A registered nurse provides step-by-step administration and monitoring information, as well as practical considerations to take into account when deciding whether to use Terlivaz.

You are about to hear from a healthcare practitioner about TERLIVAZ (terlipressin) and select relevant information about its administration, patient monitoring, and practical considerations

This speaker is a paid consultant of Mallinckrodt and has been compensated for her time in preparing this video

This presentation is for informational purposes only

You are to use your own medical judgement when making individual patient treatment decisions

Please refer to the Prescribing Information for full product information

INDICATION AND LIMITATION OF USE

TERLIVAZ (terlipressin) is indicated to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function. Patients with a serum creatinine >5 mg/dL are unlikely to experience benefit.

IMPORTANT SAFETY INFORMATION

WARNING: SERIOUS OR FATAL RESPIRATORY FAILURE
TERLIVAZ may cause serious or fatal respiratory failure. Patients with volume overload or with acute-on-chronic liver failure (ACLF) Grade 3 are at increased risk. Assess oxygenation saturation (e.g., SpO₂) before initiating TERLIVAZ. Do not initiate TERLIVAZ in patients experiencing hypoxia (e.g., SpO₂ <90%) until oxygenation levels improve. Monitor patients for hypoxia using continuous pulse oximetry during treatment and discontinue TERLIVAZ if SpO₂ decreases below 90%.

Please see additional Important Safety Information at the end of this video and full Prescribing Information, including Boxed Warning, available at www.terlivaz.com.

Hi, my name is Amy Olofson, and I am a Registered Nurse

TERLIVAZ is the first and only FDA-approved treatment to improve kidney function in adults with hepatorenal syndrome with rapid reduction in kidney function

In this video, you will learn how to properly administer TERLIVAZ and monitor your patients on this medication

First, we will begin with the proposed mechanism of action

TERLIVAZ is a synthetic vasopressin analogue that has twice the level of selectivity for vasopressin V1 receptors over V2 receptors

It is important to note that TERLIVAZ exerts its effect in the splanchnic circulation

TERLIVAZ acts both as a prodrug for lysine-vasopressin, as well as having pharmacological activity on its own

As previously mentioned, TERLIVAZ primarily works within the splanchnic circulation. It is thought to increase renal blood flow in patients with hepatorenal syndrome by reducing portal hypertension, reducing blood circulation in portal vessels, and by increasing effective arterial volume and mean arterial pressure

Please note that the mechanism for TERLIVAZ is not fully understood, and its clinical relevance requires further investigation

The pharmacokinetic and pharmacodynamic properties of TERLIVAZ have been studied in clinical trials

First, let’s discuss the pharmacokinetic properties

The terminal half-life of TERLIVAZ is approximately 50 minutes, which is shorter than the half-life of lysine-vasopressin of 3 hours

Next, let’s discuss the pharmacodynamic properties

A single 0.85 mg dose of TERLIVAZ in hepatorenal syndrome patients can have the following effects seen within 5 minutes, which are also maintained for at least 6 hours

The first effect is an increase in both systolic and diastolic pressure, as well as the mean arterial pressure with an estimated maximum increase of 16.2 millimeters of mercury

The second effect is a decrease in heart rate of an estimated maximum of 10.6 beats per minute

The maximum change for both blood pressure and heart rate was seen 1.2 to 2 hours after the initial dose

You may notice that the vial and packaging indicate that each vial contains 0.85 mg terlipressin. This is equivalent to 1 mg of terlipressin acetate, which is the dose commonly used in the published literature. Each vial contains one dose of terlipressin, and no further dose adjustments need to be made

TERLIVAZ has to be reconstituted prior to administration with 5 mL of 0.9% sodium chloride injection. Make sure to visually inspect the vial for any particulate matter or discoloration prior to administration

TERLIVAZ is supplied as a sterile, preservative-free, white to off-white lyophilized powder in a single-dose vial. The vial must be stored in the fridge between 2 and 8 °C (36 to 46 °F) for up to 48 hours, and protected from light

You may notice that the medication looks slightly different from vial to vial. This type of powder distribution within the vial is normal and does not affect the overall quality of the medication

If TERLIVAZ is not administered immediately after reconstitution, it should be stored under the refrigerated conditions mentioned earlier for up to 48 hours, but do not freeze it

The reconstituted solution does not need to be protected from light

There are a few important considerations to make prior to initiating TERLIVAZ to determine if TERLIVAZ is appropriate for your patient

TERLIVAZ carries a boxed warning of increased risk of serious or fatal respiratory failure

Prior to initiating therapy, assess patient’s ACLF grade, and measure baseline oxygen saturation and volume status

If the patient is experiencing hypoxia or SpO₂ levels of less than 90%, do not initiate TERLIVAZ unless and until oxygen levels improve

It is also important to make sure that the information needed to assess ACLF grade is readily available

For those who are not familiar with ACLF grading, it is a scale used to evaluate severity of illness and ranges from 0 to 3 depending on the number of organ failures. For instance, an ACLF grade of 0 indicates 0 organ failures, while an ACLF grade of 3 indicates 3 or more organ failures

Avoid use of TERLIVAZ in patients who have an ACLF grade of 3 as their risk of respiratory failure is increased

However, clinical judgment should be used when making treatment decisions for patients with ACLF grade 3

Finally, discuss any signs of intravascular volume overload with the healthcare team because this may warrant a change in the course of therapy

If intravascular volume overload is present prior to treatment, reduce or discontinue the use of albumin and/or other fluids and judiciously use diuretics

As a reminder, each vial of TERLIVAZ contains 0.85 mg terlipressin, which is equivalent to 1 mg of terlipressin acetate

It is important to record the last available serum creatinine value prior to initiating treatment

If previous labs are not available, a serum creatinine value should be drawn prior to treatment

Please follow your institution’s policy for appropriate recording and documentation practices

For the first 3 days of treatment, TERLIVAZ should be administered by slow intravenous bolus injection over 2 minutes every 6 hours

Day 4 provides an opportunity to assess the patient’s response to TERLIVAZ. Based on the change in serum creatinine from Day 1 of treatment to Day 4, the dose of TERLIVAZ can be adjusted

If your patient’s serum creatinine has decreased by 30% or more from baseline, which is the last available value before initiating treatment, then continue administering TERLIVAZ 0.85 mg or 1 vial every 6 hours

On the other hand, if your patient’s serum creatinine has decreased by less than 30% from baseline, then you may increase TERLIVAZ dose to 1.7 mg or 2 vials every 6 hours

It is important to discontinue TERLIVAZ if your patient’s serum creatinine is at or above the baseline value

For patients still receiving TERLIVAZ, continue the dose until 24 hours after the patient achieves a second consecutive serum creatinine value ≤1.5 mg/dL at least 2 hours apart

TERLIVAZ should be discontinued if patients are on treatment for a maximum of 14 days

It is important to note that in the CONFIRM trial, the mean duration of treatment was 6.2 days in the patients treated with TERLIVAZ compared to 6.0 days for the patients treated with placebo

This dosing algorithm can be found in Section 2.2 of the Prescribing Information

Once reconstituted, TERLIVAZ can be administered through a peripheral or central line—a dedicated central line is not required

TERLIVAZ should be administered by slow intravenous bolus injection over 2 minutes and re-administered every 6 hours

The line needs to be flushed after administration

Additionally, TERLIVAZ can be administered outside of the ICU for appropriate patients. In fact, 84.4% of patients in the clinical trial were treated on the medical floor

Keep in mind that you are advised to use your own medical judgement in making patient-specific treatment decisions

In the clinical trial, the most common adverse reactions seen in ≥10% of TERLIVAZ-treated patients were abdominal pain, nausea, diarrhea, respiratory failure, and dyspnea

The incidence of respiratory failure was higher in patients receiving TERLIVAZ (15.5%) compared to patients receiving placebo (7.1%)

In the next part of the video, we will discuss how you can help manage these patients in your care

During therapy, monitor oxygen saturation and respiratory failure status using continuous pulse oximetry and discontinue TERLIVAZ use if the patient experiences hypoxia

As mentioned before, avoid use of TERLIVAZ in patients who have an ACLF grade of 3 as their risk of respiratory failure is increased

Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and judiciously using diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves

In the clinical study, when respiratory failure occurred with TERLIVAZ, it had a median onset of 5 days, an average onset of 7.5 days, and a range of 1 to 67 days

Recurrence may occur in patients after treatment discontinuation. In these instances, patients may be retreated if appropriate

Thank you for watching this instructional video on how to use TERLIVAZ. I hope this information has been beneficial to you in your continued journey to help treat and manage patients with hepatorenal syndrome.

As mentioned earlier, we will now review some additional important safety information.

Contraindications
TERLIVAZ (terlipressin) is contraindicated:
In patients experiencing hypoxia or worsening respiratory symptoms and in patients with ongoing coronary, peripheral, or mesenteric ischemia.

Warnings and Precautions
Serious or Fatal Respiratory Failure: Obtain baseline oxygen saturation and do not initiate TERLIVAZ in hypoxic patients. Monitor patients for changes in respiratory status using continuous pulse oximetry and regular clinical assessments. Discontinue TERLIVAZ in patients experiencing hypoxia or increased respiratory symptoms.

Manage intravascular volume overload by reducing or discontinuing the administration of albumin and/or other fluids and through judicious use of diuretics. Temporarily interrupt, reduce, or discontinue TERLIVAZ treatment until patient volume status improves. Avoid use in patients with ACLF Grade 3 because they are at significant risk for respiratory failure.

Ineligibility for Liver Transplant: TERLIVAZ (terlipressin)-related adverse reactions (respiratory failure, ischemia) may make a patient ineligible for liver transplantation, if listed. For patients with high prioritization for liver transplantation (e.g., MELD ≥35), the benefits of TERLIVAZ may not outweigh its risks.

Ischemic Events: TERLIVAZ may cause cardiac, cerebrovascular, peripheral, or mesenteric ischemia. Avoid use of TERLIVAZ in patients with a history of severe cardiovascular conditions or cerebrovascular or ischemic disease. Discontinue TERLIVAZ in patients who experience signs or symptoms suggestive of ischemic adverse reactions.

Embryo-Fetal Toxicity: TERLIVAZ may cause fetal harm when administered to a pregnant woman. If TERLIVAZ is used during pregnancy, the patient should be informed of the potential risk to the fetus.

Adverse Reactions
The most common adverse reactions (≥10%) include abdominal pain, nausea, respiratory failure, diarrhea, and dyspnea.

Please see full Prescribing Information, including Boxed Warning, available at www.terlivaz.com.

For more information on TERLIVAZ, please visit www.terlivaz.com or speak to a TERLIVAZ customer service representative through email at specialtybrandspm@mnk.com.

Mallinckrodt, the “M” brand mark and the Mallinckrodt Pharmaceuticals logo are trademarks of a Mallinckrodt company. Other brands are trademarks of a Mallinckrodt company or their respective owners.

© 2022 Mallinckrodt. US-2200929. 12/2022