Table 1.
Pharmacology and Pharmacokinetics of Nintedanib and Pirfenidone52-55
| Nintedanib | Pirfenidone | |
|---|---|---|
| Mechanism of action | Tyrosine kinase inhibition | Inhibition of TGF-β production |
| Efficacy | Slows FVC decline by 50% | Slows FVC decline by 50% |
| FDA-approved dosage for IPF | 150 mg b.i.d., doses 12 hours apart, with food | 801 mg t.i.d., with food |
| Dosage forms | 100- and 150-mg capsules | 267- and 801-mg capsules |
| t max | 4 hours (with food) | 3 hours (with food) |
| Metabolism | Hydrolysis via esterases, then glucuronidation via UGT1A1, 1A7, 1A8, and 1A10; metabolized to minor extent via CYP3A4 | Hepatic CYP1A2; metabolized to lesser extent via CYP2C9, 2C19, 2D6, 2E1 |
| Elimination | Feces (93.4%) | Renal as 5-carboxy metabolite (80%) |
| t ½ (terminal) | 9.5 hours | 3 hours |
| Drug-drug interactions | Concurrent use of P-gp and CYP3A4 inhibitors may increase nintedanib exposure | CYP1A2 inhibitors can increase pirfenidone levels; CYP1A2 inducers can reduce pirfenidone levels |
| Common adverse effect | Diarrhea | Anorexia, nausea, photosensitivity |
| Monitoring | LFTs at baseline and monthly for 3 months, then periodically; pregnancy test at baseline | LFTs at baseline and monthly for the first 6 months, every 3 months thereafter, and as clinically indicated |
| Hepatic dosing adjustment | ||
| Mild impairment (Child-Pugh class A) | 100 mg b.i.d., 12 hours apart, with food | 801 mg t.i.d., with food |
| Moderate impairment (Child-Pugh class B) | Not recommended | 801 mg t.i.d., with food |
| Severe impairment (Child-Pugh class C) | Not recommended | Not recommended |
| Renal dosing adjustment | ||
| Mild to moderate impairment (CLcr of 30-90 mL/min) | 150 mg b.i.d., 12 hours apart, with food | Dosing not studied; use with caution |
| Severe impairment (CLcr of <30 mL/min) | Dosing not studied; use with caution | Dosing not studied; use with caution |
| End-stage renal disease | Dosing not studied; use with caution | Not recommended |
Abbreviations: CLcr, creatinine clearance; FVC, forced vital capacity; LFT, liver function test; P-gp, P-glycoprotein; t½, half-life; tmax, time to maximum concentration; TGF-β, transforming growth factor β.