Overview:
Migraines that last for four to 72 hours can cause throbbing head pain, light and sound sensitivity, and nausea. Two types of migraine exist. One is episodic (up to 15 days per month) and another is chronic (over 15 days per month for three months), affecting one to two percent of the population.
In the US (United States), 21 percent experience migraines, impacting women aged 15 to 49 and resulting in significant economic costs. Recent progress in migraine treatment targets calcitonin-gene-related peptide (CGRP), a neurotransmitter released during migraines. Blocking CGRP has resulted in migraine prevention, leading to the FDA's (Food and Drug Administration's) approval of Rimegepant in February 2020.
Drug Group:
Rimegepant belongs to a group of medicines known as calcitonin gene-related peptide receptor antagonists. It prevents the activity of a specific natural substance in the body responsible for causing migraine headaches.
Available Doses and Dosage Forms:
Rimegepant is approved in the USA (United States of America) and the EU (European Union) for treating acute migraines in adults with or without aura and preventing episodic migraines in adults who are experiencing at least four migraine attacks per month. It is not meant for treating chronic migraines. The recommended dose for acute migraine treatment is 75 mg (milligram) as needed, and for preventive medicine, it is 75 mg every second day. The maximum daily dose is 75 mg, and safety beyond 18 doses in 30 days is not established. Rimegepant is available in an orally dissolving tablet (ODT) form. It is important to note that its efficacy and safety have not been established in pediatric patients.
For Patients:
What Is a Migraine?
A migraine is an intense headache with throbbing pain, often on one side, causing nausea, vomiting, and sensitivity to light and sound. It can last hours to days, disrupting daily activities.
How Does Rimegepant Work?
Rimegepant falls into a group of drugs known as calcitonin gene-related peptide receptor antagonists. Its job is to hinder the effects of a specific natural substance in the body responsible for triggering migraine headaches. In simpler terms, it helps alleviate migraines by interfering with the activity of a substance that contributes to their onset.
What Is the Dosage of Rimegepant?
The dosage of Rimegepant medication varies among individuals. Follow the doctor's instructions or the label. The amount depends on the medicine's strength, how often it has to be taken, and the duration. For oral disintegrating tablets treating acute migraines, adults typically take 75 mg once a day, not exceeding 75 mg in 24 hours. To prevent episodic migraines, adults take 75 mg every other day. The doctor determines children's usage.
How Effective Is Rimegepant?
After taking Rimegepant for 24 hours, patients had 9.8 percent more prolonged relief from pain and 17.8 percent more sustained relief than a placebo. After 48 hours, 7.0 percent experienced no pain, and 15.5 percent still had lasting relief compared to the placebo.
What Are the Things to Inform the Doctor Before Taking the Rimegepant?
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Before taking Rimegepant, inform the healthcare provider about the medical conditions.
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Mention any liver or kidney problems the person may have.
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Let the healthcare provider know if the person is pregnant or planning to become pregnant, as the impact on unborn babies is uncertain.
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If the person is breastfeeding or planning to breastfeed, inform the healthcare provider, as the effects of breast milk are not well understood.
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Provide details about all medications, including prescriptions, over-the-counter drugs, vitamins, and herbal supplements the person is currently taking.
How Is Rimegepant Administered?
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Use dry hands when opening the blister pack.
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Peel back the foil from one blister and gently take out the tablet. Do not push it through the foil.
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Place the tablet on the tongue or under it as soon as the blister opens.
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The tablet will dissolve in the saliva, and the person can swallow it without needing water.
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Take the tablet right after opening the blister pack. Do not save it outside the pack for later use.
What Are the Side Effects of Rimegepant?
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Rimegepant can lead to severe allergic reactions, including difficulty in breathing and rash. These reactions may occur even days after taking the medication. Seek immediate medical attention if the person is experiencing swelling of the face, mouth, tongue, or throat or has trouble breathing.
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The primary side effect of Rimegepant in treating migraines is nausea.
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For preventive use against episodic migraines, common side effects include nausea, stomach pain, and indigestion.
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Note that these are not the only potential side effects associated with Rimegepant.
Dietary Considerations:
If the person is taking Rimegepant, it is wise to limit grapefruit intake. Grapefruit can boost Rimegepant levels, causing more side effects. If the person consumes grapefruit with Rimegepant, avoid a second dose within 48 hours. Discuss concerns with the doctor and inform them about all the medications, including vitamins. Do not stop any medication without consulting the doctor.
Missed Dose:
Rimegepant is taken on an as-needed basis. Take it less often than told by the doctor.
Overdose:
If overdosing on Rimegepant happens, the approach should involve general supportive care, like keeping an eye on vital signs and the patient's overall condition. There is no specific antidote for Rimegepant overdose, and standard treatments like dialysis may not be effective due to the drug's strong binding to proteins in the blood.
Storage:
Keep Rimegepant in a controlled room at temperatures between 68° F (Fahrenheit) to 77° F (20° C (Celsius) to 25° C). It is okay for the temperature to go between 59° F to 86° F (15° C to 30° C) for short periods. Follow the USP (United States Pharmacopeia) guidelines for controlled room temperature.
For Doctors:
Indication:
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Migraine Treatment: Rimegepant is indicated for the acute management of migraines, with or without aura, in adults.
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Migraine Prevention: Rimegepant is also approved for the prophylactic treatment of episodic migraines in adults, aiming to prevent their occurrence.
Dose:
For addressing an acute migraine episode, the suggested dosage of Rimegepant is 75 mg administered orally as required. The highest amount allowed within a 24-hour timeframe is 75 mg. It is currently unknown whether using more than 18 doses in 30 days is safe. For preventing episodic migraines, the recommended dose of Rimegepant is 75 mg taken orally every other day.
Dosing Considerations:
Rimegepant is an orally disintegrating tablet, a circular tablet that is white to off-white, bearing the symbol, and each contains 75 mg of the medication Rimegepant.
What Are the Pharmacological Aspects of Rimegepant?
Pharmacodynamics:
Rimegepant is a fast-acting medication that prevents migraines by blocking a key molecule. Its effectiveness is typically assessed within two hours. Importantly, it does not require dosage adjustment for most patients, except those with severe liver issues. As a CGRP receptor antagonist, Rimegepant effectively blocks CGRP activity, particularly at the CGRP receptor. In tests, it showed high potency in inhibiting CGRP-induced effects on facial blood flow without causing vasoconstriction in human arteries, distinguishing it from other medications like Sumatriptan. Even at high concentrations, it did not impact heart and electrical parameters. Extended daily use at high doses also did not affect cardiovascular parameters. In studies with healthy volunteers, Rimegepant, whether in standard or higher doses, did not cause clinically relevant QT interval prolongation.
When used alongside Sumatriptan, there were no significant differences in resting blood pressure. However, it is crucial to be aware of potential hypersensitivity reactions, and if they occur, discontinuing Rimegepant is recommended. Rimegepant works by preventing a molecule linked to migraine activity, making it helpful in stopping migraine headaches. It is designed for quick relief, with its effects typically assessed within two hours. Importantly, its dosage does not need adjustment for patients with various levels of kidney or liver function, except for those with severe liver impairment. In severe liver cases, it is crucial to avoid using Rimegepant due to higher drug levels. Hypersensitivity reactions have been noted, and if they occur, patients should stop using Rimegepant immediately.
Mechanism:
Migraines involve the neurotransmitter CGRP, which has been studied extensively for its role. CGRP, discovered in 1985, is produced in neurons and released during severe migraines. It has receptors in various parts of the nervous system, particularly trigeminovascular. Elevated CGRP levels may indicate chronic migraines. CGRP plays a role in triggering migraines and is associated with general pain. Its activation leads to processes like cortical spreading depression and potent vasodilation, contributing to migraine symptoms. Blocking CGRP receptors can counteract these effects. Rimegepant, a second-generation CGRP inhibiting agent, blocks CGRP receptors selectively, primarily in the peripheral nervous system. It has a higher affinity for peripheral CGRP receptors than central ones, targeting the trigeminovascular system outside the blood-brain barrier. This action helps reduce neurogenic inflammation associated with migraines.
Pharmacokinetics:
Rimegepant, administered as a sublingual ODT, is bioequivalent to the oral tablet, showing comparable pharmacokinetic parameters in a trial with healthy volunteers. The drug exhibits linear pharmacokinetics with an oral bioavailability of around 64 percent. When taken with a high-fat meal, the drug's absorption is delayed and its concentration reduced, though the clinical significance of this is unknown. Rimegepant undergoes metabolism mainly through CYP3A4 and, to a lesser extent, CYP2C9, with no major metabolites detected in the blood. Factors such as sex, age, race, body weight, migraine status, and kidney function do not significantly impact the drug's pharmacokinetics. However, severe hepatic impairment results in approximately twofold higher exposure, and its use is not recommended in such cases. The drug has not been studied in patients with end-stage renal disease (ESRD), and its use should be avoided in this population.
Toxicity:
Hepatotoxicity: In controlled trials involving thousands of patients, Rimegepant showed mild-to-moderate elevations in liver enzymes (aminotransferases) in a small percentage (1 to 2 percent) of patients, similar to placebo rates. No clinically apparent liver injuries were reported in trials or general use. Notably, a different drug, Telcagepant, was discontinued during development due to cases of significant liver injury.
Effects During Pregnancy and Lactation: For breastfeeding, there is limited information on Rimegepant's clinical use. However, the amount of the drug in breast milk is low, and it is not expected to harm infants. If a mother requires Rimegepant while breastfeeding an older infant, it is generally considered safe. However, caution is advised for newborns or preterm infants, and using an alternative drug may be preferred until more data is available.
Protein Binding: Rimegepant binds to approximately 96 percent of plasma proteins, but the specific proteins involved are unknown.
Clinical Studies:
Rimegepant received FDA approval based on findings from two key studies: a phase 3 clinical trial (Study 303) and a long-term safety study (Study 201). In the Phase 3 trial, patients taking Rimegepant experienced relief from pain and the most bothersome symptoms two hours after a single dose, compared to those on a placebo. Many patients sustained these benefits for up to 48 hours. Importantly, 86 percent of Rimegepant-treated patients did not need additional medications like NSAIDs (nonsteroidal anti-inflammatory drug) or acetaminophen within 24 hours. The long-term safety study (Study 201) focused on assessing the safety and tolerability of Rimegepant with multiple doses over one year. It involved 1,798 patients who used 75 mg of Rimegepant as needed, treating an average of at least two migraine attacks per month. However, the safety of using Rimegepant for more than 15 migraine attacks in 30 days has not been established.
What Are the Contraindications of Rimegepant?
Rimegepant should not be used in individuals who have experienced a hypersensitivity reaction to Rimegepant or any of its components. There have been instances of delayed serious hypersensitivity reactions.
Warnings and Precautions:
Rimegepant has led to hypersensitivity reactions in clinical studies, with symptoms like difficulty in breathing and skin rash. These reactions can even happen days after taking the medication, and some cases involve serious delayed hypersensitivity. If someone experiences a hypersensitivity reaction, it is crucial to stop using Rimegepant and begin suitable treatment.
What Are the Drug Interactions of Rimegepant?
Rimegepant interacts with several enzymes and transporters in the body, including CYP3A4 (Cytochrome P450 3A4), CYP2C9, P-gp, and BCRP ((Breast Cancer Resistance Protein). It also has inhibitory effects on CYP3A4. Co-administration with strong CYP3A4 inhibitors or inducers is not recommended. Avoiding an additional dose within 48 hours is advised when combining Rimegepant with moderate CYP3A4 inhibitors or strong P-gp inhibitors. Rimegepant is an inhibitor of OATP (Organic anion transporting polypeptide) 1B3, OCT2, and MATE1 and a weak inhibitor of OATP1B1 and OAT3. Notably, there are no expected clinical drug interactions with certain medications, including oral contraceptives, Midazolam, Metformin, or Sumatriptan.
Specific Considerations:
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Pregnancy: The estimated risk of birth defects and miscarriage in the general population is two to four percent and 15 to 20 percent, respectively. The result is that in women with migraines to those without migraines. Women with migraines may have an increased risk of preeclampsia and gestational hypertension during pregnancy.
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Lactation: The benefits of breastfeeding and the mother’s clinical need for Rimegepant should be considered.
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Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
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Geriatric Use: No clinically significant differences were observed between elderly patients.
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Hepatic Impairment: No dosage adjustment is required in mild or moderate hepatic impairment. Avoid use in severe hepatic impairment.
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Renal Impairment: No dosage adjustment is required in mild, moderate, or severe renal impairment. Avoid use in end-stage renal disease or dialysis patients.
