Macitentan

BRAND NAME:

Opsumit – Opsumit contains Macitentan as the main active ingredient in the tablet and is available as opsumit Macitentan tablets 10mg.

MECHANISM OF ACTION:

Endothelin-1 is a potent vasoconstrictor peptide synthesized and released by endothelial cells. Endothelin -1 plays a crucial role in the pathogenesis of PAH by inducing vasoconstriction, promoting smooth muscle cell proliferation, and stimulating fibrosis and inflammation within the pulmonary vasculature. The binding of Endothelin -1 to its receptors, endothelin receptor type A(ETA), and endothelin receptor type B(ETB) mediate these pathological effects. It exerts its therapeutic effects by selectively antagonizing both ETA and ETB receptors. By blocking these receptors,macitentan prevents the binding of Endothelin- 1, inhibiting its harmful effects. This dual inhibition is significant because while ETA receptor blockade predominantly addresses vasoconstriction and cellular proliferation, ETB receptor blockade can enhance the clearance of Endothelin -1 and reduce fibrosis and inflammation.  It has a high affinity for both receptors and exhibits a prolonged receptor binding duration. Macitentan ability to effectively penetrate tissues ensures that it can exert its effects within the pulmonary vasculature where it is needed.

PHARMACOKINETICS:

Absorption: The estimated bioavailability is determined at 74%.Food has not been found any significant effect on the absorption

Distribution: The apparent volume of distribution is 40 – 50

Metabolism: It undergoes oxidative depolarization of the sulfonamide moiety with CYP3A4, CYP2C8, CYP2C9, and CYP2C19 to form the active metabolite.

Excretion: Excreted 50 % through urine and 24% through feces.

DOSAGE AND ADMINISTRATION:

Macitentan is available in the form of tablets. The dose prescribed for the patients depends on the patient's condition the dosage may vary from patient to patient. The amount of medicine prescribed is based on the strength of the medicine.

For pulmonary arterial hypertension, the dose recommended for adults is 10mg once a day. For children, the dose must be determined by the doctor.

CONTRAINDICATIONS:

Hypersensitive reaction to drug or excipients. 

DRUG INTERACTIONS:

Before using Macitentan, it is required to discuss with the doctor the medication that has already been used for other treatments. Some medicines taken with macitentan can cause side effects or decrease the efficiency of the drug. Based on the patient's condition the doctor can reduce the dosage form. Below are some medications that you should avoid using with Macitentan.

•  Amiodarone

•  Antiviral medications – HIV, Hepatitis

•  Fungal infection medications – Fluconazoe,ketoconazole, itraconazle, posaconazole

•  Rifampin

ADVERSE EFFECTS:

• Anemia

• Swelling of the ankles or legs

• Bronchitis

• Loss of appetite

• Sore throat

• Extreme tiredness

• Headache

• Frequent and Painful urination

• Difficult in swallowing or breathing

• Rashes

• Stuffy nose

• Yellowish skin or eyes

• Pain in the upper right part of the stomach

• Dark urine

• Nausea and vomiting

• Increase in weight

• Hoarseness

• Nasopharyngitis

• Fever

• Shortness of breath especially when lying down

• Coughing and frothy sputum or blood

TOXICITY:

Drug overdose can lead to some toxic effects. Common toxic symptoms are mentioned below.

• Headache

• Vomiting

• Nausea

• Trouble breathing

• Seizures