PARICALCITOL NORMON 5 micrograms/ml INJECTABLE SOLUTION

2. What you need to know before you use Paricalcitol Normon

Do not use Paricalcitol Normon:

• If you are allergic to paricalcitol or any of the other ingredients of this medicine (see section 6).
• If you have very high levels of calcium or vitamin D in the blood. Your doctor will monitor your blood levels and will be able to tell you if these conditions apply to you.

Warnings and precautions:

• Before starting treatment, it is important that you limit the amount of phosphorus you ingest 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 Paricalcitol Normon with other medicines

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

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

• For treating fungal infections such as candida or thrush (e.g., ketoconazole)
• For treating the heart or blood pressure (e.g., digoxin and diuretics)
• That contain magnesium (e.g., some types of medicines for indigestion called antacids, such as magnesium trisilicate).
• That contain aluminium (e.g., phosphorus binders, such as aluminium hydroxide).

Consult your doctor, nurse, or pharmacist before taking any medicine.

Using Paricalcitol Normon with food and drink

Paricalcitol can be administered with or without food.

Pregnancy and breastfeeding

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

It is not known if this medicine is safe for pregnant or breastfeeding women. Therefore, it should only be used after consulting with your doctor, who will help you make the decision that is best for you.

The alcohol content should be taken into account in the case of pregnant or breastfeeding women (see Paricalcitol Normon contains ethanol and propylene glycol).

Consult your doctor, nurse, or pharmacist before using any medicine.

Driving and using machines

No studies have been performed on the effects of paricalcitol on the ability to drive or use machines. During treatment with paricalcitol, your ability to drive safely or use heavy machinery may be affected. Paricalcitol may make you feel dizzy, weak, and/or drowsy.

Do not drive or use machines if you have these symptoms.

Paricalcitol Normon contains ethanol and propylene glycol

This medicine contains 12.7% ethanol, which is equivalent to an amount of 100 mg per ampoule. The amount in an ampoule of this medicine is equivalent to less than 2.5 ml of beer or 1 ml of wine.

The small amount of alcohol in this medicine does not produce any noticeable effect.

This medicine contains 400 mg of propylene glycol in each ampoule, equivalent to 400 mg/ml.

3. How to use Paricalcitol Normon

Dosage

Your doctor will use the results of laboratory tests to decide the initial dose suitable for you. Once you have started treatment with Paricalcitol Normon, the dose should 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 Paricalcitol Normon for you.

Paricalcitol Normon 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 Paricalcitol Normon can be introduced directly into the tube being used for your treatment. You will not receive Paricalcitol Normon more frequently than every other day and no more than 3 times a week.

If you use more Paricalcitol Normon than you should

Too much Paricalcitol Normon may cause high levels of calcium (in blood and urine), phosphate, and parathyroid hormone (in blood) that may require treatment.

The symptoms that may appear after receiving an overdose of Paricalcitol Normon are:

• Feeling of weakness and/or drowsiness
• Headache
• Feeling sick
• Dry mouth, constipation
• Pain in muscles and bones
• Unusual taste in the mouth

The symptoms that may appear after a long period of receiving too much Paricalcitol Normon are:

• Loss of appetite
• Drowsiness
• Weight loss
• Irritation in the eyes
• Runny nose
• Itching of the skin
• Feeling of fever
• Loss of sexual appetite
• Severe abdominal pain
• Kidney stones
• Your blood pressure may be affected, and you may be aware of your own heartbeat (palpitations).

Paricalcitol Normon contains 38.6% v/v propylene glycol as an excipient. Isolated cases of toxic effects related to the administration of high doses of propylene glycol have been reported, although they are not expected when administered to patients undergoing treatment with a kidney machine because propylene glycol is eliminated from the blood during dialysis.

If you experience high levels of calcium in the blood after using Paricalcitol Normon, 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 administered low doses of Paricalcitol Normon.

However, your doctor will monitor your blood levels, and if you experience any of the symptoms mentioned, seek medical advice immediately.

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

4. Possible side effects

Like all medicines, Paricalcitol Normon can cause side effects, although not everybody gets them.

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

• Shortness of breath
• Difficulty breathing and swallowing
• Wheezing
• Rash, itching of the skin, 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:

The most common side effects (at least 1 in 100 patients) are:

• Headache;
• Unusual taste in the mouth;
• Itching of the skin;
• Decrease in parathyroid hormone levels;
• Increase in calcium (feeling sick, constipated, or confused) and phosphate levels in the blood (probably asymptomatic but may make bones susceptible to fracture).

Uncommon (at least 1 in 1000 patients):

• Allergic reactions (such as difficulty breathing, wheezing, rash, itching, or swelling of the face and lips); blistering with itching;
• Blood infection, decrease in the number of red blood cells (anaemia – feeling of weakness, difficulty breathing, paleness); decrease in the number of white blood cells (increased susceptibility to infections), inflammation of neck, armpit, and/or groin lymph nodes; increase in bleeding time (blood will not clot quickly);
• Heart attack, stroke, chest pain, irregular/rapid heartbeat, decrease in blood pressure, increase in blood pressure
• Coma (deep state of unconsciousness during which a person cannot interact with the environment)
• Unusual tiredness, weakness, dizziness, fainting;
• Pain at the injection site
• Pneumonia (lung infection), fluid in the lungs, asthma, wheezing, cough, difficulty breathing;
• Irritation of the throat, cold, fever, flu-like symptoms, conjunctivitis (itching and crusts on the eyelids), increase in eye pressure, ear pain, nosebleed;
• Nervous tics; confusion, which can be severe (delirium), agitation (feeling of nervousness, anxiety), nervousness, personality disorders (not feeling like oneself);
• Numbness or tingling, decrease in touch, sleep problems, night sweats, muscle spasms in arms and legs, even during sleep;
• Dry mouth, thirst, nausea, difficulty swallowing, vomiting, loss of appetite, weight loss, heartburn, diarrhoea, and stomach pain, constipation: rectal bleeding
• Difficulty having an erection, breast cancer, vaginal infection
• Chest pain, back pain, muscle/joint pain, feeling of heaviness caused by general or localized inflammation in ankles, feet, and legs (oedema); abnormal gait
• Hair loss; excessive hair growth
• Increase in liver enzymes; increase in parathyroid hormone levels, increase in potassium levels in the blood, decrease in calcium levels in the blood.

Frequency not known:

• Swelling of the face, lips, mouth, tongue, and throat that can cause difficulty swallowing or breathing; itching of the skin (hives). Seek medical help immediately.

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

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Spanish Medicines and Healthcare Products Agency website: www.notificaram.es

By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Paricalcitol Normon

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

No special storage conditions are required.

Paricalcitol Normon 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 further information

Composition of Paricalcitol Normon

• The active substance is paricalcitol. Each ml of solution contains 5 micrograms of paricalcitol.
• The other ingredients are: ethanol (alcohol), propylene glycol (E-1520), and water for injections.

Appearance and pack size

Paricalcitol Normon is a clear and colourless aqueous solution, free from visible particles. It is available in packs of 5 ampoules of 1 ml.

Marketing authorisation holder and manufacturer

LABORATORIOS NORMON, S.A.

Ronda de Valdecarrizo, 6 – 28760 Tres Cantos – Madrid (SPAIN)

Date of last revision of this leafletJuly 2014

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

Instructions for healthcare professionals

Paricalcitol Normon 5 micrograms/ml solution for injection

Preparation for solution for injection

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

Compatibility

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

This medicine must not be mixed with other medicines.

Storage and shelf-life

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

This medicine does not require any special storage conditions.

This medicine has a shelf-life of 2 years.

Dosage and administration

Paricalcitol Normon solution for injection is administered through the haemodialysis access.

Adults

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

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, with a maximum frequency of every other day and at any time during dialysis.

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

1. Dose titration:

The currently accepted ranges for PTH in subjects with end-stage renal disease undergoing dialysis are not more than 1.5 to 3 times the upper limit of normal in non-uraemic subjects, 15.9 to 31.8 pmol/l (150-300 pg/ml) for intact PTH. To achieve adequate levels of physiological variables, individualised monitoring and dose titration are necessary.

If hypercalcaemia or a corrected Ca x P product is persistently elevated, greater than 5.2 mmol2/l2 (65 mg2/dl2), the dose should be reduced or interrupted until these parameters normalise.

Then, administration of paricalcitol 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: