Macitentan and tadalafil

Macitentan and tadalafil is a combination medicine used in adults to treat pulmonary arterial hypertension (PAH), which causes high blood pressure in the lungs.

Macitentan and tadalafil is available only through a special program. You must be registered in the program and understand the risks and benefits of macitentan and tadalafil.

Macitentan and tadalafil may also be used for reasons not mentioned in this medication guide.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Macitentan and tadalafil is usually taken once per day, with or without food.

Swallow the tablet whole and do not crush, chew, or break it.

Keep the medicine in the original container, along with the packet or canister of moisture-absorbing preservative.

You will need blood tests to check your liver function and red blood cells.

Store at room temperature away from moisture and heat.

Do not use if you are pregnant.

• Use effective birth control while using macitentan and tadalafil and for at least 30 days after your last dose.
• Tell your doctor if you become pregnant.

Some drugs can cause unwanted or dangerous effects when used with macitentan and tadalafil.

You should not take macitentan and tadalafil if you are allergic to it, or if you are using other medicines to treat pulmonary arterial hypertension, such as riociguat (Adempas).

Do not take macitentan and tadalafil if you are also using certain medicines for chest pain or heart problems called nitrates. These include nitroglycerin, isosorbide dinitrate, and isosorbide mononitrate. Nitrates are also in some recreational drugs such as amyl nitrate, butyl nitrate, or nitrite ("poppers"). Taking this medicine with a nitrate can cause a sudden and serious decrease in blood pressure.

Some macitentan and tadalafil can stay in your bloodstream for 2 or more days after each dose you take (longer if you have liver or kidney disease). Avoid using nitrates during this time.

Tell your doctor if you have or have ever had:

• heart problems (chest pain, a heart rhythm disorder, congestive heart failure);
• a heart attack or stroke;
• low blood pressure;
• retinitis pigmentosa (an inherited condition of the eye);
• problems with hearing or vision;
• a blood cell disorder such as sickle cell anemia, multiple myeloma, or leukemia;
• anemia (low red blood cells);
• pulmonary veno-occlusive disease (PVOD);
• priapism (an erection that is painful or lasts longer than 4 hours);
• a penis deformity (such as Peyronie's disease);
• a stomach ulcer;
• liver disease; or
• kidney disease (or if you are on dialysis).

You will need to take a pregnancy test before, during, and after treatment with macitentan and tadalafil.

May cause birth defects. Do not use if you are pregnant. You must use effective birth control while using macitentan and tadalafil and for at least 30 days after your last dose. Tell your doctor if you become pregnant.

It may be harder for you to get a woman pregnant while you are using this medicine.

Do not breastfeed.

Get emergency medical help if you have signs of an allergic reaction (hives, difficulty breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning eyes, skin pain, red or purple skin rash with blistering and peeling).

Macitentan and tadalafil may cause serious side effects. Call your doctor immediately if you have:

• severe vision problems, including sudden vision loss;
• ringing in your ears or sudden hearing loss;
• feeling light-headed, as if you might faint;
• a painful erection or one that lasts longer than 4 hours;
• low red blood cells (anemia) - pale skin, tiredness, feeling light-headed or short of breath, cold hands and feet;
• symptoms of liver problems - loss of appetite, pain or swelling in your stomach, swelling in your legs, easy bruising or bleeding, drowsiness, confusion, or jaundice (yellowing of the skin or eyes);
• fluid retention - shortness of breath (even while lying down), swelling, rapid weight gain (especially in your face and belly); or
• heart attack symptoms - chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating.

Common side effects of macitentan and tadalafil may include:

• fluid retention;
• anemia; or
• headache, migraine headache.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Pulmonary Hypertension:

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

Take the missed dose on the same day you remember it. Take your next dose at the regular time and continue with your once-daily schedule. Do not take two doses at the same time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid drinking alcohol. Alcohol can further lower your blood pressure and may increase your risk of headache, dizziness, or fainting.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy.

Grapefruit may interact with macitentan and tadalafil and cause side effects. Avoid consuming grapefruit products.

Sometimes, it is not safe to use certain medicines together. Some drugs can change how much of other drugs is in your blood, which may increase side effects or make the medicines less effective.

Tell your doctor about all the medicines you are currently taking. Many drugs can affect macitentan and tadalafil, especially:

• medicine for chest pain--isosorbide mononitrate, isosorbide dinitrate, nitroglycerin;
• medicine for erectile dysfunction (impotence) or pulmonary arterial hypertension--riociguat, bosentan, avanafil, sildenafil, or vardenafil;
• medicine for high blood pressure or enlarged prostate--alfuzosin, amlodipine, bendroflumethiazide, doxazosin, enalapril, metoprolol, prazosin, terazosin, silodosin, tamsulosin;
• an antibiotic--clarithromycin, rifabutin, rifampin, rifapentine, telithromycin;
• antifungal medicine--itraconazole, ketoconazole, fluconazole;
• antiviral medicine for HIV or hepatitis C--boceprevir, cobicistat, dasabuvir, elvitegravir, indinavir, lopinavir/ritonavir, nelfinavir, ombitasvir, paritaprevir, saquinavir, ritonavir, telaprevir, tipranavir;
• cancer medicine--apalutamide, enzalutamide, mitotane;
• steroid medicine--dexamethasone, prednisone;
• seizure medicine--carbamazepine, oxcarbazepine, phenytoin, primidone;
• nefazodone;
• St. John's wort;
• amiodarone; or
• any other blood pressure medication.

This list is not complete, and many other drugs may affect macitentan and tadalafil. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible drug interactions are listed here.