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HomeHealth articlessubarachnoid haemorrhageHow Does Nimodipine Work for Subarachnoid Hemorrhage?

Nimodipine - Indications, Pharmacology, Warnings, and Precautions

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Nimodipine is widely employed to tackle the brain damage inflicted by a condition called subarachnoid hemorrhage. Continue reading to know more.

Medically reviewed by

Dr. Abhishek Juneja

Published At October 4, 2023
Reviewed AtOctober 4, 2023

Overview:

Nimodipine is an efficacious medicine that is advised for subarachnoid hemorrhage, in which blood piles up within the brain space. The use of Nimodipine for subarachnoid hemorrhage was validated and authorized by the drug regulatory body of the United States - the Food and Drug Administration (FDA). Though Nimodipine was endorsed by the FDA in 1988, its therapeutic application was limited to systemic hypertension (boosted blood pressure). Later various drug discovery and developmental programs exposed Nimodipine’s efficacy in dealing with patients diagnosed with subarachnoid hemorrhage. At present, Nimodipine is recognized as the sole approved and efficacious medication for dealing with the manifestation of subarachnoid hemorrhage. However, it has several out-of-label usages apart from the FDA-approved indications.

Drug Group:

Nimodipine falls under the drug group of calcium channel blockers. Within the calcium channel blockers, it belongs to the class of dihydropyridine. Nimodipine is categorized under second-generation calcium channel blockers, which are reported to have extended periods of action and better metabolism in the human body.

Available Doses and Dosage Forms:

1. Dosage Forms: Nimodipine is marketed and circulated in two distinct forms - solution and capsule form. Both the solution and capsule forms are intended to be taken by mouth. It is also available as a solution that can be directly introduced into the veins (intravenous). However, the marketing of the intravenous (IV) solution form of Nimodipine is not authorized by FDA. In addition, the FDA cautions against the intravenous use of Nimodipine. The oral solution is the routinely advised as well as preferred dosage form of Nimodipine.

2. Available Doses: Nimodipine is made available in the following doses:

  • Capsule: 30 milligrams (mg).

  • Oral Solution: The oral solution is marketed in two different concentrations. Three milligrams of Nimodipine per milliliter of the solution and 30 milligrams per milliliter of the solution are the two available strengths of Nimodipine oral solution.

For Patients:

What Is Subarachnoid Hemorrhage?

Subarachnoid hemorrhage (SAH) is a grave and potentially endangering condition in which the blood leak and gather into the brain space called subarachnoid space. The subarachnoid space is an enclosed space that is sandwiched between two protective brain layers. The human brain is a delicate and highly complex structure. Therefore, it is wrapped in triple protective layers (dura mater, arachnoid, pia mater), which offer protection against insult and trauma. These protective layers are medically known as meninges. In subarachnoid hemorrhage, the blood sweeps into the space, which is guarded on either side by arachnoid and pia meningeal layers.

Subarachnoid hemorrhages can be the result of an insult or impact on the head (cranial cavity). However, it also has a strong connection with certain nontraumatic causes. In the absence of external trauma, SAH may arise due to collapsed brain aneurysms. Blood vessels may have a certain incapacitated and fragile area; such fragile areas in the cerebral (brain) blood vessels force the blood to gather over those areas, eventually producing a bulge that resembles a blood-filled bump. This condition is known by the name brain aneurysm. As the vascular strength in that particular point is remarkably low, this bulge may break off, releasing the blood into the brain space and giving rise to subarachnoid hemorrhage.

Intolerable headaches, stiff and sore neck, visual troubles, lightheadedness, nausea, and collapse are some of the manifestations elicited during subarachnoid hemorrhage. It necessitates immediate medical attention as it can induce permanent impairment of the brain cells and even endanger one’s life.

How Does Nimodipine Work?

Nimodipine, being a potent calcium channel blocker, works by interrupting and hampering the calcium channel. Calcium ions are associated with the compression and deflation of the smooth muscle fibers. The blood vessel walls are also framed out of vascular smooth muscles. Nimodipine obstructs the calcium channel, checks the inflow of calcium ions, and thereby holds up the constriction of blood vessels. In this way, Nimodipine relieves the spasm and tightness in the cerebral blood vessel, which in turn enhances the flow rate of blood through the brain cells. It aids in easing the pressure in the brain cells created by the pooled blood in subarachnoid hemorrhage.

What Is the Dosage of Nimodipine?

Administration of 60 milligrams (capsule form) or 20 milliliters (oral solution form) of Nimodipine at an interval of four hours is the recommended dosage regime. Since the capsule form is available in 30 mg dose, the patient should take two capsules of 30 mg each to attain the overall dose of 60 mg. The Nimodipine therapy should be extended for a period of 21 days in a row without any alteration or interruption in the dosage. Dosage titration is made for patients with liver diseases like liver cirrhosis (compromised liver functions). The recommended dosage for patients with cirrhosis is half the standard dose.

How Effective Is Nimodipine?

Nimodipine is proven to be effective for subarachnoid hemorrhage by palliating the pressure on the blood vessels. In addition to its role in checking the calcium ion inflow, it also exerts remarkable protective effects on the nerve cells in the brain. Nimodipine calms down the swelling in the nerve cells and brain cells that are evoked by the subarachnoid hemorrhage. There is evidence from the clinical trials with Nimodipine suggesting the drug's potency and efficacy in dramatically minimizing exposure to life-threatening complications. Nimodipine not only checked the development of cardiovascular complications but also enhanced the survivability and longevity of the patients.

What Are the Things to Inform the Doctor Before Taking the Drug?

Proper communication between patient and doctor is essential to ensure the success of every treatment procedure. There are a set of things that the doctor should be made aware of before commencing the treatment using Nimodipine.

  • In case the patient has any prior allergic encounter with Nimodipine or with other medicine that is chemically related to Nimodipine or any of the components in the Nimodipine capsule or oral solution, the doctor should be informed about it beforehand. A clear history concerning the drug allergy should be provided so that doctors can analyze the condition and prescribe alternate medicine. Subsequent exposure to a hyperreactive medicine can evoke serious allergic issues, and hence it should be taken care of.

  • It is imperative to keep the doctor informed about all the underlying medical conditions that the person is suffering from. Even past medical history should also be disclosed to the concerned doctors.

  • In addition to medical history, the doctors should be informed about comprehensive drug history encompassing dietary supplements, herbal products, and other non-prescription medications. Certain medications like antifungal and antiviral medicines can potentially interact with Nimodipine and can bring in unwanted effects. So in order to check unwanted drug-to-drug associations and subsequent adverse effects, doctors should be made aware of the patient’s drug history beforehand.

  • The doctors should be updated about the patient’s pregnancy and lactating status before commencing the therapy using Nimodipine. If the patient is planning for conception in the near future, then that should also be informed beforehand so that the doctor can make necessary modifications in the drug choice.

How Is Nimodipine Administered?

FDA approves the administration of Nimodipine by mouth (oral route). It can also be administered through a gastric tube or nasogastric tube (tube to deliver content into the stomach) in unconscious patients. The capsule form is advised to be taken with water without breaking or powdering it. While solution form is used in unconscious patients and is delivered through the gastric or nasogastric tube. After injecting the specified dose of the Nimodipine solution into the gastric tube, about 20 mL (milliliter) of saline solution (0.9 percent) is used to flush out the leftover Nimodipine solution from the tube to the stomach.

What Are the Side Effects of Nimodipine?

Nimodipine can bring about certain adverse effects on the body. Some of the potential side effects precipitated by Nimodipine include the following:

  • Vertigo and headache are the two frequently reported side effects of Nimodipine.

  • In addition, certain patients reported swelling and puffiness over the feet (pedal edema) while undergoing therapy using Nimodipine.

  • Diarrhea, muscle pain, and nausea are some other side effects that are occasionally seen in association with Nimodipine therapy.

  • Flushing (marked skin redness), skin rashes, and heart racing (palpitation) are also reported in certain cases following Nimodipine therapy.

  • Constriction and shrinkage of the blood vessels, particularly involving the middle cerebral and internal carotid arteries, are also noted in patients with implant form of Nimodipine.

  • In certain cases, the person may encounter complex side effects like loss of consciousness and altered heart beating rate, which often entails immediate medical attention.

Dietary Considerations:

The uptake and processing of Nimodipine is largely influenced by the presence of food. Hence certain dietary considerations are advised while undergoing therapy using Nimodipine. Whatever may be the route of intake of Nimodipine, it should never be administered during food intake. A minimum of one-hour interval should be given for food intake following Nimodipine administration. Likewise, post-meal, a minimum of a two-hour gap should be given before Nimodipine administration.

Missed Dose:

Nimodipine is advised to be taken every four hours. However, at times, the patients may overlook taking the oral dose at the specified time; in such cases, the patients are instructed to take the dose once they become aware of the missed dose. At times, the patients may recall the omitted dose quite late when it is close to the time for the subsequent dose. In such cases, the patients can ignore the missed one and can move ahead with the upcoming dose. Care should be taken not to intake or administer double the specified dose to cover up for an overlooked dose.

Overdose:

Taking more than the required and advised dosage can bring in overdose issues. However, there is not much data available concerning the overdose. Since Nimodipine can bring in depreciation in blood pressure, overdose precipitates severe collapse in blood pressure and even syncope (fainting).

Storage:

Nimodipine should be guarded against sunlight as it is photosensitive (light-sensitive). 25 degrees Celsius (77 degrees Fahrenheit) is the ideal temperature that is recommended for Nimodipine. However, any temperature within the range of 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit) is acceptable for Nimodipine storage. Refrigerating the capsule or oral solution form of Nimodipine influences the structural stability and chemical properties of the medicine, which can have a direct impact on its therapeutic properties. Hence it is advised not to freeze the medicine.

For Doctors:

Indication:

  • Subarachnoid hemorrhage (for tackling the ischemic deficits).

Dose:

  • For Capsule Form: 60 mg of Nimodipine is the four hourly dosage of Nimodipine for patients with subarachnoid hemorrhage. This dosage should be extended for a period of 21 successive days.

  • For Oral Solution Form: 20 mL of Nimodipine oral solution is the recommended dosage that should be given every four hours for a period of 21 successive days. For administration through nasogastric and gastric tubes, the dosage is the same as that of oral solution form. Following the administration through the catheter tube, 0.9 percent saline is employed to flush in the remaining medicine that is left within the tube. This ensures the delivery of accurate drug dosage.

Dosing Considerations:

Considerations in the Nimodipine dosage should be made for liver cirrhosis patients. As the liver function is compromised, the Nimodipine dose should also need to be narrowed down to half its regular dose. Hence instead of 20 mL, only 10 mL need to be administered on a four-hourly basis. The treatment duration and course remain the same; only the dose needs to be altered.

What Are the Pharmacological Aspects of Nimodipine?

  • Mechanism: Being a dihydropyridine calcium channel blocker, Nimodipine elicits its action by directly hindering the activity of calcium channels. Calcium ions largely influence and govern the compression of the vascular smooth muscles, which squeezes the blood vessels bringing about enhanced pressure on the flowing blood. This compressive force is generated by the vascular smooth muscles. Nimodipine obstructs the inflow of calcium ions and thereby hinders the contraction process in the blood vessels. It tackles and calms down the cerebral vasospasm that develops during subarachnoid hemorrhage.

  • Pharmacodynamics: Nimodipine is capable of traveling across the blood-brain barrier. Studies have demonstrated pronounced effects of Nimodipine on the cerebral arteries, which enhances its effectiveness when used for subarachnoid hemorrhage.

  • Pharmacokinetics: Once the Nimodipine is given by any of the enteral routes, it is immediately up-taken from the gastrointestinal tract. The Nimodipine concentration in the blood attains its highest point within a period of one hour. It is with the help of plasma proteins the up-taken Nimodipine gets distributed within the body. Around 95 percent of Nimodipine circulates in the body as complexes after attaching to these plasma proteins. Within the body, Nimodipine undergoes extensive breakdown and metabolism. The breakdown of Nimodipine is effectuated by various liver enzymes, specifically cytochrome P450 3A4. The first-pass metabolism compromises the bioavailability of Nimodipine by almost 12 percent. The elimination of Nimodipine is chiefly in the form of metabolic products, and only a negligibly small proportion of the drug remains unprocessed. Urine is the primary route through which the drug metabolites, as well as unchanged drug molecules, are expelled out of the body. The elimination half-life was estimated to be around one to two hours, which got revised to eight to nine hours as per the latest study reports.

Toxicity:

Animal trials with Nimodipine at a very high dosage for a period of two years had demonstrated incidences of carcinogenesis. However, short-term animal studies using Nimodipine could not expose any carcinogenic association.

Nimodipine was not reported to induce mutagenic changes in animal and human cells. In addition, animal studies also fail to reveal any influence on fertility upon consumption of Nimodipine. No fertility impairment is reported in animal trials using Nimodipine with comparable doses.

Clinical Studies:

Several clinical studies were conducted to illustrate the effectiveness as well as safety concerning the use of Nimodipine for tackling the vasospasm precipitated by subarachnoid hemorrhage. Four double-blinded clinical studies with distinct control groups and placebo groups were conducted for Nimodipine, which unequivocally proved the effectiveness of Nimodipine for dealing with the neurological deficit that develops as a consequence of subarachnoid hemorrhage. Appreciable recovery is being noted with Nimodipine in the majority of the patients detected with recent subarachnoid hemorrhage. Even in patients with compromised neurological functions following subarachnoid hemorrhage, Nimodipine elicited an appreciable recovery.

What Are the Contraindications of Nimodipine?

There are no specific contraindications for Nimodipine. However, it should not be given to patients who ever had hypersensitivity issues upon the use of Nimodipine. Any form of allergic encounter with Nimodipine or other related drugs that comes under the category of Nimodipine, a potential indication of the possibility of subsequent allergic reactions while undergoing treatment using Nimodipine.

Likewise, if the patient had hyperreactivity to any of the components used in the Nimodipine capsule or oral solution form, it is advised not to prescribe Nimodipine for such patients. Simultaneous intake of Nimodipine with cytochrome P450 3A4 (CYP3A4) inhibitor drug is identified to be a relative contraindication for Nimodipine as it can impair the metabolism of the Nimodipine within the body.

Warnings and Precautions:

  • Liver Cirrhosis: Patients who are diagnosed with liver cirrhosis potentially carry the risk of enhanced Nimodipine concentration in the plasma, which can bring abnormal collapse in the blood pressure. Hence caution should be employed while advising Nimodipine therapy for liver cirrhosis patients.

  • Hypotension: An appreciable fall in blood pressure is noted, with many of the patients undergoing therapy using Nimodipine. Severe hypotension can endanger one’s life, and hence periodic blood pressure assessment should be carried out throughout the treatment period. Clinical studies also exposed an enhanced likelihood of hypotension with Nimodipine when compared with a placebo.

What Are the Drug Interactions of Nimodipine?

  • Cytochrome P450 3A4 Inhibitors: Nimodipine exhibits interactions with CYP3A4 inhibitor drugs. Simultaneous intake of both drugs can remarkably impair the metabolism of Nimodipine, which results in persistent and prolonged elevated concentrations of the medicine in the plasma. This enhanced plasma concentration intensifies the hypotensive property of Nimodipine. The influence is more with potent CYP3A4 inhibitors. However, moderate CYP3A4 inhibitors also bring about similar interactions with variable intensity. Azole antimycotics, macrolide antibiotics, and HIV (human immunodeficiency virus) protease inhibitors are some of the drug categories that inhibit the activity of CYP3A4.

  • Antihypertensive Drugs: Simultaneous intake of Nimodipine and antihypertensive drugs may deepen and strengthen the hypotensive changes in the body. Hence alterations in the dosage of the drugs should be made to diminish the risk of hypotension.

  • Cytochrome P450 3A4 Inducers: Just like CYP3A4 inhibitors, CYP3A4 inducers also influence the potency of Nimodipine when consumed simultaneously. There will be a dramatic collapse in Nimodipine’s effectiveness, and hence it is recommended not to incorporate both Nimodipine and CYP3A4 inducer drugs together. If given together, necessary dose alterations and modifications should be made to counterbalance the loss of desired effectiveness.

Specific Considerations:

  • Nimodipine During Pregnancy: Nimodipine comes under pregnancy category C drug. There is only limited information available concerning the use of Nimodipine in pregnant ladies. Animal studies have concluded the potency of Nimodipine in bringing about teratogenic effects on the embryo. However, there are no such studies conducted in humans. Hence Nimodipine is generally not preferred for expecting ladies, as it bears the risk of harmful impact on the fetus. However, it is prescribed for pregnant women only in those cases where the anticipated benefits outweigh the fetal harm.

  • Nimodipine During Breastfeeding: There is no clinical evidence suggesting a conclusive consideration for the use of Nimodipine during breastfeeding. Animal studies identified the presence of Nimodipine in breast milk. Since it carries the potential risk for the transmission of the medicine to the child through breastmilk, it is generally not advised for lactating mothers unless their health condition demands Nimodipine.

  • Nimodipine for the Pediatric Population: The usage of Nimodipine is restricted in the pediatric population as its effectiveness and safety were not demonstrated through clinical studies or trials.
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Dr. Abhishek Juneja
Dr. Abhishek Juneja

Neurology

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nimodipinesubarachnoid haemorrhage
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