Orkambi 100 mg/125 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the patient

Orkambi 100 mg/125 mg film-coated tablets

Orkambi 200 mg/125 mg film-coated tablets

lumacaftor/ivacaftor

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you. It may harm them.
• If you experience side effects, consult your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Orkambi is and what it is used for

2. What you need to know before taking Orkambi

3. How to take Orkambi

4. Possible side effects

5. How to store Orkambi

6. Contents of the pack and other information

1. What Orkambi is and what it is 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 6 years and older who have a specific genetic change (called the F508del mutation) in the gene for a protein known as the cystic fibrosis transmembrane conductance regulator (CFTR), which plays an important role in regulating the flow of mucus in the lungs. People with this mutation produce an abnormal CFTR protein. Cells contain two copies of the CFTR gene. Orkambi is used in patients in whom 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 work more normally.

Orkambi may help you breathe better by improving your lung function. You may also find it easier to gain weight.

2. What you need to know before taking Orkambi

Do not take Orkambi

• if you are 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 doctor or pharmacist before starting to take Orkambi.

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

Talk to your doctor before taking Orkambi if you have been diagnosed with hepatic or renal disease, as your doctor may need to adjust your dose of Orkambi.

Abnormal liver test results in blood tests have been frequently observed in some people taking Orkambi. Contact your doctor immediately if you experience any of the following symptoms, which could indicate liver problems:

• Pain or discomfort in the upper right part of the stomach (abdomen)
• Yellowing of the skin or whites of the eyes
• Loss of appetite
• Nausea or vomiting
• Dark urine
• Confusion

Your doctor should perform blood tests to monitor your liver function before and during treatment with Orkambi, especially during the first year.

Depression (including suicidal thoughts and suicidal behaviour) has been reported in patients taking Orkambi, usually occurring within the first three months of treatment. Contact your doctor immediately if you (or someone taking this medicine) experience any of the following symptoms: sad or changed mood, anxiety, feeling of emotional distress, or thoughts of self-harm or suicide, which may be signs of depression.

Respiratory events such as difficulty breathing, chest tightness, or airway constriction have been observed in patients starting treatment with Orkambi, particularly in those with impaired lung function. If you have impaired lung function, your doctor may monitor you closely when starting Orkambi treatment.

An increase in blood pressure has been observed in some patients treated with Orkambi. Your doctor may monitor your blood pressure during treatment with Orkambi.

In some children and adolescents treated with Orkambi and ivacaftor alone (one of the components of Orkambi), an eye lens abnormality (cataract) has been observed without any effect on vision. Your doctor may perform eye examinations before and during treatment with Orkambi.

Orkambi is not recommended for patients who have undergone organ transplantation.

Children under 6 years of age

Orkambi tablets must not be used in children under 6 years of age. Other formulations of the medicine (granules in a sachet) are more suitable for children under 6 years of age; please consult your doctor or pharmacist.

Other medicines and Orkambi

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

In particular, inform your doctor if you are taking any of the following medicines:

• Antibiotics (used to treat bacterial infections), for example:

telithromycin, clarithromycin, rifampicin, rifabutin, rifapentine, erythromycin

• Anticonvulsants (used to treat seizures [epileptic fits]), for example:

phenobarbital, carbamazepine, phenytoin

• Benzodiazepines (used to treat anxiety, insomnia, agitation, etc.), for example:

midazolam, triazolam

• Antifungals (used to treat fungal infections), for example:

fluconazole, ketoconazole, itraconazole, posaconazole, voriconazole

• Immunosuppressants (used after organ transplantation), for example: cyclosporine, everolimus, sirolimus, tacrolimus
• Herbal medicines, for example:

St. John’s wort (Hypericum perforatum)

• Antihistamines (used to treat allergies and/or asthma), for example:

montelukast, fexofenadine

• Antidepressants (used to treat depression), for example:

citalopram, escitalopram, sertraline, bupropion

• Anti-inflammatory medicines, for example:

ibuprofen

• H2 antagonists (used to reduce stomach acid), for example: ranitidine
• Cardiac glycosides (used to treat mild to moderate congestive heart failure and abnormal heart rhythm called atrial fibrillation), for example:

digoxin

• Anticoagulants (used to prevent blood clots from forming or getting larger in the blood and blood vessels), for example:

warfarin, dabigatran

• Contraceptives (used to prevent pregnancy):

oral, injectable, and implantable contraceptives as well as contraceptive patches; these may contain ethinylestradiol, norethindrone, and other progestogens. These should not be considered a reliable effective contraceptive method when administered 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

False positive results in urine screening tests for tetrahydrocannabinol (THC, an active component in cannabis) have been reported in patients receiving Orkambi. Your doctor may request additional testing to confirm the results.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor before using this medicine. It may be preferable, if possible, to avoid using Orkambi during pregnancy, and your doctor will help you decide what is best for you and your baby.

Ivacaftor and lumacaftor are excreted in breast milk. If you plan to breastfeed, consult your doctor before taking Orkambi. Your doctor will decide whether to recommend discontinuing breastfeeding or stopping treatment with lumacaftor/ivacaftor, taking into account the benefits of breastfeeding for the child and the benefits of treatment for you.

Driving and use of machines

Dizziness has been reported in patients receiving ivacaftor, a component of Orkambi, which could affect the ability to drive and operate machinery. If you experience dizziness, you should not drive or operate machinery until these symptoms resolve.

If a child experiences dizziness while taking Orkambi, it is advised that the child should not ride a bicycle or perform any activity requiring full attention until the symptoms have resolved.

Orkambi contains sodium

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

3. How to take Orkambi

Follow exactly the instructions given by your doctor for taking this medicine.

If in doubt, consult your doctor again.

Recommended dose

The recommended dose for patients aged 6 years and older is two tablets in the morning and two tablets in the evening (every 12 hours). This amounts to a total of four tablets per day, which should be taken with food containing fat.

There are different tablet strengths of Orkambi available for different age groups.

Make sure you have been prescribed the correct tablet (see below).

You may start taking Orkambi on any day of the week.

If you have moderate or severe liver problems, your doctor may need to reduce your dose of Orkambi, as your liver will not eliminate Orkambi from your body as quickly as in people with normal liver function.

• Moderate liver problems: the dose may be reduced to two tablets in the morning and one tablet in the evening.
• Severe liver problems: the dose may be reduced to one tablet in the morning and one tablet in the evening. Your doctor may decide to further adjust the dosing frequency based on clinical response and tolerability.

Method of administration

Orkambi is taken orally. Swallow the tablets whole. Do not chew, break, or dissolve the tablets.

It is important to take Orkambi with food containing fat to achieve adequate levels of the medicine in your body. A meal or snack containing fat should be taken just before or just after taking Orkambi. Meals and snacks recommended in cystic fibrosis (CF) guidelines or those recommended in standard nutritional guidelines contain adequate amounts of fat. Examples of meals or snacks containing fat include those prepared with butter or oils, or those containing eggs. Other examples of foods containing fat are:

• Cheese, whole milk, full-fat dairy products
• Meats, fatty fish
• Avocado, hummus (chickpea purée), soy-based products (tofu)
• Nutritional bars or nutritional drinks

If you take more Orkambi than you should

Consult your doctor or pharmacist for advice. If possible, show them the medicine and this leaflet. You may experience adverse effects, including those listed in section 4 below.

If you forget to take Orkambi

Take the missed dose with food containing fat if less than 6 hours have passed since the time you were supposed to take the tablet. Otherwise, wait until it is time for your next scheduled dose. Do not take a double dose to make up for a missed dose.

If you stop taking Orkambi

You should continue taking the medicine as directed by your doctor, even if you feel well.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone will experience them. The adverse effects reported with Orkambi and with ivacaftor administered alone (one of the active substances in Orkambi) are listed below and may occur with the use of Orkambi.

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

Contact your doctor immediately if you experience any of the following symptoms:

• Pain or discomfort in the upper right part of the stomach (abdominal area)
• Yellowing of the skin or the whites of the eyes
• Loss of appetite
• Nausea or vomiting
• Confusion
• Dark-colored urine

Depression

Signs of depression include a sad or depressed mood, anxiety, or a feeling of emotional discomfort.

Contact your doctor immediately if you experience any of these symptoms.

Other adverse effects

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

• Cough with phlegm
• Nasal congestion
• Difficulty breathing
• Headache
• Abdominal pain (stomach ache)
• Diarrhea
• Increased amount of phlegm
• Nausea
• Common cold*
• Dizziness*
• Changes in the type of bacteria in 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*
• Skin rash
• Gas (flatulence)
• Vomiting
• Increase in an enzyme in the blood (creatine phosphokinase in blood)
• High levels of liver enzymes (detected in blood tests)
• Irregular periods (menstruation) or painful menstruation
• Ear pain, ear discomfort*
• Ringing in the ears*
• Redness inside the ears*
• Inner ear disorder (sensation of dizziness or spinning)*
• Lump in the breast*

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

• Abnormal periods including absence of menstruation, infrequent menstruation, or more frequent or heavier menstrual bleeding
• Increased blood pressure
• Ear blockage*
• Breast inflammation*
• Enlargement of the breasts in males*
• Changes or pain in the nipples

*Adverse effects observed with ivacaftor alone.

Additional adverse effects in children

Adverse effects observed in children are similar to those observed in adults and adolescents. However, increased liver enzymes in the blood are more frequent in young children than in adults.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Orkambi

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

Do not use this medicine after the expiry date stated on the carton/blister after CAD/EXP. The expiry date is the last day of the month indicated.

This medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer needed. This will help protect the environment.

6. Contents of the pack and other information

Composition of Orkambi

The active substances are lumacaftor and ivacaftor.

Orkambi 100 mg/125 mg film-coated tablets:

Each film-coated tablet contains 100 mg of lumacaftor and 125 mg of ivacaftor.

Orkambi 200 mg/125 mg film-coated tablets:

Each film-coated tablet contains 200 mg of lumacaftor and 125 mg of ivacaftor.

Orkambi 100 mg/125 mg film-coated tablets and Orkambi 200 mg/125 mg film-coated tablets:

The other components are:

• Tablet core: microcrystalline cellulose; sodium croscarmellose; hypromellose acetate succinate; povidone (K30); sodium lauryl sulfate; and magnesium stearate (see section 2 “Orkambi contains sodium”).
• Tablet coating: polyvinyl alcohol; titanium dioxide (E171); macrogol 3350; talc; carmine (E120); brilliant blue FCF aluminium lake (E133); and indigo carmine aluminium lake (E132).
• Printing ink: shellac; black iron oxide (E172); propylene glycol; and ammonium hydroxide.

Nature and contents of the container

Orkambi 100 mg/125 mg film-coated tablets

Orkambi 100 mg/125 mg film-coated tablets are pink, oblong tablets (dimensions 14 x 7.6 x 4.9 mm), printed with “1V125” in black ink on one side.

Orkambi 100 mg/125 mg is available in packs of 112 film-coated tablets (4 packs of 28 film-coated tablets).

Orkambi 200 mg/125 mg film-coated tablets

Orkambi 200 mg/125 mg film-coated tablets are pink, oblong tablets (dimensions 14 x 8.4 x 6.8 mm), printed with “2V125” in black ink on one side.

Orkambi 200 mg/125 mg is available in multiple packs of 112 film-coated tablets (4 packs of 28 film-coated tablets).

Only certain pack sizes may be marketed.

Marketing Authorisation 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 on this medicinal product is available upon request from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Other sources of information

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