Theophylline, Ephedrine, and Hydroxyzine (Systemic )


VA CLASSIFICATION
Primary: RE190

Commonly used brand name(s): Marax; Marax-DF.

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

Unaccepted
Theophylline, ephedrine, and hydroxyzine combination is used to control bronchospastic disorders; however, the efficacy of this combination medication in these disorders has not been established. {01} Although the FDA has proposed withdrawal of approval of new drug applications (NDAs) for fixed combinations containing theophylline, ephedrine, and hydroxyzine, these products remain on the market pending further review.


Pharmacology/Pharmacokinetics

Theophylline—See Bronchodilators, Theophylline (Systemic) .

Ephedrine—See Bronchodilators, Adrenergic (Systemic) .

Hydroxyzine—See Antihistamines (Systemic) .


Precautions to Consider

Theophylline—See Bronchodilators, Theophylline (Systemic) .

Ephedrine—See Bronchodilators, Adrenergic (Systemic) .

Hydroxyzine—See Antihistamines (Systemic) .


Side/Adverse Effects
Theophylline—See Bronchodilators, Theophylline (Systemic) .
Ephedrine—See Bronchodilators, Adrenergic (Systemic) .
Hydroxyzine—See Antihistamines (Systemic) .



Overdose

Treatment of overdose
Theophylline—See Bronchodilators, Theophylline (Systemic) .
Ephedrine—See Bronchodilators, Adrenergic (Systemic) .
Hydroxyzine—See Antihistamines (Systemic) .


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Theophylline, Ephedrine, and Hydroxyzine (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, ephedrine or other sympathomimetics, or hydroxyzine

Pregnancy—Theophylline crosses placenta; decreased elimination during third trimester may require more frequent serum concentration determinations

Use of ephedrine is not recommended

Hydroxyzine is not recommended during early months of pregnancy





Breast-feeding—Theophylline and ephedrine distribute into breast milk; may result in irritability in infants

Hydroxyzine may cause unusual excitement or irritability in nursing infant





Use in children—Decreased theophylline clearance in children younger than 1 year of age, especially neonates and infants younger than 3 months of age with renal function impairment, results in lower dosage requirements; initially, use in children younger 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; severe signs or symptoms of toxicity are more common in these patients following chronic overdose that results in serum concentrations > 30 mcg per mL (165 micromoles per L)

May be more sensitive to tremor or tachycardia, especially those with pre-existing ischemic heart disease

Increased susceptibility to anticholinergic and sedative side effects of hydroxyzine





Dental—Prolonged use of hydroxyzine may decrease or inhibit salivary flow, which may contribute to development of caries, periodontal disease, oral candidiasis, and discomfort
Other medications, especially beta-adrenergic blocking agents; cimetidine; ciprofloxacin; clarithromycin; CNS-depression–producing medications; cocaine; enoxacin; erythromycin; fluvoxamine; furazolidone; guanadrel; guanethidine; interferon alpha; MAO inhibitors; methyldopa; mexiletine; moricizine; pentoxifylline; phenytoin; procarbazine; rauwolfia alkaloids; rifampin; tacrine; thiabendazole; ticlopidine; tricyclic antidepressants; troleandomycin; or urinary alkalinizers, such as calcium- and/or magnesium-containing antacids, carbonic anhydrase inhibitors, citrates, or sodium bicarbonate
Other medical problems, especially angle-closure glaucoma, congestive heart failure, convulsions (seizures), coronary insufficiency, hepatic disease, hypertension, hypothyroidism, pheochromocytoma, prostatic hypertrophy, or urinary retention

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

Caution if dizziness, lightheadedness, or drowsiness occurs




Side/adverse effects
Signs of potential side effects, especially heartburn and/or vomiting or severe difficulty breathing


General Dosing Information
The recommended doses are given as a guideline for use in the average patient. Dosage of this combination 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}.

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. {03}

Large amounts of caffeine-containing foods or beverages should be avoided, since they may increase CNS stimulant effects of theophylline bronchodilators {02}.


Oral Dosage Forms

THEOPHYLLINE, EPHEDRINE SULFATE, AND HYDROXYZINE HYDROCHLORIDE SYRUP

Usual adult dose
Oral, 20 mL two to four times a day. {01}

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose of hydroxyzine.


Usual pediatric dose
Children up to 2 years of age—Use is not recommended. {01}

Children 2 to 5 years of age—Oral, 2.5 to 5 mL three or four times a day. {01}

Children 5 years of age and over—Oral, 5 mL three or four times a day. {01}

Strength(s) usually available
U.S.—


32.5 mg of theophylline, 6.25 mg of ephedrine sulfate, and 2.5 mg of hydroxyzine hydrochloride, per 5 mL (Rx) [Marax-DF (alcohol 5%)]

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 light. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


THEOPHYLLINE, EPHEDRINE SULFATE, AND HYDROXYZINE HYDROCHLORIDE TABLETS

Usual adult dose
Oral, 1 tablet two to four times a day. {01}

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose of hydroxyzine.


Usual pediatric dose
Children up to 5 years of age—Use is not recommended. {01}

Children 5 years of age and over—Oral, 1/2 tablet two to four times a day. {01}

Strength(s) usually available
U.S.—


130 mg of theophylline, 25 mg of ephedrine sulfate, and 10 mg of hydroxyzine hydrochloride (Rx) [Marax (scored)][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 light.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Revised: 12/23/1997



References
  1. Marax Tablets & Marax DF Syrup (Pfizer—US). In: PDR Physicians' Desk Reference. 51st ed. Montvale, NJ: Medical Economics Data 1997. p. 2015.
  1. Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics. Principles of therapeutic drug monitoring. 1st ed. Vancouver, WA: Applied Therapeutics; 1980. p. 95-163.
  1. Theophylline immediate release oral dosage forms—Labeling guidance (for manufacturers), Food and Drug Administration, February 9, 1995.
  1. Reviewers' responses to Bronchodilators, Theophylline (Systemic) monograph revision of 4/95.
  1. Hendeles L, Weinberger M. Theophylline—a state of the art review. Pharmacotherapy 1983; 3: 2-44.
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