Before starting

Required

• Baseline
  • Liver function tests
  • Urea and electrolytes · potassium particularly important
  • Smoking status · advise patients to seek advice if likely to change

After started or dose changed

Required

• 5 days after starting treatment; 3 days after any dose adjustment
  • Plasma theophylline concentration · for MR preparations, take levels 4-6 hours after dose

Theophylline levels, dosing, and adverse effects

Theophylline levels

In most individuals a plasma theophylline of between 10-20mg/litre is required for satisfactory bronchodilation; however, a lower plasma theophylline concentration of 5-15mg/litre (or less) may sometimes be effective.

Dosing

Lower than normal doses may be required in older people, those with heart failure, or those with hepatic impairment.

Adverse effects

Adverse effects can occur within the range 10-20mg/litre and both the frequency and severity increase at concentrations above 20mg/litre.

Ongoing once stable

Required

• Every 6 - 12 months
  • Plasma theophylline concentration · increase frequency or monitor one-off for some patients; for MR preparations, take levels 4-6 hours after dose

Increasing monitoring frequency

Consider increasing frequency of monitoring in patients who are:

• older
• have heart failure
• have hepatic impairment
• pregnant

Monitoring one-off for some patients

Consider checking plasma theophylline where the patient:

• experiences side effects that may suggest toxicity (nausea, vomiting, tremor or palpitations)
• starts an enzyme-inhibiting drug (e.g. erythromycin, clarithromycin, allopurinol, or cimetidine)
• starts an enzyme-inducing drug (e.g. carbamazepine, rifampicin, or St John’s Wort)
• changes smoking status (tobacco can lower plasma levels of theophylline)

Alcohol at risk patients

High alcohol intake can reduce plasma theophylline

Consider

• Periodically
  • Full blood count
  • Serum potassium

Potassium at risk patients

Potassium at risk patients includes those:

• taking concomitant beta-2 agonists, corticosteroids, or diuretics
• with severe asthma

Notes

Effects of enzyme inhibiting or enzyme inducing drugs

Enzyme inhibiting or inducing drugs can affect plasma theophylline levels significantly. Check levels where necessary.

Effects of pregnancy

During pregnancy protein binding decreases; the free level of drug will increase; and so a lower therapeutic range may be appropriate. Consider checking levels frequently, in particular in pregnant women with acute severe asthma or who are critically dependent on therapeutic theophylline.

Brand prescribing and dispensing

The rate of absorption from modified-release preparations can vary between brands. Patients should therefore be maintained on the same brand.

Bibliography

• Medicines and Healthcare products Regulatory Agency. Smoking and smoking cessation: clinically significant interactions with commonly used medicines. Drug Safety Update Oct 2009, vol 3 issue 3: 9 [cited June 2000]
• Ennogen Healthcare Ltd. Summary of Product Characteristics – Uniphyllin Continus 200 mg prolonged release tablets. Last revised 2017 [cited 15/05/2023]
• Ennogen Healthcare Ltd. Summary of Product Characteristics – Phyllocontin Continus 225mg Prolonged release Tablets. Last revised 07/2019 [cited 15/05/2023]
• Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [cited 18/06/2020]
• NICE Clinical Knowledge Summaries (CKS). Asthma. Updated Apr 2020 [cited 30/07/2020]
• British Thoracic Society. BTS/SIGH British Guideline on the Management of Asthma (July 2019) [cited 30/07/2020]

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