Paricalcitol Accord 2 micrograms/ml solution for injection EFG

Patient Information Leaflet

Introduction

Patient Information Leaflet

Paricalcitol Accord 2 micrograms/ml injection solution EFG

Paricalcitol Accord 5 micrograms/ml injection solution EFG

Paricalcitol

Please read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only; do not pass it on to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents:

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

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

Paricalcitol Accord 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 naturally produced by the kidneys; however, in renal failure, the production of active vitamin D is markedly reduced. Therefore, Paricalcitol 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 high levels of parathyroid hormone that can cause bone problems. Paricalcitol is indicated in adult patients with chronic kidney disease stage 5.

2. What you need to know before starting Paricalcitol Accord

Do not use Paricalcitol Accord:

• If you are allergic to the active substance 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 can determine whether these conditions apply to you.

Warnings and precautions

Talk to your doctor or nurse before starting to use Paricalcitol Accord

• 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, nuts, and whole grain foods.
• To control phosphorus levels, phosphate binders may be needed to prevent absorption of dietary phosphorus.
• If you are taking phosphate binders containing calcium, your doctor may need to adjust your dose.
• Your doctor will need to perform blood tests to monitor your treatment.

Using Paricalcitol Accord with other medicines

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

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

• Medicines used to treat fungal infections such as candidiasis or oral thrush (e.g., ketoconazole)
• Medicines used to treat heart problems or high blood pressure (e.g., digoxin and diuretics)
• Medicines containing a source of phosphate (e.g., medicines that reduce calcium levels in the blood)
• Medicines containing calcium or vitamin D, including supplements and multivitamins available without a prescription
• Medicines containing magnesium or aluminum (e.g., certain types of antacids for dyspepsia and phosphate binders)

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine.

It is unknown whether this medicine is safe for pregnant women; therefore, its use is not recommended during pregnancy or if you may become pregnant.

It is unknown whether Paricalcitol Accord passes into human milk. Contact your doctor before breastfeeding while using Paricalcitol Accord.

Driving and using machines

Paricalcitol Accord may cause dizziness, which could affect your ability to drive safely or operate heavy machinery.

Do not drive or operate machinery if you feel dizzy.

Paricalcitol Accord contains anhydrous ethanol

5 mcg/mL:

This medicine contains up to 2.21 g of ethanol (alcohol) per dose, equivalent to approximately 32 mg/kg. The amount of alcohol in each dose is equivalent to about 55 ml of beer or 22 ml of wine.

The amount of alcohol in this medicine is unlikely to have an effect in adults and adolescents, and its effects in children are likely to be negligible. However, it may have some effects in younger children, for example, drowsiness.

The alcohol in this medicine may alter the effects of other medicines. Speak with your doctor or pharmacist if you are taking other medicines.

2 mcg/mL:

This medicine contains up to 5.52 g of ethanol (alcohol) per dose, equivalent to approximately 79 mg/kg. The amount of alcohol in each dose is equivalent to about 138 ml of beer or 55 ml of wine.

The alcohol in this formulation may affect children. These effects may include drowsiness and behavioral changes. It may also affect their ability to concentrate and participate in physical activities.

The amount of alcohol in this medicine may impair your ability to drive or operate machinery, as it may affect your judgment and reaction speed.

The alcohol content in this medicine may alter the effects of other medicines. Talk to your doctor or pharmacist if you are taking other medicines.

This medicine may be harmful to individuals with alcoholism.

The alcohol content should be taken into account in pregnant or breastfeeding women, children, and high-risk groups such as patients with liver disease or epilepsy.

3. How to use Paricalcitol Accord

Your doctor will use the results of laboratory tests to determine the appropriate initial dose for you.

Once you have started treatment with Paricalcitol Accord, the dose should be adjusted based on the results of routine laboratory tests. Using the results of your tests, your doctor will help determine the appropriate dose of Paricalcitol Accord for you.

Paricalcitol Accord will be administered by a doctor or nurse while you are being treated with the kidney machine. It will be given through the tube that connects you to the machine. You will not need to receive an injection, as Paricalcitol Accord can be introduced directly into the tube being used for your treatment.

You will not receive Paricalcitol Accord more frequently than on alternate days and no more than 3 times per week.

If you take more Paricalcitol Accord than you should

Too much Paricalcitol Accord can cause high levels of calcium in the blood. Symptoms that may occur after receiving an overdose of Paricalcitol Accord are:

• Feeling weak and/or drowsy
• Headache
• Nausea or vomiting (feeling unwell)
• Dry mouth, constipation
• Pain in muscles or bones
• Metallic taste in the mouth

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

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

Symptoms that may occur after a prolonged period of receiving too much Paricalcitol Accord are:

• Loss of appetite
• Drowsiness
• Weight loss
• Eye irritation
• Runny nose
• Itching of the skin
• Feeling feverish
• Loss of sexual appetite
• Severe abdominal pain (due to inflammation of the pancreas)
• Kidney stones
• Your blood pressure may be affected, and you may become aware of your own heartbeat (palpitations).

Your blood pressure may be affected and irregular heartbeats (palpitations) may occur. Blood and urine tests may show high cholesterol, urea, nitrogen, and elevated liver enzyme levels. Rarely, Zemplar may cause mental changes such as confusion, drowsiness, insomnia, or nervousness.

Paricalcitol Accord contains 30% by volume of propylene glycol as an excipient. Isolated cases of toxic effects related to the administration of high doses of propylene glycol have been reported; however, these are not expected when administered to patients undergoing treatment with a kidney machine, as propylene glycol is removed from the blood during dialysis.

If you use too much Paricalcitol Accord or experience any of the above effects, seek medical advice immediately.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Several allergic reactions have been reported with Paricalcitol Accord. Important: if you notice any of the following adverse effects, inform your doctor or nurse immediately:

• Shortness of breath
• Difficulty breathing and swallowing
• Wheezing
• Rash, skin itching, or hives
• Swelling of the face, lips, mouth, tongue, or throat.

Inform your doctor or nurse if you notice any of the following adverse effects:

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

• Headache;
• Unusual taste in the mouth;
• Skin itching;
• Decrease in parathyroid hormone levels;
• Increase in blood calcium levels (feeling unwell, constipation, or confusion) and blood phosphate levels (likely asymptomatic but may make bones susceptible to fracture).

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

• Blood infection, pneumonia (lung infection), sore throat, vaginal infections, flu
• Breast cancer
• Decrease in red blood cell count (anemia – feeling weak, shortness of breath, paleness); decrease in white blood cell count (increased susceptibility to infections), swelling of neck, armpit, and/or groin lymph nodes
• High levels of parathyroid hormone
• High levels of potassium in the blood, low levels of calcium in the blood, loss of appetite
• Confusion, sometimes severe (delirium), personality disorders (feeling unlike oneself), agitation (feeling nervous, anxious), trouble sleeping, restlessness
• Coma (deep state of unconsciousness during which a person cannot interact with their surroundings), stroke, fainting, muscle spasms in arms and legs, even during sleep, decreased tactile sensation, tingling or numbness, dizziness
• Increased eye pressure, red conjunctiva (itching/sticky eyelids)
• Ear pain
• Myocardial infarction, irregular/fast heartbeat
• Low blood pressure, high blood pressure
• Fluid in the lungs, asthma, wheezing, difficulty breathing, nosebleeds, cough
• Rectal bleeding, inflammation of the colon, diarrhea, stomach pain, difficulty swallowing, constipation, nausea, vomiting, dry mouth
• Skin rash with itchy blisters, hair loss, excessive hair growth, excessive and unpredictable sweating
• Joint pain, joint stiffness, back pain, muscle spasms, muscle pain
• Breast pain, difficulty achieving an erection
• Abnormal walking pattern, general swelling or localized swelling of ankles, feet, and legs, injection site pain, fever, chest pain, unusual tiredness or weakness, general feeling of discomfort, thirst
• Prolonged bleeding time (blood does not clot as quickly), increased liver enzyme, changes in laboratory test results, weight loss

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

• Swelling of face, lips, mouth, tongue, and throat that may cause difficulty swallowing or breathing; skin itching (urticaria), stomach bleeding.

You may not recognize these adverse effects unless your doctor has previously informed you about them.

If you consider any of the adverse effects you experience to be severe, or if you notice any adverse effect not listed in this leaflet, inform your doctor, nurse, or pharmacist immediately.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, hospital pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Paricalcitol Accord

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

No special temperature storage conditions are required. Keep the ampoule/vial in the outer packaging to protect it from light.

Paricalcitol Accord must be used immediately after opening.

Do not use this medicine after the expiry date stated on the packaging after EXP. The expiry date refers to the last day of the month indicated.

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

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

6. Contents of the pack and other information

Composition of Paricalcitol Accord

• The active substance is paricalcitol. Each ml of solution contains 2 micrograms or 5 micrograms of paricalcitol.
• The other components (excipients) are: anhydrous ethanol (alcohol), propylene glycol and water for injections.

Nature of the medicinal product and pack contents

Paricalcitol Accord is a clear, colourless aqueous solution, free from visible particles.

It is available in packs containing 1 vial or 5 vials of 1 ml or 2 ml.

It is also available in packs containing 5 ampoules of 1 ml or 2 ml.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder

Accord Healthcare S.L.U.

World Trade Center

Moll de Barcelona, s/n

Edifici Est, 6th floor

08039 Barcelona

Manufacturer

Accord Healthcare Polska Sp. z o.o.,

ul. Lutomierska 50, 95-200 Pabianice, Poland

or

Accord Healthcare Single Member S.A.

64th Km National Road Athens, Lamia, Schimatari, 32009

Greece

This medicinal product is authorised in the EEA Member States under the following names:

Date of the most recent review of this leaflet: June 2021

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.

Instructions for the healthcare professional

Paricalcitol Accord 2 micrograms/ml solution for injection

Paricalcitol Accord 5 micrograms/ml solution for injection

Preparation for injectable solution

Paricalcitol Accord 2 micrograms/ml or 5 micrograms/ml solution for injection is for single use. As with other parenteral medicines, the solution should be inspected visually for particulate matter and discoloration prior to administration.

Compatibility

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

This medicine must not be mixed with other medicinal products, as compatibility studies have not been conducted.

Storage and shelf life

The solution should be inspected visually before administration for the presence of particles and discoloration.

This medicine does not require special storage temperature conditions.

Keep the ampoule/vial in the outer packaging to protect it from light.

This medicine has a shelf life of 2 years.

Use immediately after opening

Dosage and method of administration

Paricalcitol Accord is administered during haemodialysis.

Dosage

Adults

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

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

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

8

or

= baseline intact PTH level in pg/ml

80

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

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

1. Dose titration:

Currently accepted target ranges for PTH levels in patients with end-stage renal failure undergoing dialysis are no more than 1.5 to 3 times the upper normal non-uraemic limit, i.e., 15.9 to 31.8 pmol/l (150–300 pg/ml) for intact PTH. To achieve appropriate levels of physiological parameters, individualized monitoring and dose titration are required. If hypercalcaemia or a persistently elevated corrected Ca x P product greater than 5.2 mmol²/l² (65 mg²/dl²) occurs, the dose should be reduced or treatment interrupted until these parameters return to normal.

Paricalcitol administration should then be restarted at a lower dose. Dose reduction may be necessary when PTH levels decrease in response to therapy.

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