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Drug Interactions between bosentan and phenobarbital

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

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Interactions between your drugs

Moderate

PHENobarbital bosentan

Applies to: phenobarbital and bosentan

MONITOR: Coadministration with potent CYP450 3A4 and/or 2C9 inducers may decrease the plasma concentrations and therapeutic effects of bosentan. The proposed mechanism is increased clearance of bosentan by induction of CYP450 3A4 and/or 2C9, the isoenzymes responsible for the metabolic clearance of bosentan. In healthy subjects, concomitant use of rifampin initially led to a mean 6-fold increase in bosentan trough levels; however, after 7 days of concomitant use with bosentan 125 mg twice daily, rifampin decreased the plasma concentrations of bosentan by 58%. It was suggested that this decrease could achieve nearly 90% in an individual case.

MANAGEMENT: Until more information is available, the possibility of a diminished therapeutic response to bosentan should be considered when it is coadministered with a potent CYP450 3A4 and/or 2C9 inducer. Clinical and laboratory monitoring should be considered whenever a potent CYP450 3A4 and/or 2C9 inducer is added to or withdrawn from therapy, and the bosentan dosage adjusted as necessary.

References (2)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."

Drug and food interactions

Major

PHENobarbital food

Applies to: phenobarbital

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 (5)
  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

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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