L

TABLE 51.7 Drug Interactions Commonly Seen with Protease Inhibitors3

Drugs Contraindicated for Use with Protease Inhibitors Because of Risk of Life-Threatening Toxicity

Cisapride (arrhythmias)4 Lovastatin (rhabdomyolysis) Simvastatin (rhabdomyolysis)

Ergot alkaloids (vasospasm) Midazolam (resp. depression) Triazolam (resp. depression)

Drugs That May Decrease Plasma Levels of Protease Drugs Whose Plasma Levels May Be Decreased by

Inhibitors Protease Inhibitors

Dexamethasone

Phenytoin

Rifampin

Phenobarbital

Rifabutin

St. John's wortc

Drugs That May Increase Plasma Levels of Protease Inhibitors

Clarithromycin

Itraconazole

Ketoconazole

Ethinyl estradiol Phenytoin

Drugs Whose Plasma Levels May Be Increased by Protease Inhibitors

Antiarrhythmic agents (some) Benzodiazepines (some)' Ketoconazole Antidepressants (some) Ca++ channel blockers (some) Rifabutin ß-Blockers (some)

HMG-CoA reductase inhibitors (some)c Sildenafil

"Interactions may be seen to varying degrees with different protease inhibitors. This list is not all-inclusive;it is important to check individual drug interactions when prescribing protease inhibitors.

'Pharmacy sales of this drug have been discontinued in the United States. It is available only via registered prescribers to patients who meet specific eligibility conditions.

^The use of St. John's wort is contraindicated in patients taking protease inhibitors because their antiviral activity may be lost and/or drug resistance may result.

'Some are absolutely contraindicated for use with protease inhibitors.

sensation, paresthesias, and hypertriglyceridemia than are other protease inhibitors. Pancreatitis may occur in the presence or absence of hypertriglyceridemia.

Of all the protease inhibitors, ritonavir is the most potent inhibitor of CYP3A4; therefore, it tends to produce more frequent and severe interactions with other drugs. It inhibits an additional cytochrome P450 isozyme, CYP2D6, and can increase plasma concentrations of drugs that are metabolized by it (e.g., most antidepres-sants, some antiarrhythmics, some opioid analgesics, some neuroleptics). For example, ritonavir should not be used in conjunction with amiodarone, bepridil, fle-cainide, propafenone, quinidine, or pimozide. In addition to CYP3A4, ritonavir induces CYP1A2 and possibly CYP2C9 and may inhibit the breakdown of drugs metabolized by these enzymes.

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