Aprocitentan

The development of Aprocitentan can be traced back to Bosentan, a dual ETA and ETB receptor antagonist developed by Roche, and the drug specification produced by Lucius is 12.5mg/30 tablets.

Aprocitentan is an oral small molecule that targets dual endothelin A/B receptor (ETA/ETB) antagonists, effectively inhibiting the binding of ET-1 to ETA and ETB.

Aprocitentan is an oral dual endothelin A/B receptor (ETA/ETB) antagonist. This antagonistic effect can block adverse reactions such as vascular constriction, myocardial hypertrophy, vascular smooth muscle cell proliferation, and fibrosis mediated by ET-1, thereby reducing blood pressure and improving cardiovascular function.

1.Main components

Aprocitentan

2.Adapt to the population

Aprocitentan combined with other antihypertensive drugs for the treatment of hypertension.

3.Medication for special populations

3.1Pregnancy

Available data from reports  of pregnancy in clinical trials with Aprocitentan are insufficient to rule out a drug-associated  risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.  Advise pregnant patients of the potential risk to a fetus.

3.2Lactation

There are no data on the presence of aprocitentan in human milk, the effects on the  breastfed infant, or the effect on milk production. Because of the potential for serious adverse reactions  in breastfed infants, advise women not to breastfeed during treatment with Aprocitentan.

3.3Females and Males of Reproductive Potential

Based on data from animal reproductive toxicity studies with other ERAs, Aprocitentan can  cause fetal harm, including birth defects and fetal death, when administered to a pregnant  patient and is contraindicated during pregnancy.

3.4Pediatric Use

The safety and efficacy of Aprocitentan in pediatric patients have not been established.

3.5Geriatric Use

No dose adjustment is required in patients over the age of 65 years.

3.6Renal Impairment

No dose adjustment is required in patients with mild to severe renal impairment (eGFR ≥15 mL/min).

3.7Hepatic Impairment

No dose adjustment is required in patients with mild hepatic impairment (Child-Pugh class A).

4.Drug overdose

Aprocitentan has been administered as a single dose of up to 600 mg, and as multiple doses of up to 100 mg daily, to healthy subjects (48 and 8 times the recommended dose, respectively). Adverse events of headache, nasal congestion, nausea, and upper  respiratory tract infection were observed. In the event of an overdose, standard supportive  measures should be taken, as required. Dialysis is unlikely to be effective because  aprocitentan is highly protein-bound.

5.Drug storage

Store at 20ºC to 25ºC (68ºF to 77ºF); excursions permitted from 15ºC to 30ºC (59ºF to  86ºF). Store in the original package. Dispense to patient in original container only. Replace cap securely each time after opening. Do not  discard desiccant. Protect from light and moisture.

6.Pharmacokinetics

The absolute oral bioavailability of aprocitentan is unknown. The time to reach Cmax is  between 4 and 5 hours after administration of 25 mg aprocitentan (twice the  recommended dose).

from FDA，2024.03