VARIQUEL Solution for injection Ref.[8893] Active ingredients: Terlipressin

For intravenous use only. The solution should be inspected prior to administration. Do not use Variquel if it contains particles or is discoloured.

Method of administration

For administration, the required volume should be extracted from the vial with a syringe and then slowly administered intravenously over a period of at least one minute.

Posology

Adults

Oesophageal varices bleeding

The administration of terlipressin serves the emergency care for acute bleeding oesophageal varices until endoscopic therapy is available. Afterwards the administration of terlipressin for the treatment of oesophageal varices is usually an adjuvant therapy to the endoscopic haemostasis.

Initial dose: The recommended initial dose is 1 to 2 mg terlipressin acetate^# (equivalent to 5 to 10 ml of solution) administered by intravenous injection over a period of at least one minute.

Depending on the patient’s body weight the dose can be adjusted as follows:

• weight less than 50 kg: 1 mg terlipressin acetate (5 ml).
• weight 50kg to 70 kg: 1.5 mg terlipressin acetate (7.5 ml).
• weight exceeding 70 kg: 2 mg terlipressin acetate (10 ml).

Maintenance dose: After the initial injection, the dose can be reduced to 1 mg terlipressin acetate every 4 to 6 hours.

^# 1 to 2 mg terlipressin acetate corresponding to 0.85 to 1.7 mg terlipressin

The approximate value for the maximum daily dose of Variquel is 120 μg/kg body weight.

The therapy is to be limited to 2–3 days in adaptation to the course of the disease.

Hepatorenal syndrome

Treatment in adults is usually started with a dose of 1 mg terlipressin acetate^# (5 ml of solution) at 4 to 6-hour intervals. The dose can be increased to a maximum of 2 mg terlipressin acetate^# (10 ml of solution) every 4 hours if the serum creatinine does not decrease by at least 25% after 3 days of treatment.

^# 1 mg terlipressin acetate corresponding to 0.85 mg terlipressin; 2 mg terlipressin acetate corresponding to 1.7 mg terlipressin

The treatment is continued until the serum creatinine has dropped below 1.5 mg/dl (133 µmol/l). In patients with a partial response (serum creatinine does not drop below 133 µmol/l) or in patients whose serum creatinine does not decrease, treatment should be stopped within 14 days.

In most clinical studies supporting the use of terlipressin for the treatment of hepatorenal syndrome, human albumin was administered simultaneously at a dosage of 1 g/kg of body weight on the first day and afterwards at a dosage of 20-40 g/day.

The usual duration of treatment of hepatorenal syndrome is 7 days, and the maximum recommended duration is 14 days.

Elderly patients

Variquel should be used with caution in patients over 70 years of age (see section 4.4). There are no dosage recommendations for the elderly.

Paediatric population

The safety and efficacy of Variquel in children and adolescents has not yet been established. No data are available. Variquel is not recommended in children and adolescents (see section 4.4).

Renal insufficiency

Variquel should only be used with caution in patients with chronic renal failure (see section 4.4).

Hepatic insufficiency

A dose adjustment is not required in patients with liver failure.

The recommended dose should not be exceeded in any case, since the risk of severe circulatory adverse effects is dose dependent.

An acute hypertensive crisis, especially in patients with recognized hypertension can be controlled with a vasodilator-type alpha-blocker, e.g. 150 microgram clonidine intravenously.

Bradycardia requiring treatment should be treated with atropine.

Unopened: 3 years.

Store in a refrigerator (2°C-8°C).

Keep the vial in the outer carton in order to protect from light.

From a microbiological point of view, after first opening, the product should be used immediately.

Colourless glass type I vials, closed with bromobutyl rubber stopper and sealed with aluminium flip-off cap (green).

Each vial contains 5 ml of solution.

Pack sizes: 5 × 5ml.

No special requirements.

For single use only. Discard any unused solution.

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