Glypressin Special Precautions

Warnings and precautions applicable to type 1 hepatorenal syndrome: Prior to treatment of type 1 hepatorenal syndrome, other types of acute kidney injury should be ruled out.
Renal impairment: Terlipressin should be avoided in patients with advanced renal dysfunction, i.e., baseline serum creatinine ≥442 μmol/L (5.0 mg/dL), when treated with terlipressin for type 1 hepatorenal syndrome, unless the benefit is judged to outweigh the risks. Reduced efficacy in reversal of hepatorenal syndrome, increased risk of adverse events, and increased mortality in this patient group have been observed in clinical trials (see Dosage & Administration).
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, when treated with terlipressin for type 1 hepatorenal syndrome, unless the benefit is judged to outweigh the risks. Reduced efficacy in reversal of hepatorenal syndrome, increased risk of respiratory failure, and increased mortality in this patient group have been observed in clinical trials (see Dosage & Administration).
Respiratory events: Fatal cases of respiratory failure, including respiratory failure due to fluid overload, have been reported in patients treated with terlipressin for type 1 hepatorenal syndrome.
Patients with a new onset of breathing difficulties or worsening of respiratory disease should be stabilised prior to receiving their first dose of terlipressin.
Caution should be exercised when terlipressin is administered together with human albumin as part of the standard of care for type 1 hepatorenal syndrome. In case of signs or symptoms of respiratory failure or fluid overload, dose reduction of human albumin should be considered. If respiratory symptoms are severe or do not resolve, treatment with terlipressin should be discontinued.
Sepsis/septic shock: Cases of sepsis/septic shock, including fatal cases, have been reported in patients treated with terlipressin for type 1 hepatorenal syndrome. Causal association to terlipressin has not been established. Patients should be monitored daily for any signs or symptoms suggestive of infection.
Warnings and precautions applicable to all indications: Monitoring during treatment: During treatment, regular monitoring of blood pressure, ECG or heart rate, oxygen saturation, serum levels of sodium and potassium, as well as fluid balance are required.
Patient with cardiovascular and pulmonary disease: Particular care is required in management of patients with cardiovascular or pulmonary disease since terlipressin may induce ischaemia and pulmonary vascular congestion. Caution should also be exercised in treating patients with hypertension.
Patients with septic shock: In patients with septic shock with a low cardiac output terlipressin should not be used.
Injection site reaction: To avoid local necrosis at the injection site, the injection must be given IV.
Skin necrosis: During post-marketing experience with terlipressin several cases of cutaneous ischaemia and necrosis unrelated to the injection site have been reported (see Adverse Reactions). Patients with diabetes mellitus and obesity seem to have a greater tendency to this reaction. Therefore, caution should be exercised when administering terlipressin in these patients.
Cardiovascular Effects: Terlipressin should only be used with caution and under strict monitoring of the patients in the following cases: uncontrolled hypertension, cerebral or peripheral vascular diseases, cardiac arrhythmias, coronary artery disease or previous myocardial infarction.
Terlipressin should not be used in patients with unstable angina or recent acute myocardial infarction.
Torsade de pointes: During clinical trials and post-marketing experience, several cases of QT interval prolongation and ventricular arrhythmias including "Torsade de pointes" have been reported (see Adverse Reactions). In most cases, patients had predisposing factors such as basal prolongation of the QT interval, electrolyte abnormalities (hypokalaemia, hypomagnesaemia) or medications with concomitant effect on QT prolongation. Therefore, extreme caution should be exercised in the use of terlipressin in patients with a history of QT interval prolongation, electrolytic abnormalities, or concomitant medications that can prolong the QT interval (see Interactions).
Respiratory Effects: Terlipressin may cause smooth muscle constriction and should be used with caution and under strict monitoring in patients with severe asthma or chronic obstructive pulmonary disease (COPD).
Laboratory Monitoring: During treatment with terlipressin, serum creatinine should be monitored at least daily as terlipressin should be used with caution in patients with renal insufficiency. Fluid balance and electrolytes should be monitored carefully as hyponatraemia, hypokalaemia, hypomagnesaemia and other electrolyte disturbances have been reported.
Sodium content: This medicinal product contains 30.7 mg of sodium per ampoule, equivalent to 1.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
Use in Children and the Elderly: Particular caution should be exercised in the treatment of children and elderly patients, as experience is limited in these groups.