Theophylline

From Anvita Health Wiki

Contents 1 Introduction 2 Indications 3 Contraindications 4 Dosage 5 Pharmacokinetics 6 Monitor 7 Adverse-effects 8 Drug-interactions 9 Test-interactions 10 Laboratory 11 Mechanism-of-action 12 More General Terms 13 Additional Terms 14 Internet Database 15 References

Introduction

• Tradenames: Slo-Phyllin, Elixophyllin, Theolair.
  
• Slo-Bid, Slo-Phyllin, Theo-Dur, Theolair-SR & Uni-Dur taken off the US market in 2001. [7]
  
• Remaining forms of theohylline include:

• Uniphyl, T-phyl, Theo-24, Theolair & generics
  

Indications

• reactive airway disease ( asthma & COPD)
• used in combination with beta-2 adrenergic receptor agonists
• neonatal apnea/ bradycardia

Contraindications

• uncontrolled arrhythmias
• uncontrolled peptic ulcer disease
  

• pregnancy category = c
• safety in lactation = ?

Dosage

• Intravenous:

• loading dose 6 mg/kg; infuse < 25 mg/min
• infusion 0.5 mg/kg/ hr

• Oral:

• 100-300 mg PO TID/ QID.

• Tabs: 60, 100, 200, 300 mg.
• Liquid: (Theolair) 80 mg/15 mL (15 mL, 19 mL, 30 mL, 480 mL).
• Sustained release (once daily):
• Tradenames: Uniphyl, Theo-24.

• 400 mg PO QHS (give once a day at bedtime)

• Tabs: 100, 200, 300, 400 mg.
• Sustained release ( twice daily):
• Tradenames: Theo-Dur, Slo- bid.

• 100-300 mg PO BID.

• Tabs: 100, 200, 300, 450 mg.
• Pediatrics: sprinkles?: Tradename: Theo-Dur.

• 10 mg/kg PO BID.

• Tabs: 50, 75, 125, 200 mg.
• Caution: dosage should be decreased by 50% in patients with:

• heart failure
• severe hypoxemia
• hepatic insuffciency
• seizures
• hyperthyroidism
• hypertension

Pharmacokinetics

• onset of action is 15 minutes after an IV loading dose
• absorption of oral formulation is variable
• food may effect absorption (+ or -)
• therapeutic range: 8-20 ug/mL, 5-12 ug/mL for COPD [8]
• metabolized in the liver by cyt P450 1A2
• elimination 1/2life:

• about 8 hours in non- smokers
• 4.4 hours in smokers
• prolonged 1/2life (> 24 hours) in patients with COPD, CHF or liver disease
  

• Conditions/disorders that alter theophylline metabolism

• conditions that decrease theophylline levels

• cor pulmonale
• congestive heart failure
• pregnancy
• hepatic cirrhosis
• viral infection

• conditions that increase theophylline levels

• smoking
• marijuana
• hyperthyroidism
  

• elimination via liver
• protein binding = 56 %
• elimination by hemodialysis = -
• elimination by hemoperfusion = -
• elimination by peritoneal dialysis = -

Monitor

• serum theophylline (see Laboratory: below)

• when intiating therapy
• before & after increasing dose
• when toxicity is suspected
• worsening illness predisposing to toxicity
• after smoking cessation
• after adding or stopping an interacting drug
• at least annually [9]

Adverse-effects

• not common (1-10%)

• nausea/vomiting, nervousness, restlessness, tachycardia

• uncommon (< 1%)

• rash, insomnia, irritability, tremor, seizures, gastric irritation, allergic reactions

• other

• arrhythmias & convulsions have occurred with serum levels > 35 ug/mL
• rapid IV administration may be associated with hypotension, syncope & cardiac arrest
• adverse effects umcommon at serum theophylline concentrations < 20 ug/mL

• Toxicity: best treated by charcoal & hemoperfusion.
  

• drug adverse effects of analeptics

Drug-interactions

• drugs that decrease theophylline levels

• phenytoin ( Dilantin)
• carbamazepine ( Tegretol)
• furosemide ( Lasix)
• rifampin
• beta-adrenergic receptor agonists
• ketoconazole
• phenobarbital
• aminoglutethimide
• any drug that induces cyt P450 1A2

• drugs that increase theophylline levels

• antibiotics

• macrolides
• quinolones

• ciprofloxacin
• norfloxacin
• enoxacin

• isoniazid
• troleandomycin
• lincomycin

• allopurinol
• propranolol
• caffeine
• cimetidine & possibly ranitidine
• mexiletine
• amiodarone
• oral contraceptives
• any drug that inhibits cyt P450 1A2

• theophylline may decrease the effects of phenytoin
• theophylline may have synergistic toxicity with sympathomimetics
  

• drug interaction(s) of lithium carbonate with xanthine

Test-interactions

• chemical interferences

• theophylline may decrease

• serum alkaline phosphate ( serum ALP)
• serum bilirubin
• serum lactate dehydrogenase ( serum LDH)

• theophylline may increase: serum uric acid

Laboratory

• see theophylline in serum or plasma
• specimen: serum, plasma ( heparin, EDTA)
• methods: GLC, HPLC, RIA, EIA, FPIA, color, FIA

Mechanism-of-action

• (proposed [2])
• inhibits breakdown of cAMP
• inhibition of cGMP
• enhanced adrenergic output to airway smooth muscle
• antagonism of adenosine receptors
• stimulation of endogenous catecholamines
• decrease in [Ca+2] into bronchial smooth muscle cells or release of [Ca+2] from sarcoplasmic reticulum
• dose-dependent increase in respiratory muscle contractility
• relaxes smooth muscle of bronchial airways & pulmonary blood vessels
• diuretic
• coronary vasodilator
• cardiac stimulant
• CNS stimulant

More General Terms

• methylxanthine
• antiasthmatic agent
• analeptic (CNS stimulant)
• smooth muscle relaxant

Additional Terms

• cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
• theophylline in serum/plasma

Internet Database

PubChem: 2153
PubChem: 77034

References

1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 741-42
3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
5. Clinical Diagnosis & Management by Laboratory Methods, 19th edition, J.B. Henry (ed), W.B. Saunders Co., Philadelphia, PA. 1996, pg 10
6. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
7. Prescriber's Letter 8(9):51 2001
8. Medical Knowledge Self Assessment Program (MKSAP) 14, American College of Physicians, Philadelphia 2006
9. Prescriber's Letter 17(7): 2010 Recommended Lab Monitoring for Common Medications Detail-Document#: [1] (subscription needed) [2]

theophylline (Slo-Phyllin, Elixophyllin, Uniphyl, Theo-24, Theo-Dur, Slo-bid, Theolair)