Difelikefalin (Topical) Monograph for Professionals - Drugs.com

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# Difelikefalin (Topical)

Brand name: Korsuva
Drug class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical name: 4-amino-1-[(2R)-6-amino-2-[[(2R)-2-[[(2R)-2-[[(2R)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid
Molecular formula: C36H53N7O6
CAS number: 1024828-77-0

Medically reviewed by Drugs.com on Sep 13, 2021. Written by ASHP.

## Introduction

Difelikefalin acetate is a kappa opiate receptor agonist that is used for its antipruritic effects.

## Uses for Difelikefalin (Topical)

### Difelikefalin acetate has the following uses:

Difelikefalin acetate is a kappa opiate receptor agonist indicated for the treatment of moderate-to-severe pruritus associated with chronic kidney disease (CKD-aP) in adults undergoing hemodialysis (HD).

### Difelikefalin acetate has the following limitations of use:

Difelikefalin acetate has not been studied in patients on peritoneal dialysis and is not recommended for use in this population.

## Difelikefalin (Topical) Dosage and Administration

### General

Difelikefalin acetate is available in the following dosage form(s) and strength(s):

Injection: 65 mcg /1.3 mL (50 mcg/mL) of difelikefalin

### Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

#### Adults

##### Dosage and Administration

- Recommended dosage is 0.5 mcg/kg.

- Administer by intravenous bolus injection into the venous line of the dialysis circuit at the end of each HD treatment.

- Do not mix or dilute difelikefalin acetate prior to administration.

- Administer within 60 minutes of syringe preparation.

Detailed Difelikefalin dosage information

## Cautions for Difelikefalin (Topical)

### Contraindications

- None.

### Warnings/Precautions

#### Dizziness, Somnolence, Mental Status Changes, and Gait Disturbances

Dizziness, somnolence, mental status changes, and gait disturbances (including falls) have occurred in patients taking difelikefalin acetate and may subside over time with continued treatment. In 2 clinical trials, 17.0% of patients randomized to receive difelikefalin acetate reported at least one of these adverse reactions, compared to 12.0% of patients who received placebo. The incidence of somnolence was higher in difelikefalin acetate-treated subjects 65 years of age and older (7.0%) than in difelikefalin acetate-treated subjects less than 65 years of age (2.8%). Concomitant use of centrally acting depressant medications, sedating antihistamines, and opiate analgesics may increase the likelihood of these adverse reactions and should be used with caution during treatment with difelikefalin acetate.

#### Risk of Driving and Operating Machinery

Dizziness, somnolence, and mental status changes have occurred in patients taking difelikefalin acetate. Difelikefalin acetate may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car and operating machinery. Advise patients not to drive or operate dangerous machinery until the effect of difelikefalin acetate on a patient’s ability to drive or operate machinery is known.

#### Specific Populations

##### Pregnancy

Risk Summary: The limited human data on use of difelikefalin acetate in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage. In animal reproduction studies, intravenous injection of difelikefalin to pregnant rats and rabbits during the period of organogenesis at doses 711 and 10 times the maximum recommended human dose (MRHD), respectively, resulted in no adverse effects in either rats or rabbits.

Animal Data: In an embryofetal development study, difelikefalin was administered by intravenous injection to pregnant rats at doses of 0.25, 2.5, and 25 mg/kg per day during the period of organogenesis. Difelikefalin was not associated with embryofetal lethality or fetal malformations. Difelikefalin increased the incidences of skeletal variations (wavy ribs and incompletely ossified ribs) at the dose of 25 mg/kg per day (711 times the MRHD based on AUC comparison). In an embryofetal development study, difelikefalin was administered by intravenous injection to pregnant rabbits at doses of 0.025, 0.05, and 0.1 mg/kg per day during the period of organogenesis. Maternal toxicity evidenced by decreased maternal body weight gain was noted in all dose groups. Difelikefalin was not associated with embryofetal lethality or fetal malformations at doses up to 0.1 mg/kg per day (10 times the MRHD based on AUC comparison). In a prenatal and postnatal development study, difelikefalin was administered by intravenous injection to pregnant rats at doses of 0.6, 2.5, and 10 mg/kg per day beginning on gestation day 7 and continuing through lactation day 20. Persisting effects on decreased maternal body weight and/or maternal body weight gain as well as food consumption were noted at doses greater than or equal to 2.5 mg/kg per day (68 times the MRHD based on AUC comparison). No maternal effects were observed at 0.6 mg/kg per day (14 times the MRHD based on AUC comparison). No difelikefalin-related effects on postnatal developmental, neurobehavioral, or reproductive performance of offspring were noted at doses up to 10 mg/kg per day (282 times the MRHD based on AUC comparison).

##### Lactation

Risk Summary: There are no data regarding the presence of difelikefalin acetate in human milk or effects on the breastfed infant or on milk production. Studies in rats showed difelikefalin was transferred into milk in lactating rats. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for difelikefalin acetate and any potential adverse effects on the breastfed child from difelikefalin acetate or from the underlying maternal condition.

Animal Data: Difelikefalin was administered to lactating rats by intravenous injection at doses of 0.6, 2.5, or 10 mg/kg per day from gestation day 7 through lactation day 14. Difelikefalin was detected in the milk of the lactating rats with the concentration ratio for milk:plasma of 0.04 to 0.05 across the doses. There was no measurable difelikefalin in the plasma of nursing pups.

##### Pediatric Use

The safety and effectiveness of difelikefalin acetate in pediatric patients have not been established.

##### Geriatric Use

Of the 848 subjects in the placebo-controlled studies who received difelikefalin acetate, 278 subjects (32.8%) were 65 years of age and older and 98 subjects (11.6%) were 75 years of age and older. No overall differences in safety or effectiveness of difelikefalin acetate have been observed between patients 65 years of age and older and younger adults, with the exception of the incidence of somnolence, which was higher in difelikefalin acetate-treated subjects 65 years of age and older (7.0%) than in difelikefalin acetate-treated subjects less than 65 years of age (2.8%), and was comparable in both placebo-treated age groups (3.0% and 2.1%, respectively). No differences in plasma concentrations of difelikefalin acetate were observed between subjects 65 years of age and older and younger adults.

##### Hepatic Impairment

The influence of mild-to-moderate hepatic impairment on the pharmacokinetics of difelikefalin acetate was evaluated in a population pharmacokinetic analysis which concluded that no difelikefalin acetate dosage adjustments are needed in these populations. The influence of severe hepatic impairment on the pharmacokinetics of difelikefalin acetate in subjects undergoing HD has not been evaluated; therefore, use of difelikefalin acetate in this population is not recommended.

### Common Adverse Effects

The most common adverse reactions (incidence ≥2% and ≥1% higher than placebo) were diarrhea, dizziness, nausea, gait disturbances (including falls), hyperkalemia, headache, somnolence, and mental status change.

## Drug Interactions

### Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Difelikefalin drug interactions (more detail)

## Actions

### Mechanism of Action

Difelikefalin acetate is a kappa opiate receptor (KOR) agonist. The relevance of KOR activation to therapeutic effectiveness is not known.

## Advice to Patients

- Inform patients that dizziness, somnolence, mental status changes, and gait disturbances (including falls) can occur during treatment with difelikefalin acetate. Somnolence is more likely to occur in patients who are age 65 years or older.

- Inform patients that concomitant treatment with centrally acting depressants, sedating antihistamines and opiate analgesics may increase the likelihood of these adverse reactions and these medications should be used with caution during treatment with difelikefalin acetate.

- Inform patients that difelikefalin acetate may impair the ability to perform potentially hazardous activities such as driving a car or operating heavy machinery. Advise patients not to drive or operate machinery until they know how they will react to difelikefalin acetate.

## Additional Information

AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

## Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Difelikefalin Acetate
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer
--- | --- | --- | --- | ---
Parenteral | Injection, for IV use | 50 mcg (of difelikefalin) per mL | Korsuva | Vifor (International) Inc.

AHFS Drug Information. © Copyright 2023, Selected Revisions September 13, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Reload page with references included

## More about difelikefalin

- Check interactions
- Side effects
- Dosage information
- During pregnancy
- Drug class: peripheral opioid receptor agonists

### Patient resources

- Advanced Reading

### Professional resources

#### Other brands

Korsuva

### Related treatment guides

- Chronic Kidney Disease-Associated Pruritus

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