Theophylline and Caffeine

The theophylline test is used to monitor the amount of theophylline in the blood. It is usually requested as a trough level – just before the next dose when the blood concentration is expected to be at its lowest level. Random tests may also be requested if a doctor suspects that a patient may be experiencing theophylline toxicity. Serial samples may be used to track theophylline concentrations in a person who has excessive theophylline levels, until therapeutic concentrations are reached.

Caffeine blood levels are not used to monitor therapy as often as theophylline tests. Usually, babies receiving caffeine are monitored clinically for episodes of apnoea and signs of toxicity, and the physiological effects of the drug are closely watched. The majority of those treated respond to standard doses of the drug. The test is usually requested if a baby is not responding to therapy as expected or if the baby is demonstrating signs of toxicity. Since daily doses and an extended half-life in premature babies generally result in stable drug levels, the sample collected is usually a random level, not a trough level.

When a person is beginning theophylline treatment, the theophylline test may be requested several times as the dose is adjusted as needed, until appropriate levels are attained. Theophylline levels are measured 5 days after starting oral treatment, and at least 3 days after any dose adjustment. The test may be requested whenever someone has symptoms that the doctor suspects are due to theophylline toxicity and whenever someone is not responding as expected to therapy. A doctor may request a series of theophylline tests when a patient is being treated for theophylline toxicity to make sure that concentrations are falling. The test may also be requested when a patient taking theophylline experiences a significant change in health status and/or when the patient starts or discontinues taking a drug that is known to affect the metabolism of theophylline.

Symptoms associated with acute theophylline toxicity may include:

• Low blood pressure
• Rapid heart rate
• Restlessness
• Tremors (shaking)
• Nausea
• Abdominal pain
• Confusion

A caffeine test may be requested whenever a premature baby is not responding as expected to treatment and/or whenever an infant has symptoms that the doctor suspects are related to excessive caffeine levels. Symptoms associated with excessive caffeine levels may include:

• Feeding intolerance
• Jitteriness
• Irritability
• Tremors (shaking)
• Rapid heart rate
• Convulsions (fits)

The target concentration for theophylline, when used as a bronchodilator, is generally considered to be 10 – 20 mg/L. Levels greater than 20 mg/L may be toxic. Some patients may experience side effects at concentrations less than 20 mg/L. When theophylline is used to treat apnoea in premature babies, the therapeutic range is 6-13 mg/L.

The target concentration for caffeine for the treatment of premature apnoea is 8-20 mg/L and concentrations greater than 20 mg/L may be toxic.

Low levels of theophylline and caffeine may indicate that the patient has not reached “target” concentrations and that there is insufficient drug present to be effective.

Blood levels in the target range mean that most people will have their symptoms relieved without experiencing significant side effects. Adverse effects and the risk of seizures increase with higher concentrations of these drugs.

Theophylline can affect, and be affected by, a wide variety of drugs and compounds. When your doctor prescribes theophylline, you should discuss all the prescribed and over-the-counter medications that you are taking as well as if taking oral contraceptives, any herbal supplements such as echinacea, chamomile, and gingko, the amount of caffeine and alcohol that you consume, and whether or not you smoke. Dosage adjustments are likely to be necessary if smoking is stopped or started during treatment.

The use of theophylline as a bronchodilator has decreased as other more effective and less toxic asthma treatments have become available. It is still in use in the UK but is not generally the first treatment choice.

Theophylline is given by injection as aminophylline, a mixture of theophylline with a compound (ethylene diamine) that makes it more soluble. Aminophylline injection is rarely needed for severe acute asthma. It must be given by very slow intravenous injection, over at least 20 minutes. Measurement of theophylline concentrations is essential if aminophylline is given to patients already taking theophylline, to assess potential toxicity.

In infants, a significant amount of the theophylline dose is metabolized to caffeine. This occurs to a much smaller degree in children and adults. In cases where the theophylline concentration is within the therapeutic index but the infant is showing signs of toxicity, caffeine levels should be determined. Likewise, theophylline is one of the metabolites of caffeine.

Yes, this is an important part of your medical history and will have an effect on other treatment plans.