Cluster headache (CH) is a primary headache disorder with relatively effective treatments. Although few sufficiently controlled trials are available, verapamil is recommended as the first-line prophylactic drug for CH by the French Headache Society (with a low level of evidence, level B) and by the EFNS (European Federation of Neurological Societies, level A). Daily doses of more than 480 mg (and up to 1200 mg daily) are frequently used off-label, while 360 mg daily is the only dosage to have demonstrated its effectiveness in a double-blind trial against placebo, and the usual label posology used by cardiologists is 240 mg daily in hypertension.
Verapamil is currently the best available prophylactic drug for patients experiencing cluster headaches (CHs). Published papers usually state 240 to 480 mg taken in three divided doses give good results, ranging from 50% to 80%; others mention higher doses—720, even 1200 mg per day. In clinical practice we found we needed to adapt dosage to individual’s time of attacks, in particular giving higher doses before going to bed to suppress severe nocturnal episodes. A few only required 120 mg daily. We therefore evolved a scheme for steady and progressive drug increase until satisfactory control had been achieved.
Human gut wall cytochrome P450 (CYP)3A4 is inhibited by grapefruit juice (G), whereas smoking increases CYP1A2 activity. Both enzymes contribute to verapamil biotransformation. This study was performed to quantitatively assess the effect of these factors on verapamil pharmacokinetics in steady state.