To measure the amount of theophylline or caffeine in the blood, to establish an appropriate dose and to maintain an appropriate level
Theophylline and Caffeine
At the start of drug therapy and at regular intervals to monitor the drug’s levels; when indicated, to detect low or possibly toxic concentrations
A blood sample taken from a vein in your arm or from pricking an infant’s heel
No specific test preparation is needed
Theophylline and caffeine are methylxanthines – drugs that ease and stimulate breathing. These tests measure the amount of theophylline or caffeine in the blood to help establish an appropriate dose and maintain the right level. Theophylline is one of several medicines that may be taken by children and adults who have asthma and by adults who have chronic obstructive pulmonary disease (COPD). It is a bronchodilator with a narrow therapeutic window – too little theophylline will not work and too much can cause toxicity. Chronic theophylline toxicity is associated with an increased risk of seizures. Both short and long-term toxicity can be life-threatening.
Theophylline may also be prescribed to treat apnoea in premature babies, but caffeine citrate is the preferred medicine. Apnoea reduces the amount of oxygen available to the body. It is a common and serious condition in premature babies that must be promptly treated and closely monitored. While both theophylline and caffeine can reduce episodes of apnoea, caffeine has fewer side effects and, thus, a lower risk of toxicity. At very high doses, symptoms similar to those found with theophylline toxicity may be seen.
Establishing and maintaining therapeutic doses can be a challenge. Both theophylline and caffeine levels may need to be monitored because the range of concentrations in which the drugs are effective, but not toxic, is narrow and in some cases the dose given does not correlate well with concentrations in the blood. The rate at which the drugs are metabolized will vary from person to person and is decreased in both the very young and the elderly. The drug levels may also be affected by other conditions such as liver disease, hypothyroidism, and by short term infections or illnesses. Many drugs interact and interfere with the metabolism of theophylline. They may increase or decrease its rate of metabolism.
Many oral preparations (e.g. Nuelin SA, Slo-Phyllin, Uniphyllin Continus) are designed to release theophylline slowly to increase the duration of action of the drug. The rate of absorption of drug can vary between different brands, so care is necessary when switching brands.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm. In infants, blood may be collected by pricking a heel.
Is any test preparation needed to ensure the quality of the sample?
No specific test preparation is needed.
How is it used?
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 is it requested?
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
- Tremors (shaking)
- Abdominal pain
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
- Tremors (shaking)
- Rapid heart rate
- Convulsions (fits)
What does the test result mean?
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.
Is there anything else I should know?
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.
Should I tell all of my doctors that I am taking theophylline?
How long does a premature baby have to take caffeine?