Lumilast

• Approved Uses:
• Reduction of risk of exacerbations in patients with severe Chronic Obstructive Pulmonary Disease (COPD) associated with chronic bronchitis and a history of exacerbations.
• Off-Label Uses:
• Occasionally used in severe asthma with neutrophilic inflammation, though this use is not officially approved.

• Adults:
• 500 micrograms (0.5 mg) orally once daily, preferably at the same time each day.
• Pediatrics:
• Safety and efficacy have not been established; use is not recommended.
• Elderly:
• No dose adjustment necessary; monitor for adverse effects.
• Renal Impairment:
• No dose adjustment required for mild to moderate impairment; caution advised in severe impairment.
• Hepatic Impairment:
• Contraindicated in moderate to severe hepatic impairment.
• Administration Route: Oral tablets.
• Duration: Long-term management.

Roflumilast selectively inhibits phosphodiesterase-4 (PDE4), leading to increased intracellular cyclic adenosine monophosphate (cAMP) in inflammatory cells. This elevation of cAMP suppresses the release of pro-inflammatory mediators such as cytokines and chemokines, resulting in reduced inflammation within the airways. The anti-inflammatory effect contributes to decreased frequency and severity of COPD exacerbations.

• Absorption: Rapid, with peak plasma concentration reached approximately 1 hour after dosing.
• Bioavailability: Approximately 80%.
• Distribution: Widely distributed; volume of distribution ~100 L.
• Metabolism: Hepatic metabolism primarily via CYP3A4 and CYP1A2 enzymes to active metabolite roflumilast N-oxide.
• Active Metabolite: Roflumilast N-oxide has similar pharmacological activity and a longer half-life.
• Elimination: Mainly excreted via urine and feces.
• Half-Life: Parent drug ~17 hours; active metabolite ~30 hours.
• Onset: Therapeutic effects typically observed after several weeks of treatment.

• Pregnancy: Classified as FDA Pregnancy Category C. Animal studies indicate potential risk; human data are insufficient. Use only if benefits outweigh risks.
• Lactation: Unknown if excreted in human milk. Breastfeeding is generally not recommended during treatment due to lack of safety data.

• Primary Class: Respiratory anti-inflammatory agent.
• Subclass: Selective phosphodiesterase-4 (PDE4) inhibitor.

• Hypersensitivity to roflumilast or any excipients.
• Moderate to severe hepatic impairment.
• Use in patients with a history of severe psychiatric disorders should be avoided or closely monitored.

• Monitor patients for psychiatric symptoms including depression, anxiety, insomnia, and suicidal ideation.
• Monitor weight regularly due to potential weight loss.
• Not intended for acute COPD exacerbations or bronchospasm.
• Caution in severe renal impairment.
• Avoid abrupt discontinuation.

• Common: Diarrhea, nausea, weight loss, headache, insomnia, decreased appetite.
• Serious/Rare: Depression, suicidal thoughts, allergic reactions such as rash or angioedema.
• Onset of side effects usually within the first weeks of therapy.

• Inducers of CYP3A4 and CYP1A2 (e.g., rifampin): May reduce effectiveness by increasing metabolism.
• Inhibitors of CYP3A4 and CYP1A2 (e.g., erythromycin): May increase toxicity risk.
• No significant food interactions reported.
• Alcohol may increase central nervous system side effects.

• GOLD guidelines recommend roflumilast as add-on therapy for severe COPD with chronic bronchitis and frequent exacerbations.
• Regulatory agencies have updated warnings on psychiatric side effects.
• No recent changes to dosing guidelines.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep tablets in original packaging until use.
• No refrigeration or special handling required.