Package leaflet: Information for the user

Zemplar 5 micrograms/ml solution for injection Paricalcitol ^{1 2 3 4 5 6 7}

-    If you are taking calcium-based phosphate binders, the doctor may need to adjust your dose.

-    Your doctor will need to do blood tests to monitor your treatment.

Other medicines and Zemplar

Please tell your doctor, nurse or pharmacist if you are taking, have recently taken or might take any other medicines.

Some medicines can affect the action of Zemplar or make side effects more likely. It is particularly important to tell your doctor if you are taking any of the following medicines:

•    to treat fungal infections such as candida or thrush, (i.e., ketoconazole)

•    to treat heart or blood pressure (e.g. digoxin and diuretics or water pills).

•    that contain magnesium (e.g. some types of indigestion medicines called antacids, such as magnesium trislilicate).

•    that contain aluminium (e.g. phosphate-binders, such as aluminium hydroxide).

Ask your doctor, nurse, or pharmacist for advice before taking any medicine.

Zemplar with food and drink

Zemplar may be given with or without food.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or planning to have a baby, ask your doctor for advice before taking this medicine

It is not known if it is safe for pregnant or breast-feeding women to use this medicine. Therefore it should only be used after discussion with your doctor, who will help you make the best decision for you.

Driving and using machines

Whilst you are being treated with Zemplar, your ability to drive safely or use heavy machines may be affected. Zemplar may make you feel dizzy, weak, and/or drowsy.

Do not drive or use machines if you feel these symptoms

Zemplar contains ethanol

This medicinal product contains 20% v/v of ethanol (alcohol). Each dose may contain up to 1.3g ethanol. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breast-feeding women, children and high risk groups such as patients with liver disease or epilepsy.

3. How Zemplar is used

Your doctor will use the results of your laboratory tests to decide the correct starting dose for you. Once treatment with Zemplar has started, the dose may be adjusted, based upon the results of routine laboratory tests. Using your lab results, your doctor will help determine the correct dose of Zemplar for you.

Zemplar will be given by a doctor or nurse while you are having your treatment on the kidney machine. It will be given through the tube (bloodline) that is used to connect you to the machine. You will not need to have an injection because Zemplar can be put directly into the tube that is being used for your treatment. You will not be given Zemplar more frequently than every other day and not more than three times a week.

If you are given too much Zemplar

Too much Zemplar may lead to high levels of calcium (in the blood and urine) and phosphate in the blood that may require treatment. Additionally too much Zemplar may reduce parathyroid hormone levels. Symptoms which can appear soon after receiving too much Zemplar include:

•    feeling weak and/or drowsy

•    headache

•    feeling sick or being sick

•    dry mouth, constipation

•    pain in muscles or bones

•    unusual taste in the mouth

Symptoms which can develop over a longer period of receiving too much Zemplar include:

•    loss of appetite

•    drowsiness

•    weight loss

•    sore eyes

•    runny nose

•    itchy skin

•    feeling hot and feverish

•    loss of sex drive

•    severe abdominal pain

•    kidney stones

•    Your blood pressure may be affected and awareness of your own heartbeat (palpitations) can occur.

Zemplar contains 30% by volume of Propylene glycol as an ingredient. Cases of poisonous effects related to the high doses of Propylene glycol have only rarely been reported and would not be expected when being given to kidney patients on a kidney machine because Propylene glycol is removed from the blood during dialysis .

If you experience high level of calcium in your blood after taking Zemplar, your doctor will ensure you receive the appropriate treatment to return your calcium to normal limits. Once your calcium levels return to normal limits, you maybe given Zemplar at a lower dose.

The following information is intended for healthcare professionals only:

Zemplar 5 microgram/ml solution for injection Preparation of solution for injection

Zemplar 5 microgram/ml solution for injection is intended for single use only. As with all drugs administered through injection, the diluted solution should be inspected for particles and discoloration, prior to administration.

Compatibility

Propylene glycol interacts with heparin and neutralises its effect. Zemplar solution for injection contains propylene glycol as an excipient and should be administered through a different injection port than heparin.

This medicinal product must not be mixed with other medicinal products.

Storage and shelf life

Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration. The solution is clear and colourless.

This medicinal product does not require any special storage conditions.

This medicinal product has a shelf life of 2 years.

Posology and Method of Administration

Zemplar solution for injection is administered via haemodialysis access.

Adults

1) 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 intactPT}_^{H level} In ^pmol/l OR

= baseline intact PTH level in pg/mL = 80

and administered as an intravenous (IV) bolus dose no more frequently then every other day at any time during dialysis.

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

However, your doctor will be checking your blood levels and if you experience any of the above seek medical advice immediately.

4. Possible side effects

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

Various allergic reactions have been seen with Zemplar. Important: Tell your doctor or nurse immediately if you notice any of the following side effects:

•    Shortness of breath

•    Difficulty breathing or swallowing

•    Wheezing

•    A rash, itchy 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:

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

-    headache

-    unusual taste in the mouth

-    itchy skin

-    low levels of parathyroid hormone

-    high levels of calcium (feeling sick or being sick, constipated or confused); phosphorous in the blood (probably no symptoms but it can make bones more likely to break)

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

-    allergic reactions (such as shortness of breath, wheezing, rash, itching or swelling of the face and lips); itchy blisters

-    blood infection; decreased number of red cells (anaemia - feeling weak, shortness of breath, looking pale); decreased number of white cells (more likely to get infections); swollen glands in the neck, armpit and/or groin; increased bleeding time (blood will not clot so quickly)

-    heart attack; stroke; chest pain; irregular/fast heartbeat; low blood pressure; high blood pressure;

-    injection site pain

-    pneumonia (lung infection); fluid on the lungs; asthma (wheezing, cough, difficulty breathing);

-    sore throat; cold; fever; flu-like symptoms; pink eye (itchy/crusty eyelids); increased pressure in the eye; earache; nose bleeds

-    nervous twitches; confusion, which is sometimes severe (delirium); agitation (feeling jittery, anxious); nervousness; personality disorders (not feeling like yourself);

-    tingling or numbness; decreased touch sensation; problems sleeping; sweating at night; muscular spasms in arms and legs, even during sleep;

-    dry mouth; thirsty; nausea; diffculty swallowing; vomiting; loss of appetite; weight loss; heart burn; diarrhoea and stomach ache; constipation: bleeding from the rectum;

-    difficulty having an erection; breast cancer; infections in the vagina

-    breast pain; back pain; joint/muscular pain; feeling of heaviness caused by general swelling or localised swelling of the ankles, feet and legs (oedema); abnormal way of walking;

-    hair loss; excessive hair growth,

-    increase of a liver enzyme; high levels of parathyroid hormones; high levels of potassium in the blood; low levels of calcium in the blood

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

-    swelling of the face, lips, mouth, tongue or throat which may cause difficulty in swallowing or breathing; itchy skin (hives) , Stomach bleeding . Get medical help immediately

You may not be able to tell if you have some of the side effects listed above unless you

are told so by your doctor.

If any of the side effects get serious, or if you notice any side effects not listed in this

leaflet, please tell your doctor, nurse or pharmacist immediately.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly (see details below)

Ireland:

Healthcare professionals are asked to report any suspected adverse reactions via HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

United Kingdom:

Yellow Card Scheme

Website: www.mhra.gov.uk/yellowcard

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

5.    How to store Zemplar

Keep this medicine out of the sight and reach of children

This medicinal product does not require any special storage conditions.

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 refers to the last date of that month.

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

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help to protect the environment.

6.    Contents of the pack and further information What Zemplar contains

-    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. What Zemplar looks like and contents of the pack

Marketing Authorisation Holder and Manufacturer Marketing Authorisation Holder:

In Ireland; AbbVie Limited, Citywest Business Campus, Dublin 24, Ireland In the UK; AbbVie Ltd., Maidenhead, SL6 4UB, UK

Vial manufacturer:

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

This leaflet was last approved in February 2016

-    coma (a deep state of unconsciousness during which the person cannot respond to the environment)

-    unusual tiredness, weakness; dizziness; fainting

The following table is a suggested approach for dose titration:

Suggested Dosing Guidelines (Dose adjustments at 2 to 4 week intervals)
iPTH Level Relative to Baseline	Paricalcitol Dose Adjustment
Same or increased	Increase by 2 to 4 micrograms
Decreased by < 30%
Decreased by > 30%, < 60%	Maintain
Decreased > 60%	Decrease by 2 to 4 micrograms
IPTH < 15.9 pmol/l (150 pg/mL)

# 10000000136686.indd 2 16.02.16 10:21

1

What is in this leaflet:

2

   What Zemplar is and what it is used for

3

   What you need to know before you are given Zemplar

4

   How Zemplar is used

5

   Possible side effects

6

   How to store Zemplar

7

   Contents of the pack and other information

1.    What Zemplar is and what is it used for

Zemplar is a synthetic analogue of activated vitamin D that is used to prevent and treat high levels of parathyroid hormone in the blood in people who have kidney failure and are being treated on a kidney machine (haemodialysis). High levels of parathyroid hormone can be caused by low levels of “activated” vitamin D in patients with kidney failure.

Activated vitamin D is required for normal functioning of many tissues of the body, including the kidneys and bones.

2.    What you need to know before you are given Zemplar You should not be given 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 your blood. Your doctor will monitor your blood levels and be able to tell you if these conditions apply to you

Warnings and precautions

-    Before the treatment begins, it is important to limit the amount of phosphorus in your diet. Examples of foods high in phosphorous include tea, soda, beer, cheese, milk, cream, fish, chicken or beef liver, beans, peas, cereals, nuts, and grains.

-    Phosphate-binding medicines, which keep phosphate from being absorbed from your food, may be needed to control phosphorus levels.