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Trazodone (Trazodone Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Drug Interactions

In vitro drug metabolism studies suggest that there is a potential for drug interactions when trazodone is given with CYP3A4 inhibitors. Ritonavir, a potent CYP3A4 inhibitor, increased the Cmax, AUC, and elimination half-life, and decreased clearance of trazodone after administration of ritonavir twice daily for 2 days. Adverse effects including nausea, hypotension, and syncope were observed when ritonavir and trazodone were co-administered. It is likely that ketoconazole, indinavir, and other CYP3A4 inhibitors such as itraconazole or nefazodone may lead to substantial increases in trazodone plasma concentrations, with the potential for adverse effects. If trazodone is used with a potent CYP3A4 inhibitor, a lower dose of trazodone should be considered.

Carbamazepine reduced plasma concentrations of trazodone when co-administered. Patients should be closely monitored to see if there is a need for an increased dose of trazodone when taking both drugs.

Increased serum digoxin or phenytoin levels have been reported to occur in patients receiving trazodone hydrochloride concurrently with either of those two drugs.

It is not known whether interactions will occur between monoamine oxidase (MAO) inhibitors and trazodone hydrochloride. Due to the absence of clinical experience, if MAO inhibitors are discontinued shortly before or are to be given concomitantly with trazodone hydrochloride, therapy should be initiated cautiously with gradual increase in dosage until optimum response is achieved.

OVERDOSAGE

Animal Oral LD50

The oral LD50 of the drug is 610 mg/kg in mice, 486 mg/kg in rats, and 560 mg/kg in rabbits.

Signs and Symptoms

Death from overdose has occurred in patients ingesting trazodone hydrochloride and other drugs concurrently (namely, alcohol; alcohol + chloral hydrate + diazepam; amobarbital; chlordiazepoxide; or meprobamate).

The most severe reactions reported to have occurred with overdose of trazodone alone have been priapism, respiratory arrest, seizures, and EKG changes. The reactions reported most frequently have been drowsiness and vomiting. Overdosage may cause an increase in incidence or severity of any of the reported adverse reactions (see ADVERSE REACTIONS).

Treatment

There is no specific antidote for trazodone. Treatment should be symptomatic and supportive in the case of hypotension or excessive sedation. Any patient suspected of having taken an overdose should have the stomach emptied by gastric lavage. Forced diuresis may be useful in facilitating elimination of the drug.

CONTRAINDICATIONS

This product is contraindicated in patients hypersensitive to trazodone.

REFERENCES

  1. Williams JBW, Ed: Diagnostic and Statistical Manual of Mental Disorders-III, American Psychiatric Association May, 1980.

  2. Lue TF, Physiology of erection and pathophysiology of impotence. In: Wash PC, Retik AB, Stamey TA, Vaughan ED, eds. Campbell’s Urology. Sixth edition. Philadelphia: W.B. Saunders; 1992: 722-725.

  3. Goldstein I, Krane RJ, Diagnosis and therapy of erectile dysfunction. In: Wash PC, Retik AB, Stamey TA, Vaughan ED, eds. Campbell’s Urology. Sixth edition. Philadelphia: W.B. Saunders; 1992: 3071-3072.

  4. Yealy DM, Hogya PT: Priapism. Emerg Med Clin North Am. 1988; 6:509-520.

  5. Banos JE, Bosch F, Farre M, Drug-induced priapism. Its aetiology, incidence and treatment. Med Toxicol Adverse Drug Exp. 1989; 4:46-58.

  6. O’Brien WM, O’Connor KP, Lynch JH. Priapism: current concepts. Ann Emerg Med. 1989: 980-983.

  7. Bardin ED, Krieger JN. Pharmacological priapism: comparison of trazodone- and papaverine-associated cases. Int Urol Nephrol. 1990; 22:147-152.

Watson Laboratories, Inc.
Corona, CA 92880 USA

Revised: August 2007
0807B

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