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ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvMTAxMTAwNy1vdmVydmlldw==\nDrugs & Diseases > Pediatrics: Cardiac Disease and Critical Care Medicine\nPediatric Theophylline Toxicity\nUpdated: Aug 18, 2016\nAuthor: Tracey H Reilly, MD; Chief Editor: Timothy E Corden, MD more...\nSections Pediatric Theophylline Toxicity\nLaboratory Studies\nAntiemetics\nDrug absorption reducers\nWhole bowel irrigation agents\nAlpha agonists\nBeta-adrenergic blocking agents\nThe frequency of theophylline overdose has greatly decreased as the use of theophylline for the treatment of asthma and chronic obstructive pulmonary disease (COPD) has declined, because of its narrow therapeutic window and the effectiveness of inhaled beta-agonists. The occurrence of adverse effects with theophylline, even at levels in the therapeutic range, and the severity of its effects in acute and chronic overdose are notable; however, theophylline continues to be prescribed for some patients. [1, 2, 3]\nTheophylline is a methylxanthine derivative that works by inhibiting phosphodiesterase and potentiating intracellular levels of cyclic adenosine monophosphate (cAMP). It is also an antagonist at adenosine receptors in the bronchial smooth muscle, peripheral vasculature, CNS, and myocardium. Peak serum levels occur 90-120 minutes after oral administration, and sustained-release preparations are common; these preparations cause delayed absorption and potential bezoar formation.\nTheophylline is 56% protein bound and has a volume of distribution of 0.5 L/kg. Approximately 90% of it is metabolized by the CYP1A2 isozyme of the hepatic cytochrome P450 system to form inactive substances, and 10% is excreted unchanged in the urine. The elimination half-life is significantly longer in neonates than in children and adolescents and is increased in patients with viral illness, congestive heart failure, and hepatic disease. Theophylline metabolism is inhibited by drugs that affect the cytochrome P450 system such as cimetidine, macrolides, and fluoroquinolones. Drugs such as phenytoin, barbiturates, carbamazepine, and tobacco can increase the metabolism of theophylline and lead to toxicity when they are discontinued.\nTheophylline affects various body systems, as follows:\nCardiovascular system: Theophylline stimulates beta1-receptors and can cause atrial tachydysrhythmias such as sinus and supraventricular tachycardia, even at therapeutic levels. Higher levels can also cause atrial fibrillation, multifocal atrial tachycardia in patients with COPD, and, occasionally, ventricular tachycardia or fibrillation. Hypotension may occur in severe overdoses secondary to beta2-receptor–stimulated vasodilatation. It may be refractory to fluids and conventional vasopressors.\nCNS: Neurologic adverse effects, including tremor, restlessness, and agitation, can also occur at therapeutic levels. Seizure is the most severe neurologic effect, occurring at levels higher than 90 mcg/mL in acute overdose, higher than 30 mcg/mL in acute-on-chronic ingestion, and as low as 20 mcg/mL in chronic toxicity.\nGI system: Nausea and vomiting are common in acute overdose. Abdominal pain and diarrhea can occur, and drug bezoars may occur with ingestion of sustained-release products.\nMetabolic system: Hypokalemia, hyperglycemia, hypercalcemia, hypophosphatemia, hypomagnesemia, and metabolic acidosis can occur secondary to beta-adrenergic stimulation.\nIn 2014, the American Association of Poison Control Centers (AAPCC) reported 133 single exposures to theophylline or aminophylline, 20 of them in children or adolescents up to 19 years of age. [2] By comparison, in 2006 the AAPCC reported 413 such exposures, 73 of them in children or adolescents. [4] The decrease in the incidence of theophylline toxicity parallels the decline in the prescription of theophylline, in response to the safety and efficacy of inhaled beta2-agonists in the treatment of asthma and COPD.\nNo current statistics on the international use of theophylline are available, although the drug continues to be available. It is potentially available without prescription in some countries.\nThe most significant morbidity and mortality of theophylline toxicity in acute overdose are secondary to the cardiovascular and CNS effects. Life-threatening tachydysrhythmias and hypotension, as well as refractory seizures, can occur.\nAlthough theophylline toxicity can occur in people of any age, it is more severe in neonates than in children and adolescents. [5]\nThe prognosis of patients with theophylline toxicity depends on the amount and severity of the ingestion. Significant ingestions increase the risk of death from dysrhythmias, refractory hypotension, or status epilepticus.\nHypoxic brain injury is a risk in patients with status epilepticus, prolonged hypotension, or significant aspiration causing hypoxia.\nPatients should be advised of the potential for serious toxicity in acute and chronic overdose and of the potential for serious drug interactions.\nPatients should be advised that current drugs for the treatment of asthma and chronic obstructive pulmonary disease (COPD), such as inhaled beta-agonists and inhaled steroids, offer better therapeutic effects without the risk of significant toxicity associated with theophylline.\nFor excellent patient education resources, visit eMedicineHealth's First Aid and Injuries Center. Also, see eMedicineHealth's patient education articles Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.\nBarnes PJ. Theophylline. Am J Respir Crit Care Med. 2013 Oct 15. 188(8):901-6. [Medline].\nMowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015. 53 (10):962-1147. [Medline].\nZhu B, Haghi M, Goud M, Young PM, Traini D. The formulation of a pressurized metered dose inhaler containing theophylline for inhalation. Eur J Pharm Sci. 2015 Aug 30. 76:68-72. [Medline].\nBronstein AC, Spyker DA, Cantilena LR Jr, et al. 2006 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS). Clin Toxicol (Phila). 2007 Dec. 45(8):815-917. [Medline].\nAdén U. Methylxanthines during pregnancy and early postnatal life. Handb Exp Pharmacol. 2011. 373-89. [Medline].\nHopkins ME, MacKenzie-Ross RV. Case Report: The risks associated with chronic theophylline therapy and measures designed to improve monitoring and management. BMC Pharmacol Toxicol. 2016 Mar 5. 17:13. [Medline].\nNovelli G, Rossi M, Morabito V, et al. Pediatric acute liver failure with molecular adsorbent recirculating system treatment. Transplant Proc. 2008 Jul-Aug. 40(6):1921-4. [Medline].\nFisher J, Graudins A. Intermittent haemodialysis and sustained low-efficiency dialysis (SLED) for acute theophylline toxicity. J Med Toxicol. 2015 Sep. 11 (3):359-63. [Medline].\nCharytan D, Jansen K. Severe metabolic complications from theophylline intoxication. Nephrology (Carlton). 2003 Oct. 8(5):239-242. [Medline].\nShannon MW. Comparative efficacy of hemodialysis and hemoperfusion in severe theophylline intoxication. Acad Emerg Med. 1997 Jul. 4(7):674-8. [Medline].\nTracey H Reilly, MD Attending Physician, Department of Emergency Medicine, United Health Services Hospitals\nTracey H Reilly, MD is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association\nChristopher P Holstege, MD Professor of Emergency Medicine and Pediatrics, University of Virginia School of Medicine; Chief, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Center; Executive Director, Department of Student Health and Wellness, University of Virginia\nChristopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American College Health Association, American College of Emergency Physicians, American College of Medical Toxicology, European Association of Poisons Centres and Clinical Toxicologists, Medical Society of Virginia, Society for Academic Emergency Medicine, Society of Toxicology, Wilderness Medical Society\nMichael E Mullins, MD Assistant Professor, Division of Emergency Medicine, Washington University in St Louis School of Medicine; Attending Physician, Emergency Department, Barnes-Jewish Hospital\nMichael E Mullins, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians\nDisclosure: Received stock ownership from Johnson & Johnson for none; Received stock ownership from Savient Pharmaceuticals for none.\nJeffrey R Tucker, MD Assistant Professor, Department of Pediatrics, Division of Emergency Medicine, University of Connecticut School of Medicine, Connecticut Children's Medical Center\nDisclosure: Received salary from Merck for employment.\nTimothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin\nTimothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society\nHalim Hennes, MD, MS Division Director, Pediatric Emergency Medicine, University of Texas Southwestern Medical Center at Dallas, Southwestern Medical School; Director of Emergency Services, Children's Medical Center\nHalim Hennes, MD, MS is a member of the following medical societies: American Academy of Pediatrics\nChandra D Aubin, MD Associate Residency Director, Division of Emergency Medicine, Assistant Professor, Washington University School of Medicine\nencoded search term (Pediatric Theophylline Toxicity) and Pediatric Theophylline Toxicity\nGenetics of Asthma\nAsthma in Pregnancy\nAllergic and Environmental Asthma\nPediatric Asthma\nAsthma Imaging\nTraffic-Related Air Pollution and Lung Growth in Very Young Children\nPediatricians Have Accomplished More With Less for Years -- See What We Do!\nAtopic Dermatitis: Five Promising Targeted Therapies\nAll About Allergies: Be Ready for Spring\nAccording to Pharmacist s\nIt's Time to Confront Student Mental Health Issues Associated With Smartphones and Social Media\nUpdates in the Management of Clostridium difficile for Adults\nManagement of Acute Ischemic Stroke: A Review of Pertinent Guideline Updates\nFast Five Quiz: Drug Side Effects\nNews Poorly-Controlled Asthma Commonly Affects Pregnancy in U.S.\nNews Asthma Control Worse for Youth in More Chaotic Families\n2001 /viewarticle/915191\nThe Demise of Short-Acting Beta-Agonist Therapy\nDiseases & Conditions Asthma"