Rifapentine for Tuberculosis

Rifapentine is a long-acting cyclopentyl rifamycin used in short regimens for latent infection and, in some settings, a 4-month regimen for drug-susceptible pulmonary tuberculosis. It acts like rifampicin but has a longer half life and stronger protein binding. Availability is limited in many low-income settings and use depends on national programmes.

Class. Rifamycin antimycobacterial.

Mechanism. Inhibits bacterial RNA polymerase (rpoB). Most rifampicin-resistant isolates are cross-resistant.

Pharmacokinetics. Absorption rises with a fatty meal, peak at 5 to 6 hours, half life 14 to 18 hours, highly protein bound. Active 25-desacetyl metabolite. Induces CYP3A4 and CYP2C8/9 less than rifampicin but still clinically important.

Latent tuberculosis infection (weekly regimen, ages 2 and over).

• Rifapentine once weekly by weight, plus isoniazid 15 mg/kg weekly (maximum 900 mg), for 12 doses.
• Rifapentine weight bands: 10 to 14 kg 300 mg; 14.1 to 25 kg 450 mg; 25.1 to 32 kg 600 mg; 32.1 to 49.9 kg 750 mg; 50 kg or over 900 mg (maximum).
• Directly observed or self-administered; completion in 12 to 16 weeks.

Latent tuberculosis infection (daily regimen, ages 13 and over). Rifapentine 600 mg with isoniazid 300 mg daily for 28 days.

Drug-susceptible pulmonary tuberculosis (4-month regimen, ages 12 and over, weight 40 kg or over).

• First 8 weeks: rifapentine 1200 mg, isoniazid, pyrazinamide and moxifloxacin 400 mg, all once daily.
• Next 9 weeks: rifapentine 1200 mg, isoniazid and moxifloxacin once daily.
• Loading and titration: none. Maximum: 1200 mg daily.

Main alternative. The 6-month regimen of rifampicin, isoniazid, pyrazinamide and ethambutol remains the usual option where rifapentine is unavailable.

Contraindications. Hypersensitivity to rifamycins, use with drugs that cannot tolerate induction, and (for the 4-month regimen) conditions making moxifloxacin unsafe, such as QT prolongation.

Serious adverse effects. Hepatitis, systemic drug reaction after weekly doses (flushing, hypotension, syncope, rash, angio-oedema), thrombocytopenia, neutropenia, severe skin reactions.

Common adverse effects. Nausea, headache, rash, orange discolouration of fluids.

Interactions.

• Hormonal contraception becomes unreliable; use a copper device or other non-hormonal method.
• Weekly regimen can be given with efavirenz and dolutegravir; avoid with other antiretrovirals unless specialist advice supports it.
• Lowers warfarin, tacrolimus, ciclosporin, azoles, methadone and many other drugs.

Common prescribing errors. Using the weekly dose daily, taking on an empty stomach, and combining it with unsuitable antiretrovirals.

Special groups.

• Pregnancy: limited data; weekly latent regimen usually deferred until after delivery unless risk is high.
• Breastfeeding: limited data.
• Children: weekly regimen from age 2 using weight bands; the 4-month regimen is not used under age 12.
• Older adults: usual dose; monitor liver tests.
• Kidney impairment: no formal adjustment; limited data.
• Liver impairment: avoid in active hepatitis; caution in chronic disease.

Formulations. Tablets 150 mg; scored tablets can be split.

Administration. Take with a meal containing fat; swallow with water. The weekly regimen is often observed.

Baseline. Liver tests, full blood count, pregnancy test, drug review; ECG and potassium for the 4-month regimen.

Monitoring. Symptom review at each dose or visit; liver tests at baseline and in at-risk patients; adherence count.

Stopping thresholds. Stop for hepatitis (ALT over three times the upper limit of normal with symptoms, or over five times without) or any systemic drug reaction with hypotension.

Referral and escalation. Specialist review for treatment failure, drug interactions, pregnancy or active disease on a preventive regimen.