ORKAMBI 100 mg/125 mg granules in sachet

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 results in liver blood tests 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 stomach area (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 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 breathor narrowing of the airwayshave been seen in patients when starting treatment with Orkambi, especially in patients with decreased lung function. If your child's lung function is decreased, 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 lens opacity (cataract) in the eyehas 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 must 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 taken 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, ask the 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 the child. Check that your child has 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 taken 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 soft food or liquid suitable for your child's age. The food or liquid should be at room temperature or cooler. 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 of 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 puree), 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 has been 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. You should keep giving the medicine as the doctor has told you, even if your child seems better.

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 taken alone (one of the active substances in Orkambi) are listed below and may occur with Orkambi.

The serious side effectsof Orkambi include increased liver enzymes 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 stomach area (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 sputum

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 levels 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 menstrual bleeding
• 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 younger children than in adults.

Reporting of side effects

If your child experiences any side effects, talk to your child's doctor or pharmacist, even if it is 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 the month shown.

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. This will help protect the environment.

6. Package Contents 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 ingredients are: microcrystalline cellulose; sodium croscarmellose; hypromellose acetate succinate; povidone (K30); and sodium lauryl sulfate (see section 2 “Orkambi contains sodium”).

Product Appearance and Package Contents

Orkambi granules are a white to off-white granule.

The granules are supplied in sachets.

Package 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 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.