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CARIPUL is a brand name for Epoprostenol, supplied as a powder for solution. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: CARIPUL® (epoprostenol sodium) is indicated for: • the long-term intravenous treatment of idiopathic pulmonary arterial hypertension (iPAH), heritable pulmonary arterial hypertension (HPAH) and pulmonary arterial hypertension associated with connective tissue disease in NYHA functional Class III and Class IV patients…
Verbatim from this product's HC label. Tap a section to expand.
9% Injection. Reconstituted solutions of CARIPUL® must not be diluted or administered with other parenteral solutions or medications. • CARIPUL® is not to be used for bolus administration. • During dose initiation and dose-finding, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output occurred rarely.
In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated. However, in the rare occurrence of pulmonary edema, chronic treatment is contraindicated. • During chronic use, CARIPUL® is delivered continuously on an ambulatory basis through a permanent indwelling central venous catheter.
Unless contraindicated, anticoagulant therapy should be administered to iPAH patients receiving CARIPUL® to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale. In order to reduce the risk of infection, aseptic technique must be used in the reconstitution and administration of CARIPUL® as well as in routine catheter care.
Because CARIPUL® is metabolized rapidly, even brief interruptions in the delivery of CARIPUL® may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia. The decision to initiate therapy with CARIPUL® should be based upon the understanding that there is a high likelihood that intravenous therapy with CARIPUL® will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a permanent intravenous catheter and infusion pump should be carefully considered.
3 Reconstitution) and administered through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Chronic infusion of CARIPUL® should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established or further increases in the infusion rate are not clinically warranted (see Dosage Adjustments below).
If dose-limiting pharmacologic effects occur, then the infusion rate should be decreased to the point that the pharmacologic effects of CARIPUL® are tolerated. In clinical trials, the most common dose-limiting adverse events were nausea, vomiting, hypotension, sepsis, headache, abdominal pain, or respiratory disorder (most treatment-limiting adverse events were not serious).
2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. During clinical trials, adverse events were classified as follows: (1) adverse events during dose escalation, (2) adverse events during chronic administration, and (3) adverse events associated with the drug delivery system.
Adverse Events During Dose Escalation In early clinical trials, epoprostenol was increased in 2 ng/kg/min increments until such time as the patients developed symptomatic intolerance. The most common adverse events and those that limited further increases in dose were generally related to vasodilation, the major pharmacologic effect of epoprostenol.
The most common dose-limiting adverse events (occurring in >1% of patients) were nausea, vomiting, headache, hypotension, and flushing, but also include chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, and musculoskeletal pain.
Table 10 lists the adverse events reported during dose escalation in decreasing order of frequency as well as the percent of cases where the event was dose limiting. Age related differences (<16 vs ≥16 years) in the incidence of adverse events are shown in Table 11.
o. o. , dizziness, syncope). Adverse events which may be related to the underlying disease include dyspnea, fatigue, chest pain, edema, hypoxia, right ventricular failure, and pallor. Several adverse events, on the other hand, can clearly be attributed to epoprostenol.
These include jaw pain, flushing, headache, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness. Adverse Events During Chronic Administration for iPAH (idiopathic pulmonary arterial hypertension) In an effort to separate the adverse effects of the drug from the adverse effects of the underlying disease, Table 12 lists adverse events that occurred at a rate at least 10% different in the two groups in controlled trials for iPAH.
, Gastrointestinal 03/2024 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES ....................................................................................
2 TABLE OF CONTENTS .......................................................................................................... 2 PART I: HEALTH PROFESSIONAL INFORMATION ............................................................. 4 1 INDICATIONS ..............................................................................................................
1 Pediatrics ............................................................................................................ 2 Geriatrics ............................................................................................................
4 2 CONTRAINDICATIONS .............................................................................................. 4 4 DOSAGE AND ADMINISTRATION ............................................................................. 1 Dosing Considerations .......................................................................................
2 Recommended Dose and Dosage Adjustment .................................................. 3 Reconstitution ..................................................................................................... 4 Administration ...................................................................................................
10 5 OVERDOSAGE ......................................................................................................... 11 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING .................. 11 7 WARNINGS AND PRECAUTIONS ...........................................................................
1 Special Populations .......................................................................................... 1 Pregnant Women .......................................................................................... 2 Breast-feeding ..............................................................................................
• CARIPUL® is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, structurally-related compounds, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.
• The chronic use of CARIPUL® (epoprostenol sodium) in patients with congestive heart failure due to severe left ventricular systolic dysfunction is contraindicated. 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.
• CARIPUL® should not be used chronically in patients who develop pulmonary edema during dose initiation. 0 Page 5 of 41
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
Other brands of Epoprostenol in Canada.
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If the initial infusion rate of 2 ng/kg/min is not tolerated, use a lower dose. 2 ng/kg/min. 1 ng/kg/min on day 7 of treatment. 2 ng/kg/min. 0 Page 6 of 41 3 weeks. Dosage Adjustments Changes in the chronic infusion rate should be based on persistence, recurrence, or worsening of the patient’s symptoms of pulmonary hypertension and the occurrence of adverse events due to excessive doses of CARIPUL®.
In general, increases in dose from the initial chronic dose should be expected. Increments in dose should be considered if symptoms of pulmonary hypertension persist or recur after improving. The infusion should be increased by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be at least 15 minutes.
In clinical trials, incremental increases in dose occurred at intervals of 24 to 48 hours or longer. Following establishment of a new chronic infusion rate, the patient should be observed, and standing and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated.
During chronic infusion, the occurrence of dose-limiting pharmacological events may necessitate a decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment. Dosage decreases should be made gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve.
Abrupt withdrawal of CARIPUL® or sudden large reductions in infusion rates should be avoided. ), infusion rates of CARIPUL® should be adjusted only under the direction of a physician. In patients receiving lung transplants, doses of epoprostenol were tapered after the initiation of cardiopulmonary bypass.
Pediatrics (< 18 years of age) The safety and effectiveness of epoprostenol in pediatric patients has not been established. 9% Injection. CARIPUL® must not be reconstituted or mixed with any other parenteral medications or solutions prior to or during administration.
Each vial is for single use only; discard any unused solution. Use after reconstitution and immediate dilution to final concentration A concentration for the solution of CARIPUL® should be selected that is compatible with the infusion pump being used with respect to minimum and maximum flow rates, reservoir capacity, and the infusion pump criteria listed above.
CARIPUL®, when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump. Outlined in Table 1 are directions for preparing different concentrations of CARIPUL® for up to a 48-hour period.
Each vial is for single use only; discard any unused […]
v. , pulmonary, gastrointestinal, epistaxis, intracranial, post-procedural, retroperitoneal) have been reported during uncontrolled clinical trials and post marketing clinical use in patients receiving epoprostenol. Table 13 lists those additional adverse events reported in iPAH patients receiving epoprostenol plus conventional therapy versus conventional therapy alone during controlled clinical trials where the difference in incidence of the event between treatment groups was <10%.
0 Page 18 of 41 Table 13: Adverse Events Regardless of Attribution Occurring During Chronic Administration in Controlled Trials with <10% Difference between Epoprostenol and Conventional Therapy Alone Adverse Event Epoprostenol (n=52) % of patients Conventional Therapy (n=54) % of patients General Asthenia 87 81 Cardiovascular Angina Pectoris Arrhythmia Bradycardia Supraventricular tachycardia Pallor Cyanosis Palpitation Cerebrovascular accident Hypotension Myocardial ischemia 19 27 15 8 21 31 63 4 27 2 20 20 9 0 30 39 61 0 31 6 Gastrointestinal Abdominal pain Anorexia Ascites Constipation 27 25 12 6 31 30 17 2 Metabolic Edema Hypokalemia Weight reduction Weight gain 60 6 27 6 63 4 24 4 Musculoskeletal Arthralgia Bone pain Chest pain 6 0 67 0 4 65 Neurological Confusion Convulsion Depression Insomnia 6 4 37 4 11 0 44 4 Respiratory Cough increase Dyspnea Epistaxis Pleural effusion 38 90 4 4 46 85 2 2 Skin and Appendages Pruritus Rash Sweating 4 10 15 0 13 20 Special Senses […]
3 Pediatrics ...................................................................................................... 4 Geriatrics ...................................................................................................... 14 8 ADVERSE REACTIONS ............................................................................................
2 Clinical Trial Adverse Reactions ....................................................................... 5 Post-Market Adverse Reactions ....................................................................... 21 9 DRUG INTERACTIONS .............................................................................................
2 Drug Interactions Overview .............................................................................. 4 Drug-Drug Interactions ..................................................................................... 5 Drug-Food Interactions .....................................................................................
6 Drug-Herb Interactions ..................................................................................... 7 Drug-Laboratory Test Interactions .................................................................... 22 10 CLINICAL PHARMACOLOGY ..................................................................................
1 Mechanism of Action ........................................................................................ 2 Pharmacodynamics .......................................................................................... 3 Pharmacokinetics .............................................................................................
24 11 STORAGE, STABILITY AND DISPOSAL ................................................................. 26 12 SPECIAL HANDLING INSTRUCTIONS .................................................................... 26 PART II: SCIENTIFIC INFORMATION ..................................................................................
27 13 PHARMACEUTICAL INFORMATION ....................................................................... 27 14 CLINICAL TRIALS .................................................................................................... 1 Clinical Trials by Indication ...............................................................................
27 Long-term treatment of idiopathic pulmonary arterial hypertension (iPAH)................ 27 Chronic infusion in pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD) ..................................................................................................
29 15 MICROBIOLOGY ....................................................................................................... 30 16 NON-CLINICAL TOXICOLOGY ................................................................................
30 PATIENT MEDICATION INFORMATION ............................................................................. 0 Page 4 of 41 PART I: HEALTH PROFESSIONAL INFORMATION 1 INDICATIONS CARIPUL® (epoprostenol sodium) is indicated for: • the long-term intravenous treatment of idiopathic pulmonary arterial hypertension (iPAH), heritable pulmonary arterial hypertension (HPAH) and pulmonary arterial hypertension associated with connective tissue disease in NYHA functional Class III and Class IV patients who did not respond adequately to conventional therapy.
Prior to initiation of therapy, the potential benefit of CARIPUL® should be weighed against the risks associated with use of the drug and the presence of an indwelling central […]