Macitentan / Tadalafil Dosage

Medically reviewed by Drugs.com. Last updated on May 20, 2024.

Usual Adult Dose for Pulmonary Hypertension

Patients treatment-naive to any pulmonary arterial hypertension (PAH)-specific therapy OR transitioning from endothelin receptor antagonist (ERA) monotherapy:

• Initial dose: Macitentan 10 mg-tadalafil 20 mg orally once a day for 1 week
• Maintenance dose: Macitentan 10 mg-tadalafil 40 mg orally once a day

Patients transitioning from phosphodiesterase 5 (PDE5) inhibitor monotherapy OR from PDE5 inhibitor and ERA combination therapy: Macitentan 10 mg-tadalafil 40 mg orally once a day

Comments:

• This drug may be started in patients of childbearing potential only after a negative pregnancy test.

Use: Chronic treatment of patients with WHO group I and WHO functional class II to III PAH

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 to 80 mL/min): No adjustment recommended
Severe renal dysfunction (CrCl 15 to 29 mL/min): Not recommended

Liver Dose Adjustments

Mild to moderate liver dysfunction (Child-Pugh A or B): No adjustment recommended
Severe liver cirrhosis (Child-Pugh C): Not recommended
Severe liver dysfunction or clinically significant elevated aminotransferases (greater than 3 times the upper limit of normal [3 x ULN]) at baseline: Do not start this drug.

If clinically significant aminotransferase elevations occur during therapy, or if elevations develop during therapy with increased bilirubin (greater than 2 x ULN) or clinical symptoms of hepatotoxicity: Discontinue this drug.

• In patients who have not experienced clinical symptoms of hepatotoxicity: Reinitiation may be considered when liver enzyme levels normalize.

Comments:

• Patients with severe liver cirrhosis or severe liver dysfunction (defined as a Model for End-Stage Liver Disease score at least 19) have not been studied.
• Liver enzyme tests should be obtained before starting this drug and repeated during therapy as clinically indicated.

Dose Adjustments

Fluid retention: Evaluate to determine the cause (e.g., drug-related or underlying condition); consider the possible need to discontinue this drug.

Patients with severe anemia: Initiation of this drug is not recommended.

Patients with confirmed pulmonary vascular obstructive disease (PVOD) during treatment: Discontinue this drug.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for macitentan-containing products. It includes elements to assure safe use and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNING:

• EMBRYOFETAL TOXICITY: This drug may cause fetal harm and should not be administered to pregnant females. In females of reproductive potential, providers should: exclude pregnancy prior to starting treatment, every month during treatment, and 1 month after stopping treatment; and prevent pregnancy during and for 1 month after stopping treatment by using acceptable methods of contraception. For all female patients, this drug is only available through a restricted program called the Macitentan-Containing Products REMS.

CONTRAINDICATIONS:

• History of hypersensitivity to either active component or to any of the ingredients
• Pregnancy
• Concomitant use with any form of organic nitrate, either regularly or intermittently; use of nitrates within 48 hours of the last dose of this drug
• Concomitant use with guanylate cyclase stimulators (e.g., riociguat)

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Not recommended

Other Comments

Administration advice:

• Obtain a pregnancy test in patients of childbearing potential before starting this drug, monthly during therapy, and 1 month after the last dose.
• Swallow tablets whole with water; do not chew, crush, or cut.
• If a dose is missed, take it as soon as remembered and then take the next dose at the regularly scheduled time. Do not take 2 doses at the same time.

Storage requirements:

• Store below 25C (77F) in original pack to protect from light and moisture.

General:

• This combination drug is comprised of 2 medications, 1 of which improves exercise ability, and the other that decreases the risk of hospitalization and clinical worsening.

Monitoring:

• Cardiovascular: Signs/symptoms of pulmonary edema
• General: For pregnancy in female patients of reproductive potential (before treatment, monthly during treatment, and 1 month after stopping this drug)
• Hematologic: Hemoglobin (prior to and during therapy)
• Hepatic: Liver function (prior to and during therapy)
• Metabolic: For signs of fluid retention (after start of therapy)

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide).
• Patients of childbearing potential:
• Monthly pregnancy tests are required; use reliable methods of contraception during therapy and for 1 month after the last dose.
• Choose 1 highly effective contraceptive (intrauterine devices, contraceptive implants, tubal sterilization) or a combination of methods (hormone and barrier methods or 2 barrier methods).
• Contact gynecologist or health care provider if you want to change the method of contraception.
• Contact physician if pregnancy is suspected; seek additional contraceptive advice from gynecologist as needed.
• For prepubertal females: Report any changes in reproductive status immediately to prescriber.
• Do not breastfeed during therapy.
• Contact physician if unexplained nausea, vomiting, right upper quadrant pain, fatigue, anorexia, jaundice, dark urine, fever, or itching occurs.
• Immediately seek medical attention if a sudden loss of vision occurs in 1 or both eyes during therapy.
• Seek prompt medical attention if a sudden decrease or loss of hearing occurs during therapy.
• Contact physician if unusual weight gain or swelling of the ankles/legs occurs.
• Seek emergency medical attention if you have an erection that lasts longer than 4 hours (with or without pain).

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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