Orenitram
treprostinil · Tablet, Extended Release · Oral
Uses
Orenitram is a prostacyclin mimetic indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): To delay disease progression and to improve exercise capacity. The 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%). ( 1.1 ) 1.1 Pulmonary Arterial Hypertension Orenitram is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to delay disease progression and to improve exercise capacity. The 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%).
Dosage and administration
Give with food. Swallow tablets whole; use only intact tablets. ( 2.1 ) Starting dose: 0.125 mg TID or 0.25 mg BID. ( 2.1 ) Titrate by 0.125 mg TID or by 0.25 mg or 0.5 mg BID, not more frequently than every 3 to 4 days as tolerated. The maximum daily dose is 120 mg. ( 2.1 ) If transitioning from intravenous (IV) or subcutaneous (SC) Remodulin ® , the Orenitram dose should be increased while simultaneously decreasing the IV/SC infusion rate. ( 2.2 ) Mild hepatic impairment (Child Pugh Class A): Initiate at 0.125 mg BID. Increment at 0.125 mg BID not more frequently than every 3 to 4 days. ( 2.3 ) Avoid use in patients with moderate hepatic impairment. ( 2.3 ) 2.1 Recommended Dosing Take Orenitram with food. Swallow Orenitram tablets whole; do not crush, split, or chew. The recommended starting dose of Orenitram is 0.125 mg three times daily (TID) with food, taken approximately 8 hours apart or 0.25 mg twice daily (BID) with food, taken approximately 12 hours apart. Titrate by 0.125 mg TID or 0.25 or 0.5 mg BID not more frequently than every 3 to 4 days. Increase the dose to the highest tolerated dose. The recommended maximum daily dose is 120 mg. If dose increments are not tolerated, consider titrating slower. If intolerable pharmacologic effects occur, decrease the dose in increments of 0.125 mg TID or 0.25 mg BID. Avoid abrupt discontinuation [see Warnings and Precautions (5.1) ] . 2.2 Transitioning from Subcutaneous or Intravenous Routes of Administration of Treprostinil Decrease the dose of Remodulin while simultaneously increasing the dose of Orenitram. The dose of Remodulin can be reduced up to 30 ng/kg/min per day and the dose of Orenitram simultaneously increased up to 6 mg per day (2 mg TID) if tolerated. The following equation can be used to estimate a target total daily dose of Orenitram in mg using a patient's dose of intravenous (IV)/subcutaneous (SC) treprostinil (in ng/kg/min) and weight (in kg). Orenitram total daily dose (mg) = 0.0072 × Remodulin dose (ng/kg/min) × weight (kg) 2.3 Dose Adjustment in Patients with Hepatic Impairment In patients with mild hepatic impairment (Child Pugh Class A) start at 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days. Avoid use of Orenitram in patients with moderate hepatic impairment (Child Pugh Class B). Orenitram is contraindicated in patients with severe hepatic impairment (Child Pugh Class C) due to increases in systemic exposure [see Contraindications (4) , Use in Specific Populations (8.6) , and Clinical Pharmacology (12.3) ] . 2.4 Dose Adjustment for Use with CYP2C8 Inhibitors When co-administered with strong CYP2C8 inhibitors (e.g., gemfibrozil) the initial dose is 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days. 2.5 Interruptions and Discontinuation If a dose of medication is missed, the patient should take the missed dose as soon as possible, with food. If a patient misses two or more doses, restart at a lower dose and re-titrate. In the event of a planned short-term treatment interruption for patients unable to take oral medications, consider a temporary infusion of subcutaneous or intravenous treprostinil. To calculate the total daily dose (mg) of treprostinil for the parenteral route use the following equation: Remodulin (ng/kg/min) = 139 × Orenitram total daily dose (mg) weight (kg) When discontinuing Orenitram, reduce the dose in steps of 0.5 to 1 mg per day [see Warnings and Precautions (5.1) ] .
Dosage forms and strengths
Orenitram (treprostinil) extended-release tablets are available in the following five strengths: - 0.125 mg [White tablet imprinted with UT 0.125] - 0.25 mg [Green tablet imprinted with UT 0.25] - 1 mg [Yellow tablet imprinted with UT 1] - 2.5 mg [Pink tablet imprinted with UT 2.5] - 5 mg [Red tablet imprinted with UT 5] Extended-Release Tablets: 0.125 mg, 0.25 mg, 1 mg, 2.5 mg, and 5 mg. ( 3 )
Contraindications
Severe hepatic impairment (Child Pugh Class C) [see Use In Specific Populations (8.6) and Clinical Pharmacology (12.3) ] . Severe hepatic impairment (Child Pugh Class C). ( 4 )
Warnings and precautions
Do not abruptly discontinue dosing. ( 2.5 , 5.1 ) In patients with diverticulosis, Orenitram tablets can become lodged in a diverticulum. ( 5.2 ) 5.1 Worsening PAH Symptoms upon Abrupt Withdrawal Abrupt discontinuation or sudden large reductions in dosage of Orenitram may result in worsening of PAH symptoms. 5.2 Use in Patients with Blind-end Pouches The tablet shell does not dissolve. In patients with diverticulosis, Orenitram tablets can lodge in a diverticulum.
Side effects
Most common adverse reactions (incidence >10%) reported in clinical studies in patients treated with Orenitram compared with placebo are headache, diarrhea, nausea, vomiting, jaw pain, and flushing. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact United Therapeutics Corp. at 1-866-458-6479 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In a 12-week, placebo-controlled, monotherapy study (Study 1; WHO Group 1; functional class II-III), and an event-driven, placebo-controlled, combination therapy study (Study 4; WHO Group 1; functional class I-III), the most commonly reported adverse reactions that occurred in patients receiving Orenitram included: headache, diarrhea, nausea, and flushing. Orenitram patients in Study 1 (N=151) had access to 0.25 mg tablets at randomization. Approximately 91% of such patients in Study 1 experienced an adverse reaction, but only 4% discontinued therapy for an adverse reaction (compared to 3% receiving placebo). Study 4 enrolled a total of 690 patients, 346 received Orenitram and 344 received placebo. Overall, 19% of patients treated with Orenitram discontinued treatment in Study 4 due to an adverse event (compared to 4% of patients receiving placebo). The exposure to Orenitram in Study 4 was up to 5.1 years with a median duration of exposure of 1.2 years. Table 1 summarizes adverse events with rates at least 5% higher on Orenitram therapy than on placebo that were reported in either Study 1 or 4. Table 1: Adverse Events with Rates at Least 5% Higher on Orenitram Therapy than on Placebo in Either Study 1 or Study 4 Reaction Study 1 N=228 Includes all subjects in the Primary Analysis Population Study 4 N=690 Orenitram n=151 Placebo n=77 Orenitram n=346 Placebo n=344 Headache 63% 19% 75% 35% Diarrhea 30% 16% 69% 29% Nausea 30% 18% 40% 23% Vomiting 17% 16% 36% 10% Flushing 15% 6% 45% 8% Pain in jaw 11% 4% 18% 3% Pain in extremity 14% 8% 18% 9% Hypokalemia 9% 3% 4% 3% Abdominal discomfort 6% 0% 8% 4% Upper abdominal pain 5% 3% 12% 5% Orenitram was studied in a long-term, open-label, extension study in which 824 patients were dosed for a mean duration of approximately 2 years. About 70% of patients continued treatment with Orenitram for at least a year. The mean dose was 4.2 mg BID at one year. The adverse reactions were similar to those observed in the placebo-controlled trials. The safety of Orenitram was also evaluated in an open-label study transitioning patients from Remodulin. The safety profile during this study was similar to that observed in the three pivotal studies. 6.2 Post-Marketing Experience The following adverse reactions have been identified during postapproval use of Orenitram: dizziness, dyspepsia, vomiting, myalgia, and arthralgia. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Drug interactions
When co-administered with strong CYP2C8 inhibitors the initial dose is 0.125 mg BID with 0.125 mg BID dose increments not more frequently than every 3 to 4 days. ( 2.4 , 7.1 ) 7.1 Effect of CYP2C8 Inhibitors on Treprostinil Co-administration of Orenitram and the CYP2C8 enzyme inhibitor gemfibrozil in healthy adult volunteers increases exposure to treprostinil. Reduce the starting dose of Orenitram to 0.125 mg BID and use 0.125 mg BID increments not more frequently than every 3 to 4 days [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] .
Use in specific populations
8.1 Pregnancy Risk Summary Limited published data from case reports with Orenitram use in pregnant women are not sufficient to assess for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations ) . Animal reproductive studies with treprostinil diolamine administered orally have shown an adverse effect on the fetus. In rats, administration of treprostinil to pregnant rats during the period of organogenesis at doses ≥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 ≥1.5 mg/kg/day (approximately 7 times the human exposure at the dose of 3.5 mg BID on an AUC basis) (see Animal Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Pulmonary arterial hypertension in pregnancy increases the risk of maternal heart failure, stroke and death, preterm delivery, low birth weight, and stillbirth. Data Animal Data In pregnant rats, reversible, dose-dependent decreases in body weight gain and food consumption were observed during the first four days of dosing in animals administered 10, 20, and 30 mg/kg/day treprostinil diolamine. In a dose range-finding study, there was a 17% decrease in the pregnancy rate in the animals administered 20 and 30 mg/kg/day. One dam in each of the 20 and 30 mg/kg/day had litters with no viable fetuses. In the definitive study (0, 5, 10, and 20 mg/kg/day), there were four treatment-related deaths, and a 32% decrease in the pregnancy rate for rats administered 20 mg/kg/day. There was an 8% decrease in the pregnancy rate in the animals administered 10 mg/kg/day. Across both studies, an increase in post-implantation loss was observed in animals administered 10 to 30 mg/kg/day, and a significant decrease in the mean number of live births was seen at dose levels ≥10 mg/kg/day. The no observed adverse effect level was 5 mg/kg/day (maternal, fetal viability and growth), and 20 mg/kg/day (teratogenicity), the highest dose tested in the definitive study. The exposures at 5 and 20 mg/kg/day doses represent 8 and 33 times, respectively, the human exposure at the dose of 3.5 mg BID on an AUC basis. For F 1 progeny, a decreased copulation index was observed at the 5 and 10 mg/kg/day treprostinil diolamine dose levels in rats. The no observed effect levels for physical development, reflex development, exploratory behavior, learning and memory, and sexual maturation was 10 mg/kg/day. The no observed effect level for F 1 progeny general development (based on body weight) was 10 mg/kg/day for females and ≤2.5 mg/kg/day for males; the no observed effect level for F 1 reproductive performance was 2.5 mg/kg/day (approximately 4 times the human exposure at the dose of 3.5 mg BID on an AUC basis). In pregnant rabbits, the primary maternal adverse effect was gastrointestinal disturbance; dose-dependent decreases in mean body weight, body weight gain, and food consumption were observed. During the post-dose phase, the effect was reversed. In a dose range-finding study, there was a 17% decrease in the pregnancy rate for animals administered 4 mg/kg/day. A dose-dependent increase in post-implantation loss was observed. Two dams administered 4 mg/kg/day had litters with no viable fetuses; the mean fetal weight was slightly decreased in animals administered 4 mg/kg/day. In the definitive study, mean fetal weights were significantly decreased in animals administered 0.5 to 3 mg/kg/day of treprostinil diolamine. At doses of 1.5 and 3 mg/kg/day, external fetal and soft tissue malformations were observed in a few fetuses, and the total fetal skeletal malformations were significantly increased. The no observed adverse effect level was less than 0.5 mg/kg/day (maternal), 1.5 mg/kg/day (fetal viability and growth), and 0.5 mg/kg/day (teratogenicity). The 0.5 mg/kg/day dose represents about 3 times the human exposure at the dose of 3.5 mg BID on an AUC basis. 8.2 Lactation Risk Summary There are no data on the presence of treprostinil in human milk, the effects on the breastfed infant, or the effects on milk production. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic or cardiac function, and of concomitant disease or other drug therapy. 8.6 Patients with Hepatic Impairment There is a marked increase in the systemic exposure to treprostinil in hepatically impaired patients [see Dosage and Administration (2.3) , Contraindications (4) , and Clinical Pharmacology (12.3) ] . 8.7 Patients with Renal Impairment No dose adjustments are required in patients with renal impairment. Orenitram is not removed by dialysis [see Clinical Pharmacology (12.3) ] .
Pregnancy
8.1 Pregnancy Risk Summary Limited published data from case reports with Orenitram use in pregnant women are not sufficient to assess for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are risks to the mother and the fetus associated with pulmonary arterial hypertension (see Clinical Considerations ) . Animal reproductive studies with treprostinil diolamine administered orally have shown an adverse effect on the fetus. In rats, administration of treprostinil to pregnant rats during the period of organogenesis at doses ≥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 ≥1.5 mg/kg/day (approximately 7 times the human exposure at the dose of 3.5 mg BID on an AUC basis) (see Animal Data ) . The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Pulmonary arterial hypertension in pregnancy increases the risk of maternal heart failure, stroke and death, preterm delivery, low birth weight, and stillbirth. Data Animal Data In pregnant rats, reversible, dose-dependent decreases in body weight gain and food consumption were observed during the first four days of dosing in animals administered 10, 20, and 30 mg/kg/day treprostinil diolamine. In a dose range-finding study, there was a 17% decrease in the pregnancy rate in the animals administered 20 and 30 mg/kg/day. One dam in each of the 20 and 30 mg/kg/day had litters with no viable fetuses. In the definitive study (0, 5, 10, and 20 mg/kg/day), there were four treatment-related deaths, and a 32% decrease in the pregnancy rate for rats administered 20 mg/kg/day. There was an 8% decrease in the pregnancy rate in the animals administered 10 mg/kg/day. Across both studies, an increase in post-implantation loss was observed in animals administered 10 to 30 mg/kg/day, and a significant decrease in the mean number of live births was seen at dose levels ≥10 mg/kg/day. The no observed adverse effect level was 5 mg/kg/day (maternal, fetal viability and growth), and 20 mg/kg/day (teratogenicity), the highest dose tested in the definitive study. The exposures at 5 and 20 mg/kg/day doses represent 8 and 33 times, respectively, the human exposure at the dose of 3.5 mg BID on an AUC basis. For F 1 progeny, a decreased copulation index was observed at the 5 and 10 mg/kg/day treprostinil diolamine dose levels in rats. The no observed effect levels for physical development, reflex development, exploratory behavior, learning and memory, and sexual maturation was 10 mg/kg/day. The no observed effect level for F 1 progeny general development (based on body weight) was 10 mg/kg/day for females and ≤2.5 mg/kg/day for males; the no observed effect level for F 1 reproductive performance was 2.5 mg/kg/day (approximately 4 times the human exposure at the dose of 3.5 mg BID on an AUC basis). In pregnant rabbits, the primary maternal adverse effect was gastrointestinal disturbance; dose-dependent decreases in mean body weight, body weight gain, and food consumption were observed. During the post-dose phase, the effect was reversed. In a dose range-finding study, there was a 17% decrease in the pregnancy rate for animals administered 4 mg/kg/day. A dose-dependent increase in post-implantation loss was observed. Two dams administered 4 mg/kg/day had litters with no viable fetuses; the mean fetal weight was slightly decreased in animals administered 4 mg/kg/day. In the definitive study, mean fetal weights were significantly decreased in animals administered 0.5 to 3 mg/kg/day of treprostinil diolamine. At doses of 1.5 and 3 mg/kg/day, external fetal and soft tissue malformations were observed in a few fetuses, and the total fetal skeletal malformations were significantly increased. The no observed adverse effect level was less than 0.5 mg/kg/day (maternal), 1.5 mg/kg/day (fetal viability and growth), and 0.5 mg/kg/day (teratogenicity). The 0.5 mg/kg/day dose represents about 3 times the human exposure at the dose of 3.5 mg BID on an AUC basis.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Geriatric use
8.5 Geriatric Use Use of Orenitram in patients aged 65 years and over demonstrated slightly higher absolute and relative adverse event rates compared to younger patients. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic or cardiac function, and of concomitant disease or other drug therapy.
Overdosage
Signs and symptoms of overdose with Orenitram during clinical trials reflect its dose-limiting pharmacologic effects and include severe headache, nausea, vomiting, diarrhea, and hypotension. Treat supportively.
Description
Orenitram is an extended-release osmotic tablet for oral administration. Orenitram is formulated as the diolamine salt of treprostinil, a tricyclic benzindene analogue of prostacyclin. The chemical name is Acetic acid, 2-[[(1 R ,2 R ,3a S ,9a S )-2,3,3a,4,9,9a-hexahydro-2-hydroxy-1-[(3 S )-3-hydroxyoctyl]-1 H -benz[f]inden-5-yl]oxy]-, complexed with 2,2'-iminobis[ethanol] (1:1). The molecular formula is C 23 H 34 O 5 ∙C 4 H 11 NO 2 , the molecular weight is 495.65, and it has the following structural formula: Orenitram tablets are formulated in five strengths, which contain 0.125 mg of treprostinil (equivalent to 0.159 mg treprostinil diolamine), 0.25 mg of treprostinil (equivalent to 0.317 mg treprostinil diolamine), 1 mg of treprostinil (equivalent to 1.27 mg treprostinil diolamine), 2.5 mg of treprostinil (equivalent to 3.17 mg treprostinil diolamine), or 5 mg of treprostinil (equivalent to 6.35 mg treprostinil diolamine). The formulations also contain xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc. In addition, tablets may contain colorants FD&C Blue #2, iron oxide yellow, and iron oxide red. The imprint ink contains shellac glaze, ethanol, isopropyl alcohol USP, iron oxide black, n-butyl alcohol, and propylene glycol. Orenitram is designed to release treprostinil at a near zero-order rate using an osmotic tablet technology. The tablet core is coated with a semi-permeable membrane and has a laser-drilled aperture through the membrane. Upon contact with water (e.g., after ingestion), the core tablet absorbs water through the semi-permeable membrane. The water dissolves the water-soluble treprostinil diolamine and the water-soluble osmotic excipients, which creates hydrostatic pressure within the membrane, eventually forcing the drug across the membrane at a controlled rate. Chemical Structure
Mechanism of action
12.1 Mechanism of Action The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds, inhibition of platelet aggregation, and inhibition of smooth muscle cell proliferation.
How supplied
16.1 How Supplied Orenitram is an 8-mm round biconvex tablet with strength identified by color and print and supplied as follows: Strength Color Printing on Tablets NDC # 100-Count Bottle NDC # 10-Count Bottle NDC # 10-Count Carton (Unit-Dose Blister) 0.125 mg White UT 0.125 66302-300-01 66302-300-10 66302-300-02 0.25 mg Green UT 0.25 66302-302-01 66302-302-10 66302-302-02 1 mg Yellow UT 1 66302-310-01 66302-310-10 66302-310-02 2.5 mg Pink UT 2.5 66302-325-01 66302-325-10 66302-325-02 5 mg Red UT 5 66302-350-01 66302-350-10 66302-350-02 Titration Kits for Orenitram are supplied in the following configurations: Titration Kit Blister Configurations NDC # Month 1 containing four weekly cartons Seven daily wallet blister packs in each weekly carton containing the following total number of tablets: Week 1 (twenty-one × 0.125 mg tablets) Week 2 (forty-two × 0.125 mg tablets) Week 3 (twenty-one × 0.125 mg tablets and twenty-one × 0.25 mg tablets) Week 4 (forty-two × 0.125 mg tablets and twenty-one × 0.25 mg tablets) 66302-361-28 Month 2 containing four weekly cartons Seven daily wallet blister packs in each weekly carton containing the following total number of tablets: Week 5 (twenty-one × 0.125 mg tablets and forty-two × 0.25 mg tablets) Week 6 (forty-two × 0.125 mg tablets and forty-two × 0.25 mg tablets) Week 7 (twenty-one × 0.125 mg tablets and sixty-three × 0.25 mg tablets) Week 8 (forty-two × 0.125 mg tablets and sixty-three × 0.25 mg tablets) 66302-362-56 Month 3 containing four weekly cartons Seven daily wallet blister packs in each weekly carton containing the following total number of tablets: Week 9 (twenty-one × 0.125 mg tablets and twenty-one × 1 mg tablets) Week 10 (forty-two × 0.125 mg tablets and twenty-one × 1 mg tablets) Week 11 (twenty-one × 0.125 mg tablets, twenty-one × 0.25 mg tablets, and twenty-one × 1 mg tablets) Week 12 (forty-two × 0.125 mg tablets, twenty-one × 0.25 mg tablets, and twenty-one × 1 mg tablets) 66302-363-84 16.2 Storage Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep out of reach of children.
Storage
16.2 Storage Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Keep out of reach of children.
Patient information
See FDA-approved patient labeling (Patient Information) . Tell patients: Abrupt discontinuation of therapy could result in worsening of PAH symptoms. Take Orenitram with food. Swallow Orenitram tablets whole. Do not split, chew, crush, or break. Do not take a tablet that is damaged or broken. The biologically inert components of the tablet remain intact during gastrointestinal transit and are eliminated in the feces as an insoluble shell.
Label text from the FDA structured product label by United Therapeutics Corporation (revised Nov 20, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Treprostinil in 5 products
Orenitram NDC products (8)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 66302-300 | Treprostinil .125 mg/1 Tablet, Extended Release | United Therapeutics Corporation | NDA |
| 66302-302 | Treprostinil .25 mg/1 Tablet, Extended Release | United Therapeutics Corporation | NDA |
| 66302-310 | Treprostinil 1 mg/1 Tablet, Extended Release | United Therapeutics Corporation | NDA |
| 66302-325 | Treprostinil 2.5 mg/1 Tablet, Extended Release | United Therapeutics Corporation | NDA |
| 66302-350 | Treprostinil 5 mg/1 Tablet, Extended Release | United Therapeutics Corporation | NDA |
| 66302-361 | Kit | United Therapeutics Corporation | NDA |
| 66302-362 | Kit | United Therapeutics Corporation | NDA |
| 66302-363 | Kit | United Therapeutics Corporation | NDA |
Frequently asked questions
What is Orenitram used for?
Orenitram is a prostacyclin mimetic indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1): To delay disease progression and to improve exercise capacity. The 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…
What are the side effects of Orenitram?
Most common adverse reactions (incidence >10%) reported in clinical studies in patients treated with Orenitram compared with placebo are headache, diarrhea, nausea, vomiting, jaw pain, and flushing. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact United Therapeutics Corp. at 1-866-458-6479 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical… See the full label for the complete list.
Who makes Orenitram?
Orenitram is listed by 1 labeler in the FDA NDC directory, including United Therapeutics Corporation.