References: JAMA 1998;279(9):657-62 Reviewed: 04/1999

Paracetamol (analgesic) Interaction with warfarin Patients taking warfarin for more than 1 month, with a target international normalized ratio (INR) of 2.0 to 3.0, were investigated as to the causes of overanticoagulation (case-control study). Those taking paracetamol showed a dose-dependent increase of INR, with a significant risk of reaching an INR value greater than 6.0. For the highest-dose category of paracetamol intake, 9100 mg/wk or more, the odds of having an INR greater than 6.0 were increased 10-fold

References: BMJ 1998;316:1724-1725 Reviewed: 04/1999

Fatal poisoning Four cases of fatal poisoning after ingestion of 10-32 g paracetamol are described. Patients presented no apparent risk factors for enhanced hepatotoxicity. They were medically reviewed within six hours of overdose; two of them were soon treated with activated charcoal only. They eventually developed acute liver failure within 48 hours of hospital discharge. No deaths have been reported in any of the major treatment trials of paracetamol overdose however high the initial serum paracetamol concentration, provided acetylcysteine was given within 10 hours of the drug's ingestion. Authors recommend that all patients presenting with a serum paracetamol concentration >150 mg/l should be treated with acetylcysteine, with a treatment threshold of 100 mg/l for those patients with known risk factors.

References: Cutis 1998;61(2):98-100 Reviewed: 04/1999

Pravastatin (antilipaemic) Lichenoid lesions A patient was reported to develop lichenoid lesions after initiation of pravastatin therapy; they resolved on discontinuation, and reappeared on rechallenge with pravastatin. Drug eruptions caused by pravastatin and other lovastatin analogs have previously been described.

References: Am J Cardiol 1998;81(3):368-9 Reviewed: 04/1999

Atorvastatin (antilipaemic) Rhabdomyolysis A case of rhabdomyolysis was reported in a patient taking gemfibrozil in combination.

References: BMJ 1998;317:252-254 Reviewed: 04/1999

Selegiline (antiparkinson) Mortality risk In a cohort study based on computerised medical records of patients receiving a prescription for an antiparkinsonian drug, there was an 11% (non-significant) increase in the risk of death associated with taking selegiline either alone or in combination with levodopa.

References: BMJ 1998;316:440 Reviewed: 04/1999

Terbinafine (antifungal) Interaction with warfarin This is a case-report of a 68 year old woman who had taken warfarin for mitral valve disease for twenty years. br>Twenty eight days after starting the treatment with oral terbinafine her international normalised ratio (INR) decreased from 2.1 to 1.1. The warfarin dose had to be increased from her usual dose of 5.5 mg to 8.0 mg and then 7.5 mg daily to maintain the INR between 2 and 3.

References: BMJ 1998;316:441 Reviewed: 04/1999

Interaction with nortriptyline A 74 year old man with depression had been on nortriptyline for several months. 14 days of treatment with terbinafine caused a more than twofold increase of the nortriptyline concentration and symptoms of increasing fatigue, vertigo, loss of energy, and loss of appetite. A positive rechallenge test was made, to confirm the hypothesis of a pharmacokinetic interaction between warfarin and terbinafine.

References: BMJ 1998;316:440-441 Reviewed: 04/1999

Parotid swelling Parotid swelling appeared in a 38 year old man 15 days after taking terbinafine. 12 days after stopping terbinafine treatment the parotid swelling had significantly diminished. By April 1997 the Committee on Safety of Medicines had received three reports of parotid swelling associated with terbinafine, against a background of more than 500 000 patients having been prescribed the drug.

The complete collection of the notes already presented in this section of PHARMALERT can be found in the: ADR database

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