macitentan

Contraindicated in:

Hypersensitivity;
OB:
Pregnancy
;
Lactation: Lactation.

Use Cautiously in:

Pulmonary veno-occlusive disease (↑ risk of pulmonary edema);
Rep:
Women of reproductive potential
;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: pruritus, rash

GI: hepatotoxicity

GU: ↓fertility (men)

Hemat: anemia

Neuro: headache

Resp: pulmonary edema

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Strong CYP3A4 inhibitors, including ketoconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
Moderate dual CYP3A4 and CYP2C9 inhibitors, including fluconazole, as well as concurrent use with a moderate CYP3A4 inhibitor and a moderate CYP2C9 inhibitor, may ↑ levels and risk of toxicity; avoid concurrent use.

Availability ⬆ ⬇

(Generic available)

Tablets: 10 mg
In combination with: tadalafil (Opsynvi); see Appendix [not included in this PDA edition])

Route/Dosage ⬆ ⬇

PO (Adults ): 10 mg once daily.

US Brand Names ⬆ ⬇

Action ⬆ ⬇

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

Therapeutic effects:

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)

Classifications ⬆ ⬇

Therapeutic Classification: vasodilators

Pharmacologic Classification: endothelin receptor antagonists

Pharmacokinetics ⬆ ⬇

Absorption: Extent of absorption unknown.

Distribution: Unknown.

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

Metabolism/Excretion: Extensively metabolized, primarily by the CYP3A4 isoenzyme 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‡)

ROUTE	ONSET	PEAK	DURATION
PO	within 6 mo	12–18 mo	unknown

‡Worsening of PAH, death, or need for other interventions.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes. Instruct patient to take as directed. Take missed doses as soon as remembered unless almost time for next dose; do not double doses.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications.
Advise patients to notify health care provider if signs or symptoms of hypersensitivity reactions, hepatotoxicity, pulmonary edema, or fluid retention occur.
Rep:
May cause fetal harm. Instruct women of reproductive potential to use effective contraception (intrauterine device, contraceptive implants, tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods) during and for ≥1 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 impair fertility in men. Advise women of reproductive potential to notify health care provider immediately if pregnancy is suspected and avoid breastfeeding during therapy. Macitentan should be discontinued as soon as possible when pregnancy is detected.

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Indications ⬇

Contraind./Precautions ⬆ ⬇