r the 3-N-acetyl-amifampridine metabolitein human milk, the effects on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with themother’s clinical need for RUZURGI and any potential adverse effects on the breastfed infantfrom RUZURGI or from the underlying maternal condition.
8.4 Pediatric Use
Safety and effectiveness of RUZURGI have been established in patients 6 to less than 17 years ofage. Use of RUZURGI in patients 6 to less than 17 years of age is supported by evidence fromadequate and well-controlled studies of RUZURGI in adults with LEMS, pharmacokinetic data inadult patients, pharmacokinetic modeling and simulation to identify the dosing regimen inpediatric patients, and safety data from pediatric patients 6 to less than 17 years of age [seeAdverse Reactions (6.1) and Clinical Pharmacology (12.3)].
Safety and effectiveness in pediatric patients below the age of 6 years have not been established.
8.6 Renal Impairment
Renal clearance is an elimination pathway for amifampridine and the inactive metabolite, 3-Nacetylamifampridine [see Clinical Pharmacology (12.3)]. Therefore, in patients with renalimpairment, RUZURGI should be initiated at the lowest recommended starting dosage andpatients should be closely monitored for adverse reactions [see Dosage and Administration (2.3)].
Consider dosage modification or discontinuation of RUZURGI for patients with renal impairmentas needed based on clinical effect and tolerability. No dosage recommendations for RUZURGIcan be made for patients with end-stage renal disease (CLcr < 15 mL/min or patients requiringdialysis).
8.7 Hepatic Impairment
The effects of RUZURGI have not been studied in patients with hepatic impairment. RUZURGIis extensively metabolized by N-acetyltransferase 2 (NAT2), and hepatic impairment may causean increase in exposure, Therefore, initiate RUZURGI in patients with any degree of hepaticimpairment at the lowest recommended starting dosage and monitor for adverse reactions [seeDosage and Administration (2.4)]. Consider dosage modification or discontinuation of RUZURGIfor patients with hepatic impairment as needed based on clinical effect and tolerability.
8.8 NAT2 Poor Metabolizers
Exposure of RUZURGI is increased in patients who are N-acetyltransferase (NAT2) poormetabolizers [see Clinical Pharmacology (12.5)]. Therefore, initiate RUZURGI in patients whoare known NAT2 poor metabolizers at the lowest recommended starting dosage and monitor foradverse reactions [see Dosage and Administration (2.5)]. Consider dosage modification ofRUZURGI for patients who are known NAT2 poor metabolizers as needed based on clinicaleffect and tolerability.
10 OVERDOSAGE
In case reports, events reported after intake of RUZURGI at doses of 300 mg per day or greater(more than three times the maximum recommended daily dosage) include vomiting, nystagmus,seizures and status epilepticus, rhabdomyolysis, chest pain, diaphoresis, palpitations, paroxysmalsupraventricular tachycardia, transient QTc prolongation, aspiration with acute respiratory failure,and cardiac arrest.
Patients with suspected overdose with RUZURGI should be monitored for signs or symptoms ofexaggerated RUZURGI adverse reactions or effects, and appropriate symptomatic treatmentinstituted immediately.
11 DESCRIPTION
RUZURGI (amifampridine) is a potassium channel blo |
