Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (31)
- 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.
- omaveloxolone
omaveloxolone 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/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.
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
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
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.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
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
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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
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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
Images
Patient Handout
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 last or get worse, 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 you have any serious side effects, including: 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, liver problems, bleeding problems, other breathing problems (such as asthma, chronic obstructive pulmonary disease-COPD).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.
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.Lab and/or medical tests (such as blood pressure) may be done while you are using this medication. Keep all medical and lab appointments. 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.
Information last revised December 2022. Copyright(c) 2023 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.
Formulary
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.
