Ritonavir is an HIV protease inhibitor.
“Low dose” ritonavir is used to pharmacokinetically increase the concentrations of other protease inhibitors. Ritonavir is not used in high enough doses to inhibit the HIV virus.
Cleavage of polyproteins by the protease enzyme is an essential step in the HIV life cycle. After cleavage the immature virus proteins are assembled into particles which bud from the cell as mature, infectious virons. Protease inhibitors compete for the active cleavage site on the protease enzyme, blocking the cleavage of the polyproteins and thus the maturation of new viral particles.
Higher levels of protease inhibitor resistance result from the accumulation of multiple protease inhibitor-resistance mutations. There are many mechanisms of resistance. These include reduced binding affinity between the inhibitor and the protease enzyme, alterations in enzyme catalysis, effects on dimer stability, alterations in inhibitor binding kinetics and re-shaping of the active site.
The fold change for IC50 in the presence of 50% human serum for ritonavir was 10.2. The predicted fold change in 100% human serum is 29.7.
The absorption soft-gel capsules is increased by 13% when taken with food. It is primarily bound to human serum albumin and alpha-1 acid glycoprotein at 98 – 99% over the concentration range of 0.01 – 30 mcg/mL. CYP450 3A is the major isoform involved in ritonavir metabolism and ritonavir is a mechanism-based inhibitor of 3A4.
The most common adverse effects are nausea, diarrhea, vomiting, anorexia, abdominal pain, taste perversion and circumoral and peripheral paresthesias. These side effects are less common in patients taking low-dose ritonavir. Severe hypertriglyceridemia is also seen especially when used at standard doses.
Capsule 100mg
Oral Solution 80mg/ml
Antiretroviral dosing in adults is 600 mg twice daily with food. However, it is most often used in combination with other protease inhibitors at doses of 100 – 400 mg. When used in 100 or 200 mg doses in such regimens, the purpose is to inhibit the metabolism of the coadministered protease inhibitor and thereby increase plasma concentrations and generally allow for decreased doses or wider dosing interval for these agents. The recommended dosing in pediatric patients calls for starting doses at 250 mg/m2 every 12 hours and titrating up to 400 mg/m2 every 12 hours
Renal Impairment:
no specified dose adjustment
Hepatic Impairment:
no dose adjustment in mild hepatic insufficiency
use with caution in patients with moderate to severe hepatic insufficicency
Ritonavir is an inhibitor of cytochrome P450 3A and CYP2D6 (to a lesser extent). It also appears to induce CYP3A as well as other enzymes, including glucuronosyl transferase, CYP1A2, and possibly CYP2C9.
Ritonavir is contraindicated with the following medications:
amiodarone, bepridil, flecainide, propafenone, quinidine, astemizole (no longer marketed in the United States), terfenadine (no longer marketed in the United States), dihydroergotamine, ergonovine, ergotamine, methylergonovine , cisapride (no longer marketed in the United States), pimozide, midazolam and triazolam.
Category B: No evidence of risk in humans but studies inadequate.
blood glucose, LFTs, serum lipid profile
Norvir®/Abbott Pharmaceutical Product Division