Posology : מינונים

4.2    Posology and method of administration

Korsuva should be restricted for in-centre haemodialysis use only.
Korsuva is intended for use by healthcare professionals experienced in the diagnosis and treatment of conditions for which difelikefalin is indicated. Causes of pruritus other than chronic kidney disease should be excluded before initiating treatment with difelikefalin.

Posology

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). Injection volumes are detailed in the table below:

Weight range                                     Injection volume1
(Dry body weight in kg)                                     (mL)
40 – 44                                               0.4
45 – 54                                               0.5
55 – 64                                               0.6
65 – 74                                               0.7
75 – 84                                               0.8
85 – 94                                               0.9



95 – 104                                               1.0
105 – 114                                              1.1
115 – 124                                              1.2
125 – 134                                              1.3
135 – 144                                              1.4
145 – 154                                              1.5
155 – 164                                              1.6
165 – 174                                              1.7
175 – 184                                              1.8
185 – 194                                              1.9
≥ 195                                                2.0
1   More than 1 vial may be necessary if an injection volume of more than 1 mL is required.
An effect of difelikefalin in reducing pruritus is expected after 2-3 weeks of treatment.

Missed doses
If a regularly scheduled haemodialysis treatment is missed, Korsuva should be administered at the next haemodialysis treatment at the same dose.

Extra treatment
If a 4th haemodialysis treatment is performed in a week, Korsuva should be administered at the end of the haemodialysis per the recommended dose. No more than 4 doses per week should be administered even if the number of haemodialysis treatments in a week exceeds 4. A 4th dose of Korsuva is unlikely to lead to accumulation of difelikefalin that would be of concern for safety, as the majority of remaining difelikefalin from the previous treatment will be cleared by haemodialysis (see sections 4.9 and 5.2). However, safety and efficacy of a 4th dose has not been fully established due to insufficient data.

Patients with incomplete haemodialysis treatment
For haemodialysis treatments less than 1 hour, administration of difelikefalin should be withheld until the next haemodialysis session.
Following administration of difelikefalin in haemodialysis subjects, up to 70% is eliminated from the body prior to the next haemodialysis session (see sections 4.9 and 5.2). Difelikefalin plasma level remaining at the time of the next haemodialysis is reduced by about 40-50% within one hour of haemodialysis.

Patients with hepatic impairment
No dose adjustment is required for patients with mild or moderate hepatic impairment (see section 5.2). Difelikefalin has not been studied in subjects with severe hepatic impairment (National Cancer Institute (NCI) Organ Dysfunction Working Group (ODWG)) and is therefore not recommended for use in this patient population.

Elderly population (≥ 65 years of age)
Dosing recommendations for elderly patients are the same as for adult patients.

Paediatric population
The safety and efficacy of difelikefalin in children aged 0-17 years has not yet been established.
No data are available.
Method of administration

Korsuva should not be diluted and should not be mixed with other medicinal products.

Difelikefalin is removed by the dialyzer membrane and must be administered after blood is no longer circulating through the dialyzer. 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.
When given after rinse-back, at least 10 mL of sodium chloride 9 mg/mL (0.9%) solution for injection rinse-back volume should be administered after injection of Korsuva. If the dose is given during rinse- back, no additional sodium chloride 9 mg/mL (0.9%) solution for injection is needed to flush the line.