TERLIPRESSIN-AFT SOLUTION FOR INJECTION 0.85MG/8.5ML [SIN17190P]

Product Info

TERLIPRESSIN-AFT SOLUTION FOR INJECTION 0.85MG/8.5ML

[SIN17190P]

4.1 THERAPEUTIC INDICATIONS

Bleeding oesophageal varices

Treatment of patients with hepatorenal syndrome (HRS) Type 1 who are actively being considered for liver transplant.

4.2 DOSE AND METHOD OF ADMINISTRATION

Bleeding Oesophageal Varices (BOV)

Posology

Adults: Initially an i.v. injection of 2 vials of Terlipressin-AFT solution for injection (equivalent to 1.7 mg terlipressin) is given every 4 hours. The treatment should be maintained until bleeding has been controlled for 24 hours, but up to a maximum of 48 hours. After the initial dose, the dose can be adjusted to 1 vial of Terlipressin-AFT solution for injection (equivalent to 0.85 mg terlipressin) i.v. every 4 hours in patients with body weight < 50 kg or if adverse effects occur.

Method of Administration

Intravenous injection

Hepatorenal Syndrome (HRS)

Posology

1 vial of Terlipressin-AFT solution for injection (equivalent to 0.85 mg terlipressin) every 6 to 12 hours by slow intravenous bolus injection for 7 to 14 days (administered in association with albumin 20% 100 mL IV twice daily for 7 to 14 days).

If serum creatinine (SCr) has not decreased by at least 30% from the baseline value after 3 days, the dose can be increased to a maximum of 2 vials of Terlipressin-AFT solution for injection (equivalent to 1.7 mg terlipressin) every 6 hours.

It is however recommended that the dose not be increased in patients with severe preexisting cardiovascular disease or in the presence of an ongoing significant adverse event e.g. pulmonary oedema, ischaemia. Treatment should be continued until about 2 days after the patient achieves HRS reversal (SCr less than or equal to 132.6 micromole/L), or be discontinued if the patient undergoes dialysis or liver transplant or if SCr remains at or above baseline after 7 days of treatment.

Management of suspected adverse drug reactions may require temporary interruption and/or dose reduction. When the patient’s symptoms resolve, Terlipressin-AFT may be re-commenced at a lower dose or at a less frequent dosing interval (e.g., every 8 – 12 hours). The lowest doses used in the clinical studies ranged from 1.7 to 2.55 mg terlipressin/day. The maximum dose studied (TAHRS Study*) was 1.7 mg terlipressin every 4 hours.

*The study of Martín–Llahí et al. (2008), also known as the TAHRS study, was a supportive open-label, comparative multicentre study in 46 patients who were randomised in a 1:1 ratio to receive either intravenous terlipressin (0.85 – 1.7 mg (as 1 to 2 mg terlipressin acetate) every 4 hours) plus 20% albumin or 20% albumin alone, for a maximum of 15 days. The majority of patients had HRS type 1 (35/46) and the remainder, HRS type 2 (11/46).

As an alternative to bolus injection, terlipressin can be administered as a continuous IV infusion with a starting dose of 2 mg of terlipressin acetate/24 hours and increased to a maximum of 12 mg of terlipressin acetate/24 hours. If volume expansion is needed, Terlipressin-AFT can be diluted before administration. See section 6.7 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information. Administration of terlipressin as continuous IV infusion has been associated with lower rates of severe adverse events than with administration by IV bolus (see section 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Special populations

Renal impairment

Terlipressin should be avoided in patients with advanced renal dysfunction, i.e., baseline serum creatinine ≥ 442 micromole/L (5.0 mg/dL), unless the benefit is judged to outweigh the risks (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

Terlipressin should be avoided in patients with severe liver disease defined as Acute-on-Chronic Liver Failure (ACLF) grade 3 and/or a Model for End-stage Liver Disease (MELD) score ≥ 39, unless the benefit is judged to outweigh the risks (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Elderly

There is no data available regarding dosage recommendation in the elderly.

Paediatric population

There is no data available regarding dosage recommendation in the paediatric population.

Method of Administration

Intravenous injection

Type 1 hepatorenal syndrome: IV injection or IV infusion

4.3 CONTRAINDICATIONS

• Pregnancy

• Hypersensitivity to terlipressin or any other excipients of the product listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information