RIFAPENTINE
Please note rifapentine is not licensed in the UK, and currently is not recommended by NICE.
DOSAGE – Active Tuberculosis
MANUFACTURER RECOMMENDATIONS
Adults, and children over 12 years:
NB. HIGHER DOSES HAVE BEEN STUDIED, e.g. in the RIFAQUIN Trial.
Adults, and children over 12 years:
DOSAGE - Latent Tuberculosis Infection
Adults: 900 mg once weekly for 12 doses (in combination with isoniazid 15mg/kg (maximum 900mg) once a week).
Children: (12 years and older): Once weekly dose for 12 weeks based on weight (in combination with isoniazid 15mg/kg (maximum 900mg) once a week):
Rifapentine should be taken with meals to maximise absorption, especially for people with active tuberculosis.
NB: In people with latent tuberculosis infection, taking rifapentine with meals may be difficult because isoniazid should be taken on an empty stomach. For this indication, we recommend that rifapentine and isoniazid are taken at the same time on an empty stomach, or with a light snack if nauseated.
PREPARATIONS
Oral: 150mg oral tablets
DRUG LEVEL MONITORING
ADVERSE EFFECTS
COMMON:
Reddish discolouration of urine, sweat, sputum, tears.
Flu-like syndrome.
Gastrointestinal: Anorexia, nausea, vomiting, heartburn.
Hepatic: Transient increases in LFTs.
Metabolic: Hypoglycaemia, hyeruricaemia
SERIOUS:
Haematological: Agranulocytosis (rare), Haemolytic anaemia (rare, usually intermittent therapy), Thrombocytopaenia (rare, usually high-dose / intermittent therapy).
Hepatic: Hepatotoxicity (rare), Hyperbilirubinaemia.
Renal: Nephrotoxicity (rare).
Immunologic: Hypersensitivity.
ADVERSE EFFECTS: MONITORING
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTONS
Analgesics: Accelerated metabolism of opiates, resulting in reduced effect (e.g. alfentanyl, codeine, fentanyl, methadone, morphine and possibly oxycodone).
Anti-arrhythmics: Accelerated metabolism of disopyramide.
Antibacterials: Reduced plasma concentrations of chloramphenicol, clarithromycin, dapsone, doxycycline and fluoroquinolones.
Anticoagulants: Accelerated metabolism of coumarins (e.g. warfarin).
Anti-diabetics: Accelerated metabolism of sulfonylureas (reduced effect).
Antiepileptics: Reduced plasma concentration of antiepileptics such as phenytoin.
Antifungals: Reduced serum concentrations of fluconazole, itraconazole and ketoconazole. If benefit outweighs the risk, monitor antifungal serum concentrations.
Antipsychotics: Accelerated metabolism of antipsychotics such as haloperidol.
Antivirals: Please seek advice from an HIV physician before considering starting rifapentine in patients on anti-retrovirals due to the frequency of drug interactions: reduced serum concentration of certain reverse transcriptase inhibitors (e.g., delavirdine, zidovudine).
Atovaquone: Reduced plasma concentrations of both rifapentine and atovaquone.
Benzodiazpeines: Reduced plasma concentrations (e.g. diazepam).
Betablockers: Reduced effect of betablockers; dosage adjustment maybe required.
Calcium-channel blockers: Accelerated metabolism of diltiazem, nifedipine, and verapamil (significant reduction in plasma concentrations).
Ciclosporin: Accelerated metabolism of ciclosporin (reduced plasma concentration).
Contraceptives: Accelerated metabolism of oestrogens and progestogens (reduced contraceptive effect). Avoid use of combined hormonal contraception (oral, patch or vaginal ring), or progestogen-only contraception (pill and implant). Suitable alternatives include barrier methods, copper-bearing intrauterine system, or progestogen-only injectable (depot medroxyprogesterone acetate, norethisterone enantate, or levonorgestrel-releasing intrauterine system, which can be continued at the usual dose and dosing/replacement interval of 12 weeks, 8 weeks and 5 years, respectively).
Corticosteroids: Possible accelerated metabolism of corticosteroids (reduced effect).
Hormone Replacement Therapy (HRT): Rifapentine would be expected to reduce the efficacy of HRT
Levothyroxine: Reduced effect of levothyroxine; dosage adjustment maybe required.
Sildenafil: Reduced plasma concentration of sildenafil.
Sirolimus: Potential for reduction in plasma concentration of sirolimus.
Tacrolimus: Reduced in plasma concentration of tacrolimus.
Theophylline: Accelerated metabolism of theophylline (reduced plasma concentration).
Tri-cyclic antidepressants: Reduced effect of tri-cyclic antidepressants; dosage adjustment maybe required.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To rifapentine or other rifamycins.
Liver Disease: Avoid if jaundiced.
Drug Interactions: Avoid concomitant use with saquinavir or ritonavir.
Cautions:
Liver Disease: Use cautiously and monitor LFTs; hyperbilirubinaemia may occur early in treatment in some patients due to competition between rifampicin and bilirubin for hepatic excretion.
Pregnancy.
Breast feeding.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.
DOSAGE – Active Tuberculosis
MANUFACTURER RECOMMENDATIONS
Adults, and children over 12 years:
- Intensive phase (maximum 2 months): 600mg twice weekly with an interval of no less than 72 hours (3 days).
- NB. The American Thoracic Society, US Centers for Disease Control and Prevention, and Infectious Diseases Society of America currently do not recommend use of rifapentine during the initial intensive phase of tuberculosis treatment.
- Continuation phase: 600mg once weekly.
NB. HIGHER DOSES HAVE BEEN STUDIED, e.g. in the RIFAQUIN Trial.
Adults, and children over 12 years:
- Intensive phase (maximum 2 months): daily rifampicin, pyrazinamide, ethambutol and moxifloxacin. (NB. Rifapentine was not used in the intensive phase).
- Continuation phase: Rifapentine 1200mg (8 x 150mg tablets) once a week for four months (in combination with moxifloxacin 400mg once a week).
DOSAGE - Latent Tuberculosis Infection
Adults: 900 mg once weekly for 12 doses (in combination with isoniazid 15mg/kg (maximum 900mg) once a week).
Children: (12 years and older): Once weekly dose for 12 weeks based on weight (in combination with isoniazid 15mg/kg (maximum 900mg) once a week):
- 10.0–14.0 kg = 300 mg once weekly.
- 14.1–25.0 kg = 450 mg once weekly.
- 25.1–32.0 kg = 600 mg once weekly.
- 32.1–49.9 kg = 750 mg once weekly.
- >50 kg = 900 mg once weekly.
Rifapentine should be taken with meals to maximise absorption, especially for people with active tuberculosis.
NB: In people with latent tuberculosis infection, taking rifapentine with meals may be difficult because isoniazid should be taken on an empty stomach. For this indication, we recommend that rifapentine and isoniazid are taken at the same time on an empty stomach, or with a light snack if nauseated.
PREPARATIONS
Oral: 150mg oral tablets
DRUG LEVEL MONITORING
- Drug levels need not be routinely measured.
ADVERSE EFFECTS
COMMON:
Reddish discolouration of urine, sweat, sputum, tears.
Flu-like syndrome.
Gastrointestinal: Anorexia, nausea, vomiting, heartburn.
Hepatic: Transient increases in LFTs.
Metabolic: Hypoglycaemia, hyeruricaemia
SERIOUS:
Haematological: Agranulocytosis (rare), Haemolytic anaemia (rare, usually intermittent therapy), Thrombocytopaenia (rare, usually high-dose / intermittent therapy).
Hepatic: Hepatotoxicity (rare), Hyperbilirubinaemia.
Renal: Nephrotoxicity (rare).
Immunologic: Hypersensitivity.
ADVERSE EFFECTS: MONITORING
Routine tests as per generic MDR-TB treatment monitoring guidelines.
INTERACTONS
Analgesics: Accelerated metabolism of opiates, resulting in reduced effect (e.g. alfentanyl, codeine, fentanyl, methadone, morphine and possibly oxycodone).
Anti-arrhythmics: Accelerated metabolism of disopyramide.
Antibacterials: Reduced plasma concentrations of chloramphenicol, clarithromycin, dapsone, doxycycline and fluoroquinolones.
Anticoagulants: Accelerated metabolism of coumarins (e.g. warfarin).
Anti-diabetics: Accelerated metabolism of sulfonylureas (reduced effect).
Antiepileptics: Reduced plasma concentration of antiepileptics such as phenytoin.
Antifungals: Reduced serum concentrations of fluconazole, itraconazole and ketoconazole. If benefit outweighs the risk, monitor antifungal serum concentrations.
Antipsychotics: Accelerated metabolism of antipsychotics such as haloperidol.
Antivirals: Please seek advice from an HIV physician before considering starting rifapentine in patients on anti-retrovirals due to the frequency of drug interactions: reduced serum concentration of certain reverse transcriptase inhibitors (e.g., delavirdine, zidovudine).
Atovaquone: Reduced plasma concentrations of both rifapentine and atovaquone.
Benzodiazpeines: Reduced plasma concentrations (e.g. diazepam).
Betablockers: Reduced effect of betablockers; dosage adjustment maybe required.
Calcium-channel blockers: Accelerated metabolism of diltiazem, nifedipine, and verapamil (significant reduction in plasma concentrations).
Ciclosporin: Accelerated metabolism of ciclosporin (reduced plasma concentration).
Contraceptives: Accelerated metabolism of oestrogens and progestogens (reduced contraceptive effect). Avoid use of combined hormonal contraception (oral, patch or vaginal ring), or progestogen-only contraception (pill and implant). Suitable alternatives include barrier methods, copper-bearing intrauterine system, or progestogen-only injectable (depot medroxyprogesterone acetate, norethisterone enantate, or levonorgestrel-releasing intrauterine system, which can be continued at the usual dose and dosing/replacement interval of 12 weeks, 8 weeks and 5 years, respectively).
Corticosteroids: Possible accelerated metabolism of corticosteroids (reduced effect).
Hormone Replacement Therapy (HRT): Rifapentine would be expected to reduce the efficacy of HRT
Levothyroxine: Reduced effect of levothyroxine; dosage adjustment maybe required.
Sildenafil: Reduced plasma concentration of sildenafil.
Sirolimus: Potential for reduction in plasma concentration of sirolimus.
Tacrolimus: Reduced in plasma concentration of tacrolimus.
Theophylline: Accelerated metabolism of theophylline (reduced plasma concentration).
Tri-cyclic antidepressants: Reduced effect of tri-cyclic antidepressants; dosage adjustment maybe required.
This information is not inclusive of all drug interactions. Please discuss with a pharmacist.
CONTRA-INDICATIONS & CAUTIONS
Contraindications:
Hypersensitivity: To rifapentine or other rifamycins.
Liver Disease: Avoid if jaundiced.
Drug Interactions: Avoid concomitant use with saquinavir or ritonavir.
Cautions:
Liver Disease: Use cautiously and monitor LFTs; hyperbilirubinaemia may occur early in treatment in some patients due to competition between rifampicin and bilirubin for hepatic excretion.
Pregnancy.
Breast feeding.
LABORATORY INFORMATION
Please find up to date information at www.assayfinder.com regarding individual providers of drug level monitoring tests. Click on the provider to discover contact details. Turnaround time varies depending on the test and whether it is run locally or sent to an external lab. By contacting laboratories in advance, turnaround time can significantly be reduced.