peer-FEH-nih-done

Therapeutic Classification: pulmonary fibrosis agents

Pharmacologic Classification:

• Treatment of idiopathic pulmonary fibrosis (IPF).

• Has antithrombotic and anti-inflammatory properties.

• Slowed progression of IPF.

Absorption: Absorption follows oral administration. Food ↓ rate and extent of absorption.

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized by the CYP1A2 enzyme system, some metabolism by other CYP enzymes. 80% excreted in urine as inactive metabolite.

Half-life: 3 hr.

(effects on pulmonary function)

Contraindicated in:

• End-stage renal disease on dialysis
• Concurrent use of strong CYP1A2 inducers
• Severe hepatic impairment
• Lactation: Lactation.

Use Cautiously in:

• Concurrent use of strong CYP1A2 inhibitors (concurrent use not recommended but if unavoidable ↓ dose)
• Mild to moderate hepatic impairment (close monitoring recommended, permanent discontinuation may be necessary)
• Renal impairment (CCr 80 mL/min) (monitor carefully/consider dose ↓)
• Exposure to sunlight
• Cigarette smokers (may have ↓ blood levels and effectiveness, encourage cessation prior to treatment)
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Safety and effectiveness not established in children.

Derm: rash, photosensitivity, pruritus.

GI: HEPATOTOXICITY, abdominal pain, anorexia, gastrointestinal reflux disease, nausea, diarrhea, dyspepsia, vomiting, weight loss, dysgeusia.

MS: arthralgia.

Neuro: dizziness, fatigue, headache, insomnia, weakness.

Drug-Drug:

• Concurrent use of strong inhibitors of CYP1A2 including fluvoxamine↑ blood levels and risk of toxicity (concurrent use not recommended, if unavoidable ↓ dose of pirfenidone).
• Concurrent use of moderate inhibitors of CYP1A2 including ciprofloxacin↑ blood levels and risk of toxicity (dosage reductions are recommended for higher dose of ciprofloxacin, close monitoring for lower dose).
• Concurrent use of other inhibitors of CYP enzymes including 2C9, 2C19, 2D6, and 2E1↑ blood levels and risk of toxicity (discontinue prior to treatment).
• Concurrent use of strong inducers of CYP1A2 may ↓ blood levels and effectiveness (discontinue prior to treatment).

• PO (Adults): Days 1–7 — 267 mg (one capsule) 3 times daily, days 8–14 — 534 mg (two capsules) 3 times daily, day 15 and onward — 801 mg (three capsules) 3 times daily. If treatment is interrupted for 14 days or more, 2–wk upward titration is recommended.Concurrent use of strong inhibitors of CYP1A2 (including fluvoxamine) — 267 mg (one capsule) 3 times daily. Concurrent use of moderate inhibitors of CYP1A2 (including ciprofloxacin 750 mg twice daily) — 534 mg (two capsules) 3 times daily (if lower dose of ciprofloxacin is used, close monitoring with no dose alteration is recommended).

(Generic available)

• Capsules: 267 mg;
• Film-coated tablets: 267 mg; 801 mg;

• Monitor for signs and symptoms of pulmonary fibrosis (dyspnea, decreased forced vital capacity (FVC), diffuse pulmonary infiltrates on chest x-ray) during therapy.
• Assess for signs and symptoms of GI disorders (nausea, diarrhea, dyspepsia, vomiting, gastroesophageal reflux disease, abdominal pain) during therapy; occur most often during first 3 mo of therapy, then decreases. May require dose reductions.
• Monitor for signs and symptoms of liver dysfunction (fatigue, anorexia, right upper abdominal discomfort, dark urine, jaundice) periodically during therapy.

• Monitor liver function before starting, monthly for first 6 mo, then every 3 mo thereafter during therapy. If AST and/or ALT >3 times but 5 time upper limit of normal without symptoms or hyperbilirubinemia after starting pirfenidone, discontinue confounding medications, exclude other causes, and monitor patient closely. Repeat liver tests as needed. Full daily dose may be maintained or reduced or interrupted until liver tests within normal limits with subsequent re-titration to full dose as tolerated. If AST and/or ALT >3 times but 5 times upper limits of normal accompanied by symptoms or hyperbilirubinemia, permanently discontinue pirfenidone; do not rechallenge patient with pirfenidone. If AST and/or ALT >5 times upper limit of normal, permanently discontinue pirfenidone; do not rechallenge patient with pirfenidone.

• PO: Administer capsules with food to minimize nausea and dizziness, at same time each day following titration schedule above.
  • If >14 days are missed, reinitiate with initial titration schedule.

• Instruct patient to take pirfenidone as directed. Take missed dose as soon as remembered; do not double doses or take more than 3 doses/day. Advise patient to read Patient Information prior to starting therapy and with each Rx refill in case of changes.
• Advise patient to notify health care professional if signs and symptoms of liver dysfunction (skin or whites of eyes turn yellow, dark brown or tea colored urine, pain on right side of stomach, bleeding or bruising, lethargy) or GI dysfunction occur.
• Advise smokers to stop smoking prior to and avoid smoking during therapy.
• Caution patient to use sunscreen (SPF 50 of higher) and protective clothing to prevent photosensitivity reactions and to avoid concurrent medications that cause photosensitivity. May require dose reduction or discontinuation.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Advise female patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
• Emphasize the importance of follow up blood tests to determine liver function.

• Decrease in rate of decline in forced vital capacity (FVC) and extension in time to first exacerbation of pulmonary fibrosis.

Esbriet

• Ineffective breathing pattern (Indications).

NDC Code^*

• 50242- Genentech, Inc.
  • 50242-121- ESBRIET
    • 50242-121-01- 1 BOTTLE, PLASTIC in 1 CARTON (50242-121-01) > 270 CAPSULE in 1 BOTTLE, PLASTIC

• 50242- Genentech, Inc.
  • 50242-121- ESBRIET
    • 50242-121-87- 1 BLISTER PACK in 1 CARTON (50242-121-87) > 63 CAPSULE in 1 BLISTER PACK

• 50242- Genentech, Inc.
  • 50242-123- ESBRIET
    • 50242-123-01- 1 BOTTLE, PLASTIC in 1 CARTON (50242-123-01) > 90 TABLET, COATED in 1 BOTTLE, PLASTIC

• 64116- InterMune, Inc.
  • 64116-121- Esbriet
    • 64116-121-01- 1 BOTTLE, PLASTIC in 1 CARTON (64116-121-01) > 270 CAPSULE in 1 BOTTLE, PLASTIC

• 64116- InterMune, Inc.
  • 64116-121- Esbriet
    • 64116-121-02- 1 BLISTER PACK in 1 CARTON (64116-121-02) > 63 CAPSULE in 1 BLISTER PACK

• 64116- InterMune, Inc.
  • 64116-121- Esbriet
    • 64116-121-03- 4 BLISTER PACK in 1 CARTON (64116-121-03) > 63 CAPSULE in 1 BLISTER PACK