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Drug Interactions between Adgyn Estro and clomipramine

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

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Interactions between your drugs

Minor

estradiol clomiPRAMINE

Applies to: Adgyn Estro (estradiol) and clomipramine

The effects of tricyclic antidepressants (TCAs) may be altered in women receiving estrogen-containing therapy. Simultaneous TCA toxicity and reduced effects have been reported. Akathisia has also been reported in some women taking this combination. The mechanism of interaction is unknown but may be related to increased TCA bioavailability or inhibition of hepatic TCA metabolism. The clinical significance of this interaction has not been established. Monitoring for altered effects may be advisable during concomitant therapy. Dose adjustments of the TCA may be required if an interaction is suspected.

References

  1. Abernethy DR, Greenblatt DJ, Shader RI "Imipramine disposition in users of oral contraceptive steroids." Clin Pharmacol Ther 35 (1984): 792-7
  2. Edelbroek PM, Zitman FG, Knoppert-van der Klein EA, van Putten PM, de Wolff FA "Therapeutic drug monitoring of amitriptyline: impact of age, smoking and contraceptives on drug and metabolite levels in bulimic women." Clin Chim Acta 165 (1987): 177-87
  3. Prange AJ, Wilson IC, Alltop LB "Estrogen may well affect response to antidepressant." JAMA 219 (1972): 143-4
  4. Khurana RC "Estrogen-imipramine interaction." JAMA 222 (1972): 702-3
  5. Somani SM, Khurana RC "Mechanism of estrogen-imipramine interaction." JAMA 223 (1973): 560
  6. Krishnan KR, France RD, Ellinwood EH, Jr "Tricyclic-induced akathisia in patients taking conjugated estrogens." Am J Psychiatry 141 (1984): 696-7
View all 6 references

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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

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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

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Minor

estradiol food

Applies to: Adgyn Estro (estradiol)

Coadministration with grapefruit juice may increase the bioavailability of oral estrogens. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits. In a small, randomized, crossover study, the administration of ethinyl estradiol with grapefruit juice (compared to herbal tea) increased peak plasma drug concentration (Cmax) by 37% and area under the concentration-time curve (AUC) by 28%. Based on these findings, grapefruit juice is unlikely to affect the overall safety profile of ethinyl estradiol. However, as with other drug interactions involving grapefruit juice, the pharmacokinetic alterations are subject to a high degree of interpatient variability. Also, the effect on other estrogens has not been studied.

References

  1. Weber A, Jager R, Borner A, et al. "Can grapefruit juice influence ethinyl estradiol bioavailability?" Contraception 53 (1996): 41-7
  2. Schubert W, Eriksson U, Edgar B, Cullberg G, Hedner T "Flavonoids in grapefruit juice inhibit the in vitro hepatic metabolism of 17B-estradiol." Eur J Drug Metab Pharmacokinet 20 (1995): 219-24

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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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