Skip to main content

Drug Interactions between clomipramine and Nuvigil

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

Edit list (add/remove drugs)

Interactions between your drugs

Moderate

clomiPRAMINE armodafinil

Applies to: clomipramine and Nuvigil (armodafinil)

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effects and serum TCA levels should be monitored more closely whenever modafinil or armodafinil is added to or withdrawn from therapy, and the TCA dosage adjusted accordingly.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 "Interaction of modafinil and clomipramine as comedication in a narcoleptic patient." Clin Neuropharmacol 21 (1998): 127-9
  2. "Product Information. Provigil (modafinil)." Cephalon, Inc PROD (2001):
  3. Robertson P, Decory HH, Madan A, Parkinson A "In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil." Drug Metab Dispos 28 (2000): 664-71
  4. "Product Information. Nuvigil (armodafinil)." Cephalon Inc (2007):
  5. Cerner Multum, Inc. "Australian Product Information." O 0
View all 5 references

Switch to consumer interaction data

Drug and food interactions

Moderate

clomiPRAMINE food

Applies to: clomipramine

MONITOR: Limited data suggest that the administration of clomipramine with grapefruit juice or cranberry juice may significantly increase plasma drug concentrations of clomipramine. Clomipramine is initially demethylated by CYP450 1A2, 3A3 and 3A4 before undergoing further metabolism to 8-hydroxyclomipramine. The increase in clomipramine bioavailability may stem from inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The precise mechanism by which cranberry juice exerts its effects is unknown, but may involve inhibition of CYP450 isoenzymes. This interaction has occasionally been exploited in attempts to improve symptomatic control of obsessive compulsive disorder.

MANAGEMENT: Patients receiving clomipramine therapy who ingest cranberry juice, grapefruits, or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References

  1. Oesterheld J, Kallepalli BR "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol 17 (1997): 62-3
  2. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther 68 (2000): 468-77
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. Cerner Multum, Inc. "Australian Product Information." O 0
View all 4 references

Switch to consumer interaction data

Moderate

clomiPRAMINE food

Applies to: clomipramine

GENERALLY AVOID: The combination of ethanol and a tricyclic antidepressant may result in additive impairment of motor skills, especially driving skills. Also, one study has suggested that clomipramine metabolism is significantly impaired for several weeks or more following discontinuation of chronic alcohol consumption.

MANAGEMENT: Patients should be warned of this interaction and advised to limit their ethanol intake while taking tricyclic antidepressants. Monitoring for TCA toxicity (CNS depression, excessive anticholinergic effects, hypotension, arrhythmias) is recommended during alcohol withdrawal.

References

  1. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M "Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving." Clin Pharmacol Ther 17 (1975): 515-22
  2. Berlin I, Cournot A, Zimmer R, et al. "Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects." Psychopharmacology (Berl) 100 (1990): 40-5
  3. Balant-Gorgia AE, Gay M, Gex-Fabry M, Balant LP "Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients." Ther Drug Monit 14 (1992): 119-24

Switch to consumer interaction data

Minor

armodafinil food

Applies to: Nuvigil (armodafinil)

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

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer