NATPAR 25 micrograms/dose powder and solvent for injectable solution

2. What you need to know before you use Natpar

Do not use Natpar

• if you are allergic to parathyroid hormone or any of the other ingredients of this medicine (listed in section 6).
• if you are receiving or have received radiation therapy to the bones
• if you have bone cancer or other cancer that has spread to the bones
• if you have a higher risk of developing a type of bone cancer called osteosarcoma (for example, if you have Paget's disease or other bone diseases)
• if a blood test shows that you have unexplained increases in bone alkaline phosphatase
• if you have pseudohypoparathyroidism, a rare condition in which the body does not respond properly to parathyroid hormone produced by the body

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Natpar.

If you are being treated with Natpar, you may experience side effects related to low or high calcium levels in the blood (see these side effects in section 4).

These effects are more likely to occur:

• when starting treatment with Natpar;
• if you change the dose of Natpar;
• if you miss one of the daily injections;
• or if you stop using Natpar for a short or long period.

You may be given medicines to treat these side effects or to help prevent them, or you may be asked to stop taking some of the medicines you are taking. These medicines include calcium or vitamin D.

If your symptoms are severe, your doctor may give you additional medical treatment.

Your doctor will check your calcium levels. You may need to change the dose of Natpar or stop the injections for a short period.

Tests and procedures

Your doctor will monitor how you respond to treatment:

• during the first 7 days after starting treatment and
• if the dose is changed.

This will be done through tests that measure calcium levels in the blood or urine. Your doctor may ask you to change the amount of calcium or vitamin D you take (in any of its forms, including calcium-rich foods).

Talk to your doctor or pharmacist before using Natpar if you have kidney stones.

Children and adolescents

Natpar must not be used in children and adolescents under 18 years.

Other medicines and Natpar

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including:

• digoxin, also known as digitalis, a heart medicine
• medicines for the treatment of osteoporosis, called bisphosphonates, such as alendronic acid
• medicines that may affect calcium levels in the blood, such as lithium or certain medicines used to increase the amount of urine (diuretics).

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. There is limited information on the safety of Natpar in pregnant women. It has been shown that Natpar passes into breast milk in rats, but it is not known if it passes into breast milk in humans.

Your doctor will decide whether it is necessary to start treatment with Natpar. Your doctor will also decide whether you should continue using this medicine if you become pregnant or start breastfeeding during treatment.

The effect of Natpar on fertility is not known.

Driving and using machines

Natpar has no influence on the ability to drive and use machines. However, hypoparathyroidism itself may affect your ability to concentrate. If your ability to concentrate is affected, do not drive or use machines until it has improved.

Natpar contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per dose. This means that it is essentially "sodium-free".

3. How to use Natpar

Follow the instructions for administration of this medicine exactly as told by your doctor or pharmacist. If you are not sure, ask your doctor or pharmacist again. Your doctor or nurse will teach you how to use the Natpar pen.

Natpar is given as a subcutaneous injection (under the skin) every day, using a pen to help inject the medicine.

In this leaflet, the "reusable Natpar pen" is referred to as the "Natpar pen" or "pen".

Dose

The recommended starting dose of Natpar is 50 micrograms per day.

• However, your doctor may tell you to start with 25 micrograms per day based on the results of a blood test.
• After 2 to 4 weeks, your doctor may adjust the dose.

The dose of Natpar varies from person to person. You may need between 25 and 100 micrograms of Natpar per day.

Your doctor may tell you to take other medicines, such as calcium or vitamin D supplements, while you are using Natpar. Your doctor will tell you how much to take per day.

How to use the pen

Read the "Section 7. Instructions for use"of this leaflet before using the pen.

Do not use the pen if the solution is cloudy or colored, or if it contains visible particles.

Before using the pen for the first time, you need to mix the medicine.

Once you have mixed the medicine, the Natpar pen is ready to use and the medicine can be injected under the skin of the thigh. The next day, inject into the other thigh and continue alternating between the two.

Each time you receive a dose of Natpar, it is strongly recommended that you write down the name and batch number of the medicine, in order to keep a record of the batches used.

Duration of treatment

Continue using Natpar for as long as your doctor tells you to.

If you use more Natpar than you should

If you accidentally inject more than one dose of Natpar in a single day, contact your doctor or pharmacist immediately.

If you forget to use Natpar

If you forget to use Natpar (or cannot inject it at the usual time), inject it as soon as you can but do not inject more than one dose on the same day.

Give the next dose of Natpar at the usual time the next day. You may need to take more calcium supplements if you have signs of low calcium levels in the blood; see symptoms in section 4.

Do not inject a double dose to make up for forgotten doses.

If you stop using Natpar

Talk to your doctor if you want to stop using Natpar.

If you have any other questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

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

Serious side effects

The following serious side effects may occur with the use of Natpar:

• Very common: high calcium levels in the blood, which may occur more often when starting treatment with Natpar.
• Very common: low calcium levels in the blood; this may occur more often if you stop using Natpar suddenly.

Symptoms related to high or low calcium levels are listed below. If you experience any of these side effects, talk to your doctor immediately.

Other side effects:

Very common(may affect more than 1 in 10 people):

• headache*,†
• tingling and numbness in the skin†
• diarrhea*,†
• nausea and vomiting*
• joint pain*
• muscle spasms†

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

• nervousness or anxiety†
• sleep problems (daytime sleepiness or difficulty sleeping at night)*
• rapid or irregular heartbeat*,†
• high blood pressure*
• cough†
• stomach pain*
• muscle twitching or cramps†
• muscle pain†
• neck pain†
• arm and leg pain
• increased calcium levels in the urine*
• need to urinate frequently†
• fatigue and lack of energy*
• chest pain
• redness and pain at the injection site
• thirst*
• antibodies (produced by your immune system) against Natpar
• in blood tests, your doctor may see decreased levels of vitamin D and magnesium†

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

• allergic reactions (hypersensitivity), such as: swelling of the face, lips, mouth, or tongue; difficulty breathing; itching; rash; hives
• Seizures (epileptic fits) due to low calcium levels in the blood†

*These side effects may be related to high calcium levels in the blood.

†These side effects may be related to low calcium levels in the blood.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Natpar

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

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

Before mixing

• Store in a refrigerator (between 2°C and 8°C).
• Do not freeze.
• Keep the cartridge in its pen and in the outer packaging to protect it from light.

After mixing

• Store in a refrigerator (between 2°C and 8°C).
• Do not freeze.
• Keep the pen with a mixed cartridge perfectly closed to protect the cartridge from light.
• Do not use this medicine for more than 14 days after it has been mixed.
• Do not use this medicine if it has not been stored correctly.
• Before putting a new needle on the Natpar pen, check that the solution is clear and colorless. It is normal to see small bubbles. Do not use this medicine if it has become cloudy, has changed color, or contains visible particles.

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. Container Contents and Additional Information

Natpar Composition

The active ingredient is parathyroid hormone (rDNA).

It comes in cartridges with 4 different concentrations (each cartridge contains 14 doses):

Natpar 25 micrograms

Each dose contains 25 micrograms of parathyroid hormone in 71.4 microliters of solution after reconstitution.

Natpar 50 micrograms

Each dose contains 50 micrograms of parathyroid hormone in 71.4 microliters of solution after reconstitution.

Natpar 75 micrograms

Each dose contains 75 micrograms of parathyroid hormone in 71.4 microliters of solution after reconstitution.

Natpar 100 micrograms

Each dose contains 100 micrograms of parathyroid hormone in 71.4 microliters of solution after reconstitution.

The other components in the cartridge (for all concentrations) are:

In the powder:

• sodium chloride
• mannitol
• citric acid monohydrate
• sodium hydroxide (for pH adjustment)

In the solvent:

• metacresol
• water for injectable preparations

Appearance of the Product and Container Contents

Each Natpar cartridge contains the medicine in powder form along with a solvent to prepare an injectable solution. The cartridge is made of glass, with a rubber stopper at the top. The cartridge is inside a plastic cartridge holder.

Natpar is available in a package with 2 cartridges in their holders.

The color of the box and the cartridge indicates the concentration of Natpar:

Natpar 25 micrograms/dose

Purple cartridge.

Natpar 50 micrograms/dose

Red cartridge.

Natpar 75 micrograms/dose

Gray cartridge.

Natpar 100 micrograms/dose

Blue cartridge.

Marketing Authorization Holder and Manufacturer

Shire Pharmaceuticals Ireland Limited

Block 2 & 3 Miesian Plaza

50 – 58 Baggot Street Lower

Dublin 2

Ireland

Tel: +44(0)1256 894 959

E-mail: [email protected]

Date of Last Revision of this Leaflet: .

This medicine has been authorized with a «conditional approval». This type of approval means that more information on this medicine is expected.

The European Medicines Agency will review the new information on this medicine at least once a year and this leaflet will be updated as necessary.

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.

1. Instructions for Use

This guide has been designed to help you prepare, inject, and store your Natpar pen.

These instructions are divided into 5 stages

If you need help at any time, contact your doctor, pharmacist, or nurse.

You can also contact Shire at phone +44(0) 1256 894959 or by email at [email protected].

What You Need to Know Before You Start

• DO NOT use your Natpar pen until your doctor or nurse has shown you how to do it.
• Use these instructions for use every time you mix the medicine, prepare the pen, or administer an injection, so you do not forget to carry out any of the steps.
• A new needle must be placed on the pen every day.
• A new cartridge must be prepared once every 14 days.
• DO NOT use this medicine if you notice that it has become cloudy, has changed color, or contains visible particles.
• Always keep the cartridge in the refrigerator (between 2°C and 8°C).
• DO NOT freeze the cartridge.
• DO NOT use a cartridge that has been frozen.
• Discard all mixed cartridges that are more than 14 days old.
• Administer your dose only once a day.
• To clean the Natpar pen, wipe the outside of the pen with a damp cloth. DO NOT put the pen in water, nor wash it or clean it with any liquid.
• Discard the used Natpar cartridge and the used needles according to the instructions of your doctor, pharmacist, or nurse.
• Your Natpar pen can be reused for a maximum of 2 years.

Get to Know the Parts of the Natpar Pen

Parts of the Natpar pen

Note:the needle guard (simulated cartridge) protects the needle during shipping from the factory. Discard the needle guard when you are ready to use the pen.