ORKAMBI 75 mg/94 mg granules in sachet

Introduction

Package Leaflet: Information for the Patient

Orkambi 75 mg/94 mg Granules in Sachet

Orkambi 100 mg/125 mg Granules in Sachet

Orkambi 150 mg/188 mg Granules in Sachet

lumacaftor/ivacaftor

Read all of this leaflet carefully before your child starts taking 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 child's doctor or pharmacist.
• This medicine has been prescribed for your child only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as your child's.
• If your child gets any side effects, talk to your child's doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

1. What is Orkambi and what is it used for
2. What you need to know before your child starts taking Orkambi
3. How to take Orkambi
4. Possible side effects
5. Storing Orkambi
6. Contents of the pack and other information

1. What is Orkambi and what is it used for

Orkambi contains two active substances: lumacaftor and ivacaftor. It is a medicine used for the long-term treatment of cystic fibrosis (CF) in patients aged 1 year and older who have a specific change (called the F508del mutation) in the gene for a protein called cystic fibrosis transmembrane conductance regulator (CFTR), which plays an important role in regulating the flow of mucus in the lungs. People with this mutation will produce abnormal CFTR protein. Cells contain two copies of the CFTR gene. Orkambi is used in patients where the F508del mutation affects both copies (homozygous).

Lumacaftor and ivacaftor work together to improve the function of the abnormal CFTR protein.

Lumacaftor increases the amount of CFTR available and ivacaftor helps the abnormal protein to work more normally.

2. What you need to know before your child starts taking Orkambi

Do not use Orkambi

• if your child is allergic to the active substances or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your child's doctor or pharmacist before your child starts taking Orkambi.

Orkambi must not be used in patients who do not have two copies of the F508del mutationin the CFTR gene.

Talk to your child's doctor before your child starts taking Orkambi if your child has been told they have liver or kidney disease, as the doctor may need to adjust the dose of Orkambi.

Abnormal liver blood test results have been commonly seen in some people taking Orkambi. If your child has any of the following symptoms, which could be signs of liver problems, tell your child's doctor right away:

• Pain or discomfort in the upper right side of the stomach (abdomen)
• Yellowing of the skin or the white part of the eyes
• Lack of appetite
• Feeling sick (nausea) or being sick (vomiting)
• Dark urine
• Confusion

Your child's doctor should do blood tests to check how well your child's liver is working before and while your child is taking Orkambi, especially during the first year.

Respiratory events such as difficulty breathing or shortness of breath or narrowing of the airwayshave been seen in patients when starting treatment with Orkambi, especially in patients with poor lung function. If your child's lung function is poor, your child's doctor may keep a close eye on them when starting treatment with Orkambi.

An increase in blood pressurehas been seen in some patients taking Orkambi. Your child's doctor may keep a close eye on your child's blood pressure during treatment with Orkambi.

In some children and adolescents taking Orkambi and ivacaftor alone (one of the ingredients in Orkambi), a clouding of the lens in the eye (cataract)has been seen without any effect on vision. Your child's doctor may do some eye examinations before and during treatment with Orkambi.

Orkambi is not recommended in patients who have had an organ transplant.

Children under 1 year of age

It is not known if Orkambi is safe and effective in children under 1 year of age. Therefore, Orkambi should not be used in children under 1 year of age.

Other medicines and Orkambi

Tell your child's doctor or pharmacist if your child is taking, has recently taken or might take any other medicines.

In particular, tell the doctor if your child is taking any of the following medicines:

• Antibiotics (used to treat infections caused by bacteria), such as:

telithromycin, clarithromycin, rifampicin, rifabutin, rifapentine, erythromycin

• Anticonvulsants (used to treat seizures [epileptic fits]), such as:

phenobarbital, carbamazepine, phenytoin

• Benzodiazepines (used to treat anxiety, insomnia, agitation, etc.), such as:

midazolam, triazolam

• Antifungals (used to treat fungal infections), such as:

fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole

• Immunosuppressants (used after an organ transplant), such as:

ciclosporin, everolimus, sirolimus, tacrolimus

• Herbal medicines, such as:

St John's Wort (Hypericum perforatum)

• Antihistamines (used to treat allergies and/or asthma), such as:

montelukast, fexofenadine

• Antidepressants (used to treat depression), such as:

citalopram, escitalopram, sertraline, bupropion

• Anti-inflammatory medicines (used to treat inflammation), such as:

ibuprofen

• H2 antagonists (used to reduce acid in the stomach), such as:

ranitidine

• Cardiac glycosides (used to treat mild or moderate heart failure and abnormal heart rhythm called atrial fibrillation), such as:

digoxin

• Anticoagulants (used to prevent blood clots from forming or getting bigger in the blood and blood vessels), such as:

warfarin, dabigatran

• Contraceptives (used to prevent pregnancy):

oral, injectable and implantable contraceptives as well as contraceptive patches; may include ethinylestradiol, norethindrone and other progestogens. These should not be considered a reliable method of contraception when given with Orkambi.

• Corticosteroids (used to treat inflammation):

methylprednisolone, prednisone

• Proton pump inhibitors (used to treat acid reflux disease and ulcers):

omeprazole, esomeprazole, lansoprazole

• Oral hypoglycaemics (used to treat type 2 diabetes):

repaglinide

There have been reports of false positive results in urine tests for tetrahydrocannabinol (THC, an active component in cannabis) in patients taking Orkambi. Your child's doctor may request another test to confirm the results.

Driving and using machines

Dizziness has been reported in patients who received ivacaftor, a component of Orkambi, which may affect the ability to drive and use machines.

If your child experiences dizziness while taking Orkambi, it is recommended that your child does not ride a bicycle or do anything that requires full attention until the symptoms go away.

Orkambi contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per dose; this is essentially “sodium-free”.

3. How to take Orkambi

Follow the instructions for administration of this medicine exactly as told by your child's doctor. If you are not sure, talk to your child's doctor again.

Your child's doctor will decide the correct dose for your child. Your child should keep using all their other medicines unless the doctor tells them to stop taking any.

Recommended dose

The recommended dose for patients aged 1 year and older is shown in the following table. Orkambi should be taken in the morning and in the evening (every 12 hours) with fat-containing foods.

There are different strengths of Orkambi depending on the age and weight of your child. Check that you have been prescribed the correct dose (below).

If your child has moderate or severe liver problems, the doctor may need to reduce the dose of Orkambi, as your child's liver will not get rid of Orkambi from their body as quickly as in children with normal liver function.

• Moderate liver problems: the dose may be reduced to one sachet per day in the morning and one sachet every other day in the evening.
• Severe liver problems: the dose may be reduced to one sachet per day or less often in the morning. No dose should be given in the evening.

Method of administration

Orkambi is taken by mouth.

Each sachet is for single use only.

You can start giving Orkambi to your child on any day of the week.

Administration of Orkambi granules to your child:

• Hold the sachet of granules with the tear line facing upwards.
• Gently shake the sachet to settle the contents.

• Open the sachet by tearing or cutting along the tear line.
• Mix all the contents of one sachet with a teaspoon (5 ml) of a soft food or liquid suitable for your child's age. The food or liquid should be at room temperature or cooler. Some examples of soft foods or liquids suitable for your child's age include fruit or vegetable puree, flavoured yoghurt, apple sauce, water, milk, breast milk, formula milk or juice.
• Once mixed, give the medicine to your child right away. If this is not possible, give it within the next hour after mixing. Make sure your child takes all the mixture right away.
• Just before or just after administration, you should give your child a food or snack that contains fat (some examples are given below).

It is important to take Orkambi with fat-containing foodsto get the right levels of the medicine in the body. Meals and snacks recommended in the cystic fibrosis guidelines or meals recommended in standard nutritional guidelines contain the right amounts of fat. Examples of fat-containing foods or snacks are those made with butter or oils or those that contain eggs. Other examples of fat-containing foods are:

• Cheese, breast milk, formula milk, whole milk, whole milk dairy products
• Meat, oily fish
• Avocado, hummus (chickpea paste), soy products (tofu)
• Nutritional bars or drinks

If your child takes more Orkambi than they should

Talk to your child's doctor or pharmacist for advice. If possible, show them the medicine and this leaflet. Your child may experience side effects, including those listed in section 4 below.

If you forget to give Orkambi to your child

Give the missed dose with fat-containing foods if it is less than 6 hours since the time your child was supposed to take the granules. Otherwise, wait until it is time for your child's next dose. Do not give your child a double dose to make up for a missed dose.

If you stop giving Orkambi to your child

Give Orkambi to your child for as long as the doctor has told you to.

Do not stop treatment unless the doctor tells you to. Your child should keep taking the medicine as the doctor has prescribed, even if they feel well.

If you have any other questions about the use of this medicine, ask your child's doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. The side effects reported with Orkambi and ivacaftor given alone (one of the active substances in Orkambi) are listed below and may occur with Orkambi.

Serious side effectsof Orkambi include increased liver enzyme levels in the blood, liver damage and worsening of existing severe liver disease. Worsening of liver function can be fatal. These serious side effects are uncommon (may affect up to 1 in 100 people).

Tell your child's doctor right awayif your child experiences:

• Pain or discomfort in the upper right side of the stomach (abdomen)
• Yellowing of the skin or the white part of the eyes
• Lack of appetite
• Feeling sick (nausea) or being sick (vomiting)
• Confusion
• Dark urine

Other side effects

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

• Cough with phlegm
• Nasal congestion
• Difficulty breathing
• Headache
• Abdominal pain (stomach pain)
• Diarrhoea
• Increased amount of phlegm
• Feeling sick (nausea)
• Common cold
• Dizziness
• Changes in the type of bacteria in the mucus

Common(may affect up to 1 in 10 people)

• Chest tightness
• Narrowing of the airways
• Sinus congestion
• Nasal congestion or runny nose
• Upper respiratory tract infection
• Sore throat
• Redness of the throat
• Rash
• Wind
• Being sick (vomiting)
• Increased level of an enzyme in the blood (creatine phosphokinase in blood)
• High levels of liver enzymes (detected in blood tests)
• Irregular or painful menstrual periods
• Ear pain, discomfort in the ear
• Ringing in the ears
• Redness inside the ears
• Inner ear disorder (feeling of dizziness or spinning)
• Lump in the breast

Uncommon(may affect up to 1 in 100 people)

• Abnormal menstrual periods, including absence of periods or infrequent periods, or more frequent or heavier periods
• Increased blood pressure
• Ear blockage
• Breast inflammation
• Breast enlargement in men
• Changes or pain in the nipples

*Side effects seen with ivacaftor alone.

Additional side effects in children

The side effects seen in children are similar to those seen in adults and adolescents. However, increased liver enzymes in the blood are more common in young children than in adults.

Reporting of side effects

If your child experiences any side effects, talk to your child's doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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. Storing Orkambi

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 carton/sachet after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your child's pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Container Content and Additional Information

Orkambi Composition

The active ingredients are lumacaftor and ivacaftor.

Orkambi 75 mg/94 mg granules in sachet:

Each sachet contains 75 mg of lumacaftor and 94 mg of ivacaftor.

Orkambi 100 mg/125 mg granules in sachet:

Each sachet contains 100 mg of lumacaftor and 125 mg of ivacaftor.

Orkambi 150 mg/188 mg granules in sachet:

Each sachet contains 150 mg of lumacaftor and 188 mg of ivacaftor.

The other components are: microcrystalline cellulose; sodium croscarmellose; hypromellose acetate succinate; povidone (K30); and sodium lauryl sulfate (see section 2 “Orkambi contains sodium”).

Product Appearance and Container Content

Orkambi granules are white to off-white granules.

The granules are supplied in sachets.

Container size of 56 sachets (contains 4 individual blister packs with 14 sachets each)

Marketing Authorization Holder

Vertex Pharmaceuticals (Ireland) Limited

Unit 49, Block 5, Northwood Court, Northwood Crescent,

Dublin 9, D09 T665,

Ireland

Tel.: +353 (0)1 761 7299

Manufacturer

Almac Pharma Services (Ireland) Limited

Finnabair Industrial Estate

Dundalk

Co. Louth

A91 P9KD

Ireland

Almac Pharma Services Limited

Seagoe Industrial Estate

Craigavon

BT63 5UA

United Kingdom

Further information about this medicinal product can be obtained from the local representative of the marketing authorization holder:

Date of the Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.