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Isoniazid
Paul A. Pham Pharm.D. and John G. Bartlett M.D.
03-30-2008
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Available formulation in Zambia: Isoniazid tablet: 100-300 mg. Tablet (scored): 50 mg. Isoniazid + ethambutol tablet: 150 mg + 400 mg. Rifampicin + isoniazid tablet: 60 mg + 30 mg; 150 mg + 75 mg; 300 mg + 150 mg. 60 mg + 60 mg (For intermittent use 3 times weekly). 150 mg + 150 mg (For intermittent use 3 times weekly). Rifampicin + isoniazid+ ethambutol tablet: 150 mg + 75 mg + 275 mg. Rifampicin + isoniazid+ pyrazinamide tablet: 60 mg + 30 mg + 150 mg; 150 mg + 75 mg + 400 mg. 150 mg + 150 mg + 500 mg (For intermittent use 3 times weekly). Rifampicin + isoniazid+ pyrazinamide+ ethambutol tablet: 150 mg + 75 mg + 400 mg + 275 mg.
- All new TB cases (smear positive, smear negative, extra-pulmonary TB, and smear negative relapse): INH, RIF, PZA, and EMB x 2 months, then INH plus EMB x 6 months.
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TB smear positive re-treatment cases (e.g treatment failure, treatment after default, smear positive relapse): INH, RIF, PZA, EMB, and SM x 2 months, then INH, RIF, PZA, and EMB x 6 months.
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May increase risk of
peripheral neuropathy
with
d4T
co-administration.
Zambia Information Author: Paul A. Pham, Pharm. D.
- Treatment and prevention of TB
brand
name
| generic
| Mfg
| brand
forms
| cost*
|
| Isoniazid | Isoniazid (INH) | Generic manufacturers (Barr, Eon and others) | oral
tablet
100mg; 300mg | $0.08; $0.20 |
|
Nydrazid
| INH | Geneva | IM
vial
100mg/ml (10ml) | $24.90 |
|
Rifamate
| INH 150mg/Rifampin (RIF) 300mg | Aventis | oral
capsule
INH 150mg/RIF 300mg | $3.12 |
|
Rifater
| INH 50mg/RIF120mg/(PZA) 300mg | Aventis | oral
capsule
INH 50mg/RIF 120mg/pyrazinamide(PZA) 30mg | $2.32 |
*Prices represent cost per unit specified and are representative of "Average Wholesale Price" (AWP).
AWP Prices were obtained and gathered by Lakshmi Vasist Pharm D using the Red Book, manufacturer's
information, and the McKesson database.
^Dosage is indicated in mg unless otherwise noted.
- Treatment of latent TB (prophylaxis): INH 5mg/kg (max300mg) PO qd x 9 mos or DOT: 15mg/kg (max 900mg) 2x/wk x 9 mos
- Active TB treatment (with other anti-TB agents): 5mg/kg (max300mg) PO qd x 6-9 mos or directly observed therapy (DOT): 15mg/kg (max 900mg) 2-3x/wk x6-9 mos
- Active TB treatment continuation phase (with other anti-TB agents):3x/wk for CD4 <100
- Active TB treatment duration: 6 mos for most forms except severe cavitary pulmonary (9 mos), bone/joint (9 mos), miliary (9 mos), CNS (9-12 mos)
- Coadminister with pyridoxine 50mg/d or 100mg 2x/wk to prevent neuropathy.
- DOT preferred for active TB in all pts
- Obtain CBC and LFTs at baseline and periodically throughout course of therapy. Monitor monthly for hepatitis sx; consider monthly LFTs in pts with other risks for hepatotoxicity.
- Administer 1 hr before or 2 hrs after meals.
Usual dose
Usual dose
If slow acetylator use 150mg po qd; HD:5 mg/kg post-dialysis
5 mg/kg post-dialysis
QD dose post dialysis (50% of dose if slow acetylator)
No data
- Increased transaminases:increased ALT in 10-20% (D/C if LFTs >5x ULN)
- GI intolerance (diarrhea with liquid INH; crushed tabls typically better tolerated in infants/children)
- Clinical hepatitis in 0.6% and fatal hepatitis in 0.02% (risk increased with age, alcohol, prior liver disease, concurrent RIF, and pregnancy). May occur even after mos on treatment. In most cases, enzyme levels return to normal with discontinuation of therapy. Recommend monthly clinical and lab monitoring. Instruct pts to report sxs of hepatitis. D/C if sxs or signs of hepatic damage. Consider non/less hepatotoxic alternatives. Reinstitute only after sxs and lab abnormalities resolved. Restart with gradual dose escalation. Withdraw with any indication of recurrent liver damage.
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Peripheral neuropathy and optic neuropathy (dose-related and prevented by pyridoxine co-administration)
- Hypersensitivity reaction (rash, exfoliative dermatitis, urticaria, and edema.)
- Fever
- CNS toxicity: psychosis
- Arthralgia
- Bone marrow suppression
- Phenytoin: may increase phenytoin levels. Monitor closely.
- Carbamazepine: may increase carbamazepine levels. Monitor closely.
- Enflurane: in rapid acetylators of INH, high output renal failure may occur. Monitor closely.
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Rifampin: possible additive hepatotoxicity due to production of secondary pathway metabolite of INH (hydrazine and isonicotinic acid). Consider rifabutin.
- Warfarin:may increase INR, monitor closely
- Antacids:may decrease INH absorption (avoid co-administration)
- Tyramine rich foods (wine, cheese, etc):- may develop monoamine poisoning (avoid tyramine rich foods)
- Ketoconazole: may decrease ketoconazole levels (based on case reports, clinical significance unknown).
- Theophylline: serum level may be increased. Dose may need to be decreased.
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Ethionamide: may increase INH serum level. Monitor for toxicity (peripheral neuritis and hepatotoxicity) with co-administration.
- Cycloserine: may increase central nervous system adverse effects. Monitor closely and discontinue if severe.
- Benzodiazepines (i.e diazepam, triazolam, midazolam): may increase benzodiazepine serum levels. Consider using oxazepam or lorazepam with INH co-administration.
- Prednisone and prednisolone: may decrease INH serum levels. Monitor INH for therapeutic efficacy.
- Ethanol: avoid.
First line agent for treatment and prophylaxis of TB. Because of high prevalence of INH resistance, treatment with RIF-containing regimen should be strongly considered in the treatment of latent TB for immigrants from Vietnam, Haiti, and the Philippines [NEJM 2002;347:1850].
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