Names and pronunciation
(treh-prah′stin-ill) Orenitram, Remodulin, Tyvaso, Tyvaso Refill, Tyvaso Starter
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Drug reference
(treh-prah′stin-ill) Orenitram, Remodulin, Tyvaso, Tyvaso Refill, Tyvaso Starter
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Func. class.: Pulmonary, vasodilator
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Chem. class.: Tricyclic benzidine prostacyclin analog
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ACTION: Direct vasodilation of pulmonary, systemic arterial vascular beds; inhibition of platelet aggregation
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USES: Pulmonary arterial hypertension (PAH) NYHA class II through IV
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CONTRAINDICATIONS: Hyper- sensitivity to this product, other prostacyclin analogs T Precautions: Pregnancy, breastfeeding, children, geriatric patients, past renal/ hepatic disease, thromboembolic dis- ease, abrupt discontinuation, IV adminis- tration
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SIDE EFFECTS CNS: Dizziness, headache, syncope CV: Vasodilation, hypotension, edema, right ventricular heart failure GI: Nausea, diarrhea INTEG: Rash, pruritus OTHER: Jaw pain, cough, throat irritation, UTI, leg cramps SYST: Infusion site reactions, pain; increased risk for infection
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INTERACTIONS • Excessive hypotension: diuretics, anti- hypertensives, vasodilators, MAOIs, β- blockers, calcium channel blockers Increase: bleeding tendencies—antico- agulants, aspirin, NSAIDs, thrombin inhibitors, SSRIs
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DOSAGE AND ROUTES Pulmonary arterial hypertension • Adult: SUBCUT CONT INFUSION/IV CONT INFUSION 1.25 ng/kg/min. If not tolerated, reduce to 0.625 ng/kg/min. Increase dose by ≤1.25 ng/kg/min per wk × first 4 wk, then ≤2.5 ng/kg/min per wk; ORAL INH: 3 breaths (18 mcg) by Tyvaso Inhalation System qid 4 hr apart during waking hours; PO: 0.25 mg q12hr or 0.125 mg q8hr, increase by 0.25 or 0.5 mg bid or 0.125 mg tid q3-4days as tolerated • Adult taking gemfibrozil (or other strong CYP2C8 inhibitor): PO 0.125 mg q12hr, increase by 0.125 mg bid q3- 4days, as tolerated For patients transitioning from IV or SUBCUT to PO • Adult: PO For patients already receiving IV or SUBCUT, use the following equation: Total daily PO dose = 0.0072 × IV or SUBCUT dose (ng/kg/min) × Weight (kg). Reduce dose of IV or SUBCUT by up to 30 ng/kg/min per day while increasing dose of PO up to 6 mg/day (2 mg PO tid), if tolerated Hepatic dose • Adult: SUBCUT INFUSION 0.625 ng/kg ideal body weight/min; increase cau tiously
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Available forms: Inj 1, 2.5, 5, 10 mg/ mL; neb sol 1.74 mg/2.9 mL; ext rel tab 0.125, 0.25, 2.5 mg
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Administer: • Sudden decreased doses, abrupt with- drawal may worsen pulmonary arterial hypertension symptoms PO route • Give with food • Swallow tablets whole; use only intact tablets Injectable route • Visually inspect for particulate matter and discoloration before use • Administer injection by continuous SUBCUT infusion. May be adminis- tered by continuous IV infusion in those who do not tolerate continuous SUBCUT (severe injection site pain or reaction) • Have immediate access to a backup infusion pump and infusion sets. Avoid abrupt discontinuation. The infusion can be restarted after a few hours at the pre- vious dose and rate; if the infusion is stopped for longer than a few hours, retitration may be needed • The infusion pump used should be: small and lightweight; adjustable to approximately 0.002 mL/hr; have alarms for occlusion, end of infusion and low battery, programming error and motor malfunctions; accurate to +/−6% of the programmed rate; posi- tive-pressure driven. The reservoir should be made of polyvinyl chloride, polypropylene, or glass • Opened vials: A single vial should be used ≤30 days after the initial entry into the vial CONTINUOUS IV route • Given via a surgically placed central venous catheter via an ambulatory infu- sion pump. A peripheral IV cannula, placed into a large vein, may be used temporarily; use of a peripheral vein for more than a few hours may increase the risk of thrombophlebitis • Infusion sets with an in-line 0.22- or 0.2-micron pore size filter should be used IV infusion preparation • May dilute with Remodulin sterile dilu- ent for injection or similar approved high-pH glycine diluents (sterile diluent for Flolan or sterile diluent for epopros- tenol sodium), sterile water for injection, or 0.9% NaCl for injection • The concentration of diluted treprosti- nil should be calculated using the follow- ing formula: diluted concentration = [dose (ng/kg/min) × weight (kg) × 0.00006] / IV infusion rate (mL/hr) • Typical ambulatory infusion pump reservoirs have volumes of 50 or 100 mL. The IV infusion rate is predeter- mined based on the volume of the reser- voir with a desired infusion length of 48 hr (i.e., for a 50-mL reservoir, the infu- sion rate would be 1 mL/hr; for a 100- mL reservoir, the infusion rate would be 2 mL/hr) • The reservoir should be filled with the calculated volume and a sufficient amount of diluent to achieve the total volume of the reservoir • Once diluted with any diluent, may be given for 48 hr at 40°C • Storage: If diluted with sterile water for injection or 0.9% NaCl, store up to 4 hr at room temperature or 24 hr if refrig- erated. If diluted with an approved high- pH glycine diluent (sterile diluent for Remodulin, Flolan, or epoprostenol so- dium), it may be stored for 14 days at room temperature at concentrations as low as 0.004 mg/mL SUBCUT continuous infusion • Give via a self-inserted SUBCUT cathe- ter using an ambulatory infusion pump designed for subcutaneous drug delivery SUBCUT infusion preparation • Further dilution is NOT required be- fore continuous SUBCUT use • Do not mix or co-infuse with other medications • The SUBCUT infusion rate can be cal- culated using the following formula: SUB- CUT infusion rate = [dose (ng/kg/min) × weight (kg) × 0.00006]/treprostinil vial strength (mg/mL) • During SUBCUT use, a single reser- voir (syringe) of product can be given ≤72 hr at a max temperature of 37°C (98.6°F) Oral inhalation administration • Must be used only with the Tyvaso In- halation System • Avoid skin or eye contact with solu- tion. Do not take PO • Have access to a backup Optineb-ir device to avoid interruptions in therapy • Do not mix with other medications in the Optineb-ir device • One ampule contains a volume for all 4 treatment sessions in a single day
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Assess: • Avoid abrupt discontinuation • CV status: monitor B/P, baseline and periodically, HR and rhythm, S3, chest pain, edema, dyspnea, fatigue, ABLs, syn- cope • Hepatic studies: AST, ALT, bilirubin, creatinine with long-term therapy • Blood studies: CBC; CBC q2wk × 3 mo, Hct, HB, PT with long-term therapy, ABGs • Bleeding time at baseline, through out treatment; levels may be 2-5× nor mal limit • Beers: use with caution in older adults; may exacerbate episodes of syncope; monitor frequently • Pregnancy/breastfeeding: use only if clearly needed, no well-controlled stud- ies; cautious use in breastfeeding, excre- tion unknown
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Evaluate: • Therapeutic response: decreased pul- monary arterial hypertension (PAH) T
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • That blood work will be necessary during treatment; that treatment may last for years • To report side effects such as diarrhea, skin rashes • That therapy will be needed for pro- longed periods of time, sometimes years • To use aseptic technique for prepara- tion, administration of treprostinil to pre- vent infection • That there are many product, herbal interactions • Tablet: to take with food; not to crush or chew tablets, not to skip doses • Subcut: about injection technique; to rotate injection sites; to avoid irritated, scarred, or bruised skin • Inhalation: to avoid contact of solution with skin or eyes; to wash hands after handling inhaler; to follow directions for use in package insert • How to use inhaled solution; how to care for equipment • About signs, symptoms of bleeding; blood in urine, stools
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PHARMACOKINETICS Metabolized by liver; excreted in urine, feces; terminal half-life 2-4 hr; 90% pro- tein binding
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• Adult: SUBCUT CONT INFUSION/IV CONT INFUSION 1.25 ng/kg/min. If not tolerated, reduce to 0.625 ng/kg/min. Increase dose by ≤1.25 ng/kg/min per wk × first 4 wk, then ≤2.5 ng/kg/min per wk; ORAL INH: 3 breaths (18 mcg) by Tyvaso Inhalation System qid 4 hr apart during waking hours; PO: 0.25 mg q12hr or 0.125 mg q8hr, increase by 0.25 or 0.5 mg bid or 0.125 mg tid q3-4days as tolerated
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• Adult taking gemfibrozil (or other strong CYP2C8 inhibitor): PO 0.125 mg q12hr, increase by 0.125 mg bid q3- 4days, as tolerated For patients transitioning from IV or SUBCUT to PO
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• Adult: PO For patients already receiving IV or SUBCUT, use the following equation: Total daily PO dose = 0.0072 × IV or SUBCUT dose (ng/kg/min) × Weight (kg). Reduce dose of IV or SUBCUT by up to 30 ng/kg/min per day while increasing dose of PO up to 6 mg/day (2 mg PO tid), if tolerated Hepatic dose
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• Adult: SUBCUT INFUSION 0.625 ng/kg ideal body weight/min; increase cau tiously
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