Description
Macitentan and tadalafil combination is used to treat pulmonary arterial hypertension (PAH), which is high blood pressure that occurs in the main artery that 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. Macitentan and tadalafil combination works by relaxing these blood vessels and increasing the supply of blood to the lungs, which reduces the workload of the heart.
This medicine is only available for female patients under a restricted distribution program called the Macitentan-Containing Products REMS (Risk Evaluation and Mitigation Strategy) program. Male patients do not need to enroll in the REMS program.
This product is available in the following dosage forms:
- Tablet
Before Using
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:
Allergies
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.
Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of macitentan and tadalafil combination in the pediatric population. Safety and efficacy have not been established.
Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of macitentan and tadalafil combination in the elderly.
Breastfeeding
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.
Drug Interactions
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.
- Amyl Nitrite
- Boceprevir
- Erythrityl Tetranitrate
- Isosorbide
- Isosorbide Dinitrate
- Isosorbide Mononitrate
- Nitroglycerin
- Pentaerythritol Tetranitrate
- Propatyl Nitrate
- Riociguat
- Sparsentan
- Telaprevir
- Vericiguat
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.
- Alfuzosin
- Amiodarone
- Amprenavir
- Apalutamide
- Atazanavir
- Avacopan
- Boceprevir
- Bunazosin
- Carbamazepine
- Ceritinib
- Clarithromycin
- Cobicistat
- Dapiprazole
- Darunavir
- Doxazosin
- Enzalutamide
- Erythromycin
- Fluconazole
- Fosamprenavir
- Fosphenytoin
- Idelalisib
- Indinavir
- Itraconazole
- Ivacaftor
- Ivosidenib
- Ketoconazole
- Lenacapavir
- Lonafarnib
- Lopinavir
- Lumacaftor
- Mavacamten
- Mifepristone
- Mitotane
- Moxisylyte
- Nefazodone
- Nelfinavir
- Nirmatrelvir
- Paritaprevir
- Phenobarbital
- Phenoxybenzamine
Other Interactions
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. 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 is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
- Grapefruit Juice
Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.
- Ethanol
Other Medical Problems
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:
- Congenital or anatomic conditions of the penis (eg, angulation, cavernosal fibrosis, or Peyronie’s disease) or
- Leukemia (blood related cancer) or
- Multiple myeloma (blood related cancer) or
- Sickle-cell anemia (blood disorder)—Use with caution. May increase risk of unwanted side effects (eg, prolonged erection of the penis).
- Age greater than 50 years or
- Diabetes or
- Heart or blood vessel disease (eg, coronary artery disease) or
- Hyperlipidemia (high lipids or fats in the blood) or
- Hypertension (high blood pressure) or
- Low cup to disc ratio (eye condition also called "crowded disc") or
- Smoking—Use with caution. May increase risk for non–arteritic anterior ischemic optic neuropathy (NAION).
- Anemia or
- Heart attack or
- Heart failure or
- Liver disease—Use with caution. May make these conditions worse.
- Anemia, severe or
- Eye or vision problems (eg, retinitis pigmentosa), known or
- Kidney disease (patients on dialysis) or
- Lung disease (eg, pulmonary veno-occlusive disease or PVOD)—Use is not recommended in patients with theses conditions.
Proper Use
Take this medicine only 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. Your dose may need to be changed several times in order to find what works best for you.
It is very important that you understand the requirements of the Macitentan-Containing Products REMS program and Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions. Ask your pharmacist for the medication guide if you do not have one.
You may take this medicine with or without food.
Swallow the tablet whole with water. Do not cut, crush, or chew it.
Do not eat grapefruit or drink grapefruit juice while you are using this medicine. Grapefruit and grapefruit juice may change the amount of this medicine that is absorbed in the body.
Dosing
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 form (tablets):
- For pulmonary arterial hypertension (patient never had PAH treatment or is transitioning from ERA monotherapy):
- Adults—One tablet once a day for 1 week. Each tablet contains 10 milligrams (mg) of macitentan and 20 mg of tadalafil. Your doctor may adjust your dose as needed and tolerated.
- Children—Use and dose must be determined by your doctor.
- For pulmonary arterial hypertension (patient already had PAH treatment):
- Adults—One tablet once a day. Each tablet contains 10 milligrams (mg) of macitentan and 40 mg of tadalafil.
- Children—Use and dose must be determined by your doctor.
- For pulmonary arterial hypertension (patient never had PAH treatment or is transitioning from ERA monotherapy):
Missed Dose
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.
Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
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.
Precautions
It is very important that your doctor check your progress closely while you are receiving this medicine to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects.
Using this medicine while you are pregnant can cause very serious birth defects. Use a highly effective birth control or 2 forms of effective birth control to keep from getting pregnant before starting, during treatment (even if the medicine is temporarily stopped), and for at least 1 month after your last dose. The most effective forms of birth control are hormone birth control pills, patches, shots, vaginal rings, or implants, or a vasectomy (for males). One of these forms of birth control should be combined with a condom, a diaphragm, or a cervical cap. If a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. If you think you have become pregnant while using this medicine, tell your doctor right away.
If you can get pregnant, you must have a negative pregnancy test before you can take this medicine. You will also be required to have a pregnancy test every month during treatment and for 1 month after treatment with this medicine. If you miss a period while you are using this medicine, tell your doctor right away.
Do not take other medicines that contains tadalafil (Cialis®) or other PDE5 inhibitors, including sildenafil (Revatio® or Viagra®) or vardenafil (Levitra®). If you take too much tadalafil or take it together with these medicines, the chance for side effects will be higher.
Do not use this medicine if you are also using riociguat or a nitrate medicine, often used to treat angina (chest pain). Nitrate medicines include nitroglycerin, isosorbide, Imdur®, Nitro-Bid®, Nitrostat®, Nitro-Dur®, Transderm Nitro®, Nitrol® Ointment, and Nitrolingual® Spray. Some street drugs called "poppers" (eg, amyl nitrate, butyl nitrate, or nitrite) also contain nitrates. If you need to use a nitrate medicine, take it at least 48 hours after your last dose of tadalafil.
Do not have 4 or more alcohol-containing drinks in a short period of time while you are taking tadalafil. Alcohol can increase your chances of getting a headache or dizziness, increase your heart rate, or lower your blood pressure.
This medicine may decrease sperm count in some males and may cause infertility (unable to have children). Talk with your doctor before using this medicine if you plan to have children.
This medicine may cause serious liver problems. Check with your doctor right away if you have dark urine, fatigue, loss of appetite, nausea or vomiting, severe stomach pain, or yellow eyes or skin.
Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help. If this problem continues or gets worse, check with your doctor right away.
Check with your doctor right away if you have pale skin, trouble breathing, unusual bleeding or bruising, or unusual tiredness or weakness. These may be symptoms of anemia.
If you experience sudden loss of vision in one or both eyes, contact your doctor immediately.
Check with your doctor right away if you have a sudden decrease in hearing or loss of hearing, which may be accompanied by dizziness and ringing in the ears.
This medicine may cause fluid retention (too much water in the body) and peripheral edema (swelling). Check with your doctor right away if you have bloating or swelling of the face, arms, hands, lower legs, or feet, decrease in amount of urine, noisy, rattling, or trouble breathing, rapid weight gain, swelling of the face, hands, feet, or lower legs, tingling of the hands or feet, or weight gain.
If you experience a prolonged erection for more than 4 hours or a painful erection, contact your doctor immediately. This condition may require prompt medical treatment to prevent serious and permanent damage to your penis.
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.
Side Effects
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.
Check with your doctor immediately if any of the following side effects occur:
More common
- Bloating or swelling of the face, arms, hands, lower legs, or feet
- confusion
- decrease in amount of urine
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- fever
- headache
- increase in vaginal bleeding
- muscle aches
- pale skin
- rapid weight gain
- sore throat
- stuffy or runny nose
- sweating
- swelling of the fingers, hands, feet, or lower legs
- tingling of the hands or feet
- trouble breathing
- unusual bleeding or bruising
- unusual tiredness or weakness
- unusual weight gain or loss
Less common
- Bladder pain
- bloody or cloudy urine
- chest pain or tightness
- continuing ringing or buzzing or other unexplained noise in the ears
- cough
- cough producing mucus
- difficult, burning, painful urination
- fast, irregular, pounding, or racing heartbeat or pulse
- feeling of warmth
- frequent urge to urinate
- hearing loss
- lower back or side pain
- redness of the face, neck, arms and occasionally, upper chest
Incidence not known
- Blindness
- blistering, peeling, or loosening of the skin
- chest discomfort
- chills
- clay colored stools
- dark urine
- decreased appetite
- decreased vision
- diarrhea
- difficulty in speaking
- double vision
- inability to move the arms, legs, or facial muscles
- inability to speak
- itching
- joint or muscle pain
- large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
- loss of appetite
- loss of memory
- nausea and vomiting
- pain or discomfort in the arms, jaw, back, or neck
- painful or prolonged erection of the penis
- problems with memory
- red irritated eyes
- red skin lesions, often with a purple center
- seizures
- slow speech
- sores, ulcers, or white spots in the mouth or on the lips
- stomach pain or tenderness
- yellow eyes or skin
Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:
More common
- Back pain
- difficulty in moving
- joint pain
- muscle aches, cramps, pains, or stiffness
- stomach pain
- swollen joints
Less common
- Arm or leg pain
- bloody nose
- face swelling
- heartburn
- indigestion
- shivering
- trouble sleeping
Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.
Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.
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