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Drug Interactions between Istodax and Levsin with Phenobarbital

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

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Interactions between your drugs

Moderate

PHENobarbital romiDEPsin

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital) and Istodax (romidepsin)

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may increase the plasma concentrations of romidepsin. The exact mechanism of interaction has not been established, particularly since romidepsin is a substrate of CYP450 3A4, and induction of the isoenzyme would be expected to reduce its plasma concentration. In patients with advanced cancer, administration of romidepsin 14 mg/m2 (4-hour infusion) with the potent CYP450 3A4 inducer, rifampin, unexpectedly increased romidepsin peak plasma concentration (Cmax) and systemic exposure (AUC) by 60% and 80%, respectively, compared to romidepsin administered alone. In addition, rifampin decreased romidepsin clearance by 44% and volume of distribution by 52%. It is not known if other potent CYP450 3A4 inducers would alter the pharmacokinetics of romidepsin in the same manner.

MANAGEMENT: The use of romidepsin in combination with potent CYP450 3A4 inducers such as carbamazepine, dexamethasone, enzalutamide, phenobarbital, phenytoin, rifamycins, and St. John's wort should generally be avoided if possible. Alternative treatment lacking CYP450 3A4-inducing activity should be considered in patients receiving romidepsin. If concomitant use is required, patients should be closely monitored for development of hematologic toxicities such as anemia, leukopenia, and thrombocytopenia as well as electrocardiographic changes such as QT interval prolongation and T-wave and ST-segment changes.

References

  1. "Product Information. Istodax (romidepsin)." Gloucester Pharmaceuticals (2009):

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Drug and food interactions

Major

PHENobarbital food

Applies to: Levsin with Phenobarbital (hyoscyamine / 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

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

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Moderate

hyoscyamine food

Applies to: Levsin with Phenobarbital (hyoscyamine / phenobarbital)

GENERALLY AVOID: Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

MANAGEMENT: Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References

  1. Linnoila M "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol 6 (1973): 107-12

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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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