Treprostinil

Treprostinil is a prescription medication used for the treatment of pulmonary arterial hypertension (PAH; WHO Group 1). Treprostinil improves the ability to exercise and prevents the condition from getting worse.

• Treprostinil is available under the following different brand names: Remodulin, Orenitram

Common side effects of Treprostinil include:

• nausea
• vomiting
• diarrhea
• headache
• dizziness
• jaw pain
• flushing (warmth, redness, or tingly feeling)
• skin rash
• injection site reactions (redness, swelling, pain, or a hard lump)

Serious side effects of Treprostinil include:

• new/worsening swelling of the arms/legs
• mental/mood changes (such as restlessness, and nervousness)
• unusual bleeding/bruising
• rash
• itching/swelling (especially of the face/tongue/throat)
• severe dizziness
• trouble breathing

Rare side effects of Treprostinil 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 and pediatric dosage

Injectable solution (Remodulin)

• 1 mg/mL
• 2.5 mg/mL
• 5 mg/mL
• 10 mg/mL

Tablet, extended-release (Orenitram)

• 0.125 mg
• 0.25 mg
• 1 mg
• 2.5 mg
• 5 mg

Pulmonary arterial hypertension

Adult dosage

Injectable

• Initial: 1.25 ng/kg/min continuous SC/IV infusion (0.625 ng/kg/min if not tolerated)
• Initial dose should be the same as the current dose the patient is receiving using the external infusion pump at the time of transition
• Titrate by no more than 1.25 ng/kg/min every week for the first 4 weeks, then no more than 2.5 ng/kg/min every week
• Little experience with doses more than 40 ng/kg/min

Extended-release tablets

• Initial: 0.125 mg orally three times a day or 0.25 mg orally two times a day
• Titrate by 0.125 mg three times a day or 0.25 or 0.5 mg two times a day not more frequently than every 3 to 4 days
• Increase the dose to the highest tolerated dose
• If dose increments are not tolerated, consider titrating slower
• If intolerable pharmacologic effects occur, decrease the dose in increments of 0.125 mg three times a day or 0.25 mg two times a day
• Avoid abrupt discontinuation
• Studies that established effectiveness included predominately patients with WHO functional class II to III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%)

Pediatric dosage

• Children younger than 16 years (injectable): Safety and efficacy not established
• Children younger than 18 years (oral tablet): Safety and efficacy not established
• Injectable (aged 16 years and older)
  • Initial: 1.25 ng/kg/min continuous SC/IV infusion (0.625 ng/kg/min if not tolerated)
  • Titrate by no more than 1.25 ng/kg/min every week for the first 4 weeks, then no more than 2.5 ng/kg/min every week
  • Little experience with doses more than 40 ng/kg/min
• Oral tablet (aged 18 years and older)
  • Initial: 0.25 mg orally two times a day with food, taken approximately 12 hours apart
  • Increase dose as tolerated to achieve optimal clinical response by increments or 0.25 to 0.5 mg two times a day every 3 to 4 days, if 0.25 mg two times a day dose increments are not tolerated consider titrating slower
  • Total daily dose can be divided and given three times a day with food (approximately 8 hours apart), titrating by increments of 0.125 mg three times a day
  • Maximum dose: Determined by tolerability; mean dose in a controlled clinical trial at 12 weeks was 3.4 mg two times a day; maximum doses studied were 12 mg two times a day in the 12-week blinded study and up to 21 mg two times a day in an open-label long-term study
  • If intolerable adverse effects occur, decrease the dose by 0.25 mg increments
• Transition from SC/IV to oral
  • Decrease the dose of the SC or IV treprostinil while simultaneously increasing the oral dose
  • The SC/IV dose can be reduced up to 30 ng/kg/min per day and the oral dose simultaneously increased up to 6 mg/day (2 mg three times a day) if tolerated
  • The following equation can be used to estimate a comparable total daily dose of oral treprostinil in mg using a patient’s dose of SC/IV treprostinil (in ng/kg/min) and weight (in kg)
  • Oral total daily dose (mg) = 0.0072 * SC/IV dose (ng/kg/min) * weight (kg)

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.

• Treprostinil has severe interactions with no other drugs
• Treprostinil has serious interactions with the following drug:
  • lofexidine
• Treprostinil has moderate interactions with at least 31 other drugs
• Treprostinil has minor interactions with at least 82 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

• Extended-release tablets: Severe hepatic impairment (Child-Pugh Class C)
• Injectable: None

Effects of drug abuse

• None

Short-Term Effects

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

Long-Term Effects

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

Cautions

• Hepatic/renal impairment (titrate up slowly); such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic or renal function
• Use caution in patients with low arterial blood pressure (may produce symptomatic hypotension)
• Do not take oral tablets with alcohol; faster release of Treprostinil from the tablet may occur
• The tablet shell does not dissolve and can lodge in a diverticulum in patients with diverticulosis
• Abrupt withdrawal may worsen pulmonary arterial hypertension symptoms
• Inhibits platelet aggregation and increases the risk of bleeding; use caution in patients receiving concurrent anticoagulant/antiplatelet therapy
• Indwelling central venous catheter-associated with serious bloodstream infections; use this method only in patients intolerant to the SC therapy
• Experienced personnel required to administer therapy
• Drug interactions overview
  • Dosage adjustment may be necessary if CYP2C8 inhibitors (e.g., atazanavir, gemfibrozil, ritonavir) or inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin) are added or withdrawn

Pregnancy and Lactation

• Limited case reports of treprostinil insufficient to inform a drug-associated risk of adverse developmental outcomes; however, there are risks to the mother and fetus associated with pulmonary arterial hypertension associated with an increased risk of maternal and fetal mortality; in animal studies, no adverse reproductive and developmental effects observed
• Lactation
  • There are no data on the presence of treprostinil in human milk, its effects on breastfed infants, or milk production