Macitentan

OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH ( 1.1 ). 1.1 Pulmonary Arterial Hypertension OPSUMIT is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) in adults to reduce the risks of disease progression and hospitalization for PAH. Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II–III symptoms treated for an average of 2 years. …

• 10 mg once daily
• Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended
• 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
• Pregnancy Testing in Females of Reproductive Potential Exclude pregnancy before initiating treatment with OPSUMIT in females of reproductive potential [see Boxed Warning , Contraindications , Warnings and Precautions , and Use in Specific Populations ]

Tablets: 10 mg, bi-convex film-coated, round, white, and debossed with "10" on both sides. Tablet: 10 mg ( 3 )

• The safety and effectiveness of OPSUMIT
• In pediatric patients have not been established
• For the treatment of PAH
• OPSUMIT was evaluated in 148
• Pediatric patients 2 to 17 years of age with PAH in a single open-label, randomized trial with an extension period in which all patients received treatment
• The trial did not demonstrate a clinical benefit of OPSUMIT compared with standard of care in the treatment of PAH
• It cannot be ruled out that a trial with a different design would demonstrate a clinical benefit in this patient population. …

Of the total number of subjects in the clinical study of OPSUMIT for PAH, 14% were 65 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

• Advise patient to read FDA-approved patient labeling (Medication Guide)
• Embryo-Fetal Toxicity Counsel female patients of reproductive potential about the need to use effective methods of contraception prior to initiation of treatment with OPSUMIT, during treatment and for one month after treatment discontinuation
• Females of reproductive potential should have a negative pregnancy test prior to treatment with OPSUMIT [see Contraindications , and Use in Specific Populations ]
• Patients should be instructed to contact their physician if they suspect they may be pregnant
• Patients should seek additional contraceptive advice from a gynecologist or similar expert as needed. …

• Pregnancy Hypersensitivity Pregnancy OPSUMIT may cause fetal harm when administered to a pregnant woman
• OPSUMIT is contraindicated in females who are pregnant
• OPSUMIT was consistently shown to have teratogenic effects when administered to animals
• If OPSUMIT is used during pregnancy, advise the patient of the potential risk to a fetus [see Warnings and Precautions and Use in Specific Populations ] . …

Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid co-administration with OPSUMIT ( 7.1 , 12.3 ). Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.2 , 12.3 ) . Moderate dual CYP3A4 and CYP2C9 inhibitors (fluconazole, amiodarone) or use of combined CYP3A4 and CYP2C9 inhibitors may increase exposure to macitentan: avoid co-administration with OPSUMIT ( 7.3 , 12.3 ). 7.1 Strong CYP3A4 Inducers Strong inducers of CYP3A4 such as rifampin significantly reduce macitentan exposure. Concomitant use of OPSUMIT with strong CYP3A4 inducers should be avoided [see Clinical Pharmacology (12.3) ] . …

ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated ( 5.2 ). Fluid retention may require intervention ( 5.3 ). Decreases in hemoglobin ( 5.4 ). Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment ( 5.5 ). Decreases in sperm count have been observed in patients taking ERAs ( 5.6 ). 5.1 Embryo-fetal Toxicity Based on data from animal reproduction studies, OPSUMIT may cause fetal harm when administered to a pregnant patient and is contraindicated during pregnancy. …

Clinically significant adverse reactions that appear in other sections of the labeling include: Embryo-fetal Toxicity [see Warnings and Precautions (5.1) ] Hepatotoxicity [see Warnings and Precautions (5.2) ] Fluid Retention [see Warnings and Precautions (5.3) ] Decrease in Hemoglobin [see Warnings and Precautions (5.4) ] Most common adverse reactions (more frequent than placebo by ≥3%) are anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza, and urinary tract infection ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Actelion at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. …

8.1 Pregnancy Risk Summary Based on data from animal reproduction studies, OPSUMIT may cause embryo-fetal toxicity, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy. There are risks to the mother and the fetus associated with pulmonary arterial hypertension in pregnancy [see Clinical Considerations ] . …

OPSUMIT has been administered as a single dose of up to and including 600 mg to healthy subjects (60 times the approved dosage). Adverse reactions of headache, nausea and vomiting were observed. 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.

Store at 20 ºC to 25 ºC (68 ºF to 77 ºF). Excursions are permitted between 15 °C and 30 °C (59 °F and 86 °F). [See USP Controlled Room Temperature] . Keep out of reach of children.

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.