Triprolidine HCl, Pseudoephedrine HCl, and Codeine Phosphate Syrup

Since Triacin-C is comprised of three pharmacologically different compounds, it is difficult to predict the exact manifestation of symptoms in a given individual. Reaction to an overdosage of this product may vary from CNS depression to stimulation. A detailed description of symptoms which are likely to appear after ingestion of an excess of the individual components follows:

Overdosage with codeine can cause transient euphoria, drowsiness, dizziness, weariness, diminution of sensitivity, loss of sensation, vomiting, transient excitement in children, and occasionally in adult women, miosis progressing to nonreactive pinpoint pupils, itching sometimes with skin rashes and urticaria and clammy skin with mottled cyanosis. In more severe cases, muscular relaxation with depressed or absent superficial and deep reflexes and a positive Babinski sign may appear. Marked slowing of the respiratory rate with inadequate pulmonary ventilation and consequent cyanosis may occur. Terminal signs include shock, pulmonary edema, hypostatic or aspiration pneumonia and respiratory arrest, with death occurring within 6-12 hours following ingestion.

Overdoses of antihistamines may cause hallucinations, convulsions, or possibly death, especially in infants and children. Antihistamines are more likely to cause dizziness, sedation, and hypotension in elderly patients.

Overdosage with triprolidine may produce reactions varying from depression to stimulation of the Central Nervous System (CNS); the latter is particularly likely in children. Atropine-like signs and symptoms (dry mouth, fixed dilated pupils, flushing, tachycardia, hallucinations, convulsions, urinary retention, cardiac arrhythmias and coma) may occur.

Overdosage with pseudoephedrine can cause excessive CNS stimulation resulting in excitement, nervousness, anxiety, tremor, restlessness and insomnia. Other effects include tachycardia, hypertension, pallor, mydriasis, hyperglycemia and urinary retention. Severe overdosage may cause tachypnea or hyperpnea, hallucinations, convulsions, or delirium, but in some individuals there may be CNS depression with somnolence, stupor or respiratory depression. Arrhythmias (including ventricular fibrillation) may lead to hypotension and circulatory collapse. Severe hypokalemia can occur, probably due to compartmental shift rather than depletion of potassium. No organ damage or significant metabolic derangement is associated with pseudoephedrine overdosage.

The toxic plasma concentration of codeine is not known with certainty. Experimental production of mild to moderate CNS depression in healthy, nontolerant subjects occurs at plasma concentrations of 0.5- 1.9ìg/mL when codeine is given by intravenous infusion. The single lethal dose of codeine in adults is estimated to be from 0.5 to 1.0 gram. It is also estimated that 5 mg/kg could be fatal in children. The LD (single, oral dose) of triprolidine is 163 to 308 mg/kg in the mouse (depending upon strain) and 840 mg/kg in the rat.

Insufficient data are available to estimate the toxic and lethal doses of triprolidine in humans. No reports of acute poisoning with triprolidine have appeared.

The LD (single, oral dose) of pseudoephedrine is 726 mg/kg in the mouse, 2206 mg/kg in the rat and 1177 mg/kg in the rabbit. The toxic and lethal concentrations in human biologic fluids are not known. Excretion rates increase with urine acidification and decrease with alkalinization. Few reports of toxicity due to pseudoephedrine have been published and no case of fatal overdosage is known.

Therapy, if instituted within 4 hours of overdosage, is aimed at reducing further absorption of the drug. In the conscious patient, vomiting should be induced even though it may have occurred spontaneously. If vomiting cannot be induced, gastric lavage is indicated. Adequate precautions must be taken to protect against aspiration, especially in infants and children. Charcoal slurry or other suitable agents should be instilled into the stomach after vomiting or lavage. Saline cathartics or milk of magnesia may be of additional benefit.

In the unconscious patient, the airway should be secured with a cuffed endotracheal tube before attempting to evacuate the gastric contents. Intensive supportive and nursing care is indicated, as for any comatose patient.

If breathing is significantly impaired, maintenance of an adequate airway and mechanical support of respiration is the most effective means of providing adequate oxygenation.

Hypotension is an early sign of impending cardiovascular collapse and should be treated vigorously. Do not use CNS stimulants. Convulsions should be controlled by careful administration of diazepam or short-acting barbiturate, repeated as necessary. Physostigmine may be also considered for use in controlling centrally mediated convulsions.

Ice packs and cooling sponge baths, not alcohol, can aid in reducing the fever commonly seen in children.

For codeine, continuous stimulation that arouses, but does not exhaust, the patient is useful in preventing coma. Continuous or intermittent oxygen therapy is usually indicated, while naloxone is useful as a codeine antidote. Close nursing care is essential.

Saline cathartics, such as milk of magnesia, help to dilute the concentration of the drugs in the bowel by drawing water into the gut, thereby hastening drug elimination.

Adrenergic receptor blocking agents are antidotes to pseudoephedrine. In practice, the most useful is the beta-blocker propranolol, which is indicated when there are signs of cardiac toxicity.

There are no specific antidotes to triprolidine. Histamine should not be given.

Pseudoephedrine and codeine are theoretically dialyzable, but the procedures have not been clinically established.

In severe cases of overdosage, it is essential to monitor both the heart (by electrocardiograph) and plasma electrolytes and to give intravenous potassium as indicated by these continuous controls. Vasopressors may be used to treat hypotension, and excessive CNS stimulation may be counteracted with parenteral diazepam. Stimulants should not be used.