Pamifos-30

Leaflet attached to the packaging: 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
(Sodium pamidronate)

You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• This medicine has been prescribed specifically for you. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should inform their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

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

1. What is Pamifos and what is it used for

The active substance of the medicine is disodium pamidronate.
Pamifos belongs to a group of medicines called bisphosphonates. Bisphosphonates are used to reduce the level of calcium in the blood.
A high level of calcium in the blood (hypercalcemia) can occur in various diseases, including some types of cancer. Hypercalcemia is often caused by excessive release of calcium from bones. Pamifos strengthens bones and reduces the release of calcium into the blood. If high calcium levels in the blood are not treated, they can cause symptoms such as nausea, fatigue, and disorientation.
Pamifos is used to treat conditions associated with increased osteoclast activity (bone tissue-destroying cells), such as:

• bone metastases and multiple myeloma;
• high calcium levels in the blood (hypercalcemia) in cancer patients. In some cancer patients, it is also used to treat bone disease and alleviate bone pain;
• Paget's disease of the bone (a chronic bone disease characterized by the presence of at least one site of abnormal bone formation).

2. Important information before taking Pamifos

When not to take Pamifos

You should inform your doctor:

• if you have been diagnosed with an allergy (hypersensitivity) to pamidronate or other bisphosphonates, or any of the other ingredients of the medicine (listed in section 6);

Children

Pamifos is not suitable for use in children.

When to exercise special caution when taking Pamifos

• if you have kidney function disorders;
• if you have heart function disorders;
• if you have liver function disorders;
• if you have had or have thyroid function disorders;
• if you have symptoms of calcium or vitamin D deficiency (caused by diet or absorption disorders);
• if you have had or have jaw pain, swelling, or numbness, a feeling of heaviness in the jaw, or loose teeth;
• if you have a disease that is accompanied by flu-like symptoms or fever;
• if during treatment, you experience any pain or discomfort in the thigh, hip, or groin area. In such a case, you should immediately consult your doctor.

Pamifos and other medicines

Some medicines may interfere with the proper functioning of Pamifos.
You should tell your doctor about all the medicines you have taken recently or plan to take, including those that are available without a prescription. This is especially true for:

• calcitonin or other medicines that lower high calcium levels in the blood;
• other bisphosphonates;
• medicines that excessively burden the kidneys (the doctor and nurse know which ones);
• thalidomide (used to treat certain cancers).

Warnings and precautions

Before starting to take Pamifos, you should discuss it with your doctor:

• if you have had or have jaw pain, swelling, or numbness, a feeling of heaviness in the jaw, or loose teeth, your doctor may recommend a dental examination before starting Pamifos;
• if you are undergoing dental treatment or are to undergo dental surgery, you should inform your dentist that you are taking Pamifos, and your doctor that you are undergoing dental treatment.

While taking Pamifos, you should maintain oral hygiene (including regular brushing of teeth) and undergo regular dental check-ups.
If you experience any problems with your mouth or teeth, such as loose teeth, pain, swelling, non-healing sores, or discharge, you should immediately contact your doctor and dentist, as these may be symptoms of jaw bone necrosis.
In patients undergoing chemotherapy and/or radiotherapy, taking corticosteroids, undergoing dental procedures, not regularly using dental care, with gum disease, smokers, or those previously treated with bisphosphonates (for the treatment or prevention of bone diseases), the risk of jaw bone necrosis may be higher.

Other special warnings

• Dental visits:
• Since Pamifos can affect the jawbone, the patient must ensure that the dentist knows that they are taking Pamifos before undergoing any dental treatment or dental surgery.
• Before starting treatment, you should visit a dentist.
• The dentist should avoid performing invasive procedures while the patient is taking Pamifos.
• You should remember to maintain good oral hygiene and regular dental visits while taking Pamifos.
• The patient should avoid dehydration while taking Pamifos. If the patient is unsure how much to drink, they should consult their doctor.
• While taking Pamifos, the doctor will monitor the progress of the treatment by performing a series of tests, such as blood tests and kidney function tests. Pamifos may affect the results of some medical tests. Before undergoing any tests, the patient should remind their doctor or nurse that they are taking Pamifos.
• Pregnancy and breastfeeding:
• If the patient is pregnant, the doctor should not prescribe Pamifos, except in the case of life-threatening hypercalcemia.
• The patient should not breastfeed while taking Pamifos.

Driving and operating machinery

Pamifos may cause drowsiness or dizziness in some patients, especially immediately after administration. In such a case, the patient should not drive vehicles or operate machinery, or perform other activities that require full physical and mental fitness until the symptoms have subsided.

3. How to take Pamifos

The dose is determined by the doctor based on the patient's overall condition. Medical personnel prepare Pamifos by dissolving the powder in water for injections, and then diluting it with infusion fluid. The prepared solution should be stored in the refrigerator and used within 24 hours.
Pamifos should be administered intravenously, in a very slow infusion (intravenous infusion). The infusion can last from one to several hours, depending on the dose used. The number of infusions and their frequency are determined by the doctor.

Dosing instructions

Hypercalcemia
15 to 90 mg administered in one or several infusions
Bone metastases and multiple myeloma
The recommended dose of pamidronate for the treatment of bone metastases is 90 mg in a single infusion administered every 4 weeks.
In patients with bone metastases undergoing chemotherapy at 3-week intervals, Pamifos can also be administered every 3 weeks.
Paget's disease of the bone
180 mg in the form of 6 single doses of 30 mg once a week or 180 mg in 3 single doses of 60 mg every other week.
The attending doctor may recommend starting treatment with an initial dose of 30 mg to check the clinical response to the treatment.
During treatment, patients may need to receive additional calcium and vitamin D.

Using a higher dose of Pamifos than recommended

In the event of administration of a higher dose of Pamifos than recommended or taking the medicine more frequently than recommended, the patient should immediately inform their doctor or medical personnel.

Missing a dose of Pamifos

In the event of missing a dose of Pamifos, the patient should inform their doctor or medical personnel.

4. Possible side effects

Like all medicines, Pamifos can cause side effects, although not everybody gets them.
These effects are usually mild and subside as the treatment progresses. Not all the mechanisms of the occurrence of side effects and their relationship to the disease or treatment are fully understood.
Very common side effects include fever and flu-like symptoms, sometimes with sore throat, chills, high temperature, and sudden flushing of the face. These symptoms accompany the beginning of treatment and subside within 24-48 hours.
Some patients report increasing bone pain noticed after starting treatment and usually subsiding 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. The patient should inform their doctor if they experience pain, weakness, or discomfort in the thigh, hip, or groin area, as this may allow for early detection of a femoral shaft fracture.

Some side effects can be serious

The patient should immediately inform their doctor if they notice:

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

These symptoms may be the result of an allergic reaction, which occurs very rarely (less than 1 in 10,000 people).

Other reported side effects

Side effects that occur very frequently (more than 1 in 10 people):

• low levels of phosphates and calcium in the blood;

Side effects that occur frequently (less than 1 in 10 people):

• pain, redness, or swelling at the injection site;
• rash on the skin or unexplained bruising/excessive bleeding;
• joint and muscle pain;
• nausea, vomiting, loss of appetite, stomach pain, gastritis, constipation, or diarrhea;
• headache, insomnia, fatigue;
• conjunctivitis;
• tingling of 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 (anemia);
• changes in blood test results (including low potassium, phosphate, magnesium, and elevated creatinine levels in the blood serum, or very rarely, elevated potassium or sodium levels);
• abnormal heart rhythm (atrial fibrillation).

Side effects that occur infrequently (less than 1 in 100 people):

• generalized pain;
• muscle cramps;
• drowsiness, lethargy, agitation, seizures;
• vision problems, red, painful eyes;
• low blood pressure,
• itching, indigestion;
• kidney function impairment (e.g., unexpected change in the amount of urine excreted and/or its appearance), abnormal liver function test results, or increased urea levels in the blood serum;
• problems with teeth or jaw.

Side effects that occur rarely (less than 1 in 1,000 people):

• kidney function change called sclerosing nephritis. Symptoms of this disease may include: fluid retention, nausea, and fatigue. If the patient suspects that they have these symptoms, they should inform their doctor.

Side effects that occur very rarely (less than 1 in 10,000 people):

• effect on the heart or respiratory system, which may include difficulty breathing and fluid retention;
• kidney function changes, including worsening of existing kidney disease, e.g., hematuria;
• herpes or shingles;
• confusion or visual hallucinations (seeing things that do not exist);
• seeing in yellow;
• if the 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 the available data):

• mouth pain, tooth pain, and/or jaw pain, non-healing sores in the mouth or jaw, discharge, numbness, feeling of heaviness in the jaw, or loose teeth. These may be symptoms of jaw bone necrosis. If such symptoms occur in the patient during or after the end of Pamifos treatment, they should immediately inform their doctor and dentist.
• atypical femoral shaft fracture, especially in patients treated long-term for osteoporosis - may occur rarely. If the patient experiences pain, weakness, or discomfort in the thigh, hip, or groin area, they should contact their doctor, as this may be an early sign of a femoral shaft fracture;
• eye pain and/or swollen eye;
• kidney disease.

If any side effect worsens or if side effects not listed in this leaflet occur, the patient should inform their doctor or pharmacist.

In patients taking pamidronate, irregular heart rhythm (atrial fibrillation) has been observed. It has not been determined whether this was caused by pamidronate. If the patient experiences irregular heart rhythm while taking Pamifos, they should inform their doctor.
In rare cases, atypical femoral shaft fractures may occur, especially in patients treated long-term for osteoporosis. The patient should consult their doctor if they experience pain, weakness, or discomfort in the thigh, hip, or groin area, as this may indicate a femoral shaft fracture.

Reporting side effects

If side effects occur, including any side effects not listed in the leaflet, the patient should inform their doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Monitoring of Adverse Reactions to Medicinal Products, Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
PL-02 222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
e-mail: ndl@urpl.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Pamifos

• The medicine should be stored in a place that is out of sight and reach of children.
• Do not store above 25°C. The reconstituted solution should be stored in a refrigerator at a temperature between 2°C and 8°C for 24 hours, including the time of reconstitution, dilution, and administration).
• Do not use this medicine if you notice that the packaging is damaged or has signs of opening.
• Do not use Pamifos after the expiry date stated on the packaging. The expiry date refers to the last day of the given month.

Medicines should not be disposed of via wastewater or household waste. The patient should ask their pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging and other information

What Pamifos contains

The active substance of the medicine is disodium pamidronate.
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 ingredients of the medicine are: povidone 17 and diluted phosphoric acid (10%) in the amount necessary to establish the appropriate pH.
The solvent ampoule contains water for injections.

What Pamifos looks like and what the packaging contains

Pamifos packaging contains vials of powder and ampoules of solvent.
The medicine is available in the following packaging:

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

Marketing authorization holder and manufacturer

Vipharm S.A.
ul. A. i F. Radziwiłłów 9
05-850 Ożarów Mazowiecki
phone: (+48 22) 679 51 35
fax: (+48 22) 678 92 87
e-mail: vipharm@vipharm.com.pl

Date of last revision of the leaflet:

INFORMATION FOR MEDICAL PERSONNEL

The powder in the vials should first be dissolved in sterile water for injections, i.e.:
30 mg dissolved in 10 ml,
60 mg dissolved in 10 ml
or 90 mg dissolved in 10 ml.
Sterile water for injections is in the ampoules attached to the medicine packaging. Note that the powder should be completely dissolved before the solution is further diluted. The pH value of the prepared solution is 6.0 to 7.4. Before administering the medicine in an intravenous infusion, the prepared solution should be further diluted with a calcium-free infusion fluid, i.e., 0.9% sodium chloride solution or 5% glucose solution.
The prepared Pamifos solution must not be mixed with solutions containing calcium ions, such as Ringer's solution.
Pamifos should not be administered as a single rapid injection.
The infusion should not be administered faster than 60 mg/h (1 mg/min), and the concentration of pamidronate in the fluid should not be higher than 90 mg/250 ml.
A dose of 90 mg should be administered in 250 ml of infusion fluid over a period of 2 hours.
However, in patients with multiple myeloma and in patients with hypercalcemia in cancer patients, it is not recommended to use a dose higher than 90 mg in 500 ml of infusion fluid, in an infusion lasting 4 hours.
In order to minimize reactions at the injection site, the cannula should be carefully inserted into a vein of suitable diameter.
The total period between preparation of the solution, its dilution, storage in the refrigerator at a temperature between 2°C and 8°C, and administration, should not exceed 24 hours.