Application 203496

Type
NDA
Sponsor
UNITED THERAP

Application Products#

Product, Drug, Ingredient table
ProductDrugIngredientFormStrengthReference drugReference standard
001ORENITRAMTREPROSTINIL DIOLAMINETABLET, EXTENDED RELEASE;ORALEQ 0.125MG BASEYesNo
002ORENITRAMTREPROSTINIL DIOLAMINETABLET, EXTENDED RELEASE;ORALEQ 0.25MG BASEYesNo
003ORENITRAMTREPROSTINIL DIOLAMINETABLET, EXTENDED RELEASE;ORALEQ 1MG BASEYesYes
004ORENITRAMTREPROSTINIL DIOLAMINETABLET, EXTENDED RELEASE;ORALEQ 2.5MG BASEYesNo
005ORENITRAMTREPROSTINIL DIOLAMINETABLET, EXTENDED RELEASE;ORALEQ 5MG BASEYesNo

Orange Book products#

Application-product, Trade name, Ingredient table
Application-productTrade nameIngredientStrengthDosage form / routeTE codesRLD / RSApproval date
N203496-001ORENITRAMTREPROSTINIL DIOLAMINEEQ 0.125MG BASETABLET, EXTENDED RELEASE / ORALRLD2013-12-20
N203496-002ORENITRAMTREPROSTINIL DIOLAMINEEQ 0.25MG BASETABLET, EXTENDED RELEASE / ORALRLD2013-12-20
N203496-003ORENITRAMTREPROSTINIL DIOLAMINEEQ 1MG BASETABLET, EXTENDED RELEASE / ORALRLD, RS2013-12-20
N203496-004ORENITRAMTREPROSTINIL DIOLAMINEEQ 2.5MG BASETABLET, EXTENDED RELEASE / ORALRLD2013-12-20
N203496-005ORENITRAMTREPROSTINIL DIOLAMINEEQ 5MG BASETABLET, EXTENDED RELEASE / ORALRLD2016-10-07

Orange Book patents#

Application-product, Patent, Expiration table
Application-productPatentExpirationUse codeCoverage / statusSubmission date
N203496-00193932032026-04-27U-1877Drug product2016-07-22
N203496-00174170702026-07-30Drug substance2014-01-09
N203496-001117238872028-12-15Drug substance2023-08-15
N203496-00195930662028-12-15Drug substance2017-03-14
N203496-00196049012028-12-15Drug substance, Delist requested2017-03-28
N203496-00184101692030-02-13Drug product2014-01-09
N203496-00183498922031-01-22Drug product2014-01-09
N203496-00187478972031-08-11U-2725Drug product2014-06-13
N203496-00187478972031-08-11U-2724Drug product2014-06-13
N203496-00293932032026-04-27U-1877Drug product2016-07-22
N203496-00274170702026-07-30Drug substance2014-01-09
N203496-002117238872028-12-15Drug substance2023-08-15
N203496-00284973932028-12-15Drug substance, Delist requested2014-01-09
N203496-00295930662028-12-15Drug substance2017-03-14
N203496-00284101692030-02-13Drug product2014-01-09
N203496-00283498922031-01-22Drug product2014-01-09
N203496-00287478972031-08-11U-2725Drug product2014-06-13
N203496-00287478972031-08-11U-2724Drug product2014-06-13
N203496-00393932032026-04-27U-1877Drug product2016-07-22
N203496-00374170702026-07-30Drug substance2014-01-09
N203496-003117238872028-12-15Drug substance2023-08-15
N203496-00384973932028-12-15Drug substance, Delist requested2014-01-09
N203496-00395930662028-12-15Drug substance2017-03-14
N203496-00384101692030-02-13Drug product2014-01-09
N203496-00383498922031-01-22Drug product2014-01-09
N203496-00387478972031-08-11U-2725Drug product2014-06-13
N203496-00387478972031-08-11U-2724Drug product2014-06-13
N203496-00493932032026-04-27U-1877Drug product2016-07-22
N203496-00474170702026-07-30Drug substance2014-01-09
N203496-004117238872028-12-15Drug substance2023-08-15
N203496-00484973932028-12-15Drug substance, Delist requested2014-01-09
N203496-00495930662028-12-15Drug substance2017-03-14
N203496-00484101692030-02-13Drug product2014-01-09
N203496-00483498922031-01-22Drug product2014-01-09
N203496-00487478972031-08-11U-2724Drug product2014-06-13
N203496-00487478972031-08-11U-2725Drug product2014-06-13
N203496-00593932032026-04-27U-1877Drug product2017-02-09
N203496-00574170702026-07-30Drug substance2017-02-09
N203496-005117238872028-12-15Drug substance2023-08-15
N203496-00595930662028-12-15Drug substance2017-03-14
N203496-00596049012028-12-15Drug substance, Delist requested2017-03-28
N203496-00584101692030-02-13Drug product2017-02-09
N203496-00583498922031-01-22Drug product2017-02-09
N203496-00587478972031-08-11U-2725Drug product2017-02-09
N203496-00587478972031-08-11U-2724Drug product2017-02-09

Orange Book exclusivity#

Application-product, Exclusivity code, Expiration table
Application-productExclusivity codeExpiration
N203496-001ODE-2722026-10-18
N203496-002ODE-2722026-10-18
N203496-003ODE-2722026-10-18
N203496-004ODE-2722026-10-18
N203496-005ODE-2722026-10-18

openFDA label cross-check#

Cross-check layer: openFDA label JSON enriches search and identifies hydration gaps. The DailyMed Structured Product Label remains the canonical label presentation on FDA.report.

Brand, Generic, Manufacturer table
BrandGenericManufacturerSPL set IDEffective dateAvailable safety fieldsJoin
OrenitramTREPROSTINILUnited Therapeutics Corporation8ed2003a-c801-411e-831e-d06079bb0d7c2024-11-20Warnings, Adverse reactionsExact identifier

Warnings cross-check#

openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.

warnings and cautions

5 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.

Adverse reactions cross-check#

openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.

adverse reactions

6 ADVERSE REACTIONS 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 w...

adverse reactions table

Table 1: Adverse Events with Rates at Least 5% Higher on Orenitram Therapy than on Placebo in Either Study 1 or Study 4ReactionStudy 1 N=228Includes all subjects in the Primary Analysis PopulationStudy 4 N=690Orenitram n=151Placebo n=77Orenitram n=346Placebo n=344Headache63%19%75%35%Diarrhea30%16%69%29%Nausea30%18%40%23%Vomiting17%16%36%10%Flushing15%6%45%8%Pain in jaw11%4%18%3%Pain in extremity14%8%18%9%Hypokalemia9%3%4%3%Abdominal discomfort6%0%8%4%Upper abdominal pain5%3%12%5%

NDC Listings For This Application#

NDC, Name, Nonproprietary name table
NDCNameNonproprietary nameLabelerMarketing categoryStatus
66302-300OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-300OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-300OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-300OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-300OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-300OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-302OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-302OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-302OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-302OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-302OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-302OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-310OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-310OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-310OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-310OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-310OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-310OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-325OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-325OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-325OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-325OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-325OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-325OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-350OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-350OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent
66302-350OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-350OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-350OrenitramtreprostinilUnited Therapeutics CorporationNDACurrent
66302-350OrenitramtreprostinilUnited Therapeutics Corp.NDACurrent

Documents#

Document, Submission type, Date table
DocumentSubmission typeDate
84389SUPPL 2025-12-12
67028SUPPL2021-04-12
60618SUPPL2019-10-22
60597SUPPL2019-10-21
48753SUPPL2017-06-16
48715SUPPL2017-06-14
47005SUPPL2017-01-27
46981SUPPL2017-01-24
40306SUPPL2016-02-11
10227SUPPL2016-01-28
24436ORIG2014-12-09
22924ORIG2014-12-09
40305SUPPL2014-10-09
10226SUPPL2014-10-08
32433ORIG2013-12-24
19478ORIG2013-12-23