Is it safe to add midodrine and terlipressin together?

From the Guidelines

Combining midodrine and terlipressin is generally not recommended due to the risk of excessive vasoconstriction. Both medications are vasoconstrictors that increase blood pressure - midodrine is an alpha-1 adrenergic agonist while terlipressin is a vasopressin analog. Using them together could potentially cause dangerous elevations in blood pressure, peripheral ischemia, or organ hypoperfusion. These medications have overlapping mechanisms and effects, making their combination redundant and potentially hazardous.

In clinical practice, they are typically used as alternative options rather than in combination. If a patient is not responding adequately to one agent, healthcare providers usually switch to the other rather than adding them together. Any consideration of using both should only occur under close specialist supervision with careful blood pressure monitoring and clear dose adjustments. Patients with cardiovascular disease, peripheral vascular disease, or kidney problems would be at particularly high risk from this combination. According to the most recent study 1, midodrine in combination with octreotide is inferior to terlipressin as a treatment for hepatorenal syndrome type 1, and there is no evidence to support the use of midodrine and terlipressin together.

Some key points to consider when managing patients with hepatorenal syndrome include:

• The use of vasoconstrictors, such as terlipressin, in combination with albumin, to improve kidney function and reduce mortality 1.
• The importance of careful monitoring and dose adjustments to minimize the risk of adverse effects, such as ischemic complications and respiratory failure 1.
• The need for close specialist supervision and consideration of alternative treatment options, such as switching to a different vasoconstrictor or using a combination of midodrine and octreotide, if a patient is not responding adequately to one agent 1.

Overall, the combination of midodrine and terlipressin is not recommended due to the risk of excessive vasoconstriction and the potential for adverse effects. Instead, healthcare providers should consider alternative treatment options and carefully monitor patients to minimize the risk of complications.

From the Research

Safety of Adding Midodrine and Terlipressin Together

There is limited research on the safety of adding midodrine and terlipressin together. However, the available studies provide some insights:

• A study published in 2021 2 compared the efficacy of midodrine/octreotide to norepinephrine for the treatment of patients with hepatorenal syndrome, but it did not investigate the combination of midodrine and terlipressin.
• Another study from 2021 3 evaluated the effectiveness of a sequential vasoconstrictor regimen of midodrine-octreotide followed by norepinephrine, but it did not assess the safety of combining midodrine and terlipressin.
• A randomized controlled trial from 2015 4 compared the effectiveness of terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome, but it did not investigate the combination of midodrine and terlipressin.
• A systematic review and meta-analysis from 2018 5 compared the efficacy of various drugs in the treatment of hepatorenal syndrome, including terlipressin and midodrine, but it did not assess the safety of combining these two drugs.
• A recent review from 2025 6 discussed the diagnosis and management of hepatorenal syndrome, including the use of vasoconstrictive agents such as terlipressin and norepinephrine, but it did not provide information on the safety of combining midodrine and terlipressin.

Key Points to Consider

• The available studies do not provide direct evidence on the safety of adding midodrine and terlipressin together.
• Terlipressin is considered a first-line treatment for hepatorenal syndrome, while midodrine is often used as an alternative when terlipressin is not available.
• The use of vasoconstrictive agents, including terlipressin and norepinephrine, requires careful patient selection and monitoring due to the risk of potentially fatal respiratory failure.
• Further research is needed to determine the safety and efficacy of combining midodrine and terlipressin in the treatment of hepatorenal syndrome.