Abstract

ADVERSE EFFECTS OF PIRFENIDONE AND RAPAMYCIN COMBINATION THERAPY IN IDIOPATHIC PULMONARY FIBROSIS - A COMPREHENSIVE REVIEW

M. Babykala*, Priyangha J., Gokul M., Adhithya S.

ABSTRACT

Idiopathic Pulmonary Fibrosis (IPF) is a persistent, slowly spreading interstitial lung disease characterized by alveolar epithelial damage, excessive deposition of extra-cellular matrix and impaired gaseous exchange, leading to serious respiratory dysfunction and low survival. Existing therapies are intended to reduce the rate of disease progression and enhance pulmonary function. This review evaluates the potential therapeutic potential and safety profile of pirfenidone and rapamycin combination therapy in the management of IPF. Anti-fibrotic and anti-inflammatory pirfenidone suppresses collagen synthesis and fibroblast proliferation whereas mTOR rapamycin regulates immune responses and T-cell proliferation with anti-fibrotic effects also mediated by TGFb 1 /Smad2/3 signalling. Preclinical findings suggest that combination can have greater anti-fibrotic than monotherapy. But side effects such as dermatological reactions, gastrointestinal discomfort, metabolic changes, fatigue and oedema are also noted which can decrease patient compliance. This review underlines the value of personalized therapy, dose optimization and close attention to monitor adverse reactions. Possible future directions are mass-clinical validation, clarification of toxicity molecular pathways, predictive biomarker discovery and optimization of drug delivery regimens including local or inhaled formulations. Pirfenidone with rapamycin combination has potential improvement of clinical outcomes and quality of life in patients with IPF with ongoing research, personalized approaches and close pharmacovigilance.

Keywords: Idiopathic Pulmonary Fibrosis, Pirfenidone, Rapamycin, Anti-fibrotic Therapy, Adverse Effects, Combination Therapy.