Could biperiden cause a prolonged QT-interval?/nBackground: a 71-year-old female patient was admitt

Fråga: Could biperiden cause a prolonged QT-interval?

Background: a 71-year-old female patient was admitted to the hospital because of syncope and a suspected myocardial infarction. Her rate-related (corrected) QT-interval was 593 ms (normally less than or equal to 440 ms (1)). Her only medication is Akineton (biperiden) 4 mg x3 that she has taken for tremor since April 1997.

Sammanfattning: No documentation concerning an increased QT-interval as an adverse effect of biperiden has been found in the literature. Based on the pharmacological properties of this drug, tachycardia would rather be expected.

Svar: Biperiden is an anticholinergic drug with an antagonistic effect on muscarine-like and nicotine-like acetylcholine receptors (2). No documention specifically concerning prolonged QT-interval due to biperiden could be found. The sinoatrial node is sensitive to muscarinic receptor blockade and therefore tachycardia is consistently seen when moderate to high doses of an antimuscarinic drug are given to patients. However, low doses cause central vagal stimulation and may result in initial bradycardia before the effects of peripheral vagal block become manifest (3). An illustrative case report was found (2), concerning a 38-year-old male patient suffering from postzosteric trigeminal neuralgia, who received 10 mg biperiden lactate intravenously. The dosage was diluted in a 10 ml solution of sodium chloride and given slowly over 15 minutes. The patient developed bradycardia, dysarthria and dysphagia. The heart rate went back to normal upon administration of orciprenaline and the remaining symptoms disappeared within 24 hours. It seems therefore, at least when biperiden is given parenterally, that bradycardia can occur when the total dose or the speed of injection is too low to block the peripheral muscarine receptors. However, the parenteral rate of administration is of no relevance to the present case, where the patient received an oral treatment during a prolonged period of time.

No reports on cardiac adverse effects due to biperiden have been reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC). The WHO adverse drug reaction monitoring center in Uppsala has received a total number of 51 reports of cardiac adverse effects possibly related to biperiden. However, these reports are relatively unevaluated and involve concomitant use of other drugs as well.

Normalization of the QT-interval upon withdrawal of biperiden would speak in favour of a causal relationship. If so, we recommend to report this case to SADRAC. 1 Harrison´s Principles of Internal Medicine, 1994; 13th edition: 956 2 Grosse Aldenhövel H, Heusler H, Gallenkamp U: Bradycardia due to biperiden. Pharmacopsychiatry 1989; 22: 42-43 3 Katzung, Basic and clinical pharmacology, 1992; 5th edition: 100-101