Some Second-Line Drugs
Kanamycin (Kantrex, and others) Amikacin (Amikin)
15 mg/kg IM or IV (max 1 g)
15 mg/kg IM or IV (max 1 g)
10-15 mg/kg in 2 doses (max 500 mg bid) PO
15-20 mg/kg in 2 doses (max 500 mg bid) PO
500-1000 mg PO or IV
15 mg/kg IM (max 1 g)
Daily adult dosage 15 mg/kg IM (max 1 g)
400 mg PO or IV
Aminosalicylic acid (PAS; Paser)
8-12 g in 2-3 doses PO
GI and hepatic toxicity, hypothyroidism
See footnote 3
GI toxicity, CNS effects, rash, dysglycemia
See footnote 3
GI toxicity, CNS effects, rash,
200-300 mg/kg, in 2-4 doses
dysglycemia GI disturbance
Daily pediatric dosage 20-40 mg/kg
Main adverse effects
Vestibular and auditory toxicity,
renal damage Auditory and vestibular toxicity,
renal damage Auditory toxicity, renal damage
15-30 mg/kg 10-15 mg/kg
Auditory toxicity, renal damage Psychiatric symptoms, seizures
Streptomycin is generally given 5-7 times per week (15 mg/kg, or a maximum of 1 g per dose) for an initial 2 to 12 week period, and then (if needed) 2 to 3 times per week (20 to 30 mg/kg, or a maximum of 1.5 g per dose). For patients >59 years old, dosage is reduced to 10 mg/kg/d (max 750 mg/d). Dosage should be decreased if renal function is diminished.
Some authorities recommend pyridoxine 50 mg for every 250 mg of cycloserine to decrease the incidence of adverse neurological effects.
According to the American Academy of Pediatrics, although fluoroquinolones are generally contraindicated in children <18 years old, their use may be justified in special circumstances. Medical Letter consultants would use these drugs to treat children with MDRTB.
Drug Intolerance – For patients who cannot tolerate rifamycins, alternative regimens include 9-12 months of isoniazid, ethambutol and pyrazinamide, with or without a fluoroquinolone (levofloxacin or moxi- floxacin). Levofloxacin has been safe for long-term use in patients with drug-resistant TB or those intolerant to isoniazid or a rifamycin. Moxifloxacin is currently in clinical trials for use in TB treatment and may be more active than levofloxacin against M. tuberculosis, but clinical data are limited.
Isoniazid plus ethambutol for 18 months has also been used for patients intolerant of rifamycins. Rifabutin has been substituted for rifampin in standard regimens for some patients who could not take rifampin because of drug interactions (such as HIV co-infected patients on a protease inhibitor). Patients who cannot take pyrazi- namide in the initial phase of treatment should receive continuation therapy with isoniazid and rifampin for 7 months (a total course of 9 months).
men has, however, been associated with development of rifamycin resistance in HIV-infected patients and should not be used in these individuals. 26-28
Twice-weekly intermittent regimens have also been associated with rifamycin resistance in HIV co-infected patients with low CD4 counts; such patients should receive daily or 3x/wk therapy.
Fixed-Dose Combinations – A combination formula- tion of rifampin, isoniazid and pyrazinamide (Rifater) is approved by the FDA for the initial 2 months of daily anti-tuberculosis therapy. A combination of rifampin and isoniazid (Rifamate) has been available in the US since 1975. Fixed-dose combinations may be particularly useful for patients self-administering their therapy. 29
Intermittent Treatment – Intermittent 4-drug regi- mens with 2 or 3 doses per week are also effective for treatment of TB, but must be given by DOT. Intermittent therapy is most commonly used in the continuation phase, after at least 2 months of daily (or 5x/wk) therapy during the initiation phase. It should never be used for treatment of drug-resistant TB. A once-weekly continuation-therapy regimen of isoni- azid plus rifapentine (instead of rifampin), started after 2 months of standard initial therapy, is also effective for susceptible TB in selected patients.2,24 This regi-
Daily adult dosage 2 capsules
(isoniazid 150 mg rifampin 300 mg)
R i f a t e r 1 (isoniazid 50 mg, rifampin 120 mg,
<44 kg: 4 tablets 45-54 kg: 5 tablets 55-90 kg: 6 tablets
pyrazinamide 300 mg)
>90 kg: 6 tablets plus additional pyrazinamide2
Pyridoxine 25-50 mg should be given to prevent neuropathy in malnourished or pregnant patients and those with HIV infection, alcoholism or diabetes.
Six tablets provide 1800 mg of pyrazinamide. Patients should take additional pyrazinamide tablets to achieve a total dose of 20-25 mg/kg/d.
Treatment Guidelines from The Medical Letter 18
Vol. 5 (Issue 55)