In the treatment of pulmonary arterial hypertension (PAH, WHO Group I )
HELP HER WRITE FUTURE CHAPTERS
Once-daily OPSUMIT® (macitentan) is the first and only oral PAH therapy indicated to
both delay disease progression and reduce hospitalization for PAH
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%).
IMPORTANT SAFETY INFORMATION
BOXED WARNING: EMBRYO-FETAL TOXICITY
Do not administer OPSUMIT to a pregnant female
because it may cause fetal harm.
Females of reproductive potential: Exclude
pregnancy before the start of treatment, monthly
during treatment, and 1 month after stopping
treatment. Prevent pregnancy during treatment
and for one month after stopping treatment by
using acceptable methods of contraception.
For all female patients, OPSUMIT is available only
through a restricted program called the OPSUMIT
Risk Evaluation and Mitigation Strategy (REMS)
CONTRAINDICATIONS
Pregnancy: OPSUMIT may cause fetal harm when
administered to a pregnant woman. OPSUMIT is
contraindicated in females who are pregnant. If OPSUMIT
is used during pregnancy, apprise the patient of the
potential hazard to a fetus.
WARNINGS AND PRECAUTIONS
Embryo-fetal Toxicity and OPSUMIT REMS Program
Due to the risk of embryo-fetal toxicity, OPSUMIT is available
for females only through a restricted program called the
OPSUMIT REMS Program. For females of reproductive
potential, exclude pregnancy prior to initiation of therapy,
ensure use of acceptable contraceptive methods, and
obtain monthly pregnancy tests.
Notable requirements of the OPSUMIT REMS Program include:
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.
Pharmacies must be certified with the program and
must only dispense to patients who are authorized to
receive OPSUMIT.
Hepatotoxicity
Other ERAs have caused elevations of aminotransferases,
hepatotoxicity, and liver failure. The incidence of elevated
aminotransferases in the SERAPHIN study >3 × ULN were
3.4% for OPSUMIT vs 4.5% for placebo, and >8 × ULN
were 2.1% vs 0.4%, respectively. Discontinuations for
hepatic adverse events were 3.3% for OPS UMIT 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