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Clinical Efficacy
Nimodipine has been 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 subarachnoid hemorrhage (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 patients 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) the fourth studied much sicker patients, Hunt and Hess Grades III-V. Two studies, on U.S., one French, were similar in design, with relatively unimpaired SAH patients randomized to nimodipine or placebo. In each, a judgement 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; the second (French) study showed fewer spasm-related deficits of all severities. No effect was seen on deficits not related to spasm.1
| | Patients |
| Study | Dose | Grade* | | Number Analyzed | Any Deficit Due to Spasm | Numbers with Severe Deficit |
| U.S. | 20-30 mg | I-III | Nimodipine
Placebo | 56
60 | 13
16 | 1
8** |
| French | 60 mg | I-III | Nimodipine
Placebo | 31
39 | 4
11 | 2
10** |
* Hunt and Hess Grade
** p=0.03
A third, large, study was performed in the United Kingdom in SAH patients with all grades of severity (but 89% were in Grades I-III). Nimodipine was dosed 60mg every 4 hours. Outcomes were not defined as spasm related or not but there was a significant reduction in the overall rate of infarction and severely disabling neurological outcome at 3 months:1
| | Nimodipine | Placebo |
| Total patients | 278 | 276 |
| Good recovery | 99* | 169 |
| Moderate disability | 24 | 16 |
| Severe disability | 12** | 31 |
| Death | 43*** | 60 |
* p = 0.0444 - good and moderate vs severe and dead
** p = 0.001 - severe disability
***p = 0.056 - death
A Canadian study entered 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 the first two studies. Analysis of delayed ischemic deficits, many of which result from spasm, showed a significant reduction in spasm-related deficits. Among analyzed patients (72 nimodipine, 82 placebo), there were the following outcomes.1
| | Delayed Ischemic Deficits (DID) | Permanent Deficits |
| | Nimodipine
n (%) | Placebo
n (%) | Nimodipine
n (%) | Placebo
n (%) |
| DID Spasm Alone | 8 (11) * | 25 (31) | 5 (7)* | 22 (27) |
| DID Spasm Contributing | 18 (25) | 21 (26) | 16 (22) | 17 (21) |
| DID Without Spasm | 7 (10) | 8 (10) | 6 (8) | 7 (9) |
| No DID | 39 (54) | 28 (34) | 45 (63) | 36 (44) |
* p = 0.001, nimodipine vs placebo
When data were combined for the Canadian and the United Kingdom studies, the treatment difference on success rate (i.e. good recovery) on the Glasgow Outcome Scale was 25.3% (nimodipine) versus 10.0% (placebo) for Hunt and Hess Grades IV or V. The table below demonstrates that nimodipine tends to improve good recovery of SAH patients with poor neurological status post-ictus, while decreasing the numbers with severe disability and vegetative survival.1
| Glasgow Outcome* | Nimodipine
(n=87) | Placebo
(n=101) |
| Good Recovery | 22 (25.3%) | 11 (10.9%) |
| Moderate Disability | 8 (9.2%) | 12 (11.9%) |
| Severe Disability | 6 (6.9%) | 15 (14.9%) |
| Vegetative Survival | 4 (4.6%) | 9 (8.9%) |
| Death | 47 (54.0%) | 54 (53.5%) |
*p = 0.045, nimodipine vs placebo
A dose-ranging study comparing 30, 60 and 90 mg doses found a generally low rate of spasm-related neurological deficits but no dose response relationship.1
Sources:
- Nimotop® (nimodipine) Capsules Prescribing
Information December 2005
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DO NOT ADMINISTER NIMOTOP INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES. DEATHS AND SERIOUS, LIFE-THREATENING ADVERSE EVENTS HAVE OCCURRED WHEN THE CONTENTS OF NIMOTOP CAPSULES HAVE BEEN INJECTED PARENTERALLY
(See
WARNINGS and DOSAGE AND ADMINISTRATION.) |
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- In patients with SAH, Nimotop® controls damage with a low side effect profile.
- Decreased blood pressure is the most common side effect, occurring in 4.4% of patients. Blood pressure should be monitored during therapy.1
- Other side effects occurring at a low frequency of ≥1.0% include headache, nausea, and bradycardia.1
- No clinically significant effects on hematologic factors, renal or hepatic function, or carbohydrate metabolism have been causally associated with oral nimodipine.1
- Nimotop® does not appear to affect anesthetic management.2
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Sources:
- Nimotop® (nimodipine) Capsules Prescribing
Information December 2005
- Stullken EH, Johnston WE, Prough DS. Implications of nimodipine prophylaxis of cerebral vasospasm on anesthetic management during intracranial aneurysm clipping. J. Neurosurg. 1985; 62:200-205.
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© Bayer HealthCare Pharmaceuticals.
Bayer HealthCare Pharmaceuticals
6 West Belt
Wayne, NJ 07470
The information provided on Bayer products is only intended for the United States audience. Regulatory requirements, regulations, laws, and distribution of information about drug products may vary from country to country. Product names and indications (product uses) also may be different in different countries. The prescribing information provided here is based on United States labeling and may not be appropriate outside of the US.
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