Pamifos-30

Package leaflet: Information for the user

PAMIFOS-30, 30 mg, powder and solvent for solution for infusion
PAMIFOS-60, 60 mg, powder and solvent for solution for infusion
PAMIFOS-90, 90 mg, powder and solvent for solution for infusion
(Dinatrii pamidronas)
Please read carefully the entire leaflet before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any doubts, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If the patient experiences any adverse reactions, including any not listed in this leaflet, inform the doctor, pharmacist, or nurse. See section 4.

Table of contents

1. What Pamifos is and what it is used for
2. Important information before using Pamifos
3. How to use Pamifos
4. Possible side effects
5. How to store Pamifos
6. Contents of the pack and other information

1. What Pamifos is and what it is used for

The active substance in Pamifos is disodium pamidronate.
Pamifos belongs to a group of medicines called bisphosphonates. Bisphosphonates are used to reduce calcium levels in the blood.
High calcium levels in the blood (hypercalcaemia) may occur in various diseases, including certain types of cancer. Hypercalcaemia is often caused by excessive release of calcium from the bones. Pamifos strengthens bones and reduces the release of calcium into the blood. If high calcium levels in the blood are not treated, they may cause symptoms such as nausea, fatigue, and confusion.
Pamifos is used in the treatment of conditions associated with increased osteoclast activity (cells that break down bone tissue), such as:

• bone metastases and multiple myeloma;
• elevated calcium levels in the blood (hypercalcaemia) associated with cancerous diseases. In some patients with cancer, it is also used to treat bone disease and relieve bone pain;
• Paget's disease of the bone (a chronic disorder of the skeletal system characterized by the presence of at least one focus of abnormal bone formation).

2. Important information before using Pamifos

When not to use Pamifos
You should inform your doctor:

• if the patient has a known allergy (hypersensitivity) to pamidronate or other bisphosphonates, or to any of the other ingredients of this medicine (listed in section 6);

Children
Pamifos is not suitable for use in children.
When to exercise special caution with Pamifos

• if the patient has impaired kidney function;
• if the patient has impaired heart function;
• if the patient has impaired liver function;
• if the patient has had or currently has thyroid dysfunction;
• if the patient has symptoms of calcium or vitamin D deficiency (caused by diet or malabsorption);
• if the patient has experienced or is experiencing jaw pain, swelling or numbness, a feeling of heaviness in the jaw, or loose teeth;
• if the patient has an illness accompanied by flu-like symptoms or fever;
• if during treatment the patient experiences any pain or discomfort in the thigh, hip, or groin. In such a case, the patient should immediately consult their doctor.

Pamifos and other medicines
Some medicines may interfere with the proper action of Pamifos.
You must inform your doctor about all medicines the patient is currently taking or intends to take, including those available without a prescription. This particularly includes:

• calcitonin or other drugs that lower high blood calcium levels;
• other bisphosphonates;
• drugs that place excessive strain on the kidneys (your doctor and nurse know which these are);
• thalidomide (used in the treatment of certain cancers).

Warnings and precautions
Before starting treatment with Pamifos, discuss the following with your doctor:

• if the patient has or has had jaw pain, swelling, or numbness, a feeling of jaw heaviness, or loose teeth, the doctor may recommend undergoing a dental examination before starting Pamifos;
• if the patient is undergoing dental treatment or is scheduled for a dental surgical procedure, the dentist should be informed about the use of Pamifos, and the doctor should be informed about the dental treatment.

While receiving Pamifos, the patient should maintain good oral hygiene (including regular tooth brushing) and undergo regular dental check-ups.
If the patient develops any problems related to the mouth or teeth, such as loose teeth, pain, swelling, non-healing wounds, or discharge, they should immediately contact their doctor and dentist, as these may be symptoms of osteonecrosis of the jaw.
The risk of osteonecrosis of the jaw may be higher in patients undergoing chemotherapy and/or radiotherapy, taking corticosteroids, undergoing dental procedures, not receiving regular dental care, suffering from gum disease, smokers, or patients previously treated with bisphosphonates (for the treatment or prevention of bone diseases).

Other special warnings

• Dental visits:
• Since Pamifos may affect the jawbone, the patient must ensure that their dentist is aware that they are receiving Pamifos before undergoing any dental treatment or oral surgery.
• A dental visit should be scheduled before starting treatment.
• The dentist should avoid performing invasive procedures during treatment with Pamifos.
• Careful oral hygiene and regular dental visits should be maintained during treatment with Pamifos.
• The patient should remember to avoid dehydration while receiving Pamifos. If the patient is unsure how much fluid to drink, they should consult their doctor.
• During treatment with Pamifos, the doctor will monitor progress by performing various tests, such as blood tests and kidney function tests. Pamifos may affect the results of certain medical tests. Before undergoing any tests, the patient should remind the doctor or nurse that they are receiving Pamifos.
• Pregnancy and breastfeeding:
• If the patient is pregnant, the doctor should not prescribe Pamifos except in cases of life-threatening hypercalcemia.
• Breastfeeding is not recommended during treatment with Pamifos.

Driving and operating machinery
Pamifos may cause drowsiness or dizziness in some patients, especially shortly after administration. In such cases, the patient should not drive, operate machinery, or perform any other activities requiring full mental and physical alertness until these symptoms have resolved.

3. How to use Pamifos

The dose size is determined by the physician according to the patient's general condition. Medical personnel prepare Pamifos by dissolving the powder in water for injections, then diluting it with an infusion fluid. The solution prepared in this way should be stored in a refrigerator and used within 24 hours.
Pamifos must be administered intravenously only, by very slow infusion (intravenous drip). The infusion may last from one to several hours, depending on the dose administered. The number of infusions and frequency of administration are determined by the physician.
Dosing guidelines
Hypercalcemia
15 to 90 mg given in one or several infusions
Bone metastases and multiple myeloma
The recommended dose of pamidronate in the treatment of malignant bone metastases is 90 mg administered as a single infusion every 4 weeks.
In patients with bone metastases undergoing chemotherapy every 3 weeks, Pamifos may also be administered every 3 weeks.
Paget's disease of bone
180 mg as 6 single doses of 30 mg once weekly, or 180 mg as 3 single doses of 60 mg every other week.
The treating physician may recommend initiating treatment with an initial dose of 30 mg to assess the clinical response to treatment.
During treatment, patients may require additional supplementation with calcium and vitamin D.
Administration of a higher than recommended dose of Pamifos
If a higher than recommended dose of Pamifos is administered, or if the drug is taken more frequently than recommended, inform the physician or medical personnel immediately.
Missed dose of Pamifos
If a dose of Pamifos is missed, inform the physician or medical personnel.

4. Possible adverse effects

Like all medicines, Pamifos may cause adverse effects, although not everyone experiences them.
These effects are usually mild and resolve during treatment. Not all mechanisms of adverse effects and their relationship to the disease or treatment are fully understood.

Very common adverse effects include fever and flu-like symptoms, sometimes with sore throat, chills, high temperature, and sudden flushing of the face. These symptoms occur at the beginning of treatment and usually resolve within 24–48 hours.

Some patients report increasing bone pain after starting treatment, which usually subsides after a few days. If the pain persists, the patient should inform their doctor.

In patients with long-term treated osteoporosis, atypical fractures of the femoral shaft may occur. Patients should inform their doctor if they experience pain, weakness, or discomfort in the thigh, hip, or groin area, as this may allow early detection of femoral shaft fracture.

Some adverse effects may be serious
Inform your doctor immediately if you notice:

• difficulty breathing, accompanied by wheezing, cough, swelling of the face, lips, or hands;
• weakness (possibly due to low blood pressure), rash, or occasional swelling of the face and itching.

These symptoms may be due to an allergic reaction, which is very rare (occurring in less than 1 in 10,000 people).

The following adverse effects have also been reported

Very common adverse effects (occurring in more than 1 in 10 people):

• low blood phosphate and calcium levels;

Common adverse effects (occurring in less than 1 in 10 people):

• pain, redness, or swelling at the injection site;
• skin rash or unexplained bruising/excessive bleeding;
• joint and muscle pain;
• nausea, vomiting, loss of appetite, stomach pain, gastric mucosal inflammation, constipation, or diarrhoea;
• headache, insomnia, fatigue;
• conjunctivitis;
• tingling in hands and feet and muscle cramps (symptoms of low calcium levels);
• high blood pressure;
• low white blood cell count (leukopenia) or red blood cell count (anaemia);
• changes in blood test results (including low potassium, phosphate, magnesium levels, increased serum creatinine, or, very rarely, increased potassium or sodium levels);
• irregular heart rhythm (atrial fibrillation).

Uncommon adverse effects (occurring in less than 1 in 100 people):

• generalized pain;
• muscle cramps;
• drowsiness, somnolence, restlessness, seizures;
• vision problems, red, painful eyes;
• low blood pressure;
• itching, indigestion;
• impaired kidney function (e.g. unexpected changes in urine volume and/or appearance), abnormal liver function tests, or increased serum urea levels;
• dental or jaw problems.

Rare adverse effects (occurring in less than 1 in 1,000 people):

• a kidney disorder called glomerulosclerosis. Symptoms of this disease may include fluid retention, nausea, and fatigue. If a patient suspects these symptoms, they should inform their doctor.

Very rare adverse effects (occurring in less than 1 in 10,000 people):

• effects on the heart or respiratory system, which may include breathing difficulties and fluid retention;
• changes in kidney function, including worsening of existing kidney disease, e.g. haematuria;
• occurrence of herpes simplex or shingles;
• confusion or visual hallucinations (seeing things that are not there);
• yellow vision;
• if a patient experiences ear pain, ear discharge, and/or ear infection, they should inform their doctor. These may be symptoms of bone tissue damage in the ear.

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

• oral cavity pain, tooth and/or jaw pain, non-healing wounds inside the mouth or jaw, discharge, numbness, heavy feeling in the jaw, or loose teeth. These may be symptoms of jaw bone damage (osteonecrosis). If such symptoms occur during or after treatment with Pamifos, the patient should inform their doctor and dentist immediately.
• atypical femoral fracture, particularly in patients treated long-term for osteoporosis – may occur rarely. If pain, weakness, or discomfort occurs in the thigh, hip, or groin, contact a doctor, as this may be an early sign of femoral fracture;
• eye pain and/or swollen eye;
• kidney disorders.

If any of the adverse effects worsen or if any adverse effects not listed in this leaflet occur, inform your doctor or pharmacist.

In patients receiving pamidronate, irregular heart rhythm (atrial fibrillation) has been observed. It has not yet been established whether this was caused by pamidronate treatment. If irregular heartbeat occurs during treatment with Pamifos, inform your doctor.

In rare cases, atypical femoral fractures may occur, particularly in patients treated long-term for osteoporosis. Patients should consult their doctor if they experience pain, weakness, or discomfort in the thigh, hip, or groin area, as this may indicate an early sign of femoral fracture.

Reporting of adverse effects
If any adverse effects occur, including those not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: [email protected]
Adverse effects can also be reported to the marketing authorization holder.
Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Pamifos

• Keep the medicine out of the sight and reach of children.
• Do not store above 25°C. The reconstituted solution should be stored at a temperature of 2°C to 8°C for up to 24 hours, including the time for dissolving, diluting, and administration.
• Do not use this medicine if you notice that the packaging is damaged or shows signs of tampering.
• Do not use Pamifos after the expiry date stated on the container. The expiry date refers to the last day of the specified month.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Pamifos contains
The active substance is pamidronic acid disodium salt.
One vial of Pamifos-30 contains 30 mg of disodium pamidronate.
One vial of Pamifos-60 contains 60 mg of disodium pamidronate.
One vial of Pamifos-90 contains 90 mg of disodium pamidronate.
Other components of the medicinal product are: povidone 17 and diluted phosphoric acid (10%) in the amount required to adjust the appropriate pH.
The solvent ampoule contains water for injections.

What Pamifos looks like and contents of the pack
Pamifos packaging contains vials with powder and ampoules with solvent.
The medicinal product is available in the following pack sizes:

• Pamifos-30: 2 vials with powder and 2 glass ampoules each containing 10 ml of water for injections, in a cardboard box
• Pamifos-60: 1 vial with powder and 1 glass ampoule containing 10 ml of water for injections, in a cardboard box
• Pamifos-90: 1 vial with powder and 1 glass ampoule containing 10 ml of water for injections, in a cardboard box

Marketing Authorisation Holder and Manufacturer
Vipharm S.A.
ul. A. i F. Radziwiłłów 9
05-850 Ożarów Mazowiecki
tel.: (+4822) 679 51 35
fax: (+4822) 678 92 87
e-mail: [email protected]

INFORMATION FOR MEDICAL PERSONNEL
The powder in the vials must first be dissolved in sterile water for injections, i.e.:
30 mg in 10 ml,
60 mg in 10 ml,
or 90 mg in 10 ml.
Sterile water for injections is provided in ampoules included in the medicinal product pack. Care must be taken to ensure that the powder is completely dissolved before further dilution of the solution. The pH of the prepared solution ranges from 6.0 to 7.4. Prior to intravenous infusion, the prepared solution must be further diluted with an infusion fluid that does not contain calcium ions, such as 0.9% sodium chloride solution or 5% glucose solution.
The prepared solution of Pamifos must not be mixed with solutions containing calcium ions, such as Ringer's solution.
Pamifos must not be administered as a single, rapid intravenous injection.
The infusion must not be administered faster than 60 mg/h (1 mg/min), and the concentration of pamidronate in the infusion fluid must not exceed 90 mg/250 ml.
A 90 mg dose should be administered in 250 ml of infusion fluid over a 2-hour infusion period.
However, in patients with multiple myeloma and in patients with tumour-induced hypercalcaemia, administration of doses exceeding 90 mg in 500 ml of infusion fluid over a 4-hour infusion period is not recommended.
To minimize infusion site reactions, the cannula should be carefully inserted into a vein of adequate diameter.
The total time from preparation of the solution, through dilution, refrigerated storage at 2°C to 8°C, to administration must not exceed 24 hours.