Difelikefalin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Tejasvi Aryaputra
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Overview
Difelikefalin is a kappa opioid receptor agonist that is FDA approved for the treatment of moderate-to-severe pruritus associated with chronic kidney disease in certain populations. Common adverse reactions include dizziness, somnolence, diarrhea, hyperkalemia, nausea, gait disturbances, and mental status change.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
- At the end of each HD treatment, 0.5 mcg/kg is the recommended dosage of Difelikefalin through intravenous bolus injection into the venous line of the dialysis circuit for patients.
- Patient dry body weight in kg is used to determine the injection volume.
Table 1 displays the amount of injection volume of Difelikefalin given based on the patients dry body weight.
Insert Table 1
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Difelikefalin in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Difelikefalin in adult patients.
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding Difelikefalin FDA-Labeled Indications and Dosage (Pediatric) in the drug label.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Difelikefalin in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Difelikefalin in pediatric patients.
Contraindications
There are no contraindications associated with Difelikefalin.
Warnings
Dizziness, Somnolence, Mental Status Changes, and Gait Disturbances
- Patients treated with Difelikefalin have experienced mental status changes, dizziness, gait disturbances, and somnolence.
- Trial studies have shown how 12% of patients receiving a placebo reported at least one of the adverse reactions mentioned above compared to 17% of patients receiving Difelikefalin.
- Patients with an age of 65 years of age and older receiving Difelikefalin were more likely to report experiencing somnolence compared to patients less than 65 years of age.
- Adverse reactions chances increases in patients who concomitant use Difelikefalin with either sedating antihistamines, centrally-acting depressant medications, and opioid analgesics.
Risk of Driving and Operating Machinery
- Physical or mental abilities may be impaired when treated with Difelikefalin which can impact a patients ability to conduct hazardous activities.
- Advise patients to not operate a vehicle when treated with Difelikefalin.
Adverse Reactions
Clinical Trials Experience
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions and durations of follow up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Placebo controlled and uncontrolled Phase 3 clinical trials was conducted on 1306 patients treated with Difelikefalin that had moderate-to-severe pruritus who are undergoing HD.
- Trial 1 and Trial 2 are two placebo-controlled Phase 3 trials conducted on 848 subjects that tested the safety of Difelikefalin for 12 weeks when compared to a placebo. 424 patients received Difelikefalin while 424 patients received a placebo. The patient population has a mean age of 59 years, largely Caucasian (61%), and included 59% males.
- Trial 1 and 2 data showed that 0.7% of patients receiving the placebo had to discontinue treatment due to adverse reactions compared to 2.6% of patients receiving Difelikefalin that needed to discontinue their treatment. Mental status change, headache, nausea, and dizziness were the most common adverse reactions leading to discontinuation of treatment. 4.5% of patients receiving Difelikefalin reported serious adverse reactions in comparison to the 2.8% of patients part of the placebo group.
Table 2 displays the Adverse Reactions reported in the Trial 1 and 2 Studies.
Insert Table 2
Description of Selected Adverse Reactions
Gait Disturbances, including Falls
- 6.6% of patients in the Difelikefalin group reported gait disturbances compared to the 5.4% of patients in the placebo group who reported it.
- < 1% of patients in either group reported falls as a serious adverse reaction.
Dizziness
- 6.8% of patients receiving Difelikefalin reported dizziness compared to the 3.8% of patients in the placebo group that reported it.
- 0.2% of patients receiving Difelikefalin reported serious dizziness compared to the 0% of patients in the placebo group that reported it.
- 0.9% of patients discontinued use of Difelikefalin due to dizziness while 0.2% discontinued placebo use to dizziness.
Somnolence
- 4.2% of patients receiving Difelikefalin reported somnolence compared to the 2.4% of patients in the placebo group that reported it.
- 0.2% of patients receiving Difelikefalin reported serious somnolence compared to the 0% of patients in the placebo group that reported it.
- No discontinuation of either treatment occurred due to somnolence.
Mental Status Change
- 3.3% of patients receiving Difelikefalin reported mental status change compared to the 1.4% of patients in the placebo group that reported it.
- 1.4% of patients receiving Difelikefalin reported serious mental status change compared to the 0.5% of patients in the placebo group that reported it.
- 0.7% of patients discontinued use of Difelikefalin due to mental status change while 0.2% discontinued placebo use to dizziness.
Hyperkalemia
- 4.7% of patients receiving Difelikefalin reported hyperkalemia change compared to the 3.5% of patients in the placebo group that reported it.
Postmarketing Experience
There is limited information about "Postmarketing Experiance" in the drug label.
Drug Interactions
There is limited information regarding Difelikefalin Drug Interactions in the drug label.
Use in Specific Populations
Pregnancy
Pregnancy Category (FDA):
There is no FDA guidance on usage of Difelikefalin in women who are pregnant.
Pregnancy Category (AUS):
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Difelikefalin in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Difelikefalin during labor and delivery.
Nursing Mothers
There is no FDA guidance on the use of Difelikefalin in women who are nursing.
Pediatric Use
There is no FDA guidance on the use of Difelikefalin in pediatric settings.
Geriatic Use
There is no FDA guidance on the use of Difelikefalin in geriatric settings.
Gender
There is no FDA guidance on the use of Difelikefalin with respect to specific gender populations.
Race
There is no FDA guidance on the use of Difelikefalin with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Difelikefalin in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Difelikefalin in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Difelikefalin in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Difelikefalin in patients who are immunocompromised.
Administration and Monitoring
Administration
There is limited information regarding Difelikefalin Administration in the drug label.
Monitoring
There is limited information regarding Difelikefalin Monitoring in the drug label.
IV Compatibility
There is limited information regarding the compatibility of Difelikefalin and IV administrations.
Overdosage
There is limited information regarding Difelikefalin overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Difelikefalin Pharmacology in the drug label.
Mechanism of Action
There is limited information regarding Difelikefalin Mechanism of Action in the drug label.
Structure
There is limited information regarding Difelikefalin Structure in the drug label.
Pharmacodynamics
There is limited information regarding Difelikefalin Pharmacodynamics in the drug label.
Pharmacokinetics
There is limited information regarding Difelikefalin Pharmacokinetics in the drug label.
Nonclinical Toxicology
There is limited information regarding Difelikefalin Nonclinical Toxicology in the drug label.
Clinical Studies
There is limited information regarding Difelikefalin Clinical Studies in the drug label.
How Supplied
There is limited information regarding Difelikefalin How Supplied in the drug label.
Storage
There is limited information regarding Difelikefalin Storage in the drug label.
Images
Drug Images
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Package and Label Display Panel
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Patient Counseling Information
There is limited information regarding Difelikefalin Patient Counseling Information in the drug label.
Precautions with Alcohol
Alcohol-Difelikefalin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
Brand Names
There is limited information regarding Difelikefalin Brand Names in the drug label.
Look-Alike Drug Names
There is limited information regarding Difelikefalin Look-Alike Drug Names in the drug label.
Drug Shortage Status
Price
References
The contents of this FDA label are provided by the National Library of Medicine.