Complete SPL Sections
1 INDICATIONS AND USAGE
INDICATIONS & USAGE SECTION
Epoprostenol for injection is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases.
2 DOSAGE AND ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
Important Note: Reconstitute epoprostenol for injection only as directed with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Do not dilute reconstituted solutions of epoprostenol for injection or administer it with other parenteral solutions or medications [see Dosage and Administration (2.4)] .
3 DOSAGE FORMS AND STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Epoprostenol for injection contains epoprostenol sodium equivalent to 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol and is supplied as a sterile lyophilized material in a 10 mL vial.
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
A large study evaluating the effect of epoprostenol on survival in NYHA Class III and IV patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving epoprostenol plus conventional therapy than in those receiving conventional therapy alone. The chronic use of epoprostenol for injection in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated. Some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease. Epoprostenol for injection should not be used chronically in patients who develop pulmonary edema during dose initiation. Epoprostenol for injection is also contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.
5 WARNINGS AND PRECAUTIONS
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
Additional reductions in blood pressure may occur when epoprostenol for injection is administered with diuretics, antihypertensive agents, or other vasodilators. When other antiplatelet agents or anticoagulants are used concomitantly, there is the potential for epoprostenol for injection to increase the risk of bleeding. However, patients receiving infusions of epoprostenol in clinical trials were maintained on anticoagulants without evidence of increased bleeding. In clinical trials, epoprostenol was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen. In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom therapy with epoprostenol was initiated, apparent oral clearance values for furosemide (n = 23) and digoxin (n = 30) were decreased by 13% and 15%, respectively, on the second day of therapy and had returned to baseline values by day 87. The change in furosemide clearance value is not likely to be clinically significant. However, patients on digoxin may show elevations of digoxin concentrations after initiation of therapy with epoprostenol, which may be clinically significant in patients prone to digoxin toxicity.
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
Signs and symptoms of excessive doses of epoprostenol during clinical trials are the expected dose-limiting pharmacologic effects of epoprostenol, including flushing, headache, hypotension, tachycardia, nausea, vomiting, and diarrhea. Treatment will ordinarily require dose reduction of epoprostenol. One patient with secondary pulmonary hypertension accidentally received 50 mL of an unspecified concentration of epoprostenol. The patient vomited and became unconscious with an initially unrecordable blood pressure. Epoprostenol was discontinued and the patient regained consciousness within seconds. In clinical practice, fatal occurrences of hypoxemia, hypotension, and respiratory arrest have been reported following overdosage of epoprostenol. Single intravenous doses of epoprostenol at 10 and 50 mg/kg (2,703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
11 DESCRIPTION
DESCRIPTION SECTION
Epoprostenol sodium is the sodium salt of epoprostenol, formulated as a sterile lyophilized cake or powder for intravenous (IV) administration. Each vial of epoprostenol for injection contains epoprostenol sodium equivalent to either 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol, 100 mg sucrose, and 5 mg glycine. Sodium hydroxide is added to adjust pH. Epoprostenol (PGI 2 , PGX, prostacyclin), a metabolite of arachidonic acid, is a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. Epoprostenol is (5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxy-prosta-5,13-dien-1-oic acid, sodium salt. Epoprostenol sodium has a molecular weight of 374.45 and a molecular formula of C 20 H 31 NaO 5 . The structural formula is: Epoprostenol for injection is a white to off-white lyophilized cake or powder material. It is reconstituted with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. The reconstituted solution of epoprostenol for injection has a pH ranging from 12.0 to 13.2 and is increasingly unstable at a lower pH.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Patients receiving epoprostenol for injection should receive the following information. Epoprostenol for injection must be reconstituted as directed using only Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Epoprostenol for injection is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump. Thus, therapy with epoprostenol for injection requires commitment by the patient to drug reconstitution, drug administration, and care of the permanent central venous catheter. Patients must adhere to sterile technique in preparing the drug and in the care of the catheter, and even brief interruptions in the delivery of epoprostenol for injection may result in rapid symptomatic deterioration. A patient’s decision to receive epoprostenol for injection should be based upon the understanding that there is a high likelihood that therapy with epoprostenol for injection will be needed for prolonged periods, possibly years. The patient’s ability to accept and care for a permanent intravenous catheter and infusion pump should also be carefully considered. Distributed by: Sun Pharmaceutical Industries, Inc. Cranbury, NJ 08512 Manufactured by: Sun Pharmaceutical Industries, Inc. Billerica, MA 01821 PL-000075 Rev. 2.0 October 2020
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.5 mg-vial
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-059-40 Epoprostenol for Injection 0.5 mg (500,000 ng)/vial For Intravenous Infusion Only Sterile, Lyophilized Product Single-dose Vial Discard Unused Portion Rx only Sun Pharma
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-0.5 mg-carton
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-059-40 Single-dose Vial Discard Unused Portion Epoprostenol for Injection 0.5 mg (500,000 ng)/vial For Intravenous Infusion Only Sterile, Lyophilized Product Rx only Sun Pharma
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-1.5 mg-vial
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-060-40 Epoprostenol for Injection 1.5 mg (1,500,000 ng)/vial For Intravenous Infusion Only Sterile, Lyophilized Product Single-dose Vial Discard Unused Portion Rx only Sun Pharma
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL-1.5 mg-carton
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
NDC 62756-060-40 Single-dose Vial Discard Unused Portion Epoprostenol for Injection 1.5 mg (1,500,000 ng)/vial For Intravenous Infusion Only Sterile, Lyophilized Product Rx only Sun Pharma