Paricalcitol Sandoz

Patient Information Leaflet: Information for the User

Paracalcitriol Sandoz 2 micrograms/ml injection solution, Sandoz 5 micrograms/ml injection solution

Generic Medicine
Please read this leaflet carefully before you are given this medicine because it contains important information for you.

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

Contents of this leaflet:

1. What Paracalcitriol Sandoz is and what it is used for
2. What you need to know before you are given Paracalcitriol Sandoz
3. How Paracalcitriol Sandoz is given to you
4. Possible side effects
5. How to store Paracalcitriol Sandoz
6. Contents of the pack and other information

1. What Paracalcitolo Sandoz is and what it is used for

Paracalcitolo Sandoz is a synthetic analogue of active vitamin D. It is indicated for the prevention and treatment of elevated levels of parathyroid hormone in the blood of patients with renal insufficiency undergoing haemodialysis. Elevated levels of parathyroid hormone may be due to low levels of "active" vitamin D in patients with renal insufficiency.
Active vitamin D ensures the normal function of numerous tissues in the body, including the kidneys and bones.

2. What you need to know before you are given Paracalcitolo Sandoz

Do not take Paracalcitolo Sandoz

• if you are allergic to paracalcitol or to any of the other ingredients of this medicine (listed in section 6).
• if you have very high levels of calcium or vitamin D in your blood. Your doctor will monitor your blood levels and will be able to advise you whether your condition falls under the above-mentioned circumstances.

Warnings and Precautions
Talk to your doctor, nurse, or pharmacist before you are given Paracalcitolo Sandoz

• Before starting treatment, it is important that you limit the amount of phosphorus you consume in your diet. Examples of foods high in phosphorus include tea, soda, beer, cheese, milk, cream, fish, chicken or beef liver, beans, peas, cereals, dried fruit, and wheat.
• Phosphate-binding medications, which prevent the absorption of phosphorus from food, may be necessary to control phosphorus levels.
• If you are taking calcium-based phosphate binders, your doctor may need to adjust your dosage.
• Your doctor will prescribe regular blood tests to monitor your treatment.

Other medicines and Paracalcitolo Sandoz
Inform your doctor, nurse, or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
Some medicines may affect the action of Paracalcitolo Sandoz or increase the likelihood of side effects. It is particularly important to inform your doctor if you are taking any of the following medicines:

• medications for fungal infections such as candidiasis or thrush (e.g. ketoconazole).
• heart or blood pressure medications (e.g. digoxin, diuretics, or water pills to remove excess fluid from the body).
• medications containing magnesium (e.g. some antacids used for digestion, such as magnesium trisilicate).
• medications containing aluminium (e.g. phosphate binders such as aluminium hydroxide).
• medications containing phosphate or vitamin D, which should not be taken concomitantly with paracalcitol.
• medications containing high doses of calcium.

Talk to your doctor, nurse, or pharmacist before taking any medicine.
Paracalcitolo Sandoz with food and drink
Paracalcitolo Sandoz can be administered with or without food.
Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor, nurse, or pharmacist before taking this medicine.
There are insufficient data available on the safe use of this medicine in pregnant women.
Therefore, the use of this medicine during pregnancy is not recommended.
It is not known whether paracalcitol passes into breast milk. Inform your doctor before breastfeeding if you are taking Paracalcitolo Sandoz.
Driving and using machines
Paracalcitolo Sandoz may cause dizziness, which could impair your ability to drive or operate machinery. Do not drive or operate machinery if you experience dizziness.
Paracalcitolo Sandoz contains ethanol (alcohol)
This medicine contains 20% v/v ethanol (alcohol), i.e. up to 1.3 g of ethanol per dose, equivalent to 33 ml of beer or 14 ml of wine per dose. The presence of ethanol in this medicine is harmful for individuals with alcoholism and should be taken into account when administering to pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.

3. How Paracalcitolo Sandoz must be administered to you

Your doctor will determine the appropriate initial dose for you based on laboratory test results.
Once treatment with Paracalcitolo Sandoz has started, your dose will likely be adjusted according to
the results of routine laboratory tests. Based on these test results, your doctor will help you establish
the most suitable dose of Paracalcitolo Sandoz for your needs.
Paracalcitolo Sandoz will be administered to you by a doctor or nurse during haemodialysis. It will
be given through the tube (bloodline) used to connect you to the dialysis machine. No injection will
be necessary, as Paracalcitolo Sandoz can be directly introduced into the tube used for your
treatment. Paracalcitolo Sandoz will be administered on alternate days, no more than three times a
week.

If you are given more Paracalcitolo Sandoz than you should
An excessive dose of Paracalcitolo Sandoz may cause abnormally high levels of calcium in the blood,
which may require treatment. Symptoms that may occur soon after taking an excessive dose of
Paracalcitolo Sandoz include:

• feeling weak and/or numb
• headache
• feeling unwell (nausea or vomiting)
• dry mouth, constipation
• muscle or bone pain
• altered taste

Symptoms that may develop over a longer period of excessive Paracalcitolo Sandoz intake include:

• loss of appetite
• drowsiness
• weight loss
• eye irritation
• runny nose
• skin itching
• feeling hot and feverish
• loss of libido
• severe abdominal pain
• kidney stones
• Blood pressure changes and irregular heartbeat (palpitations) may occur.

If you develop high calcium levels in the blood after taking Paracalcitolo Sandoz, your doctor will
ensure you receive appropriate treatment to restore normal calcium levels. Once your calcium levels
return to normal, you may be given a lower dose of Paracalcitolo Sandoz.
Your doctor will monitor your blood levels, and if you notice any of the symptoms listed above,
contact your doctor immediately.
If you have any doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Allergic reactions of various types have been reported with Paracalcitol Sandoz.
Important: Immediately inform your doctor or nurse if you experience any of the following side effects:
Uncommon (may affect up to 1 in 100 people):

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

Inform your doctor or pharmacist if you notice any of the following side effects:
Common (may affect up to 1 in 10 people):

• headache
• altered taste
• skin itching
• low levels of parathyroid hormone
• high levels of calcium (feeling unwell or malaise, constipation or confusion); phosphorus in the blood (likely without symptoms, but with increased risk of fractures)

Uncommon (may affect up to 1 in 100 people):

• allergic reactions (for example, shortness of breath, dyspnea, skin rash, itching or swelling of the face and lips); itchy blisters
• blood infections; reduced red blood cell count (anaemia – fatigue, shortness of breath, pallor); reduced white blood cell count (increased susceptibility to infections); swollen glands in the neck, armpit and/or groin; prolonged bleeding time (blood does not clot as quickly)
• heart attack; stroke; chest pain; irregular/rapid heartbeat; low blood pressure; high blood pressure
• coma (deep state of unconsciousness during which the person is unable to respond to their surroundings)
• unusual tiredness, weakness; dizziness; fainting
• pain at the injection site
• pneumonia (lung infection); fluid in the lungs; asthma (dyspnea, cough, difficulty breathing)
• sore throat; cold; fever; flu-like symptoms; pink eye (itchy/dry eyelids); increased eye pressure; earache; nosebleeds
• nervous twitching; confusion, sometimes severe (delirium); agitation (anxiety); nervousness; personality disturbances (feeling unlike oneself)
• tingling or numbness; reduced tactile sensation; insomnia; night sweats; muscle spasms in arms and legs, also during sleep
• dry mouth; thirst; nausea; difficulty swallowing; vomiting; loss of appetite; weight loss; heartburn; diarrhoea and stomach ache; constipation; anal bleeding
• erectile dysfunction; breast cancer; vaginal infections
• breast pain; back pain; joint/muscle pain; sensation of heaviness due to generalized or localized swelling of ankles, feet and legs (oedema); abnormal gait
• hair loss; excessive hair growth
• increased levels of a liver enzyme; elevated levels of parathyroid hormone; elevated levels of potassium in the blood; reduced levels of calcium in the blood

Not known (frequency cannot be estimated from the available data):

• swelling of the face, lips, mouth, tongue or throat, possibly causing difficulty in swallowing or breathing; skin itching (urticaria). Gastrointestinal bleeding. If you experience these symptoms, consult a doctor immediately.

You may not be able to tell whether you are experiencing any of the above-mentioned side effects unless your doctor informs you.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Paracalcitolo Sandoz

Keep this medicine out of the sight and reach of children.
Keep the vials in the outer packaging to protect the medicine from light.
For single use only.
Once opened, Paracalcitolo Sandoz must be used immediately.
Do not use this medicine after the expiry date stated on the packaging and on the vial after the word “Exp.”. The expiry date refers to the last day of that month.
Do not use Paracalcitolo Sandoz if you notice the presence of particles or discoloration.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Paracalcitolo Sandoz contains

• The active substance is paricalcitol. Each ml of injectable solution contains 2 micrograms of paricalcitol. Each 1 ml vial contains 2 micrograms of paricalcitol. Each 2 ml vial contains 4 micrograms of paricalcitol.

Each ml of injectable solution contains 5 micrograms of paricalcitol.
Each 1 ml vial contains 5 micrograms of paricalcitol.
Each 2 ml vial contains 10 micrograms of paricalcitol.

• The other components are: ethanol (alcohol), macrogol 15 hydroxystearate and water for injections.

Description of the appearance of Paracalcitolo Sandoz and contents of the pack
This medicinal product is a clear, colourless, particle-free injectable solution, supplied in a clear type I glass vial.
Pack sizes:
2 micrograms/ml injectable solution
Pack containing 5 vials of 1 mL injectable solution (2 micrograms/1 ml)
Pack containing 5 vials of 2 mL injectable solution (4 micrograms/2 ml)
5 micrograms/ml injectable solution
Pack containing 5 vials of 1 ml injectable solution (5 micrograms/1 ml)
Pack containing 5 vials of 2 mL injectable solution (10 micrograms/2 ml)
Not all pack sizes may be marketed.

Marketing Authorization Holder:
Sandoz Spa
Largo U. Boccioni, 1
21040 – Origgio (VA)
Italy

Manufacturer
Pharmathen S.A.
6 Dervenakion Street, 153 51 Pallini Attikis, Athens,
Greece
Lek Pharmaceuticals d.d.
Verovskova 57, 1526 Ljubljana,
Slovenia
Salutas Pharma GmbH
Otto-von Guericke-Allee 1, 39179 Barleben,
Germany

This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Denmark Paricalcitol Sandoz
Germany Paricalcitol HEXAL 2 Mikrogramm/ml Injektionslösung
Paricalcitol HEXAL 5 Mikrogramm/ml Injektionslösung
Spain Paricalcitol Sandoz 2 microgramos/ml solución inyectable EFG
Paricalcitol Sandoz 5 microgramos/ml solución inyectable EFG
Italy Paracalcitolo Sandoz
Greece Paricalcitol/Sandoz
Romania Paricalcitol Sandoz 2 micrograme/ml soluție injectabilă
Paricalcitol Sandoz 5 micrograme/ml soluție injectabilă
Croatia Caltopar

This Patient Information Leaflet was last approved on:
The following information is intended exclusively for healthcare professionals:

Paracalcitolo Sandoz 2 and 5 micrograms/ml solution for injection
Preparation of the injectable solution
Paracalcitolo Sandoz 2 micrograms/ml and 5 micrograms/ml solution for injection is for single use only.
As with all injectable medicinal products, the diluted solution should be inspected visually for particulate matter and discoloration prior to administration.

Storage and shelf life
Parenteral medicinal products should be inspected visually for the presence of particulate matter and for any change in colour before administration. The solution is clear and colourless.
Keep the vials in the outer packaging to protect the medicinal product from light.
The shelf life of this medicinal product is 2 years.
Once opened, Paracalcitolo Sandoz must be used immediately.

Dosage and method of administration
Paracalcitolo Sandoz 2 micrograms/ml and 5 micrograms/ml solution for injection must be administered via an haemodialysis access route.

Adults

1. The initial dose should be calculated based on baseline parathyroid hormone (PTH) levels:
   The initial dose of paricalcitol should be determined according to the following formula:
   Initial dose (in micrograms) = baseline intact PTH level expressed in pmol/L
   or
   = baseline intact PTH level expressed in pg/mL
   and should be administered intravenously as an intravenous bolus dose on alternate days, at any time during a haemodialysis session. In clinical studies conducted, the maximum safe dose administered was 40 mcg.

2. Dose titration:
   The currently accepted reference range for PTH levels in dialysis patients with end-stage chronic renal failure should not exceed 1.5 to 3 times the upper non-uremic normal limit of 15.9–31.8 pmol/L (150–300 pg/mL) for intact PTH. To achieve physiologically appropriate outcomes, patients must be carefully monitored and individual dose adjustments made. If hypercalcaemia or a persistently elevated corrected Ca x P product exceeding 5.2 mmol/L (65 mg/dL) is observed, the dose should be reduced or treatment interrupted until these parameters return to normal. Paricalcitol should then be restarted at a lower dose. It may be necessary to gradually reduce the paricalcitol dose as PTH levels decrease in response to therapy.

The following table provides an example of a recommended approach for dose determination: