Interaction Checker
Potential Interaction
Ritonavir (RTV)
Carbamazepine
Quality of Evidence: Moderate
Summary:
Use with caution. Ritonavir used as a pharmacokinetic booster may increase carbamazepine concentrations and a decrease in dose may be necessary. Careful monitoring of adverse effects and therapeutic concentration monitoring of carbamazepine is recommended. Two cases reported increased carbamazepine concentrations in patients receiving ritonavir (400 mg twice daily).
Description:
Ritonavir dosed as a pharmacokinetic enhancer or as an antiretroviral agent inhibits CYP3A4 and as a result is expected to increase the plasma concentrations of carbamazepine. Careful monitoring of therapeutic and adverse effects is recommended when carbamazepine is concomitantly administered with ritonavir.
Norvir Summary of Product Characteristics, AbbVie Ltd, September 2016.
Coadministration may increase carbamazepine concentrations. A dose decrease may be needed for this drug when co-administered with ritonavir and therapeutic concentration monitoring is recommended for this anticonvulsant, if available.
Norvir Prescribing Information, AbbVie Inc, December 2016.
There is a case report of carbamazepine toxicity in a patient after starting a ritonavir- and efavirenz-containing antiretroviral regimen. Prior to starting ritonavir (400 mg bd) and efavirenz (600 mg once daily), the patient was stable on carbamazepine 600 mg/day, with carbamazepine concentrations of 6.9 µg/ml (therapeutic range 4–12 µg/ml). Four days after starting the ART regimen, the patient was hospitalised with a one day history of worsening ataxia resulting in two falls; serum carbamazepine concentrations were found to be 20.4 µg/ml. Carbamazepine was discontinued for 9 days and restarted at 300 mg/day, however, over the next 3 weeks it was necessary to further reduce the carbamazepine dose to 100 mg/day. The patient remained stable on this dose for approximately 2 weeks, when it became necessary to discontinue her ART regimen. Following the withdrawal of ritonavir and efavirenz, it was found that carbamazepine concentrations were subtherapeutic requiring an increase in carbamazepine dose back to the original 600 mg/day. The authors had not expected a marked increase in carbamazepine concentrations as the change in the ART regimen involved changing from indinavir to ritonavir (a more potent CYP3A4 inhibitor), but at the same time adding in a relatively potent inducer of CYP3A4 (efavirenz).
Carbamazepine toxicity after starting combination antiretroviral therapy including ritonavir and efavirenz. Burman W & Orr L. AIDS, 2000, 14:2793–4.
There is a case report of a 36 year old man who developed carbamazepine toxicity. The subject had been stable for nearly 2 years on antiepileptic medication (phenytoin, phenobarbital and carbamazepine 400 mg three times daily) and an antiretroviral regimen of stavudine, lamivudine and indinavir. The antiretrovirals were then changed to saquinavir (400 mg bd), ritonavir (400 mg bd) and nevirapine (200 mg od). Two days after changing regimens, the subject presented to the emergency department with vertigo, drowsiness, disorientation, diplopia and severe ataxia. Plasma concentrations of carbamazepine were found to have increased by 99.4% reaching 16.6 mg/L (previous value 8.3, therapeutic range 4-12). The phenytoin concentrations had dropped by 33% and the Phenobarbital concentration remained unchanged. Carbamazepine was reduced to 200 mg three times daily, ritonavir stopped and nelfinavir 1000 mg twice daily started. There were no changes to doses of phenobarbital, phenytoin, saquinavir or nevirapine (other than standard dose escalation to 200 mg bd). Two days after these changes carbamazepine concentrations returned to the therapeutic range and the symptoms of toxicity disappeared.
Ritonavir-induced carbamazepine toxicity. Mateu-de Antonio J, Grau S, Gimeno-Bayon JL, Carmona A. Ann Pharmacother, 2001, 35:125-126.
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