Ivacaftor - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Elevated transaminases (ALT or AST): Transaminases (ALT and AST) should be assessed prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter.

In patients with a history of transaminase elevations, more frequent monitoring of liver function tests should be considered.

Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve.

Interrupt dosing in patients with ALT or AST of greater than 5 times the upper limit of normal (ULN).

Following resolution of transaminase elevations, consider the benefits and risks of resuming KALYDECO dosing. ( 5.1 , 6 ) Hypersensitivity reactions: Anaphylaxis has been reported with KALYDECO in the postmarketing setting.

Initiate appropriate therapy in the event of a hypersensitivity reaction.

Intracranial hypertension : Intracranial hypertension (IH) has been reported in the postmarketing setting with use of drugs containing the same or similar active ingredients as KALYDECO.

If an unusual headache or visual disturbances occur during treatment, and IH is suspected, interrupt KALYDECO and refer for prompt medical evaluation.

Neuropsychiatric events, including suicidal thoughts and behaviors : Serious neuropsychiatric events, including symptoms of anxiety, depression, suicidal ideation and behavior, and sleep disturbances, have been reported in the postmarketing setting for KALYDECO or drugs containing the same or similar active ingredient.

Monitor patients closely for new or worsening symptoms.

Consider the risks and benefits for the individual patient to determine if therapy with KALYDECO should be interrupted at the occurrence of neuropsychiatric symptoms.

Use with CYP3A inducers: Concomitant use with strong CYP3A inducers (e.g., rifampin, St.

John's wort) substantially decreases exposure of ivacaftor, which may diminish effectiveness.

Therefore, co-administration is not recommended. ( 5.5 , 7.2 , 12.3 ) Cataracts: Non-congenital lens opacities/cataracts have been reported in pediatric patients treated with KALYDECO.

Baseline and follow-up examinations are recommended in pediatric patients initiating KALYDECO treatment.

5.1 Transaminase (ALT or AST) Elevations Elevated transaminases have been reported in patients with CF receiving KALYDECO.

ALT and AST should be assessed prior to initiating KALYDECO, every 3 months during the first year of treatment, and annually thereafter.

For patients with a history of transaminase elevations, consider more frequent monitoring of liver function tests.

Patients who develop increased transaminase levels should be closely monitored until the abnormalities resolve.

Dosing should be interrupted in patients with ALT or AST of greater than 5 times the upper limit of normal (ULN).

Following resolution of transaminase elevations, consider the benefits and risks of resuming KALYDECO [see Adverse Reactions and Use in Specific Populations ] .

5.2 Hypersensitivity Reactions, Including Anaphylaxis Hypersensitivity reactions, including cases of anaphylaxis, have been reported in the postmarketing setting [see Adverse Reactions ] .

If signs or symptoms of serious hypersensitivity reactions develop during treatment, discontinue KALYDECO and institute appropriate therapy.

Consider the benefits and risks for the individual patient to determine whether to resume treatment with KALYDECO .

5.3 Intracranial Hypertension Cases of intracranial hypertension (IH) have been reported in the postmarketing setting with the use of drugs containing the same or similar active ingredients as KALYDECO [see Adverse Reactions ] .