What is Bosentan?

Use of bosentan may result in hepatotoxicity or liver failure. Measure serum aminotransferase levels prior to initiation of treatment and then monthly. Stop treatment if liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity, or increases in bilirubin greater than or equal to 2 times ULN occur. Use of bosentan is likely to produce major birth defects if used by pregnant women. Exclude pregnancy before initiation of therapy and prevent pregnancy thereafter by the use of 2 forms of reliable contraception for the duration of treatment and for 1 month after stopping bosentan. If the patient has an intrauterine device (IUD) or tubal sterilization, no other contraception is needed. Monthly pregnancy tests should be obtained. Bosentan may be prescribed only through the Tracleer (R) REMS Program .

Bosentan is used to treat the symptoms of pulmonary arterial hypertension (PAH) in adults or in children 3 years of age or older. It improves the ability to exercise and slows down the worsening of the patient's physical condition.

Pulmonary arterial hypertension is the high blood pressure that occurs in the main artery. This artery carries blood from the right side of the heart (the ventricle) to the lungs. When the smaller blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. Bosentan works by blocking large quantities of the hormone normally found in the blood and lungs in people with pulmonary arterial hypertension. It also helps by increasing the supply of blood to the lungs and reducing the workload of the heart.

This medicine is available only under a special restricted distribution program called the Tracleer REMS (risk evaluation and mitigation strategy) Program.

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not change the dose or stop using this medicine without checking first with your doctor.

It is very important that you understand the requirements of the Tracleer® REMS program, and become familiar with the Tracleer® educational materials and Patient Medication Guide. Ask your doctor or pharmacist if you have any questions.

You may take this medicine with or without food.

The tablet for suspension can be taken whole or divided into half along the lines cut into its surface. Do not break it into quarters. You may dissolve it in a small amount of water to make a liquid mixture before taking it.

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (tablets or tablets for oral suspension):
  • For pulmonary arterial hypertension:
    • Adults—At first, 62.5 milligrams (mg) two times a day (morning and evening) for 4 weeks. Your doctor may increase your dose up to 125 mg two times a day. If you are also taking this medicine with ritonavir for at least 10 days, starting dose is 62.5 mg once a day or every other day as directed by your doctor.
    • Children older than 12 years of age and weighs more than 40 kilograms (kg) (88 pounds)—At first, 62.5 mg two times a day. Your doctor may increase your dose to 125 mg two times a day after 4 weeks.
    • Children older than 12 years of age and weighs less than 40 kilograms (kg) (88 pounds)—62.5 mg two times a day.
    • Children 12 years of age and younger—Dose is based on body weight and must be determined by your doctor.
      • Weighs more than 24 to 40 kilograms (kg)—64 mg two times a day.
      • Weighs more than 16 to 24 kg—48 mg two times a day.
      • Weighs more than 8 to 16 kg—32 mg two times a day.
      • Weighs 4 to 8 kg—16 mg two times a day.

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Store the tablet for suspension that have been broken at room temperature in the opened blister container for up to 7 days.

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of bosentan in the pediatric population. Safety and efficacy have been established.

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of bosentan in the elderly. However, elderly patients are more likely to have age-related heart, liver, or kidney problems, which may require caution in patients receiving bosentan.

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Cyclosporine
• Glyburide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Atazanavir
• Axitinib
• Benzhydrocodone
• Buprenorphine
• Cobicistat
• Cobimetinib
• Codeine
• Daclatasvir
• Darunavir
• Deflazacort
• Desogestrel
• Dienogest
• Dihydrocodeine
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Drospirenone
• Elbasvir
• Elvitegravir
• Encorafenib
• Enzalutamide
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Fentanyl
• Fosamprenavir
• Gestodene
• Grazoprevir
• Hemin
• Hydrocodone
• Levonorgestrel
• Lopinavir
• Meperidine
• Mestranol
• Methadone
• Neratinib
• Nifedipine
• Norethindrone
• Norgestimate
• Norgestrel
• Olaparib
• Oxycodone
• Pentazocine
• Perampanel
• Piperaquine
• Ritonavir
• Saquinavir
• Simeprevir
• Sufentanil
• Tacrolimus
• Tipranavir
• Tolvaptan
• Tramadol
• Velpatasvir
• Venetoclax
• Voxilaprevir

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Atorvastatin
• Ketoconazole
• Lovastatin
• Ospemifene
• Rifampin
• Sildenafil
• Simvastatin
• Warfarin

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Edema (fluid retention or body swelling) or
• Heart failure or
• Liver disease, mild or
• Lung problems—Use with caution. Bosentan may make these conditions worse.

• Liver disease, moderate or severe—Should not be used in patients with this condition.

It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests are needed to check your liver function before you start using bosentan and each month after that. Urine tests may also be needed to check for unwanted effects.

Using this medicine while you are pregnant can cause very serious birth defects. Use two forms of effective birth control to keep from getting pregnant while you are using this medicine (even if the medicine is temporarily stopped), and for at least one month after you stop taking the medicine. The most effective forms of birth control are hormone birth control pills, patches, shots, vaginal rings, or implants, an IUD, or a vasectomy (for men). One of these forms of birth control should be combined with a condom, a diaphragm, or a cervical cap. If a woman has had tubal ligation, she does not need to use a second form of birth control. If you think you have become pregnant while using this medicine, tell your doctor right away.

You must have a negative pregnancy test before you will be allowed to take this medicine. You will also be required to have a pregnancy test every month during your treatment and for 1 month after your last dose. If you miss a period while you are using this medicine, tell your doctor right away.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

Bosentan may decrease the amount of sperm men make and affect their ability to have children. If you plan to have children, talk with your doctor before using this medicine.

This medicine may cause fluid retention (edema) in some patients. Check with your doctor right away if you are gaining weight rapidly, have swelling in your hands, ankles, feet, or all over the body, or if you have trouble with breathing while you are using this medicine.

Pulmonary edema may occur while using this medicine. Check with your doctor right away if you have chest pain, difficult, fast, noisy breathing, sometimes with wheezing, blue lips and fingernails, pale skin, increased sweating. coughing that sometimes produces a pink frothy sputum, or shortness of breath.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.