Lumacaftor and ivacaftor (Oral)

Lumacaftor and ivacaftor combination is used to treat cystic fibrosis (CF) in patients 1 year of age and older. It is only for patients who have two copies of the F508del mutation in their CF transmembrane conductance regulator (CFTR) gene. Your doctor will perform a test to check for the mutation before you get the medicine.

This medicine is available only with your doctor's prescription.

It is very important that your doctor checks your or your child's progress during regular visits to ensure that this medicine is working properly. Blood tests will be needed to check for unwanted effects. You may also need to monitor your blood pressure at home. If you notice any changes in your normal blood pressure, call your doctor right away.

Birth control pills and other hormone-based contraceptives (e.g., patches, rings, implants, and injections) may not work while you are using this medicine. To avoid getting pregnant, use another form of birth control (e.g., condoms, diaphragm, or contraceptive foam or jelly) while using Orkambi®.

Liver problems may be more likely to occur if you already have an existing liver problem (e.g., cirrhosis). Check with your doctor right away if you or your child has pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin.

This medicine may cause serious allergic reactions, including anaphylaxis and angioedema, which can be life-threatening and require immediate medical attention. Check with your doctor right away if you have chest tightness, cough, difficulty swallowing, dizziness, fast heartbeat, hives, itching, skin rash, large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, trouble breathing, or unusual tiredness or weakness.

Check with your doctor right away if you or your child has a cough, trouble breathing, chest tightness, or any type of breathing problem when starting treatment with this medicine.

This medicine may cause eye problems, including cataracts. Check with your doctor right away if you or your child experiences blindness, blurred vision, or decreased vision.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.

In deciding to use a medicine, the chances of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this drug, the following should be considered:

Allergies

Inform your doctor if you have ever had any unusual or allergic reaction to this drug or any other medications. Also inform your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of lumacaftor and ivacaftor combination in children younger than 1 year of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies on the relationship of age to the effects of lumacaftor and ivacaftor combination have not been performed in the geriatric population.

Breast Feeding

There are no adequate studies in women for determining infant chance when using this medication during breastfeeding. Weigh the potential benefits against the potential risks prior to taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially critical that your healthcare professional know if you are using any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medication with any of the following drugs is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medications you take.

• Doravirine
• Fostemsavir
• Isavuconazonium
• Lenacapavir
• Levoketoconazole
• Lorlatinib
• Mavacamten
• Nirmatrelvir
• Pacritinib
• Ritonavir

Using this drug with any of the following drugs is usually not advised, but may be required in some cases. If both medicines are prescribed together, your clinician may change the dose or how often you use one or both of the drugs.

• Abemaciclib
• Abiraterone Acetate
• Acalabrutinib
• Adagrasib
• Alfentanil
• Alpelisib
• Alprazolam
• Amiodarone
• Amprenavir
• Apixaban
• Aprepitant
• Aripiprazole
• Atazanavir
• Atogepant
• Avacopan
• Avapritinib
• Axitinib
• Belumosudil
• Belzutifan
• Bentazepam
• Benzhydrocodone
• Bictegravir
• Boceprevir
• Bortezomib
• Bosutinib
• Brigatinib
• Bromazepam
• Budesonide
• Buprenorphine
• Buspirone
• Cabozantinib
• Cannabidiol
• Capmatinib
• Carbamazepine
• Ceritinib
• Chlordiazepoxide
• Cimetidine
• Ciprofloxacin
• Clarithromycin
• Clobazam
• Clofazimine
• Clonazepam
• Clorazepate
• Cloxazolam
• Clozapine
• Cobicistat
• Codeine
• Conivaptan
• Copanlisib
• Crizotinib
• Cyclosporine
• Dabrafenib
• Daridorexant
• Darifenacin
• Darunavir
• Dasatinib
• Deflazacort
• Delorazepam
• Desogestrel
• Dexamethasone
• Diazepam
• Dienogest
• Digoxin
• Dihydrocodeine
• Dihydroergotamine
• Diltiazem
• Dofetilide
• Dronedarone
• Drospirenone
• Duvelisib
• Elacestrant
• Eletriptan
• Elexacaftor
• Eliglustat
• Encorafenib
• Entrectinib
• Enzalutamide
• Eplerenone
• Eravacycline
• Erdafitinib
• Ergotamine
• Erlotinib
• Erythromycin
• Estazolam
• Estetrol
• Estradiol
• Ethinyl Estradiol
• Ethynodiol
• Etonogestrel
• Everolimus
• Fedratinib
• Felodipine
• Fenfluramine
• Fentanyl
• Fexinidazole
• Finerenone
• Flibanserin
• Fluconazole
• Flunitrazepam
• Flurazepam
• Fluticasone
• Fluvoxamine
• Fosamprenavir
• Fosaprepitant
• Fosnetupitant
• Fosphenytoin
• Fostamatinib
• Gepirone
• Gestodene
• Glasdegib
• Glimepiride
• Glipizide
• Halazepam
• Hemin
• Hydrocodone
• Ibrexafungerp
• Ibrutinib
• Ibuprofen
• Idelalisib
• Imatinib
• Indinavir
• Infigratinib
• Istradefylline
• Itraconazole
• Ivabradine
• Ivacaftor
• Ivosidenib
• Ixabepilone
• Josamycin
• Ketazolam
• Ketoconazole
• Larotrectinib
• Lefamulin
• Lemborexant
• Lenacapavir
• Leniolisib
• Letermovir
• Levoketoconazole
• Levonorgestrel
• Linagliptin
• Lonafarnib
• Lopinavir
• Loprazolam
• Lorazepam
• Lorlatinib
• Lormetazepam
• Lovastatin
• Lumacaftor
• Lumateperone
• Lurasidone
• Lurbinectedin
• Macimorelin
• Macitentan
• Maraviroc
• Maribavir
• Mavacamten
• Medazepam
• Medroxyprogesterone
• Meperidine
• Mestranol
• Metaclazepam
• Methadone
• Mibefradil
• Midazolam
• Midostaurin
• Mifepristone
• Mirtazapine
• Mitapivat
• Mitotane
• Mobocertinib
• Morphine
• Morphine Sulfate Liposome
• Naloxegol
• Nefazodone
• Nelfinavir
• Neratinib
• Netupitant
• Nilotinib
• Nitrazepam
• Nomegestrol
• Nordazepam
• Norelgestromin
• Norethindrone
• Norgestimate
• Norgestrel
• Olanzapine
• Olaparib
• Olutasidenib
• Omaveloxolone
• Osimertinib
• Oxazepam
• Oxcarbazepine
• Oxycodone
• Pacritinib
• Paliperidone
• Palovarotene
• Pemigatinib
• Pentazocine
• Perampanel
• Pexidartinib
• Phenobarbital
• Phenytoin
• Pimavanserin
• Pimozide
• Pinazepam
• Pirtobrutinib
• Pitolisant
• Ponatinib
• Posaconazole
• Pralsetinib
• Prazepam
• Pretomanid
• Primidone
• Quazepam
• Quetiapine
• Quinidine
• Quizartinib
• Regorafenib
• Remimazolam
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Rimegepant
• Ripretinib
• Risperidone
• Ritlecitinib
• Rivaroxaban
• Romidepsin
• Ruxolitinib
• Samidorphan
• Saquinavir
• Schisandra sphenanthera
• Segesterone
• Selpercatinib
• Selumetinib
• Sildenafil
• Simvastatin
• Sirolimus
• Sirolimus Protein-Bound
• Sotorasib
• Sparsentan
• Stiripentol
• St John's Wort
• Sufentanil
• Sunitinib
• Tacrolimus
• Tamoxifen
• Tasimelteon
• Tazemetostat
• Telaprevir
• Telithromycin
• Temazepam
• Temsirolimus
• Tetrazepam
• Tezacaftor
• Thiotepa
• Ticagrelor
• Tipranavir
• Tivozanib
• Tocilizumab
• Tofacitinib
• Tolvaptan
• Tramadol
• Treosulfan
• Triazolam
• Trofinetide
• Troleandomycin
• Tucatinib
• Ubrogepant
• Ulipristal
• Upadacitinib
• Valbenazine
• Vardenafil
• Velpatasvir
• Vemurafenib
• Verapamil
• Vilazodone
• Vincristine
• Vincristine Sulfate Liposome
• Voclosporin
• Vonoprazan
• Voriconazole
• Vortioxetine
• Voxelotor
• Voxilaprevir
• Warfarin
• Zanubrutinib
• Zolpidem
• Zuranolone

Using this drug with any of the following drugs may cause an increased chance of certain adverse effects, but using both drugs may be the best therapy for you. If both medications are prescribed together, your clinician may change the dose or how frequently you use one or both of the medicines.

• Aripiprazole Lauroxil

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain drugs may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medication with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how frequently you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Grapefruit Juice

Other Medical Issues

The presence of other medical problems may affect the use of this drug. Make sure you inform your clinician if you have any other medical issues, especially:

• Cataracts or
• Hypertension (high blood pressure) or
• Lung or breathing issues or
• Organ transplant, history of—Use with caution. May make these conditions worse.

• Kidney disease, serious or
• Liver disease, moderate to serious—Use with caution. The effects may be increased since of slower removal of the drug from the body.

Along with its necessary effects, this medicine may cause some unwanted effects. Not all of these side effects may happen, but if they do, you might need medical attention.

Check with your doctor right away if any of the following side effects happen:

More common

• Body aches or pain
• Chest tightness
• Chills
• Cough
• Difficult or labored breathing
• Ear congestion
• Fever
• Headache
• Loss of voice
• Muscle aches
• Sneezing
• Sore throat
• Stuffy or runny nose
• Unusual tiredness or weakness
• Upper abdominal or stomach pain

Incidence not known

• Blurred vision
• Dark urine
• Difficulty swallowing
• Discomfort in the upper right stomach area
• Dizziness
• Fast heartbeat
• General feeling of tiredness or weakness
• Hives, itching, skin rash
• Large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• Light-colored stools
• Loss of appetite
• Nausea
• Nervousness
• Pounding in the ears
• Puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• Slow or fast heartbeat
• Ongoing stomach pain
• Vomiting
• Yellow eyes or skin

Some side effects may happen that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Additionally, your health care professional may have ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome, or if you have any questions about them:

More common

• Absent, missed, or irregular menstrual periods
• Bloated feeling
• Cough producing mucus
• Cramps
• Diarrhea
• Excess air or gas in the stomach or bowels
• Feeling of fullness
• Heavy bleeding
• Increased sputum production
• Longer or heavier menstrual periods
• Loss of voice
• Passing gas
• Rash
• Stopping of menstrual bleeding

Other side effects not listed may also happen in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You can report side effects to the FDA at 1-800-FDA-1088.

In the U.S.

• Orkambi

Available Dosage Forms:

• Granule
• Tablet

Therapeutic Class: Respiratory Agent

Take this medicine exactly as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects.

This medicine comes with a patient information insert. Read and follow the instructions carefully. Ask your doctor if you have any questions.

Take this medicine with fat-containing foods including avocados, butter, cheese pizza, eggs, nuts, peanut butter, breast milk, baby formula, or whole-milk dairy products (eg, whole milk, cheese, yogurt).

If you are using the granules, mix all the content of each packet with 1 teaspoon (5 milliliters [mL]) of cool to room temperature soft food (eg, puréed fruits, flavored yogurt, pudding, applesauce) or liquid (eg, water, milk, breast milk, baby formula, or juice). Take this mixture within 1 hour after mixing.

Tell your doctor if you stopped taking this medicine for more than 1 week. Your doctor may need to change your dose of Orkambi® or other medicines you take.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (granules, tablets):For cystic fibrosis: Adults and children 12 years of age and older—2 tablets every 12 hours, taken with fat-containing food. Each tablet contains 200 milligrams (mg) lumacaftor and 125 mg ivacaftor. Children 6 to 11 years of age—2 tablets every 12 hours, taken with fat-containing food. Each tablet contains 100 mg lumacaftor and 125 mg ivacaftor. Children 2 to 5 years of age—Dose is based on your body weight and must be determined by your doctor. Weighing 14 kilograms (kg) or more—1 packet of granules every 12 hours, taken with fat-containing food. Each packet contains 150 mg lumacaftor and 188 mg ivacaftor. Weighing less than 14 kg—1 packet of granules every 12 hours, taken with fat-containing food. Each packet contains 100 mg lumacaftor and 125 mg ivacaftor. Children 1 to 2 years of age—Dose is based on your body weight and must be determined by your doctor. Weighing 14 kilograms (kg) or more—1 packet of granules every 12 hours, taken with fat-containing food. Each packet contains 150 milligrams (mg) lumacaftor and 188 mg ivacaftor. Weighing 9 to less than 14 kg—1 packet of granules every 12 hours, taken with fat-containing food. Each packet contains 100 mg lumacaftor and 125 mg ivacaftor. Weighing 7 to less than 9 kg—1 packet of granules every 12 hours, taken with fat-containing food. Each packet contains 75 mg lumacaftor and 94 mg ivacaftor. Children younger than 1 year of age—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

If you miss a dose and it is 6 hours or less from the time you normally take your medicine, take a dose as soon as you can. If it is more than 6 hours, wait until then to use the medicine and skip the missed dose. Do not take extra medicine to make up for a missed dose.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

• What is the difference between Symdeko and Orkambi?