ILOPROST Concentrate for solution for infusion Ref.[9900] Active ingredients: Iloprost

Iloprost 100 micrograms/ml Concentrate for solution for infusion is NOT ready to use and requires dilution before administration.

Iloprost 100 micrograms/ml Concentrate for solution for infusion should be administered under strict monitoring in a hospital or out-patient clinic setting with adequate facilities.

Pregnancy should be excluded before the start of treatment in women.

Iloprost 100 micrograms/ml Concentrate for solution for infusion is administered after dilution as described in section 6.6 as an intravenous infusion over 6 hours via a peripheral vein or a central venous catheter. The dose is adjusted according to individual tolerability within the range of 0.5 to 2.0 ng iloprost/kg body weight/min.

The infusion solution should be made up just before the infusion to ensure sterility.

Iloprost 100 micrograms/ml Concentrate for solution for infusion should only be used diluted. To avoid incompatibility, no other products should be added to the infusion prepared for injection.

The content of the ampoule and the diluent must be mixed thoroughly.

Posology

Blood pressure and heart rate should be monitored at the start of the infusion and subsequently at every dose increase. During the first 2-3 days, the individually tolerated dose is established. For this reason, treatment should be started at an infusion rate of 0.5 ng/kg/min for 30 minutes. The dose should then be increased at intervals of 30 minutes by 0.5 ng/kg/min to a maximum of 2.0 ng/kg/min. The exact infusion rate should be calculated on the basis of body weight to reach an infusion within the range of 0.5 to 2.0 ng/kg/min (see tables below for use with infusion pump or syringe driver).

Method of administration

Iloprost 100 micrograms/ml Concentrate for solution for infusion is NOT ready to use and requires dilution before administration. Depending on the occurrence of adverse effects such as headache and nausea or an undesired blood pressure drop, the infusion rate should be reduced until the optimal tolerated dose is found. If the adverse effects are severe, the infusion should be temporarily interrupted. The treatment course can then be continued with the dose based on the optimal tolerated dose reached in the first 2 to 3 days of treatment.

Depending on the infusion technique used, there are two different methods to dilute the content of the ampoule. One of those two dilutions are 10-fold less concentrated than the other (0.2 micrograms/ml vs 2 micrograms/ml) and may only be administered with an infusion pump (e.g. Infusomat). A more concentrated solution may be administered via a syringe driver. For instructions on the use/handling see section 6.6.

Infusion rates (ml/hour) for different doses using an automatic infusion pump

In general, the ready-to-use infusion solution is administered intravenously using an automatic infusion pump (For instructions on the dilution for use with an infusion pump see section 6.6).

In case of an Iloprost 100 micrograms/ml Concentrate for solution for infusion concentration of 0.2 micrograms/ml, the required infusion rate must be determined according to the below described scheme, to reach a dose within the range of 0.5 to 2.0 ng/kg/min.

The following table (Table 1) can be used to calculate the infusion rate corresponding to the individual weight of the patient and the dose to be administered. Match the patient’s actual body weight on the table, then set the infusion rate on the pump, based on the desired dose in ng/kg/min.

Table 1:

Infusion rates (ml/hour) for different doses using a syringe driver

A syringe driver with a 50 ml injection syringe (e.g. Perfusor) may also be used to infuse iloprost. For instructions on the dilution for use with a syringe driver see section 6.6.

In case of an Iloprost concentration of 2 micrograms/ml, the required infusion rate must be determined according to the below described scheme (Table 2), to reach a dose within the range of 0.5 to 2.0 ng/kg/min.

The following table (Table 2) can be used to calculate the infusion rate corresponding to the individual weight of the patient and the dose to be infused. Match the patient’s actual body weight on the table, then set the infusion rate on the syringe driver based on the desired dose to be delivered in ng/kg/min.

Table 2:

The duration of treatment is up to 4 weeks.

The safety and efficacy of Iloprost 100 micrograms/ml Concentrate for solution for infusion have not been studied after treatment longer than 4 weeks or after repetitive treatment cycles.

Treatment of severe chronic ischemia of the lower limbs

The recommended dosage varies between 0.5 to 2 ng/kg/min for an infusion of 6h/per day depending on the patient’s tolerance.

Continue the treatment in general for four weeks, using the tolerated dose determined during the first two or three days of treatment.

The duration of treatment is usually four weeks. It may be less in case of early efficacy. The efficacy and safety of Iloprost 100 micrograms/ml Concentrate for solution for infusion has not been established for treatment times of more than four weeks or repeated courses of treatment in this indication. Continuous infusion over several days is not recommended. Although there were no clinical consequences, a tachyphylaxis of the effects on the platelets as well as a hyperaggregability at the stop of the treatment can occur.

Treatment of Severe Raynaud’s Phenomenon

The recommended dosage varies between 1.5 to 2 ng/kg/min depending on the patient’s tolerance. Treatment should be started at 0.5 ng/kg/min (i.e. 10 ml/h) and increased gradually every 30 minutes, according to the scheme proposed above, to reach the maximum tolerated dose by the patient. The duration of the infusion will be 6h/per day for 5 consecutive days, using the maximum tolerated dose determined during the first days of treatment.

Repeat cycles should preferably take place at intervals of 6 to 12 weeks (and never less than 4 weeks).

Special population

Renal or hepatic impairment

In patients with renal insufficiency requiring dialysis or severe hepatic impairment, caution initial titration with a reduced dose is required (e.g. half the normal dose see Section 4.4 and 5.2).

Paediatric population

Safety and efficacy of Iloprost 100 micrograms/ml Concentrate for solution for infusion in children aged up to 18 years have not been established.

Symptoms

The following symptoms might be possible: pronounced facial flush, severe headache, sometimes limb and back pain, vagal reaction with sudden pallor, sweating, nausea, vomiting, abdominal pain, cramps, diarrhoea, decreased or increase of blood pressure, bradycardia or tachycardia.

Treatment

No specific antidote is known.

Interruption of iloprost administration, monitoring and symptomatic measures are recommended.

Shelf life

Unopened: 30 months.

After opening and dilution: Chemical and physical in-use stability has been demonstrated for 24 hours at 25°C.

From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2-8°C, unless the dilution has taken place in controlled and validated aseptic conditions.

This medicinal product does not require any special storage conditions. For storage conditions after dilution of the medicinal product, see section 6.3.

Glass ampoules from glass type I (Type I hydrolytic class glass).

Iloprost 100 micrograms/ml Concentrate for solution for infusion is available in the following pack sizes:

• Box of 1 or 5 ampoules, each with 0.5 ml concentrate for solution for infusion.
• Box of 1 or 5 ampoules, each with 1 ml concentrate for solution for infusion.

Not all pack sizes may be marketed.

Iloprost 100 micrograms/ml Concentrate for solution for infusion should be used only after dilution. Due to possible interactions, no other medicinal product should be added to the ready-to-use solution for infusion.

In order to ensure sterility, the ready-to-use solution for infusion should be prepared every day.

Instructions for dilution

The ampoule contents and diluent must be thoroughly mixed.

Dilution of Iloprost 100 micrograms/ml Concentrate for solution for infusion with an infusion pump.

For this, the content of 1 ml Iloprost ampoule (i.e. 100 micrograms) is diluted with 500 ml sterile physiological sodium chloride solution or a 5% glucose solution.

The content of 0.5 ml Iloprost ampoule (i.e. 50 micrograms) is diluted with 250 ml sterile physiological sodium chloride solution or a 5% glucose solution, respectively.

Dilution of Iloprost 100 micrograms/ml Concentrate for solution for infusion with an infusion syringe pump.

For this, the contents of 1 ml Iloprost ampoule (i.e. 100 micrograms) must be diluted with 50 ml sterile physiological sodium chloride solution or 5% glucose solution.

The contents of 0.5 ml Iloprost ampoule (i.e. 50 micrograms) must be diluted with 25 ml sterile physiological sodium chloride solution or 5% glucose solution, respectively.

Handling

Keep this medicine out of the sight and reach of children.

Do NOT let Iloprost solution come into contact with your skin or eyes. If it does, rinse the skin or your eyes immediately with plenty of water.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.