AZATANAVIR
- Cytochrome P450 enzyme substrate: CYP3A4
- Action to be taken: Caution and close monitoring
- Rationale: Azatanavir 's bioavailabilty has been found to be increased with administration of grapefruit juice due to inhibition of CYP3A4.Atazanavir has also been found to interact with selected azole antifungal drugs. Caution and close monitoring of anticipated responses are recommended when administering atazanavir with azole antifungals.
DARUNAVIR
- Cytochrome P450 enzyme subsstrate: CYP3A
- P-gp substrate
- Action to be taken: Caution and close monitoring
- Rationale: Concomitant systemic use of azole antifungals with darunavir may increase plasma concentrations of darunavir.Caution and close monitoring are recommended.
FOSAMPRENAVIR
- Cytochrome P450 enzyme substrate: CYP3A4, CYP2C9, and CYP2D6
- P-gp substrate
- Action to be taken: Caution and close monitoring
- Rationale: Fosamprenavir is metabolized to the active drug amprenavir.Amprenavir is metabolized by the cytochrome P450 enzyme system. Amprenavir is a strong inhibitor and a substrate of CYP3A4, an inducer and substrate of P-glycoprotein (Pgp), and a substrate of CYP2C9, and CYP2D6. Data also suggest that amprenavir induces CYP3A4. Caution should be used when co-administering medications that are substrates, inhibitors, or inducers of CYP3A4.
INDINAVIR
- Cytochrome P450 enzyme substrate: CYP3A4
- P-gp substrate
- Action to be taken: No action needed
- Rationale: The effect of marijuana and dronabinol on the pharmacokinetics of indinavir has been evaluated in a randomized trial. Although statistically significant decrease in indinavir Cmax has been noted in the marijuana arm. The magnitude of change in indinavir pharmacokinetics is thought to be clinically insignificant. In the authors' opinion, the use of marijuana or dronabinol is unlikely to affect the antiretroviral efficacy of indinavir.
NELFINAVIR
- Cytochrome P450 enzyme substrate: CYP3A4, CYP2C19
- P-gp substrate
- Action to be taken: No action needed
- Rationale: The effect of marijuana and dronabinol, on the pharmacokinetics of nelfinavir has been evaluated in a randomized trial. The magnitude of changes in nelfinavir pharmacokinetics due to the co-administration of marijuana or dronabinol were not thought to be clinically significant. In the authors' opinion, the use of marijuana or dronabinol is unlikely to affect the antiretroviral efficacy of nelfinavir.
TIPRINAVIR
- Cytochrome P450 enzyme substrate: CYP3A4
- P-gp substrate
- Action to be taken: Caution and close monitoring
- Rationale: Nilotinib is an inhibitor of both P-gp and CYP3A4. Increased tipranavir concentrations are likely. Use of caution is neccessary when co-adminstering dronabinol with tiprinavir. Dronabinol is a CYP2C9 and 3A4 substrate and concomitant use may result in elevated plasma concentrations of dronabinol and increase in dronabinol related adverse reactions.
RITONAVIR
- Cytochrome P450 enzyme substrate: CYP3A4, CYP2D6
- Action to be taken: Caution and close monitoring
- Rationale: Ritonavir is a strong CYP3A4 inhibitor and may result in higher concentrations of THC and CBD. Patients should be monitored for enhanced adverse effects of THC and CBD when ritonavir is co -administered with marijuana.
LOPINAVIR + RITONAVIR
- Cytochrome P450 enzyme substrate: CYP3A
- Action to be taken: Caution and close monitoring
- Rationale: Ritonavir is a strong CYP3A4 inhibitor and may result in higher concentrations of THC and CBD. Patients should be monitored for enhanced adverse effects of THC and CBD when ritonavir is co -administered with marijuana.
SAQUINAVIR
- Cytochrome P450 enzyme substrate: CYP3A
- Action to be taken: Caution and close monitoring
- Rationale: Saquinavir is a strong CYP3A4 inhibitor and may result in higher concentrations of THC and CBD. Patients should be monitored for enhanced adverse effects of THC and CBD when saquinavir is co -administered with marijuana.
References
- Reyataz (atazanavir) package insert. Princeton, NJ: Bristol-Myers Squibb Company; 2015 Sept.
- Hansten P, Horn J. The Top 100 Drug Interactions: A Guide to Patient Management. includes table of CYP450 and drug transporter substrates and modifiers (appendices). H & H Publications, LLP 2014 edition.
- Prezista (darunavir) package insert. Titusville, NJ: Janssen Pharmaceuticals, Inc.; 2016 Jun.
- Lexiva (fosamprenavir calcium) package insert. Research Triangle Park, NC: ViiV Healthcare; 2016 Mar.) (Wire MB, Shelton MJ, Studenberg S. Fosamprenavir clinical pharmacokinetics and drug interactions of the amprenavir prodrug. Clin Pharmacokinet 2006;45:137—68.
- Kosel BW, Aweeka FT, Benowitz NL, et al. The effects of cannabinoids on the pharmacokinetics of indinavir and nelfinavir. AIDS 2002;16:543—50.
- Tasigna® (nilotinib) package insert. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2007 Oct.
- Clinical Pharmacology. Clinicalpharmacologycom. 2016. http://www.clinicalpharmacology.com. Accessed August 17, 2016.
- Pdr.net. (2017). Aptivus (tipranavir) dose, indications, adverse effects, interactions... from PDR.net. [online] Available at: http://www.pdr.net/drug-summary/Aptivus-tipranavir-1740 [Accessed 28 Aug. 2017].
- Norvir(ritonavir) package insert. Abbott Laboratories , North Chicago , IL; October 2005
- Kaletra (lopinavir/ritonavir) package insert. AbbVie, Inc., North Chicago , IL; October 2016
- Abrams DI, Hilton JF, Leiser RJ, Shade SB, Elbeik TA, Aweeka FT, et al. Short-Term Effects of Cannabinoids in Patients with HIV-1 Infection: A Randomized, Placebo-Controlled Clinical Trial. Ann Intern Med. 2003;139:258–266. doi: 10.7326/0003-4819-139-4-200308190-00008
- Watanabe K, Yamaori S, Funahashi T, Kimura T, Yamamoto I. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sciences. 2007;80:1415-1419