treprostinil (Rx)

Brand and Other Names:Remodulin, Orenitram
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable solution (Remodulin)

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

tablet, extended-release (Orenitram)

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

Pulmonary Arterial Hypertension

Injectable

  • Indicated for treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise
  • Patients who require transition from epoprostenol, to reduce the rate of clinical deterioration; carefully consider the risks and benefits of each drug prior to transition
  • 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 qWeek x first 4 weeks, then no more than 2.5 ng/kg/min qWeek
  • Little experience with doses >40 ng/kg/min

Extended-release tablets

  • Indicated for treatment of PAH (WHO Group 1) to delay disease progression and to improve exercise capacity
  • Initial: 0.125 mg PO TID or 0.25 mg PO BID
  • Titrate by 0.125 mg TID or 0.25 or 0.5 mg BID not more frequently than every 3-4 days
  • Increase dose to the highest tolerated dose
  • If dose increments are not tolerated, consider titrating slower
  • If intolerable pharmacologic effects occur, decrease dose in increments of 0.125 mg TID or 0.25 mg BID
  • Avoid abrupt discontinuation
  • Studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%)

Transition from epoprostenol to treprostinil

  • Remodulin only
  • Initiate treprostinil infusion and begin increasing it, while simultaneously reducing the IV epoprostenol dose
  • Transition should take place in a hospital with constant observation of response (eg, walk distance and signs and symptoms of disease progression)
  • Individually titrate dose that allows transition from epoprostenol therapy to treprostinil while balancing prostacyclin-limiting adverse events
  • Treat increases in the patient’s symptoms of PAH first with increases in the dose of treprostinil
  • Treat side effects normally associated with prostacyclin and prostacyclin analogs first by decreasing the dose of epoprostenol.
  • Recommended transition dose changes
    • Step 1: Epoprostenol dose remains unchanged; treprostinil is 10% of epoprostenol dose
    • Step 2: Epoprostenol dose is 80% of starting epoprostenol dose; treprostinil is 30% of epoprostenol dose
    • Step 3: Epoprostenol dose is 60% of starting epoprostenol dose; treprostinil is 50% of epoprostenol dose
    • Step 4: Epoprostenol dose is 40% of starting epoprostenol dose; treprostinil is 70% of epoprostenol dose
    • Step 5: Epoprostenol dose is 20% of starting epoprostenol dose; treprostinil is 90% of epoprostenol dose
    • Step 6: Epoprostenol dose is 5% of starting epoprostenol dose; treprostinil is 110% of epoprostenol dose
    • Step 7: Epoprostenol dose is discontinued; treprostinil is 110% starting epoprostenol dose + additional 5-10% increments as needed

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

  • Injectable
    • No dose adjustment necessary
  • Extended-release tablets
    • No dosage adjustment necessary
    • Not removed by dialysis

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
  • 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

Dosing considerations

Transition from SC/IV to oral

  • Decrease SC/IV dose while simultaneously increasing the oral dose
  • May reduce SC/IV dose up to 30 ng/kg/min per day and simultaneously increase oral dose 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 Forms & Strengths

injectable solution (Remodulin)

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

Pulmonary Arterial Hypertension

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

<18 years (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

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
  • 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

and treprostinil

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            Contraindicated (0)

              Serious - Use Alternative (1)

              • lofexidine

                lofexidine, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Avoid coadministration with other drugs that decrease pulse or blood pressure to mitigate risk of excessive bradycardia and hypotension.

              Monitor Closely (30)

              • aldesleukin

                aldesleukin increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.

              • amifostine

                amifostine, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Coadministration with blood pressure lowering agents may increase the risk and severity of hypotension associated with amifostine. When amifostine is used at chemotherapeutic doses, withhold blood pressure lowering medications for 24 hr prior to amifostine; if blood pressure lowering medication cannot be withheld, do not administer amifostine.

              • candesartan

                treprostinil increases effects of candesartan by pharmacodynamic synergism. Use Caution/Monitor.

              • cannabidiol

                cannabidiol will increase the level or effect of treprostinil by decreasing metabolism. Modify Therapy/Monitor Closely. Cannabidiol may potentially inhibit CYP2C8 activity. Consider reducing the dose when concomitantly using CYP2C8 substrates.

              • carbidopa

                carbidopa increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Therapy with carbidopa, given with or without levodopa or carbidopa-levodopa combination products, is started, dosage adjustment of the antihypertensive drug may be required.

              • dabigatran

                dabigatran and treprostinil both increase anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.

              • dichlorphenamide

                dichlorphenamide and treprostinil both decrease serum potassium. Use Caution/Monitor.

              • eluxadoline

                eluxadoline increases levels of treprostinil by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 substrates.

              • epoprostenol

                epoprostenol, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

              • eprosartan

                treprostinil increases effects of eprosartan by pharmacodynamic synergism. Use Caution/Monitor.

              • fenoldopam

                fenoldopam, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

              • fish oil triglycerides

                fish oil triglycerides will increase the level or effect of treprostinil by anticoagulation. Use Caution/Monitor. Prolonged bleeding reported in patients taking antiplatelet agents or anticoagulants and oral omega-3 fatty acids. Periodically monitor bleeding time in patients receiving fish oil triglycerides and concomitant antiplatelet agents or anticoagulants.

              • green tea

                green tea, treprostinil. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.

              • hydralazine

                hydralazine, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

              • ibrutinib

                ibrutinib will increase the level or effect of treprostinil by anticoagulation. Use Caution/Monitor. Ibrutinib may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies and monitor for signs of bleeding.

              • iloprost

                iloprost, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

              • irbesartan

                treprostinil increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor.

              • levodopa

                levodopa increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.

              • losartan

                treprostinil increases effects of losartan by pharmacodynamic synergism. Use Caution/Monitor.

              • maraviroc

                maraviroc, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.

              • mifepristone

                mifepristone will increase the level or effect of treprostinil by Other (see comment). Use Caution/Monitor. Inhibits CYP2C8/2C9; use smallest recommended doses for substrates and monitor

              • minoxidil

                minoxidil, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.

              • olmesartan

                treprostinil increases effects of olmesartan by pharmacodynamic synergism. Use Caution/Monitor.

              • sacubitril/valsartan

                treprostinil increases effects of sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor.

              • stiripentol

                stiripentol will increase the level or effect of treprostinil by Other (see comment). Modify Therapy/Monitor Closely. Stiripentol is a CYP2C8 inhibitor. Consider dosage reduction for CYP2C8 substrates if adverse effects are experienced when coadministered.

              • tecovirimat

                tecovirimat will increase the level or effect of treprostinil by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Tecovirimat is a weak inhibitor of CYP2C8 and CYP2C19. Monitor for adverse effects if coadministered with sensitive substrates of these enzymes.

              • telmisartan

                treprostinil increases effects of telmisartan by pharmacodynamic synergism. Use Caution/Monitor.

              • teriflunomide

                teriflunomide increases levels of treprostinil by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.

              • valsartan

                treprostinil increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.

              • xipamide

                xipamide increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor.

              Minor (82)

              • acebutolol

                treprostinil increases effects of acebutolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • agrimony

                agrimony increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.

              • alfuzosin

                treprostinil increases effects of alfuzosin by pharmacodynamic synergism. Minor/Significance Unknown.

              • amiloride

                treprostinil increases effects of amiloride by pharmacodynamic synergism. Minor/Significance Unknown.

              • amlodipine

                treprostinil increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • asenapine

                treprostinil increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.

              • atenolol

                treprostinil increases effects of atenolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • benazepril

                treprostinil increases effects of benazepril by pharmacodynamic synergism. Minor/Significance Unknown. Enhanced hypotensive effects.

              • bendroflumethiazide

                treprostinil increases effects of bendroflumethiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              • betaxolol

                treprostinil increases effects of betaxolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • bisoprolol

                treprostinil increases effects of bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • bosentan

                treprostinil increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.

              • brimonidine

                brimonidine increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.

              • bumetanide

                treprostinil increases effects of bumetanide by pharmacodynamic synergism. Minor/Significance Unknown.

              • captopril

                treprostinil increases effects of captopril by pharmacodynamic synergism. Minor/Significance Unknown. Both drugs lower blood pressure. Monitor blood pressure.

              • carvedilol

                treprostinil increases effects of carvedilol by pharmacodynamic synergism. Minor/Significance Unknown.

              • celiprolol

                treprostinil increases effects of celiprolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • chlorothiazide

                treprostinil increases effects of chlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              • chlorthalidone

                treprostinil increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.

              • clevidipine

                treprostinil increases effects of clevidipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • clonidine

                treprostinil increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • cornsilk

                cornsilk increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.

              • cyclopenthiazide

                treprostinil increases effects of cyclopenthiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              • diltiazem

                treprostinil increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.

              • doxazosin

                treprostinil increases effects of doxazosin by pharmacodynamic synergism. Minor/Significance Unknown.

              • drospirenone

                treprostinil increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.

              • enalapril

                treprostinil increases effects of enalapril by pharmacodynamic synergism. Minor/Significance Unknown.

              • eplerenone

                treprostinil increases effects of eplerenone by pharmacodynamic synergism. Minor/Significance Unknown.

              • epoprostenol

                treprostinil increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown.

              • esmolol

                treprostinil increases effects of esmolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • ethacrynic acid

                treprostinil increases effects of ethacrynic acid by pharmacodynamic synergism. Minor/Significance Unknown.

              • felodipine

                treprostinil increases effects of felodipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • fenoldopam

                treprostinil increases effects of fenoldopam by pharmacodynamic synergism. Minor/Significance Unknown.

              • forskolin

                forskolin increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.

              • fosinopril

                treprostinil increases effects of fosinopril by pharmacodynamic synergism. Minor/Significance Unknown.

              • furosemide

                treprostinil increases effects of furosemide by pharmacodynamic synergism. Minor/Significance Unknown.

              • guanfacine

                treprostinil increases effects of guanfacine by pharmacodynamic synergism. Minor/Significance Unknown.

              • hydralazine

                treprostinil increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.

              • hydrochlorothiazide

                treprostinil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              • iloprost

                treprostinil increases effects of iloprost by pharmacodynamic synergism. Minor/Significance Unknown.

              • imidapril

                treprostinil increases effects of imidapril by pharmacodynamic synergism. Minor/Significance Unknown.

              • indapamide

                treprostinil increases effects of indapamide by pharmacodynamic synergism. Minor/Significance Unknown.

              • isradipine

                treprostinil increases effects of isradipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • ketanserin

                treprostinil increases effects of ketanserin by pharmacodynamic synergism. Minor/Significance Unknown.

              • labetalol

                treprostinil increases effects of labetalol by pharmacodynamic synergism. Minor/Significance Unknown.

              • lisinopril

                treprostinil increases effects of lisinopril by pharmacodynamic synergism. Minor/Significance Unknown.

              • maitake

                maitake increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).

              • mecamylamine

                treprostinil increases effects of mecamylamine by pharmacodynamic synergism. Minor/Significance Unknown.

              • methyclothiazide

                treprostinil increases effects of methyclothiazide by pharmacodynamic synergism. Minor/Significance Unknown.

              • metolazone

                treprostinil increases effects of metolazone by pharmacodynamic synergism. Minor/Significance Unknown.

              • metoprolol

                treprostinil increases effects of metoprolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • minoxidil

                treprostinil increases effects of minoxidil by pharmacodynamic synergism. Minor/Significance Unknown.

              • moexipril

                treprostinil increases effects of moexipril by pharmacodynamic synergism. Minor/Significance Unknown.

              • moxisylyte

                treprostinil increases effects of moxisylyte by pharmacodynamic synergism. Minor/Significance Unknown.

              • moxonidine

                treprostinil increases effects of moxonidine by pharmacodynamic synergism. Minor/Significance Unknown.

              • nadolol

                treprostinil increases effects of nadolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • nebivolol

                treprostinil increases effects of nebivolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • nicardipine

                treprostinil increases effects of nicardipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • nifedipine

                treprostinil increases effects of nifedipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • nisoldipine

                treprostinil increases effects of nisoldipine by pharmacodynamic synergism. Minor/Significance Unknown.

              • penbutolol

                treprostinil increases effects of penbutolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • perindopril

                treprostinil increases effects of perindopril by pharmacodynamic synergism. Minor/Significance Unknown.

              • phenoxybenzamine

                treprostinil increases effects of phenoxybenzamine by pharmacodynamic synergism. Minor/Significance Unknown.

              • phentolamine

                treprostinil increases effects of phentolamine by pharmacodynamic synergism. Minor/Significance Unknown.

              • pindolol

                treprostinil increases effects of pindolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • prazosin

                treprostinil increases effects of prazosin by pharmacodynamic synergism. Minor/Significance Unknown.

              • propranolol

                treprostinil increases effects of propranolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • quinapril

                treprostinil increases effects of quinapril by pharmacodynamic synergism. Minor/Significance Unknown.

              • ramipril

                treprostinil increases effects of ramipril by pharmacodynamic synergism. Minor/Significance Unknown.

              • reishi

                reishi increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.

              • shepherd's purse

                shepherd's purse, treprostinil. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.

              • silodosin

                treprostinil increases effects of silodosin by pharmacodynamic synergism. Minor/Significance Unknown.

              • sotalol

                treprostinil increases effects of sotalol by pharmacodynamic synergism. Minor/Significance Unknown.

              • spironolactone

                treprostinil increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown.

              • terazosin

                treprostinil increases effects of terazosin by pharmacodynamic synergism. Minor/Significance Unknown.

              • timolol

                treprostinil increases effects of timolol by pharmacodynamic synergism. Minor/Significance Unknown.

              • tizanidine

                tizanidine increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.

              • torsemide

                treprostinil increases effects of torsemide by pharmacodynamic synergism. Minor/Significance Unknown.

              • trandolapril

                treprostinil increases effects of trandolapril by pharmacodynamic synergism. Minor/Significance Unknown.

              • triamterene

                treprostinil increases effects of triamterene by pharmacodynamic synergism. Minor/Significance Unknown.

              • verapamil

                treprostinil increases effects of verapamil by pharmacodynamic synergism. Minor/Significance Unknown.

              • zotepine

                treprostinil increases effects of zotepine by pharmacodynamic synergism. Minor/Significance Unknown.

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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%)

              Frequency Not Defined

              Angioedema

              Bone pain

              Restlessness

              Cellulitis

              Haemoptysis

              Postmarketing Reports

              Dyspepsia

              Vomiting

              Myalgia/muscle spasm

              Arthralgia

              Syncope

              Pain extremity

              Gastrointestinal effects

              Injectable

              • Thrombophlebitis associated with peripheral IV infusion, thrombocytopenia, bone pain, pruritus, dizziness, arthralgia, myalgia/muscle spasm, and pain in extremity
              • Generalized rashes, sometimes macular or papular in nature, and cellulitis have been infrequently reported
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              Warnings

              Contraindications

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

              Injectable: None

              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 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

              Drug interactions overview

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

              Pregnancy

              Limited case reports of treprostinil insufficient to inform a drug-associated risk of adverse developmental outcomes; however, there are risks to 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

              Animal data

              • Animal reproductive studies have shown an adverse effect on fetus; in rats, administration to pregnant rats during period of organogenesis at doses greater than or equal to 10 mg/kg/day (approximately 15 times the human exposure at the dose of 3.5 mg BID on an AUC basis) resulted in decreased pregnancy rate, increased post-implantation loss, and decreased fetal viability and growth
              • In rabbits, teratogenicity and decreased fetal viability and growth were observed at doses greater than or equal to 1.5 mg/kg/day (approximately 7 times the human exposure at dose of 3.5 mg BID on an AUC basis)

              Lactation

              There are no data on presence of treprostinil in human milk, effects on breastfed infant, or on milk production

              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.

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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 infusion)

              Peak plasma time: ~10 hr (SC infusion)

              Concentrations in patients treated with an average dose of 9.3 ng/kg/min SC were ~2000 ng/L

              Distribution

              Protein bound: 91%

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

              Metabolism

              Metabolized by liver, primarily by CYP2C8

              Metabolites: HU1-HU5

              Elimination

              Half-life: ~4 hr

              Total body clearance: 30 L/hr (based on 70 kg person)

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

              Five metabolites were detected in the urine (10-16%) and representing 64% of the dose administered

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              Administration

              SC/IV Preparation

              Visually inspect for particulate matter and discoloration prior to administration

              Administer by SC or IV infusion only

              Refer to Remodulin prescribing information for dosing calculations

              SC/IV Administration

              SC infusion

              • Treprostinil is preferably infused SC, but can be administered by a central IV line if the SC route is not tolerated because of severe site pain or reaction
              • Administer SC by continuous infusion, via a SC catheter, using an infusion pump designed for SC drug delivery
              • Infusion pump should be adjustable to ~0.002 mL/hour, have occlusion/no delivery, low battery, programming error and motor malfunction alarms, have delivery accuracy of ±6% or better, be positive pressure-driven, and have a reservoir made of polyvinyl chloride, polypropylene or glass
              • Alternatively, use an infusion pump cleared for use with treprostinil
              • Avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and SC infusion sets

              External IV infusion pump

              • Administer IV by continuous infusion via a surgically placed indwelling central venous catheter using an external infusion pump designed for IV drug delivery
              • If clinically necessary, a temporary peripheral IV cannula, preferably placed in a large vein, may be used for short term administration
              • Use of a peripheral IV infusion for more than a few hours increases the risk of thrombophlebitis
              • Infusion pump should have occlusion/no delivery, low battery, programming error and motor malfunction alarms, have delivery accuracy of ±6% or better of the hourly dose, be positive pressure driven, and have a reservoir made of polyvinyl chloride, polypropylene or glass
              • Alternatively, use an infusion pump cleared for use with treprostinil
              • To avoid potential interruptions in drug delivery, patient must have immediate access to a backup infusion pump and infusion sets Use infusion sets with an in-line 0.22 or 0.2 micron pore size filter

              Implantable IV infusion pump

              • Use an implantable IV infusion pump approved for use with treprostinil (eg, Implantable System for Remodulin [ISR])
              • Refer to the pump manufacturer’s manual for specific instructions regarding preparation, programing, implantation, and refilling

              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 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

              Storage

              Tablets

              • Store at 25°C (77°F); excursions are permitted between 15-30°C (59-86°F)

              SC/IV

              • Unopened vials
                • Store at 25°C (77°F), with excursions permitted to 2-30°C (36-86°F)
                • A single vial should be used for ≤30 days after the initial introduction into the vial
              • Diluted solutions
                • Sterile diluents for Remodulin: Store at room temperature for up to 14 days and can be used within 48 hr at 40°C
                • Sterile water for injection or 0.9% NaCl: Store at room temperature for up to 4 hr or 24 hr refrigerated and can be used within 48 hr at 40°C
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              Patient Handout

              Patient Education
              treprostinil inhalation

              TREPROSTINIL SOLUTION - INHALATION

              (tre-PROST-i-nil)

              COMMON BRAND NAME(S): Tyvaso

              USES: This medication is used to treat a type of high blood pressure in the lungs (pulmonary arterial hypertension). Treprostinil helps to increase your ability to exercise and improves symptoms such as shortness of breath and tiredness. It works by relaxing and widening the blood vessels (arteries) in the lungs and other parts of the body so that blood can flow more easily. This medication belongs to a class of drugs known as vasodilators.

              HOW TO USE: Read the Patient Information leaflet available from your pharmacist. This medication comes in a plastic container called an ampule. Follow the manufacturer's instructions on how to prepare each dose. This product is used with a special breathing device (nebulizer). Consult your doctor, pharmacist or respiratory therapist on how to inhale this medication properly with this equipment. Make sure you understand how to properly clean the nebulizer to prevent infections. If you have any questions, consult your health care professional.Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Do not mix with other inhaled medications in the nebulizer.Inhale this medication by mouth as directed by your doctor, usually 4 times daily during waking hours, at least 4 hours apart. Do not drink the solution. Do not get this medication on the skin or in your eye. If this happens, rinse the area with water. The dosage is based on your medical condition and response to treatment.Use this medication regularly to get the most benefit from it. To help you remember, use it at the same times each day.To avoid missing doses, be sure to have a back-up nebulizer in case your regular device stops working properly.Tell your doctor if your condition does not improve or if it worsens.

              SIDE EFFECTS: Cough, headache, throat irritation, nausea, flushing, dizziness, or jaw/muscle/bone pain may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly. Fainting is another common side effect. If fainting does occur, get medical help right away.To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.Remember that this medication has been prescribed because your doctor has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if any of these unlikely but serious side effects occur: unusual bleeding/bruising.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

              PRECAUTIONS: Before using treprostinil, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: low blood pressure, kidney problems, liver problems, bleeding problems, other breathing problems (such as asthma).This drug may make you dizzy. Alcohol or marijuana (cannabis) can make you more dizzy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Limit alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.It is unknown if this drug passes into breast milk. Consult your doctor before breast-feeding.

              DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.Treprostinil may lower your blood pressure. Your doctor may also direct you to take other medications that may also lower your blood pressure (such as "water pills"/diuretics such as furosemide, ACE inhibitors such as captopril, calcium channel blockers such as nifedipine, other vasodilators such as nitrates). Your doctor may also prescribe "blood thinners" (such as warfarin) to prevent blood clots. Treprostinil may increase your risk of bleeding if you take "blood thinners." Your doctor or pharmacist will monitor you for these possible drug interactions. Tell your doctor or pharmacist right away if you develop symptoms such as easy or unusual bleeding/bruising, severe dizziness, or fainting.

              OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe dizziness, fainting.

              NOTES: Do not share this medication with others.Laboratory and/or medical tests (such as blood pressure) may be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

              MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose. Use your next dose at the regular time. Do not double the dose to catch up.

              STORAGE: Store at room temperature away from light and moisture. Once the foil pack is opened, the ampules should be used within 7 days. After an ampule has been opened, discard any unused solution at the end of the day. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

              Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

              IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              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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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.