Mavacamten: Transforming Lives Affected by Obstructive Hypertrophic Cardiomyopathy

Overview

A recently developed medication known as Mavacamten is used to treat and manage obstructive hypertrophic cardiomyopathy (HCM). This medication is reserved especially for adult patients with obstructive heart failure (HCM), a condition in which the heart fails to pump blood as efficiently as it should. Mavacamten lessens symptoms and enhances their capacity to perform daily tasks. Mavacamten acts by specifically targeting cardiac myosin ATPase, a protein that aids in the contraction of the heart. Mavacamten received the United States Food and Drug Administration (USFDA) approval in April 2022.

Drug Group:

Mavacamten belongs to a group of drugs known as cardiac myosin inhibitors.

Indications:

Adults with obstructive hypertrophic cardiomyopathy (HCM) can benefit from taking the medication Mavacamten. It is intended for those who, according to the New York Heart Association (NYHA), are categorized as having a moderate to severe degree of this ailment and exhibiting symptoms like chest pain or difficulty breathing. By increasing heart function and easing symptoms, Mavacamten is intended to help these people feel better and carry out everyday activities more easily.

Contraindications:

It is not recommended to combine Mavacamten with:

• Medications with a significant impact on the CYP2C19 or CYP3A4 enzymes.

• Medications that significantly increase the CYP2C19 or CYP3A4 enzymes.

Dosage Forms and Available Strengths

Mavacamten is available in capsule form, with the name "Mava" and its strength printed on each capsule. The color of the capsule can be used to determine its strength:

• Capsules containing 2.5 mg (milligrams) are bright purple colored.

• Yellow caps are used on 5 mg capsules.

• The caps on 10 mg pills are pink.

• The caps on 15 mg pills are gray.

For Patients

What Is Obstructive Hypertrophic Cardiomyopathy (HCM)?

Obstructive hypertrophic cardiomyopathy (HCM) causes the heart muscle to hypertrophy or grow excessively thick, which makes it more difficult for the heart to pump blood efficiently. The thickening muscle in this illness may hinder the heart's ability to pump blood out, particularly during diastole, which can cause symptoms including exhaustion, dizziness, shortness of breath, and chest pain. In addition to increasing the risk of sudden cardiac arrest, this obstruction can also result in arrhythmias or irregular heart rhythms. Although HCM is usually inherited, it can sometimes arise from other causes. The goals of treatment are to control symptoms, enhance cardiac performance, and lower the chance of complications.

What Are the Clinical Uses of Mavacamten?

Mavacamten is a medication used to improve the symptoms of obstructive hypertrophic cardiomyopathy in adults. It is a member of the class of drugs known as cardiac myosin inhibitors. It functions by facilitating the heart's relaxation and lessening its contraction. This aids in symptom improvement and improves cardiac function.

How Should Mavacamten Be Used?

Mavacamten is available as an oral capsule. It is typically taken once a day, with or without food. Take Mavacamten each day at approximately the same time. Pay close attention to the instructions on the label of the prescription and ask the physician or pharmacist to explain anything one does not understand. Consume Mavacamten precisely as prescribed. Never take more or less of it, or take it more frequently than the doctor has instructed.

Do not split, chew, or crush the tablets or capsules; instead, swallow them whole.

The doctor will likely put the person on a low dosage of Mavacamten and then progressively raise or lower it based on how one feels and how the medication affects them.

Mavacamten does not treat obstructive hypertrophic cardiomyopathy; rather, it manages its symptoms. Take Mavacamten as prescribed even if one feels well. Mavacamten should not be stopped without the advice of the doctor.

What Are the Side Effects of Mavacamten?

Mavacamten may cause adverse reactions. If any of these symptoms are severe or persist, let the doctor know:

• Lightheadedness.

• Fainting.

Certain adverse effects may be dangerous. If one has any odd side effects while taking this medicine, contact the doctor.

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

• Allergies and Substances: Let the physician and pharmacist know if one has any allergies to any of the substances in Mavacamten capsules, other drugs, or Mavacamten itself.

• Medication Interactions: Talk about all of the drugs one is taking or intends to take with the doctor and pharmacist. Some medications may not be safe to take with Mavacamten, while others may need dose modifications or careful monitoring.

• Doctor's Advice: While taking Mavacamten, one should always get advice from the doctor or pharmacist before beginning, stopping, or altering any dosage. Mention all prescription and over-the-counter drugs, as well as vitamins, supplements, and herbal products.

• Birth Control Considerations: The effectiveness of hormonal birth control methods such as tablets, patches, rings, and injections may be impacted by Mavacamten. While taking Mavacamten and for four months after stopping it, another method of contraception, such as an intrauterine device or condoms, should be used to avoid conception.

• Medical History: Let the physician know if the patient has ever had an infection or an arrhythmia.

• Pregnancy and Breastfeeding: Tell the doctor if the patient is pregnant, intends to become pregnant, or is nursing a baby since Mavacamten may harm the unborn child. If the patient becomes pregnant while using Mavacamten, get in touch with the doctor right away. If the patient is a female, a pregnancy test will be performed before beginning Mavacamten. Use an intrauterine device, condoms, or other effective birth control for four months after quitting Mavacamten and during the treatment.

Dietary Consideration: Continue normal diet unless directed otherwise by the doctor.

Storage: Mavacamten should be kept out of children's reach and securely closed in the container it came in. Keep it out of direct sunlight and dampness, and store it at room temperature. Never keep it in the restroom. It is important to keep any medications out of children's sight and reach. Always lock safety caps and put the medication in a safe place right away, out of young children's access and sight. This will help prevent poisoning.

Disposal: It is important to dispose of leftover prescriptions correctly to avoid pets, kids, or other people accidentally ingesting them. Nonetheless, it is not advisable to flush Mavacamten down the toilet. Through a drug take-back program, this medication can be disposed of most effectively. To find out about take-back programs in the area, speak with the pharmacist or get in touch with the recycling and waste management department in the town. If there is no take-back program available, one can get advice on safe disposal techniques by visiting the FDA's Safe Disposal of Medicines website.

Missed Dose: Mavacamten should be taken as soon as remembered if a dose is missed. To prevent any possible negative effects or difficulties, it is crucial to avoid taking two doses on the same day. To preserve the medication's efficacy, Mavacamten capsules must be eaten whole, not chewed or opened.

Overdose: Contact the poison control helpline if someone accidentally consumes too much Mavacamten. Call emergency services as soon as possible if the person passes out, experiences a seizure, has trouble breathing, or is unable to awaken.

For Doctors

Pharmacodynamics:

Patients receiving Mavacamten in the EXPLORER-HCM trial demonstrated steady improvements in heart shape and function over 30 weeks as compared to those receiving a placebo. They specifically displayed indicators of decreased thickness and volume in their cardiac muscles as well as lower pressure gradients in the left ventricle, which implies less blockage to blood flow. Furthermore, patients on Mavacamten had considerably lower levels of a marker indicative of heart stress than individuals on a placebo. Nonetheless, especially at larger dosages, Mavacamten may produce a modest lengthening of the QT interval, which measures cardiac rhythm; however, this effect is not deemed clinically significant within appropriate therapeutic levels. It is crucial to remember that the effects of Mavacamten on people with specific genetic disorders that affect heart rhythm or when combined with other drugs that alter heart rhythm are still unknown.

Mechanism of Action:

Mavacamten is a drug that targets the heart muscle directly. It functions by controlling the myosin protein's activity, which is necessary for muscle contraction. In doing so, Mavacamten aids in the reduction of excessive cardiac muscle contractions, which are frequently observed in disorders such as hypertrophic cardiomyopathy (HCM). This drug facilitates improved cardiac relaxation and enhances the heart's capacity to pump blood efficiently.

Pharmacokinetics:

• Consumption: Mavacamten has a high oral bioavailability when taken orally; at least 85 percent is calculated. It takes very little time for the blood to reach its peak concentration (Tmax), which usually happens an hour after the dose.

• Food Effect: The co-administration of Mavacamten with a high-fat meal does not cause pharmacokinetic changes that are clinically meaningful. When given with food, however, the time it takes to reach peak concentration (Tmax) is around four hours longer.

• Distribution: Mavacamten shows significant levels of binding to plasma proteins, ranging from 97 percent to 98 percent. This feature implies that the medicine is mostly linked to bloodstream proteins, which may affect how the drug is distributed throughout the body.

• Elimination: Depending on the CYP2C19 enzyme's metabolic state, Mavacamten’s elimination half-life varies. The half-life in people with typical CYP2C19 metabolism is six to nine days; in people with weak metabolizers, it can be up to 23 days. Furthermore, Mavacamten tends to cause drug buildup, especially in individuals with poor metabolization, which can result in notable variations in the ratios of plasma concentrations.

• Metabolism: The cytochrome P450 enzymes (CYP2C19, CYP3A4, and CYP2C9) present in the liver are the main mediators of Mavacamten metabolism.

• Excretion: After being delivered, the majority of Mavacamten is removed through the urine, which accounts for approximately 85 percent of the total dose. The other seven percent is expelled through the stools. There is very little medication that has not been altered.

• Specific Populations: Research has not demonstrated any clinical variations in the pharmacokinetics of Mavacamten according to age, gender, race, ethnicity, or mild to severe renal impairment. On the other hand, nothing is known about the consequences of severe renal impairment and kidney failure, including dialysis patients.

• Hepatic Impairment: Compared to individuals with normal hepatic function, patients with mild to moderate hepatic impairment show higher exposure to Mavacamten. On the other hand, it is unknown how severe liver impairment affects the pharmacokinetics of Mavacamten.

• Drug Interactions: A variety of CYP2C19 and CYP3A4 inducers and inhibitors can affect the pharmacokinetics of Mavacamten, resulting in changed exposure levels. Depending on the particular inducers or inhibitors involved, the degree of interaction varies.

• Research Conducted in Vitro: Mavacamten functions as an inducer of CYP2B6, which may have consequences for its metabolism and possible interactions with other medications. However, it does not inhibit specific CYP enzymes or transporter systems.

What Is the Prescribed Dosage and Method of Administration For Mavacamten?

• Starting Medication and Monitoring: Physicians must confirm that female patients are not pregnant and are using an effective birth control technique before beginning Mavacamten medication. Furthermore, in individuals with a certain cardiac problem where the heart's pumping function is less than 55 percent, Mavacamten should not be started or increased.

• Dosage and Titration: Mavacamten is normally started at a dose of five mg once daily, whether or not food is consumed. Doctors can change the dosage to 2.5, 5, 10, or 15 mg once daily, depending on the health of each patient. To maintain ideal heart health, regular monitoring is essential for evaluating the patient's heart function and modifying the dosage as necessary.

• Time to Full Effect: Mavacamten takes a few weeks to work its way up to its utmost in the body. This is crucial to take into account because different people may metabolize the drug differently, which could lead to various reactions to the prescription. Thus, determining the appropriate dosage for each patient is crucial to guaranteeing the efficacy of the treatment.

• Guidelines for Beginning, Continuing, and Stopping Medication: Before beginning or modifying Mavacamten medication, physicians should evaluate the patient's cardiac function. Treatment should be discontinued for a short while if the patient's cardiac function falls below a specified threshold. Dosage changes or treatment pauses may be required during periods of illness or certain heart diseases to protect the patient.

• Interaction With Other Drugs: Patients' dosages may need to be changed if they currently take any drugs that interact with Mavacamten. After beginning these drugs, the patient should be monitored and evaluated, and the dosage of Mavacamten should be changed as needed to maximize therapy effectiveness and protect patient safety.

Drug Interactions:

• Possible Interactions Between Drugs and Mavacamten Plasma Concentrations: Mavacamten is mostly metabolized by CYP2C19. However, CYP3A4 and CYP2C9 also play a role in this process. The amount of Mavacamten that remains in the body may be altered by medications that either increase or decrease the activity of these enzymes.

• Possibility of Mavacamten Impacting Other Drugs’ Plasma Concentrations: Mavacamten, commonly known as Mavacamten, can affect the way the body processes other medications. It activates certain enzymes, including CYP3A4, CYP2C9, and CYP2C19. Mavacamten may lower blood levels of medications that these enzymes break down when used with other medications like birth control pills. It is critical to keep a tight eye on things and, if needed, explore alternate forms of birth control.

• Medication That Lowers Cardiac Contractility: Mavacamten may interact with other medications that have an impact on heart health. If Mavacamten is taken with drugs that lower the heart's pumping capacity, the detrimental effects on heart function may be more pronounced. To prevent potential problems, constant monitoring is required until stable doses and responses are reached if a patient requires both Mavacamten and another medicine that weakens heart contractions.

Clinical Studies:

In a study called EXPLORER-HCM, researchers looked at a new treatment, Mavacamten, for people with obstructive hypertrophic cardiomyopathy (HCM). They enrolled 251 adults with moderate to severe symptoms of this condition. The study was double-blind, meaning neither the patients nor the researchers knew who was receiving the treatment or the placebo.

They found that Mavacamten was effective in improving the condition of patients compared to those who received a placebo. Specifically, at the end of the 30-week treatment period:

• 37 percent of patients in the Mavacamten group showed improvement in their heart function, compared to only 17 percent in the placebo group.

• Patients on Mavacamten had better post-exercise heart function, increased exercise capacity, and improved overall health status compared to those on placebo.

• The treatment also helps to reduce the symptoms of shortness of breath and improves patients' quality of life.

These findings suggest that Mavacamten could be a promising treatment option for people with obstructive HCM, potentially leading to better heart function and quality of life.

Warnings and Precautions:

• Heart Failure: By weakening cardiac contractions, Mavacamten may obstruct or cause heart failure. Individuals who suffer from severe illnesses or specific cardiac rhythm disorders are more vulnerable. Physicians should monitor their patient's heart health regularly and modify the dosage of Mavacamten as necessary. Chest pain, exhaustion, and edema are examples of symptoms that could point to heart issues and require immediate attention. When initiating Mavacamten in individuals with weak cardiac contractions, extra caution is required.

• Drug Interactions: Because Mavacamten interacts with specific enzymes in the body, using it with some drugs together may be risky and increase the risk of heart failure or decrease the effectiveness of the prescription. Patients should disclose all of their medicine, including over-the-counter drugs, to their doctors. Patients should exercise caution when taking certain drugs, such as Omeprazole or Cimetidine, as they may interact with Mavacamten.

• Mavacamten REMS Program: Because of the possibility of heart failure, Mavacamten is only accessible through a limited program known as the Mavacamten REMS Program. To guarantee the safe use of Mavacamten, this program contains particular standards for prescribers, patients, pharmacies, wholesalers, and distributors.

• Embryo-Fetal Toxicity: Research on animals has shown that Mavacamten may be harmful to a growing fetus if taken during pregnancy. Doctors must verify that female patients are not pregnant before beginning therapy and must counsel them to utilize reliable contraception both before and after Mavacamten treatment. Some birth control pills may become less effective when taken with Mavacamten. Thus, other approaches might be required. If female patients become pregnant while taking Mavacamten, they should be informed of the possible dangers to the developing fetus.

Use in Specific Populations:

• Pregnancy: There is no information on the effects of Mavacamten on human pregnancy. However, animal research suggests that it may be harmful to the fetus. Given that Mavacamten has been linked to bone deformities in animals and decreased fetal weight in humans, pregnant women should be made aware of any possible hazards. Healthcare practitioners must be informed if a patient becomes pregnant while using Mavacamten.

• Lactation: It is unknown if Mavacamten enters human or animal milk, how it affects breastfed infants, or how much milk is produced. In addition to the necessity of Mavacamten and any possible hazards to the infant, doctors should take into account the benefits of nursing.

• Males and Females of Reproductive Potential: Effective contraception should be taken during therapy and for four months after quitting it, and pregnant women should be ruled out before beginning Mavacamten. Some birth control pills may become less effective when taken with Mavacamten thus, other methods might be required.

• Use in Pediatrics: It has not been determined whether Mavacamten is safe or effective in children.

• Geriatric Use: Clinical investigations suggest that Mavacamten is as safe and effective in older persons as it is in younger adults.

• Hepatic Impairment: It is not necessary to modify the dosage of Mavacamten for patients with mild to moderate liver difficulties; nevertheless, the consequences of severe liver impairment remain unknown.