Mavenclad

Mavenclad (cladribine) is used to treat relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease, in adults. Because of its risks, Mavenclad is generally used in people who have already tried another MS medicine that they could not tolerate or that did not work well enough. Mavenclad is not recommended for people with clinically isolated syndrome (CIS).

Mavenclad contains cladribine, a purine antimetabolite. Cladribine is a prodrug that becomes active after it is phosphorylated inside cells to its active form (2-chlorodeoxyadenosine triphosphate). The way it works in MS is not fully understood, but cladribine is thought to act through cytotoxic effects on B and T lymphocytes by interfering with DNA synthesis, which reduces (depletes) the number of these immune cells. Mavenclad belongs to the drug class called selective immunosuppressants.

Cladribine, the active ingredient in Mavenclad, was first approved in the U.S. in 1993. Mavenclad received FDA approval on March 29, 2019.

It is not known if Mavenclad is safe and effective in children under 18 years of age.

• Mavenclad is given as two yearly treatment courses.
• Each yearly treatment course consists of 2 treatment weeks (also called cycles) about a month apart. Your healthcare provider will tell you when you have to start your treatment weeks and how many tablets per week you need, depending on your weight. Each treatment week is 4 or 5 days.
• Your pharmacist will dispense a carton of Mavenclad for each treatment week. The prescribed number of tablets per day are provided in child-resistant day packs.
• Take Mavenclad exactly as your healthcare provider tells you. Do not change your dose or stop taking it unless your healthcare provider tells you to.
• Take Mavenclad with water and swallow the tablet whole without chewing. Mavenclad can be taken with or without food.
• Swallow Mavenclad right away after opening the blister pack.
• Mavenclad is a cytotoxic medicine. Your hands must be dry when handling the tablets and washed well with water afterward. Limit contact with your skin, and avoid touching your nose, eyes, and other parts of the body. If Mavenclad gets on your skin or on any surface, wash it off right away with water.
• Take Mavenclad at least 3 hours apart from any other medicines taken by mouth during the 4- to 5-day treatment week.
• If you miss a dose, take it as soon as you remember on the same day. If the whole day passes before you remember, take your missed dose the next day. Do not take 2 doses at the same time. Instead, you will extend the number of days in that treatment week.

Your healthcare provider will continue to monitor your health during the 2 yearly treatment courses, and for atleast another 2 years during which you do not need to take Mavenclad. It is not known if Mavenclad issafe and effective in people who restart Mavenclad treatment more than 2 years after completing 2 yearlytreatment courses.

Mavenclad has a Boxed Warning, the FDA's most prominent warning, for the risk of cancer (malignancies) and the risk of harm to an unborn baby.

Risk of cancer (malignancies)

Treatment with Mavenclad may increase your risk of developing cancer. Mavenclad must not be used if you have a current cancer. Talk to your healthcare provider about your risk of cancer, and follow your healthcare provider's instructions about cancer screening.

Risk of harm to an unborn baby

Mavenclad can cause birth defects if it is used during pregnancy. Females must not be pregnant when they start Mavenclad and must not become pregnant during dosing or within 6 months after the last dose of each yearly treatment course. Males with female partners who can become pregnant must use effective birth control during dosing and for at least 14 weeks after the last dose of each course. Stop Mavenclad and call your healthcare provider right away if you or your partner becomes pregnant during treatment.

• For females who can become pregnant: Your healthcare provider should order a pregnancy test for you before you begin your first and second yearly treatment course of Mavenclad to make sure that you are not pregnant. Your healthcare provider will decide when to do the test. Use effective birth control (contraception) on the days on which you take Mavenclad and for at least 6 months after the last dose of each yearly treatment course. Ask your healthcare provider which contraception method is right for you.
• For males with female partners who can become pregnant: Use effective birth control (contraception) during the days on which you take Mavenclad and for at least 14 weeks after the last dose of each yearly treatment course.
• Mavenclad Pregnancy Safety Study For females treated with Mavenclad: if you become pregnant while taking Mavenclad or during the 6 months after your last dose. For males treated with Mavenclad with a female partner: if your partner becomes pregnant while you are taking Mavenclad or during the 14 weeks after your last dose.

The purpose of this program is to assess the effect of Mavenclad exposure on pregnancy and infant outcomes. Either you or your healthcare provider can report your information by calling 1-800-283-8088 ext. 5563 or by fax 1-781-681-2961.

Do not take Mavenclad if you:

• have cancer (malignancy)
• are pregnant, plan to become pregnant, or are a woman of childbearing age or a man able to father a child, and you are not using birth control (see Important information above)
• are human immunodeficiency virus (HIV) positive
• have active infections, including tuberculosis (TB), hepatitis B or C
• are allergic to cladribine
• are breastfeeding.

Before you take Mavenclad, tell your healthcare provider about all of your medical conditions, including if you:

• think you have an infection
• have heart failure
• have liver or kidney problems
• have taken, take, or plan to take medicines that affect your immune system or your blood cells, or other treatments for MS. Certain medicines can increase your risk of getting an infection
• have had a recent vaccination or are scheduled to receive any vaccinations (you should not receive live or live-attenuated vaccines within 4 to 6 weeks before starting Mavenclad, during treatment, or until your healthcare provider tells you your immune system is no longer weakened)
• have or have had cancer
• are pregnant or plan to become pregnant. Do not take Mavenclad
• are breastfeeding or plan to breastfeed. Mavenclad can pass into your breast milk and may harm your baby. Do not breastfeed on the days you take Mavenclad, and for 10 days after the last dose.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Common side effects

The most common side effects of Mavenclad are:

• upper respiratory infection
• headache
• low white blood cell counts (lymphopenia)

Serious side effects

Mavenclad may cause the following serious side effects:

• Risk of cancer and risk of harm to an unborn baby. See Important information above.
• Low blood cell counts. Mavenclad lowers lymphocyte counts and may also lower other blood cell counts, which can increase your risk of infection. Your healthcare provider will do blood tests before you start treatment, during treatment, and afterward as needed.
• Serious infections, such as: Infections caused by bacteria, viruses, parasites, or fungi that may be life-threatening or cause death. TB, hepatitis B or C, and shingles (herpes zoster). Fatal cases of TB and hepatitis have happened with cladribine during clinical studies. Tell your healthcare provider right away if you get any symptoms of the following infection-related problems or if any of the symptoms get worse, including: fever, loss of appetite, aching, painful muscles, burning, tingling, numbness or itchiness of the skin in the affected area, headache, skin blotches, blistered rash, severe pain, feeling of being generally unwell. Progressive multifocal leukoencephalopathy (PML). PML is a rare brain infection that usually leads to death or severe disability. Although PML has not been seen in MS patients taking Mavenclad, it may happen in people with weakened immune systems. Symptoms of PML get worse over days to weeks. Call your healthcare provider right away if you have any new or worsening neurologic signs or symptoms of PML that have lasted several days, including weakness on one side of your body, changes in your vision, loss of coordination in your arms and legs, changes in your thinking or memory, decreased strength, confusion, problems with balance, changes in your personality.
• Liver problems. Your risk of developing serious liver problems may be higher if you already have liver problems or take other medicines that also affect your liver. Your healthcare provider should do blood tests to check your liver: before you start taking Mavenclad before each course and cycle of Mavenclad treatment.

Call your healthcare provider right away if you have any of the following symptoms of liver problems:

• nausea loss of appetite vomiting your skin or the whites of your eyes turn yellow stomach pain tiredness dark urine.

• Allergic reactions (hypersensitivity). Mavenclad can cause serious allergic reactions. Stop your treatment with Mavenclad and go to the closest emergency room for medical help right away if you have any signs or symptoms of allergic reactions. Symptoms of an allergic reaction may include: skin rash, swelling or itching of the face, lips, tongue, or throat, or trouble breathing.
• Heart failure. Mavenclad may cause heart failure, which means your heart may not pump as well as it should. Call your healthcare provider or go to the closest emergency room for medical help right away if you have any signs or symptoms such as shortness of breath, a fast or irregular heartbeat, or unusual swelling in your body.

Your healthcare provider may delay or completely stop treatment with Mavenclad if you have severe side effects.

These are not all the possible side effects of Mavenclad. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Assessments are required before starting each Mavenclad treatment course.

• Cumulative dosage of 3.5 mg/kg administered orally and divided into 2 treatment courses (1.75 mg/kg per treatment course).
• Each treatment course is divided into 2 treatment cycles.

Mavenclad is a cytotoxic drug.

• Separate administration from any other oral drug by at least 3 hours.

Some medicines should be avoided or used with care while you are taking Mavenclad, including:

• medicines that suppress or modulate the immune system, or that lower blood cell counts (using these with Mavenclad is generally not recommended, although short-term corticosteroids may be used)
• other medicines that can be toxic to the blood
• antiviral and antiretroviral medicines (for example, lamivudine or zidovudine), which may interfere with how cladribine works
• medicines that strongly affect certain transporter proteins (such as ritonavir, cyclosporine, eltrombopag, or dipyridamole), which should be avoided during the 4- to 5-day treatment cycles

Because Mavenclad contains hydroxypropyl betadex, a compound used to improve the solubility and bioavailability of poorly water soluble drugs, take it at least 3 hours apart from other medicines taken by mouth during a treatment week. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

Store Mavenclad at room temperature between 68°F and 77°F (20°C and 25°C).

Keep it in the original package to protect it from moisture.

Mavenclad comes in a child-resistant package.

Ask your healthcare provider or pharmacist how to safely throw away any unused or expired tablets and packaging.

Keep out of the reach of children.

Active ingredient: cladribine

Inactive ingredients: hydroxypropyl betadex, magnesium stearate, and sorbitol.

Mavenclad is available as 10 mg tablets.

Mavenclad (cladribine) is distributed by EMD Serono, Inc., Boston, MA 02210. Mavenclad is a registered trademark of Merck KGaA, Darmstadt, Germany.