DIRA 1.0: Atlas of Drug-induced Rhabdomyolysis

THEOPHYLLINE

DIR Classification Postmarketing Surveillance Drug Property Information Reference

DIR Classification

Classification:Less-DIR concern

Severity Score:1

Description in Drug Labeling: View Full Labeling: SPL in DailyMed | PDF

ADVERSE REACTIONS
Adverse reactions associated with theophylline are generally mild when peak serum theophylline concentrations are <20 mcg/mL and mainly consist of transient caffeine-like adverse effects such as nausea, vomiting, headache, and insomnia. When peak serum theophylline concentrations exceed 20 mcg/mL, however, theophylline produces a wide range of adverse reactions including persistent vomiting, cardiac arrhythmias, and intractable seizures which can be lethal (see OVERDOSAGE). The transient caffeine-like adverse reactions occur in about 50% of patients when theophylline therapy is initiated at doses higher than recommended initial doses (e.g., >300 mg/day in adults and >12 mg/kg/day in children beyond >1 year of age). During the initiation of theophylline therapy, caffeine-like adverse effects may transiently alter patient behavior, especially in school age children, but this response rarely persists. Initiation of theophylline therapy at a low dose with subsequent slow titration to a predetermined age-related maximum dose will significantly reduce the frequency of these transient adverse effects (see DOSAGE AND ADMINISTRATION, TABLE V). In a small percentage of patients (<3% of children and <10% of adults) the caffeine-like adverse effects persist during maintenance therapy, even at peak serum theophylline concentrations within the therapeutic range (i.e., 10-20 mcg/mL). Dosage reduction may alleviate the caffeine-like adverse effects in these patients, however, persistent adverse effects should result in a re-evaluation of the need for continued theophylline therapy and the potential therapeutic benefit of alternative treatment.
Other adverse reactions that have been reported at serum theophylline concentrations <20 mcg/mL include diarrhea, irritability, restlessness, fine skeletal muscle tremors, and transient diuresis. In patients with hypoxia secondary to COPD, multifocal atrial tachycardia and flutter have been reported at serum theophylline concentrations ≥15 mcg/mL. There have been a few isolated reports of seizures at serum theophylline concentrations <20 mcg/mL in patients with an underlying neurological disease or in elderly patients. The occurrence of seizures in elderly patients with serum theophylline concentrations <20 mcg/mL may be secondary to decreased protein binding resulting in a larger proportion of the total serum theophylline concentration in the pharmacologically active unbound form. The clinical characteristics of the seizures reported in patients with serum theophylline concentrations <20 mcg/mL have generally been milder than seizures associated with excessive serum theophylline concentrations resulting from an overdose (i.e., they have generally been transient, often stopped without anticonvulsant therapy, and did not result in neurological residua).

Postmarketing Surveillance

Contingency Table:

Current Drug

Other Drugs

Rhabdomyolysis

42839

Other ADRs

1903

14115376

Odds Ratio = 12.64

Drug Property Information

ATC Code(s):

R03DA54 - theophylline

R03DA - Xanthines
R03D - OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R03 - DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R - RESPIRATORY SYSTEM

R03DA74 - theophylline

R03DA - Xanthines
R03D - OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R03 - DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R - RESPIRATORY SYSTEM

R03DB04 - theophylline

R03DB - Xanthines and adrenergics
R03D - OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R03 - DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R - RESPIRATORY SYSTEM

R03DA04 - theophylline

R03DA - Xanthines
R03D - OTHER SYSTEMIC DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R03 - DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES
R - RESPIRATORY SYSTEM

Active Ingredient:theophylline

Active Ingredient UNII:C137DTR5RG

Drugbank ID:DB00277

PubChem Compound:2153

CAS Number:58-55-9

Dosage Form(s):solution

Route(s) Of Administrator:oral

Daily Dose:

400.0 mg/day R03DA04

Chemical Structure:

SMILE Code:
CN1C2=C(C(=O)N(C1=O)C)NC=N2

Reference

COHORT STUDY:

N/A

OTHER REFERENCE(S):

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Lancet.1985 Jun 22;1(8443):1451-2. PMID: 2861396

29: Rhabdomyolysis and acute renal failure after theophylline overdose.

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Lancet.1985 Apr 20;1(8434):932-3. PMID: 2858780

30: Fatal overdose from a sustained-release theophylline preparation.

[Robertson N J]
Ann Emerg Med.1985 Feb;14(2):154-8. PMID: 3970401

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