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Drug Interaction Report

2 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

PENTobarbital DOXOrubicin liposomal

Applies to: Nembutal Sodium (pentobarbital), Lipodox 50 (doxorubicin liposomal)

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of doxorubicin, which is primarily metabolized by the isoenzyme. One group of investigators reported a nearly 60% increase in the plasma clearance of doxorubicin in patients receiving barbiturates compared to those not receiving barbiturates. Reduced therapeutic effects of doxorubicin may occur. In addition, when two or more medications with similar adverse effect profiles are given concurrently, the likelihood of experiencing these adverse reactions may be increased. For example, coadministration with other agents that can prolong the QT interval (e.g., apalutamide, encorafenib, enzalutamide) may result in additive effects and an increased risk of ventricular arrhythmias like torsade de pointes.

MANAGEMENT: Concomitant use of doxorubicin with CYP450 3A4 inducers should generally be avoided, particularly potent ones like carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, primidone (partially metabolized to phenobarbital), rifamycins, and St. John's wort. Close monitoring for potentially reduced efficacy of doxorubicin is recommended if coadministration is required. If the CYP450 3A4 inducer also carries a risk of prolonging the QT interval, then obtaining more frequent electrocardiograms (ECGs) to monitor the QT interval may be advisable. Patients should be counseled to seek immediate medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, syncope, palpitations, irregular heartbeat, and/or shortness of breath..

References

  1. Riggs CE Jr, Engel S, Wesley M, Wiernik PH, Bachur NR (1982) "Doxorubicin pharmacokinetics: prochlorperazine and barbiturate effects." Clin Pharmacol Ther, 31, p. 263
  2. (2001) "Product Information. Adriamycin PFS (doxorubicin)." Pharmacia and Upjohn
  3. (2001) "Product Information. Doxil (doxorubicin liposomal)." Sequus Pharmaceuticals Inc
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
View all 4 references

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Drug and food interactions

Major

PENTobarbital food

Applies to: Nembutal Sodium (pentobarbital)

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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Therapeutic duplication warnings

No duplication 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.

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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.

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Further information

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

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