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Drug Interactions between olanzapine / samidorphan and phenobarbital

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

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Interactions between your drugs

Moderate

PHENobarbital OLANZapine

Applies to: phenobarbital and olanzapine / samidorphan

MONITOR: Coadministration with inducers of CYP450 1A2 may decrease the plasma concentrations of olanzapine. Data from available studies indicate that olanzapine is primarily metabolized by CYP450 1A2 and, to a lesser extent, by CYP450 2D6 and uridine diphosphate glucuronosyltransferase (UGT) 1A4. When coadministered with rifampin, a moderate CYP450 1A2 inducer that also induces UGT 1A4, olanzapine peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 11% and 48%, respectively. Coadministration with 200 mg twice daily of carbamazepine, another CYP450 1A2 inducer, caused an approximately 50% increase in the clearance of olanzapine. Higher daily dosages of carbamazepine may cause an even greater increase in olanzapine clearance.

MANAGEMENT: The potential for diminished pharmacologic effects of olanzapine should be considered during coadministration with CYP450 1A2 inducers. Alternative treatments may be required if an interaction is suspected.

References (3)
  1. (2002) "Product Information. Tegretol (carbamazepine)." Novartis Pharmaceuticals
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  3. (2021) "Product Information. Lybalvi (olanzapine-samidorphan)." Alkermes, Inc
Moderate

PHENobarbital samidorphan

Applies to: phenobarbital and olanzapine / samidorphan

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of samidorphan. According to the prescribing information, samidorphan is primarily metabolized by CYP450 3A4, with minor contributions from CYP450 2C8, 2C19, and 3A5. When olanzapine-samidorphan was coadministered with rifampin, a potent CYP450 3A4 inducer, samidorphan peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 44% and 73%, respectively. Olanzapine Cmax and AUC also decreased by 11% and 48%, respectively, most likely due to induction of CYP450 1A2 and/or uridine diphosphate glucuronosyltransferase (UGT) 1A4 by rifampin.

MANAGEMENT: Concomitant use of olanzapine-samidorphan with potent CYP450 3A4 inducers is not recommended.

References (1)
  1. (2021) "Product Information. Lybalvi (olanzapine-samidorphan)." Alkermes, Inc

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
Moderate

OLANZapine food

Applies to: olanzapine / samidorphan

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc

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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