Theophylline

Theophylline and caffeine tests are used to monitor the amount of the drugs in the blood to establish appropriate doses and to maintain therapeutic levels. Theophylline and caffeine are used to ease breathing and stimulate respiration.

Theophylline is usually ordered as a trough level – prior to the next dose when the concentration is expected to be at its lowest level. Tests may also be ordered if a health practitioner suspects that a person may be experiencing theophylline toxicity. A series of blood samples may be collected and tested over a period of time to track theophylline concentrations in someone who has had high theophylline levels, until therapeutic concentrations are reached.

Caffeine blood levels are not used to monitor therapy as routinely as theophylline tests. Usually, newborns receiving caffeine are monitored clinically for episodes of apnea and signs of toxicity, and physiological effects of the drug are closely watched. The majority of those treated respond to standardized doses of the medication without the need for monitoring blood caffeine levels. The test is primarily ordered if an infant is not responding to therapy as expected or if the infant is demonstrating signs of toxicity. Since daily doses and an extended half-life in the premature neonate 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 ordered several times as the dosage is adjusted as needed, until therapeutic levels are attained. The test may be ordered whenever a person has symptoms that the health practitioner suspects are due to theophylline toxicity and whenever a person is not responding as expected to therapy. A healthcare provider may order multiple theophylline tests when someone is being treated for theophylline toxicity. The health practitioner may order a test when a person taking theophylline experiences a significant change in health status and/or when the person 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
• Nausea
• Abdominal pain
• Confusion
• Loss of appetite (anorexia)

A caffeine test may be ordered whenever a premature neonate is not responding as expected to treatment and/or whenever an infant has symptoms that the health practitioner suspects are related to high caffeine levels. Signs and symptoms associated with high caffeine levels in a newborn may include:

• Inability to take in or digest infant formula or breast milk
• Jitteriness, shakiness
• Irritability
• Tremors
• Rapid heart rate
• Convulsions

The therapeutic concentration for theophylline, when used as a bronchodilator to treat asthma, is generally considered to be 5–15 mcg/mL (28-83 micromol/L) for adults, 5–10 mcg/mL (28–55 micromol/L) for children and neonates. Levels greater than 20 mcg/mL (111 micromol/L) are considered toxic. Some people may experience significant side effects at concentrations less than 20 mcg/mL (111 micromol/L). When theophylline is used to treat apnea in premature neonates, the therapeutic range is 6-11 mcg/mL (33-61 micromol/L).

Therapeutic concentration for caffeine for the treatment of premature neonate apnea is much wider, 5-20 mcg/mL (25-103 micromol/L), while concentrations greater than 20 mcg/mL (103 micromol/L) are considered toxic, and greater than 50 mcg/mL (257 micromol/L) are considered critical values.

Low levels of theophylline and caffeine may indicate that the drug has not reached a therapeutic level for the individual tested and there is insufficient drug present to be effective.

Blood levels in the therapeutic range mean that most people will have their symptoms relieved without experiencing significant side effects. Adverse side 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 a health practitioner prescribes theophylline, it is important for a person to list and discuss all of the prescribed and over-the-counter medications that they are taking, including oral contraceptives and any herbal supplements such as echinacea, chamomile, and gingko. The healthcare provider will also want to know the amount of caffeine and alcohol that a person is consuming and whether or not the person smokes.

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 throughout the United States but is not generally the first treatment choice.

In infants, a significant amount of the theophylline dose (8.5%) is metabolized to caffeine. This occurs to a much lesser degree in children and adults. In cases where the theophylline concentration is within the therapeutic range but the infant is showing signs of toxicity, caffeine levels should be determined. Likewise, theophylline is one of the metabolites of caffeine.