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Mavenclad ® Dosing and Evaluation App

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.'

Assessments Prior to Starting Each MAVENCLAD Treatment Course

  1.  Has the patient undergone standard cancer screening?  


  2. Has pregnancy been excluded in females of reproductive potential? 
     

  3. 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? 
     
  4. Liver assessment:  Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels.


  5. Infections (Select 'yes' if evaluated/performed)
    •   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
      -------------------
    •   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)

  6. Patient's weight:  
     

Prescribing info

DESCRIPTION CLINICAL PHARMACOLOGY INDICATIONS AND USAGE
CONTRAINDICATIONS PRECAUTIONS ADVERSE REACTIONS
DOSAGE AND ADMINISTRATION HOW SUPPLIED WARNINGS
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)]  

WARNINGS  top of page

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

DESCRIPTION  top of page

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:

Chemical Structure

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.


CLINICAL PHARMACOLOGY: top of page

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.

INDICATIONS AND USAGE  top of page

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)].

CONTRAINDICATIONS top of page

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)].

PRECAUTIONS top of page

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

ADVERSE REACTIONS top of page

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

DOSAGE AND ADMINISTRATION  top of page

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

*The use of MAVENCLAD in patients weighing less than 40 kg has not been investigated.

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

HOW SUPPLIED  top of page

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.

Storage and Stability top of page

 
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
NDC 44087-4000-4 Box of 4 tablets: Four day packs each containing one tablet.
NDC 44087-4000-5 Box of 5 tablets: Five day packs each containing one tablet.
NDC 44087-4000-6 Box of 6 tablets: One day pack containing two tablets. Four day packs each containing one tablet.
NDC 44087-4000-7 Box of 7 tablets: Two day packs each containing two tablets. Three day packs each containing one tablet.
NDC 44087-4000-8 Box of 8 tablets: Three day packs each containing two tablets. Two day packs each containing one tablet.
NDC 44087-4000-9 Box of 9 tablets: Four day packs each containing two tablets. One day pack containing one tablet.
NDC 44087-4000-0 Box of 10 tablets: Five day packs each containing two tablets.


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

Reference:

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

Disclaimer

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. Read the disclaimer