of drospirenone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.eluxadolineMonitor Closely (1)eluxadoline increases levels of epoprostenol by decreasing metabolism. Use Caution/Monitor. Eluxadoline may increase the systemic exposure of coadministered OATP1B1 substrates.enoxaparinMonitor Closely (1)enoxaparin and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.ethacrynic acidMinor (1)epoprostenol increases effects of ethacrynic acid by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.etodolacMonitor Closely (1)etodolac and epoprostenol both increase anticoagulation. Use Caution/Monitor.fennelMonitor Closely (1)epoprostenol and fennel both increase anticoagulation. Use Caution/Monitor.fenoldopamMonitor Closely (1)epoprostenol, fenoldopam. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.fenoprofenMonitor Closely (1)fenoprofen and epoprostenol both increase anticoagulation. Use Caution/Monitor.feverfewMonitor Closely (1)epoprostenol and feverfew both increase anticoagulation. Use Caution/Monitor.fish oil triglyceridesMonitor Closely (1)fish oil triglycerides will increase the level or effect of epoprostenol 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.flurbiprofenMonitor Closely (1)flurbiprofen and epoprostenol both increase anticoagulation. Use Caution/Monitor.fondaparinuxMonitor Closely (1)fondaparinux and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.forskolinMonitor Closely (1)epoprostenol and forskolin both increase anticoagulation. Use Caution/Monitor.Minor (1)forskolin increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown.furosemideMinor (1)epoprostenol increases effects of furosemide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.garlicMonitor Closely (1)epoprostenol and garlic both increase anticoagulation. Use Caution/Monitor.gingerMonitor Closely (1)epoprostenol and ginger both increase anticoagulation. Use Caution/Monitor.ginkgo bilobaMonitor Closely (1)epoprostenol and ginkgo biloba both increase anticoagulation. Use Caution/Monitor.heparinMonitor Closely (1)heparin and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.horse chestnut seedMonitor Closely (1)epoprostenol and horse chestnut seed both increase anticoagulation. Use Caution/Monitor.hydralazineMonitor Closely (1)epoprostenol, hydralazine. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.hydrochlorothiazideMinor (1)epoprostenol increases effects of hydrochlorothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.ibrutinibMonitor Closely (1)ibrutinib will increase the level or effect of epoprostenol 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. ibuprofenMonitor Closely (1)ibuprofen and epoprostenol both increase anticoagulation. Use Caution/Monitor.ibuprofen IVMonitor Closely (1)ibuprofen IV and epoprostenol both increase anticoagulation. Use Caution/Monitor.iloprostMonitor Closely (1)epoprostenol, iloprost. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.indapamideMinor (1)epoprostenol increases effects of indapamide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.indomethacinMonitor Closely (1)indomethacin and epoprostenol both increase anticoagulation. Use Caution/Monitor.ketoprofenMonitor Closely (1)ketoprofen and epoprostenol both increase anticoagulation. Use Caution/Monitor.ketorolacMonitor Closely (1)ketorolac and epoprostenol both increase anticoagulation. Use Caution/Monitor.ketorolac intranasalMonitor Closely (1)ketorolac intranasal and epoprostenol both increase anticoagulation. Use Caution/Monitor.levodopaMonitor Closely (1)levodopa increases effects of epoprostenol by pharmacodynamic synergism. Use Caution/Monitor. Consider decreasing dosage of antihypertensive agent.lofexidineSerious - Use Alternative (1)lofexidine, epoprostenol. 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.lornoxicamMonitor Closely (1)lornoxicam and epoprostenol both increase anticoagulation. Use Caution/Monitor.maitakeMinor (1)maitake increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown. Maitake mushroom has anti-tumor effects (animal/in vitro research).meclofenamateMonitor Closely (1)meclofenamate and epoprostenol both increase anticoagulation. Use Caution/Monitor.mefenamic acidMonitor Closely (1)mefenamic acid and epoprostenol both increase anticoagulation. Use Caution/Monitor.meloxicamMonitor Closely (1)meloxicam and epoprostenol both increase anticoagulation. Use Caution/Monitor.methyclothiazideMinor (1)epoprostenol increases effects of methyclothiazide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.metolazoneMinor (1)epoprostenol increases effects of metolazone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.minoxidilMonitor Closely (1)epoprostenol, minoxidil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.mistletoeMonitor Closely (1)epoprostenol increases and mistletoe decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.nabumetoneMonitor Closely (1)nabumetone and epoprostenol both increase anticoagulation. Use Caution/Monitor.naproxenMonitor Closely (1)naproxen and epoprostenol both increase anticoagulation. Use Caution/Monitor.nettleMonitor Closely (1)epoprostenol increases and nettle decreases anticoagulation. Effect of interaction is not clear, use caution. Use Caution/Monitor.oxaprozinMonitor Closely (1)oxaprozin and epoprostenol both increase anticoagulation. Use Caution/Monitor.panax ginsengMonitor Closely (1)epoprostenol and panax ginseng both increase anticoagulation. Use Caution/Monitor.parecoxibMonitor Closely (1)parecoxib and epoprostenol both increase anticoagulation. Use Caution/Monitor.pau d'arcoMonitor Closely (1)epoprostenol and pau d'arco both increase anticoagulation. Use Caution/Monitor.phenindioneMonitor Closely (1)phenindione and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.phytoestrogensMonitor Closely (1)epoprostenol and phytoestrogens both increase anticoagulation. Use Caution/Monitor.piroxicamMonitor Closely (1)piroxicam and epoprostenol both increase anticoagulation. Use Caution/Monitor.protamineMonitor Closely (1)protamine and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.reishiMonitor Closely (1)epoprostenol and reishi both increase anticoagulation. Use Caution/Monitor.Minor (1)reishi increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown.reteplaseMonitor Closely (1)reteplase and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.salicylates (non-asa)Monitor Closely (1)salicylates (non-asa) and epoprostenol both increase anticoagulation. Use Caution/Monitor.salsalateMonitor Closely (1)salsalate and epoprostenol both increase anticoagulation. Use Caution/Monitor.shepherd's purseMinor (1)shepherd's purse, epoprostenol. Other (see comment). Minor/Significance Unknown. Comment: Theoretically, shepherd's purse may interfere with BP control.Siberian ginsengMonitor Closely (1)epoprostenol and Siberian ginseng both increase anticoagulation. Use Caution/Monitor.sildenafilMonitor Closely (1)epoprostenol increases effects of sildenafil by additive vasodilation. Use Caution/Monitor. Sildenafil has systemic vasodilatory properties and may further lower blood pressure in patients taking antihypertensive medications. Monitor blood pressure response to sildenafil in patients receiving concurrent blood pressure lowering therapy.spironolactoneMinor (1)epoprostenol increases effects of spironolactone by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.sulfasalazineMonitor Closely (1)sulfasalazine and epoprostenol both increase anticoagulation. Use Caution/Monitor.sulindacMonitor Closely (1)sulindac and epoprostenol both increase anticoagulation. Use Caution/Monitor.tenecteplaseMonitor Closely (1)tenecteplase and epoprostenol both increase anticoagulation. Modify Therapy/Monitor Closely.tizanidineMinor (1)tizanidine increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown. Risk of hypotension.tolfenamic acidMonitor Closely (1)tolfenamic acid and epoprostenol both increase anticoagulation. Use Caution/Monitor.tolmetinMonitor Closely (1)tolmetin and epoprostenol both increase anticoagulation. Use Caution/Monitor.torsemideMinor (1)epoprostenol increases effects of torsemide by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.treprostinilMonitor Closely (1)epoprostenol, treprostinil. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor.Minor (1)treprostinil increases effects of epoprostenol by pharmacodynamic synergism. Minor/Significance Unknown.triamtereneMinor (1)epoprostenol increases effects of triamterene by pharmacodynamic synergism. Minor/Significance Unknown. Additive hypotensive effects.warfarinMonitor Closely (1)epoprostenol, warfarin. Either increases effects of the other by pharmacodynamic synergism. Modify Therapy/Monitor Closely. Drugs with antiplatelet properties may increase anticoagulation effect of warfarin.xipamideMonitor Closely (1)xipamide increases effects of epoprostenol by pharmacodynamic synergism. Use Caution/Monitor. >10% Flushing (58%) Jaw pain (54%) Headache (49%) Myalgia (44%) Diarrhea (37%) Nausea (32%) Vomiting (32%) Flu-like symptoms (25%) Eczema (25%) Rash (25%) Urticaria (25%) Hypotension (16%) Anxiety (11%) Nervousness (11%) 1-10% Musculoskeletal pain (2%) Hyperesthesia (1%) Tachycardia (1%) Frequency Not Defined Hemorrhage Thrombocytopenia Postmarketing Reports Blood and lymphatic: Anemia, hypersplenism, pancytopenia, splenomegaly, thrombocytopenia Endocrine and Metabolic: Hyperthyroidism Gastrointestinal: Hepatic failure Respiratory, Thoracic, and Mediastinal: Pulmonary embolism Cardiovascular: High output cardiac failure Contraindications Hypersensitivity to epoprostenol Chronic use in patients with CHF due to left ventricular systolic dysfunction Development of pulmonary edema during initial dose titration Cautions Initiate therapy in a setting with adequate personnel and equipment for physiologic monitoring and emergency care; dose initiation has been performed during right heart catheterization and without cardiac catheterization; during dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output reported rarely; in such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated Abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia; in clinical trials, death attributable to interruption of therapy reported; avoid abrupt withdrawal Use caution in patients with risk factors of bleeding Serious blood stream infectiosn may develop from chronic infusions requiring an indwelling central venous catherer Asymptomatic increase in pulmonary artery pressure Some patients may develop pulmonary edema during dosing adjustments Chronic use and dose adjustment During chronic use, deliver drug continuously on an ambulatory basis through a permanent indwelling central venous catheter; unless contraindicated Administer anticoagulant therapy to patients receiving therapy to reduce risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale To reduce risk of infection, use aseptic technique in reconstitution and administration of therapy and in routine catheter care Because drug is metabolized rapidly, even brief interruptions in delivery of drug may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia Intravenous therapy will likely be needed for prolonged periods, possibly years, so consider patient’s capacity to accept and care for a permanent intravenous catheter and infusion pump Adjust dosage during chronic use at first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or occurrence of adverse events associated with drug; following dosage adjustments, monitor standing and supine blood pressure and heart rate closely for several hours Pregnancy Limited published data from case series and case reports have not established an association with therapy and major birth defects, miscarriage or adverse maternal or fetal outcomes when treatment is used during pregnancy; there are risks to the mother and fetus from untreated pulmonary arterial hypertension; in animal reproduction studies, pregnant rats and rabbits received epoprostenol sodium during organogenesis at exposures of 2.5 and 4.8 times the maximum recommended human dose (MRHD), respectively, and there was no effect on the fetus Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death Lactation There are no data on presence of epoprostenol in either human or animal milk, effects on breastfed infant, or on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal conditionPregnancy 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. Mechanism of Action Potent peripheral vasodilator of all vascular beds; also prevents platelet aggregation Pharmacokinetics Half-life: 3-6 min Metabolism: rapidly hydrolyzed in blood to metabolites Metabolite: 6-keto-prostaglandin F1-alpha (inactive), dihydro-prostaglandin F1-alpha metabolites (unknown activity) Excretion: Urine (84%); feces (4%) IV Preparation Flolan 3000 ng/mL: 0.5 mg vial/5 mL mfr supplied sterile diluent; withdraw 3 mL; and add sufficient diluent to make 100 mL 5000 ng/mL: 0.5 mg vial/5 mL mfr supplied sterile diluent; withdraw entire vial; and add sufficient diluent to make 100 mL 10,000 ng/mL: two 0.5 mg vials each in 5 mL mfr supplied sterile diluent; withdraw entire vial; and add sufficient diluent to make 100 mL 15,000 ng/mL: 1.5 mg vial/5 mL mfr supplied sterile diluent; withdraw entire vial; and add sufficient diluent to make 100 mL Do not use preparation and administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG); PET/PETG products may become damaged when used with Flolan’s mfr supplied with sterile diluent which is alkaline (pH 12) Veletri Reconstituted in vial with only 5 mL of either sterile water for injection or 0.9% NaCl Further dilute reconstituted product with same diluent used for reconstitution Solutions of 15,000 ng/mL or above may be used for up to 25 hr at room temperature Lower concentrations may be used with pump reservoir changed q12hr at room temperature IV Administration Continuous IV infusion via central venous catheter using ambulatory infusion pump Do not mix with any other parenteral medications or solutions prior or during administration During treatment initiation, may be administered peripherally Storage Flolan Unopened vials are stable until date indicated on package when stored at room temperature (25 degrees C [77 degrees F]) in carton and protected from light Reconstituted vial: May be refrigerated (2-8 degrees C [36-46 degrees F]) for up to 48 hr Room temperature administration: When administered at room temperature, reconstituted solutions may be used for no longer than 8 hr Use with cold packs: May be administered for up to 24 hr with cold packs (change cold packs q12hr during infusion) Do not freeze Do not expose to direct sunlight Veletri Unopened vials are stable until date indicated on package when stored at room temperature (25 degrees C [77 degrees F]) in carton and protected from light Reconstituted vial: May be refrigerated (2-8 degrees C [36-46 degrees F]) for as long as 5 days or held at up to 25 degrees C (77 degrees F) for up to 48 hr prior to use Final solutions of 15,000 ng/mL or above are stable at room temperature