Treprostinil

Dosage Forms & Strengths

injectable solution (Remodulin)

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

inhalation solution (Tyvaso)

• 600mcg/mL

tablet, extended-release (Orenitram)

• 0.125mg
• 0.25mg
• 1mg
• 2.5mg

Pulmonary Arterial Hypertension

Injectable

• 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 qWeek x first 4 weeks, then no more than 2.5 ng/kg/min qWeek
• Little experience with doses >40 ng/kg/min
• Must carefully titrated dose
• Avoid abrupt withdrawal
• If infusion is stopped and then restarted within a few hours after discontinuing it, may use the same rate; interruptions for long periods may require retitration

Oral inhalation

• Initial: 18 mcg (3 breaths), per treatment session, QID; if 3 breaths not tolerated, decrease to 1-2 breaths and later increase to 3 breaths as tolerated
• If tolerated, increase by 3 breaths/dose (18 mcg) q1-2Weeks
• Target maintenance: 54 mcg (9 breaths), per treatment session QID

Oral tablet

• Initial: 0.25 mg PO BID with food, taken ~12 hr apart
• Increase dose as tolerated to achieve optimal clinical response by increments or 0.25-0.5 mg BID q3-4 days; if 0.25 mg BID dose increments are not tolerated consider titrating slower
• Total daily dose can be divided and given TID with food (~8 hr apart), titrating by increments of 0.125 mg TID
• Maximum dose: Determined by tolerability; mean dose in a controlled clinical trial at 12 weeks was 3.4 mg BID; maximum doses studied were 12 mg BID in the 12-week blinded study and up to 21 mg BID in an open-label long-term study
• If intolerable adverse effects occur, decrease 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 TID) 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 x SC/IV dose (ng/kg/min) x weight (kg)

Dosage Modifications

Coadministration with strong CYP2C8 inhibitors: Initiate at 0.125 mg PO BID; may increase by 0.125 mg BID dose increments every 3-4 days

Renal impairment

• Titrate slowly with moderate renal insufficiency
• Monitor for greater systemic concentrations relative to that of normal renal function  

Hepatic impairment

• Injectable
  • Mild-to-moderate (Child-Pugh A or B): Initiate SC dose at 0.625 ng/kg/min (ideal body weight)
  • Severe (Child Pugh C): Not studied
• Oral inhalation
  • Mild-to-moderate (Child-Pugh A or B): Titrate dose slowly
  • Severe (Child Pugh C): Not studied
• Extended-release tablets
  • Mild (Child-Pugh Class A): Initiate at 0.125 mg PO BID; may increase by 0.125 mg BID dose increments every 3-4 days
  • Moderate (Child-Pugh Class B): Avoid use
  • Severe (Child-Pugh Class C): Contraindicated

Dosage Forms & Strengths

injectable solution (Remodulin)

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

inhalation solution (Tyvaso)

• 600mcg/mL

tablet, extended-release (Orenitram)

• 0.125mg
• 0.25mg
• 1mg
• 2.5mg

Pulmonary Arterial Hypertension

<16 years (injectable): Safety and efficacy not established

<18 years (oral inhalation, oral tablet): Safety and efficacy not established

Injectable (≥16 years)

• 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 qWeek x first 4 weeks, then no more than 2.5 ng/kg/min qWeek  
• Little experience with doses >40 ng/kg/min
• Must carefully titrated dose
• Avoid abrupt withdrawalIf infusion is stopped and then restarted within a few hours after discontinuing it, may use the same rate; interruptions for long periods may require retitration

Oral inhalation (≥18 years)

• Initial: 18 mcg (3 breaths), per treatment session, QID; if 3 breaths not tolerated, decrease to 1-2 breaths and later increase to 3 breaths as tolerated
• If tolerated, increase by 3 breaths/dose (18 mcg) q1-2Weeks
• Target maintenance: 54 mcg (9 breaths), per treatment session QID

Oral tablet (≥18 years)

• Initial: 0.25 mg PO BID with food, taken ~12 hr apart
• Increase dose as tolerated to achieve optimal clinical response by increments or 0.25-0.5 mg BID q3-4 days; if 0.25 mg BID dose increments are not tolerated consider titrating slower
• Total daily dose can be divided and given TID with food (~8 hr apart), titrating by increments of 0.125 mg TID
• Maximum dose: Determined by tolerability; mean dose in a controlled clinical trial at 12 weeks was 3.4 mg BID; maximum doses studied were 12 mg BID in the 12-week blinded study and up to 21 mg BID in an open-label long-term study
• If intolerable adverse effects occur, decrease 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 TID) 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 x SC/IV dose (ng/kg/min) x weight (kg)

Dosage Modifications

Coadministration with strong CYP2C8 inhibitors: Initiate at 0.125 mg PO BID; may increase by 0.125 mg BID dose increments every 3-4 days

Renal impairment

• Titrate slowly with moderate renal insufficiency
• Monitor for greater systemic concentrations relative to that of normal renal function  

Hepatic impairment

• Injectable
  • Mild-to-moderate (Child-Pugh A or B): Initiate SC dose at 0.625 ng/kg/min (ideal body weight)
  • Severe (Child Pugh C): Not studied
• Oral inhalation
  • Mild-to-moderate (Child-Pugh A or B): Titrate dose slowly
  • Severe (Child Pugh C): Not studied
• Extended-release tablets
  • Mild (Child-Pugh Class A): Initiate at 0.125 mg PO BID; may increase by 0.125 mg BID dose increments every 3-4 days
  • Moderate (Child-Pugh Class B): Avoid use
  • Severe (Child-Pugh Class C): Contraindicated

Treprostinil is a prescription medication used to treat pulmonary arterial hypertension (PAH). It is also used to switch those taking Flolan (epoprostenol) to treprostinil. Treprostinil belongs to a group of drugs called vasodilators, which help to relax the blood vessels within and around the lungs. This helps increase your ability to breathe, especially during exercise. It also acts as a blood thinner, which decreases the chance of a blood clot.

This medication is available in an injectable form to be given directly into a vein (IV) or just under the skin (subcutaneously) by a healthcare professional.

This medication also comes as an inhalant that is to be used 4 times a day, at least 4 hours apart per inhalation.

Treprostinil is also available as extended release tablets. It is usually taken 2 or 3 times a day with food. Swallow tablets whole, do not crush, divided or chew tablets.

Common side effects of treprostinil injectable include diarrhea, jaw pain, and pain at the site of injection. It can also cause dizziness. Do not drive or operate heavy machinery until you know how treprostinil affects you.

Common side effects of treprostinil inhalant include headache, nausea, and flushing. It can also cause dizziness. Do not drive or operate heavy machinery until you know how treprostinil affects you.

Common side effects of treprostinil tablets include headache, nausea, and diarrhea. 

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 condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

Injectable:

The recommended starting dose dose for those new to prostacyclin infusion therapy: 1.25 ng/kg/minute (or 0.625 ng/kg/minute if not tolerated). Your dose may be increased according to response to therapy and/or adverse effects.

Inhalational:

• Take undiluted (do not mix with any other liquid).
• Take in 4 separate treatment sessions each day approximately 4 hours apart (during waking hours).
• Starting dose: 3 breaths [18 mcg] per session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths.
• Dose may be increased by an additional 3 breaths at about 1-2 week intervals, if tolerated.
• Increase to target maintenance (long-term) dose of 9 breaths [54 mcg] per session as tolerated.

Oral:

• 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.

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.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• gemfibrozil;

• blood pressure medication;

• a blood thinner--warfarin, Coumadin, Jantoven;

• other medicine to prevent blood clots--dalteparin, tinzaparin, Fragmin, Lovenox, and others; or

• other forms of treprostinil--Remodulin, Tyvaso.

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.

Treprostinil is used to treat symptoms of pulmonary arterial hypertension, which is high blood pressure in the main artery that carries blood from the right side of the heart (the ventricle) to the lungs. When the small blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. Treprostinil works by relaxing these blood vessels and increasing the supply of blood to the lungs, which reduces the workload of the heart.

treprostinil is available only with your doctor's prescription.

Take treprostinil 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 stop taking treprostinil without checking with your doctor first.

treprostinil comes with a patient information insert. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Swallow the extended-release tablet whole. Do not crush, break, or chew it. Take treprostinil with food.

Dosing

The dose of treprostinil 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 treprostinil. 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 (extended-release tablets):
  • For pulmonary arterial hypertension:
    • Adults—At first, 0.25 milligrams (mg) two times a day with food, taken 12 hours apart, or 0.125 mg three times a day, taken 8 hours apart. Your doctor may increase your dose as needed and tolerated.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of treprostinil, 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.

If you missed two or more doses, call your doctor if you need to change your dose.

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.

(tre PROST in il)

• Orenitram
• Remodulin
• Tyvaso
• Tyvaso Refill
• Tyvaso Starter

Injection solution: For SubQ infusion, product should not be diluted prior to use. For IV infusion, dilute in SWFI, NS, Remodulin sterile diluent, or Flolan sterile diluent to a final volume of either 50 mL or 100 mL (dependent on system reservoir and calculated dose).

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Prostacyclin Analogues may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Alcohol (Ethyl): May increase the absorption of Treprostinil. Specifically, a more rapid and/or complete absorption of Treprostinil from extended-release tablets is possible. Management: Avoid administration of treprostinil extended release tablets with alcohol, and advise patients to avoid this combination. No such interaction is expected with other treprostinil formulations. Consider therapy modification

Anticoagulants: Prostacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Monitor therapy

Blood Pressure Lowering Agents: Prostacyclin Analogues may enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

CYP2C8 Inducers (Strong): May decrease the serum concentration of Treprostinil. Monitor therapy

CYP2C8 Inhibitors (Strong): May increase the serum concentration of Treprostinil. Management: Reduce the initial treprostinil extended release tablet dose to 0.125 mg twice daily, titrating by 0.125 mg twice daily every 3 to 4 days. No preemptive dose adjustment is recommended for other treprostinil products. Consider therapy modification

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Thrombolytic Agents: May enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Monitor therapy

Adverse events have been observed in some animal reproduction studies. Women with pulmonary arterial hypertension (PAH) are encouraged to avoid pregnancy (McLaughlin 2009; Taichman 2014).