Ritonavir

Ritonavir, with trade name Norvir (Abbott Laboratories), is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS.

Ritonavir is frequently prescribed with HAART, not for its antiviral action, but as it inhibits the same host enzyme that metabolizes other protease inhibitors. This inhibition leads to higher plasma concentrations of these latter drugs, allowing the clinician to lower their dose and frequency and improving their clinical efficacy.

Method of action

Ritonavir was originally developed as an inhibitor of HIV protease. It is one of the most complex inhibitors. It is now rarely used for its own antiviral activity, but remains widely used as a booster of other protease inhibitors. More specifically, ritonavir is used to inhibit a particular liver enzyme that normally metabolizes protease inhibitors, cytochrome P450-3A4 (CYP3A4).[3] The drug's molecular structure inhibits CYP3A4, so a low dose can be used to enhance other protease inhibitors. This discovery, which has drastically reduced the adverse effects and improved the efficacy of PI's and HAART, was first communicated in an article published in the AIDS Journal in 1997 by the University of Liverpool. This effect does come with a price: it also affects the efficacy of numerous other medications, making it difficult to know how to administer them concurrently. In addition it can cause a large number of side-effects on its own.

Drug interactions
Concomitant therapy of ritonavir with a variety of medications may result in serious and sometimes fatal drug interactions.[4] These interactions can occur with strong inhibitors, strong or moderate inducers or substrates of hepatic cytochrome P450 CYP3A4 isoform.

The list of clinically significant interactions of ritonavir includes but is not limited to following drugs:

• amiodarone - decreased metabolism, possible toxicity
• midazolam and triazolam - contraindicated
• carbamazepine - decreased metabolism, possible toxicity
• cisapride - decreased metabolism, possible prolongation of Q-T interval and life-threatening arrythmias
• disulfiram (with ritonavir oral preparation) - decreased metabolism of ritonavir
• eplerenone
• etravirine
• flecainide - decreased metabolism, possible toxicity
• MDMA
• meperidine - build-up of toxic concentrations of a metabolite possible
• nilotinib
• nisoldipine
• pimozide
• quinidine
• ranolazine
• salmeterol
• St John's wort
• statins - decreased metabolism, without dosage modification increased risk of rhabomyolisis
• thioridazine
• topotecan
• voriconazole - ritonavir increases metabolism of voriconazole
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