Levodopa or Whole broad beans and Monoamine oxidase inhibitors

A rapid, serious and potentially life-threatening hypertensive reaction can occur in patients being treated with MAOI for hypertension or depression if they are concurrently given levodopa, or if they eat whole broad beans which contain dopa. An interaction with compound levodopa preparations containing carbidopa or benserazide (Sinemet, Madopar) is unlikely Selegiltne (Deprenyl) does not interact adversely with levodopa.

Clinical evidence

(a) Levodopa and monoamine oxidase inhibitor

A patient who had been taking phenelzine daily for 10 days was given 50 mg levodopa by mouth Within an hour his blood pressure had risen from 135/90 to about 190/130 mm Hg, and despite the IV injection of 5 mg phentolamine it continued to rise over the next 10 mm to 200/135 mm Hg, before falling in reponse to a further 4 mg injection of phentolamine. Next day the experiment was repeated with 25 mg levopa but no blood pressure changes were seen, and three weeks after withdrawal of the phenelzine even 500 mg levodopa had no effect on the blood pressure.

Similar cases of severe hypertension, accompanied in most instances by flushing, throbbing and pounding in the head, neck and chest, and lightheadedness have been described in other case reports and studies involving the concurrent use of levodopa with pargyhne, nialamide, tranylcypro-rrune, phenelzine and isocarboxazid.

(b) Whole broad beans + monoamine oxidase inhibitor

A similar hypertensive reaction can occur in patients taking MAOI who have eaten WHOLE cooked broad beans (View faba L), that is to say the beans with pods, the latter normally containing dopa. The reports involve pargyhne and phenelzine.

Mechanism

Not fully understood Levodopa is enzyrrucally converted in the body, firstly to doparrune and then to noradrenalme (norepinephnne), both of which are normally under enzymic attack by monoamine oxidase. But m the presence of a monoamine oxidase inhibitor this attack is suppressed-which means that the total levels of dopamine and noradrenalme are increased. Precisely how this then leads to a sharp rise in blood pressure is not clear, but either dopamine or noradrenalme, or both, directly or indirectly stimulate the alpha-receptors of the cardiovascular system.

Importance and management

A well-documented, serious and potentially life-threatenmg interaction Patients should not be given levodopa during treat ment with any of the older MAOI cited here, whether used for depression or hypertension, and for a period of 2-3 weeks after their withdrawal. The same precautions apply to the eating of WHOLE cooked broad beans, the dopa being m the pods but not in the beans. If accidental mgestion occurs the hypertensive reaction can be controlled by the IV injection of an alpha-blocker such as phentolamine This interaction has been shown to be inhibited in man by the presence of dopa decarboxylase inhibitors5 such as carbidopa (in Sinemet) and benserazide (in Madopar) so that a serious interaction is unlikely to occur with these preparations. Even so the manufacturers of both list the MAOI among their contraindications Selegilrne (Deprenyl) which is an inhibitor of MAO-B does not interact adversely with levodopa.

© 2013 Sinemet