KORSUVA

1 Dosing Considerations  KORSUVA is intended for use only in hemodialysis centres and by health care professionals trained in hemodialysis administration.  Causes of pruritus other than chronic kidney disease should be excluded before initiating treatment with KORSUVA.

 KORSUVA should be administered by intravenous (IV) bolus injection only at the end of the hemodialysis treatment.  KORSUVA has not been studied in patients on peritoneal dialysis. 2 Recommended Dose and Dosage Adjustment KORSUVA is administered 3 times per week by intravenous bolus injection into the venous line of the dialysis circuit at the end of the hemodialysis treatment during rinse -back or after rinse- back.

, the target post-dialysis weight). 1 mL). For patients with a dry body weight equal to or above 195 kg, the recommended dose is 100 micrograms (2 mL). KORSUVA difelikefalin Page 5 of 34 Recommended injection volumes based on target dry body weight are provided in Table 1, below.

0 *More than 1 vial may be necessary if an injection volume of more than 1mL is required. 0 kg. Population pharmacokinetic simulations demonstrated comparable difelikefalin exposure up to 200 kg. Extra treatment In the pivotal Phase 3 clinical trials conducted with KORSUVA, patients were permitted to receive up to 4 doses of KORSUVA per week if they required 4 hemodialysis treatments in a particular week.

A 4th dose 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 hemodialysis. 3 Pharmacokinetics – Elimination.

2%) received a 4th dose of KORSUVA in a week 3 times during 12 weeks. The safety and efficacy of a 4th dose has therefore not been fully established due to insufficient data. If a 4th hemodialysis treatment in a week is performed, KORSUVA should be administered at the end of hemodialysis per the recommended dose.

No more than 4 doses per week should be administered even if the number of hemodialysis treatments in a week exceeds 4. KORSUVA difelikefalin Page 6 of 34 Patients with incomplete hemodialysis treatment For incomplete hemodialysis treatments less than 1 hour, administration of KORSUVA should be withheld until the next hemodialysis session.

For incomplete hemodialysis treatments of 1 hour or more, clinical judgement should be used to determine if the benefits of KORSUVA administration following the incomplete hemodialysis treatment outweigh the potential risks. As the remaining plasma concentrations of difelikefalin at the time of pre -dialysis is largely cleared by each hemodialysis treatment, patients whose dialysis treatment is interrupted prematurely may not have complete removal of difelikefalin.

Advise patients not to drive or operate dangerous machinery until the effect of KORSUVA on a patient’s ability to drive or operate machinery is known. 5%; 15 / 424 patients). 2%). The clinical relevance of these Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Intravenous injection 50 mcg difelikefalin (as acetate) per 1 mL solution in a 2 mL single-use glass vial.

Acetic acid Sodium acetate trihydrate Sodium chloride* Water for injections KORSUVA difelikefalin Page 9 of 34 findings is unknown as a causal relationship was not established. See 8 ADVERSE REACTIONS. Frequent monitoring of potassium levels is recommended.

Neurologic Dizziness and Somnolence Dizziness and somnolence have occurred in patients taking KORSUVA and may subside over time with continued treatment. See 8 ADVERSE REACTIONS. 8%). 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 KORSUVA.

See

Cardiovascular Cardiac failure and atrial fibrillation KORSUVA has not been studied in patients with New York Heart Association Class IV heart failure. In the pooled data from two Phase 3 placebo-controlled clinical trials, a numerical imbalance of cardiac failure events and cardiac arrhythmia events, including atrial fibrillation, was observed in patients treated with KORSUVA compared to placebo, in particular among patients with a medical history of atrial fibrillation, some of whom had discontinued or missed their atrial fibrillation treatment.

The clinical significance of these findings is unknown as a causal relationship was not established. Driving and Operating Machinery Dizziness, somnolence, and mental status changes have occurred in patients taking KORSUVA. KORSUVA may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car and operating machinery.

See 7 WARNINGS AND PRECAUTIONS - Neurologic and

KORSUVA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.