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treprostinil (Tyvaso, Remodulin, Orenitram): Dosing and Uses

 

Classes: PAH, Prostacyclin Analogs

Medically reviewed by Min Clinic Staff | Updated: January 2026

Dosing and uses of Tyvaso, Remodulin, Orenitram (treprostinil)

 

Adult dosage forms and 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

 

Pediatric dosage forms and 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

 

Tyvaso, Remodulin, Orenitram (treprostinil) adverse (side) effects

>10%

Infusion site reaction, pain (80-85%)

Headache (27-41%)

Nausea (19-22%)

Diarrhea (20-30%)

Vasodilation (10-20%)

Jaw pain (13%)

Rash (10-20%)

 

1-10%

Dizziness 9%)

Edema (9%)

Pruritis (8%)

Hypotension (4%)

inhalation solution

  • Flushing
  • Headache
  • Nausea
  • Throat Irritation
  • Cough

 

Frequency not defined

Angioedema

Bone pain

Restlessness

Cellulitis

Haemoptysis

Inhalation solution

  • Flushing
  • Headache
  • Nausea
  • Throat irritation
  • Nasal discomfort

 

Warnings

Contraindications

Extended-release tablets: Severe hepatic impairment (Child Pugh Class C)

 

Cautions

Hepatic/renal impairment (titrate up slowly), concomitant anticoagulants (increased bleeding risk), lung infections, asthma/COPd

Dosage adjustment may be necessary if CYP2C8 inhibitors (eg, atazanavir, gemfibrozil, ritonavir) or inducers (eg, carbamazepine, phenobarbital, phenytoin, rifampin ) are added or withdrawn

Use caution in patients with low areterial 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

Use a lower dose for the initial dose in patients with mild-to-moderate hepatic insufficiency and titrate dose slowly

Not studied in renal impairment; use caution; titrate dose slowly

Abrupt withdrawal may worsen pulmonary arterial hypertension symptoms

Inhalation therapy not studied in patients with other types of pulmonary diseases (eg, COPD, asthma); monitor closely patients with pulmonary infections

Inhibits platelet aggregation and increases risk of bleeding; use caution in patients receiving concurrent anticoagulant/antiplatelet therapy

Indwelling central venous catherer associated with serious blood stream infections; use this method only in patients intolerant to the SC therapy

Experienced personnel required to administer therapy

 

Pregnancy and lactation

Pregnancy category: B

Lactation: Unknown if excreated in breast milk; use caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Tyvaso, Remodulin, Orenitram (treprostinil)

Mechanism of action

Peripheral prostacyclin vasodilator of both pulmonary and systemic arterial vascular bed; decreases ventricular afterload; also inhibits platelet aggregation

 

Absorption

Bioavailability: ~100% (SC); 64-72% (inhalation)

Peak plasma time: 10 hr

Peak plasma concentration: 2 mcg/L

 

Distribution

Protein bound: 91%

Vd: 14 L/70 kg (ideal body weight)

 

Metabolism

Metatoblized by liver

Metabolites: HU1-HU5

 

Elimination

Half-life: 2-4 hr

Total body clearance: 30 L/hr

Excretion: Urine (79% ); feces (13%)

 

Administration

SC/IV Administration

Administration by continuous SC infusion (undiluted) is preferred

May administer by IV infusion (dilution required) if SC infusion not tolerated

IV administration following dilution with a high pH glycine diluent (eg, sterile diluent for Flolan or sterile diluent for epoprostenol sodium) has been associated with a lower incidence of catheter-related infections compared to neutral diluents (sterile water, 0.9% sodium chloride) when used along with catheter care guidelines

Avoid abrupt discontinuation

 

Oral Administration Extended-release tablets

Administer with food

Swallow tablets whole; do not chew, crush, or split

Avoid abrupt discontinuation; when discontinuing, reduce dose by 0.5-1 mg/day increments

Missed doses

  • If 1 dose is missed, take the missed dose as soon as possible, with food
  • If ≥2 doses are missed, restart at a lower dose and retitrate
  • In the event of a planned short-term treatment interruption for patients unable to take oral medications, consider a temporary infusion of SC or IV treprostinil
  • Calculate the total daily dose (mg) of treprostinil for the parenteral route using the following equation
    • SC/IV dose (ng/kg/min) = 139 x oral daily dose (mg) ÷ weight (kg)