General

**REMS Drug**

Pronunciation:
ma-si-ten-tan


Trade Name(s)

  • Opsumit

Ther. Class.
vasodilators

Pharm. Class.
endothelin receptor antagonists

Indications

Treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression.

Action

Acts as an endothelin receptor antagonist. Endothelin mediates vasocontriction, fibrosis, proliferation, hypertrophy and inflammation. Antagonizing endothelin effects delays vascular hypertrophy and organ damage.

Therapeutic Effect(s):

Delayed sequelae of progression of PAH (death, need for initiation of parenteral prostanoids, increased frequency of hospitalization, diminished exercise tolerance or need for other interventions)

Pharmacokinetics

Absorption: Absorption follows oral administration, bioavailability Unknown.

Distribution: Unknown.

Protein Binding: Macitentan– >99%; active metabolite– >99%

Metabolism and Excretion: Extensively metabolized, primarily by the CYP3A4 enzyme system with conversion to a pharmacologically active metabolite that contributes 40% of activity. 50% excreted in urine as metabolites, 24% in feces.

Half-life: Macitentan– 16 hr; active metabolite– 48 hr

TIME/ACTION PROFILE (improvement in primary endpoints†)

ROUTEONSETPEAKDURATION
POwithin 6 mos12–18 mosunknown
†Worsening of PAH, death, or need for other interventions.

Contraindication/Precautions

Contraindicated in:

  • Strong inhibitors or inducers of the CYP3A4 enzyme system (can significantly alter drug effectiveness/risk of toxicity)
  • OB: Causes fetal harm, should not be used during pregnancy;
  • Lactation:Discontinue drug or breastfeeding

Use Cautiously in:

  • Pulmonary veno-occlusive disease (↑ risk of pulmonary edema);
  • Rep: Females with childbearing potential (pregnancy must be excluded prior to treatment and for 1 mo following treatment, effective contraception must be utilized);
  • Pedi: Safety and effectiveness not established.

Adverse Reactions/Side Effects

CNS: headache

Derm: pruritis, rash

Resp: pulmonary edema

GI: hepatotoxicity

GU: ↓ sperm count

Hemat: anemia

Misc: ANGIOEDEMA

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • Strong CYP3A4 inducers including rifampin ↓ blood levels and effectiveness and should be avoided
  • Strong CYP3A4 inhibitors including ketoconazole ↑ blood levels and risk of toxicity and should be avoided

Route/Dosage

PO: (Adults) 10 mg once daily.

Availability

Tablets: 10 mg

Assessment

  • Monitor hemodynamic parameters and exercise tolerance prior to and periodically during therapy.
  • Assess for signs and symptoms of pulmonary edema (shortness of breath). If confirmed, discontinue therapy.
  • Monitor for signs and symptoms of hypersensitivity reactions (angioedema, pruritus, rash). May need to discontinue macitentan.

Lab Test Considerations: Obtain a negative pregnancy test prior to beginning, monthly during therapy, and 1 mo following treatment.

  • Monitor hepatic function periodically during therapy. May cause ↑ AST, ALT, and bilirubin. If clinically relevant ↑ of AST or ALT occur, or if ↑ are accompanied by ↑ bilirubin >2 x upper limit of normal, or by clinical symptoms of hepatotoxicity, discontinue therapy. May re­ initiate therapy when hepatic enzyme levels normalize in patients who have not experienced clinical symptoms of hepatotoxicity.
  • Monitor CBC before starting and periodically during therapy. May cause ↓ hemoglobin. Avoid therapy in patients with severe anemia.

Potential Diagnoses

Implementation

  • Only available through a restricted program, Opsumit Risk Evaluation and Mitigation Strategy (REMS). Prescribers and pharmacies must be enrolled and certified. All female patients must enroll and comply with pregnancy testing and contraception requirements. Male patients do not need to enroll.
  • PO: Administer once daily at the same time each day. Swallow tablets whole, do not break, crush, or chew.

Patient/Family Teaching

  • Instruct patient to take macitentan as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double doses.
  • Advise patients to notify health care professional if symptoms of hepatic injury (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, itching) occur.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Rep: Caution female patients that macitentan may harm fetus. Instruct females to use effective contraception (intrauterine device IUD, contraceptive implants, tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods) during and for at least a mo following discontinuation of therapy. If a partner's vasectomy is method of contraception, a hormone or barrier method must be used along with this method. Counsel patient on emergency contraception. May decrease sperm count in male patients. Advise female patient to notify health care professional immediately if pregnancy is suspected and avoid breastfeeding.

Evaluation/Desired Outcomes

Increased exercise tolerance.

macitentan is a sample topic from the Davis's Drug Guide.

To view other topics, please or purchase a subscription.

Emergency Central is a collection of disease, drug, and test information including 5-Minute Emergency Medicine Consult, Davis’s Drug, McGraw-Hill Medical’s Diagnosaurus®, Pocket Guide to Diagnostic Tests, and MEDLINE Journals created for emergency medicine professionals. Learn more.

Citation

* When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - macitentan ID - 110120 A1 - Quiring,Courtney, AU - Sanoski,Cynthia A, AU - Vallerand,April Hazard, BT - Davis's Drug Guide UR - https://emergency.unboundmedicine.com/emergency/view/Davis-Drug-Guide/110120/all/macitentan PB - F.A. Davis Company ET - 16 DB - Emergency Central DP - Unbound Medicine ER -