General Information

Nymalize (nimodipine) is an oral solution formulation of nimodipine, a dihydropyridine calcium channel blocker. The precise mechanism of action of nimodipine in reducing the incidence and severity of ischemic deficits in adult patients with SAH from ruptured intracranial berry aneurysms is unknown.

Nymalize is specifically indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in adult patients with subarachnoid hemorrhage (SAH) from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition.

Nymalize is supplied as a solution for oral administration. Nymalize should only be administered via the oral, nasogastric tube, or gastric tube route. The recommended oral dosage is 20 mL (60 mg) every 4 hours for 21 consecutive days.

Clinical Results

FDA Approval
The safety and efficacy of Nymalize in the treatment of SAH is based on adequate and well-controlled studies of nimodipine oral capsules. Nymalize has comparable bioavailability to nimodipine oral capsules. Nimodipine was shown in 4 randomized, double-blind, placebo-controlled trials to reduce the severity of neurological deficits resulting from vasospasm in patients who have had a recent SAH. The trials used doses ranging from 20-30 mg to 90 mg every 4 hours, with drug given for 21 days in 3 studies, and for at least 18 days in the other. Three of the four trials followed subjects for 3-6 months. Three of the trials studied relatively well patients, with all or most patients in Hunt and Hess Grades I - III (essentially free of focal deficits after the initial bleed). Study 4 studied much sicker patients with Hunt and Hess Grades III - V. Studies 1 and 2: these studies were similar in design, with relatively unimpaired SAH patients randomized to nimodipine or placebo. In each, a judgment was made as to whether any late-developing deficit was due to spasm or other causes, and the deficits were graded. Both studies showed significantly fewer severe deficits due to spasm in the nimodipine group; Study 2 showed fewer spasm-related deficits of all severities. No effect was seen on deficits not related to spasm. Study 3: A total of 554 subjects were enrolled, including SAH patients with all grades of severity (89% were in Hunt and Hess Grades I-III). Subjects were treated with placebo or 60 mg of nimodipine every 4 hours. Outcomes were not defined as spasm related or not but there was a significant reduction in the overall rate of brain infarction and severely disabling neurological outcome at 3 months. Study 4: this study enrolled much sicker patients, (Hunt and Hess Grades III-V), who had a high rate of death and disability, and used a dose of 90 mg every 4 hours, but was otherwise similar to Study 1 and Study 2.. Analysis of delayed ischemic deficits, many of which result from spasm, showed a significant reduction in spasm-related deficits. When data were combined for Study 3 and Study 4, the treatment difference on success rate (i.e., good recovery) on the Glasgow Outcome Scale was 25.3% (nimodipine) versus 10.9% (placebo) for Hunt and Hess Grades IV or V.

Mechanism of Action

Nimodipine is a dihydropyridine calcium channel blocker. The contractile processes of smooth muscle cells are dependent upon calcium ions, which enter these cells during depolarization as slow ionic transmembrane currents. Nimodipine inhibits calcium ion transfer into these cells and thus inhibits contractions of vascular smooth muscle. The precise mechanism of action of nimodipine in reducing the incidence and severity of ischemic deficits in adult patients with SAH from ruptured intracranial berry aneurysms is unknown.