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treprostinil (Rx)Brand and Other Names:Tyvaso, Remodulin, more...Orenitram

 
 
 

Dosing & Uses

AdultPediatric

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
more...

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
more...

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
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Interactions

Interaction Checker

treprostinil and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            Sort by :  
             activity indicator 
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            Adverse 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
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            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

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            Pregnancy & 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.

            more...
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            Pharmacology

            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%)

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            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)
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            Images

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            Formulary

            FormularyPatient Discounts

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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