Dosing & Uses
Dosage Forms & Strengths
Pulmonary Arterial Hypertension
Indicated for the treatment of pulmonary arterial hypertension (WHO Group I) to delay disease progression
10 mg PO qDay
- Severe (CrCl 15-29 mL/min): No dosage modification needed
- Systemic Exposure to macitentan and its active metabolite were increased by 30% and 60% respectively (this increase ise not considered clinically relevant)
- Mild, moderate, or severe (Child-Pugh Class A, B, and C): No dosage modification needed
- System exposure decreased by 21%, 34%, and 6% and exposure to the active metabolite was decreased by 20%, 25%, and 25% in subjects with mild, moderate, or severe hepatic impairment respectively (this decrease is not considered clinically relevant)
Pulmonary Arterial Hypertension (Orphan)
Orphan designation of a fixed dose combination of macitentan and tadalafil for treatment of pulmonary arterial hypertension
- Actelion Clinical Research, Inc; 1820 Chapel Avenue West, Suite 300; Cherry Hill, New Jersey 08002
Safety and efficacy not established
Serious - Use Alternative
Significant - Monitor Closely
Urinary tract infection (9%)
Hypersensitivity reactions (angioedema, pruritus and rash)
Elevations of liver aminotransferases (ALT, AST) and liver injury
Black Box Warnings
- Likely to produce serious birth defects if used by pregnant women; this effect has been seen consistently when administered to animals
- Negative pregnancy test result required before initiating and prevention of pregnancy required monthly during treatment and for 1 month after treatment by the use of at least 2 reliable methods of contraception (unless tubal sterilization or Copper T 380A IUD or LNg 20 IUD inserted, in which case no other contraception required)
- If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method
Restricted distribution program
- Because of risks of birth defects, available only through restricted distribution program called the Opsumit REMS program
- May be dispensed only to patients enrolled in and meet all conditions of the REMS program
Other endothelin receptor antagonists (ERAs) have been associated with elevated liver aminotransferases, hepatotoxicity, and liver failure; obtain liver enzymes tests before initiating and repeat as clinically warranted; discontinue if aminotransferase elevations are accompanied by clinical symptoms of hepatoxicity
ERAs associated with decreased hemoglobin and hematocrit concentrations; initiation not recommended if severe anemia present
If pulmonary edema occurs, consider the possibility of associated pulmonary veno-occlusive disease, and if confirmed, discontinue drug
Avoid coadministration with strong CYP3A4 inhibitors
ERAs associated with adverse effects on spermatogenesis; counsel men about potential effects on fertility
Pregnancy & Lactation
Pregnancy Category: X; consistently shown to have teratogenic effects when administered to animals
In both rabbits and rats, there were cardiovascular and mandibular arch fusion abnormalities; administration to female rats from late pregnancy through lactation caused reduced pup survival and impairment of the male fertility of the offspring at all dose levels tested
Lactation: Unknown if distributed in human breast milk; due to presence of macitentan and metabolites in milk of lactating rats and potential for serious adverse effects in nursing infants, do not recommend use while nursing
A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA:Information not available.
Mechanism of Action
Endothelin receptor antagonist (ET); prevents binding of ET-1 to both ET-A and ET-B receptors with high affinity to ET receptors in pulmonary arterial smooth muscle cells; active metabolite 20% as potent as parent compound
Peak plasma time: 8 hr
Absolute bioavailability: Unknown
Protein bound: >99%; mainly to albumin and to a lesser extent alpha-1-glycoprotein
Vd: 50 L; 40 L (active metabolite)
Metabolized by liver: Mainly by CYP3A4, minor amount by CYP2C19; primarily metabolized by oxidative depropylation of the sulfamide to active metabolite
Active metabolite: At steady state, systemic exposure of active metabolite is 3-times the exposure of macitentan; active metabolite thought to contribute approximately 40% of total pharmacologic activity
Half-life: 16 hr; 48 hr (active metabolite)
Excretion: 50% urine; 24% feces
May take with or without food
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|1||This drug is available at the lowest co-pay. Most commonly, these are generic drugs.|
|2||This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.|
|3||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.|
|4||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|5||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|6||This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.|
|NC||NOT COVERED – Drugs that are not covered by the plan.|
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