Macitentan

Development of peripheral edema due to treatment and/or disease state (pulmonary arterial hypertension) may occur. There have been postmarketing reports of fluid retention requiring treatment (eg, diuretics, fluid management, hospitalization) associated with other endothelin antagonists. Further evaluation may be necessary to determine cause and appropriate treatment or discontinuation of therapy. Use with caution in patients with severe chronic heart failure.

A reduction in hematocrit/hemoglobin has been observed and may occur early in therapy with subsequent stabilization. Decreases in hemoglobin rarely required transfusion. Measure hemoglobin prior to initiating therapy and repeat as clinically appropriate. Use is not recommended in patients with severe anemia.

Increases in serum liver aminotransferases, hepatotoxicity, and liver failure have been reported. Monitor transaminases prior to initiation of therapy and repeat as clinically appropriate. Discontinue treatment in patients who develop elevated transaminases either in combination with symptoms of hepatic injury (eg, anorexia, dark urine, fatigue, fever, itching, jaundice, nausea, right upper quadrant pain, vomiting) or elevated bilirubin (>2 x the upper limit of normal [ULN]). Upon normalization of hepatic enzymes, may consider reinitiation of therapy in patients not experiencing clinical signs of hepatotoxicity.

Sperm count may be reduced in men during treatment. No changes in sperm function or hormone levels have been noted in animal studies. Advise male patients of potential effects on fertility. Disease-related concerns:

If signs of pulmonary edema occur, consider the possibility of PVOD; discontinue if PVOD is confirmed. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Macitentan may cause fetal harm if given to pregnant women; do not administer to women who are pregnant. All females of reproductive potential should have a negative pregnancy test prior to beginning therapy and testing should continue monthly during treatment and one month after discontinuing therapy. Females of childbearing potential should not become pregnant during therapy or for 1 month following discontinuation of macitentan. Women may use one highly effective form of contraception (intrauterine device, contraceptive implant, or tubal sterilization) or a combination of methods (hormonal contraceptive with a barrier method or two barrier methods). A hormonal contraceptive or barrier method must be used in addition to a partner’s vasectomy, if that method is chosen. Females should be counseled on pregnancy prevention and planning and instructed to notify their prescriber immediately if a pregnancy should occur.

Macitentan is available to females only through the restricted OPSUMIT Risk Evaluation and Mitigation Strategy (REMS) Program. All females regardless of their reproductive potential must be enrolled in the REMS program; prescribers and pharmacies must also be enrolled in the program. Females of reproductive potential must be able to comply with pregnancy testing and contraception requirements of the program. Call 1-866-228-3546 or visit http://www.opsumitrems.com for more information.