macitentan

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)

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.

Contraind./Precautions ⬆ ⬇

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.

Route/Dosage ⬆ ⬇

PO (Adults ): 10 mg once daily.

Availability ⬆ ⬇

(Generic available)

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

Assessment ⬆ ⬇

Monitor hemodynamic parameters and exercise tolerance prior to and periodically during therapy.
Assess for signs and symptoms of pulmonary edema (shortness of breath, crackles, wheezing), peripheral edema, and fluid retention (weight gain; swelling of feet, ankles, or hands). If confirmed, discontinue therapy.
Assess for hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, itching).
Monitor for signs and symptoms of hypersensitivity reactions (angioedema, pruritus, rash). May need to discontinue therapy.

Lab Test Considerations:

Verify 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 times the upper limit of normal or by clinical symptoms of hepatotoxicity, discontinue therapy. May reinitiate 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 ↓ hemoglobin. Avoid therapy in patients with severe anemia.

Implementation ⬆ ⬇

PO: Administer once daily at the same time each day. DNC: Swallow tablets whole; do not break, crush, or chew.

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.

Evaluation/Desired Outcomes ⬆ ⬇

Delayed sequelae of PAH progression.

US Brand Names ⬆ ⬇

Code ⬆

NDC Code

11722- TAPI Croatia Industries Ltd.
- 11722-058-
  - 11722-058-00- 1 kg in 1 CARTON (11722-058-00)

59651- Aurobindo Pharma Limited
- 59651-122-
  - 59651-122-37- 50 kg in 1 DRUM (59651-122-37)

65015- MYLAN LABORATORIES LIMITED
- 65015-872-
  - 65015-872-61- 100 kg in 1 DRUM (65015-872-61)

66215- Actelion Pharmaceuticals US, Inc.
- 66215-501- OPSUMIT
  66215-501-15- 1 BLISTER PACK in 1 CARTON (66215-501-15) / 15 TABLET, FILM COATED in 1 BLISTER PACK

66215- Actelion Pharmaceuticals US, Inc.
- 66215-501- OPSUMIT
  - 66215-501-30- 1 BOTTLE in 1 CARTON (66215-501-30) / 30 TABLET, FILM COATED in 1 BOTTLE

69037- Honour Lab Limited
- 69037-0030-
  - 69037-0030-1- 25 kg in 1 DRUM (69037-0030-1)

69766- MSN Life Sciences Private Limited
- 69766-006-
  69766-006-02- 25 kg in 1 DRUM (69766-006-02)

69766- MSN Life Sciences Private Limited
- 69766-006-
  69766-006-04- 20 kg in 1 DRUM (69766-006-04)

76397- Zhejiang Ausun Pharmaceutical Co., Ltd.
- 76397-014-
  76397-014-01- 1000 g in 1 DRUM (76397-014-01)

76397- Zhejiang Ausun Pharmaceutical Co., Ltd.
- 76397-014-
  76397-014-07- 20 g in 1 DRUM (76397-014-07)

76397- Zhejiang Ausun Pharmaceutical Co., Ltd.
- 76397-014-
  76397-014-08- 100 g in 1 DRUM (76397-014-08)

76397- Zhejiang Ausun Pharmaceutical Co., Ltd.
- 76397-044-
  76397-044-04- 5 kg in 1 DRUM (76397-044-04)

76397- Zhejiang Ausun Pharmaceutical Co., Ltd.
- 76397-044-
  76397-044-05- 10 kg in 1 DRUM (76397-044-05)

82245- Viyash Life Sciences Private Limited
- 82245-0117-
  82245-0117-1- 20 kg in 1 DRUM (82245-0117-1)

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇