Revlimid - Lenalidomide uses, dose and side effects

Multiple myeloma is a form of cancer that affects a certain type of white blood cell, called plasma cells. These cells are found in the bone marrow and multiply uncontrollably. This can damage the skeleton and kidneys.

Multiple myeloma can generally not be cured. However, signs and symptoms can be greatly reduced and occasionally disappear. This is called a “treatment response” or just a “response”.

Newly diagnosed multiple myeloma – in patients who have undergone a bone marrow transplant

Revlimid is used alone as a maintenance treatment after the patient has recovered sufficiently after the bone marrow transplant.

Newly diagnosed multiple myeloma – in patients who cannot be treated with bone marrow transplantation

Revlimid is taken with other medicines. These may include:

a cytostatic drug (also called cytotoxic drug ) called ‘bortezomib’
an anti-inflammatory drug called dexamethasone
a chemotherapy drug called melphalan and
an immunosuppressive drug called prednisone.

You take these other medicines at the beginning of treatment and then continue to take Revlimid only.

If you are 75 years of age or older or have moderate to severe kidney problems, your doctor should check carefully before starting treatment.

Multiple myeloma – in patients who have undergone treatment before

Revlimid is taken with an anti-inflammatory drug called dexamethasone.

Revlimid may prevent the signs and symptoms of multiple myeloma from getting worse. Revlimid has also been shown to delay the recurrence of multiple myeloma after treatment.

Myelodysplastic syndrome (MDS)

MDS is a collective name for several different diseases of the blood and bone marrow. The blood cells become abnormal and do not work properly. Patients may experience several different signs and symptoms, e.g. a low number of red blood cells ( anemia ), need for blood transfusions, and are at risk of infection.

Revlimid is used alone to treat adult patients who have been diagnosed with MDS when all of the following points apply:

you need regular blood transfusions to treat low levels of red blood cells (“transfusion-dependent anemia”)
you have abnormal cells in the bone marrow which is called an “isolated part (5q) cytogenetic abnormality”. This means that your body does not produce enough healthy blood cells
other treatments that have been used in the past, are inappropriate or do not work well enough.

Revlimid can increase the number of healthy red blood cells that the body produces by reducing the number of abnormal cells:

this can reduce the number of blood transfusions you need. No transfusion may be needed at all.

Mantle cell lymphoma (MCL)

MCL is a cancer of a part of the immune system (lymph tissue). It occurs in a type of white blood cell called B lymphocytes or B cells and causes them to grow in an uncontrolled manner and accumulate in the lymph tissue, bone marrow, or blood.

Revlimid is used alone to treat adult patients who have been previously treated with other medicines.

Follicular lymphoma (FL)

FL is slow-growing cancer that affects the B‑ lymphocytes, a type of white blood cell that is involved in the body’s defense against infection. When you have FL, too many of these B‑ lymphocytes can accumulate in the blood, bone marrow, lymph nodes, or spleen.

Revlimid is taken with another medicine called rituximab to treat adult patients with previously treated follicular lymphoma.

How Revlimid works

Revlimid works by affecting the body’s immune system and directly attacking the cancerous tumor. It works in several different ways:

by inhibiting the development of cancer cells
by preventing blood vessels from growing in the cancerous tumor
by stimulating parts of the immune system to attack the cancer cells.

2. What you need to know before you take Revlimid

You must read the package leaflets for all medicines to be taken in combination with Revlimid before starting treatment with Revlimid.

Do not take Revlimid

if you are pregnant, think you may be pregnant or are planning to have a baby, as Revlimid is expected to harm the fetus (see section 2, “Pregnancy, breast-feeding and contraception – information for women and men”).
if you may become pregnant and do not take all the necessary measures to prevent getting pregnant (see section 2 “Pregnancy, breast-feeding and contraception – information for women and men”). If you could become pregnant, your doctor will note at each prescription that the necessary steps have been taken and give you this confirmation.
if you are allergic to lenalidomide or any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, ask your doctor for advice.

If any of these apply to you, do not take Revlimid. Talk to your doctor if you are unsure.

Warnings and cautions

Talk to your doctor, pharmacist, or nurse before taking Revlimid if:

If you have had blood clots before – you are at increased risk of getting blood clots in your veins and arteries during treatment
you have any signs of an infection, e.g. cough or fever
If you have kidney problems – your doctor may adjust the dose of Revlimid if necessary
you have or have had a viral infection, in particular: hepatitis B infection, varicella-zoster, or HIV. Consult a doctor if you are unsure. Treatment with Revlimid may reactivate the virus in patients who carry this virus. This leads to a recurrence of infection. Your doctor will test you for hepatitis B infection
you have had a heart attack, if you have ever had a blood clot or if you smoke, have high blood pressure or high cholesterol
you have had an allergic reaction such as skin rash, itching, swelling, dizziness, or difficulty breathing after taking thalidomide (another medicine used to treat multiple myeloma )
you have previously experienced a combination of the following symptoms: widespread rash, red skin, high body temperature, flu-like symptoms, elevated liver enzyme levels, abnormal blood counts ( eosinophilia ), enlarged lymph nodes – these are signs of a severe skin reaction called a drug reaction with eosinophilia and systemic also known as DRESS or drug hypersensitivity syndrome (see also section 4 “Possible side effects”).

If any of the above apply to you, tell your doctor, pharmacist, or nurse before starting treatment.

Always tell your doctor or nurse immediately if you get any of the following during or after treatment:

blurred vision, loss of vision or double vision, difficulty speaking, weakness in an arm or leg, change in gait or problems with balance, persistent numbness, decreased feeling or loss of feeling, memory loss or confusion. All of these symptoms can indicate a serious and potentially fatal brain disease called progressive multifocal leukoencephalopathy (PML). If you have had these symptoms before treatment with Revlimid, tell your doctor if the symptoms change in any way.
experiencing shortness of breath, fatigue, dizziness, chest pain, faster heartbeat, or swelling in the legs or ankles. These symptoms may indicate a serious condition called pulmonary hypertension (see section 4).

Samples and controls

Before and after treatment with Revlimid, you will be given regular blood tests. This is because Revlimid can reduce the number of blood cells that help fight infections ( white blood cells ) and help the blood to coagulate ( platelets ). Your doctor will ask you to submit a blood test:

before treatment
every week for the first 8 weeks of treatment
thereafter at least once a month.

You may be examined for signs of heart-lung problems before and during treatment with lenalidomide.

For patients with MDS taking Revlimid

If you have MDS, you may be more likely to get a more advanced condition called acute myeloid leukemia (AML). It is also not known how Revlimid affects your chances of getting AML. Your doctor may therefore take samples and check for signs that may better predict the likelihood of you getting AML during treatment with Revlimid.

For patients with MCL taking Revlimid

Your doctor will ask you to submit a blood test:

before treatment
every week for the first 8 weeks of treatment (2 cycles)
since every other week during cycles 3 and 4 (see section “Treatment cycles” for more information)
then at the start of each cycle and
at least once a month.

For patients with FL taking Revlimid

Your doctor will ask you to submit a blood test:

before treatment
every week for the first 3 weeks of treatment (1 cycle)
since every other week during cycles 2 to 4 (see section 3 “Treatment cycles” for more information)
then at the start of each cycle and
at least once a month.

Your doctor can check if you have a high total tumor spread throughout your body including the bone marrow. This can lead to a condition where your tumor breaks down and can cause unusually high levels of chemicals in the blood. This in turn can lead to kidney failure (“tumor light syndrome”).

Your doctor may examine you to see if you have any skin changes, e.g. red spots/dots or rash.

Your doctor may adjust the dose of Revlimid or discontinue treatment depending on the results of your blood tests and your general condition. If you have recently been diagnosed, your doctor may also decide what treatment to take based on your age and any other medical conditions you have.

Blood donation

You should not donate blood during treatment and until at least 7 days after the end of treatment.

Children and young people

Revlimid is not recommended for use in children and adolescents under 18 years of age.

Elderly people and people with kidney problems

If you are 75 years of age or older or have moderate to severe kidney problems, your doctor should check carefully before starting treatment.

Other medicines and Revlimid

Tell your doctor or nurse if you are taking, have recently taken, or might take any other medicines. This is because Revlimid may affect the effectiveness of other medicines. In addition, some other medicines may affect the way Revlimid works.

In particular, tell your doctor or nurse if you are taking any of the following medicines:

some contraceptives such as birth control pills may stop working.
certain heart medications such as digoxin.
certain blood thinners such as warfarin.

Pregnancy, breastfeeding, and contraception – information for women and men

Pregnancy

For women taking Revlimid

You must not take Revlimid if you are pregnant as it is expected to harm the fetus.
You must not become pregnant while taking Revlimid. If you are a woman of childbearing potential, you must therefore use a safe method of contraception. (see “Contraceptives”).
If you become pregnant during treatment with Revlimid, you must stop treatment and inform your doctor immediately.

For men taking Revlimid

If your partner becomes pregnant while you are taking Revlimid, tell your doctor immediately. It is recommended that your partner consult a doctor.
You must also use effective contraceptive methods (see “Contraceptives”).

Breast-feeding

You must not breastfeed during treatment with Revlimid, as it is not known if Revlimid passes into breast milk.

Contraceptive

For women taking Revlimid

Before starting treatment, ask your doctor if you could become pregnant, even if you think it is unlikely.

If you can get pregnant

you should undergo pregnancy tests under the supervision of your doctor (before each treatment, at least every 4 weeks during treatment, and at least once 4 weeks after the end of treatment), except in cases where it has been confirmed that the fallopian tubes have been cut off and blocked so that the eggs cannot reach the uterus (tube sterilization)

AND

you must use effective contraception for at least 4 weeks before starting treatment, during treatment, and for at least 4 weeks after stopping treatment. Your doctor will advise you on appropriate contraceptive methods.

For men taking Revlimid

Revlimid passes into semen in humans. If your partner is pregnant or may become pregnant, you must use a condom during the entire treatment period and for at least 7 days after the end of the treatment, even if you have undergone sterilization (vasectomy)

Driving and using machines

Do not drive or use machines if you feel dizzy, tired, sleepy, dizzy, or have blurred vision.

Revlimid contains lactose

Revlimid contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

How to take Revlimid

Only healthcare professionals with experience in the treatment of multiple myeloma, MDS, MCL, or FL may give you Revlimid.

When Revlimid is used for the treatment of multiple myeloma in patients who are not suitable for transplantation or who have received other treatments before, it is taken with other medicines (see section 1 “What Revlimid is used for”).
When Revlimid is used for the treatment of multiple myeloma in patients who have undergone a bone marrow transplant or for the treatment of patients with MDS or MCL, it is taken alone.
When Revlimid is used to treat follicular lymphoma, it is taken together with another medicine called rituximab

Always take Revlimid exactly as your doctor has told you. Ask your doctor or pharmacist if you are unsure.

If you are taking Revlimid in combination with other medicines, read the package leaflets of these medicines for more information on their use and effects.

Treatment cycles

Revlimid is taken on certain days for 3 weeks (21 days).

Every 21 days is called a “treatment cycle”.
Depending on the day of the cycle, you should take one or more of the medicines. But some days you should not take any of the medicines.
When each 21-day cycle is over, start a new “cycle” that lasts for the next 21 days.

Revlimid is taken on certain days for 4 weeks (28 days).

Every 28 days is called a “treatment cycle”.
Depending on the day of the cycle, you should take one or more of the medicines. But some days you should not take any of the medicines.
At the end of each 28-day cycle, start a new cycle that will last for the next 28 days.

How much Revlimid should you take?

Before starting treatment, tell your doctor:

how much Revlimid to take
how much of the other medicines you should take in combination with Revlimid (if you are taking any others)
on which days of the treatment cycle you should take each medicine.

How and when to take Revlimid capsules

Swallow the capsules whole, preferably with water.
The capsules must not be crushed, opened, or chewed. If powder from an opened capsule Revlimid comes in contact with the skin, wash the skin immediately with soap and water.
Healthcare professionals, carers, and family members should use disposable gloves when handling the blister or capsule. The gloves should then be carefully removed to prevent contact with the skin, placed in a resealable plastic bag made of polyethylene, and disposed of by local regulations. Then wash your hands thoroughly with soap and water. Women who are pregnant or suspect they may be pregnant should not handle the blister or capsule.
The capsules can be taken with or without food.
You should take Revlimid at about the same time on the scheduled day.

How to take this medicine

When removing the capsule from the blister:

you should only press one end of it so that it slides out through the foil
do not press in the middle of the capsule, as this may cause it to break.

Remove the capsule from the blister by pressing on one end.

How long does the treatment with Revlimid lasts

Revlimid is taken during treatment cycles and each cycle is 21 or 28 days long (see “Treatment cycle” above). You should continue with the treatment cycles until your doctor tells you to stop the treatment.

If you take more Revlimid than you should

If you have taken more Revlimid than you were told to, tell your doctor immediately.

If you forget to take Revlimid

If you forget to take Revlimid at the usual time and:

less than 12 hours have passed – take the capsule immediately.
more than 12 hours have passed – do not take the capsule. Take the next capsule at the usual time the next day.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Stop taking Revlimid and see a doctor immediately if you get any of the following serious side effects – you may need urgent medical attention:

Hives, skin rash, swelling of the eyes, mouth, or face, difficulty breathing, or itching, can be symptoms of severe types of allergic reactions called angioedema or anaphylactic reaction.
A severe allergic reaction that can start as a rash on an area but spreads with extensive loss of skin throughout the body ( Stevens-Johnson syndrome and/or toxic epidermal necrolysis ).
Widespread rash, high body temperature, elevated liver enzyme levels, abnormal blood levels ( eosinophilia ), enlarged lymph nodes, and effects on other organs in the body (drug reaction with eosinophilia and systemic symptoms also known as DRESS or drug hypersensitivity syndrome). See also section 2.

Tell your doctor immediately if you get any of the following serious side effects:

Fever, chills, sore throat, cough, cold sores, or any other symptoms of infection including infection in the blood (blood poisoning, sepsis )
Bleeding or bruising without injury
Pain in the chest or legs
Shortness of breath
Skeletal pain, muscle weakness, confusion, or fatigue may be due to high levels of calcium in the blood.

Revlimid can reduce the number of white blood cells that fight infection and also the blood cells that help the blood to coagulate ( platelets ) which can lead to bleeding problems such as nosebleeds and bruises.

Revlimid can also cause blood clots in veins ( thrombosis ).

Other side effects ar

It is important to note that a small proportion of patients develop other cancers and that treatment with Revlimid may increase this risk. Your doctor should therefore carefully evaluate the benefits and risks when you are prescribed Revlimid.

Very common side effects (may affect more than 1 in 10 people):

A decrease in the number of red blood cells can cause anemia and lead to fatigue and weakness
Skin rash, itching
Muscle cramps, muscle weakness, muscle pain, muscle aches, skeletal pain, joint pain, back pain, pain in arms and legs
General swelling including swelling of the arms and legs
Weakness, fatigue
Fever and flu-like symptoms such as fever, muscle aches, headache, earache, cough, and chills
Numbness, tingling or burning in the skin, pain in hands or feet, dizziness, trembling
Decreased appetite, altered sense of taste
Increased pain, tumor size, or redness around tumor one
Weight loss
Constipation, diarrhea, nausea, vomiting, abdominal pain, heartburn
Low levels of potassium or calcium and/or sodium in the blood
Lower thyroid function than normal
Bone pain (which can be a symptom of a blood clot), chest pain, or shortness of breath (which can be a symptom of blood clots in the lungs, called pulmonary embolism )
Infections of all kinds, including in the sinuses around the nose, in the lungs, and in the upper respiratory tract
Shortness of breath
Dimsyn
Clouding of the eye (cataracts)
Kidney problems, include the kidneys not functioning properly or being unable to maintain normal function
Abnormal liver values
Elevated liver values
Changes in a protein in the blood that can cause swelling of the arteries ( vasculitis )
Elevated blood sugar level ( diabetes )
Lowered blood sugar level
Headache
Nasal blood
Dry skin
Depression, mood swings, difficulty sleeping
Cough
Drop-in blood pressure
A vague feeling of discomfort in the body, a feeling of illness
Sore inflamed mouth, dry mouth
Dehydration

Common side effects (may affect up to 1 in 10 people):

Degradation of red blood cells (hemolytic anemia )
Certain types of skin tumors
Bleeding from gums, stomach, or intestines
High blood pressure, slow, fast or irregular heartbeat
The increased amount of a substance that is the result of normal and abnormal degradation of red blood cells
The increased amount of a protein that indicates inflammation in the body
Darker skin, discolored skin due to bleeding under the skin, usually caused by bruising, swelling of the skin filled with blood; bruise
The increased amount of uric acid in the blood
Skin rash, reddened skin, cracked, flaky or scaly skin, hives
Increased sweating, night sweats
Difficulty swallowing, sore throat, poor voice quality, or voice changes
Suva
Production of much more or much less urine than usual or inability to control urine
Blood in the urine
Shortness of breath, especially in a supine position (which can be a symptom of heart failure )
Difficulty getting an erection
Stroke, fainting, dizziness (problems in the inner ear that lead to a feeling that everything around is spinning), temporary unconsciousness
Chest pain radiating to the arms, neck, jaws, back or stomach, sweating and shortness of breath, nausea or vomiting. All of these symptoms can be a sign of a heart attack
Muscle weakness, lack of energy
Neck pain, chest pain
Overindulge
Joint swelling
Slow or blocked bile flow from the liver
Low levels of phosphate or magnesium in the blood
Hard to talk
Liver damage
Impaired balance, difficult to move
Deafness, ringing in the ears ( tinnitus )
Nerve pain, unpleasant abnormal sensation especially when touched
Excess iron in the body
Thirst
Confusion
Toothache
Cases that can lead to injuries

Uncommon side effects (may affect up to 1 in 100 people):

Bleeding inside the skull
Circulation problem
Loss of vision
Impaired libido _
Large urine output with skeletal pain and weakness, which may be a symptom of kidney disease (Fanconi’s syndrome)
Yellowing of the skin, mucous membranes or eyes (jaundice), light stools, dark urine, itchy skin, rash, stomach pain, or bloated stomach – these may be symptoms of liver damage (liver failure)
Stomach pain, bloating or diarrhea, may be symptoms of inflammation of the colon ( colitis or appendicitis)
Damage to the kidney cells (called renal tubular necrosis )
Changes in skin color, sensitivity to sunlight
Tumor light syndrome – metabolic complications that can occur during treatment of cancer and sometimes even without treatment. These complications are caused by the breakdown products of dying cancer cells and may include the following: changes in blood chemistry; high levels of potassium, phosphorus, and uric acid as well as low levels of calcium which leads to changes in kidney function and heart rhythm, seizures and sometimes death.
Elevated blood pressure in the blood vessels that supply the lungs with blood ( pulmonary hypertension ).

No known frequency (can not be calculated from the available data):

Sudden pain or mild pain that worsens in the upper abdomen and/or back, which persists for a few days, possibly in combination with nausea, vomiting, fever, and rapid pulse. These symptoms may be due to inflammation of the pancreas.
Wheezing, shortness of breath, or dry cough, may be symptoms caused by inflammation of the lung tissue.
In rare cases, muscle breakdown (muscle pain, weakness, or swelling), which can lead to kidney problems ( rhabdomyolysis ), has been observed. Some of the cases occurred when Revlimid was administered with a statin (a type of cholesterol-lowering drug).
A condition that affects the skin and is caused by inflammation of the small blood vessels, along with joint pain and fever (leukocytoclastic vasculitis ).
Degradation of the stomach wall or intestinal wall. This can lead to a very serious infection. Tell your doctor if you experience severe abdominal pain, fever, nausea, vomiting, blood in the stool, or changed bowel habits.
Viral infections, including herpes zoster (also known as shingles, a viral disease that causes painful skin rashes with blisters) and recurrence of hepatitis B infection (which can lead to yellowing of the skin and whites of the eyes, dark brown urine, pain in the right side of the stomach, fever and nausea or vomiting).
Rejection of transplanted organs (eg kidney, heart).

How to store Revlimid

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the blister and carton after “EXP”. The expiration date is the last day of the specified month.
No special storage instructions.
Do not use this medicine if the package is damaged or appears to have been tampered with.
Medicines should not be disposed of via wastewater or household waste. Leftover medicines must be returned to the pharmacy staff. These measures will help to protect the environment.

Contents of the pack and other information

Content declaration

Revlimid 2.5 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 2.5 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin, titanium dioxide (E171), indigo carmine (E132), and yellow iron oxide (E172)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).

Revlimid 5 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 5 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin and titanium dioxide (E171)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).

Revlimid 7.5 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 7.5 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin, titanium dioxide (E171), and yellow iron oxide (E172)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).

Revlimid 10 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 10 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin, titanium dioxide (E171), indigo carmine (E132), and yellow iron oxide (E172)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).

Revlimid 15 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 15 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin, titanium dioxide (E171), and indigo carmine (E132)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).

Revlimid 20 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 20 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin and titanium dioxide (E171), indigo carmine (E132), and yellow iron oxide (E172)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).

Revlimid 25 mg hard capsules:

The active substance is lenalidomide. Each capsule contains 25 mg of lenalidomide.
Other ingredients are:
- Capsule content: anhydrous lactose (see section 2), microcrystalline cellulose, croscarmellose sodium, and magnesium stearate
- Capsule shell: gelatin and titanium dioxide (E171)
- printing ink: shellac, propylene glycol (E1520), potassium hydroxide, and black iron oxide (E172).