How to dilute terlipressin for intravenous (IV) infusion to administer 3 milligrams (mg) per day?

From the Guidelines

To administer terlipressin at 3 mg per day, it is recommended to prepare a 24-hour infusion by adding 3 mg (3 vials) of terlipressin to 250 mL of normal saline and setting the infusion rate at approximately 10 mL per hour. This approach is based on the principle of continuous infusion, which may help reduce ischemic side effects and provide more stable plasma concentrations of the medication, as suggested by the expert review in Clinical Gastroenterology and Hepatology 1. The dose of 3 mg per day is not explicitly mentioned in the guidelines, but it is lower than the maximum recommended dose of 12 mg/d, and the continuous infusion method is an alternative approach to bolus doses. When preparing the infusion, it is essential to use normal saline (0.9% sodium chloride) as the diluent and to check the specific product information for any variations in concentration recommendations. Monitoring the patient for signs of peripheral ischemia, cardiac arrhythmias, and electrolyte disturbances during administration is also crucial.

Some key considerations for the administration of terlipressin include:

• Using a continuous infusion method to minimize side effects
• Monitoring patients for signs of peripheral ischemia, cardiac arrhythmias, and electrolyte disturbances
• Checking specific product information for concentration recommendations
• Being aware of the maximum recommended dose of 12 mg/d and the potential need to adjust the dose based on patient response, as outlined in the expert review 1.

It is also important to note that terlipressin should not be used in patients with a serum creatinine ≥5 mg/dL or oxygen saturation of <90%, as per Food and Drug Administration restrictions, as mentioned in the study 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Prior to initial dosing, assess patients for ACLF Grade 3 and obtain patient baseline oxygenation level. Monitor patient oxygen saturation with pulse oximetry. (2.1) Recommended Dosage Regimen: (2.2) Days 1 to 3 administer TERLIVAZ 0. 85 mg (1 vial) intravenously every 6 hours.

The recommended dosage regimen for terlipressin is 0.85 mg every 6 hours, which is equivalent to 3.4 mg per day (0.85 mg x 4 doses). However, to administer 3 mg per day, the dosing would need to be adjusted.

• The total daily dose of 3 mg could be achieved by administering 0.75 mg every 6 hours (0.75 mg x 4 doses = 3 mg).
• To prepare this dose, first reconstitute the 0.85 mg vial with 5 mL of 0.9% Sodium Chloride Injection, USP, as instructed in the label 2.
• Then, the reconstituted solution would need to be diluted to achieve the desired dose of 0.75 mg. However, the label does not provide explicit instructions for diluting terlipressin to achieve a specific dose of 3 mg per day. Therefore, the exact method of dilution to achieve this dose is not directly stated in the provided drug labels 2, 2, or 2.

From the Research

Dilution of Terlipressin for Infusion

To administer 3 milligrams (mg) of terlipressin per day via intravenous (IV) infusion, the dilution process is crucial for accurate dosing.

• The study 3 compared the administration of terlipressin as a continuous intravenous infusion versus intravenous boluses in the treatment of type 1 hepatorenal syndrome, indicating that terlipressin can be effectively given as a continuous infusion.
• According to 4, terlipressin was administered by intravenous infusion, initially at 3 mg/24 hours, which can be adjusted based on the patient's response.
• For a continuous infusion aimed at delivering 3 mg of terlipressin per day, the medication should be diluted appropriately to achieve the desired concentration for infusion.

Calculation for Dilution

• The exact dilution ratio may depend on the specific formulation of terlipressin and the infusion system used.
• Generally, terlipressin is diluted in a solution compatible with the medication, such as saline or dextrose, to achieve the desired concentration for infusion.
• The calculation for dilution should consider the total volume of the infusion, the desired dose of terlipressin (3 mg/day in this case), and the concentration of the terlipressin solution after dilution.

Administration Considerations

• The administration of terlipressin should be closely monitored, especially when adjusting doses or infusion rates, to minimize potential side effects and ensure efficacy.
• Studies like 5 have shown the safety and efficacy of continuous terlipressin infusion in an outpatient setting for treating portal hypertensive complications in cirrhosis, highlighting the importance of careful patient selection and monitoring.
• The choice of infusion method (continuous vs. bolus) may influence the tolerability and effectiveness of terlipressin, as suggested by 3, which found continuous infusion to be better tolerated with potentially lower effective doses.