Label: Information for the User

NIPENT® 10 mg

Powder for injectable solution and for infusion

Pentostatin

Read this label carefully before starting to use this medication, because it contains important information for you.

• Keep this label. You may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this label. See section 4.

Nipent is a cancer medication used to treat adults with hairy cell leukemia, a type of cancer that affects lymphocytes (white blood cells to fight viruses and bacteria).

No use Nipent:

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

Inform your doctor if any of the above circumstances affect you.

Nipent is not recommended for use in children.

Be especially careful with Nipent:

• If you have liver problems

Inform your doctor if any of the above circumstances affect you.

Tests

Before receiving Nipent for the first time, your kidneys must be examined to ensure they are functioning normally. You will also have a blood test that will be repeated regularly throughout your treatment with Nipent.

Discuss with your doctor if after receiving Nipent you experience: confusion, dizziness, sleep disturbances, tingling and pins, memory loss, stumbling, tremors, agitation, fainting, headaches, seizures, or other central nervous system conditions.

Other medications and Nipent

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

Nipent should not be used with:

• fludarabine (another cancer medication)

Inform your doctor if you are taking the following medications:

• vidarabine (antiviral medication)
• cyclophosphamide, etoposide, carmustine (other anticancer medications)
• allopurinol (medication 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. Inform your doctor if you are pregnant, trying to become pregnant, or breastfeeding.

If you areof childbearing ageyou should take appropriate contraceptive measures. If you become pregnant, consult your doctor.

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

Driving and operating machines

After administration of this medication, you may feel unwell or experience dizziness and vision problems. Do not drive or operate machines if you experience these adverse effects.

Nipent contains sodium

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

Nipent will be administered under the supervision of a specialist doctor in this type of treatments.

This treatment.

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 medication will be administered in a short injection or in a long intravenous infusion through a vein (drip) for 20 to 30 minutes.

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

Treatment duration

You will be treated with Nipent until the cancer cells have been destroyed. Your doctor will perform a review 6-12 months after the start of 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 the recommended dose, important organs (brain, liver, kidney, lung) may be affected, potentially triggering a serious medical condition. If you experience any of the following symptoms, contact your doctor immediately, as this may be an acute and potentially life-threatening medical emergency: confusion; drowsiness; seizures; loss of consciousness for a period of time; 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: yellow discoloration of the skin and white of the eyes (jaundice); itching; pain in the upper right abdomen; rash, inexplicable 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 down.

Like all medications, Nipent can cause side effects, although not everyone will experience them.

Nipent works by eliminating cancer cells, but sometimes it also eliminates normal blood cells, which can increase the risk of infection. It may 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 must take to reduce the risk of infection or bleeding. If possible, avoid contact with people who have infections.

• Inform your doctor immediatelyif you think you have an infection or if you have fever, chills, or sweating, cough or sore throat, difficulty breathing, mouth or lip sores, inflamed nose and runny nose, breast pain, lower back or side pain, urinary difficulties (urination), headache with confusion (encephalitis).
• Inform your doctor immediatelyif you experience any abnormal bleeding, nasal or gum bleeding, black stools, blood in urine or stool, 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 inflammation, painful mouth sores), 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 (occurs in more than 1 in 10 patients)

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

Common (occurs in less than 1 in 10 patients)

• abdominal pain, indigestion, bloating, gas, constipation, weight change
• gum inflammation (gingivitis), mouth or lip inflammation, or throat inflammation
• tooth problems, changes in taste, dry mouth
• dehydration
• mood changes, aggression, anxiety, nervousness, depression, strange dreams, strange thoughts, hallucinations, neurosis
• confusion, memory loss
• dizziness, body or limb tremors, seizures, fainting
• sleep problems or somnolence
• stumbling, speech problems, paralysis, inflammation of the membranes covering the brain, nerve damage
• rash, peeling, inflammation, redness, infection, or itching of the skin
• 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, nasal bleeding
• irregular, slow, or rapid heartbeats, changes in ECG, high or low blood pressure, shock
• chest pain, angina, fluid around the heart, heart failure, cardiac arrest
• blood clots and vein inflammation, bleeding
• infections such as sinusitis, pneumonia, or bronchitis, abscesses, bones, skin, kidney or urinary tract infections, fungal infections (e.g., through the mouth), herpes
• skin cancer or other types of cancer, leukemia
• problems after a transplant
• enlarged spleen, bruises, lymph node enlargement
• gout, changes in blood electrolytes (e.g., sodium, potassium, and calcium)
• arthritis, joint problems
• kidney problems, urinary difficulties or pain, kidney failure, kidney stones, inability to empty the bladder
• menstrual irregularities, breast lumps, impotence

Rare (occurs in less than 1 in 100 patients)

• gastroenteritis, Clostridium difficile infection of the gallbladder
• urinary tract infections (cystitis), CMV (Citomegalovirus), pulmonary fungal infection
• tumor lysis syndrome (includes products of cell death)
• 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 respiratory problems

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

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

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

• severe eye pain with vision loss

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

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

• blood disorders affecting red blood cells, white blood cells, and platelets (coagulation factors)
• changes in blood test results due to liver or kidney function

Common (occurs in less than 1 in 10 patients)

• kidney stones
• inflammation of the glands
• heart and circulation problems
• inflamed spleen

Sometimes the effects of Nipent may not occur until months or years after the use of the medication, and in rare cases, the side effects have been severe with a risk of mortality.

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

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect not listed in this prospectus. You can also report them directly through the Spanish System for Pharmacovigilance of Medicinal Products for Human Use: www.notificaRAM.es. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the packaging after “CAD:”. The expiration date is the last day of the month indicated.

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

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

Medications should not be disposed of through drains or trash. Dispose of packaging and unused medications at the SIGRE drop-off point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medications. By doing so, you will help protect the environment.

Composition of Nipent:

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

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

Appearance of the product and contents of the package

Nipent is a white powder that transforms into a solution by adding sterile water before it is administered as an injection or infusion.

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

The Marketing Authorization Holder:

Pfizer, S.L.

Avenida de Europa 20B

Parque Empresarial La Moraleja

28108 Alcobendas (Madrid)

Spain

Responsible for manufacturing is:

Pfizer Service Company BV,

Hoge Wei, 10,

B-1930, Zaventem,

Belgium

Date of the last review of this leaflet: 12/2020

The detailed and updated information of this medicine is available on the website of the Spanish Agency of Medicines and Medical Devices (AEMPS)http://www.aemps.gob.es/

NIPENT 10 mg powder for solution for injection and for infusion

The following information is only for doctors or healthcare professionals:

To be administered by intravenous injection in bolus or by intravenous infusion. Do not administer by any other route.

Instructions for preparation and dilution

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

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

They must follow the appropriate procedures for the handling and disposal of anticancer drugs:

1. The reconstitution of Nipent should only be performed by a trained person in a specific area for cytotoxics.
2. Appropriate protective gloves should be used.
3. Pregnant women of the staff should not handle the cytotoxic preparation.
4. Care should be taken and the necessary precautions should be followed for the disposal of syringes, needles, etc. used to reconstitute cytotoxic drugs.
5. Contaminated surfaces should be washed with abundant 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 complete dissolution. The solution should be colorless or pale yellow and contain 2 mg/ml of pentostatin. Parenteral medications should be visually inspected for particles and discoloration before administration.

Nipent may be administered intravenously by injection in bolus or diluted in a larger volume (25 to 50 ml) with 5% glucose for injection (5% glucose solution) or 0.9% sodium chloride for injection (0.9% saline solution). The dilution of the entire contents of the reconstituted vial with 25 ml or 50 ml results in a concentration of pentostatin 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 for injection (5% glucose solution) or with 0.9% sodium chloride for injection (0.9% saline solution) does not interact with PVC infusion bags or administration equipment at concentrations of 0.18 mg/ml to 0.33 mg/ml.

Solutions that are acidic (the pH of the reconstituted powder is 7.0 to 8.2) should be avoided.

Storage and shelf life:

The reconstituted solution for injection reconstituted and subsequently diluted for infusion should be used within an interval not exceeding 8 hours and should be stored at temperatures below 25°C. It is recommended to administer immediately after reconstitution.