First-line TB drugs include INH, RIF, PZA, EMB, rifabutin, and rifapentine. Second-line drugs include cycloserine, ethioamide (ETH), streptomycin (Strep), para-aminosalicylic acid (PAS), capreomycin, amikacin/kanamycin, levofloxacin, moxifloxacin, gatifloxacin, and ciprofloxacin.
First Line Drugs
TB Drugs: Isonicotinic Hydrazide (INH)
INH is a bactericidal drug which inhibits the fatty acid synthase II complex which produces mycolic acids that are unique to mycobacteria and are incorporated into a waxy sheath. This sheath encapsulates mycobacteria and provides resistance of the mycobacteria to the immune system of the patient’s body, thereby decreasing entry of the drug into the mycobacterium. INH has profound early bactericidal activity against rapidly dividing organisms. The dose in adults is 300 mg po qd or 15 mg/kg (about 900 mg) po three times per week (tiw).
Adverse effects include
Asymptomatic elevation of aminotransferase with elevations up to 3 to 5 times normal. This occurs in 10 to 20 % of patients. These values usually return to normal with continued administration of the drug.
Clinical hepatitis is a particular risk in older patients (rare in patients less than 20, and 2 % in patients from 50 to 64 years of age). It also may occur in patients who have liver disease, patients with a history of heavy alcohol intake, and in postpartum women (especially Hispanic women). Death from hepatitis occurs in less than 0.023 % of patients who have taken INH. INH therapy should be terminated if aminotransferase levels rise 3 to 5 times above normal..
Peripheral neurotoxicity occurs particularly in patients who are taking more than 400 mgs of INH qd and is associated with nutritional deficiency, diabetes mellitus, HIV infection, renal failure, and alcoholism. These patients require 25 mg po qd of pyridoxine (Vitamin B6).
Drug interactions with INH include an increase in phenytoin (Dilantin) and disulfuram (Antabuse).
Routine monitoring of INH is not necessary beyond obtaining initial liver chemistries.
TB Drugs: Rifampin (RIF)
RIF is a bactericidal drug, which inhibits bacterial RNA polymerase and is particularly effective against rapidly growing (dividing) organisms as well as semi dormant organisms. The dose of RIF is 600 mgs po qd or 600 mgs po 2 times per week (tiw).
Adverse effects include:
Rash with pruritis
Hepatotoxicity – hepatitis
Orange discoloration of body fluids, including tears (can permanently stain contact lenses)
Drug interactions include:
RIF reduces the level of oral contraceptives, methacholine, warfarin, glucocorticoids, hypoglycemic agents, digitalis, ketoconazole, and cyclosporine
RIF is contraindicated or should be used with extreme caution in HIV-infected patients, especially those taking protease inhibitors (PIs) and/or nucleotide reverse transcriptase inhibitors (NNRTIs). Rifabutin can be used as an alternative under these circumstances. (Consult CDC guidelines for proper dosing of Rifabutin and PIs as well as NNRTIs in patients who are being treated for active TB and AIDS or HIV infections.)(See CDC Guidelines: Drug Interactions)
Routine monitoring beyond initial liver chemistries is not needed.
TB Drugs: Pyrazinamide (PZA)
PZA is a bactericidal drug which inhibits mycobacterial fatty acid synthesis by targeting fatty acid synthase I complex. PZA exerts its greatest activity against dormant and semi-dormant organisms contained within macrophages or the acidic environment of caseous foci.
The dose of PZA is 20 mg/kg po qd.
Adverse effects include:
Hepatotoxicity – occurs in less than 1 % of patients at the above dose.
Asymptomatic – an expected effect
Acute gouty arthritis – rare
Non-gouty polyarthritis occurs in up to 40 % of patients, but is not a significant problem and responds to aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs).
Monitoring is not necessary beyond initial serum uric acid and liver chemistry measurements. The drug should not be used in patients with gout and should be used with care in patients with liver disease.
TB Drugs: Ethambutol (EMB)
EMB is a bactericidal drug at high dose and bacteriostatic at low doses. It inhibits the formation of an arabinogalactan polysaccharide layer that tethers the mycolic acid shell to the interior cell membrane of mycobacteria. EMB is effective against rapidly growing organisms and is used primarily to prevent growth of drug-resistant organisms.
The dose is 15 to 25 mg/kg po qd.
Adverse effects include:
Retrobulbar neuritis, which results in decreased visual acuity, missing words during reading from central scotomas (blind spots), and decreased green and red color discrimination. At a dose of 15 mg/kg qd, this is most unlikely. It is more likely at 25 mg/kg po qd.
Hyperuricema – an expected effect
Monitoring requires a visual acuity test (Snellen test) and testing for color discrimination (Ishawara test) as a baseline when starting the drug. At each visit, the patient should be asked about normal visual acuity and color discrimination (problem with red and/or green colors while watching television).
TB Drugs: Rifabutin
Rifabutin is an alternative to RIF, especially in patients receiving antiviral therapy such as protease inhibitors (PIs) or non-nucleoside transcriptase inhibitors (NNRTIs) for HIV infection.
The usual dose is 300 mg po per day, or twice or three times weekly, but depends on whether an antiviral is being used. With some antiviral medications, rifabutin is contraindicated.