Version May 2024
| Drug | Adult dose* | Main or rare but serious adverse effects | CSF penetration¶ | Pregnancy |
| AmikacinΔ◊§ | 15 mg/kg IM or IV once daily (usual maximum 1 g) adjusted according to serum concentrations. Alternative dosing: 25 mg/kg IM or IV three times per week. | Ototoxicity, vestibular toxicity, nephrotoxicity, electrolyte disturbances, local pain with IM injection. | Low-Moderate | Avoid |
| Amoxicillin-clavulanate (coadministered with imipenem-cilastatin or meropenem) | 2000 mg amoxicillin/125 mg clavulanate orally every 8 to 12 hours | GI toxicity. | Poor | May be used |
| Bedaquiline | When given as part of BPaLM (guided by the protocol in the TB-PRACTECAL study)[7]: 400 mg orally once daily for 2 weeks, followed by 200 mg 3 times weekly for 22 weeks (total duration 24 weeks) or When given as part of BPaL (guided by the protocol in the ZeNix study)[8]: 200 mg orally once daily for 8 weeks, followed by 100 mg orally once daily for 18 weeks (total duration 26 weeks) | QT prolongation, hepatitis, GI toxicity, others.¥ | Excellent | May be used |
| Capreomycin◊§‡ | 15 mg/kg IM or IV once daily (usual maximum 1 g) adjusted according to serum concentrations | Ototoxicity, vestibular toxicity, nephrotoxicity, electrolyte disturbances, local pain with IM injections. | Insufficient data | Avoid |
| Clofazimine (not commercially available in the United States)† | 100 mg orally once daily | Red discoloration of skin, eyes, body fluids; GI toxicity; photosensitivity; others.¥ | Insufficient data | Avoid |
| Cycloserine**,¶¶,ΔΔ | 10 to 15 mg/kg (250 to 750 mg/day) orally in 2 divided doses (maximum 500 mg twice daily) adjusted according to serum concentrations | CNS toxicity (psychiatric symptoms, seizures usually occur at peak concentrations >35 mcg/mL but may occur in the normal therapeutic range), peripheral neuropathy, dermatologic effects include serious cutaneous hypersensitivity reactions. Administration of pyridoxine (50 mg orally once daily for every 250 mg of cycloserine) may be useful in preventing or reducing neurotoxicity. | Good | Potential choice when there are no suitable alternatives |
| Delamanid | 100 mg orally twice daily with food (maximum duration studied 26 weeks) | GI toxicity, QT prolongation.¥ | No data | Avoid |
| Ethambutol | 15 mg/kg once daily (lower dose when used as a companion drug), or 25 mg/kg (higher dose, for use as a bacteriostatic agent to complete a fully active drug regimen) | Visual disturbance (optic neuropathy, manifested as decreased visual acuity or red-green colorblindness) at higher doses. | Poor-Low | May be used |
| Ethionamide**,¶¶,◊◊ | 15 to 20 mg/kg orally (usually 500 mg per day) as a single daily dose or 2 divided doses (maximum 1 g per day) | GI toxicity (antiemetic premedication is often helpful), hepatic toxicity, metallic taste, neurotoxicity including optic neuritis (administer with pyridoxine 100 mg orally once daily), endocrine effects including hypothyroidism (treat with thyroid replacement). | Excellent | Potential choice when there are no suitable alternatives |
| Imipenem-cilastatin | 1000 mg IV every 6 to 8 hours; each dose must be given with clavulanate 125 mg orally (available as amoxicillin-clavulanate; refer to above) | GI toxicity, seizures. | Poor-Low | Potential choice when there are no suitable alternatives |
| Isoniazid, high dose¶¶ | 15 mg/kg orally, IM, or IV once daily | Hepatitis, peripheral neuropathy (administer with pyridoxine 100 mg orally once daily), hypersensitivity, others. | Excellent | May be used |
| KanamycinΔ◊§ | 15 mg/kg IM or IV once daily (usual maximum 1 g) adjusted according to serum concentrations | Ototoxicity, vestibular toxicity, nephrotoxicity, electrolyte disturbances. | Low | Avoid |
| Levofloxacin | 750 to 1000 mg orally or IV once daily§§ | GI toxicity, CNS effects, rash, dysglycemia, tendonitis, tendon rupture, QT prolongation.¥ | Good | Potential choice when there are no suitable alternatives |
| Linezolid¶¶,¥¥ | When given as part of BPaL: 600 mg orally or IV once daily‡‡ When given as part of BPaLM[7]: 600 mg once daily for 16 weeks, followed by 300 mg once daily for 8 weeks | Myelosuppression, GI toxicity, neuropathy (optic and peripheral); pyridoxine (100 mg orally once daily) may be useful in preventing or reducing peripheral neuropathy. | Good and rapid, following IV administration | Avoid (limited data) |
| Meropenem | 1000 mg IV every 8 hours (based on published study); each dose must be given with clavulanate 125 mg orally (available as amoxicillin-clavulanate; refer to above) | GI toxicity, seizures. | Moderate | Potential choice when there are no suitable alternatives |
| Moxifloxacin | 400 mg orally or IV once daily (doses up to 800 mg once daily have been used, but lack adequate safety data) | GI toxicity, CNS effects, rash, dysglycemia, tendonitis, tendon rupture, QT prolongation, hepatotoxicity.¥ | Moderate | Potential choice when there are no suitable alternatives |
| Para-aminosalicylic acid** | 4 g orally twice or 3 times daily | GI toxicity, hepatotoxicity, hypothyroidism (treat with thyroid replacement). | Insufficient data, poor | Potential choice when there are no suitable alternatives |
| Pretomanid | 200 mg orally once daily | In trial of pretomanid, bedaquiline, and linezolid for extensively drug-resistant tuberculosis, peripheral and optic neuropathy, myelosuppression, hepatotoxicity, lactic acidosis were all reported; these were largely attributed to adverse effects of high-dose linezolid. | No data | No adequate human data in pregnancy are available |
| Pyrazinamide | 25 to 40 mg/kg orally once daily | Hepatotoxicity, rash, arthropathy. | Excellent | Detailed teratogenicity data are not available. Often excluded from use in pregnant women in the United States; however, the World Health Organization does not exclude its use in pregnancy. |
| Streptomycinפ | 15 mg/kg IM or IV once daily (usual maximum 1 g) adjusted according to serum concentrations. Alternative dosing: 25 mg/kg IM or IV three times per week. | Ototoxicity, vestibular toxicity, nephrotoxicity, electrolyte disturbances, local pain with IM injections. | Low | Avoid |
| Thioacetazone (not available in the United States)†† | 150 mg once daily | GI toxicity, myelosuppression, hepatitis, peripheral neuropathy, serious cutaneous hypersensitivity reactions. | Insufficient data | Potential choice when there are no suitable alternatives |
BPaL: regimen of bedaquiline, pretomanid, and linezolid; BPaLM: BPaL plus moxifloxacin; CNS: central nervous system; CSF: cerebrospinal fluid; GI: gastrointestinal; IM: intramuscular; IV: intravenous.
* Dose may need to be adjusted for renal impairment. Dosing of oral medications for treatment of multidrug-resistant tuberculosis (MDR-TB) or extensively drug-resistant tuberculosis (XDR-TB) should be daily, not intermittent.
¶ Grade of CSF penetration: Excellent: >80%; Good: 60 to 80%; Moderate: 40 to 59%; Low: 20 to 39%; Poor: <20%.
Δ For patients who are overweight or obese, dose is based on ideal body weight or dosing weight (a calculator is available in UpToDate). Adjust dose based on serum concentration monitoring for target trough <1 mcg/mL and target peak of 56 to 64 mcg/mL for once-daily administration.
◊ Injectable agents (ie, aminoglycosides and capreomycin) are typically given 5 days per week; injectable agents should be administered 7 days per week for patients who are severely ill. The initial duration of therapy is at least 2 to 3 months (and until culture conversion is documented). After documentation of culture conversion, 3-days-per-week dosing can be used for the remaining duration of injectable use (normally through at least 6 months beyond culture conversion).
§ For patients over 59 years of age, some favor administering a lower dose (10 mg/kg), with standard target drug levels.
¥ Check baseline electrolytes; check baseline and monthly liver function tests.
‡ Capreomycin is not available in the United States; availability in other countries is limited.
† Clofazimine is not commercially available in the United States; its use requires an investigational new drug application to the US Food and Drug Administration (telephone 301-796-0797).
** Administration of cycloserine, para-aminosalicylic acid, and ethionamide should be via dose escalation (drug ramping) over a 2-week period. The initial dose of cycloserine should be 250 mg orally once daily for 3 to 4 days, followed by 250 mg orally twice daily for 3 to 4 days, followed by 250 mg orally in the morning and 500 mg orally in the evening; the goal peak serum cycloserine concentration is <35 mcg/mL. The initial dose of para-aminosalicylic acid is 2 g orally twice daily for 3 to 4 days, followed by 2 g orally in the morning and 4 g orally in the evening for 3 to 4 days, followed by 4 g orally twice daily. The initial dose of ethionamide is 250 mg orally daily for 3 to 4 days, followed by 250 mg orally twice daily for 3 to 4 days, followed by 250 mg orally in the morning and 500 mg orally in the evening.
¶¶ Patients on regimens including high-dose isoniazid, ethionamide, cycloserine, or linezolid should receive oral pyridoxine for prevention of neurotoxicity.
ΔΔ Clinicians experienced with using cycloserine suggest starting with 250 mg once daily and gradually increasing as tolerated. Serum concentrations often are useful in determining the appropriate dose for a given patient. Few patients tolerate 500 mg twice daily.
◊◊ Ethionamide can be given at bedtime or with a main meal in an attempt to reduce nausea. Clinicians experienced with using ethionamide suggest starting with 250 mg once daily and gradually increasing as tolerated. Serum concentrations may be useful in determining the appropriate dose for a given patient. Few patients tolerate 500 mg twice daily.
§§ Greater efficacy has been observed with administration of 1000 mg (compared with 500 mg) for treatment of MDR-TB. For treatment of contacts to MDR-TB: 500 mg/day if ≤45.5 kg and 750 mg/day if >45.5 kg.
¥¥ Prolonged linezolid use is associated with risk of adverse effects including peripheral neuropathy and myelosuppression, particularly at high doses.
‡‡ The optimal linezolid dose when given as part of BPaL (eg, in combination with pretomanid and bedaquiline for 26 weeks) is uncertain; we favor 600 mg once daily rather than 1200 mg daily; prolonged linezolid use is associated with risk of adverse effects including peripheral neuropathy and myelosuppression, particularly at high doses. Refer to UptoDate topic on treatment of drug-resistant tuberculosis for further discussion.
†† Thioacetazone should not be administered to HIV-infected patients.آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
