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Drug Interactions between clomipramine and dextrothyroxine sodium

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

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Interactions between your drugs

Moderate

dextrothyroxine sodium clomiPRAMINE

Applies to: dextrothyroxine sodium and clomipramine

MONITOR: Coadministration of thyroid hormone replacement therapy with tricyclic antidepressants may accelerate the onset or potentiate the action of tricyclic antidepressants, increasing the risk of cardiac arrhythmias and CNS stimulation. The proposed mechanism may be an increased receptor sensitivity to catecholamines. Some clinicians have used this interaction therapeutically. However, individual cases of paroxysmal tachycardia, hypothyroidism, and thyrotoxicosis have also been reported.

MANAGEMENT: Patients receiving concomitant thyroid hormone replacement therapy and tricyclic antidepressant therapy should be closely monitored for cardiac arrhythmias and CNS stimulation. Advise patients to contact their doctor if they experience toxicity symptoms such as: anxiety, agitation, insomnia, shortness of breath, irregular or fast heartbeat, and lightheadedness or dizziness.

References (20)
  1. Prange AJ, Wilson IC, Rabon AM, Lipton MA (1969) "Enhancement of imipramine antidepressant activity by thyroid hormone." Am J Psychiatry, 126, p. 457-69
  2. Wilson IC, Prange AJ, McClane TK, Rabon AM, Lipton MA (1970) "Thyroid-hormone enhancement of imipramine in nonretarded depressions." N Engl J Med, 282, p. 1063-7
  3. Wheatley D (1972) "Potentiation of amitriptyline by thyroid hormone." Arch Gen Psychiatry, 26, p. 229-33
  4. (2002) "Product Information. Elavil (amitriptyline)." Stuart Pharmaceuticals
  5. (2002) "Product Information. Synthroid (levothyroxine)." Abbott Pharmaceutical
  6. (2001) "Product Information. Anafranil (clomipramine)." Basel Pharmaceuticals
  7. (2001) "Product Information. Cytomel (liothyronine)." Monarch Pharmaceuticals Inc
  8. Altshuler LL, Bauer M, Frye MA, et al. (2001) "Does thyroid supplementation accelerate tricyclic antidepressant response? A review and meta-analysis of the literature." Am J Psychiatry, 158, p. 1617-22
  9. Joffe RT (1998) "The use of thyroid supplements to augment antidepressant medication." J Clin Psychiatry, 59 Suppl 5, 26-9; discussion 30-1
  10. Joffe RT, Singer W, Levitt AJ, MacDonald C (1993) "A placebo-controlled comparison of lithium and triiodothyronine augmentation of tricyclic antidepressants in unipolar refractory depression." Arch Gen Psychiatry, 50, p. 387-93
  11. Cooke RG, Joffe RT, Levitt AJ (1992) "T3 augmentation of antidepressant treatment in T4-replaced thyroid patients." J Clin Psychiatry, 53, p. 16-8
  12. Cooke RG (1990) "T3 augmentation of a tricyclic antidepressant in a patient receiving T4 maintenance therapy." Am J Psychiatry, 147, p. 255
  13. Extein IL, Gold MS (1988) "Thyroid hormone potentiation of tricyclics." Psychosomatics, 29, p. 166-74
  14. Schwarcz G, Halaris A, Baxter L, Escobar J, Thompson M, Young M (1984) "Normal thyroid function in desipramine nonresponders converted to responders by the addition of L-triiodothyronine." Am J Psychiatry, 141, p. 1614-6
  15. Goodwin FK, Prange AJ Jr, Post RM, Muscettola G, Lipton MA (1982) "Potentiation of antidepressant effects by L-triiodothyronine in tricyclic nonresponders." Am J Psychiatry, 139, p. 34-8
  16. Swartz CM (1982) "Dependency of tricyclic antidepressant efficacy on thyroid hormone potentiation: case studies." J Nerv Ment Dis, 170, p. 50-2
  17. (2005) "Product Information. Triostat (liothyronine)." JHP Pharmaceuticals
  18. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  19. Cerner Multum, Inc. "Australian Product Information."
  20. Posternak M, Novak S, Stern R, et al. (2008) "A pilot effectiveness study: placebo-controlled trial of adjunctive L-triiodothyronine (T3) used to accelerate and potentiate the antidepressant response." Int J Neuropsychopharmacol, 11, p. 15-25

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 (4)
  1. Oesterheld J, Kallepalli BR (1997) "Grapefruit juice and clomipramine: shifting metabolitic ratios." J Clin Psychopharmacol, 17, p. 62-3
  2. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Cerner Multum, Inc. "Australian Product Information."
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 (3)
  1. 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
  2. Berlin I, Cournot A, Zimmer R, et al. (1990) "Evaluation and comparison of the interaction between alcohol and moclobemide or clomipramine in healthy subjects." Psychopharmacology (Berl), 100, p. 40-5
  3. Balant-Gorgia AE, Gay M, Gex-Fabry M, Balant LP (1992) "Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients." Ther Drug Monit, 14, p. 119-24

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.

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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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