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Drug Interactions between Asendin and modafinil

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

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Interactions between your drugs

Moderate

amoxapine modafinil

Applies to: Asendin (amoxapine) and modafinil

MONITOR: Coadministration with modafinil (the racemate) or armodafinil (the R-enantiomer) may increase the plasma concentrations of tricyclic antidepressants (TCAs) in patients who are deficient in CYP450 2D6 (approximately 7% to 10% of the Caucasian population; similar or lower in other populations). Modafinil and armodafinil are modest inhibitors of CYP450 2C19, an isoenzyme that provides an ancillary pathway for the metabolism of certain TCAs normally metabolized by CYP450 2D6 such as clomipramine or desipramine. In a study of healthy volunteers, coadministration of a single 50 mg dose of clomipramine on the first three days of modafinil therapy (200 mg/day) showed no effect on the pharmacokinetics of either drug. However, increased levels of clomipramine and its active metabolite desmethylclomipramine have been reported in a patient receiving modafinil for narcolepsy. The patient was a CYP450 2D6 poor metabolizer.

MANAGEMENT: Caution is advised if tricyclic antidepressants are coadministered with modafinil or armodafinil in CYP450 2D6-deficient patients. Pharmacologic effects and serum TCA levels should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy, and the TCA dosage adjusted accordingly. Patients should be advised to notify their physician if they experience possible signs of TCA toxicity such as excessive drowsiness, restlessness, agitation, ataxia, blurred vision, tachycardia, arrhythmia, and seizures.

References

  1. Grozinger M, Hartter S, Hiemke C, Griese EU, Roschke J (1998) "Interaction of modafinil and clomipramine as comedication in a narcoleptic patient." Clin Neuropharmacol, 21, p. 127-9
  2. (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
  3. Robertson P, Decory HH, Madan A, Parkinson A (2000) "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos, 28, p. 664-71
  4. (2007) "Product Information. Nuvigil (armodafinil)." Cephalon Inc
  5. Cerner Multum, Inc. "Australian Product Information."
View all 5 references

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Drug and food interactions

Moderate

amoxapine food

Applies to: Asendin (amoxapine)

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References

  1. Dorian P, Sellers EM, Reed KL, et al. (1983) "Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction." Eur J Clin Pharmacol, 25, p. 325-31
  2. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R (1983) "Biotransformation of amitriptyline in alcoholic depressive patients." Eur J Clin Pharmacol, 24, p. 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH (1988) "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther, 43, p. 509-18
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M (1975) "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther, 17, p. 515-22
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF (1990) "Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls." J Stud Alcohol, 51, p. 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA (1982) "Imipramine disposition in alcoholics." J Clin Psychopharmacol, 2, p. 2-7
View all 7 references

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Minor

modafinil food

Applies to: modafinil

Administration with food may delay the absorption of modafinil (the racemate) and armodafinil (the R-enantiomer) without significantly affecting their overall bioavailability. According to the product labeling, modafinil's absorption may be delayed by approximately one hour if taken with food. Similarly, the time to reach peak plasma concentration (Tmax) of armodafinil may be delayed by approximately 2 to 4 hours in the fed state.

References

  1. (2001) "Product Information. Provigil (modafinil)." Cephalon, Inc
  2. (2007) "Product Information. Nuvigil (armodafinil)." Cephalon 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

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