pirfenidone

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

Distribution: Unknown.

Metabolism/Excretion: Mostly metabolized by the CYP1A2 isoenzyme, with some metabolism by other CYP isoenzymes. 80% excreted in urine as inactive metabolite.

Half-Life: 3 hr.

Time/Action Profile ⬆ ⬇

(effects on pulmonary function)

ROUTE	ONSET	PEAK	DURATION
PO	within 3 mo	6–7 mo	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

End-stage renal disease on dialysis;
Severe hepatic impairment;
Lactation: Lactation.

Use Cautiously in:

Mild to moderate hepatic impairment;
Renal impairment (CCr ≤80 mL/min) (monitor carefully/consider dose ↓);
Exposure to sunlight;
Cigarette smokers (may have ↓ 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.

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), photosensitivity, pruritus, STEVENS-JOHNSON SYNDROME (SJS), TOXIC EPIDERMAL NECROLYSIS (TEN)

GI: abdominal pain, gastrointestinal reflux disease, nausea, diarrhea, dyspepsia, HEPATOTOXICITY, vomiting

Metab: ↓appetite, weight loss

MS: arthralgia

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

Interactions ⬆ ⬇

Drug-drug:

Concurrent use of strong inhibitors of CYP1A2, including fluvoxamine, ↑ levels and risk of toxicity (concurrent use not recommended; if unavoidable ↓ dose of pirfenidone).
Concurrent use of moderate inhibitors of CYP1A2, including ciprofloxacin, ↑ 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↑ levels and risk of toxicity (discontinue prior to treatment).
Concurrent use of strong inducers of CYP1A2 may ↓ levels and effectiveness (discontinue prior to treatment).

Route/Dosage ⬆ ⬇

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).

Availability ⬆ ⬇

(Generic available)

Capsules: 267 mg
Film-coated tablets: 267 mg; 534 mg; 801 mg

Assessment ⬆ ⬇

Monitor for signs and symptoms of pulmonary fibrosis (dyspnea, decreased forced vital capacity, 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 patient for development of rash. May cause SJS or TEN. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis, and/or eosinophilia.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, facial swelling, eosinophilia) periodically during therapy. If symptoms occur, discontinue therapy.

Lab Test Considerations:

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 times upper limit of normal (ULN) 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 retitration to full dose as tolerated. If AST and/or ALT >3 times but ≤5 times ULN accompanied by symptoms or hyperbilirubinemia, permanently discontinue pirfenidone; do not rechallenge patient with pirfenidone. If AST and/or ALT >5 times ULN, permanently discontinue pirfenidone; do not rechallenge patient with pirfenidone.

Implementation ⬆ ⬇

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.

Patient/Family Teaching ⬆ ⬇

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 severe skin reactions (painful sores or ulcers on skin, lips, or mouth; severe rash with blisters; or peeling skin), 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), GI dysfunction, or DRESS occur.
Advise smokers to stop smoking prior to and avoid smoking during therapy.
Caution patient to use sunscreen (SPF 50 or 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.
Rep: 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.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇