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Drug Interactions between SGard and Zelboraf

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

melatonin vemurafenib

Applies to: SGard (melatonin) and Zelboraf (vemurafenib)

MONITOR: Coadministration with vemurafenib may increase the plasma concentrations of drugs that are substrates of the CYP450 1A2 and/or 2D6 isoenzymes. The mechanism is decreased clearance due to inhibition of CYP450 1A2 and 2D6 activity by vemurafenib. The interaction has been studied with caffeine and dextromethorphan, probe substrates for CYP450 1A2 and 2D6, respectively. In an in vivo phenotypic cocktail drug-drug interaction study in patients with cancer, caffeine systemic exposure (AUC) increased by 2.6-fold when a single dose of the CYP450 probe substrate cocktail was administered following treatment with vemurafenib 960 mg twice daily for 15 days, while dextromethorphan AUC increased by 47%.

MANAGEMENT: Caution is advised if vemurafenib must be used concurrently with drugs that undergo metabolism by CYP450 1A2 and/or 2D6. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vemurafenib is added to or withdrawn from therapy. Concomitant use of vemurafenib and substrates of CYP450 1A2 and/or 2D6 with a narrow therapeutic index (e.g., antiarrhythmics; theophylline) should be avoided if possible.

References

  1. "Product Information. Zelboraf (vemurafenib)." Genentech (2011):

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Drug and food interactions

Moderate

melatonin food

Applies to: SGard (melatonin)

MONITOR: Oral caffeine may significantly increase the bioavailability of melatonin. The proposed mechanism is inhibition of CYP450 1A2 first-pass metabolism. After administration of melatonin 6 mg and caffeine 200 mg orally (approximately equivalent to 1 large cup of coffee) to 12 healthy subjects, the mean peak plasma concentration (Cmax) of melatonin increased by 137% and the area under the concentration-time curve (AUC) increased by 120%. The metabolic inhibition was greater in nonsmokers (n=6) than in smokers (n=6). The greatest effect was seen in subjects with the *1F/*1F genotype (n=7), whose melatonin Cmax increased by 202%. The half-life did not change significantly. The clinical significance of this interaction is unknown.

According to some authorities, alcohol may reduce the effect of melatonin on sleep. The mechanism of this interaction is not fully understood.

In addition, CYP450 1A2 inducers like cigarette smoking may reduce exogenous melatonin plasma levels. In a small clinical trial (n=8), habitual smokers had their melatonin plasma levels measured two times, each after a single oral dose of 25 mg of melatonin. They had smoked prior to the first measurement but had not smoked for 7 days prior to the second. Cigarette smoking significantly reduced melatonin plasma exposure (AUC) as compared to melatonin levels after 7 days of smoking abstinence (7.34 +/- 1.85 versus 21.07 +/- 7.28 nmol/L*h, respectively).

MANAGEMENT: Caution and monitoring are recommended if melatonin is used with inhibitors of CYP450 1A2 like caffeine or inducers of CYP450 1A2 like cigarette smoking. Consumption of alcohol should be avoided when taking melatonin.

References

  1. Hartter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K "Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity." Br J Clin Pharmacol 56 (2003): 679-682
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Ursing C, Bahr CV, Brismar K, Rojdmark S "Influence of cigarette smoking on melatonin levels in man" Eur J Clin Pharmacol 61 (2005): 197-201

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

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