Source: European Medicines Agency (EU) Revision Year: 2018 Publisher: Merck Europe B.V., Gustav Mahlerplein 102, 1082 MA Amsterdam, The Netherlands
MAVENCLAD is indicated for the treatment of adult patients with highly active relapsing multiple sclerosis (MS) as defined by clinical or imaging features (see section 5.1).
Treatment with MAVENCLAD must be initiated and supervised by a physician experienced in the treatment of MS.
The recommended cumulative dose of MAVENCLAD is 3.5 mg/kg body weight over 2 years, administered as 1 treatment course of 1.75 mg/kg per year. Each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year. Each treatment week consists of 4 or 5 days on which a patient receives 10 mg or 20 mg (one or two tablets) as a single daily dose, depending on body weight. For details, see Tables 1 and 2 below.
Following completion of the 2 treatment courses, no further cladribine treatment is required in years 3 and 4 (see section 5.1). Re-initiation of therapy after year 4 has not been studied.
Lymphocyte counts must be
If necessary, the treatment course in year 2 can be delayed for up to 6 months to allow for recovery of lymphocytes. If this recovery takes more than 6 months, the patient should not receive MAVENCLAD anymore.
The distribution of the total dose over the 2 years of treatment is provided in Table 1. For some weight ranges the number of tablets may vary from one treatment week to the next. Use of oral cladribine in patients weighing less than 40 kg has not been investigated.
Table 1. Dose of MAVENCLAD per treatment week by patient weight in each treatment year:
| Weight range | Dose in mg (number of 10 mg tablets) per treatment week | |
|---|---|---|
| kg | Treatment week 1 | Treatment week 2 |
| 40 to <50 | 40 mg (4 tablets) | 40 mg (4 tablets) |
| 50 to <60 | 50 mg (5 tablets) | 50 mg (5 tablets) |
| 60 to <70 | 60 mg (6 tablets) | 60 mg (6 tablets) |
| 70 to <80 | 70 mg (7 tablets) | 70 mg (7 tablets) |
| 80 to <90 | 80 mg (8 tablets) | 70 mg (7 tablets) |
| 90 to <100 | 90 mg (9 tablets) | 80 mg (8 tablets) |
| 100 to <110 | 100 mg (10 tablets) | 90 mg (9 tablets) |
| 110 and above | 100 mg (10 tablets) | 100 mg (10 tablets) |
Table 2 shows how the total number of tablets per treatment week is distributed over the individual days. It is recommended that the daily cladribine doses in each treatment week be taken at intervals of 24 hours at approximately the same time each day. If a daily dose consists of two tablets, both tablets are taken together as a single dose.
Table 2. MAVENCLAD 10 mg tablets per week day:
| Total number of tablets per week | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 |
|---|---|---|---|---|---|
| 4 | 1 | 1 | 1 | 1 | 0 |
| 5 | 1 | 1 | 1 | 1 | 1 |
| 6 | 2 | 1 | 1 | 1 | 1 |
| 7 | 2 | 2 | 1 | 1 | 1 |
| 8 | 2 | 2 | 2 | 1 | 1 |
| 9 | 2 | 2 | 2 | 2 | 1 |
| 10 | 2 | 2 | 2 | 2 | 2 |
A missed dose must be taken as soon as remembered on the same day according to the treatment schedule.
A missed dose must not be taken together with the next scheduled dose on the following day. In the case of a missed dose, the patient must take the missed dose on the following day, and extend the number of days in that treatment week. If two consecutive doses are missed, the same rule applies, and the number of days in the treatment week is extended by two days.
It is recommended that administration of any other oral medicinal product be separated from that of MAVENCLAD by at least 3 hours during the limited number of days of cladribine administration (see section 4.5).
No dedicated studies have been conducted in patients with renal impairment.
In patients with mild renal impairment (creatinine clearance 60 to 89 mL/min), no dosage adjustment is considered necessary (see section 5.2).
Safety and efficacy in patients with moderate or severe renal impairment have not been established. Therefore, MAVENCLAD is contraindicated in these patients (see section 4.3).
No studies have been conducted in patients with hepatic impairment.
Although the importance of hepatic function for the elimination of cladribine is considered negligible (see section 5.2), in the absence of data, use of MAVENCLAD is not recommended in patients with moderate or severe hepatic impairment (Child-Pugh score >6).
Clinical studies with oral cladribine in MS did not include patients over 65 years of age; therefore, it is not known whether they respond differently from younger patients.
Caution is recommended when MAVENCLAD is used in elderly patients, taking into account the potential greater frequency of decreased hepatic or renal function, concomitant diseases and other medicinal therapies.
The safety and efficacy of MAVENCLAD in patients below the age of 18 years have not been established. No data are available.
MAVENCLAD is for oral use. The tablets must be taken with water, and swallowed without chewing. The tablets can be taken independent of food intake.
As the tablets are uncoated, they must be swallowed immediately once removed from the blister and not be left exposed on surfaces or handled for any period of time greater than that required for dosing. If a tablet is left on a surface, or if a broken or fragmented tablet is released from the blister, the area must be thoroughly washed.
The patient’s hands must be dry when handling the tablets and washed thoroughly afterwards.
There is limited experience with overdose of oral cladribine. Lymphopenia is known to be dose-dependent (see sections 4.4 and 4.8).
Particularly close monitoring of haematological parameters is recommended in patients who have been exposed to an overdose of cladribine.
There is no known specific antidote to an overdose of cladribine. Treatment consists of careful observation and initiation of appropriate supportive measures. Discontinuation of MAVENCLAD may need to be considered. Because of the rapid and extensive intracellular and tissue distribution, haemodialysis is unlikely to eliminate cladribine to a significant extent.
Shelf-life: 3 years.
Store in the original package in order to protect from moisture.
Oriented polyamide (OPA)/aluminium (Al)/polyvinyl chloride (PVC) – aluminium (Al) blister sealed in a cardboard wallet and fixed in a child-resistant outer carton.
Pack sizes of 1, 4, 5, 6, 7 or 8 tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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