II. 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

III. 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

IV. 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)

V. 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)

VI. 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

VII. 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

VIII. 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

IX. 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

XI. References

  1. Olson (2020) Clinical Pharmacology, Medmaster Miami, p. 90
  2. Falk (2016) Am Fam Physician 94(6): 454-62 [PubMed]

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Cost: Medications

theophylline (on 3/15/2023 at Medicaid.Gov Survey of pharmacy drug pricing)
THEOPHYLLINE ER 300 MG TAB Generic $2.38 each
THEOPHYLLINE ER 300 MG TABLET Generic $2.54 each
THEOPHYLLINE ER 400 MG TABLET Generic $0.64 each
THEOPHYLLINE ER 600 MG TABLET Generic $0.96 each