Mavenclad ® Dosing and Evaluation App
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MAVENCLAD is a purine antimetabolite indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, use of MAVENCLAD is generally recommended for patients who have had an inadequate response to, or are unable to tolerate, an alternate drug indicated for the treatment of MS.
Instructions:
The following questions
are required in order to ensure the safe prescribing of Mavenclad (cladribine).
Additional guidance is provided after submitting the form - press:
'Evaluate Entries.'
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Assessments Prior to Starting Each MAVENCLAD
Treatment Course
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- Has the patient undergone standard cancer screening?
- Has pregnancy been excluded in females of reproductive potential?
- Has a Complete Blood Count (CBC) with differential including
lymphocyte count obtained and are the lymphocytes within normal limits
before initiating the first treatment course or at least 800 cells per
microliter before initiating the second treatment course?
- Liver assessment: Obtain serum aminotransferase, alkaline phosphatase, and
total bilirubin levels.
- Infections (Select 'yes' if evaluated/performed)
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Exclude HIV Infection
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Perform Tuberculosis screening
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Screened for hepatitis B and C
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Evaluated for acute infection
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Vaccination of patients who are antibody-negative for varicella
zoster virus
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Administer all immunizations according to immunization guidelines
prior to starting MAVENCLAD. Administer live-attenuated or live
vaccines at least 4 to 6 weeks prior to starting MAVENCLAD
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Obtain a baseline (within 3 months) magnetic resonance
imaging prior to the first treatment course because of the
risk of progressive multifocal leukoencephalopathy (PML)
- Patient's weight:
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Prescribing info
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| PRESCRIBING HIGHLIGHTS: Please see package insert for additional information and possible updates to ensure safe and effective use of this medication. The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material. Please read the disclaimer carefully BEFORE accessing or using this site. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.
Drug UPDATES: [Drug information (pdf)] | |
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BOXED WARNING:
WARNING: MALIGNANCIES and RISK OF TERATOGENICITY See full prescribing
information for complete boxed warning.
• Malignancies
MAVENCLAD may increase the risk of malignancy. MAVENCLAD is
contraindicated in patients with current malignancy; evaluate the
benefits and risks on an individual basis for patients with prior or
increased risk of malignancy. (5.1)
• Risk of Teratogenicity
MAVENCLAD is contraindicated for use in pregnant women and in women and
men of reproductive potential who do not plan to use effective
contraception because of the risk of fetal harm. (5.2)
[Drug information] |
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Description:
MAVENCLAD contains the nucleoside metabolic inhibitor
cladribine, which is a white or almost white, non-hydroscopic,
crystalline powder with the molecular formula C10H12ClN5O3
and molecular weight 285.69. It differs in structure from the naturally
occurring nucleoside, deoxyadenosine, by the substitution of chlorine
for hydrogen in the 2-position of the purine ring.
The chemical name of cladribine is 2-chloro-2′-deoxy-adenosine. The
structural formula is shown below:
Cladribine is stable at slightly basic and at neutral pH. The main
degradation pathway is hydrolysis and at acidic pH significant
decomposition occurs with time. The ionization behavior of the molecule
over the pH range 0 to 12 is characterized by a single pKa of
approximately 1.21.
MAVENCLAD is provided as 10 mg tablets for oral use. Each MAVENCLAD
10 mg tablet contains cladribine as an active ingredient and
hydroxypropyl betadex, magnesium stearate, and sorbitol as inactive
ingredients.
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Mechanism of Action:
The mechanism by
which cladribine exerts its therapeutic effects in patients with
multiple sclerosis has not been fully elucidated but is thought to
involve cytotoxic effects on B and T lymphocytes through impairment of
DNA synthesis, resulting in depletion of lymphocytes. |
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INDICATIONS AND USAGE:
MAVENCLAD is indicated for the treatment of relapsing forms
of multiple sclerosis (MS), to include relapsing-remitting disease and
active secondary progressive disease, in adults. Because of its safety
profile, use of MAVENCLAD is generally recommended for patients who have
had an inadequate response to, or are unable to tolerate, an alternate
drug indicated for the treatment of MS [see Warnings and Precautions
(5)].
Limitations of Use
MAVENCLAD is not recommended for use in patients with clinically
isolated syndrome (CIS) because of its safety profile [see Warnings and
Precautions (5)].
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Contraindications:
MAVENCLAD is contraindicated:
- in patients with current malignancy [see
Warnings and Precautions (5.1)].
- in pregnant women and in women and men of reproductive potential
who do not plan to use effective contraception during MAVENCLAD
dosing and for 6 months after the last dose in each treatment
course. May cause fetal harm [see Warnings and
Precautions (5.2) and Use in Specific Populations (8.1, 8.3)].
- in patients infected with the human immunodeficiency virus (HIV)
[see Warnings and Precautions (5.4)].
- in patients with active chronic infections (e.g., hepatitis or
tuberculosis) [see Warnings and Precautions
(5.4)].
- in patients with a history of hypersensitivity to cladribine
[see Warnings and Precautions (5.8)].
- in women intending to breastfeed on a MAVENCLAD treatment day
and for 10 days after the last dose [[see Use
in Specific Populations (8.2)].
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WARNINGS AND PRECAUTIONS::
- Lymphopenia: Monitor lymphocyte counts before, during and
after treatment. (5.3)
- Infections: Screen patients for latent infections; consider
delaying treatment until infection is fully controlled.
Vaccinate patients antibody-negative to varicella zoster virus
prior to treatment. Administer anti-herpes prophylaxis in
patients with lymphocyte counts less than 200 cells per
microliter. Monitor for infections. (5.4)
- Hematologic toxicity: Monitor complete blood count before,
during and after treatment. (5.5)
- Graft-versus-host-disease with blood transfusion:
Irradiation of cellular blood components is recommended. (5.6)
- Liver injury: Obtain tests prior to treatment. Discontinue
if clinically significant injury is suspected. (5.7)
- [Drug information]
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ADVERSE REACTIONS:
Most common adverse
reactions (incidence > 20%) are upper respiratory tract infection,
headache, and lymphopenia.
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.
Drug information
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DOSAGE AND ADMINISTRATION:
2.1 Assessments Prior to Starting Each
MAVENCLAD Treatment Course
Cancer Screening
Follow standard cancer screening guidelines because of the risk of
malignancies [see Boxed Warning and Warnings and Precautions (5.1)].
Pregnancy
Exclude pregnancy prior to treatment with MAVENCLAD in females of
reproductive potential [see Contraindications (4), Warnings and
Precautions (5.2), and Use in Specific Populations (8.1, 8.3)].
Complete Blood Count (CBC)
Obtain a CBC with differential including lymphocyte count [see Dosage
and Administration (2.5) and Warnings and Precautions (5.3)].
Lymphocytes must be:
- within normal limits before initiating the first
treatment course
- at least 800 cells per microliter before initiating the
second treatment course
If necessary, delay the second treatment course for up to 6
months to allow for recovery of lymphocytes to at least 800
cells per microliter. If this recovery takes more than 6 months,
the patient should not receive further treatment with MAVENCLAD.
Infections
[see
Warnings and Precautions (5.4)]
- Exclude HIV infection.
- Perform tuberculosis screening.
- Screen for hepatitis B and C.
- Evaluate for acute infection. Consider a delay in
MAVENCLAD treatment until any acute infection is fully
controlled.
- Vaccination of patients who are antibody-negative for
varicella zoster virus is recommended prior to initiation of
MAVENCLAD.
- Administer all immunizations according to immunization
guidelines prior to starting MAVENCLAD. Administer
live-attenuated or live vaccines at least 4 to 6 weeks prior
to starting MAVENCLAD.
- Obtain a baseline (within 3 months) magnetic resonance
imaging prior to the first treatment course because of the
risk of progressive multifocal leukoencephalopathy (PML).
Liver Injury
Obtain serum aminotransferase, alkaline phosphatase, and
total bilirubin levels [see
Warnings and Precautions (5.7)].
2.2 Recommended Dosage
The recommended cumulative dosage of MAVENCLAD is 3.5 mg per kg body
weight administered orally and divided into 2 yearly treatment courses
(1.75 mg per kg per treatment course) (see Table 1). Each treatment
course is divided into 2 treatment cycles:
Administration of First Treatment Course
- First Course/First Cycle: start any time.
- First Course/Second Cycle: administer 23 to 27 days
after the last dose of First Course/First Cycle.
Administration of
Second Treatment Course
- Second Course/First Cycle: administer at least 43 weeks
after the last dose of First Course/Second Cycle.
- Second Course/Second Cycle: administer 23 to 27 days
after the last dose of Second Course/First Cycle.
Table 1 Dose of MAVENCLAD per Cycle by
Patient Weight in Each Treatment Course
| Weight
Range |
Dose in mg (Number of 10 mg Tablets) per Cycle |
| kg |
First Cycle |
Second Cycle |
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*The use of MAVENCLAD in patients
weighing less than 40 kg has not been
investigated.
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| 40*
to less than 50 |
40 mg (4 tablets) |
40 mg (4 tablets) |
| 50 to less
than 60 |
50 mg (5 tablets) |
50 mg (5 tablets) |
| 60 to less
than 70 |
60 mg (6 tablets) |
60 mg (6 tablets) |
| 70 to less
than 80 |
70 mg (7 tablets) |
70 mg (7 tablets) |
| 80 to less
than 90 |
80 mg (8 tablets) |
70 mg (7 tablets) |
| 90 to less
than 100 |
90 mg (9 tablets) |
80 mg (8 tablets) |
| 100 to less
than 110 |
100 mg (10 tablets) |
90 mg (9 tablets) |
| 110 and above |
100 mg (10 tablets) |
100 mg (10 tablets) |
Administer the cycle dosage as 1 or 2 tablets once
daily over 4 or 5 consecutive days [see How Supplied/Storage and
Handling (16.1)]. Do not administer more than 2 tablets daily.
Following the administration of 2 treatment courses, do not
administer additional MAVENCLAD treatment during the next 2 years.
Treatment during these 2 years may further increase the risk of
malignancy [see Warnings and Precautions (5.1)]. The safety and
efficacy of reinitiating MAVENCLAD more than 2 years after
completing 2 treatment courses has not been studied.
2.3 Missed Dose
If a dose is missed, patients should not take
double or extra doses.
If a dose is not taken on the scheduled day, then the patient
must take the missed dose on the following day and extend the number
of days in that treatment cycle. If two consecutive doses are
missed, the treatment cycle is extended by 2 days.
2.4 Administration
MAVENCLAD tablets are taken orally, with water, and swallowed whole
without chewing. MAVENCLAD can be taken with or without food.
Separate administration of MAVENCLAD and any other oral drugs by at
least 3 hours during the 4 to 5 day MAVENCLAD treatment cycles [see
Clinical Pharmacology (12.6)].
MAVENCLAD is a cytotoxic drug. Follow applicable special handling and
disposal procedures [see References (15)]. MAVENCLAD is an uncoated
tablet and must be swallowed immediately once removed from the blister.
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 with
water.
The patient's hands must be dry when handling the tablets and washed
thoroughly afterwards. Avoid prolonged contact with skin.
2.5 Laboratory Testing and Monitoring to
Assess Safety
Cancer Screening
Follow standard cancer screening guidelines in patients treated with
MAVENCLAD [see Dosage and Administration (2.1) and Warnings and
Precautions (5.1)].
Complete Blood Count
Obtain complete blood count (CBC) with differential including lymphocyte
count:
- before initiating the first treatment course of
MAVENCLAD
- before initiating the second treatment course of
MAVENCLAD
- 2 and 6 months after start of treatment in each
treatment course; if the lymphocyte count at month 2 is
below 200 cells per microliter, monitor monthly until month
6. See
Warnings and Precautions (5.3,
5.4) for instructions based on the patient's
lymphocyte counts and clinical status (e.g., infections).
Hold MAVENCLAD therapy if the lymphocyte count is below 200
cells per microliter
- periodically thereafter and when clinically indicated
[see
Warnings and Precautions (5.5)] [Drug information]
2.6 Recommended Concomitant Medication
Herpes Prophylaxis
Administer anti-herpes prophylaxis in patients with lymphocyte counts
less than 200 cells per microliter [see Warnings and Precautions (5.4)].
[Drug information]
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DOSAGE FORMS AND STRENGTHS:
MAVENCLAD
is available as 10 mg tablets. The tablets are uncoated, white, round,
biconvex, and engraved with a "C" on one side and "10" on the other
side.
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16.1 How Supplied
MAVENCLAD tablets, 10 mg, are uncoated, white, round, biconvex, and
engraved with a "C" on one side and "10" on the other side. Each tablet
is packaged in a child-resistant day pack containing one or two tablets
in a blister card.
Dispense one box for each treatment cycle with a Medication Guide [see
Dosage and Administration (2.2)].
Presentations
16.2 Storage and Handling
Store at controlled room temperature, 20°C to 25°C (68°F to 77°F);
excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled
Room Temperature]. Store in original package in order to protect from
moisture.
MAVENCLAD is a cytotoxic drug. Follow applicable special handling and
disposal procedures
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Reference:
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Package insert data:
MAVENCLAD ® (cladribine) tablets, for oral use
Initial U.S. Approval: 1993
Distributed by:
EMD Serono, Inc.
Rockland, MA 02370
MAVENCLAD is a registered trademark of Merck KGaA, Darmstadt,
Germany.
Revised: 4/2019 |
