NIPENT 10 mg POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

2. What you need to know before you use Nipent

Do not use Nipent:

• If you have had an allergic reaction to Nipent (pentostatin) or mannitol
• If you have kidney problems (creatinine clearance <60 ml min)< li>
• If you have an infection (high temperature or fever, chills or feeling cold)

Tell your doctor if any of the above circumstances apply to you.

Nipent is not recommended for use in children.

Be careful with Nipent:

• If you have liver problems

Tell your doctor if any of the above circumstances apply to you.

Tests

Before you receive Nipent for the first time, your kidneys will be checked to make sure they are working normally. You will also have a blood test that will be repeated regularly throughout your treatment with Nipent.

Tell your doctor if, after receiving Nipent, you experience any of the following: confusion, dizziness, sleep disturbances, tingling and numbness, memory loss, stumbling when walking, tremors, agitation, fainting, headaches, epileptic seizures, or other central nervous system conditions.

Other medicines and Nipent

Tell your doctor or pharmacist if you are using or have recently used or may need to use other medicines, including those obtained without a prescription.

Nipent should not be used with:

• fludarabine (another cancer medicine)

Tell your doctor if you are taking any of the following medicines:

• vidarabine (antiviral medicine)
• cyclophosphamide, etoposide, carmustine (other anticancer medicines)
• allopurinol (medicine used for gout, high levels of uric acid in the body caused by certain cancer treatments, and kidney stones)

Pregnancy, breastfeeding, and fertility

Nipent is not recommended during pregnancy. Tell your doctor if you are pregnant, trying to become pregnant, or breastfeeding.

If you are of childbearing age, you should use appropriate contraceptive measures. If you become pregnant, consult your doctor.

Men should not father childrenduring treatment and for up to 6 months after treatment with Nipent.

Driving and using machines

After receiving this medicine, you may feel unwell or experience dizziness and have vision problems. Do not drive or operate machinery if you experience these side effects.

Nipent contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per vial; it is essentially "sodium-free".

3. How to use Nipent

Nipent will be administered under the supervision of a specialist doctor.

Dose

Your doctor will know exactly how much you need based on your height, weight, and health status. The usual dose for adults, including the elderly, is 4 mg/m² of body surface area, once every two weeks. This medicine will be administered as a short injection or as a long intravenous infusion (drip) into a vein over 20 to 30 minutes.

Before and after administration of Nipent, you will receive an intravenous solution (glucose or saline) to ensure that your body is full of fluid. This will help the medicine reach the place where it is needed and reduce side effects.

Duration of treatment

You will be treated with Nipent until the cancer cells are destroyed. Your doctor will review you 6-12 months after starting treatment with Nipent to see if you have responded to it.

If you use more Nipent than you should

If you receive a dose of Nipent higher than recommended, important organs (brain, liver, kidney, lung) may be affected, and a serious medical condition may occur. If you experience any of the symptoms listed below, contact your doctor immediately, as this may be a life-threatening medical emergency: confusion; drowsiness; seizures; loss of consciousness for a period; pain, burning, numbness, or tingling in the hands or feet; weakness in the arms or legs, loss of ability to move the arms or legs, or visual and auditory disturbances (difficulty concentrating and tinnitus).

You may also notice: yellowing of the skin and whites of the eyes (jaundice); itching; pain in the upper right abdomen; rash, fatigue, and weakness, or loss of appetite. Other symptoms may include: frequent urination, especially at night (nocturia); swelling of the legs and swelling around the eyes (fluid retention); difficulty breathing, dry cough, and general discomfort when breathing or worsening of symptoms when lying on your back.

4. Possible side effects

Like all medicines, Nipent can cause side effects, although not everyone gets them.

Nipent works by eliminating cancer cells, but sometimes it also eliminates normal blood cells, which can increase the risk of infection. It can also decrease the number of platelets (necessary for blood clotting). Your doctor will monitor your condition and inform you if this occurs. There are certain precautions you should take to reduce the risk of infection or bleeding. If possible, avoid contact with people who have infections.

• Tell your doctor immediatelyif you think you have an infection or if you have a fever, sweats, or chills, cough or hoarseness, difficulty breathing, mouth sores or lip sores, inflamed nose and runny nose, breast pain, lower back pain or pain on one side, inability or difficulty urinating (passing water), headache with confusion (encephalitis).
• Tell your doctor immediatelyif you experience any abnormal bleeding, nosebleeds, or bruising, black stools, blood in urine or stools, red spots on the skin, throat sores, jaundice (yellowing of the eyes and skin, pale stools, or dark urine), allergic reactions (e.g., severe rash, difficulty breathing, runny nose, facial swelling, painful sores in the mouth), tremors, spasms, severe chest pain that may also affect your arm and neck (heart attack).

Consult your doctor or nurse as soon as possible if you experience any of the following effects:

Very common (occur in more than 1 in 10 patients)

• stomach pain or feeling sick
• loss of appetite
• diarrhea or blood in the stool
• headache
• cough, runny nose, cold, hoarseness, or breathing problems
• rash, skin problems, or itching
• muscle pain, bone problems, or joint problems
• fatigue, weakness, or pain
• fever, sweating, or chills
• jaundice

Common (occur in less than 1 in 10 patients)

• abdominal pain, indigestion, bloating, gas, constipation, weight change
• gum inflammation (gingivitis), mouth or lip sores, or throat inflammation
• tooth problems, taste changes, dry mouth
• dehydration
• mood changes, aggression, anxiety, nervousness, depression, vivid dreams, unusual thoughts, hallucinations, neurosis
• confusion, memory loss
• dizziness, body tremors, tremors, seizures, fainting
• sleep problems or drowsiness
• stumbling when walking, speech problems, paralysis, inflammation of the membranes covering the brain, nerve damage
• rash, skin peeling, inflammation, redness, skin infection, or itching
• dry skin, acne, oily skin, skin discoloration, skin sensitivity to light
• hair loss
• dry eyes or altered tear production, eye pain, eye infections, light sensitivity, vision changes, and damage to the back of the eyes (retina)
• ringing in the ears, ear pain, hearing loss, balance problems, vertigo
• shortness of breath, asthma, blood clots or fluid in the lungs, nosebleeds
• irregular heartbeat, slow or fast heartbeat, changes in ECG, high or low blood pressure, shock
• chest pain, angina, fluid around the heart, heart failure, cardiac arrest
• blood clots and inflammation of the veins, bleeding
• infections such as sinusitis, pneumonia, or bronchitis, abscesses, bone, skin, kidney, or urinary tract infections, fungal infections (e.g., thrush), herpes
• skin cancer or other types of cancer, leukemia
• problems after a transplant
• spleen enlargement, bruising, lymph node enlargement
• gout, changes in blood electrolytes (e.g., sodium, potassium, and calcium)
• arthritis, joint problems
• kidney problems, difficulty or pain when passing urine, kidney failure, kidney stones, inability to empty the bladder
• loss of period, breast lumps, impotence

Uncommon (occur in less than 1 in 100 patients)

• gastroenteritis, Clostridium difficile infection of the bladder
• infections of the bladder (cystitis), CMV (cytomegalovirus), fungal lung infection
• tumor lysis syndrome (including breakdown products of dying cancer cells)
• specific problems with red blood cells (pure red cell aplasia and certain types of anemia), red or purple spots on the skin due to low platelet count
• transplant failure
• heart attack, heart muscle problems, low oxygen levels in the blood
• organ failure
• severe breathing problems

Rare (occur in less than 1 in 1,000 patients)

• Alzheimer's disease (memory loss, problems thinking and speaking)
• epileptic seizures
• migraine
• Parkinson's disease (loss of coordination, body and limb agitation)
• inflammation of the eyelids
• inflammation of the heart lining, reduced heart function
• fungal infection of the esophagus

Very rare (occur in less than 1 in 10,000 patients)

• severe eye pain with vision loss

This medicine may also cause the following side effects that your doctor should monitor:

Very common (occur in more than 1 in 10 patients)

• blood disorders that affect red blood cells, white blood cells, and platelets (clotting factors).
• changes in blood test results due to liver or kidney function

Common (occur in less than 1 in 10 patients)

• kidney stones
• gland inflammation
• heart and circulation problems
• spleen inflammation

Sometimes the effects of Nipent may not occur until months or years after using the medicine, and in rare cases, the side effects have been serious and life-threatening.

These delayed effects may include the development of certain types of cancer (e.g., skin cancer and acute leukemia). Discuss these possible effects with your doctor.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report them directly through the Spanish Medicines and Healthcare Products Agency (AEMPS) website: www.notificaRAM.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Nipent

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

Do not use this medicine after the expiry date stated on the packaging after "EXP:". The expiry date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C).

Prepared injections or infusions should be used immediately; however, if this is not possible, they can be stored for up to 8 hours at a temperature below 25°C.

Medicines should not be disposed of via wastewater or household waste. Return the packaging and any unused medicine to the pharmacy's SIGRE collection point. If you are unsure, ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Contents of the pack and other information

Composition of Nipent:

The active ingredient is pentostatin. Each glass vial contains 10 mg of the active ingredient.

The other ingredients (excipients) are: mannitol, sodium hydroxide, or hydrochloric acid.

Appearance and packaging of the product

Nipent is a white powder that is transformed into a solution by adding sterile water before administration as an injection or infusion.

Nipent is presented in single-dose vials, 10 mg vials packaged in individual cardboard boxes (packs of 1 vial).

Marketing Authorization Holder

Pfizer, S.L.

Avenida de Europa 20B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Manufacturer:

Pfizer Service Company BV,

Hoge Wei, 10,

B-1930, Zaventem,

Belgium

Date of last revision of this leaflet: 12/2020

Detailed and up-to-date information on this medicine is available on the Spanish Medicines and Healthcare Products Agency (AEMPS) website: http://www.aemps.gob.es/

NIPENT 10 mg powder for solution for injection and infusion

The following information is only for healthcare professionals:

For administration by intravenous injection or infusion. Do not administer by any other route.

Instructions for preparation and dilution

Any remaining product or waste material should be disposed of in accordance with local regulations.

Healthcare professionals should refer to national or recognized guidelines for the handling of cytotoxic agents.

Proper procedures should be followed for the handling and disposal of anticancer drugs:

1. The reconstitution of Nipent should only be performed by trained personnel in a designated area for cytotoxics.
2. Appropriate protective gloves should be used.
3. Pregnant women should not handle the preparation of the cytotoxic agent.
4. Caution should be taken and proper precautions followed for the disposal of syringes, needles, etc. used to reconstitute cytotoxic drugs.
5. Contaminated surfaces should be washed with plenty of water.
6. Any remaining solution should be discarded.

Transfer 5 ml of sterile water for injection to the vial containing Nipent and mix well until completely dissolved. The solution should be colorless or pale yellow and contain 2 mg/ml of pentostatin. Parenteral medicines should be visually inspected for particulate matter and discoloration before administration.

Nipent can be administered intravenously by injection or diluted in a larger volume (25 to 50 ml) with 5% glucose injection solution or 0.9% sodium chloride injection solution. Dilution of the entire contents of the reconstituted vial with 25 ml or 50 ml results in a pentostatin concentration of 0.33 mg/ml or 0.18 mg/ml, respectively, for the diluted solutions.

The Nipent solution, when diluted for infusion with 5% glucose injection solution or 0.9% sodium chloride injection solution, does not interact with PVC infusion bags or administration equipment at concentrations of 0.18 mg/ml to 0.33 mg/ml.

Acidic solutions should be avoided (the pH of the reconstituted powder is 7.0 to 8.2).

Storage and validity period:

The reconstituted solution for injection and subsequent dilution for infusion should be used within 8 hours and stored at temperatures below 25°C. Administration immediately after reconstitution is recommended.