serzone, nefazodone, interactions

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Serzone - Nefazodone Hydrochloride - Interactions and Warnings

Nefazadone should be added to the list of agents that cause acute dystonic reactions.
- Vet Hum Toxicol 1999 Oct;41(5):321-2 -- Nefazadone-induced acute dystonic reaction. -- Burda A, Webster K, Leikin JB, Chan SB, Stokes KA.

Pharmacokinetic interactions (e.g. increased bioavailability), myositis, and rhabdomyolysis have been reported following concurrent use of atorvastatin, cerivastatin, simvastatin or lovastatin and cyclosporine A, mibefradil or nefazodone.
- Atheroscler Suppl 2002 May;3(1):35-40 -- Pharmacological interactions of statins. -- Paoletti R, Corsini A, Bellosta S.

Nefazodone is a potent inhibitor of CYP3A4 and is therefore absolutely contraindicated with concurrent administration of terfenadine, astemizole, and cisapride.
- Depress Anxiety 1998;7 Suppl 1:24-32 -- New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine. -- Owen JR, Nemeroff CB.

Report of serotonin syndrome associated with nefazodone and paroxetine.
- Ann Emerg Med 1997 Feb;29(2):287-9 -- Serotonin syndrome associated with nefazodone and paroxetine. -- John L, Perreault MM, Tao T, Blew PG.

Because digoxin has a narrow therapeutic index, monitoring of plasma digoxin levels and appropriate adjustment of dosage are recommended when nefazodone and digoxin are administered concurrently.
- J Clin Pharmacol 1996 Feb;36(2):160-7 -- Assessment of pharmacokinetic and pharmacodynamic drug interactions between nefazodone and digoxin in healthy male volunteers. -- Dockens RC, Greene DS, Barbhaiya RH.

Because alprazolam concentrations in plasma are increased in the presence of nefazodone, a reduction in alprazolam dosage is recommended when the two agents are coadministered.
- J Clin Psychopharmacol 1995 Dec;15(6):399-408 -- Coadministration of nefazodone and benzodiazepines: III. A pharmacokinetic interaction study with alprazolam. -- Greene DS, Salazar DE, Dockens RC, Kroboth P, Barbhaiya RH.

Some cardiovascular side effects were noted such as asymptomatic reduced systolic blood pressure and asymptomatic sinus bradycardia. Treatment should be initiated at a reduced dose in elderly patients because of reduced hepatic clearance of nefazodone in this age group. Final dose range may be similar in healthy younger and older patients. Coadministration of terfenadine or astemizole with nefazodone is contraindicated because nefazodone can increase the plasma levels of these two drugs. Therapeutic benefits include a low incidence of clinically troublesome side effects and lack of unwanted psychic activation, sexual dysfunction, weight change, and the cardiotoxicity of other antidepressants.
- J Clin Psychiatry 1996;57 Suppl 2:31-8 -- The safety profile of nefazodone. -- Robinson DS, Roberts DL, Smith JM, Stringfellow JC, Kaplita SB, Seminara JA, Marcus RN.

Nefazodone was associated with an elevation in the plasma concentration of zopiclone, possibly resulting in enhanced hypnosedative efficacy.
- Ann Pharmacother 2001 Nov;35(11):1378-80 -- Possible interaction of zopiclone and nefazodone. -- Alderman CP, Gebauer MG, Gilbert AL, Condon JT.

In healthy men and women, concomitant nefazodone treatment at a therapeutic dose increases exposure to both terfenadine and carboxyterfenadine. A similar interaction occurs with loratadine, although it is of lesser magnitude.
- Clin Pharmacol Ther 2001 Mar;69(3):96-103 -- Loratadine and terfenadine interaction with nefazodone: Both antihistamines are associated with QTc prolongation. -- Abernethy DR, Barbey JT, Franc J, Brown KS, Feirrera I, Ford N, Salazar DE.

The results from this study suggest that nefazodone has only modest pharmacokinetic and pharmacodynamic interactions with haloperidol. Although no specific recommendations can be made, dosage adjustment may be necessary for haloperidol when coadministered with nefazodone.
- J Clin Psychopharmacol 1996 Feb;16(1):26-34 -- Investigation of pharmacokinetic and pharmacodynamic interactions after coadministration of nefazodone and haloperidol. -- Barbhaiya RH, Shukla UA, Greene DS, Breul HP, Midha KK.

The reported incidence of hepatic adverse reactions to nefazodone seems to be higher than that estimated so far. Given the high prevalence of depression and the widespread use of antidepressants, physicians should be alert to the possibility that these medications cause hepatitis and consider early discontinuation of an antidepressant if the condition is suspected.
- J Clin Psychiatry 2002 Feb;63(2):135-7 -- Hepatotoxicity associated with the new antidepressants. -- Carvajal GP, Garcia D, Sanchez SA, Velasco MA, Rueda D, Lucena MI.

(NYSE:BMY - News) on Friday said it is discussing the safety of its antidepressant Serzone with Canadian regulators, but declined to say whether it is on the verge of pulling the medicine from Canadian drugstores. ADVERTISEMENT Due to liver failure among some patients taking the drug, Bristol-Myers has already stopped selling Serzone in Europe -- leaving Canada, the United States and Australia as its only remaining major markets. Rob Hutchison, a spokesman for the New York-based drugmaker, verified that the company was in talks with Health Canada, but declined to speculate on the outcome of the discussions. Sales of Serzone have already been crimped by a prominent warning about the liver problems on the drug's package insert label, a so-called "black box" warning. The medicine generates about $150 million in annual sales, making it a relatively minor product for a company with yearly revenue of more than $14 billion. The U.S. Food and Drug Administration (News - Websites) has received reports of liver failure leading to death or the need for a transplant. The agency pegs the incidence of liver problems at one patient per 250,000 to 300,000 taking the drug.

Dangerous interactions and/or reactions can occur if used with other types of antidepressants, MAO inhibitors and other drugs that have an effect on mood, the brain or cholesterol levels. Caution should be exercised with herbs and supplements that have an effect on mood and the brain or the liver.

last update: November 2008

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