ductive Potential
Pregnancy Testing
In females of reproductive potential, pregnancy should be excluded before the initiation of eachtreatment course of MAVENCLAD [see Use in Specific Populations (8.1)].
Contraception
Females
Females of reproductive potential should prevent pregnancy by use of effective contraceptionduring MAVENCLAD dosing and for at least 6 months after the last dose in each treatmentcourse.
It is unknown if MAVENCLAD may reduce the effectiveness of the systemically actinghormonal contraceptives. Women using systemically acting hormonal contraceptives should adda barrier method during MAVENCLAD dosing and for at least 4 weeks after the last dose ineach treatment course. Women who become pregnant during MAVENCLAD therapy shoulddiscontinue treatment [see Warnings and Precautions (5.2) and Drug Interactions (7.7)].
Males
As cladribine interferes with DNA synthesis, adverse effects on human gametogenesis could beexpected. Therefore, male patients of reproductive potential should take precautions to preventpregnancy of their partner during MAVENCLAD dosing and for at least 6 months after the lastdose in each treatment course [see Warnings and Precautions (5.2) and Nonclinical Toxicology(13.1)].
8.4 Pediatric Use
The safety and effectiveness in pediatric patients (below 18 years of age) have not beenestablished. Use of MAVENCLAD is not recommended in pediatric patients because of the riskof malignancies [see Warnings and Precautions (5.1)].
8.5 Geriatric Use
Clinical studies with MAVENCLAD did not include sufficient numbers of patients aged 65 andover to determine whether they respond differently from younger patients. Other reportedclinical experience has not identified differences in responses between the elderly and youngerpatients. Caution is recommended when MAVENCLAD is used in elderly patients, taking intoaccount the potential greater frequency of decreased hepatic, renal, or cardiac function,concomitant diseases, and other drug therapy.
8.6 Patients with Renal Impairment
The concentration of cladribine is predicted to increase in patients with renal impairment [seeClinical Pharmacology (12.3)].
No dosage adjustment is recommended in patients with mildrenal impairment (creatinine clearance 60 to 89 mL per minute). MAVENCLAD is notrecommended in patients with moderate to severe renal impairment (creatinine clearancebelow 60 mL per minute) [see Clinical Pharmacology (12.3)].
8.7 Patients with Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of cladribine is unknown [see ClinicalPharmacology (12.3)]. No dosage adjustment is recommended in patients with mild hepaticimpairment. MAVENCLAD is not recommended in patients with moderate to severe hepaticimpairment (Child-Pugh score greater than 6) [see Clinical Pharmacology (12.3)].
10 OVERDOSAGE
There is no experience with overdose of MAVENCLAD. Lymphopenia is known to be dosedependent.
Particularly close monitoring of hematological parameters is recommended inpatients who have been exposed to an overdose of MAVENCLAD [see Warnings andPrecautions (5.3, 5.5)].
There is no known specific antidote to an overdose of MAVENCLAD. Treatment consists ofcareful observation and initiation of appropriate supportive measures. Discontinuation ofMAVENCLAD may need to be considered. Because of the rapid and extensive intracellular andtissue distribution, hemodialysis is unlikely to elimi |
