Drugs for Tuberculosis
ritonavir alone or combined with other protease inhibitors. Saquinavir (Invirase) alone should not be used. Higher rifabutin doses (450 mg daily or 600 mg 2-3 times per week) are needed if the HAART regimen contains efavirenz.
ferase activity reaches five times the upper limit of normal or if the patient has symptoms of hepatitis. In patients with active TB disease it can sometimes be restarted later. Rechallenge with isoniazid is not rec- ommended for patients with latent TB infection.
TB IN PREGNANCY
Active TB disease during pregnancy requires treat- ment. The treatment of latent TB infection during pregnancy is more controversial because of the risk of isoniazid hepatotoxicity. In general, it is recom- mended that treatment of latent TB be delayed until 2 or 3 months after delivery. However, for women who are HIV-positive or have been infected with TB recently, initiation of therapy should not be delayed because of pregnancy.
Peripheral neuropathy occurs rarely and can usually be prevented by supplementation with pyridoxine (vita- min B6, 25-50 mg/day), which is recommended for patients with chronic alcohol use, diabetes, chronic renal failure or HIV infection, and for those who are pregnant, breastfeeding or malnourished. Some Medical Letter consultants routinely use pyridoxine for all patients taking isoniazid. Pyridoxine does not need to be given to a nursing infant unless the baby is also being given isoniazid.
Treatment of active TB disease should be initiated in pregnancy when there is moderate to high suspicion of disease because the risk to the fetus is much greater than the risk of adverse drug effects. The initial regi- men should include isoniazid, rifampin and ethambu- tol. Each of these drugs crosses the placenta, but none is teratogenic. Pyrazinamide has not been extensively studied in pregnancy, but some Medical Letter con- sultants would use it in addition to isoniazid, rifampin and ethambutol.40 If pyrazinamide is not used, treat- ment should be continued for a total of at least 9 months. Pyrazinamide is always recommended as part of the initial regimen in pregnant women who are HIV co-infected or when drug resistance is suspected.
Limited data are available on the treatment of MDRTB in pregnancy. Regimens using various com- binations of amikacin, ethionamide, PAS, cycloser- ine, capreomycin and fluoroquinolones have been successful without causing fetal adverse effects, even though these drugs are generally not considered safe in pregnancy. 41-43
Rifamycins – Rifampin, like isoniazid, is potentially hepatotoxic, and gastrointestinal disturbances, morbil- liform rash and thrombocytopenic purpura can occur. Whenever possible, rifampin should be continued despite minor adverse reactions such as pruritus and gastrointestinal upset. When taken erratically, the drug can cause a febrile “flu-like” syndrome and, very rarely, shortness of breath, hemolytic anemia, shock and acute renal failure. Patients should be warned that rifampin may turn urine, tears and other body fluids reddish-orange and can permanently stain contact lens- es and lens implants.
Rifampin is an inducer of CYP isozymes 3A4, 2C9, 2C19, 2D6, 2B6, and 2C8. It can increase the metabo- lism and decrease the effect of many other drugs, including hormonal contraceptives (patients should be advised to use another method of contraception), sul- fonylureas such as glyburide (Diabeta, and others), corticosteroids, warfarin (Coumadin, and others), quinidine, methadone (Dolophine, and others), delavirdine (Rescriptor), clarithromycin (Biaxin, and others), ketoconazole (Nizoral, and others), itracona- zole (Sporanox, and others) and fluconazole (Diflucan, and others), as well as protease inhibitors and most statins (such as atorvastatin and simvastatin). 44
Isoniazid – Serum aminotransferase activity increases in 10-20% of patients taking isoniazid, especially in the early weeks of treatment, but often returns to nor- mal even when the drug is continued. Severe liver damage due to isoniazid is less common than previ- ously thought. It is more likely to occur in patients more than 35 years old. Clinical monitoring should occur monthly; monitoring of serum transaminases is not routinely recommended except for patients with pre-existing liver disease and those at increased risk for isoniazid hepatotoxicity, such as those patients who drink alcohol regularly. Medical Letter consultants rec- ommend stopping isoniazid when serum aminotrans-
Rifabutin and rifapentine have adverse effects simi- lar to those of rifampin. Rifabutin can also cause uveitis, skin hyperpigmentation and neutropenia, but is less likely than rifampin to interact with other drugs.
Other Drugs – Pyrazinamide can cause gastrointesti- nal disturbances, hepatotoxicity, morbilliform rash, arthralgias and asymptomatic hyperuricemia, and can block the hypouricemic action of allopurinol (Zyloprim, and others). Ethambutol can cause optic neuritis, but only very rarely when using a dosage of 15 mg/kg daily. Testing of visual acuity and color per-
Treatment Guidelines from The Medical