Iloprost

FDA Drug Information • Also known as: Aurlumyn

Brand Names: Aurlumyn
Dosage Form: LIQUID
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION AURLUMYN contains iloprost, a synthetic analog of prostacyclin PGI 2 . The chemical name for iloprost is (5 E )-[3a S ,4 R ,5 R ,6a S )-5-hydroxy-4-[(1 E )-(3 S ,4 RS )-3-hydroxy-4-methyloct-1-en-6-ynyl]-hexahydropentalen-2(1 H )-ylidene]pentanoic acid. Iloprost consists of a mixture of the 4R and 4S diastereoisomers at a ratio of approximately 53:47. Iloprost is an oily substance, which is soluble in methanol, ethanol, ethyl acetate, acetone, and pH 7 buffer, sparingly soluble in buffer pH 9, and very slightly soluble in distilled water, buffer pH 3, and buffer pH 5. The molecular formula of iloprost is C 22 H 32 O 4 and its molecular weight is 360.49. The structural formula is shown below: AURLUMYN (iloprost) injection is a clear, colorless, sterile solution formulated for intravenous use. AURLUMYN is supplied in single-use glass vials containing 1-mL per vial. Each mL of the solution contains 100 mcg (0.1 mg) of iloprost as the active ingredient and the following inactive ingredients: 8.1 mg ethanol, 9 mg sodium chloride, and 0.242 mg tromethamine. Hydrochloric acid and sodium hydroxide is added to adjust pH to 8.3. The solution contains no preservatives. Chemical Structure

What Is Iloprost Used For?

1 INDICATIONS AND USAGE AURLUMYN is a prostacyclin mimetic indicated for the treatment of severe frostbite in adults to reduce the risk of digit amputations. Effectiveness was established in young, healthy adults who suffered frostbite at high altitudes ( 1.1 ). 1.1 Frostbite AURLUMYN is indicated for the treatment of severe frostbite in adults to reduce the risk of digit amputations. Effectiveness was established in young, healthy adults who suffered frostbite at high altitudes.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Initiate intravenous infusion at 0.5 ng/kg/minute and titrate in 0.5 ng/kg/minute increments based on tolerability at intervals of 30 minutes to a maximum of 2 ng/kg/minute ( 2.1 ). Administer as continuous infusion for 6 hours each day up to a maximum of 8 consecutive days ( 2.1 ). Patients with moderate or severe hepatic impairment (Child-Pugh Class B or C): initiate infusion at 0.25 ng/kg/minute and titrate as described above ( 2.3 ). Patients with renal impairment with eGFR less than 30 mL/min: initiate infusion at 0.5 ng/kg/minute and titrate as described above. If the patient cannot tolerate the starting dose of 0.5 ng/kg/minute, the dose can be decreased to 0.25 ng/kg/minute ( 2.4 ). See Full Prescribing Information for instructions on preparation and administration ( 2.2 ). 2.1 Recommended Dosage Monitor vital signs prior to the start of the infusion and with every dose increase. Administer AURLUMYN as a continuous intravenous infusion over 6 hours each day for up to a maximum of 8 consecutive days. Start the initial infusion on day 1 at a rate of 0.5 ng/kg/minute and increase in increments of 0.5 ng/kg/minute every 30 minutes according to tolerability up to 2 ng/kg/minute. Dosage is based on actual patient body weight (kg). Repeat dose titration steps on day 2 and day 3. From day 4 onward, start the infusion at the highest tolerated dose from the previous day, and adjust the rate as needed, based on tolerability. Adverse reactions such as headache, flushing, jaw pain, myalgia, nausea, and vomiting may be dose-limiting. If dose-limiting adverse reactions occur that cannot be tolerated by the patient, then decrease the dose in a stepwise manner by 0.5 ng/kg/min every 30 minutes, until a tolerated dose is reached. If a dose-limiting adverse reaction occurs during administration of AURLUMYN at the starting dose, the infusion should be discontinued, and re-initiation of the infusion can be attempted after the event has resolved or been treated. If infusion is stopped at any point for a dose-limiting adverse event, infusion can be reinitiated at a previously tolerated dose/infusion rate once the event has resolved. The maximum tolerated dose should be maintained for the remaining 6-hour daily infusion. 2.2 Preparation and Administration Preparation: Use aseptic technique to prepare AURLUMYN. Inspect the vial for particulate matter prior to administration. Do not use if the solution is discolored or cloudy or if foreign particles are present. Dilution: AURLUMYN should only be diluted using 0.9% Sodium Chloride Injection, USP. Do not dilute or mix AURLUMYN with any other parenteral medications or solutions prior to or during administration. Withdraw 1 mL (100 mcg) of AURLUMYN solution from the vial and transfer into 100 mL of 0.9% Sodium Chloride Injection, USP polyvinyl chloride (PVC) infusion bag to make a final concentration of 1 mcg/mL (1,000 ng/mL). AURLUMYN can be added to commercially available infusion bags...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Most common adverse events include headache, flushing, palpitations/tachycardia, nausea, vomiting, dizziness, and hypotension (6.1). To report SUSPECTED ADVERSE REACTIONS, contact BTG International, Inc. at 1-877-377-3748 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Studies Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse events reported with the use of intravenous iloprost in patients with frostbite from the published literature include headache, flushing, palpitations/tachycardia, nausea, vomiting, dizziness, and hypotension. Pre-marketing safety data on AURLUMYN were obtained from 116 patients with Systemic Sclerosis receiving iloprost in 2 multicenter, double-blind, randomized, placebo-controlled studies in patients with Systemic Sclerosis experiencing symptomatic digital ischemic episodes (Raynaud's Phenomenon). Patients received intravenous AURLUMYN administered as a continuous infusion over 6 hours each day for 5 consecutive days and the dose was adjusted according to individual tolerability within the range of 0.5 to 2.0 ng /kg /min. The observed safety profile in these patients was similar to that observed with IV iloprost.

Contraindications

4 CONTRAINDICATIONS None. None ( 4 ).

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data with AURLUMYN during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are limited published cases of inhaled iloprost use during pregnancy, primarily during the second and third trimesters, that have not identified a drug-associated risk of adverse maternal or fetal outcomes. In animal reproductive studies, administration of continuous intravenous iloprost to pregnant Han-Wistar rats during organogenesis at doses 2-times the maximum recommended human dose on a mg/m 2 basis resulted in adverse developmental outcomes. However, there were no adverse developmental outcomes with oral or intravenous administration of iloprost to pregnant Sprague-Dawley rats, rabbits, and monkeys at doses 1111-, 1061-, and 12-times, respectively, the maximum recommended human dose by Cmax ( see Data ). The background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In developmental toxicity studies in pregnant Han-Wistar rats, continuous intravenous administration of iloprost at a dosage of 0.01 mg/kg daily (2 times the maximum recommended human dose on a mg/m 2 basis, serum levels not available) led to shortened digits of the thoracic extremity in fetuses and pups. In similar studies in pregnant Sprague-Dawley rats that received iloprost clathrate (13% iloprost by weight) orally at dosages of up to 50 mg/kg/day (C max of 90 ng/mL), in pregnant rabbits at intravenous dosages of up to 0.5 mg/kg/day (C max of 86 ng/mL), and in pregnant monkeys at dosages of up to 0.04 mg/kg/day (serum levels of 1 ng/mL), at 1111-, 1062- and 12-times,...

Overdosage

10 OVERDOSAGE Cases of overdose of intravenous iloprost have not been reported. Hypotension, vomiting, and diarrhea are likely. A specific antidote is not known. Interruption of the infusion session, monitoring, and symptomatic measures are recommended.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING AURLUMYN (iloprost) injection is a clear, colorless sterile solution supplied as 100 mcg per mL single-dose glass vial per carton (NDC 50633-340-01). Unopened vials of AURLUMYN are stable until the date indicated on the package when stored at 20°C to 25°C (68°F to 77°F), with excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature] . The unopened vial should be kept in the carton and not exposed to direct sunlight. Do not freeze.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.