic even at very high concentrations. It stops TB bacteria from spreading by interfering with processes that are vital to the functioning of the cell wall in bacteria. Side Effects ------------ Some common symptoms of thioacetazone include nausea, vomiting, diarrhea, loss of appetite, skin rashes, aching joints and muscles, clumsiness or unsteadiness, and a tingling or burning sensation in the hands and feet. Some uncommon side effects are blurred vision, seizures, fever, and mood changes. Liver problems (indicated by darkening of urine and/or yellowing of skin) are rare, but more frequent in patients over the age of 50. Rare cases of exfoliative dermatitis, thrombocytopenia, agranulocytosis, and aplastic anemia have been recorded. Adverse reactions are more common and severe in HIV-positive patients, and can sometimes lead to death. There has been a significant number of cases in which Thioacetozone has led to the development of a skin condition called severe cutaneous hypersensitivity in patients co-infected with HIV. Severe cutaneous hypersensitivity, which includes a condition called Stevens-Johnson syndrome, refers to when the skin’s epidermis (outer layer) begins to separate from the dermis (inner layer). For this reason, thioacetazone should not be given to HIV positive patients. Pricing ------- Thiacetazone 50 mg and isoniazid 100 mg, 1000 tablets: R33.55 / US $4.71 (exchange rate 09/09/2011)[^drug prices] (A combination of thioacetazone and isoniazid is almost as cheap as isoniazid alone). Clinical studies and approval ----------------------------- Thioacetazone is categorized by the WHO as a Group 5 medication, only to be used when medication regimens involving drugs from Groups 1-4 are not possible. The WHO placed thioacetazone in Group 5 because, even though the drug is known to be active against TB, “its role in the treatment of DR-TB is not well established.” More studies are needed to determine whether thioacetazone is effective in the treatment of MDR / XDR TB. Thioacetazone is not recommended for patients known, or suspected, to be infected with HIV. The serious risk of adverse skin reactions, particularly in HIV co-infected patients, has been well documented. A 1991 study in Zambia monitored, over an 18 month period, the drug reactions in 237 TB-infected children receiving some combination of medications that included thioacetazone. 22 (9%) of these children developed hypersensitivity skin reactions. These reactions were seen mostly in HIV-infected children 2-4 weeks after beginning treatment. 12 of the 22 children, all of whom were HIV-positive, developed Steven Johnson syndrome. The mortality rate among these children was 91%.[^Chintu] Another study done in Tanzania in 1995 examined patients of all ages receiving TB treatment. The study determined that the frequency of death from using thioacetazone was 3.1 per 1000 patients. Over half of the adverse reactions to the medication happened within 20 days of starting the drug. The study concluded that, because the frequency of death was lower than previously thought, “improved management might allow retention of thiacetazone in the armamentarium of national tuberculosis programmes even where infection with HIV is prevalent.”[^Ipuge] When prescribing thioacetazone, it is important to keep in mind that the medication has cross-resistance with some other anti-TB drugs. Cross-resistance between two different drugs means that a patient who has an infection that is resistant to one drug will also be resistant to the other drug. Advocacy issues --------------- - Further studies are needed to determine the effectiveness of thioacetazone for the treatment of MDR / XDR TB. - The extremely low cost of thioacetazone is particularly beneficial in developing countries that do not have access to higher-cost medications. The low cost may promote compliance because patients are better able to afford their medications. - The use of thioacetazone is very controversial due to the terrible and relatively common side effects in patients co-infected with HIV. Some institutions, such as the U.S. Centers for Disease Control, suggest that the risks of the drug outweigh the benefits. MSF has suggested that thioacetazone be used only for treatment of pregnant women who are HIV-negative and need the treatment.[^Bouros] - Lowering the cost of other TB medications, such as ethambutol, would reduce the need for riskier medications such as thioacetazone. [^drug prices]: [International Drug Price Indicator Guide](http://erc.msh.org/dmpguide/resultsdetail.cfm?language=english&code=IST100T&s_year=2009&year=2009&str=50%20mg%2B100%20mg&desc=Thiacetazone%2BIsoniazid&pack=new&frm=TAB-CAP&rte=PO&class_code2=06.2.4.&supplement=&class_name=%2806.2.4.%29Antituberculosis%20medicines%3Cbr%3E "Prices") [^Chintu]: C. Chintu et al. Cutaneous hypersensitivity reactions due to t heacetazone in the treatment of tuberculosis in Zambian children infectd with HIV-I. Arch Dis Child. May 1993; 68(5): 665-668. [^Ipuge]: YA Ipuge et al. Adverse cutaneous reactions to thiacetazone for tuberculosis treatment in Tanzania. Lancet. Sep. 1995; 346(8976):657-60 [^Bouros]: Bouros, Demosthenes. Pleural Disease. CRC Press, 2004. P677.