Trinalin (Azatadine / Pseudoephedrine)

TRINALIN® Schering Azatadine Maleate–Pseudoephedrine Sulfate Antihistamine–Decongestant

Action and Clinical

Azatadine is an antihistamine, related to cyproheptadine, with antiserotonin, anticholinergic, and sedative effects. Antihistamines appear to compete with histamine for histamine H1-receptor sites on effector cells and antagonize the vasodilator effect of endogenously released histamine. Consequently antihistamines antagonize the physiological manifestations of histamine release in the nose following antigen-antibody interaction, such as congestion related to vascular engorgement, mucosal edema, and profuse, watery secretion, and irritation and sneezing resulting from histamine action on afferent nerve terminals.:

Pseudoephedrine is an orally effective nasal decongestant. In effective recommended oral dosage, pseudoephedrine produces minimal other sympathomimetic effects, such as pressor activity and CNS stimulation. Use of an orally administered vasoconstrictor for shrinkage of congested nasal mucosa produces a gradual but sustained decongestant effect, causing little, if any “rebound” congestion; it facilitates shrinkage of swollen mucosa in upper respiratory areas that are relatively inaccessible to topically applied sprays or drops and it relieves nasal obstruction without the additional irritation that may result from local medication.

The apparent elimination half-life of pseudoephedrine was approximately 6.5 hours while the apparent elimination half-life of azatadine available from the outer layer of the tablets was approximately 12 hours.

Indications And Clinical Uses:

The relief of the symptoms of upper respiratory mucosal congestion in perennial and allergic rhinitis, and for the relief of nasal congestion and eustachian tube congestion.

Contra-Indications:

Antihistamines should not be used to treat lower respiratory tract symptoms.:

Patients with narrow-angle glaucoma, urinary retention and patients receiving MA0 inhibitor therapy or within 10 days of stopping such treatment (see Precautions, Drug Interactions), patients with severe hypertension, severe coronary artery disease, hyperthyroidism, and those who have shown hypersensitivity or idiosyncrasy to its components.

Precautions:

Trinalin should be used with caution in patients with glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy or bladder neck obstruction, cardiovascular disease, those with increased intraocular pressure or diabetes mellitus. Because of the atropine-like action of antihistamines, this product should be used with caution in patients with a history of bronchial asthma.:

Drug Interactions:

MAO inhibitors prolong and intensify the effects of antihistamines. Concomitant use of antihistamines with alcohol, tricyclic antidepressants, barbiturates, or other CNS depressants may have an additive effect. The action of oral anticoagulants may be inhibited by antihistamines.

When sympathomimetic drugs are given to patients receiving MAO inhibitors, hypertensive reactions, including hypertensive crises, may occur. Beta-adrenergic blocking agents may also interact with sympathomimetics. Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis. Antacids increase the rate of absorption of pseudoephedrine, while kaolin decreases it.

Occupational Hazards: Patients should be warned about engaging in activities requiring mental alertness, such as driving a car or operating appliances, or machinery.

Antihistamines are more likely to cause dizziness, sedation, and hypotension in patients over 60 years of age. In these patients, sympathomimetics are also more likely to cause adverse reactions, such as confusion, hallucinations, convulsions, CNS depression and death.

Overdosage of antihistamines, particularly in infants and children may produce convulsions and death.

Antihistamines should be discontinued approximately 4 days prior to skin testing procedures since these may prevent or diminish otherwise positive reactions to dermal reactivity indicators.

Pregnancy and Lactation: The safe use of this product during pregnancy and lactation has not been established and therefore the compound should be used only if the potential benefit justifies the potential risk to the fetus or infant.

Children: Safety and effectiveness in children below the age of 12 years have not been established.

Adverse Reactions:

Trinalin has caused no serious or unusual adverse reaction. Drowsiness was the most frequently reported side effect.

Adverse effects with antihistamines vary in incidence and severity. Among them are cardiovascular, hematologic (pancytopenia, thrombocytopenia, hemolytic anemia), neurologic (confusion, hallucinations, tremor), gastrointestinal, genitourinary (urinary retention), respiratory adverse reactions and mood changes. The most common include sedation, sleepiness, dizziness, disturbed coordination, epigastric distress, rash, dry mouth and thickening of bronchial secretions.

Sympathomimetic drugs have been associated with fear, anxiety, tenseness, weakness, pallor, respiratory difficulty, dysuria, insomnia, CNS stimulation and depression, convulsions, arrhythmias, and cardiovascular collapse with accompanying hypotension. Ephedrine-like reactions in hyperreactive individuals include: palpitations, tachycardia, hypertension, headache, dizziness or nausea.

Symptoms And Treatment Of Overdose:

Symptoms: Manifestations of overdosage may vary from CNS depression (sedation, apnea, diminished mental alertness, cyanosis, coma, cardiovascular collapse) to stimulation (insomnia, hallucinations, tremors, or convulsions) to death. Other signs and symptoms may be euphoria, excitement, tachycardia, palpitations, thirst, perspiration, nausea, dizziness, tinnitus, ataxia, blurred vision, and hypertension or hypotension. Stimulation is particularly likely in children as are atropine-like signs and symptoms (dry mouth; fixed, dilated pupils, flushing; hyperthermia; and gastrointestinal symptoms).

In large doses, sympathomimetics may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty in micturition, muscular weakness and tenseness, anxiety, restlessness, and insomnia. Many patients can present a toxic psychosis with arrhythmias, circulatory collapse, convulsions, coma, and respiratory failure.

Treatment: Emergency treatment should be started immediately. The patient should be induced to vomit, even if emesis has occurred spontaneously. Pharmacologically induced vomiting by the administration of ipecac syrup is a preferred method. However, vomiting should not be induced in patients with impaired consciousness. Following emesis, any drug remaining in the stomach may be absorbed by activated charcoal administered as a slurry with water. If vomiting is unsuccessful or contraindicated, gastric lavage should be performed. Dialysis is of little value in antihistamine poisoning. After emergency treatment the patient should continue to be medically monitored.

Treatment of the signs or symptoms of overdosage is symptomatic and supportive. Stimulants (analeptic agents) should not be used. Vasopressors may be used to treat hypotension. Short-acting barbiturates, diazepam, or paraldehyde may be administered to control seizures. Hyperpyrexia, especially in children, may require treatment with tepid water sponge baths or a hypothermic blanket. Apnea is treated with ventilatory support.

Dosage And Administration:

Trinalin tablets are not intended for use in children under 12 years of age. The usual adult dosage is 1 tablet twice a day.

Availability And Storage:

Each light grey, sugar-coated tablet contains: azatadine maleate 1 mg and pseudoephedrine sulfate USP 60 mg in the outer layer for immediate action and pseudoephedrine sulfate USP 60 mg in the tablet core for repeat action 4 to 6 hours later. Nonmedicinal ingredients: cornstarch, lactose, magnesium stearate and povidone; coating: acacia, calcium sulfate, calcium sulfate anhydrous, dye, Opalux Gray, gelatin, gum rosin, oleic acid, powdered wax mix, P-2 powder, P-101 powder, soap powder, White Neutral, sucrose, talc and zein. Tartrazine-free. Bottles of 100. Store between 2 and 30°C.

TRINALIN® Schering Azatadine Maleate–Pseudoephedrine Sulfate Antihistamine–Decongestant