Paricalcitol fresenius

Package leaflet: Information for the user

Paricalcitol Fresenius 2 micrograms/ml, solution for injection
Paricalcitol Fresenius 5 micrograms/ml, solution for injection
Paricalcitol
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. See section 4.

Leaflet contents:

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

1. What Paricalcitol Fresenius is and what it is used for

The active substance in Paricalcitol Fresenius is paricalcitol, a synthetic form of active vitamin D.

Active vitamin D is necessary for the proper functioning of many tissues in the body, including the kidneys and bones.

In people with normally functioning kidneys, this active form of vitamin D is naturally produced by the kidneys. However, in kidney failure, its production is significantly reduced. Paricalcitol Fresenius provides a source of active vitamin D when the body is unable to produce sufficient amounts. Thus, it helps prevent the consequences of low levels of active vitamin D in patients with kidney failure, such as high levels of parathyroid hormone, which may lead to bone disorders. Paricalcitol Fresenius is used in adult patients with stage 5 chronic kidney disease.

2. Important information before using Paricalcitol Fresenius

When not to use Paricalcitol Fresenius

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6).
• if the patient has very high levels of calcium or vitamin D in the blood.

The treating physician will inform the patient if any of these situations apply.
Warnings and precautions
Before starting treatment with Paricalcitol Fresenius, discuss this with the doctor or
nurse.

• Before starting treatment, the amount of phosphorus in the diet should be reduced. Examples of foods rich in phosphorus include: tea, carbonated water, beer, cheese, milk, cream, fish, chicken or beef liver, beans, peas, breakfast cereals, nuts, and grains.
• To maintain appropriate phosphorus levels in the body, it may be necessary to take phosphate-binding medications, which prevent the absorption of phosphates from food.
• If the patient is taking phosphate-binding medications containing calcium, the doctor may recommend adjusting their dose.
• The treating physician will order blood tests to monitor the course of treatment.

Children and adolescents
The safety and efficacy of paricalcitol in children have not been established. There is no available data in children under 5 years of age. Paricalcitol Fresenius should not be used in this patient group.
Paricalcitol Fresenius with other medicines
Tell the doctor about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
Some medicines may affect the action of this medicine or increase the likelihood of adverse effects. It is particularly important that the patient informs the doctor if they are taking any of the following medicines:

• used to treat fungal infections such as candidiasis or aspergillosis (e.g. ketoconazole),
• used to treat heart conditions or hypertension (e.g. digoxin and diuretics),
• containing phosphate (e.g. medications reducing blood calcium levels),
• containing calcium or vitamin D, including supplements and multivitamins available without a prescription,
• containing magnesium or aluminium, e.g. certain types of antacids (neutralizing gastric hydrochloric acid) and phosphate binders,
• used to treat elevated blood cholesterol levels (e.g. cholestyramine).

Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor before using this medicine.
It is not known whether using this medicinal product is safe during pregnancy; therefore, its use is not recommended during pregnancy or when there is a possibility of becoming pregnant.
It is not known whether Paricalcitol Fresenius passes into human breast milk. The patient should inform the doctor about taking Paricalcitol Fresenius before starting breastfeeding.
Driving and operating machinery
Paricalcitol Fresenius may cause dizziness, which could affect the patient's ability to drive safely or operate heavy machinery.
The patient should not drive or operate machinery if they experience dizziness.
Paricalcitol Fresenius contains ethanol and propylene glycol
Paricalcitol Fresenius 2 micrograms/ml
This medicine contains 1.8 g of alcohol (ethanol) in the maximum dose of 20 ml, equivalent to 88 mg/ml (11 vol%).
The amount of alcohol in 20 ml of this medicine is equivalent to 45 ml of beer or 18 ml of wine.
The amount of alcohol in this medicine is unlikely to have an effect on adults and adolescents, and its effect in children is likely to be unnoticeable. It may cause some effects in younger children, for example, drowsiness.
Alcohol in this medicine may alter the effects of other medicines. If the patient is taking other medicines, they should consult their doctor or pharmacist.
If the patient is pregnant or breastfeeding, she should consult her doctor or pharmacist before using this medicine.
If the patient is alcohol-dependent, they should consult their doctor or pharmacist before using this medicine.
Paricalcitol Fresenius 5 micrograms/ml
This medicine contains 0.7 g of alcohol (ethanol) in the maximum dose of 8 ml, equivalent to 88 mg/ml (11 vol%).
The amount of alcohol in 8 ml of this medicine is equivalent to less than 18 ml of beer or 7 ml of wine.
The small amount of alcohol in this medicine will not cause noticeable effects.
Paricalcitol Fresenius 2 micrograms/ml
This medicine contains 8.1 g of propylene glycol in the maximum dose of 20 ml, corresponding to 404 mg/ml.
Women who are pregnant or breastfeeding should not use this medicine without a doctor's recommendation. Patients with impaired liver or kidney function should not use this medicine without a doctor's recommendation.
The doctor may decide to perform additional tests in such patients.
Paricalcitol Fresenius 5 micrograms/ml
This medicine contains 3.2 g of propylene glycol in the maximum dose of 8 ml, corresponding to 404 mg/ml.

3. How to use Paricalcitol Fresenius

Your treating physician will use laboratory test results to determine the appropriate initial dose for the individual patient. When starting paricalcitol treatment, dose adjustments may be necessary depending on the results of routine laboratory tests. Based on these laboratory results, your physician will help establish the correct paricalcitol dose.

Paricalcitol Fresenius will be administered by a doctor or nurse during a hemodialysis procedure. There is no need for intravenous injection, as Paricalcitol Fresenius can be given directly into the dialysis tubing used during the procedure.

Paricalcitol Fresenius will not be administered more frequently than every other day and no more than three times per week.

Use in children
There is no information regarding the use of paricalcitol in children under 5 years of age, and experience with use in children over 5 years of age is limited. The treating physician will decide whether treatment is necessary.

Use of a higher than recommended dose of Paricalcitol Fresenius
Using a higher than recommended dose of Paricalcitol Fresenius may cause abnormally high levels of calcium in the blood, which can be harmful.

Symptoms that may occur soon after taking an excessive dose of Paricalcitol Fresenius may include weakness and (or) drowsiness, headache, nausea or vomiting, dry mouth, constipation, muscle or bone pain, and metallic taste in the mouth.

If high calcium levels in the blood occur after administration of Paricalcitol Fresenius, your physician will initiate appropriate treatment to return calcium levels to normal. Once calcium levels return to normal, your physician may recommend continuing Paricalcitol Fresenius at a lower dose.

Your physician will monitor blood levels. If any of the above symptoms occur, the patient should seek immediate medical advice.

Symptoms that may occur if an excessive dose of Paricalcitol Fresenius is taken over a prolonged period include loss of appetite, drowsiness, weight loss, eye irritation, runny nose, skin itching, sensation of heat and fever, loss of libido, severe abdominal pain (caused by pancreatitis), and kidney stones.

Changes in blood pressure and occurrence of irregular heartbeat (palpitations) may also develop. Blood and urine tests may show elevated levels of cholesterol, urea, nitrogen, and increased liver enzymes. Paricalcitol Fresenius may rarely cause mental changes including disorientation, drowsiness, insomnia, or nervousness.

A component of Paricalcitol Fresenius is propylene glycol. Cases of toxic effects related to high doses of propylene glycol are rarely reported and are not expected when propylene glycol is administered to patients with renal failure during hemodialysis, as it is removed from the blood during the procedure.

If a patient receives too high a dose of Paricalcitol Fresenius or experiences any of the above symptoms, they should seek immediate medical advice.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Various allergic reactions have been observed with the use of paricalcitol.
Warning: If any of the following adverse symptoms occur,
contact your doctor or nurse immediately:

• shortness of breath,
• difficulty breathing or swallowing,
• wheezing,
• rash, skin itching or hives,
• swelling of the face, lips, mouth, tongue or throat.

If any of the following adverse reactions occur,
inform your doctor or nurse:
Common (may occur in up to 1 in 10 patients):

• low levels of parathyroid hormone in the blood,
• high levels of calcium in the blood (nausea or vomiting, constipation or confusion), high levels of phosphorus in the blood (likely without symptoms, but may increase the risk of bone fractures),
• headache,
• unusual taste in the mouth,
• skin itching.

Uncommon (may occur in up to 1 in 100 patients):

• blood infection, pneumonia (lung infection), sore throat, vaginal infections, flu,
• breast cancer,
• decreased number of red blood cells (anaemia – weakness, shortness of breath, pale skin),
• decreased number of white blood cells (increased risk of infections), swollen lymph nodes in the neck, under the arms and/or in the groin,
• high levels of parathyroid hormone in the blood,
• high levels of potassium in the blood, low levels of calcium in the blood, loss of appetite,
• disorientation, sometimes severe (delirium), personality changes (patient does not feel like themselves), agitation (feeling shaky, anxious), sleep problems, nervousness,
• coma (a state of deep unconsciousness in which the person does not respond to surroundings), stroke, fainting, muscle spasms in the arms and legs, even during sleep, reduced sense of touch, tingling or numbness, dizziness,
• increased intraocular pressure, conjunctivitis (itching/dry discharge on eyelids),
• ear pain,
• heart attack, irregular or rapid heartbeat,
• low blood pressure, high blood pressure,
• fluid in the lungs, asthma (wheezing), breathing difficulties, nosebleeds, cough,
• rectal bleeding, inflammation of the large intestine, diarrhoea, stomach pain, difficulty swallowing, constipation, nausea, vomiting, dry mouth,
• rash with itchy blisters on the skin, hair loss, excessive hair growth, excessive and unpredictable sweating,
• joint pain, joint stiffness, back pain, muscle twitching, muscle pain,
• chest pain, difficulty achieving or maintaining erection,
• abnormal gait, generalized swelling or localized swelling of ankles, feet and legs, injection site pain, fever, chest pain, inappropriate feeling of tiredness or weakness, general feeling of discomfort, thirst,
• prolonged bleeding time (blood clots more slowly), increased liver enzyme activity, abnormal laboratory test results, weight loss.

Adverse reactions with unknown frequency (frequency cannot be determined from available data):

• swelling of the face, lips, mouth, tongue or throat, which may cause difficulty in swallowing or breathing; skin itching (urticaria). Gastrointestinal bleeding.

Some of the symptoms listed above may not be detectable by the patient without information from the doctor.
Reporting of adverse reactions
If any adverse symptoms occur, including any not listed in this leaflet, inform your doctor or nurse. Adverse reactions 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 181 C, PL-02-222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309,
Website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Paricalcitol Fresenius

Keep this medicine out of the sight and reach of children.
There are no special requirements for storage of this medicine.
Paricalcitol Fresenius should be used immediately after opening.
Do not use this medicine after the expiry date stated on the carton after the words “Expiry date (EXP)”. The expiry date refers to the last day of the stated month.
Do not use this medicine if the solution has changed colour or becomes cloudy.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the package and other information

What Paricalcitol Fresenius contains

• The active substance is paricalcitol.
• Other components of the medicine are: ethanol, propylene glycol, and water for injections.

What Paricalcitol Fresenius looks like and contents of the pack
Paricalcitol Fresenius is a clear, colourless solution without visible particles.
Paricalcitol Fresenius 2 micrograms/ml is supplied in packs containing 1 or 5
glass ampoules of 1 ml and in packs containing 1 or 5 glass vials of 1 ml.
Paricalcitol Fresenius 5 micrograms/ml is supplied in packs containing 1 or 5
glass ampoules of 1 ml or 2 ml and in packs containing 1 or 5 glass vials of 1 ml or 2 ml.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Fresenius Medical Care Nephrologica Deutschland GmbH
Else-Kröner-Straße 1
61352 Bad Homburg v.d.H.
Germany

Manufacturer
Fresenius Medical Care Deutschland GmbH
Else-Kröner-Straße 1
61352 Bad Homburg v.d.H.
Germany

Distributor:
Fresenius Medical Care Polska S.A.,
60-118 Poznań,
Krzywa 13 Street
Tel.: 0-61 83-92-600
Fax: 0-61 83-92-601

Information intended exclusively for healthcare professionals
Paricalcitol Fresenius, 2 and 5 micrograms/ml, solution for injection
Paricalcitol Fresenius is intended for single use only. As with all injectable medicinal products, the solution should be visually inspected before administration to ensure there are no particles or discolouration.

Pharmaceutical incompatibilities
Propylene glycol interacts with heparin and neutralizes its effect. Paricalcitol Fresenius contains propylene glycol as an excipient and therefore must be administered via a different access route than heparin.
This medicinal product must not be mixed with other medicinal products.

Shelf life
2 years.

Dosage and method of administration
Paricalcitol Fresenius is administered through the vascular access used for haemodialysis procedures.

Adults

1. The initial dose should be calculated based on the initial parathyroid hormone (PTH) concentration.
   The initial dose of paricalcitol is calculated according to the following formula:
   Initial dose (in micrograms) = initial concentration of native PTH ("intact PTH") in pmol/l
   8 Or
   = initial concentration of native PTH ("intact PTH") in pg/ml
   and is administered as a rapid intravenous injection no more frequently than every other day, at any time during dialysis.
   The maximum dose safely administered in clinical studies was 40 micrograms.

2. Dose adjustment
   Currently, the target PTH concentration range for dialysis patients with end-stage renal disease should not exceed 1.5 to 3 times the upper limit of normal for native PTH (iPTH) in non-uraemic individuals, i.e., 15.9 to 31.8 pmol/l (150–300 pg/ml). Achieving appropriate physiological target values requires careful monitoring and individual dose adjustment. In case of hypercalcaemia or a persistently elevated corrected calcium-phosphate product (Ca x P) above 5.2 mmol/l (65 mg/dl), the dose should be reduced or administration of the drug should be suspended until these parameters return to normal. Paricalcitol should then be restarted at a lower dose. Dose reductions may also be necessary when PTH levels decrease in response to treatment.

The table below provides guidance on dose adjustment: