Drug Interaction:
Strong CYP3A4 inducers (rifampin) reduce exposure to macitentan: avoid
co-administration with OPSUMIT
Strong CYP3A4 inhibitors (ketoconazole, ritonavir) increase exposure
to macitentan: avoid co-administration with OPSUMIT
Indication:
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 Evaluation and Mitigation
Strategy (REMS) (5.2)
Drug Name- Opsumit
Active Ingredient - Macitentan
To treat adults with pulmonary arterial hypertension (PAH) , a chronic .progressive
and debilating disease than can lead to death or need for lung transplantation
Indication-
Pulmonary arterial hypertension(PAH)
Approved by FDA on 18-10--2013 (Ref- FDA approved List- 2013)
Adverse Reaction:
Most common adverse reactions (more frequent than placebo by .3%) are
anemia, nasopharyngitis/pharyngitis, bronchitis, headache, influenza,
and urinary tract infection
Contra-Indications:
CONTRAINDICATIONS
Pregnancy
WARNINGS AND PRECAUTIONS
Other ERAs cause hepatotoxicity and liver failure. Obtain baseline liver
enzymes and monitor as clinically indicated
.Decreases in hemoglobin
.Pulmonary edema in patients with pulmonary veno-occlusive disease.
If confirmed, discontinue treatment .
Decreases in sperm count have been observed in patients taking ERAs
Dosages/ Overdosage Etc:
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
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
DOSAGE FORMS AND STRENGTHS.
Tablet: 10 mg
Patient Information:
PATIENT COUNSELING INFORMATION
See FDA-approved patient labeling (Medication Guide).
Embryo-Fetal Toxicity
Instruct patients on the risk of fetal harm when OPSUMIT is used in pregnancy
Instruct females of reproductive potential to use effective contraception and
to contact her physician if they suspect they may be pregnant.
Female patients must enroll in the OPSUMIT REMS program.
Male patients are not enrolled in the OPSUMIT REMS
Inform female patients (and their guardians, if applicable) of the following
notable requirements.
Female patients must sign an enrollment form.
Female patients of reproductive potential must comply with the pregnancy
testing and contraception requirements.
Educate and counsel females of reproductive potential on the use of emergency
contraception in the event of unprotected sex or contraceptive failure.
Advise pre-pubertal females to report any changes in their reproductive
status immediately to her prescriber.
Review the Medication Guide and REMS educational materials with
female patients.
Decrease in Hemoglobin
Advise patients on the importance of hemoglobin testing.
Hepatotoxicity
Some members of this pharmacological class are hepatotoxic.
Educate patients on signs of hepatotoxicity.
Advise patients that they should contact their doctor if they have unexplained
nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice,
dark urine, fever, or itching.
Administration
Patients should be advised not to split, crush, or chew tablets.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Endothelin (ET)-1 and its receptors (ETA and ETB) mediate a variety of
deleterious effects, such as vasoconstriction, fibrosis, proliferation,
hypertrophy, and inflammation.
2. Pharmacokinetics
The pharmacokinetics of macitentan and its active metabolite have been studied
primarily in healthy subjects. The pharmacokinetics of macitentan are dose
proportional over a range from 1 mg to 30 mg after once daily administration.
.
Absorption and Distribution
The maximum plasma concentration of macitentan is achieved about 8 hours
after oral administration. The absolute bioavailability after oral administration
is not known.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category X.
Risk Summary
OPSUMIT may cause fetal harm when administered to a pregnant woman and
is contraindicated during pregnancy. Macitentan was teratogenic in rabbits
and rats at all doses tested.
If this drug is used during pregnancy, or if the patient becomes pregnant
while taking this drug, advise the patient of the potential hazard to a fetus
2. Nursing Mothers
It is not known whether OPSUMIT is present in human milk. Macitentan and
its metabolites were present in the milk of lactating rats. Because many drugs
are present in human milk and because of the potential for serious adverse
reactions from macitentan in nursing infants, nursing mothers should
discontinue nursing or discontinue OPSUMIT.
3.Pediatric use
The safety and efficacy of OPSUMIT in children have not been established.
4. Geriatric use
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.
Manufacturer Details