Pirfenidone

May cause dizziness and/or fatigue which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Incidence of dizziness may be reduced by administering with food. Dose reduction or discontinuation may be necessary if symptoms fail to improve or worsen.

Adverse effects including nausea/vomiting, diarrhea, dyspepsia, gastroesophageal reflux disease, and abdominal pain have been reported; incidence may be reduced by administering with food. The incidence of gastrointestinal events was highest early in the course of treatment (initial 3 months) and decreased over time. Consider dose reduction or discontinuation of therapy if lack of improvement or worsening of symptoms.

Increased transaminases (ALT/AST) and hyperbilirubinemia have been reported with use; evaluate liver function prior to therapy initiation and during therapy. Dose reduction or discontinuation of therapy may be necessary. Discontinue therapy immediately for transaminases >5 x ULN or for increased transaminases that are accompanied by symptoms (eg, jaundice) or hyperbilirubinemia; monitor closely and do not rechallenge with pirfenidone.

Photosensitivity reactions and rash have been reported with the majority of reactions occurring during the initial 6 months of therapy (severe reactions are uncommon); instruct patients to avoid or minimize exposure to the sun and/or sun lamps, to apply sunscreen (SPF ≥50 against UVA and UVB), wear protective clothing/hats, and to avoid concurrent use of other photosensitizing drugs. Patients should promptly report symptoms, reaction, or rash; dose reduction or therapy interruption may be necessary. If appropriate, may reinitiate therapy with re-escalation of dose as tolerated.

Weight loss/anorexia have been reported with use; monitor weight during therapy. Disease-related concerns:

Use with caution in mild to moderate impairment (Child-Pugh class A and B); pirfenidone systemic exposure increased by 60% in moderate impairment. Use in severe impairment (Child-Pugh class C) is not recommended (has not been studied).

Use with caution in patients with renal impairment; consider dose reduction and/or discontinuation as necessary; use in patients with end stage renal disease requiring dialysis is not recommended. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Clearance may be increased and systemic exposure decreased in cigarette smokers due to hepatic enzyme (ie, CYP1A2) induction. Patients should be instructed to quit smoking prior to initiation of therapy; cigarette smoking should be avoided during therapy.