MAVENCLAD
Cladribine Tablets for Highly Active Relapsing Multiple Sclerosis
Quick Facts About MAVENCLAD
Key Takeaways About MAVENCLAD
- Short treatment courses: MAVENCLAD is taken orally for a maximum of 20 days over 2 years, with no further treatment needed for at least 2 additional years while disease control is maintained
- Lymphocyte monitoring is essential: Blood tests are required before, during and after treatment to ensure lymphocyte levels remain within safe limits
- Shingles risk: Herpes zoster (shingles) is a very common side effect; vaccination against varicella zoster may be recommended before starting treatment
- Strict contraception required: Women must use effective contraception during treatment and for at least 6 months after the last dose; men for at least 3 months after the last dose
- Not for immunocompromised patients: MAVENCLAD must not be used in patients with HIV, active tuberculosis, active hepatitis, active cancer, or those already on other immunosuppressive therapies
What Is MAVENCLAD and What Is It Used For?
MAVENCLAD contains the active substance cladribine, a cytotoxic (cell-killing) agent that primarily targets lymphocytes – the immune cells involved in the inflammatory process that drives multiple sclerosis. It is approved for the treatment of highly active relapsing forms of MS in adults.
Multiple sclerosis (MS) is a chronic autoimmune disease in which the body’s immune system mistakenly attacks the protective myelin sheath surrounding nerve fibres in the brain and spinal cord. This demyelination disrupts the transmission of nerve signals, leading to a wide range of neurological symptoms including visual disturbances, numbness, weakness, fatigue, and difficulties with balance and coordination. In relapsing forms of MS, patients experience episodes of new or worsening symptoms (relapses) followed by periods of partial or complete recovery.
MAVENCLAD belongs to a class of medications known as selective immunosuppressants. Unlike many other MS therapies that require continuous daily or frequent administration, cladribine tablets offer a unique treatment paradigm. The drug selectively depletes peripheral B and T lymphocytes through a mechanism involving its intracellular accumulation as a phosphorylated metabolite. Lymphocytes are particularly susceptible because they have a high ratio of the activating enzyme deoxycytidine kinase (DCK) relative to the deactivating enzyme 5’-nucleotidase. This results in preferential accumulation of the active drug in lymphocytes, leading to DNA strand breaks and apoptosis (programmed cell death).
Clinical trials, most notably the CLARITY study (CLAdRIbine Tablets treating multiple sclerosis orallY), demonstrated that cladribine tablets significantly reduced the annualised relapse rate by approximately 55–58% compared to placebo. The drug also substantially reduced the risk of 3-month and 6-month confirmed disability progression and led to marked reductions in new or enlarging T2 lesions on MRI. The CLARITY Extension study further showed sustained efficacy over 4 years, even without additional treatment in years 3 and 4, supporting the concept of immune reconstitution therapy.
MAVENCLAD was approved by the European Medicines Agency (EMA) in 2017 and by the U.S. Food and Drug Administration (FDA) in 2019 for the treatment of relapsing forms of MS, including relapsing-remitting MS (RRMS) and active secondary progressive MS. It is generally positioned as a treatment option for patients with highly active disease, defined by clinical or imaging features indicative of ongoing disease activity despite treatment with at least one disease-modifying therapy, or for patients with rapidly evolving severe relapsing MS.
Unlike many other MS medications that require continuous treatment, MAVENCLAD uses an immune reconstitution approach. After two short annual treatment courses (a maximum of 20 days of tablet-taking over 2 years), the immune system gradually recovers while maintaining long-term disease control. This means patients are treatment-free for at least the following 2 years.
What Should You Know Before Taking MAVENCLAD?
Before starting MAVENCLAD, your doctor will perform blood tests and check for infections. You must not take MAVENCLAD if you are HIV-positive, have active tuberculosis or hepatitis, active cancer, moderate to severe kidney problems, are pregnant or breastfeeding, or are already on other immunosuppressive therapies.
Contraindications
You must not take MAVENCLAD if any of the following apply to you:
- Allergy to cladribine or any of the other ingredients in this medicine (hydroxypropylbetadex, sorbitol, magnesium stearate)
- HIV infection – if you are infected with human immunodeficiency virus
- Active tuberculosis or active hepatitis – these infections must be treated and resolved before MAVENCLAD can be considered
- Compromised immune system due to medical conditions or other medicines that weaken your immune system or reduce blood cell production in the bone marrow, including ciclosporin, cyclophosphamide, azathioprine, methotrexate, and long-term corticosteroids
- Active cancer (malignancy) – MAVENCLAD should not be used in patients with current malignancies
- Moderate to severe kidney impairment – reduced kidney function affects the clearance of cladribine and may increase the risk of toxicity
- Pregnancy or breastfeeding – cladribine can cause serious harm to an unborn baby
Warnings and Precautions
Talk to your doctor or pharmacist before taking MAVENCLAD. Several important precautions must be considered before and during treatment.
Blood Tests
You will need to have blood tests taken before treatment starts to check that MAVENCLAD is suitable for you. Your doctor will also take blood tests during and after treatment to check that you can continue taking MAVENCLAD and that you are not developing any complications as a result of the treatment. Lymphocyte counts must be within normal limits before each treatment course can begin. If levels are too low, the treatment course will be delayed until recovery occurs.
Infections
You will be assessed for infections before starting MAVENCLAD. It is vital that you tell your doctor if you think you have any infection, as these can become serious or even life-threatening during treatment with MAVENCLAD. Symptoms of infection may include fever, aching, muscle pain, headache, generally feeling unwell, or yellowing of the whites of the eyes. Your doctor may delay or discontinue treatment until the infection has resolved.
Herpes Zoster (Shingles)
If needed, you will be vaccinated against herpes zoster (shingles) before starting treatment. You must wait 4 to 6 weeks for the vaccine to take full effect. Contact your doctor immediately if you develop symptoms of shingles – a common complication of MAVENCLAD. Shingles typically presents as a painful, blistering rash that appears in a band or strip pattern, usually on one side of the body or face. Early symptoms may include headache, burning, tingling, numbness, or itching in the affected area, along with a general feeling of being unwell or fever.
Progressive Multifocal Leukoencephalopathy (PML)
If you feel that your MS is getting worse, or if you notice any new symptoms such as changes in mood or behaviour, memory lapses, speech difficulties, or difficulty communicating, contact your doctor as soon as possible. These could be symptoms of a rare brain disorder caused by infection called progressive multifocal leukoencephalopathy (PML). PML is a serious condition that can lead to severe disability or death. Although PML has not been reported with MAVENCLAD, as a precaution your doctor may arrange for an MRI scan of the brain before you start treatment.
Cancer Risk
Isolated cases of cancer have been observed in patients treated with cladribine in clinical studies. Tell your doctor if you have previously had cancer. Your doctor will determine the best treatment options for you. As a precaution, you should follow standard cancer screening recommendations as advised by your doctor throughout and after treatment.
Liver Problems
MAVENCLAD can cause liver problems. Tell your doctor before taking MAVENCLAD if you have or have ever had liver problems. Contact your doctor immediately if you develop one or more of the following symptoms: nausea, vomiting, abdominal pain, fatigue, loss of appetite, yellowing of the skin or eyes (jaundice), or dark urine. These may be symptoms of serious liver injury, and treatment with MAVENCLAD may need to be temporarily or permanently discontinued.
Pregnancy and Breastfeeding
Do not take MAVENCLAD if you are pregnant or trying to become pregnant. This is critically important because cladribine can cause serious harm to your unborn baby. MAVENCLAD has been shown to be teratogenic in animal studies, and its mechanism of action (targeting rapidly dividing cells) poses a significant risk to foetal development.
Women must use effective contraception during treatment with MAVENCLAD and for at least 6 months after the last dose. If you become pregnant more than 6 months after the last dose during year 1, no safety risk is expected, but you cannot receive the year 2 treatment course while pregnant. Your doctor will advise you on suitable contraceptive methods.
Men must use effective contraception during treatment with MAVENCLAD and for at least 3 months after the last dose to prevent the potential transfer of the drug to a partner.
Do not take MAVENCLAD if you are breastfeeding. If your doctor considers MAVENCLAD necessary for you, they will advise you to stop breastfeeding during treatment and for at least one week after the last dose.
Children and Adolescents
MAVENCLAD is not recommended for patients under 18 years of age because the medicine has not been studied in this age group. The safety and efficacy of cladribine tablets in paediatric MS patients have not been established.
Driving and Operating Machinery
MAVENCLAD is not expected to affect your ability to drive or use machines. However, as with any medication, if you experience side effects that could impair your concentration or reflexes, exercise appropriate caution.
How Does MAVENCLAD Interact with Other Drugs?
MAVENCLAD must not be taken with other immunosuppressive drugs. Other oral medications should be taken at least 3 hours apart from MAVENCLAD. Live vaccines are contraindicated during treatment. Several drugs can affect how MAVENCLAD works or increase side effects.
Tell your doctor or pharmacist about all medicines you are taking, have recently taken, or might take. Drug interactions with MAVENCLAD can be clinically significant due to the drug’s immunosuppressive mechanism and the presence of hydroxypropylbetadex as an excipient, which can affect absorption of other oral medications in the stomach.
Major Interactions (Contraindicated)
Do not start MAVENCLAD with any of the following immunosuppressive or myelosuppressive drugs, as the combined effect could dangerously suppress your immune system:
| Drug | Typical Use | Interaction Severity |
|---|---|---|
| Ciclosporin | Immune suppression (e.g., after organ transplant) | Contraindicated |
| Cyclophosphamide | Immune suppression, cancer treatment | Contraindicated |
| Azathioprine | Immune suppression (autoimmune diseases) | Contraindicated |
| Methotrexate | Psoriasis, rheumatoid arthritis | Contraindicated |
| Long-term corticosteroids | Chronic inflammation (e.g., asthma) | Contraindicated |
| Other MS disease-modifying therapies | Multiple sclerosis treatment | Contraindicated (unless specifically directed) |
Note that short-term use of corticosteroids (e.g., for managing an acute MS relapse) may be permitted if prescribed by your doctor.
Moderate Interactions (Use with Caution)
The following drugs may interact with MAVENCLAD and require careful monitoring or dose adjustment:
| Drug | Concern | Action Required |
|---|---|---|
| Carbamazepine | May affect blood cell counts | Closer monitoring of blood counts |
| Rifampicin | May affect intracellular cladribine levels via BCRP/P-gp induction | Doctor will advise on management |
| St John’s Wort | Enzyme induction may reduce cladribine efficacy | Doctor will advise on management |
| Dilazep, Nifedipine, Nimodipine, Reserpine, Cilostazol, Sulindac | May inhibit BCRP/ENT1 transporters affecting cladribine distribution | Doctor will advise; possible timing adjustment |
| Eltrombopag | BCRP inhibitor affecting cladribine distribution | Doctor will advise on management |
| Live or live-attenuated vaccines | Risk of active infection from vaccine strain | Vaccinate 4–6 weeks before starting; avoid during treatment until immune recovery |
Timing of Other Oral Medications
Do not take MAVENCLAD at the same time as any other oral medicine. Allow at least 3 hours between taking MAVENCLAD and any other oral medicine. MAVENCLAD contains hydroxypropylbetadex which can interact with or be affected by other drugs in the stomach, potentially altering absorption of either medicine.
What Is the Correct Dosage of MAVENCLAD?
MAVENCLAD is given as two treatment courses over 2 years. Each course consists of two treatment weeks, approximately one month apart, during which you take 1 or 2 tablets daily for 4 or 5 days. The total dose per treatment course is determined by your body weight.
Treatment Schedule
The complete MAVENCLAD treatment programme spans 2 years and is structured as follows:
Year 1 – First Treatment Course
- Treatment Week 1: 1 or 2 tablets daily for 4 or 5 days (e.g., mid-April)
- Treatment Week 2: 1 or 2 tablets daily for 4 or 5 days, approximately one month later (e.g., mid-May)
Year 2 – Second Treatment Course
- Treatment Week 1: 1 or 2 tablets daily for 4 or 5 days (approximately 12 months after Year 1 start)
- Treatment Week 2: 1 or 2 tablets daily for 4 or 5 days, approximately one month later
Before each treatment course, your doctor will take a blood test to confirm that your lymphocyte count is within acceptable limits. If levels are too low, the treatment course will be delayed until sufficient recovery has occurred.
Dosage by Body Weight
The number of tablets you receive for each treatment week is determined by your body weight. The recommended cumulative dose is approximately 3.5 mg/kg body weight over 2 years (1.75 mg/kg per treatment course). The following table shows the number of tablets per treatment week:
| Body Weight | Year 1 – Week 1 | Year 1 – Week 2 | Year 2 – Week 1 | Year 2 – Week 2 |
|---|---|---|---|---|
| 40 to <50 kg | 4 tablets | 4 tablets | 4 tablets | 4 tablets |
| 50 to <60 kg | 5 tablets | 5 tablets | 5 tablets | 5 tablets |
| 60 to <70 kg | 6 tablets | 6 tablets | 6 tablets | 6 tablets |
| 70 to <80 kg | 7 tablets | 7 tablets | 7 tablets | 7 tablets |
| 80 to <90 kg | 8 tablets | 7 tablets | 8 tablets | 7 tablets |
| 90 to <100 kg | 9 tablets | 8 tablets | 9 tablets | 8 tablets |
| 100 to <110 kg | 10 tablets | 9 tablets | 10 tablets | 9 tablets |
| 110 kg and above | 10 tablets | 10 tablets | 10 tablets | 10 tablets |
How to Take Your Tablets
Take your tablet(s) at approximately the same time each day. Swallow them whole with water – do not chew, crush, or dissolve the tablets. You can take them with or without food. If your daily dose is 2 tablets, take both at the same time.
- Ensure your hands are dry before touching the tablets
- Push the tablet(s) through the blister and swallow immediately
- Do not leave tablets on surfaces or handle them longer than necessary
- If a tablet is left on a surface or breaks, clean the area thoroughly
- Wash your hands thoroughly with soap and water after handling tablets
- If you lose a tablet, contact your doctor for advice
Daily Distribution of Tablets
Depending on the total number of tablets prescribed for each treatment week, the daily distribution is as follows:
| Total 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 |
Missed Dose
If you miss a dose and remember on the same day, take it as soon as you remember. If you do not remember until the following day, do not take the missed dose together with the next scheduled dose. Instead, take the missed dose on the next day and extend the number of days in that treatment week accordingly. For example, if you forget your day 3 dose and do not remember until day 4, take the day 3 dose on day 4 and extend the treatment week by one day. If you miss two consecutive doses, apply the same rule and extend the treatment week by two days.
Overdose
If you take more tablets than you should, contact your doctor immediately. There is limited experience with cladribine overdose. The primary concern is that higher doses will lead to more profound and prolonged lymphopenia, increasing the risk of serious infections. Your doctor will determine whether treatment needs to be interrupted and will monitor your blood counts closely.
What Are the Side Effects of MAVENCLAD?
Like all medicines, MAVENCLAD can cause side effects, although not everybody gets them. The most important side effect is lymphopenia (low lymphocyte count), which is very common and expected. This increases the risk of infections, particularly herpes zoster (shingles).
The side effects of MAVENCLAD are largely related to its mechanism of action – the selective depletion of lymphocytes. Because lymphocytes play a central role in immune defence, a reduction in their numbers can increase susceptibility to infections. Your doctor will monitor your lymphocyte counts closely throughout treatment to manage this risk. Most side effects are manageable with appropriate monitoring and intervention.
Very Common
- Lymphopenia (low lymphocyte count) – this is the most significant side effect and an expected pharmacological effect of MAVENCLAD. It increases the risk of developing infections
- Herpes zoster (shingles) – a painful, blistering rash caused by reactivation of the varicella-zoster virus. It typically appears as a band of blisters on one side of the body or face. Early symptoms may include tingling, burning, or itching
Common
- Oral herpes (cold sores) – reactivation of herpes simplex virus causing blisters around the mouth
- Skin rash – various types of skin eruptions
- Hair loss (alopecia) – thinning or loss of hair, usually temporary
- Decreased neutrophil count (neutropenia) – reduction of another type of white blood cell
- Allergic reactions – including itching, hives (urticaria), skin rash, and swelling of the lips, tongue or face
Uncommon
- Liver problems (hepatotoxicity) – symptoms may include nausea, vomiting, abdominal pain, fatigue, loss of appetite, jaundice, or dark urine. Treatment may need to be stopped temporarily or permanently
Very Rare
- Tuberculosis – reactivation of latent tuberculosis infection
- Symptoms of shingles (painful blistering rash, usually on one side of the body)
- Signs of liver problems (nausea, vomiting, abdominal pain, yellowing of skin/eyes, dark urine)
- Signs of a serious infection (high fever, severe malaise, persistent symptoms)
- Signs of PML (new or worsening neurological symptoms, cognitive changes, personality changes)
If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed above. You can also report suspected adverse reactions to your national medicines regulatory authority, which helps in the ongoing monitoring of the benefit-risk balance of the medicine.
How Should You Store MAVENCLAD?
Keep MAVENCLAD out of the sight and reach of children. Store in the original packaging to protect from moisture. Do not use after the expiry date printed on the carton.
Proper storage of MAVENCLAD is essential to maintain the integrity and effectiveness of the medication. Cladribine tablets are sensitive to moisture and must be protected from humid environments. Follow these guidelines carefully:
- Keep out of the sight and reach of children – the child-resistant packaging is designed to prevent accidental access, but additional precautions should be taken
- Do not use after the expiry date – the expiry date (marked as EXP on the wallet and carton) refers to the last day of that month
- Store in the original packaging – keep the tablets in the blister pack inside the wallet, which is sealed inside the child-resistant carton to protect from moisture
- Do not remove tablets from the blister until ready to take them – do not store tablets loose or in any other container
- Dispose of unused medicines properly – do not throw medicines into household waste or down the drain. Return unused tablets to your pharmacy for safe disposal to protect the environment
The MAVENCLAD packaging is specifically designed with a child-resistant carton that requires a specific opening sequence. Follow the step-by-step instructions provided with your medicine to correctly open and close the packaging. Always re-seal the carton after each use.
What Does MAVENCLAD Contain?
Each MAVENCLAD tablet contains 10 mg of cladribine as the active substance. The tablets are white, round, biconvex and marked with “C” on one side and “10” on the other.
Active Substance
The active ingredient in MAVENCLAD is cladribine (also known as 2-chloro-2’-deoxyadenosine or 2-CdA). Each tablet contains 10 mg of cladribine. Cladribine is a synthetic purine nucleoside analogue that acts as a prodrug – it is converted into its pharmacologically active form (2-chlorodeoxyadenosine triphosphate) inside cells through phosphorylation by the enzyme deoxycytidine kinase.
Other Ingredients (Excipients)
- Hydroxypropylbetadex – a cyclodextrin derivative used to enhance the solubility and stability of cladribine. This excipient can interact with other oral medicines in the stomach, which is why a 3-hour gap is recommended between MAVENCLAD and other oral medications
- Sorbitol – a sugar alcohol used as a sweetening agent and bulking agent. Each tablet contains 64 mg of sorbitol. Patients with hereditary fructose intolerance should be aware of this
- Magnesium stearate – used as a lubricant in tablet manufacturing to prevent the ingredients from sticking to machinery during production
Tablet Appearance and Pack Sizes
MAVENCLAD tablets are white, round, biconvex tablets debossed with “C” on one side and “10” on the other side. Each pack contains 1, 4, 5, 6, 7, or 8 tablets in a blister, sealed in a card wallet and affixed inside a child-resistant carton. Not all pack sizes may be available in your country.
Frequently Asked Questions About MAVENCLAD
MAVENCLAD (cladribine) is a prescription medicine used to treat highly active relapsing forms of multiple sclerosis (MS) in adults. It is classified as a disease-modifying therapy that works by selectively reducing certain white blood cells (lymphocytes) involved in the abnormal immune response that drives MS. It is typically prescribed for patients with highly active disease despite previous treatment, or for those with rapidly evolving severe relapsing MS.
The active treatment with MAVENCLAD lasts 2 years. Each year consists of two treatment weeks separated by approximately one month, during which you take tablets for 4 or 5 days per week. After completing both treatment years, no further MAVENCLAD treatment is needed for at least 2 additional years. Your doctor will continue to monitor you during this treatment-free period. In total, the actual days of tablet-taking amount to a maximum of approximately 20 days over the entire 2-year treatment programme.
There is no specific contraindication against alcohol with MAVENCLAD. However, since MAVENCLAD can affect the liver, and alcohol also stresses the liver, it is generally advisable to limit alcohol consumption during the treatment weeks. Discuss your alcohol intake with your doctor, who can provide personalised advice based on your overall health and liver function.
Contact your doctor immediately if you develop symptoms of shingles, such as a painful, blistering rash typically appearing in a band on one side of your body or face. Shingles requires prompt antiviral treatment (e.g., aciclovir or valaciclovir), and your MAVENCLAD treatment may need to be paused until the infection has fully resolved. Early treatment of shingles is important to reduce the severity and duration of symptoms and to prevent complications such as postherpetic neuralgia.
While cladribine (the active ingredient in MAVENCLAD) was originally developed as a chemotherapy drug for certain blood cancers (hairy cell leukaemia), MAVENCLAD tablets are used at much lower doses for MS. The dose used for MS is approximately 10–20 times lower than that used in cancer treatment. At these lower doses, cladribine selectively targets lymphocytes rather than broadly affecting rapidly dividing cells like traditional chemotherapy. This selectivity results in a different and generally more favourable side effect profile compared to conventional chemotherapy.
Live or live-attenuated vaccines must not be given during MAVENCLAD treatment or while your lymphocyte counts are below normal levels, due to the risk of active infection from the vaccine strain. If you have been vaccinated with live vaccines within the past 4 to 6 weeks, treatment with MAVENCLAD must be delayed. Inactivated vaccines (such as influenza or COVID-19 mRNA vaccines) are generally considered safe but may be less effective while lymphocyte counts are low. Your doctor will check your blood to ensure your immune system has recovered before administering any live vaccines.
References
- European Medicines Agency (EMA). MAVENCLAD – Summary of Product Characteristics. Last updated January 2026. Available at: ema.europa.eu/mavenclad
- Giovannoni G, Comi G, Cook S, et al. A Placebo-Controlled Trial of Oral Cladribine for Relapsing Multiple Sclerosis (CLARITY Study). N Engl J Med. 2010;362(5):416-426. doi:10.1056/NEJMoa0902533
- Giovannoni G, Soelberg Sorensen P, Cook S, et al. Safety and efficacy of cladribine tablets in patients with relapsing-remitting multiple sclerosis: Results from the randomized extension trial of the CLARITY study. Mult Scler. 2018;24(12):1594-1604. doi:10.1177/1352458517727603
- Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96-120. doi:10.1177/1352458517751049
- Rae-Grant A, Day GS, Marrie RA, et al. Practice guideline recommendations summary: Disease-modifying therapies for adults with multiple sclerosis. Neurology. 2018;90(17):777-788. doi:10.1212/WNL.0000000000005347
- World Health Organization (WHO). Model List of Essential Medicines – 23rd list, 2023. Geneva: WHO; 2023.
- Cook S, Leist T, Comi G, et al. Safety of cladribine tablets in the treatment of patients with multiple sclerosis: An integrated analysis. Mult Scler Relat Disord. 2019;29:157-167. doi:10.1016/j.msard.2018.11.021
- U.S. Food and Drug Administration (FDA). MAVENCLAD prescribing information. Approved March 2019. Available at: fda.gov.
Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, comprising licensed specialist physicians in neurology, immunology, and clinical pharmacology. All medical content follows the GRADE evidence framework and adheres to international guidelines from the EMA, FDA, AAN, and ECTRIMS/EAN.
Our editorial process includes systematic literature review, cross-referencing with approved product information (Summary of Product Characteristics), and peer review by at least two independent medical specialists. We maintain strict independence from pharmaceutical companies and accept no commercial funding.