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Perhexiline toxicity related to citalopram use

Karin Nyfort-Hansen
The Medical Journal of Australia 3 June 2002 176 (11): 560-561

To the Editor: Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for patients with cardiovascular disease, including those taking perhexiline for severe ischaemic heart disease. Elevated serum perhexiline concentrations have been observed during therapy with the SSRIs fluoxetine and paroxetine, which are known to be strong inhibitors of cytochrome P450 2D6, the enzyme system responsible for the hepatic metabolism of perhexiline.1 The Adverse Drug Reactions Advisory Committee has received five reports of a possible interaction between perhexiline and SSRIs, but none of these involved the SSRIs citalopram or fluvoxamine, which are generally considered to be weak inhibitors of cytochrome P450 2D6. I describe here a case of perhexiline toxicity that occurred within 10 days of starting citalopram therapy.

An 82-year-old man was admitted to hospital for drainage of a femoral abscess. His medical history included bilateral hip replacements, ischaemic heart disease, hypertension, renal artery stenosis, renal calculi, gout, gastroesophageal reflux disease and prostate cancer. His medications included (daily) aspirin 100 mg, isosorbide mononitrate 120 mg, pravastatin 40 mg, allopurinol 300 mg, celecoxib 200 mg, lorazepam 2 mg, nitrazepam 10 mg; (twice daily) perhexiline 100 mg; and paracetamol and tramadol as needed.

On Day 51 after admission the patient underwent first-stage revision of an infected hip implant under general anaesthesia, and on Day 60 citalopram was commenced (10 mg daily for four days, then 20 mg daily). On Day 70, the patient complained of diarrhoea, nausea and dizziness. Citalopram was discontinued but the nausea was slow to settle. After a perhexiline assay on Day 75 revealed a high serum concentration (see Box), the perhexiline dose was reduced to 100 mg daily and the patient's nausea settled.

Previous perhexiline concentrations on a dose of 100 mg twice daily had ranged from 0.29 to 0.34 mg/L over a two-year period. Tests of renal and hepatic function were normal throughout the patient's hospital stay. While in hospital, the patient was given celecoxib (a cytochrome P450 2D6 inhibitor) at a constant dose between Days 1 and 95, and meropenem (not a documented cytochrome P450 2D6 inhibitor) between Days 51 and 95. These patterns of administration suggest that neither of these drugs had a significant effect on perhexiline concentration. On the other hand, the laboratory evidence of a marked inhibition of perhexiline metabolism during treatment with citalopram suggests that caution is required when prescribing citalopram (or any other SSRI) for a patient taking perhexiline.2

Serum concentrations (mg/L) of perhexiline and perhexiline metabolite

Day 48

Day 75

Day 95

Perhexiline (therapeutic range, 0.15–0.60 mg/L)




Perhexiline metabolite




Ratio of perhexiline to perhexiline metabolite




  1. Alderman CP, Hundertmark JD, Soetratma TW. Interaction of serotonin re-uptake inhibitors with perhexiline. Aust N Z J Psychiatry 1997; 31: 601-603. <PubMed>
  2. Pexsig product information. 2001 MIMS Annual. Sydney: MediMedia Australia Pty Ltd, 2001.

(Received 6 Mar 2002, accepted 18 Apr 2002)

Pharmacy Department, Repatriation General Hospital, Daw Park, SA.

KarinNyfort-Hansen, BPharm Grad DipEd (Health) CGPClinical Pharmacist

Correspondence: Ms Karin Nyfort-Hansen, Pharmacy Department, Repatriation General Hospital, Daw Park, SA 5041. karin.nyfort-hansenATrgh.sa.gov.au

©The Medical Journal of Australia 2002 ISSN: 0025-729X http://www.mja.com.au/public/issues/176_11_030602/www.mja.com.au

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