Orenitram

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• severe headache;
• vomiting; or
• a light-headed feeling, like you might pass out.

Common side effects may include:

• headache;
• pain in your arms or legs;
• diarrhea, nausea; or
• flushing (warmth, redness, or tingly feeling).

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.

Do not drink alcohol. Alcohol can cause the tablet to release treprostinil too quickly.

Tell your doctor about all medicines you use, and those you start or stop using during your treatment with treprostinil, especially medicine used to prevent blood clots, such as:

• dalteparin;
• enoxaparin;
• fondaparinux; or
• tinzaparin.

This list is not complete. Other drugs may interact with treprostinil, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• diuretics such as
  • acetazolamide (Diamox)
  • amiloride (Midamor)
  • bumetanide (Bumex)
  • chlorothiazide (Diuril)
  • chlorthalidone (Thalitone)
  • ethacrynic acid (Edecrin)
  • furosemide (Lasix)
  • hydrochlorothiazide (Microzide, HCTZ)
  • metolazone (Zaroxolyn)
  • torsemide (Demadex)
  • triamterene (Dyrenium, Dyazide, Maxzide)
• angiotensin-converting enzyme (ACE) blockers such as
  • benazepril (Lotensin, Lotensin HCT)
  • captopril (Capoten, Capozide)
  • enalapril (Vasotec, Vaseretic)
  • fosinopril (Monopril, Monopril HCT)
  • lisinopril (Prinivil, Prinzide, Zestril, Zestoretic)
  • moexipril (Univasc, Uniretic)
  • quinapril (Accupril, Accuretic, Quinaretic)
  • ramipril (Altace)
  • trandolapril (Mavik, Tarka)
• angiotensin receptor II blockers such as
  • azilsartan (Edarbi)
  • candesartan (Atacand)
  • irbesartan (Avapro)
  • losartan (Cozaar)
  • olmesartan (Benicar)
  • telmisartan (Micardis, Twynsta)
  • valsartan (Diovan)
• beta blockers such as
  • metoprolol (Toprol XL, Lopressor)
  • carvedilol (Coreg)
  • bisoprolol (Zebeta)
  • betaxolol (Kerlone)
  • nebivolol (Bystolic)
  • propranolol (Inderal)
• calcium channel blockers such as
• nifedipine (Adalat, Nifedical, Procardia)
• amlodipine (Norvasc)
• verapamil (Calan, Isoptin, Covera, Verelan)
• diltiazem (Cardizem)
• vasodilators such as
  • doxazosin (Cardura)
  • prazosin (Minipress)
  • terazosin (Hytrin)
  • clonidine (Catapres)
  • hydralazine (Bidil, Hydra-Zide)
  • minoxidil

• medications that affect your platelets such as clopidogrel (Plavix), aspirin, prasugrel (Effient), ticagrelor (Brilinta), ticlopidine (Ticlid), abciximab (ReoPro), eptifibatide (Integrilin), tirofiban (Aggrastat), and cilostazol (Pletal)
• anticoagulant (blood thinner) medications such as warfarin (Coumadin, Jantoven), heparin, enoxaparin (Lovenox), fondaparinux (Arixtra), rivaroxaban (Xarelto), and apixaban (Eliquis) 
• alcohol

This is not a complete list of all drug interactions. Ask your doctor or pharmacist for more information.

Take exactly as your healthcare provider tells you to take it.

• Your healthcare provider will slowly increase your dose to find the dose of that is right for you.
• Do not change your dose or suddenly stop taking this medication without first talking to your healthcare provider. Stopping this medication suddenly may cause worsening of your PAH symptoms.
• Tablets are usually taken every 12 hours, but may be taken three times daily (approximately every 8 hours). If you have side effects, your healthcare provider may tell you to change your dose or when you take this medication.
• Take with food.
• Swallow tablets whole. Do not split, chew, crush, or break your tablets. Do not take tablets that are damaged or broken. If tablets are not taken whole, they may release too much medicine at one time. This can lead to side effects.
• You may see the tablet shell in your stools (bowel movements). This is usually normal. The tablet shell is not digested. If you have diverticulosis, the tablet shell may get stuck in a blind pouch or diverticulum in your intestine.
• If you miss your dose of this medication, take the dose as soon as possible with food.
• If you miss two or more doses of this medication, call your healthcare provider to see if you need to change your dose.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

The starting recommended dose is 0.25 mg twice daily.

Your doctor may increase your dose by 0.25 mg or 0.5 mg twice daily or 0.125 mg three times daily, not more than every 3 to 4 days as tolerated.

The maximum dose is determined by tolerability.

For patients whose liver does not work as well, the dose will be adjusted. 

You should not use treprostinil if you are allergic to it, or if you have severe liver disease.

To make sure treprostinil is safe for you, tell your doctor if you have:

• diverticulosis (an intestinal disorder); or

• liver disease.

It is not known whether treprostinil will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medicine.

It is not known whether treprostinil passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine.

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Do not crush, chew, or break an extended-release tablet. Swallow it whole. Do not use a broken pill.

Take with food.

Take your doses at regular intervals to keep a steady amount of the drug in your body at all times.

You should not reduce your dose or stop using treprostinil suddenly. Stopping suddenly may make your condition worse.

Tell your doctor if you need to stop taking treprostinil for any reason. You may need an alternate treatment during that time.

Treprostinil is made with a shell that is not absorbed or melted in the body. Part of the tablet shell may appear in your stool. This is a normal side effect of treprostinil and will not make the medication less effective.

Call your doctor if you have new or worsening PAH symptoms such as feeling short of breath (even with mild exertion), tiredness, chest pain, and pale skin.

Use treprostinil regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. You will probably have to use this medicine for several months or years to control your condition and keep it from getting worse.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Call your doctor if you miss 2 or more doses of treprostinil.

In the U.S.

• Orenitram

Available Dosage Forms:

• Tablet, Extended Release

Therapeutic Class: Vasodilator

Pharmacologic Class: Prostaglandin

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 treprostinil 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 treprostinil in the elderly. However, elderly patients are more likely to have liver or heart problems, which may require caution and an adjustment in the dose for patients receiving this medicine.

Pregnancy

Breast Feeding

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.

Interactions with Medicines

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.

• Defibrotide

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.

• Aceclofenac
• Acemetacin
• Alipogene Tiparvovec
• Alteplase, Recombinant
• Amtolmetin Guacil
• Anagrelide
• Apixaban
• Ardeparin
• Argatroban
• Aspirin
• Bemiparin
• Betrixaban
• Bivalirudin
• Bromfenac
• Bufexamac
• Celecoxib
• Certoparin
• Choline Salicylate
• Citalopram
• Clonixin
• Dabigatran Etexilate
• Dalteparin
• Danaparoid
• Desirudin
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Dipyridamole
• Dipyrone
• Droxicam
• Edoxaban
• Enoxaparin
• Eptifibatide
• Escitalopram
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Heparin
• Ibuprofen
• Indomethacin
• Ketoprofen
• Ketorolac
• Lepirudin
• Levomilnacipran
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Morniflumate
• Nabumetone
• Nadroparin
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Parnaparin
• Paroxetine
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Piracetam
• Piroxicam
• Pixantrone
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Reviparin
• Rivaroxaban
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sertraline
• Sodium Salicylate
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tinzaparin
• Tolfenamic Acid
• Tolmetin
• Valdecoxib
• Vilazodone
• Vortioxetine
• Warfarin

Interactions with Food/Tobacco/Alcohol

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.

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:

• Hypotension (low blood pressure) or
• Stomach or bowel problems (eg, diverticulosis, ulcers) or
• Stroke, history of—Use with caution. May make these conditions worse.

• Liver disease, mild—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

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

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:

• Decreased urine
• dry mouth
• increased thirst
• irregular heartbeat
• muscle pain or cramps
• nausea or vomiting
• pain in the jaw, arms, or legs
• unusual tiredness or weakness

Get emergency help immediately if any of the following symptoms of overdose occur:

• Blurred vision
• confusion
• diarrhea
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• headache, severe
• sweating

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:

• Abdominal or stomach discomfort
• diarrhea
• feeling of warmth
• headache
• redness of the face, neck, arms, and occasionally, upper chest

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.

You should not use Orenitram if you have severe liver disease.

Usual Adult Dose of Orenitram for Pulmonary Hypertension:

Oral formulation:
Initial dose: 0.25 mg orally every 12 hours with food
Recommended titration: 0.25 or 0.5 mg 2 times daily every 3 to 4 days (if 0.25 mg 2 times daily increments are not tolerated consider titrating slower)
-The total daily dose can be divided and given every 8 hours with food, titrating by increments of 0.125 mg 3 times daily.
Mean dose: 3.5 mg orally every 12 hours with food.
Maximum dose: Determined by tolerability. The maximum dose studied was 21 mg orally every 12 hours with food.

Infusion:
Initial dose: 1.25 nanogram/kg per minute by continuous infusion. The subcutaneous route is preferred but the drug may be administered by a central intravenous line if the subcutaneous route is not tolerated. The rate may be decreased to 0.625 nanogram/kg/minute if the initial dose is not tolerated by the patient.
Maintenance dose: The infusion rate may be increased in increments of no more than 1.25 nanogram/kg/minute per week for the first 4 weeks, and thereafter by no more than 2.5 nanograms/kg/minute per week. Dosage adjustments should be titrated to a dose where PAH symptoms are improved and adverse effects are minimized (headache, nausea, emesis, restlessness, anxiety, and infusion site pain or reaction). Although doses of up to 100 nanograms/kg/minute have been reported, there is little experience with doses greater than 40 nanograms/kg/minute.

Inhalation:
Use only with the Tyvaso (R) Inhalation System. Administer undiluted, as supplied. A single breath of Tyvaso (R) delivers approximately 6 mcg of Orenitram
Initial dosage: 3 breaths [18 mcg] per treatment session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths. Administer in 4 separate treatment sessions each day approximately four hours apart, during waking hours.
Maintenance dose: Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated. Titrate to target maintenance dosage of 9 breaths or 54 mcg per treatment session as tolerated.

Usual Pediatric Dose of Orenitram for Pulmonary Hypertension:

Oral formulation: Safety and effectiveness have not been established in pediatric patients (less than 18 years of age).

Inhalation:
Less than 16 years: Safety and efficacy have not been established.
16 to 18 years:
Initial dose: 1.25 nanogram/kg per minute by continuous infusion. The subcutaneous route is preferred but the drug may be administered by a central intravenous line if the subcutaneous route is not tolerated. The rate may be decreased to 0.625 nanogram/kg/minute if the initial dose is not tolerated by the patient.
Maintenance dose: The infusion rate may be increased in increments of no more than 1.25 nanogram/kg/minute per week for the first 4 weeks, and thereafter by no more than 2.5 nanograms/kg/minute per week. Dosage adjustments should be titrated to a dose where PAH symptoms are improved and adverse effects are minimized (headache, nausea, emesis, restlessness, anxiety, and infusion site pain or reaction). There is little experience with doses greater than 40 nanograms/kg/minute.

This drug should be used during pregnancy only if clearly needed. AU TGA pregnancy category: B3 US FDA pregnancy category: C (tablets) US FDA pregnancy category: B (oral inhalation, parenteral)

Animal studies in pregnant rats have failed to reveal evidence of teratogenicity at higher doses when administered by continuous subcutaneous infusion during organogenesis and late gestational development. Animal studies in pregnant rabbits have revealed evidence of increased fetal skeletal variations (bilateral full rib or rudimentary right rib on lumbar 1) at doses that produced maternal toxicity. Animal studies with the extended-release tablets revealed dose-dependent decreases in body weight gain and food consumption as well as increased post-implantation loss, decreased pregnancy rates, and fetal skeletal malformations at higher doses. Animal reproduction studies with the inhalation formulation have not been conducted. There are no controlled data in human pregnancy. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use with caution; according to some authorities, use is not recommended. Excreted into human milk: Unknown Excreted into animal milk: Unknown Comments: The effects in the nursing infant are unknown.