WHAT IS MAVENCLAD?
MAVENCLAD is a prescription medicine used to treat relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults. Because of its safety profile, MAVENCLAD is generally used in people who have tried another MS medicine that they could not tolerate or that has not worked well enough.

MAVENCLAD is not recommended for use in people with clinically isolated syndrome (CIS).

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

IMPORTANT SAFETY INFORMATION
MAVENCLAD may cause serious side effects, including:

Risk of cancer (malignancies). You should follow healthcare provider instructions about screening for cancer.
MAVENCLAD may cause birth defects if used during pregnancy. Women must not be pregnant when they start treatment with MAVENCLAD or become pregnant during MAVENCLAD dosing and within 6 months after the last dose of each yearly treatment course. You should stop treatment with MAVENCLAD and contact your healthcare provider right away if you become pregnant during treatment with MAVENCLAD.

• For women who are able to become pregnant:
  • Your healthcare provider should order a pregnancy test before you begin your first and second yearly treatment course of MAVENCLAD to make sure that you are not pregnant.
• Ask your healthcare provider which contraceptive method is right for you. Women and men being treated with MAVENCLAD should use effective birth control (contraception) on the days on which they take MAVENCLAD and for at least 6 months after the last dose of each yearly treatment course.

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.
• are breastfeeding.
• are human immunodeficiency virus (HIV) positive.
• have active infections, including tuberculosis (TB), hepatitis B or C.
• are allergic to cladribine.

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

• think you have an infection.
• have taken, take, or plan to take medicines that affect your immune system or 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 the 4 to 6 weeks preceding treatment with MAVENCLAD or receive these types of vaccines during your treatment with MAVENCLAD and unless directed by your healthcare provider.
• have heart failure.
• have or have had cancer.
• have liver or kidney problems.
• are breastfeeding or plan to breastfeed. It is not known if MAVENCLAD passes into your breast milk. Do not breastfeed on the days on which you take MAVENCLAD, and for 10 days after the last dose.

How should I take MAVENCLAD?

• MAVENCLAD is given as two yearly treatment courses, consisting of 2 treatment weeks (cycles) about a month apart.
• Handle MAVENCLAD with dry hands and take immediately after opening the blister pack. Take with water and do not chew the tablet. MAVENCLAD can be taken with or without food and should be taken at least 3 hours apart from other medicines.
• Wash your hands after handling MAVENCLAD. Limit contact with your skin (especially on your face). Wash skin and surfaces with water if contact occurs.
• 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 at least another 2 years during which you do not need to take MAVENCLAD. It is not known if MAVENCLAD is safe and effective in people who restart MAVENCLAD treatment more than 2 years after completing 2 yearly treatment courses.

MAVENCLAD can cause serious side effects. If you have any of these symptoms listed below, call your healthcare provider right away:

• low blood cell counts have happened and can increase your risk of infections during treatment with MAVENCLAD. Blood tests are needed before you start treatment with MAVENCLAD, during your treatment with MAVENCLAD, and afterward, as needed.
• serious infections such as:
  • life-threatening or fatal infections caused by bacteria, viruses, parasites or fungi.
  • 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, aching painful muscles, headache, feeling of being generally unwell, loss of appetite, burning, tingling, numbness or itchiness of the skin in the affected area, skin blotches, blistered rash, or severe pain.
  • 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. Tell your healthcare provider right away if you have any new or worsening neurologic signs or symptoms. These may include: weakness on 1 side of your body, loss of coordination in your arms and legs, decreased strength, problems with balance, changes in your vision, changes in your thinking or memory, confusion, or changes in your personality.
• liver problems. Symptoms of liver problems may include: nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or your skin or the whites of your eyes turn yellow. Your doctor will perform blood tests to check your liver during treatment.
• allergic reactions (hypersensitivities). You should stop treatment and seek immediate medical attention if any signs or symptoms of allergic reactions occur. 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.

The most common side effects of MAVENCLAD include: upper respiratory infection, headache, and low white blood cell counts.

These are not all the possible side effects of MAVENCLAD. Call your doctor for medical advice about side effects. To report SUSPECTED ADVERSE REACTIONS, contact EMD Serono at: 1-800-283-8088 ext. 5563 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information and Medication Guide, including serious side effects.

--Brand Name--
US Brand Name: Mavenclad

--Description--
Cladribine is used to treat the relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease, in patients who have been previously treated with other medicines that did not work well. Cladribine will not cure MS, but it may slow some of the disabling effects and decrease the number of relapses of the disease.

This medicine is available only with your doctor's prescription.

This product is available in the following dosage forms: Tablet

--Before Using--
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of cladribine in the pediatric population. Use is not recommended in children. Safety and efficacy have not been established.

Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of cladribine in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require caution in patients receiving this medicine.

Breastfeeding
Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using this medicine.

Drug Interactions
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bacillus of Calmette and Guerin Vaccine, Live
• Dengue Tetravalent Vaccine, Live
• Measles Virus Vaccine, Live
• Mumps Virus Vaccine, Live
• Rubella Virus Vaccine, Live
• Smallpox Monkeypox Vaccine
• Typhoid Vaccine
• Varicella Virus Vaccine, Live
• Yellow Fever Vaccine

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Adenovirus Vaccine Type 4, Live
• Adenovirus Vaccine Type 7, Live
• Cholera Vaccine
• Ebola Zaire Vaccine, Live
• Influenza Virus Vaccine, Live
• Rotavirus Vaccine, Live

Other Interactions
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems
The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Cancer or
• Hepatitis infection, chronic, active or
• Human immunodeficiency virus (HIV) infection or
• Tuberculosis infection, chronic, active—Should not be used in patients with these conditions.
• Cancer, history of or
• Heart disease—Use with caution. May increase risk for more side effects.
• Hepatitis B or C or
• Tuberculosis, latent—Use with caution. May make these infections active again.
• Infection (eg, bacterial, viral, parasitic, and fungal), acute—Must be treated first before using this medicine.
• Kidney disease, moderate to severe or
• Liver disease, moderate to severe—Use is not recommended in patients with these conditions.

--Proper Use--
Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

You may take this medicine with or without food.

Swallow the tablet whole with water. Do not crush, break, or chew it. Remove the tablet from the blister once you are ready to use it.

Your hands must be dry when handling the tablet. Wash your hands with soap and water afterwards. Limit direct skin contact with the tablets and wash the exposed areas thoroughly.

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.

If you are taking any other oral medicines, take them at least 3 hours before or after using this medicine.

Dosing
The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For oral dosage form (tablets):
For relapsing forms of multiple sclerosis:

• Adults—Dose is based on body weight and must be determined by your doctor. The dose is 3.5 milligrams (mg) per kilograms (kg) of body weight divided into 2 yearly treatment courses (1.75 mg per kg per treatment course). Each treatment course is divided into 2 treatment cycles and will be determined by your doctor.
• Children—Use is not recommended.

Missed Dose
If you miss a dose of this medicine, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

This will extend the number of days in that treatment cycle. If you miss 2 doses in a row, extend the treatment cycle by 2 days.

Storage
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

--Precautions--
It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood and urine tests may be needed to check for any unwanted effects.

If you are a woman who can get pregnant, your doctor may do tests to make sure you are not pregnant before starting this medicine. Using this medicine while you are pregnant can harm your unborn baby. Birth control pills may not work as well to prevent pregnancy when used with this medicine. Use another form of birth control (eg, condoms, spermicide) along with your pills during treatment and for at least 6 months after the last dose in each treatment course. Men should use an effective form of birth control during treatment and for at least 6 months after the last dose in each treatment course to prevent pregnancy in a sexual partner. If a pregnancy occurs while using the medicine, tell your doctor right away.

Using this medicine may increase your risk of getting cancer. Talk to your doctor if you have concerns about this risk.

Cladribine can temporarily lower the number of white blood cells in your blood, which will increase the risk of getting an infection. It can also lower the number of platelets, which are necessary for proper blood clotting. If this occurs, these are precautions you can take, especially when your blood count is low, to reduce the risk of infection or bleeding:

• If you can, avoid people with infections. Check with your doctor right away if you think you are getting an infection or if you get a fever or chills, cough or hoarseness, lower back or side pain, or painful or difficult urination.
• Check with your doctor right away if you notice any unusual bleeding or bruising, black, tarry stools, blood in the urine or stools, or pinpoint red spots on your skin.
• Be careful when using a regular toothbrush, dental floss, or toothpick. Your medical doctor, dentist, or nurse may recommend other ways to clean your teeth and gums. Check with your medical doctor before having any dental work done.
• Do not touch your eyes or the inside of your nose unless you have just washed your hands and have not touched anything else in the meantime.
• Be careful not to cut yourself when you are using sharp objects such as a safety razor or fingernail or toenail cutters.
• Avoid contact sports or other situations where bruising or injury could occur.

This medicine may increase your risk for serious infections (eg, bacterial, fungal, viral, parasitic). Check with your doctor right away if you have chest tightness, stomach pain, fever, itching, pain or redness of the skin, indigestion, nausea, vomiting, chills, confusion, dizziness, fast heartbeat, bone pain, diarrhea, loss of appetite, weakness, bleeding in the eye, blurred vision, trouble breathing, sneezing, or cough.

You will need to have a skin test for tuberculosis (TB) before you start this medicine. Tell your doctor if you or anyone in your home has ever had a positive TB skin test or been exposed to TB.

This medicine may increase your risk of developing infections, including a serious brain infection called progressive multifocal leukoencephalopathy. Check with your doctor if you have weakness on one side of the body, clumsiness, blurred vision, changes in thinking, memory problems, confusion, or personality changes.

While you are being treated with cladribine, and after you stop treatment with it, do not have any immunizations (vaccinations) without your doctor's approval. You may receive live or live-attenuated vaccines at least 4 weeks to 6 weeks before starting this medicine. Cladribine may lower your body's resistance and there is a chance you might get the infection the immunization is meant to prevent. In addition, other persons living in your household should not take oral polio vaccine since there is a chance they could pass the polio virus on to you. Also, avoid persons who have taken oral polio vaccine within the last several months. Do not get close to them, and do not stay in the same room with them for very long. If you cannot take these precautions, you should consider wearing a protective face mask that covers the nose and mouth.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause serious allergic reactions, which can be life-threatening and requires immediate medical attention. Tell your doctor right away if you have a rash, itching, hoarseness, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth after using this medicine.

Check with your doctor right away if you have chest pain or tightness, decreased urine output, dilated neck veins, extreme fatigue, irregular breathing, irregular heartbeat, swelling of the face, fingers, feet, or lower legs, trouble breathing, or weight gain. These may be signs of a heart condition called heart failure.

This medicine may cause blood transfusion problems (eg, transfusion-associated graft-versus-host disease). Talk with your doctor if you have concerns about this.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (eg, St. John's wort) or vitamin supplements.

--Side Effects--
Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Body aches or pain
• chest tightness
• chills
• cough
• ear congestion
• fast heartbeat
• fever
• headache
• hives, itching, skin rash
• hoarseness
• irritation
• joint pain, stiffness, or swelling
• loss of voice
• lower back or side pain
• painful or difficult urination
• redness of the skin
• runny or stuffy nose
• sneezing
• sore throat
• swelling of the eyelids, face, lips, hands, or feet
• trouble breathing or swallowing
• unusual tiredness or weakness

Less common

• Blurred vision
• cough producing mucus
• discouragement
• dizziness
• feeling sad or empty
• lack of appetite
• loss of interest or pleasure
• nervousness
• pounding in the ears
• slow heartbeat
• trouble concentrating
• trouble sleeping

Rare

• Burning or stinging of the skin
• confusion
• painful cold sores or blisters on the lips, nose, eyes, or genitals
• seizures
• stiff neck
• vomiting

Incidence not known

• Blistering, peeling, loosening of the skin
• chest pain
• diarrhea
• muscle pain
• pain, itching, or tingling of the skin
• red skin lesions, often with a purple center
• red, irritated eyes
• sensitivity to light
• sores, ulcers, or white spots in the mouth or on the lips
• stomach upset
• swollen glands
• unusual bleeding or bruising
• weight loss

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Back pain
• difficulty in moving
• muscle stiffness
• trouble sleeping

Less common

• Thinning or loss of hair

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.