Orkambi - Lumacaftor / Ivakaftor uses, dose and side effects

Orkambi contains two active substances, luma kaftar and ivakaftar. It is a drug used for the long-term treatment of cystic fibrosis (CF) in patients aged 6 years and older with a specific change (called F508del – mutation ) in the gene for a protein called CFTR (which stands for Cystic Fibrosis Transmembrane Conductance Regulator) and is important for the regulation of mucus in the lungs. In people with mutation one, the CFTR protein is formed abnormally. The cells contain two copies of the CFTR gene. Orkambi is used in patients in whom both copies have F508del – mutation one (homozygous is).

Luma caftans and ivakaftor work together to make the abnormal CFTR protein work better. Lumacaftor increases the amount of CFTR and ivacaftor helps the abnormal protein to function more normally.

Orkambi can make it easier to breathe by improving your lung function. It may also be easier to gain weight.

What you need to know before using Orkambi

Do not use Orkambi

if he/she is allergic to luma caftans, ivacaftor, or any of the other ingredients of this medicine (listed in section 6).

Warnings and cautions

Talk to your doctor or pharmacist before taking Orkambi.

Orkambi should not be used by patients other than those who have two copies of the F508del mutation one in their CFTR gene.

Talk to your doctor if you have been told that you have liver or kidney disease, as your doctor may need to adjust the dose of Orkambi.

Abnormal results have often been seen on liver tests in some people who receive Orkambi. Tell your doctor immediately if you have any of these symptoms, which may be signs of liver problems:

Pain or discomfort in the upper right part of the abdomen
Yellowing of the skin or whites of the eyes
Poor appetite
Nausea or vomiting
Dark colored urine
Confusion

Your doctor will take some blood samples to check your liver while you are taking Orkambi, especially during the first year.

Breathing problems have been seen such as shortness of breath or pressure over the chest or that the airways become narrower in some patients when they have started taking Orkambi, especially in patients with poor lung function. If you have poor lung function, your doctor may monitor you more closely when you start taking Orkambi.

An increase in blood pressure has been seen in some patients treated with Orkambi. Your doctor may need to check your blood pressure during treatment with Orkambi.

Changes in the lens of the eye (cataracts) that do not affect vision have been noted in some children and adolescents treated with Orkambi and ivakaftor only (one of the components in Orkambi).

Your doctor may perform an eye examination before and during treatment with Orkambi.

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

Children and young people

Orkambi tablets should not be used in children under 6 years of age. There are other forms of medicine ( granules in sachets ) that are more suitable for children under 6 years. Ask a doctor or pharmacist.

Other medicines and Orkambi

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

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

Antibiotics (used to treat bacterial infections), for example:telithromycin, clarithromycin, rifampicin, rifabutin, rifapentin, erythromycin
Anticonvulsant drugs (used to treat epileptic seizures), for example: phenobarbital, carbamazepine, phenytoin
Benzodiazepines (used to treat anxiety or insomnia (difficulty falling asleep), anxiety, etc., for example: midazolam, triazolam
Antifungals (used to treat fungal infections), for example:fluconazole , ketoconazole , itraconazole, posaconazole, voriconazole
Immunosuppressive drugs (used after an organ transplant), for example: ciclosporin, everolimus, sirolimus, tacrolimus
Traditional herbal medicines, for example: St. John’s wort ( Hypericum perforatum )
Antiallergic drugs (used to treat allergies or asthma ), for example: montelukast, fexofenadine
Antidepressants (used to treat depression), for example: citalopram , escitalopram, sertraline , bupropion
Anti-inflammatory drugs (used to treat inflammation ), for example: ibuprofen
H2 antagonist (used to reduce stomach acid), for example: ranitidine
Cardiac glycosides (used to treat mild to moderate heart failure and a type of abnormal heart rhythm called atrial fibrillation ), for example: digoxin
Anticoagulants (used to prevent blood clots from forming or increasing in size in blood and blood vessels), for example: warfarin , dabigatran
Contraceptives (used to prevent pregnancy), for example: contraceptives taken by mouth, as syringes or in the form of implants and contraceptive patches . This may include ethinyl estradiol, norethindrone and other progestogens. These should not be used as reliable contraceptive methods during treatment with Orkambi
Corticosteroid drugs (used to treat inflammation ): methylprednisolone, prednisone
Proton pump inhibitors (used to treat reflux disease and stomach ulcers ): omeprazole, esomeprazole, lansoprazole
Oral hypoglycaemia (used to treat type 2 diabetes ): repaglinide

There have been reports of false-positive urine test results regarding THC (tetrahydrocannabinol – an active ingredient in cannabis) in patients receiving Orkambi. The doctor may order another test to confirm the result.

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 for advice before taking this medicine. If possible, it may be best not to use Orkambi during pregnancy, and your doctor will help you decide what is best for you and your baby.

It is not known whether luma caftans or ivacaftor are excreted in human milk. If you are planning to breastfeed, talk to your doctor before taking Orkambi. Your doctor will decide if you should be advised to stop breastfeeding or discontinue treatment with lumbar or ivory. The doctor will take into account the benefits of breastfeeding for the baby and the benefits of the treatment for you.

Driving and using machines

Dizziness has been reported in patients receiving Ivaaftar, an ingredient in Orkambi, which may affect the ability to drive and use machines. If you get dizzy, do not drive or use machines until the dizziness has disappeared.

If a child experiences dizziness while taking Orkambi, it is recommended that the child does not cycle or do anything that requires full attention until the symptoms disappear.

Orkambi contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, ie essentially ‘sodium-free’. is next to “sodium-free”.

How to use Orkambi

Always take this medicine exactly as your doctor has told you. Consult a doctor if you are unsure.

Recommended dose

The recommended dose for patients aged 6 years and older is two tablets twice daily (at 12-hour intervals). This means a total of four tablets per day to be taken with foods that contain fat.

There are different strengths of the Orkambita tablets for different age groups. Make sure you have received the correct tablet (below).

Age	Tablets	Dose
6 to 11 years	Orkambi 100 mg / 125 mg	2 tablets in the morning2 tablets in the evening
12 years and older	Orkambi 200 mg / 125 mg	2 tablets in the morning2 tablets in the evening

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

If you have moderate or severe problems with liver function, your doctor may need to reduce the dose of Orkambi, as your liver does not take care of the medicine as quickly as those with normal liver function.

Moderate liver problems : dose one can be reduced to two tablets in the morning and one tablet in the evening (total lumacaftor 600 mg / ivacaftor 375 mg per day)
Severe liver problems : dose one can be reduced to one tablet (200 mg lumacaftor / 125 mg ivacaftor) in the morning and one tablet in the evening

Method of administration

Orkambi should be taken by mouth. Swallow the tablets whole. Do not chew, divide or dissolve tablets.

It is important to take Orkambi with foods that contain fat for you to get the right level of the drug in your body. A meal or snack that contains fat should be eaten just before or after taking Orkambi. Meals and snacks according to the CF guidelines or the meals recommended in the usual nutritional guidelines contain enough fat. Examples of meals and snacks that contain fat are those that are prepared with butter or oil or that contain eggs. Examples of other high-fat foods are:

cheese, whole milk, whole fat dairy products
meat, oily fish
avocado, hummus, soy-based products (tofu)
nutrition bars or nutrition drinks

If you use more Orkambi than you should

Contact a doctor or pharmacist for advice. If possible, take your medicine and this leaflet with you. You may experience side effects, including those mentioned in section 4 below.

If you forget to use Orkambi

Take the missed dose one with fatty foods if less than 6 hours have passed since you would have taken the one dose. Otherwise, wait until the next scheduled dose and take it as usual. Do not take a double dose to make up for a forgotten dose.

If you stop using Orkambi

You should continue to take the medicine according to your doctor’s instructions even if you feel well.

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

Possible side effects

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

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

Tell your doctor immediately if you get any of the following symptoms:

pain or discomfort in the upper right part of the abdomen (abdomen)
yellowing of the skin or whites of the eyes
poor appetite
nausea or vomiting
confusion
dark-colored urine

Other side effects ar

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

slemhosta
nasal congestion
respiratory distress
headache
abdominal pain
diarrhea
increased mucus formation
nausea
cold*
dizziness*
changes in the type of bacteria in expectorations *

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

pressure over the chest
narrower airways
sinus problems *
stuffy or runny nose
upper respiratory tract infection
sore throat
redness in the throat *
rash
gas formation
vomiting
elevation of an enzyme in the blood (creatine phosphokinase)
high levels of liver enzymes, which are seen on blood tests
irregular menstruation or pain associated with menstruation
earache, discomfort from the ears *
öronsus *
redness inside the ear *
disease of the inner ear (dizziness) *
lump in the breast*

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

abnormal periods, including missed or irregular periods, or more frequent and frequent periods
high blood pressure
caps for ear*
inflammation of the breasts *
breast augmentation in men *
changes or pain in the nipples *

* Side effects that have only been seen with vigilantes.

Side effects are in children

Side effects seen in children are similar to those seen in adults and adolescents. However, elevated levels of liver enzymes in the blood are more common in young children than in adults.

How to store 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 and blister after “EXP”. The expiration date is the last day of the specified month.

No special storage instructions.

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

Contents of the pack and other information

Content declaration

The active substances are luma kaftar and ivakaftor.

Orkambi 100 mg / 125 mg film-coated tablets:

Each film-coated tablet contains 100 mg luma caftan and 125 mg iva caftan.

Orkambi 200 mg / 125 mg film-coated tablets:

Each film-coated tablet contains 200 mg luma caftan and 125 mg iva caftar.

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

Other ingredients are:

Tablet core: microcrystalline cellulose, croscarmellose sodium, hypromellose acetate succinate, povidone (K30), sodium lauryl sulphate and magnesium stearate (see section 2 “Orkambi contains matrix”).
Tablet cover: polyvinyl alcohol, titanium dioxide (E171), macrogol 3350, talc, carmine (E120), brilliant blue FCF aluminum lacquer (E133) and indigo carmine aluminum lacquer (E132)
Ink: shellac, iron oxide black (E172), propylene glycol and ammonium hydroxide

What the medicine looks like and contents of the pack

Orkambi 100 mg / 125 mg film-coated tablets

Orkambi 100 mg / 125 mg film-coated tablets (dimensions 14 × 7.6 × 4.9 mm) are pink, oval tablets imprinted 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 (dimensions 14 × 8.4 × 6.8 mm) are pink, oval tablets debossed with “2V125” in black ink on one side.

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

Not all pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorisation Holder

Vertex Pharmaceuticals (Ireland) Limited

Unit 49, Block F2, Northwood Court, Santry,

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

Contact the representative of the marketing authorization holder to find out more about this medicine: