Xanthines


 

Aminophylline, Theophylline


  Issues for Surgery


Increased risk of bronchospasm if omitted.


  Advice in the Perioperative period


Elective and Emergency Surgery

Continue.

Ensure that the patient is maintained on a specific manufacturer’s product (see Further Information).

For patients who may decide to quit smoking during the perioperative period see Further Information.

Post-operative Advice

Restart post-operatively as soon as next dose is due. 


  Interaction(s) with Common Anaesthetic Agents


Theophylline and aminophylline have narrow therapeutic ranges – a small difference in serum concentrations may lead to therapeutic failure or adverse drug reactions (see Further Information).

The clinical significance of the following interactions is unclear – bear them in mind in case of an unexpected response to treatment1.

Ketamine / Esketamine

There have been case reports describing seizures in patients given ketamine and aminophylline or theophylline1, 2.

The UK manufacturer of esketamine states that it may lower the seizure threshold when used concomitantly with aminophylline or theophylline and advise that this combination should be avoided1, 3.

Pancuronium

Although not commonly used bear in mind that resistance to pancuronium, and in one case supraventricular tachycardia, has been seen in patients taking aminophylline. Theophylline may be expected to interact similarly1.


  Interaction(s) with other Common Medicines used in the Perioperative Period


Antimicrobials

Theophylline Toxicity (see Further Information)
Theophylline has been shown to interact with some quinolone antibiotics4, 5, 6. In particular, ciprofloxacin has been reported to increase theophylline concentrations by more than 100% in some studies1, 4.

Theophylline clearance can be reduced by erythromycin (onset may be delayed for 2 – 7 days)1, 2, 5, 6. In some cases this has led to increased theophylline levels, and toxicity may develop. Monitor theophylline levels after 48 hours and adjust the dose accordingly. Consider using an alternative antimicrobial if possible1.

In general clarithromycin does not interact with theophylline (and therefore probably not aminophylline) but there are isolated reports of possible theophylline toxicity with concomitant use1, 4, 5, 6. A clinically relevant interaction seems unlikely; however, consider the interaction if any unexplained reduction in theophylline efficacy or adverse effects (e.g. headache, nausea) occur, and monitor theophylline concentrations accordingly1.

Risk of Seizures
Rare reports of seizures (and potentially fatalities) have occurred following concurrent use of theophylline / aminophylline and quinolones. Monitor theophylline concentrations and adjust dose accordingly; the dose should be modified based on day 2 of ciprofloxacin therapy1.

Seizures have developed in 2 patients taking theophylline / aminophylline when given imipenem – the general relevance of this interaction is unclear1, 2.

Macrolide Antibiotics (also see Theophylline Toxicity above)
Oral erythromycin exposure may be reduced by theophylline (intravenous erythromycin is not affected). Monitor effects of oral erythromycin to ensure adequate therapy1, 4

Hypokalaemia

Theophylline may cause hypokalaemia, potentially increasing the risk of torsades de pointes when given with the following4: -

  • macrolide antibiotics (e.g. clarithromycin) (also see under Antimicrobials above)
  • ondansetron
  • quinolones (e.g. ciprofloxacin) (also see under Antimicrobials above)

Concomitant administration of theophylline and dexamethasone or hydrocortisone can increase the risk of hypokalaemia2, 4, 5, 6. This is unlikely to be an issue where corticosteroids are used as single doses to reduce post-operative nausea and vomiting or as cover for patients at risk of adrenal insufficiency. However, bear in mind should continued corticosteroid treatment be necessary post-operatively.

Monitor potassium levels closely1.


  Further Information


Prescribing Information

The rate of absorption from modified-release preparations can vary between brands. It is essential that a patient should be maintained on the same brand4.

Theophylline Drug Interactions, Monitoring and Toxicity

Theophylline and aminophylline have narrow therapeutic ranges – a small difference in serum concentrations may lead to therapeutic failure or adverse drug reactions. Hence, it is necessary to carefully consider concomitant prescription of any potentially interacting medication. In some cases it may be prudent to monitor serum theophylline levels.

Aminophylline is a combination of theophylline and ethylenediamine4, thus it will have the same drug interactions as theophylline alone. In addition, aminophylline levels are measured in terms of theophylline concentrations.

Smoking Cessation

Quitting smoking pre-operatively improves surgical outcomes through reducing risk of post-operative complications7. If a patient decides to quit smoking during the perioperative period it must be remembered that smoking cessation can reduce theophylline clearance (potential for increased plasma theophylline levels) – dosage adjustments are likely to be necessary1, 5, 6. Consider monitoring theophylline levels.

 

  References


  1. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 18th March 2019]
  2. Theophylline. In: Brayfield A (Ed), Martindale: The Complete Drug Reference. London: The Royal Pharmaceutical Society of Great Britain. http://www.medicinescomplete.com [Accessed 18th May 2019]
  3. Summary of Product Characteristics – Vesierra® (esketamine) 25mg/ml solution for injection/infusion. Pfizer Limited. Accessed via www.medicines.org.uk 05/10/2019 [date of revision of the text July 2019]
  4. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 18th March 2019]
  5. Summary of Product Characteristics – Phyllocontin Continus® (aminophylline) tablets 225mg. Napp Pharmaceuticals Limited. Accessed via www.medicines.org.uk 05/10/2019 [date of revision of the text April 2017]
  6. Summary of Product Characteristics – Uniphyllin Continus® (theophylline) prolonged release tablets. Napp Pharmaceuticals Limited. Accessed via www.medicines.org.uk 05/01/2019 [date of revision of the text September 2018]
  7. Faculty of Public Health, The Royal College of Surgeons of Edinburgh, The Royal College of Anaesthetists, ash (action on smoking and health). Joint Briefing: Smoking and surgery. April 2016. Available at www.rcoa.ac.uk [Accessed on 18th March 2019]