Pharm

Theophylline

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Theophylline, Methylxanthine, Aminophylline

  • Precautions
  1. Theophylline is listed here for completeness, not for recommended use
  2. In the developed world, Theophylline and its adverse effects are largely supplanted by better agents
    1. Limited roles may be found in refractory cases under specialty care, and in underdeveloped world regions
  • Indications
  1. Limited utility where standard of care Asthma Management is available
  2. Theophylline and Aminophylline were replaced by Inhaled Beta Adrenergic Agonists (e.g. Albuterol) and Ipratropium Bromide
  • Preparations
  • Methylxanthines
  1. Theophylline
    1. Oral administration only
  2. Aminophylline
    1. IV form of Theophylline
    2. Water soluble salt of Theophylline
    3. Aminophylline has higher solubility allows for IV administration
  3. Other Methylxanthines
    1. Caffeine
    2. Pentoxifylline (Trental)
  • Mechanism
  1. Xanthines are isolated from plants Camellia sinensis and Coffea arabica
  2. Activity: Xanthines and Methylxanthines in general
    1. Xanthines at high dose inhibit phosphodiesterase (PDE) and Prostaglandin production
      1. PDE catalyzes cAMP, with increased cAMP levels when PDE is inhibited
      2. cAMP mediates adrenergic induced bronchodilation
    2. Block Adenosine
      1. Results in CNS and cardiac stimulation
    3. Moderate cellular Calcium
  3. Effects: Theophylline
    1. Bronchial Smooth Muscle relaxation (high doses of Theophylline)
    2. Peripheral vasodilation (not central)
    3. CNS and cardiac stimulant
    4. Diuretic
    5. Anti-inflammatory (at low doses of Theophylline)
  • Dosing
  1. Theophylline 150 to 300 mg orally twice daily
  2. Patients should not modify dose from prescribed (even for missed dosing)
    1. Doubling dose for a missed dose may result in Theophylline toxicity
  • Pharmacokinetics
  • Oral Theophylline
  1. Slow onset
  2. Well absorbed from the intestinal tract
  3. Half-Life: 8.5 hours in adults (3.5 hours in children)
  4. Liver metabolism
  5. Renal excretion
  • Adverse Effects
  1. Serum Theophylline Level <20 mg/L
    1. Headache
    2. Insomnia
    3. Nausea
    4. Vomiting
  2. Serum Theophylline Level >20 mg/L
    1. Arrhythmias
    2. Seizures
  • Drug Interactions
  1. Agents that increase Theophylline half life and serum concentrations
    1. Alcohol
    2. Cimetidine
    3. Ciprofloxacin
    4. Diltiazem
    5. Erythromycin
    6. Oral Contraceptives
    7. Propranolol (very strong effect, doubles the Theophylline concentration)
    8. Verapamil
  2. Agents that decrease Theophylline half life and serum concentrations
    1. Phenytoin (Dilantin)
    2. Phenobarbital
  3. Sympathomimetics
    1. Increased CNS and cardiac toxicity
  • Resources
  1. Theophylline XR Tablet (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=699a4e05-95cb-4b28-8927-d97a4afbf463
  2. Aminophylline Intravenous Solution (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=9a663ef3-881f-48bd-2689-3713b24545c2
  • References
  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 90
  2. Falk (2016) Am Fam Physician 94(6): 454-62 [PubMed]