|
OPSUMIT(macitentan)tablets, for oral use
|
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use OPSUMIT safely and effectively. See full prescribing information for OPSUMIT
OPSUMIT® (macitentan) tablets, for oral use
Initial U.S. Approval: 2013
WARNING: EMBRYO-FETAL TOXICITY
See full prescribing information for complete boxed warning
Do not administer OPSUMIT to a pregnant female because it may cause fetal harm (4.1, 5.1, 8.1).
Females of reproductive potential: exclude pregnancy before start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after treatment by using acceptable methods of contraception (2.2, 8.6).
For all female patients, OPSUMIT is available only through a restricted program called the OPSUMIT Risk eva luation and Mitigation Strategy (REMS) (5.2).
INDICATIONS AND USAGE
OPSUMIT® is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). OPSUMIT also reduced hospitalization for PAH (1.1).
DOSAGE AND ADMINISTRATION
10 mg once daily. Doses higher than 10 mg once daily have not been studied in patients with PAH and are not recommended (2.1).
DOSAGE FORMS AND STRENGTHS
Tablet: 10 mg (3)
CONTRAINDICATIONS
Pregnancy (4.1)
WARNINGS AND PRECAUTIONS
Other ERAs cause hepatotoxicity and liver failure. Obtain baseline liver enzymes and monitor as clinically indicated (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).
ADVERSE REACTIONS
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 1-866-228-3546 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
DRUG INTERACTIONS
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).
USE IN SPECIFIC POPULATIONS
Nursing mothers: discontinue OPSUMIT or breastfeeding (8.3).
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 10/2013
Back to Highlights and Tabs
Back to Highlights and Tabs
FULL PRESCRIBING INFORMATION
WARNING: EMBRYO-FETAL TOXICITY
1 INDICATIONS AND USAGE
1.1 Pulmonary Arterial Hypertension
OPSUMIT® is an endothelin receptor antagonist (ERA) indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression. Disease progression included: death, initiation of intravenous (IV) or subcutaneous prostanoids, or clinical worsening of PAH (decreased 6-minute walk distance, worsened PAH symptoms and need for additional PAH treatment). OPSUMIT also reduced 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. Patients were treated with OPSUMIT monotherapy or in combination with phosphodiesterase-5 inhibitors or inhaled prostanoids. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%) [see Clinical Studies (14.1)].
2 DOSAGE AND ADMINISTRATION
2.1 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.
2.2 Pregnancy Testing in Females of Reproductive Potential
Initiate treatment with OPSUMIT in females of reproductive potential only after a negative pregnancy test. Obtain monthly pregnancy test during treatment [see Use in Specific Populations (8.6)].
3 DOSAGE FORMS AND STRENGTHS
Tablets: 10 mg, bi-convex film-coated, round, white, and debossed with "10" on one side.
4 CONTRAINDICATIONS
4.1 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, apprise the patient of the potential hazard to a fetus [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Embryo-fetal Toxicity
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 [see Dosage and Administration (2.2) and Use in Specific Populations (8.1, 8.6)].
OPSUMIT is available for females through the OPSUMIT REMS Program, a restricted distribution program [see Warnings and Precautions (5.2)].
5.2 OPSUMIT REMS Program
For all females, OPSUMIT is available only through a restricted program called the OPSUMIT REMS Program, because of the risk of embryo-fetal toxicity [see Contraindications (4.1), Warnings and Precautions (5.1), and Use in Specific Populations (8.1, 8.6)].
Notable requirements of the OPSUMIT REMS Program include the following:
-
Prescribers must be certified with the program by enrolling and completing training.
-
All females, regardless of reproductive potential, must enroll in the OPSUMIT REMS Program prior to initiating OPSUMIT. Male patients are not enrolled in the REMS.
-
Females of reproductive potential must comply with the pregnancy testing and contraception requirements [see Use in Specific Populations (8.6)].
-
Pharmacies must be certified with the program and must only dispense to patients who are authorized to receive OPSUMIT.
Further information is available at www.OPSUMITREMS.com or 1-866-228-3546. Information on OPSUMIT certified pharmacies or wholesale distributors is available through Actelion Pathways at 1-866-228-3546.
5.3 Hepatotoxicity
Other ERAs have caused elevations of aminotransferases, hepatotoxicity, and liver failure. The incidence of elevated aminotransferases in the study of OPSUMIT in PAH is shown in Table 1.
Table 1 Incidence of Elevated Aminotransferases in the SERAPHIN Study
|
|
OPSUMIT 10 mg
(N=242) |
Placebo
(N=249) |
|
>3 × ULN |
3.4% |
4.5% |
|
>8 × ULN |
2.1% |
0.4% |
In the placebo-controlled study of OPSUMIT, discontinuations for hepatic adverse events were 3.3% in the OPSUMIT 10 mg group vs. 1.6% for placebo. Obtain liver enzyme tests prior to initiation of OPSUMIT and repeat during treatment as clinically indicated.
Advise patients to report symptoms suggesting hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching). If clinically relevant aminotransferase elevations occur, or if elevations are accompanied by an increase in bilirubin >2 × ULN, or by clinical symptoms of hepatotoxicity, discontinue OPSUMIT. Consider re-initiation of OPSUMIT when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity.
5.4 Hemoglobin Decrease
Decreases in hemoglobin concentration and hematocrit have occurred following administration of other ERAs and were observed in clinical studies with OPSUMIT. These decreases occurred early and stabilized thereafter. In the placebo-controlled study of OPSUMIT in PAH, OPSUMIT 10 mg caused a mean decrease in hemoglobin from baseline to up to 18 months of about 1.0 g/dL compared to no change in the placebo group. A decrease in hemoglobin to below 10.0 g/dL was reported in 8.7% of the OPSUMIT 10 mg group and in 3.4% of the placebo group. Decreases in hemoglobin seldom require transfusion. Initiation of OPSUMIT is not recommended in patients with |
|
