theophylline (Theo 24, Theochron, Elixophyllin, aminophylline, Uniphyl)

Dosing and uses of Theo 24, Theochron (theophylline)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

capsule, extended-release (24 hours)

• 100mg
• 200mg
• 300mg
• 400mg

tablet, extended release (12 hours)

• 100mg
• 200mg
• 300mg
• 450mg

tablet, extended-release (24 hours)

• 400mg
• 600mg

oral elixir

• 80mg/15mL

intravenous solution

• 400mg/250mL D5W
• 400mg/500mL D5W
• 800mg/500mL D5W

 

Acute Bronchospasm

Loading

• Patients not currently taking theophylline: 5-7 mg/kg IV/PO; not to exceed 25 mg/min IV
• Aminophylline: 6-7 mg/kg IV/PO; IV infused over 20 minutes

Maintenance

• 0.4-0.6 mg/kg/hr IV or 4.8-7.2 mg/kg PO (extended release) q12hr to maintain levels 10-15 mg/L
• Smokers: 0.79 mg/kg/hr IV for next 12 hours after loading dose, then 0.63 mg/kg/hr or 5 mg/kg PO (extended release) q8hr
• Coadmininstration with drugs that decrease theophylline clearance (eg, cimetidine, ciprofloxacin, and erythromycin and other macrolides): 0.2-0.3 mg/kg/hr IV or PO (extended release) q12-24hr
• Congestive heart failure: 0.39 mg/kg/hr IV for next 12 hours after loading dose, then 0.08-0.16 mg/kg/hr
• Aminophylline: 3.125 mg/kg PO q6hr

 

Dosing Considerations

If administering aminophylline, increase dose by 25% (aminophylline is approximately 79-86% theophylline;)

For PO loading, use immediate-release theophylline or aminophylline

If patient is already taking theophylline, give smaller loading dose

Use ideal body weight to calculate dose

1 mg/kg results in 2 mg/L (34.4 mmol/L) increase in serum theophylline

Therapeutic range: 10-20 mg/L (172-344 mmol/L)

 

Dosing Modifications

Hepatic impairment: After loading dose, 0.39 mg/kg/hr IV for next 12 hours, then 0.08-0.16 mg/kg/hr

 

Pediatric dosage forms and strengths

capsule, extended-release (24 hours)

• 100mg
• 200mg
• 300mg
• 400mg

tablet, extended-release (12 hours)

• 100mg
• 200mg
• 300mg
• 450mg

tablet, extended-release (24 hours)

• 400mg
• 600mg

oral elixir

• 80mg/15mL

intravenous solution

• 400mg/250mL D5W
• 400mg/500mL D5W
• 800mg/500mL D5W

 

Bronchospasm

Loading

• No theophylline administered in previous 24 hours: 5-7 mg/kg IV/PO; IV infused over 20-30 minutes

Maintenance

• 1.5-6 months: 0.5 mg/kg/hr IV or 10 mg/kg/day PO in divided doses
• 6-12 months: 0.6-0.7 mg/kg/hr IV or 12-18 mg/kg/day PO in divided doses
• 1-9 years: 1 mg/kg/hr IV or 8 mg/kg PO (extended release) q8hr
• 9-12 years: 0.8-0.9 mg/kg/hr IV or 6.4 mg/kg PO (extended release) q8hr
• 12-16 years: 0.7 mg/kg/hr IV or 5.6 mg/kg PO (extended release) q8hr

 

Neonatal Apnea

Loading: 4-5 mg/kg PO/IV once

Maintenance: 3-6 mg/kg/day PO/IV divided q8hr

 

Dosing Considerations

If administering aminophylline, increase dose by 20-25% (aminophylline is approximately 79-86% theophylline)

Use ideal body weight to calculate dose

1 mg/kg results in 2 mg/L (34.4 mmol/L) increase in serum theophylline

 

Geriatric dosage forms and strengths

 

Acute Bronchospasm

After loading dose, 0.47 mg/kg/hr IV for next 12 hours, then 0.24 mg/kg/hr

 

Theo 24, Theochron (theophylline) adverse (side) effects

Frequency not defined

Peak serum concentration <20 mcg/mL

• Central nervous system excitement, headache, insomnia, irritability, restlessness, seizure
• Diarrhea, nausea, vomiting
• Diuresis (transient)
• Exfoliative dermatitis
• Skeletal muscle tremors
• Tachycardia, flutter
• Hypercalcemia (with concomitant hyperthyroid disease)
• Difficulty urinating (elderly males with prostatism)

Peak serum concentration >30 mcg/mL

• Acute myocardial infarction
• Seizures (resistant to anticonvulsants)
• Urinary retention

 

Warnings

Contraindications

Hypersensitivity

 

Cautions

Patients, who develop CNS abnormalities, reported (rarely) to experience nonconvulsive status epilepticus

Theophylline clearance may decrease in patients with congestive heart failure, acute pulmonary edema, hepatic disease, cor pulmonale, acute hepatitis, hypothyroidism, cirrhosis, fever, or sepsis with multiorgan failure and shock

Use with caution in patients with hyperthyroidism, seizure disorder, peptic ulcer, or cardiovascular disease

Some dosage forms may contain propylene glycol; use caution; seizures, hyperosmolality, lactic acidosis, and respiratory depression reported associated with use of large amounts of propylene glycoL

Measure serum levels and withhold subsequent doses if patient develops signs and symptoms of theophylline toxicity

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Theophylline is excreted into breast milk and may cause irritability or other signs of mild toxicity in nursing human infants; serious adverse effects in infant are unlikely unless mother has toxic serum theophylline concentration

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Theo 24, Theochron (theophylline)

Mechanism of action

Theophylline relaxes smooth muscles of respiratory tract and suppresses the response of the airways to stimuli

May increase tissue concentration of cyclic adenine monophosphate (cAMP) by inhibiting 2 isoenzymes of phosphodiesterase (PDE III and, to a lesser extent, PDE IV), which ultimately induces release of epinephrine from the adrenal medulla cells

 

Absorption

Onset: Variable

Duration: Variable

Peak plasma time: 1-2 hr

Peak plasma concentration: 10 mcg/mL

 

Distribution

Protein bound: 40-55%

Vd: 0.3-0.7 L/kg

 

Metabolism

Metabolized in liver by CYP1A2 and CYP3A4

Metabolites: 1,3-Dimethyluric acid, 1-methyluric acid, 3-methylxanthine

 

Elimination

Half-life: Nonsmoker, 8 hr; smoker, 4-5 hr

Clearance: 1.45 mL/min/kg

Excretion: Urine

 

Administration

IV Incompatibilities

Additive: Clindamycin, dobutamine, epinephrine, erythromycin, meperdine, morphine, norepinephrine, vancomycin, vitamins B and C

Y-site: Amiodarone, dobutamine, fenoldopam

Not specified: Carbenicillin, tetracycline

 

IV Compatibilities

Additive: Calcium gluconate, dopamine, esmolol, heparin, hydrocortisone, hydroxyzine, lidocaine, nitroglycerin, pentobarbital, potassium chloride, sodium bicarbonate, verapamiL

Syringe: Heparin, pentobarbitaL

Y-site: Ampicillin, cefazolin, esmolol, heparin, potassium chloride, vitamins B and C

Not specified: Diazepam