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Drug Interactions between Mebaral and sirolimus protein-bound

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

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Interactions between your drugs

Moderate

mephobarbital sirolimus protein-bound

Applies to: Mebaral (mephobarbital) and sirolimus protein-bound

MONITOR: Coadministration of protein-bound sirolimus intravenous suspension with inducers of CYP450 3A4 may decrease the systemic exposure to sirolimus, which is primarily metabolized by the isoenzyme and also a substrate of the P-glycoprotein (P-gp) efflux transporter. No formal studies evaluating the drug interaction potential of protein-bound sirolimus have been conducted. However, data are available for oral sirolimus coadministered with rifampin, a potent inducer of CYP450 3A4 and P-gp. When a single 20 mg dose of sirolimus oral solution was administered to 14 healthy volunteers following pretreatment with rifampin 600 mg daily for 14 days, mean sirolimus peak blood concentration (Cmax) and systemic exposure (AUC) decreased by 71% and 82%, respectively. Reduced efficacy of protein-bound sirolimus may occur.

MANAGEMENT: The potential for diminished pharmacologic effects of protein-bound sirolimus should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

References

  1. (2001) "Product Information. Rapamune (sirolimus)." Wyeth-Ayerst Laboratories
  2. (2022) "Product Information. Fyarro (sirolimus protein-bound)." Aadi Bioscience, Inc.

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Drug and food interactions

Major

mephobarbital food

Applies to: Mebaral (mephobarbital)

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

References

  1. Gupta RC, Kofoed J (1966) "Toxological statistics for barbiturates, other sedatives, and tranquilizers in Ontario: a 10-year survey." Can Med Assoc J, 94, p. 863-5
  2. Misra PS, Lefevre A, Ishii H, Rubin E, Lieber CS (1971) "Increase of ethanol, meprobamate and pentobarbital metabolism after chronic ethanol administration in man and in rats." Am J Med, 51, p. 346-51
  3. Saario I, Linnoila M (1976) "Effect of subacute treatment with hypnotics, alone or in combination with alcohol, on psychomotor skills related to driving." Acta Pharmacol Toxicol (Copenh), 38, p. 382-92
  4. Stead AH, Moffat AC (1983) "Quantification of the interaction between barbiturates and alcohol and interpretation of fatal blood concentrations." Hum Toxicol, 2, p. 5-14
  5. Seixas FA (1979) "Drug/alcohol interactions: avert potential dangers." Geriatrics, 34, p. 89-102
View all 5 references

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Moderate

sirolimus protein-bound food

Applies to: sirolimus protein-bound

GENERALLY AVOID: Coadministration of protein-bound sirolimus intravenous suspension with grapefruit juice may increase the systemic exposure to sirolimus. The proposed mechanism is inhibition of CYP450 3A4-mediated metabolism of sirolimus by certain compounds present in grapefruit. However, grapefruit juice primarily inhibits CYP450 3A4-mediated first-pass metabolism in the gut wall and may have limited effects on medications that are not administered orally. No formal studies evaluating the drug interaction potential of protein-bound sirolimus have been conducted. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition.

MANAGEMENT: The manufacturer recommends avoiding grapefruit and grapefruit juice during treatment with protein-bound sirolimus.

References

  1. (2022) "Product Information. Fyarro (sirolimus protein-bound)." Aadi Bioscience, Inc.

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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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