Aprocitentan

Aprocitentan is a prescription medication indicated for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure in adult patients who are not adequately controlled on other drugs.

• Aprocitentan is available under the following different brand names: Tryvio.

Common side effects of Aprocitentan include:

• edema/fluid retention
• anemia

Serious side effects of Aprocitentan include:

• liver problems include nausea or vomiting, yellowing of the skin or whites of the eyes, pain in the upper right stomach, dark urine, tiredness, fever, loss of appetite, itching
• fluid retention
• low red blood cell levels (anemia)
• decreased sperm count

Rare side effects of Aprocitentan include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 12.5 mg

Hypertension

Adult dosage

• 12.5 mg orally once a day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Aprocitentan has no noted severe interactions with any other drugs
• Aprocitentan has no noted serious interactions with any other drugs
• Aprocitentan has no noted moderate interactions with any other drugs
• Aprocitentan has no noted minor interactions with any other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Pregnancy
• Hypersensitivity to aprocitentan or its excipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Aprocitentan?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Aprocitentan?”

Cautions

• Embryofetal toxicity
• Contraindicated during pregnancy
• Based on animal reproduction studies with endothelin receptor antagonists (ERAs), Aprocitentan can cause fetal harm when administered during pregnancy
• REMS
  • Available only through a restricted program under a REMS called the TRYVIO REMS because of the risk of embryofetal toxicity
  • Further information is available at www.TRYVIOREMS.com or 1-866-429-8964
• Requirements include
  • Prescribers must be certified by enrolling and completing training
  • Pharmacies that dispense Aprocitentan must be certified with the TRYVIO REMS
• Hepatotoxicity
  • Elevated aminotransferases and hepatotoxicity are known effects of ERAs, including Aprocitentan
  • To reduce the risk of potential serious hepatotoxicity, measure serum aminotransferase levels and total bilirubin before initiating and periodically during treatment as clinically indicated
  • Do not initiate in patients with elevated aminotransferases (more than 3x ULN) or moderate to severe hepatic impairment
  • Advise patients with symptoms suggesting hepatotoxicity (nausea, vomiting, right upper quadrant pain, fatigue, anorexia, scleral icterus, jaundice, dark urine, fever, or itching) to immediately discontinue Aprocitentan and seek medical attention
  • If sustained, unexplained, clinically relevant aminotransferase elevations occur, or if elevations are accompanied by increased bilirubin more than 2x ULN, or if clinical symptoms of hepatotoxicity occur, discontinue Aprocitentan
• Fluid retention
  • Fluid retention and peripheral edema are known effects of ERAs
  • Older age and chronic kidney disease are risk factors for edema/fluid retention with Aprocitentan
  • Not recommended or studied in patients with heart failure New York Heart Association stage III-IV, unstable cardiac function, or with NTproBNP more than 500 pg/mL
  • Monitor for signs and symptoms of fluid retention, weight gain, and worsening heart failure
  • Advise patients experiencing signs of fluid retention, including unusual weight increase, or swelling of the ankles or legs, to contact their physician
  • If clinically significant fluid retention develops, treat appropriately, and consider discontinuing Aprocitentan
• Hemoglobin decreased
  • Decreased hemoglobin concentration and hematocrit reported
  • Hemoglobin decreases usually presented early, stabilized thereafter, and was reversible after discontinuation
  • Not recommended in patients with severe anemia
  • Obtain hemoglobin levels before initiating and periodically during treatment as clinically indicated
• Decreased sperm counts
  • Similar to other ERAs, it may harm spermatogenesis
  • Counsel men about potential effects on fertility

Pregnancy and Lactation

• Contraindicated during pregnancy
• Based on animal reproductive toxicity studies with other ERAs, Aprocitentan can cause embryofetal harm, including birth defects and fetal death, when administered to a pregnant patient
• Available data from reports of pregnancy in clinical trials 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
• Healthcare providers should report any prenatal exposure to Aprocitentan by calling 1-866-429-8964
• Females and males of reproductive potential
• Pregnancy testing
  • Verify the pregnancy status of women of reproductive potential before initiating
  • Exclude pregnancy with a negative pregnancy test monthly during treatment and 1 month after discontinuing
  • Patients should contact their physician immediately if the onset of menses is delayed or pregnancy is suspected
  • Discuss risks with the patient if the pregnancy test is positive
• Contraception
  • Patients using Aprocitentan who can become pregnant should use acceptable contraception before initiating, during treatment, and for 1 month after discontinuing treatment
• Infertility
  • Other ERAs have shown an adverse effect on spermatogenesis in humans and/or animals
  • Aprocitentan may impair fertility in males of reproductive potential
  • Unknown whether effects on fertility would be reversible
• Lactation
  • Data are unavailable on the presence in human milk, effects on breastfed infants, or effect on milk production
  • In rats, Aprocitentan was excreted into milk during lactation; when a drug is present in animal milk, the drug will likely be present in human milk
  • Owing to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment