IPLEDGE program
Although the goal of the program is to prevent pregnancies of women who take the drug, male patients must also participate in anti-pregnancy restrictions, primarily due to fears that male isotretinoin users might share their prescriptions with females without their physicians' knowledge. There has been no link to birth defects from Accutane associated with males using the drug, though male sexual dysfunction has been suggested by one study. As this has not been conclusively proven, this is not acknowledged as a side effect in the official literature accompanying the medication.
Management of hypertension
The best first-line medication is disputed, but the Cochrane collaboration, World Health Organization and the United States guidelines support low-dose thiazide-based diuretic as first-line treatment. The UK guidelines emphasise calcium channel blockers (CCB) in preference for people over the age of 55 years or if of African or Caribbean family origin, with angiotensin-converting enzyme inhibitors (ACE-I) used first line for younger people. In Japan starting with any one of six classes of medications including: CCB, ACEI/ARB, thiazide diuretics, beta-blockers, and alpha-blockers is deemed reasonable, while in Canada and Europe all of these but alpha-blockers are recommended as options. When compared to placebo, beta-blockers have greater benefit in stroke reduction, but no difference on coronary heart disease or all-cause mortality. However, three-quarters of active beta-blocker treatment in the randomised controlled trials included in the review were with atenolol and none with the newer vasodilating beta-blockers.