Mavenclad 10mg Tabs (9) Pak
WARNING: This drug may lower the ability of the bone marrow to make blood cells that the body needs. If blood cell counts get very low, this can lead to bleeding problems, infections, or anemia. If you have questions, talk with the doctor.This drug may raise the risk of cancer. Do not take this drug to treat MS if you have cancer. If you have a risk for cancer or have ever had cancer, talk with your doctor.This drug may cause harm to the unborn baby if you take it while pregnant. Do not take this drug if you are pregnant, or if you are able to get pregnant but are not using birth control.If you are able to get pregnant, a pregnancy test will be done to show that you are NOT pregnant before starting this drug. Talk with your doctor.If you or your sex partner may become pregnant, you must use birth control while taking this drug and for 6 months after the last dose. Ask your doctor how long to use birth control and what kind of birth control to use. If you or your sex partner gets pregnant while taking this drug or within 6 months after stopping it, call the doctor right away. @ COMMON USES: It is used to treat MS (multiple sclerosis).
Drug Class
Disease-modifying therapy (DMT) for Multiple Sclerosis (MS)
Pharmacologic Class
Purine antimetabolite; Selective immunosuppressant
Pregnancy Category
Category X
FDA Approved
Mar 2019
DEA Schedule
Not Controlled
Overview
What is this medicine?
Mavenclad is an oral medication used to treat relapsing forms of multiple sclerosis (MS). It works by reducing the number of certain white blood cells (lymphocytes) that are involved in the immune system's attack on nerve cells in MS. It is given in two short treatment courses over two years, with no daily dosing in between.
How to Use This Medicine
Taking Your Medication Correctly
To ensure you get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole with a glass of water. Do not chew the tablet.
If you take other oral medications, take them at least 3 hours before or 3 hours after this medication. If this is not possible, consult your doctor for guidance.
Handling Your Medication
You will need to take special precautions when handling this medication. Consult your doctor or pharmacist for instructions on how to handle it safely. Only remove the medication from the blister pack when you are ready to take it, and take it immediately after opening the pack. Do not store the removed medication for future use. Make sure your hands are dry before touching the medication, and wash your hands after handling it.
Storing and Disposing of Your Medication
Store your medication in its original container at room temperature in a dry place. Avoid storing it in a bathroom. Keep all medications in a safe location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember on the same day. If you don't remember until the next day, take the missed dose and then take your next dose the day after. This will extend your treatment week by one day. Do not take two doses at the same time or take extra doses.
To ensure you get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Swallow the tablet whole with a glass of water. Do not chew the tablet.
If you take other oral medications, take them at least 3 hours before or 3 hours after this medication. If this is not possible, consult your doctor for guidance.
Handling Your Medication
You will need to take special precautions when handling this medication. Consult your doctor or pharmacist for instructions on how to handle it safely. Only remove the medication from the blister pack when you are ready to take it, and take it immediately after opening the pack. Do not store the removed medication for future use. Make sure your hands are dry before touching the medication, and wash your hands after handling it.
Storing and Disposing of Your Medication
Store your medication in its original container at room temperature in a dry place. Avoid storing it in a bathroom. Keep all medications in a safe location, out of the reach of children and pets.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember on the same day. If you don't remember until the next day, take the missed dose and then take your next dose the day after. This will extend your treatment week by one day. Do not take two doses at the same time or take extra doses.
Lifestyle & Tips
- Avoid live or live-attenuated vaccines during and for at least 6 months after treatment.
- Practice good hygiene to reduce infection risk (e.g., frequent hand washing).
- Report any signs of infection (fever, chills, sore throat) immediately.
- Report any new lumps, skin changes, or unusual symptoms to your doctor.
- Use effective contraception during treatment and for at least 6 months after the last dose for both males and females.
- Do not breastfeed during treatment and for at least 10 days after the last dose.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Cumulative dose of 3.5 mg/kg over 2 years, administered as 1.75 mg/kg per year. Each annual dose is divided into 2 treatment courses, 1 month apart. Each course consists of 4-5 days of daily oral administration.
Condition-Specific Dosing:
Year 1:
1.75 mg/kg total, divided into 2 treatment courses (Course 1 and Course 2) separated by approximately 1 month. Each course is 4-5 days of daily dosing.
Year 2:
1.75 mg/kg total, divided into 2 treatment courses (Course 3 and Course 4) separated by approximately 1 month. Each course is 4-5 days of daily dosing. Administered approximately 12 months after the first treatment course of Year 1.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established (Safety and effectiveness not established in pediatric patients)
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required (CrCl 60-89 mL/min)
Moderate:
No dose adjustment required (CrCl 30-59 mL/min)
Severe:
Contraindicated (CrCl < 30 mL/min)
Dialysis:
Contraindicated (Not studied, but significant renal excretion)
Hepatic Impairment:
Mild:
No dose adjustment required
Moderate:
No dose adjustment required
Severe:
Not studied; caution advised. No specific recommendations.
Pharmacology
Mechanism of Action
Cladribine is a purine nucleoside analog. It is a prodrug that is phosphorylated intracellularly by deoxycytidine kinase (DCK) to its active triphosphate form, 2-chlorodeoxyadenosine triphosphate (Cd-ATP). Cd-ATP incorporates into DNA, leading to DNA strand breaks and inhibition of DNA synthesis and repair. It also inhibits ribonucleotide reductase, reducing deoxyribonucleotide pools. These actions are particularly toxic to lymphocytes, especially B and T cells, which have high levels of DCK and low levels of deoxynucleotidase, leading to selective depletion of these cells. This selective lymphocytotoxicity is thought to be the primary mechanism by which cladribine exerts its therapeutic effects in MS.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 40%
Tmax:
0.5 to 1.5 hours
FoodEffect:
Food does not significantly affect bioavailability.
Distribution:
Vd:
Approximately 98 L (intravenous)
ProteinBinding:
Approximately 20%
CnssPenetration:
Yes (Cladribine crosses the blood-brain barrier, with CSF concentrations approximately 25% of plasma concentrations)
Elimination:
HalfLife:
Approximately 15-24 hours (terminal half-life)
Clearance:
Approximately 660 mL/min (renal clearance is ~50% of total clearance)
ExcretionRoute:
Renal (primary), fecal (minor)
Unchanged:
Approximately 50% (excreted unchanged in urine)
Pharmacodynamics
OnsetOfAction:
Lymphocyte count reduction typically begins within days to weeks.
PeakEffect:
Maximum lymphocyte reduction typically occurs within 2-3 months after each treatment course.
DurationOfAction:
Immunosuppressive effects (lymphocyte depletion) can persist for up to 2 years or longer after the last dose of the 2-year treatment regimen.
Safety & Warnings
BLACK BOX WARNING
MALIGNANCY: Mavenclad may increase the risk of malignancy. Patients with a current malignancy should not be treated with Mavenclad. Prior to initiating Mavenclad, patients should be screened for malignancy. Follow standard cancer screening guidelines in patients treated with Mavenclad. SERIOUS INFECTIONS: Mavenclad may increase the risk of serious infections, including opportunistic infections. Patients with active chronic infections (e.g., hepatitis, tuberculosis) should not be treated with Mavenclad. Prior to initiating Mavenclad, patients should be screened for latent infections, including tuberculosis and hepatitis B and C. Delay Mavenclad until active infections are adequately treated. Consider interrupting Mavenclad if a serious infection occurs.
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Shingles: Pain, itching, or tingling, fever, muscle aches, or a rash (with or without blisters).
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Severe Skin Reaction (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis): Red, swollen, blistered, or peeling skin (with or without fever), red or irritated eyes, or sores in the mouth, throat, nose, or eyes.
Other Serious Symptoms: Extreme fatigue or weakness, shortness of breath, sudden weight gain, or swelling in the arms or legs, rapid or irregular heartbeat, severe headache or dizziness, fainting, or changes in vision.
Depression: Mood changes, loss of interest in activities, or other symptoms of depression.
Progressive Multifocal Leukoencephalopathy (PML): A rare but serious brain condition that can cause disability or be life-threatening. Seek medical help immediately if you experience confusion, memory problems, depression, changes in behavior, uneven strength, speech or thinking difficulties, balance problems, or vision changes.
Liver Problems: Sometimes life-threatening, liver problems can cause dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes. Contact your doctor right away if you notice any of these symptoms.
Other Possible Side Effects
While many people may not experience side effects or only have mild symptoms, it's essential to be aware of the following possible side effects:
Common cold symptoms
Upset stomach
Headache
Back pain
Joint pain
Sleep disturbances
Hair thinning or loss
If you're concerned about any side effects or if they persist or worsen, contact your doctor for guidance. Not all side effects are listed here, so if you have questions or concerns, don't hesitate to reach out to your doctor.
Reporting Side Effects
You can report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can also provide guidance on managing side effects and answering any questions you may have.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor immediately or seek emergency medical attention:
Allergic Reaction: Rash, hives, itching, red, swollen, blistered, or peeling skin (with or without fever), wheezing, tightness in the chest or throat, difficulty breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infection: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or discolored sputum, painful urination, mouth sores, or a wound that won't heal.
Shingles: Pain, itching, or tingling, fever, muscle aches, or a rash (with or without blisters).
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Severe Skin Reaction (Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis): Red, swollen, blistered, or peeling skin (with or without fever), red or irritated eyes, or sores in the mouth, throat, nose, or eyes.
Other Serious Symptoms: Extreme fatigue or weakness, shortness of breath, sudden weight gain, or swelling in the arms or legs, rapid or irregular heartbeat, severe headache or dizziness, fainting, or changes in vision.
Depression: Mood changes, loss of interest in activities, or other symptoms of depression.
Progressive Multifocal Leukoencephalopathy (PML): A rare but serious brain condition that can cause disability or be life-threatening. Seek medical help immediately if you experience confusion, memory problems, depression, changes in behavior, uneven strength, speech or thinking difficulties, balance problems, or vision changes.
Liver Problems: Sometimes life-threatening, liver problems can cause dark urine, fatigue, decreased appetite, stomach upset or pain, light-colored stools, vomiting, or yellow skin and eyes. Contact your doctor right away if you notice any of these symptoms.
Other Possible Side Effects
While many people may not experience side effects or only have mild symptoms, it's essential to be aware of the following possible side effects:
Common cold symptoms
Upset stomach
Headache
Back pain
Joint pain
Sleep disturbances
Hair thinning or loss
If you're concerned about any side effects or if they persist or worsen, contact your doctor for guidance. Not all side effects are listed here, so if you have questions or concerns, don't hesitate to reach out to your doctor.
Reporting Side Effects
You can report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch. Your doctor can also provide guidance on managing side effects and answering any questions you may have.
Seek Immediate Medical Attention If You Experience:
- Fever, chills, body aches, or other signs of infection
- Unusual bleeding or bruising
- Extreme tiredness or weakness
- New or worsening skin lesions, lumps, or swollen lymph nodes
- Persistent cough or shortness of breath
- Severe headache or confusion
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
Existing health conditions, including kidney disease or liver disease.
Infections such as hepatitis B, hepatitis C, HIV, or tuberculosis (TB).
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. Certain medications, such as those used to treat hepatitis C, HIV, or infections, should not be taken with this drug. There are many other medications that may interact with this drug, so it is crucial to disclose all medications you are taking.
A health condition known as clinically isolated syndrome (CIS).
If you are breast-feeding or plan to breast-feed. You should not breast-feed while taking this medication, and you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration of breast-feeding avoidance after your last dose.
This list is not exhaustive, and it is vital to discuss all your medications and health conditions with your doctor and pharmacist to ensure safe use of this medication. Do not initiate, discontinue, or modify the dosage of any medication without first consulting your doctor.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Describe the allergic reaction you experienced, including the symptoms that occurred.
Existing health conditions, including kidney disease or liver disease.
Infections such as hepatitis B, hepatitis C, HIV, or tuberculosis (TB).
Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. Certain medications, such as those used to treat hepatitis C, HIV, or infections, should not be taken with this drug. There are many other medications that may interact with this drug, so it is crucial to disclose all medications you are taking.
A health condition known as clinically isolated syndrome (CIS).
If you are breast-feeding or plan to breast-feed. You should not breast-feed while taking this medication, and you may need to avoid breast-feeding for a period after your last dose. Consult your doctor to determine the necessary duration of breast-feeding avoidance after your last dose.
This list is not exhaustive, and it is vital to discuss all your medications and health conditions with your doctor and pharmacist to ensure safe use of this medication. Do not initiate, discontinue, or modify the dosage of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication.
While taking this drug, you may be at a higher risk of developing infections, some of which can be severe or even life-threatening. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Additionally, this medication may increase your likelihood of bleeding easily. To reduce the risk of injury, exercise caution in your daily activities and use a soft toothbrush and an electric razor for personal grooming.
Regular monitoring of your blood work and other laboratory tests is crucial, as directed by your doctor. If you are not up to date with all recommended vaccinations, consult with your doctor, as you may need to receive certain vaccines before starting treatment with this drug.
Before receiving any vaccinations, discuss the potential risks and benefits with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication.
If you have taken this drug and are scheduled to receive a blood transfusion, inform your doctor, as they may need to order an MRI scan before initiating treatment.
There is a risk of developing herpes zoster (shingles) while taking this medication. Your doctor may recommend a vaccine against shingles before starting treatment.
Furthermore, cases of hepatitis and tuberculosis (TB) have been reported in patients taking this drug, and in some instances, these infections have been fatal. To assess your risk, you will undergo testing for hepatitis and TB before the first and second treatment courses.
While taking this drug, you may be at a higher risk of developing infections, some of which can be severe or even life-threatening. To minimize this risk, practice good hygiene by washing your hands frequently and avoid close contact with individuals who have infections, colds, or flu.
Additionally, this medication may increase your likelihood of bleeding easily. To reduce the risk of injury, exercise caution in your daily activities and use a soft toothbrush and an electric razor for personal grooming.
Regular monitoring of your blood work and other laboratory tests is crucial, as directed by your doctor. If you are not up to date with all recommended vaccinations, consult with your doctor, as you may need to receive certain vaccines before starting treatment with this drug.
Before receiving any vaccinations, discuss the potential risks and benefits with your doctor, as some vaccines may not be effective or may increase the risk of infection when taken with this medication.
If you have taken this drug and are scheduled to receive a blood transfusion, inform your doctor, as they may need to order an MRI scan before initiating treatment.
There is a risk of developing herpes zoster (shingles) while taking this medication. Your doctor may recommend a vaccine against shingles before starting treatment.
Furthermore, cases of hepatitis and tuberculosis (TB) have been reported in patients taking this drug, and in some instances, these infections have been fatal. To assess your risk, you will undergo testing for hepatitis and TB before the first and second treatment courses.
Overdose Information
Overdose Symptoms:
- Severe myelosuppression (e.g., neutropenia, thrombocytopenia, anemia)
- Immunosuppression
What to Do:
There is no specific antidote. Treatment should consist of supportive measures, including close monitoring of hematologic parameters and management of potential complications (e.g., infection, bleeding). Contact a poison control center (e.g., 1-800-222-1222) or seek emergency medical attention.
Drug Interactions
Contraindicated Interactions
- Immunosuppressants (e.g., methotrexate, cyclosporine, azathioprine) - due to additive immunosuppressive effects and risk of myelosuppression.
- Live or live-attenuated vaccines - due to risk of vaccine-induced infection.
Major Interactions
- Other myelosuppressive agents (e.g., carbamazepine, chloramphenicol, clozapine, ticlopidine) - increased risk of hematologic toxicity.
- Drugs that affect nucleoside transport (e.g., eltrombopag, rifampin, cyclosporine, nifedipine) - potential to alter cladribine exposure.
Moderate Interactions
- Corticosteroids (concurrent or prolonged use) - potential for additive immunosuppression.
- P-glycoprotein (P-gp) inhibitors (e.g., verapamil, quinidine) - may increase cladribine exposure.
- P-glycoprotein (P-gp) inducers (e.g., St. John's Wort) - may decrease cladribine exposure.
Minor Interactions
- Not specifically identified as minor interactions with clinical significance in the label.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with differential (lymphocyte count)
Rationale: To ensure baseline lymphocyte count is within normal limits and to assess for pre-existing cytopenias.
Timing: Within 10 days prior to the first dose of each treatment course.
Tuberculosis (TB) screening
Rationale: To rule out active or latent TB infection, as cladribine can increase risk of opportunistic infections.
Timing: Prior to initiation of Mavenclad.
Hepatitis B and C virus (HBV/HCV) screening
Rationale: To rule out active infection, as cladribine can lead to reactivation.
Timing: Prior to initiation of Mavenclad.
Malignancy screening (e.g., mammogram, Pap test, skin exam)
Rationale: To assess for pre-existing malignancies, as cladribine carries a risk of malignancy.
Timing: Prior to initiation of Mavenclad, and as clinically indicated.
Routine Monitoring
Complete Blood Count (CBC) with differential (lymphocyte count)
Frequency: Before each treatment course, and at months 2 and 6 of Year 1 and Year 2. More frequently if lymphocyte counts are low.
Target: Lymphocyte count ≥ 800 cells/mm³ before starting any treatment course.
Action Threshold: If lymphocyte count < 800 cells/mm³, delay treatment until count recovers. If count remains < 500 cells/mm³ after 6 months, consider discontinuing treatment.
Signs and symptoms of infection
Frequency: Regularly throughout treatment and for at least 6 months after the last dose.
Target: Not applicable
Action Threshold: Promptly evaluate and treat any signs of infection. Consider delaying or interrupting treatment if serious infection occurs.
Signs and symptoms of malignancy
Frequency: Regularly throughout treatment and for at least 4 years after the last dose.
Target: Not applicable
Action Threshold: Promptly evaluate any suspicious findings. Consider discontinuing treatment if malignancy is diagnosed.
Symptom Monitoring
- Fever
- Chills
- Sore throat
- Unusual fatigue
- Swollen lymph nodes
- Unexplained weight loss
- New or worsening skin lesions
- Persistent cough
- Painful urination
Special Patient Groups
Pregnancy
Contraindicated in pregnant women and women of childbearing potential not using effective contraception due to potential for fetal harm. Cladribine is genotoxic and causes teratogenicity and embryofetal lethality in animals.
Trimester-Specific Risks:
First Trimester:
High risk of major birth defects and embryofetal lethality.
Second Trimester:
High risk of fetal harm.
Third Trimester:
High risk of fetal harm.
Lactation
Contraindicated during treatment and for at least 10 days after the last dose due to the potential for serious adverse reactions in the breastfed infant.
Infant Risk:
High risk of serious adverse effects due to cladribine's mechanism of action and potential for excretion into breast milk.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients. Not recommended for use in this population.
Geriatric Use
Clinical studies did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Use with caution in elderly patients, generally starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Monitor lymphocyte counts closely.
Clinical Information
Clinical Pearls
- Mavenclad is a high-efficacy DMT for MS, but requires careful patient selection and monitoring due to its safety profile (malignancy, serious infections).
- The dosing regimen is unique: two short courses over two years, with no further treatment needed for at least two years after the last dose.
- Strict adherence to lymphocyte monitoring is crucial before and during treatment to manage infection risk.
- Patients must be screened for active and latent infections (TB, HBV, HCV) and malignancy prior to initiation.
- Live vaccines are contraindicated during and for at least 6 months after treatment.
- Effective contraception is mandatory for both male and female patients during treatment and for 6 months after the last dose.
Alternative Therapies
- Interferon beta (e.g., Avonex, Betaseron, Rebif, Plegridy)
- Glatiramer acetate (e.g., Copaxone, Glatopa)
- Natalizumab (Tysabri)
- Fingolimod (Gilenya)
- Dimethyl fumarate (Tecfidera)
- Teriflunomide (Aubagio)
- Ocrelizumab (Ocrevus)
- Alemtuzumab (Lemtrada)
- Siponimod (Mayzent)
- Ozanimod (Zeposia)
- Ponesimod (Ponvory)
Cost & Coverage
Average Cost:
Highly variable, typically >$100,000 per year of treatment per treatment course/year
Insurance Coverage:
Specialty Tier (requires prior authorization, step therapy, and/or quantity limits)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe use, never share your medication with others or take someone else's medication. This medication is accompanied by a Medication Guide, which is a valuable patient fact sheet. Please read this guide carefully and review it again whenever you receive a refill of this medication. If you have any questions or concerns about this medication, we encourage you to discuss them with your doctor, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide information about the medication taken, the amount, and the time it occurred.