INTERFERON ALPHA- 2B
INTERFERON BETA- 1B
PEGINTERFERON ALPHA- 2A
PEGINTERFERON ALPHA- 2B
PEGINTERFERON BETA- 1A
- Cytochrome P450 enzyme substrate: Possibly CYP1A2, CYP2D6, CYP2C19
- Action to be taken: Monitor side effects of marijuana.
- Rationale: Based on available data the pharmacokinetics of interferon alpha2b have not been fully studied. However it appears to be majorly metabolized by the kidneys. Interactions between INTRON A and other drugs have not been fully evaluated. Study by Islam et al, showed that Interferon alpha 2b has significant inhibition of CYP1A2 and CYP2D6 enzymes. Furthermore case report with gemfibrozil and interferon alpha 2b noted a possible interaction between these drugs due to inhibition of CYP1A2 and CYP2C19. In vitro studies have shown that certain cannabinoids and their metabolites are potential substrates of CYP1A2, CYP2D6 and CYP2C19. Furthermore data shows that CBD exerts weak inhibition of CYP2C enzymes while synthetic THC is a weak inhibitor of CYP1A2. Therefore based on the available data, marijuana may interact interferon alpha 2b.
- Action to be taken: Monitor side effects of marijuana.
- Rationale: No interaction studies have been performed with interferonbeta-1a in humans.
Interferons have been reported to reduce the activity of hepatic cytochromeP450-dependent enzymes in humans and animals. Caution should be exercised when administering Rebif in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance.
INTERFERON BETA- 1B
- Action to be taken: Monitor side effects of marijuana.
- Rationale: Interferons have been reported to reduce the activity of hepatic cytochrome P450-dependent enzymes in humans and animals. Caution should be exercised when Betaferon is administered in combination with medicinal products that have a narrow therapeutic index and are largely dependent on the hepatic cytochrome P450 system for clearance. In vitro studies have shown that cannabinoids and their metabolites are substrates for CYP450 enzymes. Therefore based on the available data, interferon beta 1b may increase serum concentration of marijuana.
PEGINTERFERON ALPHA- 2A
- Cytochrome P450 enzyme substrate: Possibly CYP1A2, CYP2D6, CYP2C19
- Action to be taken: Monitor side effects of marijuana.
- Rationale: Study by Brennan et al showed There were no significant differences in the mean serum drug profiles for tolbutamide (CYP2C9), mephenytoin (CYP2C19), debrisoquine (CYP2D6) and dapsone (CYP3A4) in the presence of PEG-IFN alfa-2a as compared with when the drugs were administered alone. In addition, no statistically significant differences were observed in the pharmacokinetics of these four probe drugs after administration of PEG-IFN alfa-2a. From this it can be inferred that the drug had no apparent effect on the hepatic isoenzymes CYP2C9, CYP2C19, CYP2D6 or CYP3A4. However, the mean serum concentrations for theophylline (CYP1A2) were slightly higher and measurable for longer periods in the presence of PEG-IFN alfa-2a than when theophylline was administered alone. In vitro studies have shown that certain cannabinoids and their metabolites are potential substrates of CYP1A2, CYP2D6 and CYP2C19. Furthermore data shows that CBD exerts weak inhibition of CYP2C enzymes while synthetic THC is a weak inhibitor of CYP1A2. Therefore based on the available data, marijuana may interact peginterferon alpha 2a.
PEGINTERFERON ALPHA- 2B
- Cytochrome P450 enzyme substrate: Possibly CYP1A2, CYP2D6, CYP2C9, CYP2C8
- Action to be taken: Monitor side effects of marijuana.
- Rationale: Results of the pharmacokinetic probe study showed that multiple doses of PEG-IFN alfa-2b inhibit CYP1A2 activity to a limited extent, increase CYP2C8/9 activity to a limited extent, increase CYP2D6 activity and had no effect on the activity of CYP3A isoenzymes.In vitro studies have shown that certain cannabinoids and their metabolites are potential substrates of CYP1A2, CYP2D6 and CYP2C19. Furthermore data shows that CBD exerts weak inhibition of CYP2C enzymes while synthetic THC is a weak inhibitor of CYP1A2. Therefore based on the available data, marijuana may interact peginterferon alpha 2b.
PEGINTERFERON BETA- 1A
- Cytochrome P450 enzyme substrate: Possibly CYP1A2
- Action to be taken: Monitor side effects of marijuana.
- Rationale: As a class,IFN was reported to be a weak inhibitor of CYP1A2 but no effects on the other major CYP enzymes or
transporters. Therefore, peginterferon beta-1a was not considered to have a significant risk on impacting the pharmacokinetics of concomitantly administered medications.
References
- Intron A(interferon alpha 2b) package insert. Marc & Co Inc. Whitehouse Station, NJ 2016
- Islam M, Frye RF, Richards TJ, et al. Differential effect of IFNalpha-2b on the cytochrome P450 enzyme system: A potential basis of lFN toxicity and its modulation by other drugs. Clin CancerRes. 2002;8:2480-2487.
- Wong, S. F., Jakowatz, J. G., & Taheri, R. (2005). Potential drug—Drug interaction between interferon alfa-2b and gemfibrozil in a patient with malignant melanoma. Clinical therapeutics, 27(12), 1942-1948.
- Rebif (interferon beta 1a) package insert. Serono, Inc.Rockland, MA and Pfizer Inc. New York, NY 2003
- Betaferon (interferon beta 1b) package insert. Bayer HealthCare Pharmaceuticals Inc. Whippany, NJ 2016
- Brennan BJ, Xu Z-X, Grippo JF. Effect of peginterferon alfa-2a (40KD) on cytochrome P450 isoenzyme activity. British Journal of Clinical Pharmacology. 2013;75(2):497-506. doi:10.1111/j.1365-2125.2012.04373.x.
- Gupta, S. K., Kolz, K., & Cutler, D. L. (2011). Effects of multiple-dose pegylated interferon alfa-2b on the activity of drug-metabolizing enzymes in persons with chronic hepatitis C. European journal of clinical pharmacology, 67(6), 591-599.
- Plegridy.(peginterferon beta 1a) package insert. Biogen Idec Inc. Cambridge, MA 2014
- Watanabe K, Yamaori S, Funahashi T, et al. Cytochrome P450 enzymes involved in the metabolism of tetrahydrocannabinols and cannabinol by human hepatic microsomes. Life Sci. 2007;80:1415-1419.
- Stout SM, Cimino NM. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2014;46:86-95.