MHRA released a drug safety update to disseminate recommendations for safe and effective use of terlipressin.

Terlipressin is a synthetic pituitary hormone, an analog of the vasoconstrictor vasopressin which acts by reducing portal venous pressure in the liver, in patients with portal hypertension, and also contributes to improved blood circulation in the kidney helping to restore renal function. It is authorized for treatment of following indications:

1. Bleeding from dilated veins in the food pipe leading to the stomach (bleeding oesophageal varices)
2. For emergency treatment of type 1 hepatorenal syndrome (rapidly progressive renal (kidney) failure in patients with liver cirrhosis (scarring of the liver) and ascites (fluid accumulation in the abdomen)).

Note: The recommendations in this article is applicable only to the use of terlipressin for type 1 hepatorenal syndrome. (Not relevant to use of terlipressin for bleeding oesophageal varices)

Reasons for new recommendations: Below two safety findings were observed from a recent clinical trial in patients with type 1 hepatorenal syndrome who were treated with terlipressin.

• Serious or fatal respiratory failure at a frequency higher than previously known.
• Increased risk of sepsis and septic shock.

Recommendations to Healthcare professionals:

Occurrences of these two significant safety concerns mentioned above are high in patients with below two underlying medical conditions.

1. Advanced renal impairment (severe kidney disease) – baseline serum creatinine at or above 442 µmol/L (5.0 mg/dL.
2. Advanced liver impairment (severe liver disease) – defined as Acute-on-Chronic Liver Failure (ACLF) grade 3, a Model for End-stage Liver Disease (MELD) score ≥ 39, or both

• Prescribers should avoid use of terlipressin in the patients with above two conditions, unless the individual benefit-risk assessment considered favorable (benefits outweigh risks).
• Stabilize patients with new-onset breathing difficulties or worsening of existing respiratory disease before administering terlipressin and monitor closely during treatment.
• Consider a reduction in albumin dose in patients with signs or symptoms of respiratory failure or fluid overload; discontinue terlipressin if symptoms are severe or do not resolve.
• Monitor patients daily for signs and symptoms of infection, monitor blood pressure, heart rate, oxygen saturation, serum sodium and potassium levels, and fluid balance;
• Terlipressin may induce myocardial ischaemia and pulmonary vascular congestion, especially in those with pre-existing cardiopulmonary disease, hence consider benefit-risk estimate specific to patient conditions.
• Terlipressin can be administered as a continuous intravenous infusion as an alternative to bolus injection as infusion may be associated with lower rates of severe adverse events than bolus injection.
• Counselling should be provided to patients on both the benefits and risks of using terlipressin, even if circumstance necessitates that counselling occurs after treatment with terlipressin is given.

Benefit-risk analysis specific to individual patient is quintessential for safe and effective use of medicines.

Voluntary ADR reporting:

Every medicinal product has both benefits and risks. Medicines are authorized to market based on the favorable benefit-risk profile anticipated at the time of regulatory approval/entry into market. However, the safety profile of medicine would continuously updates owing to the emerging safety data from the post marketing experience from public. If the rate of reporting of suspected adverse drug reactions (ADR) from public is line with the actual occurrence of ADRs, the time lapse for taking regulatory action can be reduced and thereby improving patient safety.

All health care professionals and consumers of pharmaceutical medicinal products are encouraged to be aware of this fact and observe/monitor for any possible adverse events, reactions, medication errors, or quality complaints of medicinal products and report the same to your respective national health authority.

This would accumulate safety evidence for medicinal products which in turn help health authorities to take regulatory actions at the earliest possibility for a better patient safety and overall public health.