Ephedrine + Hydroxyzine + Theophylline

Usage

This combination was previously used to treat asthma and bronchospasm. It combines a bronchodilator (theophylline), a decongestant (ephedrine), and an antihistamine (hydroxyzine). However, due to the potential for increased side effects and the availability of more effective and safer alternatives, this specific fixed-dose combination is no longer commonly prescribed. Specifically, the FDA has withdrawn approval for fixed-dose combinations containing ephedrine and theophylline. Theophylline and hydroxyzine can still be prescribed individually, but the fixed combination is no longer available.

Alternate Names

• Marax (brand name, no longer available)

How It Works

Ephedrine: Acts as a sympathomimetic amine, stimulating alpha and beta-adrenergic receptors leading to bronchodilation and vasoconstriction. It also indirectly increases norepinephrine release. It is metabolized in the liver and excreted renally.

Hydroxyzine: An antihistamine that works by blocking the effects of histamine at H1 receptors. This can help relieve itching and reduce allergic reactions. It also has some sedative and anticholinergic properties. It is metabolized in the liver, primarily by CYP3A4 and CYP3A5, and its major metabolite is cetirizine.

Theophylline: A methylxanthine that acts as a bronchodilator by relaxing the smooth muscles of the airways. Its mechanism of action involves nonselective phosphodiesterase inhibition, adenosine receptor antagonism, and potentially other pathways. It is metabolized in the liver by CYP1A2 and CYP3A4. Elimination is primarily through renal excretion.

Dosage

The fixed-dose combination of ephedrine, hydroxyzine, and theophylline is no longer available and therefore no dosage guidelines can be given. Individualized dosing for theophylline and hydroxyzine can be determined based on patient-specific factors and clinical guidelines for each drug.

Side Effects

Common Side Effects

• Insomnia
• Nervousness
• Gastrointestinal complaints (nausea, vomiting)
• Tachycardia
• Palpitations
• Tremors
• Dizziness
• Headache

Rare but Serious Side Effects

• Seizures
• Cardiac arrhythmias
• QT prolongation

Long-Term Effects

The long-term effects of this combination have not been extensively studied due to its discontinuation. However, chronic use of theophylline can lead to tolerance and dependence.

Contraindications

• Hypersensitivity to any component of the medication
• Severe cardiovascular disease
• Hyperthyroidism
• Seizure disorders
• Angle-closure glaucoma
• Urinary retention
• Concurrent use of MAO inhibitors

Drug Interactions

Numerous drug interactions are possible with this combination. Some clinically significant interactions include:

• Adrenergic agonists: May potentiate cardiovascular effects.
• Beta-blockers: May antagonize the bronchodilating effects of ephedrine.
• MAO inhibitors: May cause severe hypertension.
• CYP450 interacting drugs: Many drugs can affect the metabolism of theophylline and hydroxyzine.
• Other CNS depressants: May increase sedation.

Pregnancy and Breastfeeding

This combination should be avoided during pregnancy and breastfeeding due to potential risks to the fetus/infant.

Drug Profile Summary

This section is not applicable as the fixed-dose combination is no longer available.

Popular Combinations

This section is not applicable as the fixed-dose combination is no longer available.

Precautions

This combination should be used with caution in patients with renal or hepatic impairment, cardiovascular disease, and other medical conditions. Pre-screening and close monitoring are essential.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Ephedrine + Hydroxyzine + Theophylline?

A: This fixed-dose combination is no longer available, so there is no recommended dosage.

Q2: Why is this combination no longer prescribed?

A: It is no longer preferred due to the potential for increased side effects, lack of demonstrated benefit over theophylline alone, and the development of safer and more effective alternatives for asthma.

Q3: What are the alternatives for this combination?

A: Inhaled corticosteroids, long-acting beta-agonists, leukotriene modifiers, and other bronchodilators are now preferred for asthma management.

Q4: Can the components be prescribed individually?

A: Yes, theophylline and hydroxyzine can be prescribed individually, but ephedrine is less frequently used due to safety concerns.

Q5: What are the serious side effects of ephedrine?

A: Serious side effects include cardiac arrhythmias, hypertension, seizures, and stroke.

Q6: How does theophylline interact with caffeine?

A: Both are methylxanthines, and concurrent use can increase the risk of side effects like nervousness, insomnia, and tremors.

Q7: Can hydroxyzine be used during pregnancy?

A: Hydroxyzine is generally avoided during pregnancy, especially in the first trimester, due to potential risks.

Q8: How is theophylline metabolized?

A: Theophylline is metabolized in the liver by the CYP1A2 and CYP3A4 enzyme systems.

Q9: What should I monitor in patients taking theophylline?

A: Serum theophylline levels should be monitored to ensure therapeutic levels and avoid toxicity. Also, monitor for adverse events such as seizures, arrhythmias, and gastrointestinal distress.