Drug News
TOBI Podhaler for cystic fibrosis patients with Pseudomonas aeruginosa By Abimbola Farinde, PhD, PharmD
Cystic fibrosis (CF) is one of the most common and fatal autosomal recessive diseases among White Americans.1 It is estimated that about 30,000 people are affected with the disease in the United States.1 CF occurs in various degrees of severity and affects multiple systems (digestive, respiratory, and reproductive). The leading cause of death in patients with CF is related to the progressive pulmonary disease.1,2 CF develops as a result of a mutation in the CF transmembrane conductance regulator (CFTR), a gene on chromosome 7 that encodes the CF transmembrane conduction
morbidity and mortality.2,4 Delta F508 (70%) is the most commonly identified phenotype for the majority of these mutations in a patient with CF and causes the abnormal clearance of mucus from the lungs.4 Environmental factors have been shown to contribute to the progression of the disease, such as chronic bronchopulmonary pathogenic colonization due to mucoid Pseudomonas (P.) aeruginosa.4,5 The available treatment options for CF have improved within recent years, and the most commonly observed treatment interventions include antibiotics, chest physical therapy, and exercise. The primary
TOBI Podhaler is delivered into the patient’s lungs through a pocket-size dry powder inhaler. regulation protein. Mutations of CFTR (delta F508) impair the transport of chloride ions and water and result in the buildup of mucus on the epithelial surfaces located in the pancreas, respiratory, and gastrointestinal tract.1-3 ■ Treatment options There are approximately 1,500 identified mutations and 300 polymorphisms in the CFTR gene that are placed into five classes with classes I, II, and III believed to produce the most severe consequence of the pulmonary disease and higher rates of associated
goal of most treatments is to prevent and control infections within the lungs, remove mucus from the lungs, and prevent intestinal obstruction.6 The tobramycin inhalation powder (TOBI Podhaler) is one of the newer agents for the management of CF patients with P. aeruginosa bacterial infection in the lungs and is developed by Novartis. TOBI Podhaler, a powder formulation of tobramycin, was approved in March 2013 by the FDA7 ■ Indication TOBI Podhaler is a plastic, handheld inhaler device that contains a
dry powder formulation of tobramycin that is used to manage adult and pediatric patients age 6 years and older with CF who have P. aeruginosa.8,9 ■ Mechanism of action TOBI Podhaler is dry formulation of the aminoglycoside antibiotic that is bactericidal and disrupts protein synthesis causing an alteration in cell membrane permeability and eventually cell death.9,10 ■ Dosing and administration For the management of CF patients with P. aeruginosa, TOBI Podhaler is delivered into the patient’s lungs through a pocket-size dry powder inhaler that contains four 28-mg capsules (capsules are supplied in a unit-dose blister pack) every 12 hours for repeated cycles of 28 days on the drug followed by 28 days off the drug.8-10 The same dosing regimen is applied to adults and children 6 years and older. TOBI Podhaler should not to be given in doses that are less than 6 hours apart.9 There is no requirement for a dosage adjustment in those with hepatic impairment, but caution should be exercised in those with kidney dysfunction.9,10 ■ Warning and precautions TOBI Podhaler is contraindicated in individuals with a hypersensitivity to tobramycin, other aminoglycosides, or any component of the formulation.9
16 The Nurse Practitioner • Vol. 40, No. 7
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.tnpj.com
Drug News
TOBI Podhaler is associated with the risk of nephrotoxicity, neurotoxicity, ototoxicity, neuromuscular disorders, and bronchospasm with an alert for these potential effects.9 The risk factors for the development of nephrotoxicity include advanced age, preexisting kidney impairment, or the concurrent use of other nephrotoxic drugs.8,10 The drug also carries a warning for its use during pregnancy, as it may cause fetal harm. There are reports of total, irreversible, bilateral congenital deafness in patients exposed to the drug in utero.9 Tobramycin can be excreted in breast milk, and breastfeeding is not recommended by the manufacturer. The drug may cause ototoxicity and nephrotoxicity in infants and a decision to stop breastfeeding or stop the drug needs to be made based on the clinical importance of the drug to the mother.9 ■ Adverse reactions The most commonly reported adverse reactions during clinical trials included cough, hemoptysis, dysphonia, shortness of breath, headache, fever, and oropharyngeal pain.9,11 ■ Drug interactions The major drug interactions associated with the use of TOBI Podhaler include its use with other nephrotoxic drugs (for example, amphotericin B, cephalosporins, gallium nitrate, or vancomycin), which may enhance the nephrotoxic effect. The use of TOBI Podhaler with bumetanide, ethacrynic acid, furosemide, and I.V. mannitol should be avoided, or another alternative drug should be used due to the risk of ototoxicity and/or nephrotoxicity.9-11 ■ Pharmacokinetics TOBI Podhaler’s absorption is approximately 1 mcg/mL after a www.tnpj.com
112-mg dose (4 capsules × 28 mg/ capsule). The drug is approximately less than 30% protein bound with a half-life elimination of about 3 hours after 112-mg single dose. The metabolism is negligible. It undergoes excretion in the urine (about 90% to 95%) in about 24 hours in
Patients should be informed about missed doses of TOBI Podhaler, since it requires repeated cycles of 28 days. The dose should be taken as soon as possible, if there is at least 6 hours to the next dose. Patients should also be told not to double the dose to make up for a missed dose.9
TOBI Podhaler should not to be given in doses that are less than 6 hours apart. CF patients with normal kidney function.8-11 ■ Clinical pearls • TOBI Podhaler is a pregnancy category D drug. • Capsules are not to be swallowed and should only be used with the oral inhalation podhaler device. • Capsules should be protected from moisture, stored in the unit-dose blister pack, and only removed from the pack immediately before use. • TOBI Podhaler should be used with caution in patients with impaired kidney function. • Patients should be instructed to contact their healthcare provider if they experience an adverse reaction that is thought to be due to TOBI Podhaler. • Patients should be educated about the importance of informing their healthcare providers regarding all prescription and over-the-counter medications, herbal products, vitamins, nutraceuticals, and supplements that they are taking (in particular patients need to inform their healthcare providers if they are taking any drugs that are nephrotoxic, neurotoxic, ototoxic or those that cause neuromuscular blockade that can be associated with drug interactions with TOBI Podhaler.
REFERENCES 1. Green DM. Cystic fibrosis: a model for personalized genetic medicine. N C Med J. 2013;74(6):486-487. 2. Schippa S, Iebba V, Santangelo F, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PLoS One. 2013;8(4):e61176. 3. Boucher RC. An overview of the pathogenesis of cystic fibrosis lung disease. Adv Drug Deliv Rev. 2002;54(11):1359-1371. 4. Cantón R, del Campo R. Cystic fibrosis: deciphering the complexity. Clin Microbiol Infect. 2010;16(7):793-797. 5. Buchanan PJ, Ernst RK, Elborn JS, Schock B. Role of CFTR, Pseudomonas aeruginosa and Toll-like receptors in cystic fibrosis lung inflammation. Biochem Soc Trans. 2009;37(Pt 4):863-867. 6. Davies JC, Alton EW, Bush A. Cystic fibrosis. BMJ. 2007;335(7632):1255-1259. 7. U.S Food and Drug Administration. FDA approves TOBI Podhaler to treat a type of bacterial lung infection in cystic fibrosis patients. 2013. http://www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm345123.htm. 8. TOBI.™ Lexi-Comp Online, Hudson, Ohio: Lexi-Comp, Inc.; 2004; January 31, 2014. 9. Novartis Pharmaceuticals Corporation. TOBI Podhaler prescribing information. http:// www.accessdata.fda.gov/drugsatfda_docs/ label/2014/201688s002lbl.pdf. 10. TOBI Podhaler. Epocrates. Epocrates, Inc, 2014. January 31, 2014. 11.Pierart F. Tobi podhaler for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. Rev Med Liege. 2013;68(9): 486-488.
Abimbola Farinde is a clinical supervisor in the Pharmacy Department, at Bayshore Medical Center, Pasadena, Tex. The author has disclosed that she has no financial relationships related to this article. DOI-10.1097/01.NPR.0000459736.07899.73
The Nurse Practitioner • July 2015 17
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
TOBI Podhaler for cystic fibrosis patients with Pseudomonas aeruginosa By Abimbola Farinde, PhD, PharmD
Cystic fibrosis (CF) is one of the most common and fatal autosomal recessive diseases among White Americans.1 It is estimated that about 30,000 people are affected with the disease in the United States.1 CF occurs in various degrees of severity and affects multiple systems (digestive, respiratory, and reproductive). The leading cause of death in patients with CF is related to the progressive pulmonary disease.1,2 CF develops as a result of a mutation in the CF transmembrane conductance regulator (CFTR), a gene on chromosome 7 that encodes the CF transmembrane conduction
morbidity and mortality.2,4 Delta F508 (70%) is the most commonly identified phenotype for the majority of these mutations in a patient with CF and causes the abnormal clearance of mucus from the lungs.4 Environmental factors have been shown to contribute to the progression of the disease, such as chronic bronchopulmonary pathogenic colonization due to mucoid Pseudomonas (P.) aeruginosa.4,5 The available treatment options for CF have improved within recent years, and the most commonly observed treatment interventions include antibiotics, chest physical therapy, and exercise. The primary
TOBI Podhaler is delivered into the patient’s lungs through a pocket-size dry powder inhaler. regulation protein. Mutations of CFTR (delta F508) impair the transport of chloride ions and water and result in the buildup of mucus on the epithelial surfaces located in the pancreas, respiratory, and gastrointestinal tract.1-3 ■ Treatment options There are approximately 1,500 identified mutations and 300 polymorphisms in the CFTR gene that are placed into five classes with classes I, II, and III believed to produce the most severe consequence of the pulmonary disease and higher rates of associated
goal of most treatments is to prevent and control infections within the lungs, remove mucus from the lungs, and prevent intestinal obstruction.6 The tobramycin inhalation powder (TOBI Podhaler) is one of the newer agents for the management of CF patients with P. aeruginosa bacterial infection in the lungs and is developed by Novartis. TOBI Podhaler, a powder formulation of tobramycin, was approved in March 2013 by the FDA7 ■ Indication TOBI Podhaler is a plastic, handheld inhaler device that contains a
dry powder formulation of tobramycin that is used to manage adult and pediatric patients age 6 years and older with CF who have P. aeruginosa.8,9 ■ Mechanism of action TOBI Podhaler is dry formulation of the aminoglycoside antibiotic that is bactericidal and disrupts protein synthesis causing an alteration in cell membrane permeability and eventually cell death.9,10 ■ Dosing and administration For the management of CF patients with P. aeruginosa, TOBI Podhaler is delivered into the patient’s lungs through a pocket-size dry powder inhaler that contains four 28-mg capsules (capsules are supplied in a unit-dose blister pack) every 12 hours for repeated cycles of 28 days on the drug followed by 28 days off the drug.8-10 The same dosing regimen is applied to adults and children 6 years and older. TOBI Podhaler should not to be given in doses that are less than 6 hours apart.9 There is no requirement for a dosage adjustment in those with hepatic impairment, but caution should be exercised in those with kidney dysfunction.9,10 ■ Warning and precautions TOBI Podhaler is contraindicated in individuals with a hypersensitivity to tobramycin, other aminoglycosides, or any component of the formulation.9
16 The Nurse Practitioner • Vol. 40, No. 7
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.tnpj.com
Drug News
TOBI Podhaler is associated with the risk of nephrotoxicity, neurotoxicity, ototoxicity, neuromuscular disorders, and bronchospasm with an alert for these potential effects.9 The risk factors for the development of nephrotoxicity include advanced age, preexisting kidney impairment, or the concurrent use of other nephrotoxic drugs.8,10 The drug also carries a warning for its use during pregnancy, as it may cause fetal harm. There are reports of total, irreversible, bilateral congenital deafness in patients exposed to the drug in utero.9 Tobramycin can be excreted in breast milk, and breastfeeding is not recommended by the manufacturer. The drug may cause ototoxicity and nephrotoxicity in infants and a decision to stop breastfeeding or stop the drug needs to be made based on the clinical importance of the drug to the mother.9 ■ Adverse reactions The most commonly reported adverse reactions during clinical trials included cough, hemoptysis, dysphonia, shortness of breath, headache, fever, and oropharyngeal pain.9,11 ■ Drug interactions The major drug interactions associated with the use of TOBI Podhaler include its use with other nephrotoxic drugs (for example, amphotericin B, cephalosporins, gallium nitrate, or vancomycin), which may enhance the nephrotoxic effect. The use of TOBI Podhaler with bumetanide, ethacrynic acid, furosemide, and I.V. mannitol should be avoided, or another alternative drug should be used due to the risk of ototoxicity and/or nephrotoxicity.9-11 ■ Pharmacokinetics TOBI Podhaler’s absorption is approximately 1 mcg/mL after a www.tnpj.com
112-mg dose (4 capsules × 28 mg/ capsule). The drug is approximately less than 30% protein bound with a half-life elimination of about 3 hours after 112-mg single dose. The metabolism is negligible. It undergoes excretion in the urine (about 90% to 95%) in about 24 hours in
Patients should be informed about missed doses of TOBI Podhaler, since it requires repeated cycles of 28 days. The dose should be taken as soon as possible, if there is at least 6 hours to the next dose. Patients should also be told not to double the dose to make up for a missed dose.9
TOBI Podhaler should not to be given in doses that are less than 6 hours apart. CF patients with normal kidney function.8-11 ■ Clinical pearls • TOBI Podhaler is a pregnancy category D drug. • Capsules are not to be swallowed and should only be used with the oral inhalation podhaler device. • Capsules should be protected from moisture, stored in the unit-dose blister pack, and only removed from the pack immediately before use. • TOBI Podhaler should be used with caution in patients with impaired kidney function. • Patients should be instructed to contact their healthcare provider if they experience an adverse reaction that is thought to be due to TOBI Podhaler. • Patients should be educated about the importance of informing their healthcare providers regarding all prescription and over-the-counter medications, herbal products, vitamins, nutraceuticals, and supplements that they are taking (in particular patients need to inform their healthcare providers if they are taking any drugs that are nephrotoxic, neurotoxic, ototoxic or those that cause neuromuscular blockade that can be associated with drug interactions with TOBI Podhaler.
REFERENCES 1. Green DM. Cystic fibrosis: a model for personalized genetic medicine. N C Med J. 2013;74(6):486-487. 2. Schippa S, Iebba V, Santangelo F, et al. Cystic fibrosis transmembrane conductance regulator (CFTR) allelic variants relate to shifts in faecal microbiota of cystic fibrosis patients. PLoS One. 2013;8(4):e61176. 3. Boucher RC. An overview of the pathogenesis of cystic fibrosis lung disease. Adv Drug Deliv Rev. 2002;54(11):1359-1371. 4. Cantón R, del Campo R. Cystic fibrosis: deciphering the complexity. Clin Microbiol Infect. 2010;16(7):793-797. 5. Buchanan PJ, Ernst RK, Elborn JS, Schock B. Role of CFTR, Pseudomonas aeruginosa and Toll-like receptors in cystic fibrosis lung inflammation. Biochem Soc Trans. 2009;37(Pt 4):863-867. 6. Davies JC, Alton EW, Bush A. Cystic fibrosis. BMJ. 2007;335(7632):1255-1259. 7. U.S Food and Drug Administration. FDA approves TOBI Podhaler to treat a type of bacterial lung infection in cystic fibrosis patients. 2013. http://www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm345123.htm. 8. TOBI.™ Lexi-Comp Online, Hudson, Ohio: Lexi-Comp, Inc.; 2004; January 31, 2014. 9. Novartis Pharmaceuticals Corporation. TOBI Podhaler prescribing information. http:// www.accessdata.fda.gov/drugsatfda_docs/ label/2014/201688s002lbl.pdf. 10. TOBI Podhaler. Epocrates. Epocrates, Inc, 2014. January 31, 2014. 11.Pierart F. Tobi podhaler for treating chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. Rev Med Liege. 2013;68(9): 486-488.
Abimbola Farinde is a clinical supervisor in the Pharmacy Department, at Bayshore Medical Center, Pasadena, Tex. The author has disclosed that she has no financial relationships related to this article. DOI-10.1097/01.NPR.0000459736.07899.73
The Nurse Practitioner • July 2015 17
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
