Pharmaceuticals
Management of Idiopathic Pulmonary Fibrosis
Source: pharmacypracticenews
Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and often fatal interstitial lung disease characterized by scarring of the lungs with unknown etiology.1 This scarring causes the alveolar walls to become stiff and thick, preventing inflation, which reduces lung capacity and makes the exchange of oxygen and carbon dioxide more difficult. The decreased lung capacity and oxygen exchange increases breathlessness and decreases mobility and independence.2
Epidemiology
Although the precise cause of IPF is unknown, there is evidence that risk factors including age and environmental exposures play a role. The disease tends to affect adults in their sixth or seventh decade of life.3 In addition, there is a strong correlation between smoking and IPF, as well as evidence of a detrimental effect of smoking on survival.4 Environmental exposures to certain types of manufacturing-related dust and genetic factors also are contributors.5
Prognosis and Disease Course
Common symptoms of IPF include dry cough, shortness of breath, fatigue, chest pain, and unintentional weight loss.2 Because these symptoms are nonspecific and are associated with other diseases, such as asthma, chronic obstructive pulmonary disease, emphysema, and heart disease, the diagnosis of IPF often is delayed.1 Thus, significant declines in lung function can occur by the time a patient is correctly diagnosed. It is imperative to start patients on FDA-approved therapies as soon as possible to preserve lung function, reduce the risk for acute exacerbations, and improve outcomes.1
The prognosis of patients with IPF is poor; median survival duration is less than 4 years.1 The clinical course of IPF can vary by patient, with some patients experiencing a slowly progressive course and others rapidly progressing. At diagnosis, there are no distinguishing clinical characteristics to indicate the clinical course a patient is likely to experience. Acute exacerbations with clinically significant worsening of lung function and/or dyspnea can occur at any time during the course of the disease and are associated with a high risk for mortality.1
Treatment
Historically, the only treatment options available to patients with IPF were focused on symptom relief and not slowing the disease course. In 2014, the FDA approved 2 oral antifibrotic therapies for IPF: nintedanib (Ofev, Boehringer Ingelheim) and pirfenidone (Esbriet, Genentech) (Table).3 Current guidelines from respiratory societies recommend antifibrotic agents as first-line therapy for patients with IPF.6
In addition, patients can benefit from a holistic approach to care that includes pulmonary rehabilitation, education and support, vaccinations, and supplemental oxygen.2,7 Although there is no cure for IPF, medications combined with lifestyle changes can help to slow the decline in lung function, decrease respiratory symptoms, and reduce acute exacerbations.1
| Table. Antifibrotic Agents Approved to Treat Idiopathic Pulmonary Fibrosis | ||||
| Medication | Dose | Common AEs | Warnings/ Precautions | Counseling Notes |
|---|---|---|---|---|
| Nintedanib (Ofev, Boehringer Ingelheim) | Recommended dose: 150 mg twice daily every 12 h with food Mild hepatic impairment (Child-Pugh A): 100 mg twice daily every 12 h with food | Diarrhea Nausea Stomach pain Decreased appetite Headache Weight loss High blood pressure | Hepatic impairment Elevated liver enzymes GI disorders Embryo-fetal toxicity Arterial thromboembolic events Bleeding events GI perforation | If AEs occur, consider a temporary dose reduction to 100 mg twice daily Pregnancy category D |
| Pirfenidone (Esbriet, Genentech) | Titration dose: Days 1-7: 267 mg 3 times daily (801 mg/d) Days 8-14: 534 mg 3 times daily (1,602 mg/d) Days 15 and beyond: 801 mg 3 times daily (2,403 mg/d) | Nausea Rash Abdominal pain Upper RTI Diarrhea Fatigue | Elevated liver enzymes Photosensitivity reaction or rash GI disorders | Patients who miss =14 d should restart with 2-wk titration regimen Take with food Pregnancy category C |
| AEs, adverse events; GI, gastrointestinal; RTI, respiratory tract infectionBased on references 8 and 9. |
Antifibrotic Agents
Nintedanib
Nintedanib is a tyrosine kinase inhibitor that targets multiple growth receptors involved in the pathogenesis of fibrotic tissue remodeling in interstitial lung disease. The recommended dose is 150 mg orally twice daily with food.8 A dose reduction to 100 mg orally twice daily should be considered for patients with mild hepatic impairment or for the management of adverse events (AEs).8 The most common AEs are diarrhea, nausea, and vomiting. The nintedanib labeling includes warnings and precautions related to hepatic impairment, elevated liver enzymes, gastrointestinal disorders, embryo-fetal toxicity, arterial thromboembolic events, and bleeding events.8
In clinical trials, nintedanib resulted in statistically significant reductions in the annual rate of lung function decline, as measured by forced vital capacity (FVC), preserving lung function, and reduced the risk for acute exacerbations in the first year of therapy.8
Pirfenidone
Pirfenidone is an antifibrotic medication that is thought to have multiple effects. It has been shown to regulate important profibrotic and pro-inflammatory cytokine cascades in vitro and to reduce fibroblast proliferation and collagen synthesis in animal models.9 The recommended maintenance dose of pirfenidone is 801 mg 3 times daily taken with food, but patients will titrate to the full dosage over a 14-day period.9 The most common AEs are nausea, rash, and abdominal pain. The labeling for pirfenidone includes warnings and precautions about elevated liver enzymes, photosensitivity, rash, and gastrointestinal disorders.9
In clinical trials, pirfenidone was shown to significantly reduce the risk for lung function decline as measured by FVC and to preserve lung function.9
Role of the Specialty Pharmacist
At AllianceRx Walgreens Prime, due to the complex nature of IPF, specialty pharmacists play a critical role educating, counseling and monitoring patients. Educating patients about the disease and the importance of receiving all recommended vaccinations is essential.1 Specialty pharmacists can provide counseling and support related to healthy lifestyle changes, such as smoking cessation, improved nutrition, and increased exercise.1,59 Because the diagnosis of IPF often is delayed due to misdiagnosis, patients likely will have had declining lung function for quite some time. Thus, it is crucial for pharmacists to educate patients about the importance of starting antifibrotic therapy as soon as possible to preserve lung function, slow disease progression, and improve outcomes.1 In addition, specialty pharmacists can educate patients and monitor for AEs associated with antifibrotic therapies. Both medications approved for IPF have warnings and precautions associated with their use. Pharmacists can counsel patients about signs and symptoms to be aware of and when to seek medical attention. Pharmacists also can help ensure patients keep their appointments for laboratory monitoring. By supporting IPF patients in these ways, specialty pharmacists can help optimize outcomes for this population.