Theophylline and Aminophylline

What is Theophylline and Aminophylline

Theophylline is a xanthine derivative that is used both orally or intravenously in the treatment of asthma and bronchospasm; aminophylline is a pro-drug of theophylline and is also used intravenously and orally.

Aminophylline is converted to theophylline; 1 mg aminophylline is equivalent to 0.8 mg theophylline. The drugs have a narrow therapeutic range and theophylline toxicity is well documented.

Theophylline occurs naturally in tea and is chemically similar to caffeine and theobromine.

Theophylline was introduced in 1900 to treat asthma, but its use did not become widespread until after 1936, and it was not approved by the FDA until 1940.

During the 1970s and 1980s, theophylline dosing was intensively studied, its pharmacokinetics were accurately described, and sustained-release preparations were marketed.

There is contradictory evidence regarding the effectiveness of low-dose theophylline on exacerbation rates in chronic obstructive pulmonary disease (COPD); in general, the drug has a moderate bronchodilator effect that may result in additive but mild improvements in FEV-1 when added to beta-agonists.

However, the risk for toxicity increases at dosages that produce therapeutic benefit.

According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, theophylline and aminophylline are not recommended for the treatment of COPD and should not be used in acute COPD exacerbations due to the low efficacy at recommended doses and the potential for adverse reactions and toxicity.

Use of theophylline is also not routinely recommended for asthma maintenance therapy.

The FDA no longer includes acute bronchospasm due to status asthmaticus as an approved indication for parenteral products.

The Expert Panel of the National Asthma Education and Prevention Program (NAEPP) does not recommend theophylline or aminophylline for acute asthma exacerbations because it appears to provide no additional benefit to optimal inhaled beta-2-agonist therapy and may increase risk of adverse effects.

Sustained-release oral theophylline is considered an alternate, but not preferred, therapy to the use of inhaled corticosteroids (ICSs) in the treatment of mild persistent asthma (step 2 care) according to the Expert Panel of the NAEPP.

In addition, the Panel recommends theophylline as an alternate, adjunct therapy with low-dose ICS for patients with inadequately controlled moderate persistent asthma (step 3 care).

An alternate treatment in step 4 care includes the combined use of theophylline and ICS.

Modest clinical effectiveness as well as the need for monitoring theophylline levels should be taken into consideration when evaluating the benefits and risks of chronic theophylline treatment compared to other asthma and COPD treatments.

Indications

  • asthma
  • bradycardia
  • bronchospasm prophylaxis
  • chronic bronchitis
  • chronic obstructive pulmonary disease (COPD)
  • emphysema
  • neonatal apnea
  • sleep apnea
  • status asthmaticus

Side Effects

  1. abdominal pain
  2. agitation
  3. anaphylactoid reactions
  4. anorexia
  5. anxiety
  6. atrial fibrillation
  7. atrial flutter
  8. atrial tachycardia
  9. cardiac arrest
  10. contact dermatitis
  11. diarrhea
  12. diuresis
  13. dizziness
  14. exfoliative dermatitis
  15. gastroesophageal reflux
  16. headache
  17. hematemesis
  18. hyperactivity
  19. hypercalcemia
  20. hyperglycemia
  21. hypokalemia
  22. hypotension
  23. insomnia
  24. irritability
  25. metabolic acidosis
  26. nausea
  27. palpitations
  28. premature ventricular contractions (PVCs)
  29. pruritus
  30. rash
  31. restlessness
  32. rhabdomyolysis
  33. seizures
  34. sinus tachycardia
  35. supraventricular tachycardia (SVT)
  36. tremor
  37. urticaria
  38. ventricular tachycardia
  39. vitamin B6 deficiency
  40. vomiting

Monitoring Parameters

  • blood pressure
  • heart rate
  • LFTs
  • pulmonary function tests (PFTs)
  • serum theophylline concentrations

Contraindications

  • acidemia
  • breast-feeding
  • cardiac arrhythmias
  • cardiac disease
  • cholestasis
  • cor pulmonale
  • corn hypersensitivity
  • coronary artery disease
  • cystic fibrosis
  • fever
  • gastritis
  • gastroesophageal reflux disease (GERD)
  • geriatric
  • heart failure
  • hepatic disease
  • hepatitis
  • hiatal hernia
  • hyperthyroidism
  • hypothyroidism
  • hypoxemia
  • infants
  • myocardial infarction
  • neonates
  • peptic ulcer disease
  • pregnancy
  • prostatic hypertrophy
  • pulmonary edema
  • renal impairment
  • seizure disorder
  • sepsis
  • shock
  • tobacco smoking

Interactions

  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Acetaminophen; Caffeine
  • Acetaminophen; Caffeine; Dihydrocodeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
  • Acetaminophen; Dextromethorphan; Phenylephrine
  • Acetaminophen; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Dichloralphenazone; Isometheptene
  • Acetaminophen; Guaifenesin; Phenylephrine
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