Presentation and Status in Health Basket
| Presentation | Basket | Yarpa | Pharmasoft |
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Solution for Injection 3 x 1 ml |
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Solution for Infusion 12 x 1 ml |
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87432 | 11340 |
Dosage
This medical product should be restricted for in-centre haemodialysis use only.
Difelikefalin is administered 3 times per week by intravenous bolus injection into the venous line of the dialysis circuit at the end of the haemodialysis treatment during rinse-back or after rinse-back.
The recommended dose of difelikefalin is 0.5 micrograms/kg dry body weight (i.e., the target postdialysis weight). The total dose volume (mL) required from the vial should be calculated as follows: 0.01 × dry body weight (kg), rounded to the nearest tenth (0.1 mL). For patients with a dry body weight equal to or above 195 kg the recommended dose is 100 micrograms (2 mL).
See prescribing information for full details.
Indications
Treatment of moderate-to-severe pruritus associated with chronic kidney disease in adult patients on haemodialysis
Contra-Indications
Hypersensitivity to the active substance or to any of the excipients
Special Precautions
Hyperkalaemia
Hyperkalaemia frequently occurs in chronic kidney disease patients on haemodialysis. In the placebo- controlled clinical studies a numerically higher rate of adverse events of hyperkalaemia was reported for the difelikefalin treated patients (4.7%; 20 / 424 patients) compared to placebo (3.5%; 15 / 424 patients). No causal relationship was established. Frequent monitoring of potassium levels is recommended.
Patients with impaired blood-brain barrier
Difelikefalin is a peripherally acting kappa opioid receptor agonist with restricted access to the central nervous system (CNS). The blood-brain barrier (BBB) integrity is important for minimizing difelikefalin uptake into the CNS. Patients with clinically important disruptions to the BBB (e.g., primary brain malignancies, CNS metastases or other inflammatory conditions, active multiple sclerosis, advanced Alzheimer’s disease) may be at risk for difelikefalin entry into the CNS. This medical product should be prescribed with caution in such patients taking into account their individual benefit-risk balance with observation for potential CNS effects.
Dizziness and somnolence
Dizziness and somnolence have occurred in patients taking difelikefalin and may subside over time with continued treatment. Concomitant use of sedating antihistamines, opioid analgesics or other CNS depressants may increase the likelihood of these adverse reactions and should be used with caution during treatment with difelikefalin.
Compared to placebo, the incidence of somnolence was higher in difelikefalin treated subjects 65 years of age and older (7.0%) than in difelikefalin treated subjects less than 65 years of age (2.8%).
See prescribing information for full details.
Side Effects
Common: Somnolence, Paraesthesia
See prescribing information for full details.
Drug interactions
No clinical interaction studies have been performed. Difelikefalin does not inhibit or induce CYP450 enzymes, and is not a substrate of CYP450 enzymes. It is not an inhibitor of glucuronidating enzymes either. Difelikefalin is not a substrate or an inhibitor of human transporters.
Therefore, interactions of difelikefalin with other medicinal products are unlikely.
See prescribing information for full details.
Pregnancy and Lactation
Pregnancy: There are no or limited amount of data from the use of difelikefalin in pregnant women. As a precautionary measure, it is preferable to avoid the use of difelikefalin during pregnancy.
Lactation: It is unknown whether difelikefalin is excreted in human breast milk. A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from difelikefalin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Overdose
Single dose of difelikefalin up to 12 times and multiple doses of difelikefalin up to 5 times the clinical dose of 0.5 micrograms/kg were administered in clinical studies in patients undergoing haemodialysis. A dose-dependent increase in adverse events including dizziness, somnolence, mental status changes, paraesthesia, fatigue, hypertension and vomiting, was observed.
In the event of overdose, the appropriate medical attention based on patient’s clinical status should be provided. Haemodialysis for 4 hours using a high-flux dialyzer effectively cleared approximately 70-80% of difelikefalin from plasma, and difelikefalin was not detectable in plasma at the end of the second of two dialysis cycles.
