ZEMPLAR 5 micrograms/ml INJECTABLE SOLUTION

Introduction

Package Leaflet: Information for the Patient

Zemplar5 micrograms/ml solution for injection

paricalcitol

Read all of this leaflet carefully before you start 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, pharmacist or nurse.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Zemplar and what is it used for

Zemplar contains the active substance paricalcitol, which is a synthetic form of active vitamin D.

Active vitamin D is required for the normal functioning of many tissues in the body, including the parathyroid gland and bones. In people with normal kidney function, this active form of vitamin D is produced naturally by the kidneys, but in kidney failure, the production of active vitamin D is significantly reduced. Therefore, Zemplar provides a source of active vitamin D when the body cannot produce enough and helps prevent the consequences of low levels of active vitamin D in patients with chronic kidney disease, specifically with high levels of parathyroid hormone that can cause bone problems. Zemplar is indicated in adult patients with chronic kidney disease Stage 5.

2. What you need to know before you use Zemplar

Do not use Zemplar

• if you are allergic to paricalcitol or any of the other ingredients of this medicine (listed in section 6).
• if you have very high levels of calcium or vitamin D in the blood.

Your doctor will be able to tell you if these conditions apply to you.

Warnings and precautions

Talk to your doctor or nurse before you start using Zemplar.

• before starting treatment, it is important that you limit the amount of phosphorus ingested in your diet. Examples of foods that contain high levels of phosphorus are: tea, soda, beer, cheese, milk, cream, fish, chicken or beef liver, beans, peas, cereals, nuts, and whole foods.
• to control phosphorus levels, it may be necessary to use phosphorus-binding agents that prevent the absorption of phosphorus from the diet.
• if you are taking phosphorus-binding agents with calcium content, your doctor may need to adjust the dose.
• your doctor will need to perform blood tests to monitor your treatment.

Using Zemplar with other medicines

Tell your doctor, nurse or pharmacist if you are using, have recently used or might use any other medicines.

Some medicines may affect the action of this medicine or may increase the risk of side effects. It is particularly important that you tell your doctor if you are using any of the following medicines:

• to treat fungal infections such as thrush (e.g., ketoconazole)
• to treat heart problems or high blood pressure (e.g., digoxin and diuretics)
• that contain a source of phosphate (e.g., medicines that lower calcium levels in the blood)
• that contain calcium or vitamin D, including supplements and multivitamins that can be purchased without a prescription
• that contain magnesium or aluminum (e.g., some types of medicines for indigestion (antacids) and phosphorus binders.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before using this medicine.

It is not known if this medicine is safe for pregnant women, therefore its use is not recommended during pregnancy or if you can become pregnant.

It is not known if paricalcitol passes into human breast milk. Tell your doctor before breastfeeding while using Zemplar.

Driving and using machines

Zemplar may make you feel dizzy, this may affect your ability to drive safely or use heavy machinery.

Do not drive or use machines if you feel dizzy.

Zemplar contains ethanol

This medicine contains up to 1.3 mg of alcohol (ethanol) in each dose, which is equivalent to approximately 18 mg/kg. The amount in each dose of this medicine is equivalent to approximately 32 ml of beer or 13 ml of wine.

It is unlikely that the amount of alcohol contained in this medicine will have any noticeable effect on adults or adolescents. It may have some effects on young children, such as drowsiness.

The amount of alcohol contained in this medicine may alter the effect of other medicines. Consult your doctor or pharmacist if you are taking other medicines.

If you are pregnant or breastfeeding, consult your doctor or pharmacist before this medicine is administered to you.

If you have an addiction to alcohol, consult your doctor or pharmacist before this medicine is administered to you.

3. How to use Zemplar

Your doctor will use the results of laboratory tests to decide the initial dose suitable for you. Once you have started treatment with Zemplar, the dose must be adjusted based on the results of routine laboratory tests. Using the results of your tests, your doctor will help you determine the suitable dose of Zemplar for you.

Zemplar will be administered by your doctor or nurse while you are being treated with the kidney machine. It will be administered through the tube that connects you to the machine. You will not need to receive an injection as Zemplar can be introduced directly into the tube being used for your treatment. You will not receive Zemplar more frequently than every other day and no more than 3 times a week.

If you use more Zemplar than you should

An overdose of Zemplar may produce abnormally high levels of calcium in the blood, which can be harmful. The symptoms that may appear soon after taking too much Zemplar may include a feeling of weakness and/or drowsiness, headache, nausea (feeling sick) or vomiting (being sick), dry mouth, constipation, muscle or bone pain, and a metallic taste in the mouth.

If you experience high levels of calcium in the blood after using Zemplar, your doctor will prescribe the appropriate treatment to return to normal calcium levels. Once your calcium levels return to normal, it is likely that you will be given low doses of Zemplar.

Your doctor will monitor your blood levels. If you experience any of the above symptoms, seek medical advice immediately.

The symptoms that may occur after long-term overdose of Zemplar include loss of appetite, drowsiness, weight loss, dry eyes, runny nose, itching of the skin, feeling of heat, and fever, loss of sexual appetite, severe abdominal pain (due to pancreas inflammation), and kidney stones. Your blood pressure may be affected, and irregular heartbeats (palpitations) may occur. Blood and urine test results may show high cholesterol, urea, nitrogen, and elevated liver enzyme levels. Rarely, Zemplar may cause mental changes such as confusion, drowsiness, insomnia, or nervousness.

Zemplar contains 30% v/v propylene glycol as an excipient. Isolated cases of toxic effects related to the administration of high doses of propylene glycol have been described, although they are not expected when administered to patients undergoing kidney machine treatment because propylene glycol is eliminated from the blood during dialysis.

If you receive an overdose of Zemplar or experience any of the above symptoms, seek medical advice immediately.

In case of overdose or accidental ingestion, go immediately to a medical center or call the Toxicological Information Service, phone 91 562 04 20, indicating the medicine and the amount ingested.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Several allergic reactions have been reported with Zemplar. Important: if you notice any of the following side effects, tell your doctor or nurse immediately:

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

Tell your doctor or nurse if you notice any of the following side effects:

Common(may affect up to 1 in 10 people):

• low levels of parathyroid hormone
• high levels of calcium (feeling sick or being sick, constipated, or confused); phosphorus in the blood (probably asymptomatic but may make bones susceptible to fracture)
• headache
• unusual taste in the mouth
• itching of the skin

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

• blood infection, pneumonia (lung infection), sore throat, vaginal infections, flu
• breast cancer
• decrease in the number of red blood cells (anemia – feeling weak, difficulty breathing, paleness); decrease in the number of white blood cells (increased susceptibility to infections), inflammation of lymph nodes in the neck, armpit, and/or groin
• high levels of parathyroid hormone
• high levels of potassium in the blood, low levels of calcium in the blood, loss of appetite
• confusion, which can be severe (delirium), personality disorders (not feeling like oneself), agitation (feeling nervous, anxious), sleep problems, nervousness
• coma (deep state of unconsciousness during which a person cannot interact with the environment), stroke, fainting, muscle spasms in arms and legs, even during sleep, decreased sense of touch, tingling, or numbness, dizziness
• increased pressure in the eye, red conjunctiva (itchy/ sticky eyelids)
• ear pain
• heart attack, irregular/fast heartbeat
• low blood pressure, high blood pressure
• fluid in the lungs, asthma, wheezing, difficulty breathing, nosebleeds, cough
• rectal bleeding, colon inflammation, diarrhea, stomach pain, difficulty swallowing, constipation, nausea, vomiting, dry mouth
• skin rash with blisters and itching, hair loss, excessive hair growth, excessive and unpredictable sweating
• joint pain, joint stiffness, back pain, muscle spasms, muscle pain
• breast pain, difficulty having an erection
• abnormal gait, general or localized swelling of the ankles, feet, and legs, pain at the injection site, fever, chest pain, unusual tiredness or weakness, a general feeling of discomfort, thirst
• increased bleeding time (blood does not clot as quickly), increased liver enzyme, change in laboratory test results, weight loss

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

• swelling of the face, lips, mouth, tongue, or throat that can cause difficulty swallowing or breathing; itching of the skin (hives); stomach bleeding.

You may not identify these side effects unless your doctor has previously informed you.

If you think any of the side effects you are experiencing are serious or if you notice any side effects not listed in this leaflet, tell your doctor, nurse, or pharmacist immediately.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are not listed in this leaflet. You can also report side effects directly through the Spanish Medicines Monitoring System for Human Use: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Zemplar

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

No special storage conditions are required.

Zemplar should be used immediately after opening.

Do not use this medicine after the expiry date which is stated on the carton after EXP. The expiry date is the last day of the month shown.

Do not use this medicine if you notice particles or discoloration.

Medicines should 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

Composition of Zemplar

• The active substance is paricalcitol. Each ml of solution contains 5 micrograms of paricalcitol.

The other ingredients are: ethanol (alcohol), propylene glycol, and water for injections.

Appearance and packaging

Zemplar is a clear and colorless aqueous solution, free from visible particles. It is available in packs of 5 ampoules of 1 ml or 2 ml or 5 glass vials of 1 ml or 2 ml.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

ABBVIE SPAIN, S.L.U.

Avenida de Burgos, 91 - 28050 Madrid, SPAIN.

Manufacturer:

Ampoules:

AbbVie S.r.l., S.R.148 Pontina km 52 snc, 04011 Campoverde di Aprilia (LT), Italy.

Vials:

AbbVie S.r.l., S.R.148 Pontina km 52 snc, 04011 Campoverde di Aprilia (LT), Italy.

AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061 Ludwigshafen, Germany

This medicine is authorized in the Member States of the European Economic Area under the following names:

Austria:Zemplar 5 Mikrogramm/ml Injektionslösung

Czech Republic:Zemplar

Germany:Zemplar 5 Mikrogramm/ml Injektionslösung

Ireland:Zemplar 5 micrograms/ml solution for injection

Italy:Zemplar 5 microgrammi/ml soluzione iniettabile

Slovakia:Zemplar 5 mikrogramov/ml injekčný roztok

Spain:Zemplar 5 microgramos/ml solución inyectable

United Kingdom:Zemplar 5 micrograms/ml solution for injection

This leaflet was last revised in October 2024

Detailed and up-to-date information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/

To listen to or request a copy of this leaflet in , , or

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This information is intended for healthcare professionals:

Zemplar 5 micrograms/ml solution for injection

Preparation for solution for injection

Zemplar 5 micrograms/ml solution for injection is for single use. As with other parenteral medicines, the solution should be inspected for particles and coloration before administration.

Compatibility

Propylene glycol interacts with heparin and neutralizes its effects. Zemplar solution for injection contains propylene glycol as an excipient and should be administered through a different administration site than heparin.

This medicine should not be mixed with other medicines.

Storage and shelf-life

Parenteral products should be inspected before administration for the presence of visible particles and coloration. The solution is clear and colorless.

This medicine does not require special storage conditions.

This medicine has a shelf-life of 3 years (vial) or 2 years (ampoule).

Posology and method of administration

Zemplar solution for injection is administered through the hemodialysis access.

Adults

1. The initial dose should be calculated based on the basal levels of parathyroid hormone (PTH)

The initial dose of paricalcitol is based on the following formula:

Initial dose (micrograms) = basal intact PTH level in pmol/l

8

Or

= basal intact PTH level in pg/ml

80

and administered as an intravenous bolus dose, with a maximum frequency of every other day and at any time during dialysis.

The maximum safely administered dose in clinical studies was 40 micrograms.

1. Dose titration:

The currently accepted levels for the range of PTH in subjects with end-stage renal disease undergoing dialysis are no more than 1.5 to 3 times the upper normal limit for non-uremic patients, 15.9 to 31.8 pmol/l (150-300 pg/ml) for intact PTH. To achieve adequate levels of physiological variables, individualized monitoring and dose titration are necessary. If hypercalcemia or an elevated corrected Ca x P product, greater than 5.2 mmol^2/l^2 (65 mg^2/dl^2), is persistently observed, the dose should be reduced or interrupted until these parameters normalize. Then, paricalcitol administration should be restarted at a lower dose. It may be necessary to reduce the dose when PTH levels decrease in response to therapy.

The following table is suggested as a guide for dose titration: