Roflumilast

INTRODUCTION

Indications

To ↓ the risk of exacerbations in severe COPD patients that have a history of chronic bronchitis with exacerbations.

Action

Roflumilast and 1 active metabolite (roflumilast N-oxide) act as selective inhibitors of phosphodiesterase-4 (PDE4), responsible for breaking down 3′,5′-adenosine monophosphate (cAMP). Resulting intracellular accumulation of cAMP in lung tissue. Reduces cells (neutrophils, eosinophils and total cells) in sputum. Therapeutic Effects: ↓ exacerbations in COPD patients.

Adverse Reactions/Side Effects

CNS: SUICIDAL THOUGHTS, anxiety, depression, dizziness, headache, insomnia. GI: diarrhea, abdominal pain, ↓ appetite, dyspepsia, gastritis, nausea, vomiting. Metab: weight loss. MS: muscle spasms. Neuro: tremor.

PHYSICAL THERAPY IMPLICATIONS

Examination and Evaluation

• Be alert for suicidal thoughts and ideology; notify physician immediately if patient exhibits suicidal behaviors, depression, anxiety, or other adverse changes in mood and behavior.

• Perform pulmonary function tests periodically (See Appendices I, J, K) to document effects of drug therapy on ventilation and respiratory function.

• Monitor any muscle spasms or tremor. Report any neuromuscular problems that affect gait or other functional activities.

• Assess dizziness that might affect gait, balance, and other functional activities (See Appendix C). Report balance problems and functional limitations to the physician and nursing staff, and caution the patient and family/caregivers to guard against falls and trauma.

• Periodically assess body weight and other anthropometric measures (body mass index, body composition). Report a rapid or unexplained weight loss or decreased body fat.

Interventions

• When implementing airway clearance techniques or respiratory muscle training, attempt to intervene when the airway is maximally bronchodilated. Peak responses typically occur about 1 hr after oral administration.

Patient/Client-Related Instruction

• Advise patient to not exceed the recommended dose or frequency of administration. Contact physician if COPD exacerbations are not adequately controlled by the current medication regimen, or if respiratory symptoms continue to worsen.

• Instruct patient and family/caregivers to report other troublesome side effects, including severe or prolonged headache, sleep loss, or GI problems (nausea, vomiting, diarrhea, indigestion, abdominal pain, decreased appetite).

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Parent drug and metabolites probably enter breast milk.

Protein Binding: Roflumilast—99%; roflumilast N-oxide—97%.

Metabolism and Excretion: Mostly metabolized (87.5%), primarily by CYP3A4 and CYP1A2 enzyme systems. 1 metabolite, roflumilast N-oxide, is pharmacologically active. Inactive metabolites excreted in urine.

Half-life: Roflumilast—17 hr; roflumilast N-oxide—30 hr.