Theophylline and Guaifenesin (Systemic)
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VA CLASSIFICATION
Primary: RE190
Commonly used brand name(s): Bronchial; Broncomar GG; Ed-Bron G; Elixophyllin-GG; Equibron G; Glyceryl-T; Quibron; Quibron-300; Slo-Phyllin GG; Theocon; Theolate.
Another commonly used name is
theophylline and glyceryl guaiacolate .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
†Not commercially available in Canada.
Category:
Bronchodilator—
Indications
Accepted
Asthma (prophylaxis and treatment)—Theophylline and guaifenesin combination is indicated in the management of asthma symptoms {01}. Theophylline may benefit those patients with an inadequate response to anti-inflammatory medications and beta-adrenergic bronchodilators; however, theophylline bronchodilators are not considered to be first-line therapy {02}.
Bronchitis, chronic (treatment) or
Emphysema, pulmonary (treatment) or
Pulmonary disease, chronic obstructive, other (treatment)—Theophylline and guaifenesin combination is indicated in the management of bronchitis, pulmonary emphysema, or other chronic obstructive lung diseases {01}.
Pharmacology/Pharmacokinetics
Theophylline—See Bronchodilators, Theophylline (Systemic).
Guaifenesin—See Guaifenesin (Systemic).
Precautions to Consider
Theophylline—See Bronchodilators, Theophylline (Systemic).
Guaifenesin—See Guaifenesin (Systemic).
Side/Adverse Effects
Theophylline—See Bronchodilators, Theophylline (Systemic).
Guaifenesin—See Guaifenesin (Systemic).
Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).
Theophylline—See Bronchodilators, Theophylline (Systemic).
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Theophylline and Guaifenesin (Systemic).
In providing consultation, consider emphasizing the following selected information (» = major clinical significance):
Before using this medication
» Conditions affecting use, especially:
Sensitivity to theophylline bronchodilators
Pregnancy—Theophylline crosses placenta; decreased elimination during third trimester may require more frequent serum concentration determinations
Breast-feeding—Theophylline distributes into breast milk; may result in irritability in infants
Use in children—Decreased theophylline clearance in children less than 1 year of age, especially neonates and infants less than 3 months of age with renal function impairment, results in lower dosage requirements; initially, use in children less than 1 year of age may require more frequent serum concentration determinations
Use in the elderly—Possible decreased theophylline clearance in patients 60 years of age or older may result in lower dosage requirements
Other medications, especially beta-adrenergic blocking agents; cimetidine; ciprofloxacin; clarithromycin; enoxacin; erythromycin; fluvoxamine; mexiletine; moricizine; pentoxifylline; phenytoin; rifampin; tacrine; thiabendazole; ticlopidine; or troleandomycin
Other medical problems, especially congestive heart failure, convulsions (seizures), hepatic disease, or hypothyroidism
Proper use of this medication
» Taking on empty stomach with a glass of water for faster absorption or, if necessary, taking with meals or immediately after meals to lessen gastrointestinal irritation
» Importance of not taking more medication than the amount prescribed
» Compliance with therapy; not missing any doses
» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses
» Proper storage
Precautions while using this medication
» Regular visits to physician to check progress during initial period of therapy, including blood levels
» Caution in eating or drinking large amounts of caffeine-containing foods or beverages during therapy with this medication
» Notifying physician of factors that may alter theophylline concentrations, such as:
—fever (³ 102 °F ³ 24 hours or a lower temperature elevation for a longer period)
—other medicines started or stopped
—smoking started or stopped
—an extended change in diet
» Notifying the physician before having myocardial perfusion studies; results may be affected by this medicine
Side/adverse effects
Signs of potential side effects, especially heartburn and/or vomiting
General Dosing Information
Theophylline does not distribute into fatty tissue; therefore, all dosages should be calculated on the basis of lean (ideal) body weight {03}.
The recommended doses are given as a guideline for use in the average patient. Dosage of theophylline must be adjusted to meet the individual requirements of each patient on the basis of patient characteristics, clinical response, and steady-state serum theophylline concentrations {04}.
Administration of a single loading dose of theophylline is intended to produce a serum concentration in the therapeutic range as quickly as possible. A theophylline loading dose may be considered for all patient groups. {02} Although the intravenous route of administration provides the most rapid effect, immediate-release oral liquids, tablets, or capsules may also be used {03} {05}. Delayed- or extended-release dosage forms should not be used when rapid achievement of a therapeutic serum theophylline concentration is required.
Before a loading dose is administered, it is extremely important to determine the time, amount, dosage form, and route of administration of previous doses of aminophylline, oxytriphylline, or theophylline {04}.
Once the desired theophylline serum concentration is obtained with a loading dose, it can be maintained with an oral or intravenous dosage form {04}.
The goal of chronic therapy is to obtain maximum potential benefit with minimal risk of adverse effects. Transient caffeine-like side effects and excessively high serum concentrations can be avoided in most patients by starting with a lower dose and slowly increasing the dose by 25% at approximately three-day intervals. {11}
For final dosage adjustment in chronic therapy after serum peak theophylline measurement, the following dosage adjustments are recommended {11}:
| Steady-state Peak Serum Theophylline Concentration (mcg/mL)/(micromoles/L) |
Recommended Dosage Adjustment |
|---|---|
| Below 9.9/55 |
If clinically indicated, about 25% increase to nearest dose increment; recheck serum theophylline concentration after 3 days for further dosage adjustment |
| 10–14.9/55–82 |
If clinically indicated, maintain dose and recheck serum theophylline concentration at 6- to 12-month intervals; if symptoms are not controlled, consider adding additional medication to treatment regimen |
| 15–19.9/83–109 |
Consider 10% decrease in dose to increase margin of safety even if current dosage is tolerated |
| 20–24.9/110–137 |
Decrease dose by 25% even if no adverse effects are present; recheck serum theophylline concentration after 3 days |
| 25–30/138–165 |
Omit next dose; 25% decrease in subsequent doses even if no adverse effects are present; recheck serum theophylline concentration after 3 days; if symptomatic, consider whether overdose treatment is indicated |
| Above 30/165 |
Treatment of overdose may be indicated; when theophylline is resumed, decrease subsequent dose by at least 50%; recheck serum theophylline concentration after 3 days |
Note: If asthma is well controlled and there are no side effects or intervening factors that would alter dose requirements, follow-up serum concentration measurements can be obtained at 6- to 12-month intervals. However, whenever a patient develops nausea, vomiting, central nervous system stimulation, or any other symptom of theophylline toxicity, even if another cause is suspected (e.g., viral gastroenteritis), the next dose should be withheld and a serum concentration measurement obtained. In addition, various drug interactions and physiologic abnormalities can alter theophylline elimination and require serum concentration measurement and/or dose adjustment. {11}
The dosing frequency should be individualized. When rapidly absorbed dosage forms such as liquids are used, dosing to maintain therapeutic serum concentrations usually requires administration every 6 hours, especially in smoking adults. A dosing interval of up to 8 hours may be appropriate in some nonsmoking adults or elderly or debilitated patients due to a slower clearance rate. In patients with hepatic disease, dosing every 12 hours or longer will usually provide relatively constant serum concentrations.
Patients requiring higher-than-usual doses (i.e., patients with rapid clearance rates) may be more effectively controlled during chronic therapy by being given extended-release dosage forms. These products have the potential to achieve relatively constant serum concentrations with 12-hour dosing intervals. Patients who metabolize theophylline rapidly may require an extended-release product every 8 hours. Patients who metabolize theophylline at a normal or slow rate (elimination half-life longer than 8 hours {10}) are potential candidates for once-a-day formulations. {09}
Alcohol-free liquid dosage forms are generally preferred {04}.
Diet/Nutrition
Dietary changes are of clinical importance only if a sustained and extreme change in the usual eating pattern occurs {05}. High-carbohydrate, low-protein diets have been shown to decrease theophylline elimination. Low-carbohydrate, high-protein diets and daily ingestion of charcoal-broiled beef have been shown to increase theophylline elimination. {11}
Large amounts of caffeine-containing foods or beverages should be avoided, since they may increase central nervous system stimulant effects of theophylline bronchodilators {07}.
Oral Dosage Forms
THEOPHYLLINE AND GUAIFENESIN CAPSULES USP
Usual adult dose
Bronchodilator
Loading dose:
For patients not currently receiving theophylline preparations—Oral, the equivalent of 5 mg of anhydrous theophylline per kg of lean (ideal) body weight {03} as a single dose {02} {06} to provide an average peak serum concentration of 10 mcg per mL (55 micromoles per L), range 5 to 15 mcg per mL (27.5 to 82.5 micromoles per L). {02} {03} {11}
For patients currently receiving theophylline preparations—Obtaining a serum theophylline concentration prior to administering a partial loading dose is recommended {04}. Once the theophylline concentration is known, the loading dose for theophylline is based on the principle that each 0.5 mg of theophylline per kg of lean (ideal) body weight will result in a 1 mcg per mL (5.5 micromoles per L) increase in serum theophylline concentration {01}.
Maintenance:
Oral, the equivalent of anhydrous theophylline, initially, 300 mg per day. After three days, the dosage may be increased, if tolerated, to 400 mg per day. After three more days, the dosage may be increased, if tolerated, to 600 mg per day without measurement of serum concentration. {11}
The total daily adult dose is administered in three or four divided doses given about six to eight hours apart. Patients with risk factors for impaired theophylline clearance may require a dosing interval of every twelve hours. Young adult smokers and patients with more rapid metabolism may require a dosing interval of every six hours. {11}
Note: If the 600-mg-per-day dose is to be maintained or exceeded, monitoring of serum theophylline concentration and patient response is recommended to achieve the optimal therapeutic theophylline dosage and minimize the risk of toxicity.
Usual pediatric dose
Bronchodilator
Loading dose:
For patients not currently receiving theophylline preparations—Children 1 to 16 years of age: Oral, the equivalent of 5 mg of anhydrous theophylline per kg of lean (ideal) body weight {03} as a single dose {02} {06} to provide an average peak serum concentration of 10 mcg per mL (55 micromoles per L), range 5 to 15 mcg per mL (27.5 to 82.5 micromoles per L). {02} {03} {11}
For patients currently receiving theophylline preparations—Obtaining a serum theophylline concentration prior to administering a partial loading dose is recommended {04}. Once the theophylline concentration is known, the loading dose for theophylline is based on the principle that each 0.5 mg of theophylline per kg of lean (ideal) body weight will result in a 1 mcg per mL increase in serum theophylline concentration {01}.
Maintenance:
Children 1 year of age and older, weighing less than 45 kg—Oral, the equivalent of anhydrous theophylline, 12 to 14 mg per kg of body weight, up to a maximum of 300 mg, per day in divided doses. The dosage may be increased, if tolerated, after three days to 16 mg per kg of body weight, up to a maximum of 400 mg, per day. After three more days, if tolerated, the dosage may be increased to 20 mg per kg of body weight, up to a maximum of 600 mg, per day. The total daily dose is administered in four to six divided doses and given every four to six hours. {11}
Children weighing more than 45 kg—See Usual adult dose {11}.
Note: If the above maintenance dose is to be maintained or exceeded, monitoring of serum theophylline concentration and patient response is recommended to achieve the optimal therapeutic theophylline dosage and minimize the risk of toxicity.
Strength(s) usually available
U.S.—
150 mg of anhydrous theophylline and 90 mg of guaifenesin (Rx) [Bronchial] [Glyceryl-T] [Quibron] [Slo-Phyllin GG] [Theolate]
300 mg of anhydrous theophylline and 180 mg of guaifenesin (Rx) [Quibron-300]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.
THEOPHYLLINE AND GUAIFENESIN ELIXIR
Usual adult dose
See Theophylline and Guaifenesin Capsules USP.
Usual pediatric dose
See Theophylline and Guaifenesin Capsules USP.
Strength(s) usually available
U.S.—
50 mg of anhydrous theophylline and 30 mg of guaifenesin, per 5 mL (Rx) [Theocon]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.
THEOPHYLLINE AND GUAIFENESIN ORAL SOLUTION USP
Usual adult dose
See Theophylline and Guaifenesin Capsules USP.
Usual pediatric dose
See Theophylline and Guaifenesin Capsules USP.
Strength(s) usually available
U.S.—
33.3 mg of anhydrous theophylline and 33.3 mg of guaifenesin, per 5 mL (Rx) [Elixophyllin-GG]
50 mg of anhydrous theophylline and 30 mg of guaifenesin, per 5 mL (Rx) [Broncomar GG] [Glyceryl-T] [Theolate][Generic]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container, unless otherwise specified by manufacturer. Protect from freezing.
THEOPHYLLINE AND GUAIFENESIN SYRUP
Usual adult dose
See Theophylline and Guaifenesin Capsules USP.
Usual pediatric dose
See Theophylline and Guaifenesin Capsules USP.
Strength(s) usually available
U.S.—
50 mg of anhydrous theophylline and 30 mg of guaifenesin, per 5 mL (Rx) [Slo-Phyllin GG (alcohol free) (dye free) (glycerin) (methylparaben) (propylene glycol) (saccharin sodium) (sodium benzoate) (sorbitol) (sucrose)]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.
THEOPHYLLINE SODIUM GLYCINATE AND GUAIFENESIN ELIXIR
Usual adult dose
See Theophylline and Guaifenesin Capsules USP.
Usual pediatric dose
See Theophylline and Guaifenesin Capsules USP.
Strength(s) usually available
U.S.—
100 mg of theophylline sodium glycinate (equivalent to 50 mg of anhydrous theophylline) and 33.3 mg of guaifenesin, per 5 mL (Rx) [Ed-Bron G] [Equibron G]
Canada—
Not commercially available.
Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing.
Revised: 12/23/1997
References
- Quibron (Roberts—US). In: PDR Physicians' desk reference. 51st ed. Montvale, NJ; Medical Economics Data Production Co; 1997. p. 2227.
- National Asthma Education Program. Expert Panel Report. Guidelines for the diagnosis and management of asthma. National Heart, Lung, and Blood Institute, 1991.
- Edwards DJ, Zarowitz BJ, Slaughter RL. Theophylline. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics: principles of therapeutic drug monitoring. Vancouver, WA: Applied Therapeutics; 1992. p. 13-1–13-38.
- Reviewers' responses to Bronchodilators, Theophylline (Systemic) monograph revision of 4/95.
- Hendeles L, Weinberger M. Theophylline—a state of the art review. Pharmacotherapy 1983; 3: 2-44.
- Carrier JA, Shaw RA, Porter RS, et al. Comparison of intravenous and oral routes of theophylline loading in acute asthma. Ann Emerg Med 1985; 14: 1145-51.
- Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. Principles of therapeutic drug monitoring. 1st ed. Vancouver, WA: Applied Therapeutics; 1980. p. 95-163.
- Hendeles L, Jenkins J, Temple R. Revised FDA labeling guidelines for theophylline oral dosage forms. Pharmacotherapy 1995; 15: 409-27.
- Hendeles L, Iafrate RP, Weinberger M. A clinical and pharmacokinetic basis for the selection and use of slow release theophylline products. Clin Pharmacokinet 1984; 9: 95-135.
- Panel comment, Rec 4/12/95.
- Theophylline immediate release oral dosage forms—Labeling guidance (for manufacturers), Food and Drug Administration, February 9, 1995.
- Reviewers' consensus: Bronchodilators, Theophylline (Systemic) monograph revision, 4/95.
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