SIMDAX Injection Ref.[8654] Active ingredients: Levosimendan

Method of Administration

Simdax is for in-hospital use only. It should be administered in a hospital setting where adequate monitoring facilities and expertise with the use of inotropic agents are available.

Simdax 2.5mg/mL injection concentrate is to be diluted prior to administration.

Simdax 2.5mg/mL injection concentrate is intended for single use only. As for all parenteral medicinal products, inspect the diluted solution visually for particulate matter and discoloration prior to administration.

The colour of the concentrate may turn to orange during storage, but there is no loss of potency, and the product may be used until the indicated expiration date if storage instructions have been followed.

The infusion is for intravenous use only and can be administered by the peripheral or central route.

Dosing Schedule

The dose and duration of treatment should be individualised according to the patient’s clinical condition and response.

The treatment may be initiated with a loading dose of 6-12 μg/kg infused over 10 minutes followed by a continuous infusion of 0.1 μg/kg/min (see section 5.1, Pharmacodynamics). The lower loading dose of 6 μg/kg is recommended for patients on concomitant intravenous vasodilators or inotropes or both at the start of the infusion. Higher loading doses within this range will produce a stronger haemodynamic response but may be associated with a transient increased incidence of adverse reactions. The response of the patient should be assessed with the loading dose or within 30 to 60 minutes of dose adjustment and as clinically indicated. If the response is deemed excessive (hypotension, tachycardia), the rate of the infusion may be decreased to 0.05 μg/kg/min or discontinued (see section 4.4, Special warnings and precautions for use). If the initial dose is tolerated and an increased haemodynamic effect is required, the rate of the infusion can be increased to 0.2 μg/kg/min.

The recommended duration of infusion in patients with acute decompensation of severe chronic heart failure is 24 hours. No signs of development of tolerance or rebound phenomena have been observed following discontinuation of Simdax infusion. Haemodynamic effects persist for at least 24 hours and may be seen up to 9 days after discontinuation of a 24 hour infusion (see section 5.1, Pharmacodynamics; section 4.4, Special warnings and precautions for use; section 4.5, Interaction with other medicines and other forms of interaction).

Experience of repeated administration of Simdax is limited. Experience with concomitant use of vasoactive agents, including inotropic agents (except digoxin), is limited. In the REVIVE programme, a lower loading dose (6 μg/kg) was administered with baseline concomitant vasoactive agents.

Elderly

No dose adjustment is required for elderly patients.

Renal impairment

Simdax must be used with caution in patients with mild to moderate renal impairment. Simdax should not be used in patients with severe renal impairment (creatinine clearance <30mL/min) (see section 5.2, Pharmacokinetics; section 4.3, Contraindications; section 4.4, Special warnings and precautions for use).

Hepatic impairment

Simdax must be used with caution in patients with mild to moderate hepatic impairment. Simdax should not be used in patients with severe hepatic impairment (see section 5.2, Pharmacokinetics; section 4.3, Contraindications; section 4.4, Special warnings and precautions for use).

Children

Simdax should not be administered to children and adolescents under 18 years of age (see section 5.2, Pharmacokinetics; section 4.4, Special warnings and precautions for use).

Infusion Preparation and Schedule

To prepare the 0.05mg/mL infusion, mix 10mL of Simdax 2.5mg/mL injection concentrate with 500mL of 5% glucose (dextrose) solution.

Table 1 provides detailed infusion rates for both the loading and maintenance infusion doses of a 0.05 mg/mL preparation of Simdax infusion:

Table 1:

To prepare the 0.025mg/mL infusion, mix 5mL of Simdax 2.5mg/mL injection concentrate with 500mL of 5% glucose (dextrose) solution.

Table 2 provides detailed infusion rates for both the loading and maintenance infusion doses for a 0.025 mg/mL preparation of Simdax infusion:

Table 2:

Compatibilities

Incompatibilities with Simdax and the following medications have not been observed in connected intravenous lines:

• Frusemide 10mg/mL
• Digoxin 0.25mg/mL
• Glyceryl trinitrate 0.1mg/mL

Incompatibilities

This medicinal product must not be mixed with other medicinal products or diluents except those stated in Dosage and Administration – Infusion Preparation and Schedule; Dosage and Administration – Compatibilities.

After 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. To reduce microbiological hazard, use as soon as practicable after dilution. If storage is necessary, hold at 2 o -8 o C for not more than 24 hours. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user. Storage and in-use time after dilution should never exceed 24 hours.

Contains no antimicrobial agent. Product is for single use in one patient only. Discard any residue.

Monitoring of Treatment

Consistent with current medical practice, ECG, blood pressure, and heart rate must be monitored during treatment and the urine output measured. Monitoring of these parameters for at least 3 days after the end of infusion or until the patient is clinically stable is recommended (see section 4.4, Special warnings and precautions for use). In patients with mild to moderate renal or mild to moderate hepatic impairment monitoring is recommended for at least 5 days.

Overdose of Simdax may induce hypotension and tachycardia. In clinical trials with Simdax, hypotension has been successfully treated with vasopressors (e.g. dopamine in patients with congestive heart failure and adrenaline in patients following cardiac surgery). Excessive decreases in cardiac filling pressures may limit the response to Simdax and can be treated with parenteral fluids. High doses (at or above 0.4 μg/kg/min) and infusions over 24 hours increase the heart rate and are sometimes associated with prolongation of the QTc interval. In the event of an overdose of Simdax, continuous ECG monitoring, repeated determinations of serum electrolytes and invasive haemodynamic monitoring should be undertaken. Simdax overdose leads to increased plasma concentrations of the active metabolite, which may lead to a more pronounced and prolonged effect on heart rate requiring a corresponding extension of the observation period.

For advice on the management of overdose please contact the National Poisons Centre on 0800 POISON (0800 764766).

24 months from the date of manufacture.

Store at 2°-8°C. Refrigerate. Do not freeze.

The colour of the concentrate may turn to orange during storage, but there is
no loss of potency, and the product may be used until the indicated expiration
date if storage instructions have been followed.

Levosimendan 2.5 mg/mL concentrate is available in 5 mL and 10 mL vials.

• 8 or 10 mL Type I glass vials containing 2.5mg levosimendan/mL.
• Chlorobutyl or Bromobutyl rubber closure with fluoropolymer coating

Pack sizes:

• 1, 4, 10 vials of 5 mL
• 1, 4, 10 vials of 10 mL

No data available.