Imnovid 4 mg hard capsules: detailed information

Package Leaflet: Information for the User

Introduction

Package Leaflet: Information for the Patient

Imnovid 1mg Hard Capsules

Imnovid 2mg Hard Capsules

Imnovid 3mg Hard Capsules

Imnovid 4mg Hard Capsules

pomalidomide

Imnovid is expected to cause severe birth defects and may result in fetal death.

Do not take this medicine if you are pregnant or may be pregnant.
You must follow the contraceptive measures described in this leaflet.

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

Keep this leaflet, as you may need to read it again.
If you have any questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
If you experience any adverse effects, consult your doctor, pharmacist, or nurse,
even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

What Imnovid is and what it is used for
What you need to know before taking Imnovid
How to take Imnovid
Possible side effects
How to store Imnovid
Contents of the pack and other information

1. What Imnovid is and what it is used for

What Imnovid is

Imnovid contains the active substance “pomalidomide”. This medicine is related to thalidomide and belongs to a group of medicines that affect the immune system (the body's natural defenses).

What Imnovid is used for

Imnovid is used to treat adults with a type of cancer called “multiple myeloma”.

Imnovid is used with:

Two other medicines called “bortezomib” (a type of chemotherapy medicine) and “dexamethasone” (an anti-inflammatory medicine) in people who have received at least one other treatment, including lenalidomide.

Another medicine called “dexamethasone” in people whose myeloma has worsened despite having received at least two other types of treatment, including the medicines lenalidomide and bortezomib.

What is multiple myeloma

Multiple myeloma is a type of cancer that affects a specific type of white blood cells (called “plasma cells”). These cells grow uncontrollably and accumulate in the bone marrow, damaging bones and kidneys.

Multiple myeloma usually cannot be cured. However, treatment can reduce or eliminate the signs and symptoms of the disease for a period of time. When this occurs, it is called a “response”.

How Imnovid works

Imnovid works in several ways:

It stops the growth of myeloma cells;
It stimulates the immune system to attack cancer cells;
It stops the formation of blood vessels that supply nutrients to cancer cells.

Benefit of using Imnovid with bortezomib and dexamethasone

When Imnovid is used with bortezomib and dexamethasone in people who have received at least one other treatment, it can delay the progression of multiple myeloma:

Typically, the combination of Imnovid with bortezomib and dexamethasone delayed the return of multiple myeloma for up to 11 months, compared to 7 months observed in patients receiving only bortezomib and dexamethasone.

Benefit of using Imnovid with dexamethasone

When Imnovid is used with dexamethasone in people who have received at least two other treatments, it may delay the progression of multiple myeloma:

Typically, the combination of Imnovid and dexamethasone delayed the return of multiple myeloma for up to 4 months, compared to 2 months observed in patients receiving dexamethasone alone.

2. What you need to know before taking Imnovid

Do not take Imnovid:

if you are pregnant, think you may be pregnant, or intend to become pregnant, as Imnovid is expected to be harmful to the fetus. (Men and women taking this medicine should read the section “Pregnancy, contraception and breastfeeding – information for women and men” below);
if you could become pregnant, unless you are taking all necessary measures to avoid pregnancy (see “Pregnancy, contraception and breastfeeding – information for women and men”). If you could become pregnant, your doctor will document with each prescription that all necessary precautions have been taken and will provide you with this confirmation;
if you are allergic to pomalidomide or any of the other ingredients of this medicine (listed in section 6). If you think you may be allergic, consult your doctor.

If you are unsure whether any of the above situations apply to you, consult your doctor, pharmacist, or nurse before taking Imnovid.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting Imnovid if:

you have ever had blood clots in the past. During treatment with Imnovid, you have an increased risk of developing blood clots in your veins or arteries. Your doctor may recommend additional treatments (e.g., warfarin) or reducing your dose of Imnovid to lower the risk of blood clots;
you have previously experienced an allergic reaction, such as rash, itching, swelling, dizziness, or breathing problems while taking related medicines called “thalidomide” or “lenalidomide”;
you have had a heart attack, have heart failure, have difficulty breathing, or if you are a smoker, have high blood pressure or high cholesterol levels;
you have a high total tumor burden in the body, including in the bone marrow. This could lead to a condition in which tumors break down and release unusual levels of chemicals into the blood, which in turn may cause kidney failure. You may also experience irregular heartbeats. This condition is called tumor lysis syndrome;
you suffer from or have previously had neuropathy (nerve damage causing tingling or pain in your feet or hands);
you have or have had hepatitis B virus infection. Treatment with Imnovid may reactivate the hepatitis B virus in patients carrying the virus, causing the infection to reappear (recurrence). Your doctor should check whether you have ever had hepatitis B virus infection.
you are currently experiencing or have previously experienced a combination of any of the following symptoms: facial or generalized rash, skin redness, high fever, flu-like symptoms, swollen lymph nodes (symptoms of a serious skin reaction called drug reaction with eosinophilia and systemic symptoms, or DRESS syndrome, drug hypersensitivity syndrome, toxic epidermal necrolysis [TEN], or Stevens-Johnson syndrome [SJS]). See also section 4 “Possible side effects”.

It is important to note that patients with multiple myeloma treated with pomalidomide may develop other types of cancer; therefore, your doctor must carefully evaluate the benefits and risks before prescribing this medicine.

At any time during or after treatment, inform your doctor or nurse immediately if you experience: blurred vision, loss of vision or double vision, difficulty speaking, weakness in one arm or leg, change in the way you walk or problems with balance, persistent numbness, reduced sensation or loss of sensation, memory loss or confusion. All of these may be symptoms of a serious and potentially life-threatening brain disease called progressive multifocal leukoencephalopathy (PML). If you had any of these symptoms before starting treatment with Imnovid, inform your doctor if you notice any changes in these symptoms.

At the end of treatment, you must return all unused capsules to the pharmacist.

Pregnancy, contraception and breastfeeding: information for men and women

You must follow the instructions outlined in the Imnovid Pregnancy Prevention Program.

Men and women taking Imnovid must not father children or become pregnant. This is because pomalidomide is expected to be harmful to the fetus. You and your partner must use effective contraceptive methods while taking this medicine.

Women

Do not take Imnovid if you are pregnant, think you may be pregnant, or intend to become pregnant. This is because the medicine is expected to be harmful to the fetus. Before starting treatment, you must inform your doctor if there is any possibility you could become pregnant, even if you consider this unlikely.

If you could become pregnant:

you must use effective contraception starting at least 4 weeks before beginning treatment, throughout the entire treatment period, and for at least 4 weeks after stopping treatment. Your doctor will advise you on the most appropriate contraceptive methods;
each time your doctor prescribes a new prescription, they will ensure you understand the necessary measures to prevent pregnancy;
your doctor will schedule pregnancy tests before treatment, at least every 4 weeks during treatment, and at least 4 weeks after stopping treatment.

If you become pregnant despite preventive measures:

you must stop treatment immediately and inform your doctor immediately.

Breastfeeding

It is unknown whether Imnovid passes into human breast milk. Inform your doctor if you are breastfeeding or intend to breastfeed. Your doctor will advise you whether you should continue or stop breastfeeding.

Men

Imnovid passes into human semen.

If your partner is pregnant or could become pregnant, you must use condoms throughout the entire treatment period and for 7 days after stopping treatment.
If your partner becomes pregnant while you are taking Imnovid, inform your doctor immediately. Your partner must also inform her doctor immediately.

You must not donate semen or sperm during treatment and for 7 days after stopping treatment.

Blood donation and blood tests

You must not donate blood during treatment and for 7 days after stopping treatment.

Before starting treatment with Imnovid and during treatment, you will have periodic blood tests. This is because your medicine may cause a decrease in the number of blood cells that help fight infections (white blood cells) and in the number of cells that help stop bleeding (platelets).

Your doctor will ask you to have blood tests:

before starting treatment;
weekly during the first 8 weeks of treatment;
at least once a month while continuing Imnovid.

Your doctor may adjust the dose of Imnovid or interrupt your treatment, depending on the results of these tests. Your doctor may also adjust the dose or interrupt treatment due to your overall health status.

Children and adolescents

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

Other medicines and Imnovid

Inform your doctor, pharmacist, or nurse if you are taking, have recently taken, or might need to take any other medicines. This is because Imnovid may affect how other medicines work. In addition, some medicines may affect how Imnovid works.

In particular, inform your doctor, pharmacist, or nurse before taking Imnovid if you are taking any of the following medicines:

certain antifungals such as ketoconazole
certain antibiotics (e.g., ciprofloxacin, enoxacin)
certain antidepressants such as fluvoxamine.

Driving and using machines

Some people experience fatigue, fainting, confusion, or reduced level of alertness while taking Imnovid. If this happens to you, do not drive or operate tools or machinery.

Imnovid contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per capsule; i.e., essentially “sodium-free”.

3. How to take Imnovid

Imnovid must be administered by a physician experienced in the treatment of multiple myeloma.

Follow exactly the dosing instructions provided by your doctor. If in doubt, consult your doctor, pharmacist, or nurse.

When to take Imnovid with other medicines

Imnovid in combination with bortezomib and dexamethasone

Refer to the package leaflet accompanying bortezomib and dexamethasone for additional information on their use and effects.
Imnovid, bortezomib, and dexamethasone are taken in treatment cycles. Each cycle lasts 21 days (3 weeks).
Refer to the following chart to see which medicines you should take each day of the 3-week cycle:
- Each day, check the chart and identify the correct day to see which medicines you should take.
- On some days you will take all three medicines, on other days only one or two medicines, and on some days none of them.

IMN: Imnovid; BOR: bortezomib; DEX: dexamethasone

Cycles 1 to 8				Cycles 9 and beyond

	Drug Name				Drug Name
Day	IMN	BOR	DEX			Day	IMN	BOR	DEX
1	√	√	√			1	√	√	√
2	√		√			2	√		√
3	√					3	√
4	√	√	√			4	√
5	√		√			5	√
6	√					6	√
7	√					7	√
8	√	√	√			8	√	√	√
9	√		√			9	√		√
10	√					10	√
11	√	√	√			11	√
12	√		√			12	√
13	√					13	√
14	√					14	√
15						15
16						16
17						17
18						18
19						19
20						20
21						21

After completing each 3-week cycle, begin a new one.

Imnovid with dexamethasone only

Refer to the package leaflet provided with dexamethasone for additional information on its use and effects.
Imnovid and dexamethasone are taken in treatment cycles. Each cycle lasts 28 days (4 weeks).
Follow the chart below to determine which medication(s) to take each day of the 4-week cycle:
- Each day, consult the chart and identify the correct day to see which medications you should take.
- On some days, you will take both medications, on other days only one medication, and on some days neither.

IMN: Imnovid; DEX: dexamethasone

	Medication Name
Day	IMN	DEX
1	√	√
2	√
3	√
4	√
5	√
6	√
7	√
8	√	√
9	√
10	√
11	√
12	√
13	√
14	√
15	√	√
16	√
17	√
18	√
19	√
20	√
21	√
22		√
23
24
25
26
27
28

After completing each 4-week cycle, start a new one.

How much Imnovid to take with other medicines

Imnovid with bortezomib and dexamethasone

The recommended starting dose of Imnovid is 4 mg once daily.
The starting dose of bortezomib will be calculated by your doctor according to your height and weight (1.3 mg/m2 body surface area).
The recommended starting dose of dexamethasone is 20 mg per day. However, if you are over 75 years of age, the recommended starting dose is 10 mg per day.

Imnovid with dexamethasone alone

The recommended dose of Imnovid is 4 mg once daily.
The recommended starting dose of dexamethasone is 40 mg per day. However, if you are over 75 years of age, the recommended starting dose is 20 mg per day.

Your doctor may need to reduce the dose of Imnovid, bortezomib, or dexamethasone, or interrupt one or more of these medicines based on your blood test results and general condition, whether you are taking other medicines (e.g., ciprofloxacin, enoxacin, and fluvoxamine), and whether you experience adverse effects (especially rash or swelling) as a result of treatment.

If you have liver or kidney problems, your doctor will carefully monitor your condition while you are receiving this medicine.

How to take Imnovid

Do not break, open, or chew the capsules. If the powder from a broken capsule comes into contact with the skin, wash the skin immediately and thoroughly with soap and water.
Healthcare professionals, caregivers, and family members should wear disposable gloves when handling the blister pack or capsule. Afterwards, gloves should be carefully removed to avoid skin exposure, placed into a sealable polyethylene plastic bag, and disposed of according to local requirements. Hands should then be washed thoroughly with soap and water. Pregnant women or those who suspect they may be pregnant must not handle the blister pack or capsule.
Swallow the capsules whole, preferably with water.
You may take the capsules with or without food.
You should take the capsules at approximately the same time each day.

To remove the capsule from the blister pack, press only on one end of the capsule so that it comes through the foil. Do not press in the middle of the capsule as this may break it.

Black and white schematic drawing showing the steps to open a pill package by pressing with the thumb on the upper edge

Your doctor will advise you on how and when to take Imnovid if you have kidney problems and are receiving dialysis treatment.

Duration of treatment with Imnovid

You should continue the treatment cycles until your doctor tells you to stop.

If you take more Imnovid than you should

If you take more Imnovid than you should, inform your doctor or go to hospital immediately. Bring the medicine packaging with you.

If you forget to take Imnovid

If you forget to take Imnovid on the day it was due, take the next capsule the following day at your usual time. Do not take extra capsules to make up for the missed dose of Imnovid from the previous day.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone gets them.

Serious adverse effects

If you experience any of the following serious adverse effects, stop treatment with Imnovid and see a doctor immediately, as you may require urgent medical treatment:

Fever, chills, sore throat, cough, mouth ulcers, or any other sign of infection (due to a decrease in white blood cells that fight infection).
Bleeding or bruising without apparent cause, including nosebleeds and intestinal or stomach bleeding (due to effects on blood cells called "platelets").
Rapid breathing, fast pulse, fever and chills, little or no urine production, nausea and vomiting, confusion, unconsciousness (due to a blood infection called sepsis or septic shock).
Severe, persistent or bloody diarrhoea (possibly accompanied by stomach pain or fever) caused by the bacterium Clostridium difficile.
Chest or leg pain and swelling, especially in the lower leg or calves (caused by blood clots).
Difficulty breathing (due to a severe chest infection, lung inflammation, heart failure, or blood clots).
Swelling of the face, lips, tongue and throat, which may cause difficulty breathing (due to severe allergic reactions called angioedema and anaphylactic reaction).
Certain types of skin cancer (squamous cell carcinoma and basal cell carcinoma), which may cause changes in the appearance of the skin or lumps on the skin. If you notice changes in your skin while taking Imnovid, inform your doctor as soon as possible.
Reactivation of hepatitis B virus infection, which may cause yellowing of the skin and eyes, dark brown urine, abdominal pain on the right side, fever, nausea or feeling unwell. Inform your doctor immediately if you notice any of these symptoms.
Widespread rash, high body temperature, enlarged lymph nodes and effects on other organs in the body (drug reaction with eosinophilia and systemic symptoms, also known as DRESS syndrome or drug hypersensitivity syndrome, toxic epidermal necrolysis or Stevens-Johnson syndrome). Stop taking pomalidomide if you experience these symptoms and contact your doctor or go to a doctor immediately. See also section 2.

If you experience any of the following serious adverse effects, stop treatment with Imnovid and see a doctor immediately, as you may require urgent medical treatment.

Other adverse effects

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

Difficulty breathing (dyspnoea).
Lung infection (pneumonia and bronchitis).
Infections of the nose, sinuses and throat caused by bacteria or viruses.
Flu-like symptoms (flu).
Low red blood cell count, which may cause anaemia leading to tiredness and weakness.
Low levels of potassium in the blood (hypokalaemia), which may cause weakness, cramps and muscle pain, palpitations, tingling or numbness, dyspnoea and mood changes.
High blood sugar levels.
Fast and irregular heartbeat (atrial fibrillation).
Loss of appetite.
Constipation, diarrhoea or nausea.
Vomiting.
Abdominal pain.
Lack of energy.
Difficulty falling or staying asleep.
Dizziness, tremor.
Muscle spasms, muscle weakness.
Bone pain, back pain.
Numbness, tingling or burning sensation in the skin, pain in hands or feet (peripheral sensory neuropathy).
Generalised swelling including swelling of arms and legs.
Skin rashes.
Urinary tract infection, which may cause a burning sensation when urinating or the need to urinate more frequently.

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

Fall.
Bleeding inside the skull.
Reduced ability to move or feel (sensation) in the hands, feet and legs due to neurological damage (peripheral sensorimotor neuropathy).
Numbness, itching or tingling in the skin (paraesthesia).
Sensation of dizziness or spinning, making it difficult to stand and move normally.
Swelling due to fluid retention.
Hives (urticaria).
Itching of the skin.
Shingles (herpes zoster).
Heart attack (chest pain spreading to arms, neck and jaw, sweating, shortness of breath, nausea or vomiting).
Chest pain, chest infection.
Increased blood pressure.
Reduction in the number of red blood cells, white blood cells and platelets at the same time (pancytopenia), making you more prone to bleeding and bruising. You may feel tired and weak and have difficulty breathing. You will also be more susceptible to infections.
Decrease in the number of lymphocytes (a type of white blood cell), often caused by infection (lymphopenia).
Low levels of magnesium in the blood (hypomagnesaemia), which may cause tiredness, generalised weakness, muscle cramps and irritability, and may lead to low levels of calcium in the blood (hypocalcaemia), causing numbness or tingling in the hands, feet or lips, muscle cramps, muscle weakness, dizziness, confusion.
Low levels of phosphate in the blood (hypophosphataemia), which may cause muscle weakness, irritability or confusion.
High levels of calcium in the blood (hypercalcaemia), which may slow reflexes and cause weakness in skeletal muscles.
High levels of potassium in the blood, which may cause an abnormal heart rhythm.
Low levels of sodium in the blood, which may cause tiredness and confusion, muscle twitching, seizures (epileptic fits) or coma.
High levels of uric acid in the blood, which may cause a type of arthritis called gout.
Low blood pressure, which may cause dizziness or fainting.
Pain or dryness in the mouth.
Changes in taste.
Bloating.
Confusion.
Feeling low in mood (depressive mood).
Loss of consciousness, fainting.
Cloudiness in the eye (cataract).
Kidney damage.
Inability to urinate.
Abnormal results in liver function tests.
Pelvic pain.
Weight loss.

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

Stroke.
Inflammation of the liver (hepatitis), which may cause itchy skin, yellowing of the skin and whites of the eyes (jaundice), pale stools, dark urine and abdominal pain.
Breakdown of tumour cells resulting in the release of toxic substances into the bloodstream (tumour lysis syndrome). This may lead to kidney problems.
Underactive thyroid gland, which may cause symptoms such as tiredness, sluggishness, muscle weakness, slow heart rate and weight gain.

Frequency not known (cannot be estimated from available data):

Rejection of solid organ transplants (such as heart or liver).

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor, pharmacist or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Imnovid

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the blister pack and outer carton following EXP/CAD. The expiry date refers to the last day of the month indicated.

No special storage conditions are required.

Do not use Imnovid if you notice any visible signs of deterioration or evidence of improper handling of the medicine.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging when they are no longer needed. This helps protect the environment.

6. Contents of the pack and other information

Composition of Imnovid

The active substance is pomalidomide.
The other components are mannitol (E421), starch, pregelatinized, and sodium stearyl fumarate.

Imnovid 1 mg hard capsule:

Each capsule contains 1 mg of pomalidomide.
The capsule shell contains: gelatin, titanium dioxide (E171), indigo carmine (E132), yellow iron oxide (E172), and white and black ink.
The printing ink contains: shellac, titanium dioxide (E171), simethicone, propylene glycol (E1520), and ammonium hydroxide (E527) (white ink); and shellac, black iron oxide (E172), propylene glycol (E1520), and ammonium hydroxide (E527) (black ink).

Imnovid 2 mg hard capsule:

Each capsule contains 2 mg of pomalidomide.
The capsule shell contains: gelatin, titanium dioxide (E171), indigo carmine (E132), yellow iron oxide (E172), erythrosine (E127), and white ink.
The printing ink contains: white ink - shellac, titanium dioxide (E171), simethicone, propylene glycol (E1520), and ammonium hydroxide (E527).

Imnovid 3 mg hard capsule:

Each capsule contains 3 mg of pomalidomide.
The capsule shell contains: gelatin, titanium dioxide (E171), indigo carmine (E132), yellow iron oxide (E172), and white ink.
The printing ink contains: white ink - shellac, titanium dioxide (E171), simethicone, propylene glycol (E1520), and ammonium hydroxide (E527).

Imnovid 4 mg hard capsule:

Each capsule contains 4 mg of pomalidomide.
The capsule shell contains: gelatin, titanium dioxide (E171), indigo carmine (E132), brilliant blue FCF (E133), and white ink.
The printing ink contains: white ink - shellac, titanium dioxide (E171), simethicone, propylene glycol (E1520), and ammonium hydroxide (E527).

Appearance of Imnovid and contents of the pack

Imnovid 1 mg hard capsules: opaque dark blue cap and opaque yellow body with the imprint “POML 1 mg”.

Imnovid 2 mg hard capsules: opaque dark blue cap and opaque orange body with the imprint “POML 2 mg”.

Imnovid 3 mg hard capsules: opaque dark blue cap and opaque green body with the imprint “POML 3 mg”.

Imnovid 4 mg hard capsules: opaque dark blue cap and opaque blue body with the imprint “POML 4 mg”.

Each pack contains 14 or 21 capsules. Only certain pack sizes may be marketed.

Marketing Authorization Holder

Bristol-Myers Squibb Pharma EEIG
Plaza 254
Blanchardstown Corporate Park 2
Dublin 15, D15 T867
Ireland

Manufacturer

Celgene Distribution B.V.
Orteliuslaan 1000
3528 BD Utrecht
The Netherlands

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Belgium/Belgium/Belgium

N.V. Bristol-Myers Squibb Belgium S.A.

Tel/Tel: + 32 2 352 76 11