3.8.2017 | Victoria Lawman
Theophylline interactions Learning article Pharmaceutical Journal
Since qualifying she has worked in hospital, community and prison pharmacy. She completed her pre-registration year in St George’s Hospital, South West London. Stephanie Jones, MPharm, MRPharmS, studied pharmacy at Liverpool John Moores University graduating in 2011. In 2013 she worked within the Pharmacovigilance team at the Medicines and Healthcare Regulatory Agency. Stephanie joined the Pharmaceutical Press in January 2014 as a Clinical Writer for the Editorial Team.
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She has been using salbutamol and fluticasone/salmeterol inhalers and taking oral modified-release theophylline (400mg twice a day) to manage her emphysema, a form of chronic obstructive pulmonary disease (COPD), for several years. She asks your advice about whether she can start nicotine replacement therapy (NRT) while taking theophylline. She has been a heavy smoker for most of her life and has recently decided to quit. Kate Jones is a 50-year-old teacher.
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The drug is metabolised in the liver by cytochrome P450 isoenzymes, principally CYP1A2, to demethylated and hydroxylated products. Induction of CYP1A2 results in a more rapid clearance of theophylline, which leads to reduced, and most likely sub-therapeutic, serum theophylline concentrations. Benzodiazepines. Many drugs interact with theophylline by inhibiting or potentiating its metabolism by CYP1A2 (see ’Commonlyused drugs that interact with theophylline’).
Phenytoin increases the clearance of theophylline, and theophylline might also reduce serum concentrations.
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The manufacturers of bupropion state that the concurrent use of theophylline might lower the convulsive threshold, further increasing patients’ risk of seizures, and recommend a maximum bupropion dose of 150mg daily. However, bupropion has a small dose-related risk of seizures. Bupropion or varenicline can also be prescribed to help Kate Jones stop smoking.
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Citation: The Pharmaceutical Journal, 12 July 2014, Vol 293, No 7818, online| DOI: 10.1211/PJ.2014.
The alveoli of the lungs are damaged by emphysema, reducing the surface area for gaseous exchange and restricting oxygen uptake.
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Thyroid dysfunction can modestly affect theophylline requirements; isolated cases of theophylline toxicity have been reported in patients being treated for hypothyroidism Methotrexate.
Theophylline concentrations are increased by cimetidine, however, famotidine, nizatidine, and ranitidine do not appear to interact Ciprofloxacin.
H 2 -receptor antagonists.
An invaluable reference for interactions of conventional medicines with herbal medicines, dietary supplements and nutraceuticals. 10 NOV 2016 28 FEB 2004 28 FEB 2012 6 MAR 2012.
Methotrexate reduces theophylline clearance, and theophylline might reduce methotrexate-induced neurotoxicity; there is the possibility that it may also reduce methotrexate efficacy Phenytoin.
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The metabolism of theophylline can be affected by other factors such as smoking and possibly sex. However, another study found sex did not appear to affect theophylline clearance. A higher theophylline clearance has been reported in healthy premenopausal women compared with healthy men; this difference was thought to be caused by sex-related factors in hepatic metabolism3.
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Smoking cessation will therefore result in an increase in serum theophylline concentrations, and possibly toxicity, if the dose is not reduced. Smokers taking theophylline generally tend to require higher doses than non-smokers as tobacco smoke contains polycyclic hydrocarbons, which induce CYP1A2.
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Sonia Khan, MPharm, PGCertPharmPrac, studied pharmacy at the University of East Anglia, graduating in 2007. After becoming an information pharmacist at the National Pharmacy Association, Sonia joined the Pharmaceutical Press in 2013 as a Clinical Writer for the Editorial Team. She completed her preregistration year in Middlesex, Greater London and began working as a community pharmacist. She then became a clinical rotational pharmacist at a hospital in Hertfordshire where she obtained her Post Graduate Certificate.
For oral theophylline, the British National Formulary states that serum concentrations should be measured five days after starting therapy, and at least three days after each dose adjustment. Once a maintenance dose is established, theophylline levels can be monitored every 6–12 months.
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Currently it is not known to what extent these differences may affect metabolism, or the proportion of patients who are affected. Genetic differences in CYP1A2 function can also affect the metabolism of theophylline.
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Because it is the polycyclic hydrocarbons in tobacco smoke — not the nicotine — that increase theophylline clearance, NRT will not affect Mrs Jones’s theophylline concentrations and it can be prescribed or sold to her.
Small increases in serum concentrations can result in toxicity, particularly in patients with a level of more than 20mg/L. Patients may experience serious symptoms of toxicity, such as convulsions and arrhythmias, before symptoms like nausea and vomiting appear.
Theophylline clearance can be reduced by erythromycin, and erythromycin exposure might be reduced by theophylline Levothyroxine.
Ciprofloxacin causes large increases in theophylline concentrations Erythromycin.
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Claire has been the Lead Editor for Drug Interactions for the Pharmaceutical Press since March 2012. Claire L. Preston, BPharm, PGDipMedMan, MRPharmS, studied pharmacy at the University of Nottingham, graduating in 1998. She completed her pre-registration year in Ashford, Kent before working as a community pharmacist for several years. She then became a medicines management pharmacist at a Primary Care Trust in Kent where she undertook her Clinical Diploma. Claire started at the Pharmaceutical Press in 2007 as a Staff Editor on the British National Formulary and later became an Assistant Editor.
Kate Jones should be advised to discuss her desire to stop smoking, and the effects this will have on her theophylline treatment, with her GP before setting a date to quit smoking. If Kate Jones wishes to quit smoking she will need to be monitored for changes in her serum theophylline concentrations; a dose reduction of up to a third might be needed after just one week.
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This avoids unnecessary changes to their serum theophylline concentrations because of possible variations in absorption rates between different brands. It is important to maintain patients on the same brand of modified-release theophylline throughout their treatment.
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Theophylline appears to antagonise the sedative and anxiolytic effects of benzodiazepines.
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Theophylline is a xanthine derivative used in the treatment of asthma and stable COPD to relax the bronchial smooth muscle. It has a narrow therapeutic index; a serum theophylline concentration of 10–20mg/L is required in the majority of patients, although some may find lower theophylline levels to be sufficient to control their symptoms.
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Can someone start nicotine replacement therapy while taking theophylline to manage COPD?Nicotine and benzodiazepines interaction