Elexacaftor, tezacaftor, ivacaftor and ivacaftor (Oral)

Elexacaftor/tezacaftor/ivacaftor and ivacaftor combination is used to treat cystic fibrosis (CF) in patients who have at least one copy of the F508del mutation in their CF transmembrane conductance regulator (CFTR) gene or another mutation that responds to this medicine. Your doctor will perform a test to check for the mutation before you receive the medicine.

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

It is very important for your doctor to check you or your child's progress at regular visits to ensure that this medicine is working properly. Blood tests will be necessary to check for side effects.

This medicine may cause serious allergic reactions, including anaphylaxis and angioedema, which can be life-threatening and need immediate medical attention. Contact your doctor right away if you experience 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.

Contact your doctor right away if you have dark urine, clay-colored stools, stomach pain, or yellow eyes or skin. These may indicate a serious liver issue.

Contact your doctor right away if you experience blurred vision, difficulty with reading, or any other change in vision during or after treatment. Your doctor may want your child's eyes to be checked by an ophthalmologist (eye doctor).

Do not take other medicines unless your doctor has discussed them with you. 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, it is important to consider the risks of taking it compared to the benefits it may provide. This is a decision you and your doctor will make together. For this medicine, please consider the following:

Allergies

Inform your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also, let your healthcare professional know if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For over-the-counter products, read the label or package ingredients carefully.

Pediatric

There have not been appropriate studies on the effects of Trikafta® in children younger than 2 years old. Its safety and effectiveness have not been established for this age group.

Geriatric

Appropriate studies on the effects of Trikafta® in older adults have not been conducted. However, no specific problems related to older adults have been documented so far.

Breast Feeding

There are no adequate studies in women to determine the risk to infants when using this medication while breastfeeding. Consider the potential benefits against the potential risks before using this medication during breastfeeding.

Interactions with Medicines

Some medicines should not be used together at all, while in other cases, two different medicines may be taken together even if there is a possibility of interaction. If you are taking this medicine, it is particularly important for your healthcare professional to know if you are taking any of the medicines listed below. The following interactions have been selected based on their potential significance and may not include all possible interactions.

Using this medicine with any of the following medicines is not recommended. Your doctor may choose not to treat you with this medication or alter some of the other medicines you take.

• Levoketoconazole
• Nirmatrelvir
• Ritonavir

Using this medicine with any of the following medicines is generally not recommended but may be necessary in some cases. If both medicines are prescribed together, your doctor may adjust the dose or frequency of one or both medicines.

• Abametapir
• Adagrasib
• Alfentanil
• Alprazolam
• Amiodarone
• Amprenavir
• Apalutamide
• Aprepitant
• Atazanavir
• Atorvastatin
• Belzutifan
• Bentazepam
• Benzhydrocodone
• Boceprevir
• Bosentan
• Bromazepam
• Buprenorphine
• Carbamazepine
• Ceritinib
• Chlordiazepoxide
• Cimetidine
• Ciprofloxacin
• Clarithromycin
• Clobazam
• Clofazimine
• Clonazepam
• Clorazepate
• Cloxazolam
• Clozapine
• Cobicistat
• Codeine
• Conivaptan
• Crizotinib
• Cyclosporine
• Dabrafenib
• Darunavir
• Delorazepam
• Diazepam
• Digoxin
• Dihydrocodeine
• Dihydroergotamine
• Diltiazem
• Dofetilide
• Dronedarone
• Duvelisib
• Elagolix
• Eliglustat
• Enzalutamide
• Ergotamine
• Erythromycin
• Estazolam
• Everolimus
• Fedratinib
• Fentanyl
• Fexinidazole
• Finerenone
• Flibanserin
• Fluconazole
• Flunitrazepam
• Flurazepam
• Fluvoxamine
• Fosamprenavir
• Fosnetupitant
• Fosphenytoin
• Glimepiride
• Glipizide
• Glyburide
• Grazoprevir
• Halazepam
• Hydrocodone
• Idelalisib
• Imatinib
• Indinavir
• Itraconazole
• Ivosidenib
• Josamycin
• Ketazolam
• Ketoconazole
• Larotrectinib
• Lefamulin
• Lemborexant
• Lenacapavir
• Letermovir
• Lonafarnib
• Lopinavir
• Loprazolam
• Lorazepam
• Lorlatinib
• Lormetazepam
• Lumacaftor
• Mavacamten
• Medazepam
• Meperidine
• Metaclazepam
• Methadone
• Methotrexate
• Mibefradil
• Midazolam
• Mifepristone
• Mitotane
• Morphine
• Morphine Sulfate Liposome
• Nefazodone
• Nelfinavir
• Netupitant
• Nilotinib
• Nitrazepam
• Nordazepam
• Olutasidenib
• Omaveloxolone
• Oxazepam
• Oxycodone
• Pacritinib
• Pentazocine
• Phenobarbital
• Phenytoin
• Pimavanserin
• Pimozide
• Pinazepam
• Pirtobrutinib
• Pitavastatin
• Posaconazole
• Pravastatin
• Prazepam
• Primidone
• Quazepam
• Quinidine
• Remimazolam
• Repaglinide
• Revefenacin
• Ribociclib
• Rifabutin
• Rifampin
• Rifapentine
• Ritlecitinib
• Ritonavir
• Rosuvastatin
• Saquinavir
• Schisandra sphenanthera
• Simvastatin
• Sirolimus
• Sirolimus Protein-Bound
• St John's Wort
• Sufentanil
• Tacrolimus
• Telaprevir
• Telithromycin
• Temazepam
• Temsirolimus
• Tetrazepam
• Tocilizumab
• Tramadol
• Treosulfan
• Triazolam
• Trofinetide
• Troleandomycin
• Tucatinib
• Ubrogepant
• Verapamil
• Voriconazole
• Voxelotor
• Warfarin
• Zolpidem

Interactions with Food/Tobacco/Alcohol

Some medicines should not be taken around the time of eating food or specific types of food due to possible interactions. Using alcohol or tobacco with certain medicines can also lead to interactions. The following interactions have been selected based on their potential significance and may not include all possible interactions.

Using this medicine with any of the following is generally not recommended, but may be unavoidable in some cases. If used together, your doctor may adjust the dose or frequency of this medicine, or provide special instructions regarding food, alcohol, or tobacco use.

• Grapefruit Juice

Other Medical Problems

Having other medical issues may affect how this medicine works. Be sure to tell your doctor if you have any other medical problems, especially:

• Exposure to radiation—Use with caution. May increase the risk of developing cataracts.

• Kidney disease, severe or
• Liver disease, moderate—Use with caution. The effects may be stronger because the body removes the medicine more slowly.

• Liver disease (e.g., ascites, cirrhosis, hepatic encephalopathy, portal hypertension), or history of or—Use with caution. May worsen this condition.

• Liver disease, severe—Should not be used in patients with this condition.

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

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

Incidence not known

• Chest tightness
• cough
• dark urine
• difficulty swallowing
• dizziness
• fast heartbeat
• headache
• hives, itching, skin rash
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• light-colored stools
• nausea and vomiting
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• stomach pain or bloating
• trouble breathing
• yellow eyes or skin
• unusual tiredness or weakness

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

More common

• Body aches or pain
• chills
• diarrhea
• ear congestion
• fever
• loss of voice
• sneezing
• sore throat
• stuffy or runny nose

Less common

• Anxiety
• bladder pain
• blemishes on the skin
• bloated
• bloody or cloudy urine
• blurred vision
• burning, dry, or itching eyes
• cold sweats
• coma
• confusion
• cool, pale skin
• cramps
• depression
• difficult, burning, or painful urination
• discharge, excessive tearing
• excess air or gas in the stomach or intestines
• fast heartbeat
• frequent urge to urinate
• full feeling
• heavy bleeding
• increased hunger
• lower back or side pain
• nervousness
• nightmares
• pain
• passing gas
• pimples
• redness, pain, swelling of the eye, eyelid, or inner lining of the eyelid
• seizures
• shakiness
• skin rash, encrusted, scaly, and oozing
• slurred speech

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 may report side effects to the FDA at 1-800-FDA-1088.

In the U.S.

• Trikafta

Available Dosage Forms:

• Tablet
• Granule

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.

Swallow the tablets whole. Do not crush, break, or chew them.

If you are using the oral granules, mix the entire contents of each packet with 1 teaspoon (5 milliliters [mL]) of cool to room temperature soft food (eg, pureed fruits or vegetables, yogurt, applesauce) or liquid (eg, water, milk, juice). Take this mixture within 1 hour after mixing.

Take this medicine with fat-containing foods, including food prepared with butter or oils, cheese, eggs, peanut butter, meat, nuts, or whole milk.

Do not eat grapefruit or drink grapefruit juice while you are using this medicine.

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 and tablets):For cystic fibrosis: Adults and children 12 years of age and older—2 orange tablets (containing elexacaftor 100 milligrams (mg), tezacaftor 50 mg, and ivacaftor 75 mg) taken in the morning and 1 light blue tablet (containing ivacaftor 150 mg) taken in the evening, about 12 hours apart. Children 6 to younger than 12 years of age—Dose is based on your body weight and must be determined by your doctor. Weighing 30 kilograms (kg) or more—2 orange tablets (containing elexacaftor 100 milligrams (mg), tezacaftor 50 mg, and ivacaftor 75 mg) taken in the morning and 1 light blue tablet (containing ivacaftor 150 mg) taken in the evening, about 12 hours apart. Weighing less than 30 kg—2 light orange tablets (containing elexacaftor 50 mg, tezacaftor 25 mg, and ivacaftor 37.5 mg) taken in the morning and 1 light blue tablet (containing ivacaftor 75 mg) taken in the evening, about 12 hours apart. Children 2 to younger than 6 years of age—Dose is based on your body weight and must be determined by your doctor. Weighing 14 kilograms (kg) or more—1 white and orange packet of granules (each packet contains 100 mg tezacaftor, 50 mg tezacaftor, and 75 mg ivacaftor) taken in the morning and 1 white and pink packet of granules (containing ivacaftor 75 mg) taken in the evening, about 12 hours apart. Weighing less than 14 kg—1 white and blue packet of granules (each packet contains 80 mg tezacaftor, 40 mg tezacaftor, and 60 mg ivacaftor) taken in the morning and 1 white and green packet of granules (containing ivacaftor 59.5 mg) taken in the evening, about 12 hours apart. Children younger than 2 years 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 since the missed morning dose, take the missed dose as soon as you can, but don't take the evening dose. Take the next morning dose at its usual time. If it is more than 6 hours since the missed evening dose, skip the missed dose and take the next morning dose at the regular time. 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.