Macitentan

What is Macitentan?

• Macitentan (OPSUMIT) is an endothelin receptor antagonist (ERA) used to treat pulmonary arterial hypertension (PAH).

What are the uses of this medicine?

• This medicine is used to treat pulmonary arterial hypertension (PAH), which is high blood pressure in the arteries of your lungs.
• OPSUMIT can improve your ability to exercise, improve some of your symptoms, and help slow down the progression of your disease. OPSUMIT can also lower your chance of being hospitalized for PAH.

How does this medicine work?

• Macitentan (ma" si ten' tan) is a nonselective inhibitor of the endothelin-1 receptors, both type A and B.
• Inhibition of endothelin receptors disrupts the intracellular pathways that lead to vasoconstriction, thus causing vasodilation.
• Because macitentan has high affinity for pulmonary endothelin receptors, it preferentially causes vasodilation in the pulmonary vasculature, thereby decreasing pulmonary vascular pressure.
• In prospective, randomized controlled trials, macitentan was effective in alleviating symptoms, improving exercise capacity and prolonging the time to clinical worsening in patients with idiopathic PAH.

Who Should Not Use this medicine ?

This medicine cannot be used:

• in females who are pregnant.

What drug interactions can this medicine cause?

• Concomitant use of OPSUMIT with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's Wort and phenytoin) should be avoided.
• Avoid concomitant use of OPSUMIT with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) .
• Avoid concomitant use of OPSUMIT with moderate dual inhibitors of CYP3A4 and CYP2C9 (such as fluconazole and amiodarone).

Is this medicine FDA approved?

• Initial U.S. Approval: 2013

How should this medicine be used?

• Obtain a pregnancy test in females of reproductive potential prior to OPSUMIT treatment, monthly during treatment and one month after stopping OPSUMIT.

Recommended Dosage:

• The recommended dosage of OPSUMIT is 10 mg once daily for oral administration. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended.

Administration

• Take OPSUMIT exactly as your healthcare provider tells you to take it. Do not stop taking OPSUMIT unless your healthcare provider tells you.
• You can take OPSUMIT with or without food.
• Do not split, crush, or chew OPSUMIT tablets.
• If you take too much OPSUMIT, call your healthcare provider or go to the nearest hospital emergency room right away.
• If you miss a dose of OPSUMIT, take it as soon as you remember that day. Take the next dose at your regular time. Do not take 2 doses at the same time to make up for a missed dose.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form: As Tablet: 10 mg

This medicine is available in fallowing brand namesː

• OPSUMIT

What side effects can this medication cause?

The most common side effects of this medicine include:

• Stuffy nose or sore throat
• Irritation of the airways (bronchitis)
• Headache
• Flu
• Urinary tract infection

OPSUMIT can cause serious side effects, including:

• Serious birth defects
• Fluid retention
• Low red blood cell levels (anemia) can occur with OPSUMIT treatment, usually during the first weeks after starting therapy. In some cases a blood transfusion may be needed, but this is not common
• Decreased sperm count

What special precautions should I follow?

• OPSUMIT may cause fetal harm when administered during pregnancy and is contraindicated for use in females who are pregnant. In females of reproductive potential, exclude pregnancy prior to initiation of therapy, ensure use of acceptable contraceptive methods and obtain monthly pregnancy tests.
• ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching).
• Peripheral edema and fluid retention are known clinical consequences of PAH and known effects of ERAs. Monitor for signs of fluid retention after OPSUMIT initiation. If clinically significant fluid retention develops, evaluate the patient to determine the cause, such as OPSUMIT or underlying heart failure, and the possible need to discontinue OPSUMIT.
• Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in clinical studies with OPSUMIT. Initiation of OPSUMIT is not recommended in patients with severe anemia. Measure hemoglobin prior to initiation of treatment and repeat during treatment as clinically indicated.
• Signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue OPSUMIT.
• OPSUMIT, like other ERAs, may have an adverse effect on spermatogenesis. Counsel men about potential effects on fertility.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• headache, nausea and vomiting

Management of overdosage:

• In the event of an overdose, standard supportive measures should be taken, as required.
• Dialysis is unlikely to be effective because macitentan is highly protein-bound.

Can this medicine be used in pregnancy?

• OPSUMIT may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy.

Can this medicine be used in children?

• The safety and efficacy of OPSUMIT in children have not been established.

What are the active and inactive ingredients in this medicine?

• Active ingredient: macitentan
• Inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, polysorbate 80, povidone, and sodium starch glycolate Type A. The tablets are film-coated with a coating material containing polyvinyl alcohol, soya lecithin, talc, titanium dioxide, and xanthan gum.

Who manufactures and distributes this medicine?

• Made in Switzerland.

Manufactured for:

• Actelion Pharmaceuticals US, Inc.,
• a Janssen Pharmaceutical Company
• South San Francisco, USA

What should I know about storage and disposal of this medication?

• Store OPSUMIT tablets at room temperature between 68°F and 77°F (20°C and 25°C).
• Keep OPSUMIT and all medicines out of the reach of children.

• Dailymed label info on Macitentan
• FDA Macitentan

Macitentan Resources
Latest articles Most recent articles Ongoing trials	Wikipedia

Pulmonary Disease Agents

• Chronic Obstructive Pulmonary Disease (COPD) Agents
  • Anticholinergic Agents
    • Ipratropium, Tiotropium, Aclidinium
  • Beta-2 Adrenergic Agonists
    • Albuterol, Formoterol, Salmeterol, Terbutaline
  • Corticosteroids
    • Budesonide, Fluticasone
  • Miscellaneous
    • Roflumilast, Theophylline

• Pulmonary Arterial Hypertension Agents
  

• • Endothelin Receptor Antagonists
    • • Ambrisentan, Bosentan, Macitentan
  • Phosphodiesterase Type 5 (PDE5) Inhibitors
    • Avanafil, Sildenafil, Tadalafil, Vardenafil
  •  Prostacyclin Analogs
    • Epoprostenol, Iloprost, Treprostinil
  •  Miscellaneous
    • Riociguat, Selexipag

• Pulmonary Fibrosis Agents
  • Nintedanib, Pirfenidone