THEOPHYL-SR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for THEOPHYL-SR (THEOPHYL-SR).

How it works

Theophylline is a methylxanthine that inhibits phosphodiesterase, increasing cyclic AMP levels, and antagonizes adenosine receptors, leading to bronchodilation and anti-inflammatory effects.

What the body does with it

Metabolism	Hepatic via CYP1A2, CYP2E1, and CYP3A4; demethylation and oxidation to inactive metabolites (1-methyluric acid, 3-methylxanthine, 1,3-dimethyluric acid).
Excretion	Renal: ~10% unchanged; Hepatic metabolism (90%) via CYP1A2, 3A4; metabolites (caffeine, 3-methylxanthine) excreted renally. Total clearance predominantly hepatic.
Half-life	Adults: 8-10 hours (range 3-12); Neonates: 20-30 hours; Smokers: 4-5 hours; Cirrhosis: 30-40 hours. Dose adjustments needed based on half-life variations.
Protein binding	40-60% primarily to albumin.
Volume of Distribution	0.3-0.5 L/kg (1.0-1.5 L/kg in neonates). Reflects distribution into total body water; higher in dehydrated states.
Bioavailability	Oral immediate-release: 96-100%; Sustained-release: 90-100% (variable among formulations).
Onset of Action	Oral immediate-release: 30-60 min; Oral sustained-release (Theophyll-SR): 1-3 hours; IV: 5-15 min.
Duration of Action	Sustained-release: 12-24 hours depending on formulation; Immediate-release: 4-6 hours. Therapeutic effect correlates with serum concentration 10-20 mcg/mL.

Classification & Brands

Dosing & administration

300 mg orally every 12 hours, with dosing titrated to achieve serum trough concentrations of 5-15 mcg/mL.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	No specific GFR-based adjustment required, but serum concentrations should be monitored due to altered clearance. For GFR <10 mL/min, reduce dose by 50% and monitor levels.
Liver impairment	Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: reduce dose by 60%; Child-Pugh Class C: reduce dose by 80% and monitor serum concentrations closely.
Pediatric use	Initial dose: 5 mg/kg/day orally in 2 divided doses, increasing by 2 mg/kg/day every 3 days to maximum 20 mg/kg/day, with monitoring of serum concentrations.
Geriatric use	Start at lower end of dosing range (e.g., 200 mg every 12 hours) and titrate slowly due to reduced hepatic clearance; monitor serum concentrations and adjust to therapeutic trough of 5-15 mcg/mL.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for THEOPHYL-SR (THEOPHYL-SR).

Breastfeeding	Excreted into breast milk; M/P ratio approximately 0.6-0.7. Infant dose ~1-10% of maternal weight-adjusted dose; monitor infant for irritability or insomnia. AAP considers compatible with breastfeeding with caution.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: No increased risk of major malformations reported in humans; animal studies show fetal harm at high doses. Second trimester: Potential for maternal tachycardia and uterine relaxation, not teratogenic. Third trimester: Risk of neonatal apnea, bradycardia, and jitteriness at birth if maternal levels are supratherapeutic; no structural anomalies.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to theophylline or any component of the formulation; active peptic ulcer disease; seizure disorder (unless appropriately controlled with anticonvulsants).

Clinical Precautions

Precautions

Use with caution in patients with cardiac disease (e.g., arrhythmias), seizure disorders, peptic ulcer disease, hepatic impairment, and in elderly patients. Monitor serum theophylline levels to avoid toxicity.

Clinical Tips & Counseling

Drug interactions

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THEOPHYL-SR

Clinical safety rating: caution

Comprehensive clinical and safety monograph for THEOPHYL-SR (THEOPHYL-SR).

How it works

Theophylline is a methylxanthine that inhibits phosphodiesterase, increasing cyclic AMP levels, and antagonizes adenosine receptors, leading to bronchodilation and anti-inflammatory effects.

What the body does with it

Metabolism	Hepatic via CYP1A2, CYP2E1, and CYP3A4; demethylation and oxidation to inactive metabolites (1-methyluric acid, 3-methylxanthine, 1,3-dimethyluric acid).
Excretion	Renal: ~10% unchanged; Hepatic metabolism (90%) via CYP1A2, 3A4; metabolites (caffeine, 3-methylxanthine) excreted renally. Total clearance predominantly hepatic.
Half-life	Adults: 8-10 hours (range 3-12); Neonates: 20-30 hours; Smokers: 4-5 hours; Cirrhosis: 30-40 hours. Dose adjustments needed based on half-life variations.
Protein binding	40-60% primarily to albumin.
Volume of Distribution	0.3-0.5 L/kg (1.0-1.5 L/kg in neonates). Reflects distribution into total body water; higher in dehydrated states.
Bioavailability	Oral immediate-release: 96-100%; Sustained-release: 90-100% (variable among formulations).
Onset of Action	Oral immediate-release: 30-60 min; Oral sustained-release (Theophyll-SR): 1-3 hours; IV: 5-15 min.
Duration of Action	Sustained-release: 12-24 hours depending on formulation; Immediate-release: 4-6 hours. Therapeutic effect correlates with serum concentration 10-20 mcg/mL.

Classification & Brands

Dosing & administration

300 mg orally every 12 hours, with dosing titrated to achieve serum trough concentrations of 5-15 mcg/mL.

Dosage form	CAPSULE, EXTENDED RELEASE
Renal impairment	No specific GFR-based adjustment required, but serum concentrations should be monitored due to altered clearance. For GFR <10 mL/min, reduce dose by 50% and monitor levels.
Liver impairment	Child-Pugh Class A: reduce dose by 50%; Child-Pugh Class B: reduce dose by 60%; Child-Pugh Class C: reduce dose by 80% and monitor serum concentrations closely.
Pediatric use	Initial dose: 5 mg/kg/day orally in 2 divided doses, increasing by 2 mg/kg/day every 3 days to maximum 20 mg/kg/day, with monitoring of serum concentrations.
Geriatric use	Start at lower end of dosing range (e.g., 200 mg every 12 hours) and titrate slowly due to reduced hepatic clearance; monitor serum concentrations and adjust to therapeutic trough of 5-15 mcg/mL.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for THEOPHYL-SR (THEOPHYL-SR).

Breastfeeding	Excreted into breast milk; M/P ratio approximately 0.6-0.7. Infant dose ~1-10% of maternal weight-adjusted dose; monitor infant for irritability or insomnia. AAP considers compatible with breastfeeding with caution.
Teratogenic Risk	FDA Pregnancy Category C. First trimester: No increased risk of major malformations reported in humans; animal studies show fetal harm at high doses. Second trimester: Potential for maternal tachycardia and uterine relaxation, not teratogenic. Third trimester: Risk of neonatal apnea, bradycardia, and jitteriness at birth if maternal levels are supratherapeutic; no structural anomalies.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Serious Effects

Absolute Contraindications

Hypersensitivity to theophylline or any component of the formulation; active peptic ulcer disease; seizure disorder (unless appropriately controlled with anticonvulsants).