ESBRIET
Clinical safety rating
cautionComprehensive clinical and safety monograph for ESBRIET (ESBRIET).
Pirfenidone inhibits TGF-β stimulated collagen production and reduces fibroblast proliferation, exhibiting anti-inflammatory and antifibrotic effects in pulmonary fibrosis.
| Metabolism | Primarily hepatic via CYP1A2 (major), with minor contributions from CYP2C9, CYP2C19, CYP2D6, and CYP2E1. |
| Excretion | Renal excretion of parent drug and metabolites accounts for approximately 99% of elimination, with about 82% recovered in urine and 1% in feces. Pirfenidone is extensively metabolized, with less than 1% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 3 hours (range 1.5-5 hours) in healthy adults. In patients with idiopathic pulmonary fibrosis, half-life is similar but exhibits interindividual variability. |
| Protein binding | Protein binding is approximately 50-58%, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 1.0 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 80% (range 70-90%) under fed conditions; food reduces peak concentration but increases total exposure. |
| Onset of Action | Oral: Onset of action is not immediate; clinical effects on lung function decline are typically observed after 3-6 months of continuous therapy. |
| Duration of Action | Duration of action is continuous with regular dosing; trough concentrations are maintained with three times daily administration. Clinical benefit requires sustained treatment and may be lost upon discontinuation. |
| Molecular Weight | 185.22 |
801 mg three times daily orally with food.
| Dosage form | TABLET |
| Renal impairment | GFR 30-50 mL/min: 267 mg three times daily; GFR < 30 mL/min: not recommended. |
| Liver impairment | Child-Pugh A: 801 mg three times daily; Child-Pugh B: 267 mg three times daily; Child-Pugh C: contraindicated. |
| Pediatric use | Not established; safety and efficacy in pediatric patients have not been studied. |
| Geriatric use | No specific dose adjustment recommended; monitor renal function and consider lower starting dose due to age-related decline in renal function. |
| 1st trimester | Avoid. Based on animal studies, there is evidence of fetal harm. There are no adequate human studies in pregnant women. Pirfenidone is only recommended during pregnancy if the potential benefit justifies the potential risk to the fetus. |
| 2nd trimester | Avoid. Same as first trimester. Limited human data; animal studies show teratogenicity and embryotoxicity at clinically relevant exposures. |
| 3rd trimester | Avoid. Same as previous trimesters. Potential risk of adverse fetal effects including reduced fetal weight and skeletal abnormalities in animal studies. |
Clinical note
Comprehensive clinical and safety monograph for ESBRIET (ESBRIET).
| Placental transfer | Pirfenidone crosses the placenta in animals (rats) and is detected in fetal plasma at concentrations similar to maternal plasma. Human data are absent, but due to its molecular weight and lipophilicity, placental transfer is expected. |
| Breastfeeding | It is unknown if pirfenidone is excreted in human milk. In animal studies, pirfenidone and its metabolites were present in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in nursing infants from pirfenidone, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Lactation Rating | L4 |
| Teratogenic Risk | Pirfenidone is teratogenic in animal studies, causing fetal malformations and embryotoxicity at clinically relevant exposures. There are no adequate human studies. Use during pregnancy is contraindicated; effective contraception is required before and during treatment. First trimester carries the highest risk for major congenital anomalies; second and third trimester risks include fetal growth restriction and potential pulmonary toxicity. |
| Fetal Monitoring | Baseline and periodic liver function tests (ALT, AST, bilirubin). Monitor for gastrointestinal symptoms and skin photosensitivity. During pregnancy, monitor fetal growth via serial ultrasound (e.g., every 4 weeks) and consider fetal echocardiography. Assess maternal pulmonary function and oxygen saturation regularly. |
| Fertility Effects | Animal studies show no adverse fertility effects in males or females. Human fertility data are lacking. No known effect on conception or gamete quality. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to pirfenidone or any of its excipientsSevere hepatic impairment (Child-Pugh Class C)Severe renal impairment requiring dialysis (eGFR < 30 mL/min/1.73 m²)Concomitant use with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) unless benefit outweighs risk and no alternative therapy exists
| Precautions | Hepatotoxicity: monitor liver function tests before and during treatment; discontinue if significant elevation., Photosensitivity and rash: avoid sun exposure; use sunscreen., Gastrointestinal effects: nausea, diarrhea, dyspepsia; take with food., Elevated liver enzymes: dose reduction or interruption may be required. |
| Food/Dietary | Take with meals to reduce GI intolerance. Grapefruit and grapefruit juice may increase pirfenidone blood levels and should be avoided. Avoid smoking as it induces CYP1A2 and may reduce drug efficacy. |
| Clinical Pearls | Pirfenidone (Esbriet) is an antifibrotic agent approved for idiopathic pulmonary fibrosis (IPF). It reduces decline in lung function but does not reverse fibrosis. Monitor liver function tests (LFTs) monthly for 6 months then every 3 months due to risk of hepatotoxicity. Photosensitivity is common; advise strict sun avoidance and broad-spectrum sunscreen. Dosage titration over 14 days reduces GI side effects. Avoid use with strong CYP1A2 inhibitors (e.g., fluvoxamine, ciprofloxacin) as they increase pirfenidone exposure. |
| Patient Advice | Take with food to reduce nausea and upset stomach. · Avoid sun exposure; wear protective clothing and apply sunscreen daily due to risk of severe sunburn. · Do not stop or change dose without consulting your doctor; taper is not required but missed doses should be skipped. · Report any signs of liver problems: yellowing of skin/eyes, dark urine, fatigue, or abdominal pain. · Avoid smoking and grapefruit products as they may affect drug levels. |
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