REMODULIN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for REMODULIN (REMODULIN).
Treprostinil is a synthetic prostacyclin analog that directly vasodilates pulmonary and systemic arterial beds, inhibits platelet aggregation, and suppresses smooth muscle proliferation.
| Metabolism | Hepatic metabolism via CYP2C8 and CYP2C9 (major), with minor contributions from CYP2C19 and CYP2D6; major metabolite is a glucuronide conjugate. |
| Excretion | Renal: 20-30% as unchanged drug; fecal: 70-80% as metabolites (via biliary elimination). |
| Half-life | Terminal elimination half-life is approximately 4 hours (range 2-7 hours) following continuous subcutaneous infusion; clinical context: requires continuous infusion due to short half-life. |
| Protein binding | Approximately 58% bound to human plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution (Vd) is 1.3 L/kg (range 0.8-2.0 L/kg); clinical meaning: extensive distribution into tissues, exceeding total body water. |
| Bioavailability | Subcutaneous: approximately 100% bioavailable compared to intravenous; oral: negligible (not administered orally). |
| Onset of Action | Subcutaneous: within 5 minutes; intravenous: immediate; peak effect at steady state (4-8 hours after infusion start). |
| Duration of Action | Duration of action: 2-6 hours after infusion cessation; clinical note: continuous infusion required to maintain hemodynamic effects; abrupt discontinuation may lead to rebound pulmonary hypertension. |
Continuous subcutaneous infusion: Initially 1.25 ng/kg/min; increase by 1.25 ng/kg/min every week for first 4 weeks, then by 2.5 ng/kg/min every week as tolerated. Intravenous infusion: same dosing.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Mild to moderate hepatic impairment (Child-Pugh class A or B): no adjustment. Severe hepatic impairment (Child-Pugh class C): contraindicated. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to age-related renal/hepatic decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for REMODULIN (REMODULIN).
| Breastfeeding | It is unknown if teriprostinil is excreted in human milk. M/P ratio not established. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 48 hours after the last dose. |
| Teratogenic Risk | Teriprostinil (REMODULIN) is contraindicated in pregnancy due to teratogenic effects in animal studies (increased cardiovascular and skeletal malformations). There are no adequate human data; however, based on animal findings, fetal risk cannot be excluded, particularly in the first trimester. In later trimesters, risks include potential fetal harm from maternal hypotension and hypoxia. |
■ FDA Black Box Warning
None. However, infusion site reactions (pain, erythema, induration) and risk of catheter-related bloodstream infections are significant concerns.
| Common Effects | Urinary tract infection Nausea Vomiting Diarrhea Abdominal pain Loss of appetite Hypoglycemia low blood glucose level |
| Serious Effects |
["Known hypersensitivity to treprostinil or any excipient","Patients with severe hepatic impairment (Child-Pugh class C) due to lack of safety data"]
| Precautions | ["Sudden discontinuation may worsen PAH; taper if possible.","Infusion site reactions are common; avoid extravasation.","Risk of bleeding due to antiplatelet effects; use with caution in patients with peptic ulcer disease or on anticoagulants.","Hepatic impairment may increase exposure; dosage adjustment may be needed.","May cause systemic hypotension; monitor blood pressure."] |
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| Fetal Monitoring | Monitor maternal vital signs (blood pressure, heart rate), oxygen saturation, signs of pulmonary edema, and infusion site reactions. Perform fetal monitoring by ultrasound for growth and well-being, and consider non-stress tests in the third trimester if maternal condition warrants. |
| Fertility Effects | No clinical studies on fertility. Animal studies have not revealed impaired fertility at clinically relevant doses. Theoretical risk of reproductive impairment due to underlying disease (pulmonary arterial hypertension) rather than drug effect. |