AdultPediatricDosage 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 Interaction CheckerEnter a drug name and treprostinilNo Results No Interactions Found Interactions FoundContraindicatedSerious - Use AlternativeSignificant - Monitor CloselyMinorAll Interactions Sort By: SeverityName Contraindicated (0)Serious - Use Alternative (1)lofexidinelofexidine, 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 (31)aldesleukinaldesleukin increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Risk of hypotension.amifostineamifostine, 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.candesartantreprostinil increases effects of candesartan by pharmacodynamic synergism. Use Caution/Monitor.cannabidiolcannabidiol 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.carbidopacarbidopa 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.dabigatrandabigatran and treprostinil both increase anticoagulation. Use Caution/Monitor. Both drugs have the potential to cause bleeding. Concomitant use may increase risk of bleeding.dichlorphenamidedichlorphenamide and treprostinil both decrease serum potassium. Use Caution/Monitor.eluxadolineeluxadoline increases levels of treprostinil by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 substrates.epoprostenolepoprostenol, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.eprosartantreprostinil increases effects of eprosartan by pharmacodynamic synergism. Use Caution/Monitor.fenoldopamfenoldopam, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.fish oil triglyceridesfish 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 teagreen tea, treprostinil. Other (see comment). Use Caution/Monitor. Comment: Combination may increase risk of bleeding.hydralazinehydralazine, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.ibrutinibibrutinib 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.iloprostiloprost, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.irbesartantreprostinil increases effects of irbesartan by pharmacodynamic synergism. Use Caution/Monitor.levodopalevodopa increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.losartantreprostinil increases effects of losartan by pharmacodynamic synergism. Use Caution/Monitor.maravirocmaraviroc, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Increased risk of orthostatic hypotension.mifepristonemifepristone 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 monitorminoxidilminoxidil, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.olmesartantreprostinil increases effects of olmesartan by pharmacodynamic synergism. Use Caution/Monitor.omaveloxoloneomaveloxolone will decrease the level or effect of treprostinil by Other (see comment). Use Caution/Monitor. Omaveloxolone may reduce systemic exposure of sensitive CYP2C8 substrates. Check prescribing information of substrate if dosage modification is needed. sacubitril/valsartantreprostinil increases effects of sacubitril/valsartan by pharmacodynamic synergism. Use Caution/Monitor.stiripentolstiripentol 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.tecovirimattecovirimat 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.telmisartantreprostinil increases effects of telmisartan by pharmacodynamic synergism. Use Caution/Monitor.teriflunomideteriflunomide increases levels of treprostinil by Other (see comment). Use Caution/Monitor. Comment: Teriflunomide inhibits CYP2C8; caution when coadministered with CYP2C8 substrates.valsartantreprostinil increases effects of valsartan by pharmacodynamic synergism. Use Caution/Monitor.xipamidexipamide increases effects of treprostinil by pharmacodynamic synergism. Use Caution/Monitor.Minor (82)acebutololtreprostinil increases effects of acebutolol by pharmacodynamic synergism. Minor/Significance Unknown.agrimonyagrimony increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.alfuzosintreprostinil increases effects of alfuzosin by pharmacodynamic synergism. Minor/Significance Unknown.amiloridetreprostinil increases effects of amiloride by pharmacodynamic synergism. Minor/Significance Unknown.amlodipinetreprostinil increases effects of amlodipine by pharmacodynamic synergism. Minor/Significance Unknown.asenapinetreprostinil increases effects of asenapine by pharmacodynamic synergism. Minor/Significance Unknown.atenololtreprostinil increases effects of atenolol by pharmacodynamic synergism. Minor/Significance Unknown.benazepriltreprostinil increases effects of benazepril by pharmacodynamic synergism. Minor/Significance Unknown. Enhanced hypotensive effects.bendroflumethiazidetreprostinil increases effects of bendroflumethiazide by pharmacodynamic synergism. Minor/Significance Unknown.betaxololtreprostinil increases effects of betaxolol by pharmacodynamic synergism. Minor/Significance Unknown.bisoprololtreprostinil increases effects of bisoprolol by pharmacodynamic synergism. Minor/Significance Unknown.bosentantreprostinil increases effects of bosentan by pharmacodynamic synergism. Minor/Significance Unknown.brimonidinebrimonidine increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.bumetanidetreprostinil increases effects of bumetanide by pharmacodynamic synergism. Minor/Significance Unknown.captopriltreprostinil increases effects of captopril by pharmacodynamic synergism. Minor/Significance Unknown. Both drugs lower blood pressure. Monitor blood pressure.carvediloltreprostinil increases effects of carvedilol by pharmacodynamic synergism. Minor/Significance Unknown.celiprololtreprostinil increases effects of celiprolol by pharmacodynamic synergism. Minor/Significance Unknown.chlorothiazidetreprostinil increases effects of chlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.chlorthalidonetreprostinil increases effects of chlorthalidone by pharmacodynamic synergism. Minor/Significance Unknown.clevidipinetreprostinil increases effects of clevidipine by pharmacodynamic synergism. Minor/Significance Unknown.clonidinetreprostinil increases effects of clonidine by pharmacodynamic synergism. Minor/Significance Unknown.cornsilkcornsilk increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.cyclopenthiazidetreprostinil increases effects of cyclopenthiazide by pharmacodynamic synergism. Minor/Significance Unknown.diltiazemtreprostinil increases effects of diltiazem by pharmacodynamic synergism. Minor/Significance Unknown.doxazosintreprostinil increases effects of doxazosin by pharmacodynamic synergism. Minor/Significance Unknown.drospirenonetreprostinil increases effects of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown.enalapriltreprostinil increases effects of enalapril by pharmacodynamic synergism. Minor/Significance Unknown.eplerenonetreprostinil increases effects of eplerenone by pharmacodynamic synergism. Minor/Significance Unknown.epoprostenoltreprostinil increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown.esmololtreprostinil increases effects of esmolol by pharmacodynamic synergism. Minor/Significance Unknown.ethacrynic acidtreprostinil increases effects of ethacrynic acid by pharmacodynamic synergism. Minor/Significance Unknown.felodipinetreprostinil increases effects of felodipine by pharmacodynamic synergism. Minor/Significance Unknown.fenoldopamtreprostinil increases effects of fenoldopam by pharmacodynamic synergism. Minor/Significance Unknown.forskolinforskolin increases effects of treprostinil by pharmacodynamic synergism. Minor/Significance Unknown.fosinopriltreprostinil increases effects of fosinopril by pharmacodynamic synergism. Minor/Significance Unknown.furosemidetreprostinil increases effects of furosemide by pharmacodynamic synergism. Minor/Significance Unknown.guanfacinetreprostinil increases effects of guanfacine by pharmacodynamic synergism. Minor/Significance Unknown.hydralazinetreprostinil increases effects of hydralazine by pharmacodynamic synergism. Minor/Significance Unknown.hydrochlorothiazidetreprostinil increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown.iloprosttreprostinil increases effects of iloprost by pharmacodynamic synergism. Minor/Significance Unknown.imidapriltreprostinil increases effects of imidapril by