antibioticsbooks

232 PART 5 Antiviral Drugs
• The PIs pose tremendous drug interaction challenges.
They are all substrates of the common
drug-metabolizing enzymes and thus can have
their concentrations substantially increased or
decreased by drugs that inhibit or induce these
enzymes. Ritonavir is one of the most potent
inhibitors of the cytochrome P450 enzyme
system; hence its use in boosting levels of the
other PIs (at the boosting doses used, it has
minimal direct antiviral effect). Generally,
co-administering other drugs that are P450
substrates (such as statins, macrolides, benzodiazepines,
and calcium channel blockers) with
ritonavir leads to increased serum concentrations
of these drugs. However, more unpredictable
effects can occur, perhaps as a result
of shunting to alternative pathways or mixed
inhibition/induction, leading to the reduction in
serum levels of P450 substrates (as can be seen
with voriconazole and methadone). The bottom
line: for patients on PIs, carefully screen all of
their medications for drug interactions using
the most up-to-date references.
• Ritonavir is now used almost exclusively as a
pharmacokinetic booster in much lower doses
than its originally approved dose of 400 mg
BID. It is not well-tolerated at the higher dose
and the majority of prescriptions or orders
for it are an error. At the least, it warrants a
double-check.
What They’re Good For
Several PI-based combinations are among the preferred
regimens for treatment of initial HIV infection.
They are also often used in salvage regimens