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Drug Interactions between Rex Paracetamol and vemurafenib

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

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Interactions between your drugs

Moderate

acetaminophen vemurafenib

Applies to: Rex Paracetamol (acetaminophen) and 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever vemurafenib is added to or withdrawn from therapy.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

Major

acetaminophen food

Applies to: Rex Paracetamol (acetaminophen)

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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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.

See also

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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