Products
Ritonavir is commercially available as a monopreparation in the form of film-coated tablets (Norvir). It was approved in many countries, in the United States and in the EU in 1996, and is also used as a pharmacokinetic booster in combination with antiviral agents (eg, lopinavir). Norvir syrup is no longer marketed in many countries.
Structure and properties
Ritonavir (C37H48N6O5S2, Mr = 720.9 g/mol) is a peptidomimetic. It exists as a white powder with a bitter, metallic taste and is practically insoluble in water.
Effects
Ritonavir (ATC J05AE03) has antiviral properties. The effects are due to inhibition of the HIV protease. This prevents processing of the Gag-Pol polyprotein, resulting in immature and noninfectious HIV particles. Viral replication is inhibited. The half-life is in the range of 3 to 5 hours.
Indications
- In combination with other antiretroviral drugs for the treatment of infection with HIV-1.
- As a pharmacokinetic booster (CYP3A inhibitor) for combination therapy in HIV (e.g., lopinavir) and in hepatitis C (+ ombitasvir + paritaprevir + dasabuvir).
Dosage
According to the professional information. The tablets are usually taken twice daily (morning and evening) with food. As a booster, ritonavir is dosed lower (low-dose) and sometimes given only once daily.
Contraindications
- Hypersensitivity
- Severe liver dysfunction
- Combination with agents metabolized by CYP3A4, CYP2D6 and CYP2C9.
- Concurrent administration of rifabutin.
For complete precautions, see the drug label.
Interactions
Ritonavir has a high potential for drug-drug interactions because it interacts with various CYP450 isozymes to varying degrees. It is an inhibitor of CYP3A and CYP2D6 and induces several CYP isoenzymes, including CYP3A, CYP1A2, CYP2C9, CYP2C19, and CYP2B6. Ritonavir is also a substrate of CYP3A and CYP2D6 simultaneously.
Adverse effects
The most common potential adverse effects include nausea, diarrhea, vomiting, weakness, taste disturbances, and perioral and peripheral sensory disturbances (paresthesias).
