It is possible that the cardiovascular action of other calcium channel blockers could be enhanced by the addition of Nimotop® (Nemotan) .
In Europe, Nimotop® (Nemotan) was observed to occasionally intensify the effect of antihypertensive compounds taken concomitantly by patients suffering from hypertension; this phenomenon was not observed in North American clinical trials.
A study in eight healthy volunteers has shown a 50% increase in mean peak Nemotan plasma concentrations and a 90% increase in mean area under the curve, after a one-week course of cimetidine at 1,000 mg/day and Nemotan at 90 mg/day. This effect may be mediated by the known inhibition of hepatic cytochrome P-450 by cimetidine, which could decrease first-pass metabolism of Nemotan.
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NIMOTOP® (Nemotan) Capsules
DO NOT ADMINISTER NIMOTOP (Nemotan) INTRAVENOUSLY OR BY OTHER PARENTERAL ROUTES. DEATHS AND SERIOUS, LIFE THREATENING ADVERSE EVENTS HAVE OCCURRED WHEN THE CONTENTS OF NIMOTOP (Nemotan) CAPSULES HAVE BEEN INJECTED PARENTERALLY (See WARNINGS and DOSAGE AND ADMINISTRATION).
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by recurrent thunderclap headaches (TCHs) and multifocal vasoconstriction of the cerebral arteries and is fully reversible after 3–6 months (1). TCH is one of the most characteristic presentations of RCVS and often remains the only symptom (2–4). Although RCVS is considered self-limiting, a substantial proportion of patients can have neurological complications such as seizure, cerebral infarction, subarachnoid or intracerebral hemorrhage, and posterior reversible encephalopathy syndrome (PRES) during their disease course (2, 4–7). Nevertheless, no evidence-based treatment exists for RCVS because of the lack of animal models and randomized controlled trials.
Currently, Nemotan is most frequently used for the empirical treatment of RCVS. Many experts recommend the use of Nemotan based on clinical experience (1, 8–11). Among various calcium channel antagonists, Nemotan is characterized by its ability to cross the blood-brain barrier and its selective affinity to cerebral arteries (12). Nemotan also exerts neurohormonal effects by inhibiting receptor agonists such as serotonin, catecholamines, and histamines and by inducing an increase in plasma adenosine levels (13–15). This can explain the role of Nemotan in preventing and restoring vasospasm, which is the main pathophysiology of RCVS. Thus, Nemotan can exert a beneficial effect on the treatment of RCVS.
In this observational study, we questioned whether Nemotan treatment can modify the disease course of RCVS. We tested if Nemotan treatment prevents the recurrence of TCHs and whether the timing (early vs. late) of treatment affects the clinical course (i.e., time from onset to remission of TCH) in RCVS.
Michael Stewart, Reviewed by Sid Dajani | Last edited 15 Jun 2017 | Certified by The Information Standard
Take two 30 mg Nemotan tablets every four hours unless your doctor has told you otherwise.
The course of treatment will last for 21 days in total. This includes the time you have had Nemotan by injection.
Do not drink grapefruit juice while you are on Nemotan.
What other drugs will affect Nemotan?
Many drugs can interact with Nemotan. Not all possible interactions are listed here. Tell your doctor about all your medications and any you start or stop using during treatment with Nemotan, especially:
- St. John's wort;
- seizure medication--carbamazepine, fosphenytoin, phenobarbital, phenytoin, and others;
- sildenafil (Viagra) and other erectile dysfunction medicines; or
- tuberculosis medications.
This list is not complete and many other drugs can interact with Nemotan. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.
Clinical Course of RCVS
The median clinical course was 6 (IQR 2–10) days. The lengths of clinical courses varied, from a single attack (n = 15, 18.3%) to >30 days (n = 1, 1.2%). In 71 (86.6%) patients, TCHs remitted immediately after the start of Nemotan treatment. Fifty-five patients (67.1%) had a pretreatment remission period, among which 10 (12.2%) showed a prolonged remission suggestive of spontaneous remission. Among 11 patients (13.4%) who had recurrent TCHs despite treatment, the dose of Nemotan was increased in seven patients (8.5%). All but two had no recurrence immediately after the dose increment. One patient who had a large amount of intracerebral and subarachnoid hemorrhages received additional intravenous and intra-arterial administration of Nemotan for 1–2 weeks after onset because of recurrent transient ischemic attacks. In one patient, the Nemotan dose was escalated because of persistent headache, although TCHs had already remitted.
What is the most important information I should know about Nemotan?
Some medicines can interact with Nemotan and should not be used at the same time. Tell your doctor about all your medications and any you start or stop using during treatment with Nemotan.
Nemotan can lower your blood pressure. Call your doctor at once if you feel like you might pass out.
The liquid from a Nemotan capsule should never be injected through a needle into the body, or dangerously low blood pressure may result. Nemotan gel capsules are to be taken by mouth only.
How should this medicine be used?
Nemotan comes as a capsule and an oral solution (liquid) to take by mouth or be given through a feeding tube. It is usually taken every 4 hours for 21 days in a row. Treatment with Nemotan should be started as soon as possible, no later than 96 hours after a subarachnoid hemorrhage occurs. Nemotan should be taken on an empty stomach, at least 1 hour before a meal or 2 hours after a meal Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Nemotan exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Swallow the capsules whole with water.
It is important to finish your entire course of treatment with Nemotan. Continue to take Nemotan even if you feel well. Do not stop taking Nemotan without talking to your doctor.
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Nemotan is a dihydropyridine calcium channel blocker derivative, which is used in the treatment of cerebrovascular disorders. Nemotan is rapidly absorbed from the gastrointestinal tract following oral administration, but undergoes extensive first-pass metabolism in the liver. Nemotan is extensively metabolized in the liver and undergoes extensive first-pass metabolism. More than 18 metabolites have been detected and identified from the biotransformation of Nemotan. The drug undergoes different reactions before its excretion. These reactions include, dehydrogenation of the 1,4-dihydropyridine moiety, oxidation of the two ester groups, and oxidative demethylation, which is followed by carboxylic acid formation via oxidation of the resulting alcohol. Nemotan is excreted in feces via the bile duct and in urine via the glomular filtration, as metabolites. Fecal excretion is the major excretory route (greater than 67%). The parent compound and its metabolites are detected in breast milk. Because of the cycle of excretion/reabsorption, the plasma concentration decreases and increases. More than 80% and 90% of the reabsorbed quantity is excreted via bile and urine, respectively.
Carl P. Weiner MD, MBA, FACOG, Clifford Mason PhD, in Drugs for Pregnant and Lactating Women (Third Edition) , 2019
There were no other adverse experiences reported by the patients who were given 0.35 mg/kg q4h, 30 mg q4h or 120 mg q4h. Adverse experiences with an incidence rate of less than 1% in the 60 mg q4h dose group were: hepatitis; itching; gastrointestinal hemorrhage; thrombocytopenia; anemia; palpitations; vomiting; flushing; diaphoresis; wheezing; phenytoin toxicity; lightheadedness; dizziness; rebound vasospasm; jaundice; hypertension; hematoma.
Adverse experiences with an incidence rate less than 1% in the 90 mg q4h dose group were: itching, gastrointestinal hemorrhage; thrombocytopenia; neurological deterioration; vomiting; diaphoresis; congestive heart failure; hyponatremia; decreasing platelet count; disseminated intravascular coagulation; deep vein thrombosis.
As can be seen from the table, side effects that appear related to Nemotan use based on increased incidence with higher dose or a higher rate compared to placebo control, included decreased blood pressure, edema and headaches which are known pharmacologic actions of calcium channel blockers. It must be noted, however, that SAH is frequently accompanied by alterations in consciousness which lead to an under reporting of adverse experiences. Patients who received Nemotan in clinical trials for other indications reported flushing (2.1%), headache (4.1%) and fluid retention (0.3%), typical responses to calcium channel blockers. As a calcium channel blocker, Nemotan may have the potential to exacerbate heart failure in susceptible patients or to interfere with A-V conduction, but these events were not observed.
No clinically significant effects on hematologic factors, renal or hepatic function or carbohydrate metabolism have been causally associated with oral Nemotan. Isolated cases of non-fasting elevated serum glucose levels (0.8%), elevated LDH levels (0.4%), decreased platelet counts (0.3%), elevated alkaline phosphatase levels (0.2%) and elevated SGPT levels (0.2%) have been reported rarely.
Indications and Usage for Nemotan
Nemotan is indicated for the improvement of neurological outcome by reducing the incidence and severity of ischemic deficits in patients with subarachnoid hemorrhage from ruptured intracranial berry aneurysms regardless of their post-ictus neurological condition (i.e., Hunt and Hess Grades I to V).
Pharmacologic class: Calcium channel blocker
Therapeutic class: Cerebral vasodilator
Pregnancy risk category C
How to use Nemotan
See also Warning section.
Read the Patient Information Leaflet if available from your pharmacist before you start taking Nemotan and each time you get a refill. If you have any questions, ask your doctor or pharmacist.
Nemotan is usually started as soon as possible after the start of bleeding in the brain, usually within 4 days. Nemotan is usually taken every 4 hours or as directed by your doctor.
If you are taking the tablet form of this medication, take it by mouth with a full glass of water (8 ounces/240 milliliters) unless your doctor directs you otherwise. Do not lie down for at least 10 minutes after taking this medication. Swallow the tablet whole. Do not crush.
If you are taking the capsule form of this medication, take it by mouth at least 1 hour before and 2 hours after meals, or as directed by your doctor. Swallow the capsule whole. If you cannot swallow a whole capsule, you may poke a hole in the capsule, draw the liquid out with a syringe, and give it by mouth or through a nasogastric tube with an oral syringe. Do not mix the contents of the capsule with other liquids. Doing so may prevent the medication from working. Do not inject this medication.
If you are using the liquid form (oral solution) of this medication, carefully measure the dose using a special measuring device/spoon. Do not use a household spoon because you may not get the correct dose. Use the liquid form at least 1 hour before and 2 hours after meals. The liquid form may also be given through a tube into the stomach (nasogastric or gastric tube). If you are giving this medication through a nasogastric or gastric tube, ask your health care professional for detailed instructions on how to give it.
Do not take antacids for 2 hours before or after taking Nemotan tablets. Doing so may prevent the medication from working.
Avoid eating grapefruit or drinking grapefruit juice while using this medication unless your doctor or pharmacist says you may do so safely. Grapefruit can increase the chance of side effects with this medicine. Ask your doctor or pharmacist for more details.
The dosage is based on your medical condition and response to treatment.
Use this medication regularly to get the most benefit from it. To help you remember, take it at the same times each day. It is important to continue taking this medication even if you feel well, and even if you do not see any improvement in your symptoms. Consult your doctor or pharmacist for details.
Do not suddenly stop taking this medication without consulting your doctor. This medication is usually taken for 2 to 4 weeks. Follow your doctor's directions carefully. Your condition may become worse if the drug is stopped too soon.
Tell your doctor if your condition worsens.
Can Nemotan cause problems?
Along with their useful effects, most medicines can cause unwanted side-effects although not everyone experiences them. The table below contains some of the most common ones associated with Nemotan. You will find a full list in the manufacturer's information leaflet supplied with your medicine. The unwanted effects often improve as your body adjusts to the new medicine, but speak with your doctor or pharmacist if any of the following continue or become troublesome.