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Elevated liver enzymes: Increases in ALT and AST >3× ULN have been reported in patients treated with Esbriet. In some cases these have been associated with concomitant elevations in bilirubin. Patients treated with Esbriet had a higher incidence of elevations in ALT or AST than placebo patients (3.7% vs 0.8%, respectively). No cases of liver transplant or death due to liver failure that were related to Esbriet have been reported. However, the combination of transaminase elevations and elevated bilirubin without evidence of obstruction is generally recognized as an important predictor of severe liver injury that could lead to death or the need for liver transplants in some patients. Conduct liver function tests (ALT, AST, and bilirubin) prior to initiating Esbriet, then monthly for the first 6 months and every 3 months thereafter. Dosage modifications or interruption may be necessary.

Photosensitivity reaction or rash: Patients treated with Esbriet had a higher incidence of photosensitivity reactions (9%) compared with patients treated with placebo (1%). Patients should avoid or minimize exposure to sunlight (including sunlamps), use a sunblock (SPF 50 or higher), and wear clothing that protects against sun exposure. Patients should avoid concomitant medications that cause photosensitivity. Dosage reduction or discontinuation may be necessary.

Gastrointestinal disorders: Gastrointestinal events of nausea, diarrhea, dyspepsia, vomiting, gastroesophageal reflux disease, and abdominal pain were more frequently reported in patients treated with Esbriet. Dosage reduction or interruption for gastrointestinal events was required in 18.5% of patients in the 2403 mg/day group, as compared to 5.8% of patients in the placebo group; 2.2% of patients in the ESBRIET 2403 mg/day group discontinued treatment due to a gastrointestinal event, as compared to 1.0% in the placebo group. The most common (>2%) gastrointestinal events that led to dosage reduction or interruption were nausea, diarrhea, vomiting, and dyspepsia. Dosage modifications may be necessary in some cases.

Adverse reactions: The most common adverse reactions (≥10%) are nausea, rash, abdominal pain, upper respiratory tract infection, diarrhea, fatigue, headache, dyspepsia, dizziness, vomiting, anorexia, gastroesophageal reflux disease, sinusitis, insomnia, weight decreased, and arthralgia.

Drug interactions: Concomitant administration with strong inhibitors of CYP1A2 (eg, fluvoxamine) significantly increases systemic exposure of Esbriet and is not recommended. Discontinue prior to administration of Esbriet. If strong CYP1A2 inhibitors cannot be avoided, dosage reductions of Esbriet are recommended. Monitor for adverse reactions and consider discontinuation of Esbriet as needed.

Concomitant administration of Esbriet and ciprofloxacin (a moderate inhibitor of CYP1A2) moderately increases exposure to Esbriet. If ciprofloxacin at the dosage of 750 mg twice daily cannot be avoided, dosage reductions are recommended. Monitor patients closely when ciprofloxacin is used.

Agents that are moderate or strong inhibitors of both CYP1A2 and CYP isoenzymes involved in the metabolism of Esbriet should be avoided during treatment.

The concomitant use of a CYP1A2 inducer may decrease the exposure of Esbriet, and may lead to loss of efficacy. Concomitant use of strong CYP1A2 inducers should be avoided.

Specific populations: Esbriet should be used with caution in patients with mild to moderate (Child Pugh Class A and B) hepatic impairment. Monitor for adverse reactions and consider dosage modification or discontinuation of Esbriet as needed. The safety, efficacy, and pharmacokinetics of Esbriet have not been studied in patients with severe hepatic impairment. Esbriet is not recommended for use in patients with severe (Child Pugh Class C) hepatic impairment.

Esbriet should be used with caution in patients with mild (CLcr 50–80 mL/min), moderate (CLcr 30–50 mL/min), or severe (CLcr less than 30 mL/min) renal impairment. Monitor for adverse reactions and consider dosage modification or discontinuation of Esbriet as needed. The safety, efficacy, and pharmacokinetics of Esbriet have not been studied in patients with end-stage renal disease requiring dialysis. Use of Esbriet in patients with end-stage renal diseases requiring dialysis is not recommended.

Smoking causes decreased exposure to Esbriet, which may alter the efficacy profile of Esbriet. Instruct patients to stop smoking prior to treatment with Esbriet and to avoid smoking when using Esbriet.

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional important safety information at esbriet.com.