Applies to elexacaftor / ivacaftor / tezacaftor: oral granule, oral tablet.

Serious side effects

Along with its needed effects, elexacaftor/ivacaftor/tezacaftor may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking elexacaftor/ivacaftor/tezacaftor:

Incidence not known

• Dark urine
• headache
• light-colored stools
• nausea and vomiting
• stomach pain or bloating
• yellow eyes or skin
• unusual tiredness or weakness

Other side effects

Some side effects of elexacaftor / ivacaftor / tezacaftor may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about 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

• Body aches or pain
• chills
• cough
• diarrhea
• difficulty in breathing
• ear congestion
• fever
• itching skin or rash
• 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
• dizziness
• 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

For Healthcare Professionals

Applies to elexacaftor / ivacaftor / tezacaftor: oral granule, oral tablet.

General

The most commonly reported adverse reactions have included headache, upper respiratory infection, abdominal pain, diarrhea, rash, and increased ALT levels.^[Ref]

Hepatic

ALT or AST elevations to greater than 8, 5, or 3 times the upper limit of normal (ULN) occurred in 1%, 2%, and 8% of patients receiving this drug, respectively. The incidence of maximum total bilirubin elevation greater than 2 x ULN was 4%. Maximum indirect and direct bilirubin elevations greater than 1.5 x ULN occurred in 11% and 3% of patients, respectively. In a clinical study of subjects with moderate hepatic impairment (n=11), one subject developed total and direct bilirubin elevations greater than 2 x ULN and a second subject developed direct bilirubin elevation of greater than 4.5 x ULN.

Very common (10% or more): Increased ALT (10%)

Common (1% to 10%): Increased AST, increased bilirubin levels

Postmarketing report: Liver failure leading to transplantation in a patient with preexisting cirrhosis and portal hypertension, liver injury characterized by concomitant transaminase and total bilirubin elevations

Dermatologic

Rash occurred in approximately 10% of patients with a higher incidence in females (16%) compared with males (5%). It may be that hormonal contraceptive played a role in the occurrence of rash. If a rash develops while on hormonal contraceptives, consider interrupting both this drug and the hormonal contraceptive. With resolution of the rash, consider resuming therapy with this drug without the hormonal contraceptive. If rash does not recur, may consider resuming the hormonal contraceptive.

Common (1% to 10%): Rash, acne, eczema, pruritus

Nervous system

Very common (10% or more): Headache (17%)

Common (1% to 10%): Dizziness

Ocular

Elexacaftor / ivacaftor / tezacaftor:

Common (1% to 10%): Conjunctivitis

Ivacaftor-Containing Regimens:

Frequency not reported: Non-congenital lens opacities/cataracts (pediatric patients)

Cases of non-congenital lens opacities have been reported in pediatric patients treated with ivacaftor-containing regimens. Although other risk factors were present in some cases (such as corticosteroid use, exposure to radiation), a possible risk attributable to treatment with ivacaftor cannot be excluded. Findings of cataracts were observed in juvenile rats dosed from postnatal Day 7 through 35 with ivacaftor dose levels of 10 mg/kg/day and higher (0.24 times the MRHD based on systemic exposure of ivacaftor and its metabolites). This finding has not been observed in older animals.

Metabolic

Common (1% to 10%): Hypoglycemia

Gastrointestinal

Very common (10% or more): Abdominal pain (14%), diarrhea (13%)

Common (1% to 10%): Flatulence, abdominal distension

Genitourinary

Common (1% to 10%): Dysmenorrhea, urinary tract infection

Immunologic

Common (1% to 10%): Influenza

Musculoskeletal

Common (1% to 10%): Blood creatine phosphokinase increased

Cardiovascular

Common (1% to 10%): Elevated blood pressure

Other

Common (1% to 10%): C-reactive protein increased

Respiratory

Very common (10% or more): Upper respiratory tract infection (16%)

Common (1% to 10%): Nasal congestion, rhinorrhea, rhinitis, sinusitis, pharyngitis, respiratory tract infection, tonsillitis