Loratadine – Pseudoephedrine Sulfate
Histamine H1-Receptor Antagonist – Sympathomimetic Amine
Action And Clinical Pharmacology: Loratadine is a long-acting tricyclic antihistamine with selective peripheral H1 receptor antagonistic activity. It exhibits a dose-related inhibition of the histamine-induced skin wheal and flare response in humans which is rapid in onset, is apparent at 2 hours and persists throughout the 24 hour observation period. Single oral doses up to 160 mg and repeat daily doses of 40 mg for up to 13 weeks were well tolerated with the incidence of sedation and dry mouth being no different from placebo.
4-loratadine is rapidly absorbed reaching Cmax values (4.7, 10.8 and 26.1 ng/mL) at 1.5, 1.0 and 1.3 hours for the 10, 20 and 40 mg dose, respectively. The loratadine elimination half-life (t1/2) ranged from 7.8 to 11 hours.
Descarboethoxyloratadine, the major active metabolite, reached Cmax values (4.0, 9.9 and 16.0 ng/mL at 3.7, 1.5 and 2.0 hours after a dose of 10, 20 and 40 mg, respectively. Its t1/2 ranged from 17 to 24 hours. The accumulation indices, calculated by Cmax and the area under the curve (AUC) ratios did not change after the 5th day, indicating little or no accumulation of either loratadine or its metabolite after a multiple once per day dosage regimen. The t1/2 at steady state levels for loratadine and its active metabolite were 14.4 and 18.7 hours, respectively, similar to that reported following a single oral dose.
Approximately 82% of the 4-loratadine dose is excreted in the urine (40%) and feces (42%) over a 10-day period. Approximately 27% of the dose is eliminated in the urine during the first 24 hours largely in the conjugated form. Unchanged drug is present only in trace quantities in the urine and the active metabolite descarboethoxyloratadine represents only 0.4 to 0.6% of the administered loratadine dose.
Pseudoephedrine sulfate, one of the naturally occurring alkaloids of Ephedra and an orally administered vasoconstrictor, produces a gradual but sustained decongestant effect facilitating shrinkage of congested mucosa in upper respiratory areas. The mucous membrane of the respiratory tract is decongested through the action of the sympathetic nerves.
Indications And Clinical Uses: For the relief of nasal and ocular symptoms of upper respiratory mucosal congestion, such as in allergic rhinitis. For short-term use only unless taken under medical supervision.
Contra-Indications: In those patients who have shown sensitivity or idiosyncrasy to the components, to adrenergic agents or to other drugs of similar chemical structures. Also contraindicated in patients receiving MAO inhibitor therapy or within 14 days of discontinuing such treatment and in patients with narrow-angle glaucoma, urinary retention, hypertension, severe coronary artery disease and hyperthyroidism.
Precautions: General: Sympathomimetics should be used with caution in patients with stenosing peptic ulcer, pyloroduodenal obstruction, prostatic hypertrophy or bladder neck obstruction, cardiovascular disease, increased intraocular pressure or diabetes mellitus.
Sympathomimetics should be used with caution in patients receiving digitalis.
Sympathomimetics may cause central nervous system (CNS) stimulation and convulsions or cardiovascular collapse with accompanying hypotension.
Patients with severe liver impairment should be administered a lower dose because they may have reduced clearance of loratadine; an initial dose of 1 tablet daily is recommended.
Geriatrics: In patients 60 years of age or older, sympathomimetics are also more likely to cause adverse reactions such as confusion, hallucination, convulsions, CNS depression and death. Consequently, caution should be exercised when administering a repeat-action formulation to this patient group.
Dependence Liability: There are no data available to indicate that abuse or dependency occurs with loratadine.
Pseudoephedrine, like other CNS stimulants, has been abused. At high doses, subjects commonly experience mood elevation, decreased appetite and a sense of increases energy, physical strength, mental capacity and alertness. Anxiety, irritability and loquacity also have been reported. With continued use, tolerance develops; the user increased the dose and ultimately toxicity occurs. Depression may follow rapid withdrawal.
Children: Safety and efficacy in children younger than 12 years of age have not yet been established.
Pregnancy: The safe use of Claritin Extra during pregnancy or lactation has not been established and therefore, this product should be used only if the potential benefit justifies the potential risk to fetus or infant.
Lactation: Loratadine and its active metabolite are eliminated in the breast milk of lactating women with milk concentrations being similar to plasma concentrations.Through 48 hours after dosing, only 0.029% of the loratadine dose is eliminated in the milk as unchanged loratadine and its active metabolite, descarboethoxyloratadine.
Since loratadine and pseudoephedrine sulfate are excreted in breast milk, a decision should be made whether to discontinue nursing or to discontinue the use of this product.
Other: Because of the lack of experience with long-term use of this drug, its use should be limited to 3 months unless recommended by a physician.
Drug Interactions: When administered concomitantly with alcohol, loratadine has no potentiating effect as measured by psychomotor performance studies.
When sympathomimetic drugs are given to patients receiving MAO inhibitors, hypertensive reactions, including hypertensive crises, may occur. The antihypertensive effects of methyldopa, mecamylamine, reserpine and veratrum alkaloids may be reduced by sympathomimetics. Beta-adrenergic blocking agents may also interact with sympathomimetics. Increased ectopic pacemaker activity can occur when pseudoephedrine sulfate is used concomitantly with digitalis. Antacids increase the rate of pseudoephedrine sulfate absorption; kaolin decreases it.
Increases in plasma concentrations of loratadine have been reported after concomitant use with ketoconazole, erythromycin or cimetidine in controlled clinical trials, but without clinically significant changes (including electrocardiographic). Other drugs known to inhibit hepatic metabolism should be coadministered with caution until definitive interaction studies can be completed.
Antihistamines should be discontinued approximately 48 hours prior to skin testing procedures since these may prevent or diminish otherwise positive reactions to dermal reactivity indicators.
Adverse Reactions: During controlled clinical studies with the recommended dosage, the incidence of adverse effects associated with Claritin Extra was comparable to that of placebo, with the exception of insomnia and dry mouth both of which were commonly reported.
Rare adverse reactions in decreasing order of frequency included, nausea, abdominal distress, anorexia, thirst, tachycardia, pharyngitis, rhinitis, acne, prutitus, rash, urticaria, arthralgia, confusion, dysphonia, hyperkinesia, hypoesthesia, decreased libido, paresthesia, tremor, vertigo, flushing, postural hypotension, increased sweating, eye disorders, earache, tinnitus, taste abnormality, agitation, apathy, depression, euphoria, paroniria, increased appetite, change in bowel habits, dyspepsia, eructation, hemorrhoids, tongue discoloration, tongue disorder, vomiting, transient abnormal hepatic function, dehydration, increased weight, hypertension, palpitation, migraine, bronchospasm, coughing, dyspnea, epistaxis, nasal congestion, sneezing, nasal irritation, dysuria, micturition disorder, nocturia, polyuria, urinary retention, asthenia, back pain, leg cramps, malaise and rigors.
During the marketing of loratadine, alopecia, anaphylaxis and abnormal hepatic function have been reported rarely.
As with other sympathomimetic amines, CNS stimulation, muscular weakness, tightness in the chest and syncope may also be encountered.
Symptoms And Treatment Of Overdose: Symptoms: In the event of overdosage, treatment, which should be started immediately, is symptomatic and supportive. Discontinuation of use, gastric lavage or induction of emesis (except in patients with impaired consciousness) and support of vital functions are advised.
Manifestations: They may vary from CNS depression (sedation, apnea, diminished mental alertness, cyanosis, coma, cardiovascular collapse) to stimulation (insomnia, hallucination, 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 delusions and hallucinations. Some may develop cardiac arrhythmias, circulatory collapse, convulsions, coma and respiratory failure.
Treatment: 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. The action of ipecac is facilitated by physical activity and by the administration of 240 to 360 mL of water. If emesis does not occur within 15 minutes, the dose of ipecac should be repeated. Precautions against aspiration must be taken, especially in children. Following emesis, adsorption of any drugs remaining in the stomach may be attempted by the administration of activated charcoal as a slurry with water. If vomiting is unsuccessful, or contraindicated, gastric lavage should be performed. Physiologic saline solution is the lavage solution of choice, particularly in children. In adults, tap water can be used; however, as much as possible of the amount administered should be removed before the next instillation. Saline cathartics draw water into the bowel by osmosis and therefore may be valuable for their action in rapid dilution of bowel content. Loratadine is not removed by hemodialysis; it is not known if loratadine is removed by peritoneal dialysis. After emergency treatment, the patient should continue to be medically monitored.
Treatment of the signs and 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 hypothermic blanket. Apnea is treated with ventilatory support.
Dosage: Adults and Children 12 years of age and over: 1 tablet twice a day.
Availability And Storage: Each white to off-white, round, biconvex, coated tablet contains: loratadine 5 mg in the tablet coating and pseudoephedrine sulfate 120 mg equally distributed between the tablet coating and the barrier-coated core. The two active components in the coating are quickly liberated; release of the decongestant in the core is delayed for several hours. Nonmedicinal ingredients: lactose, starch, polyvinylpyrrolidone, magnesium stearate, acacia, sucrose, calcium sulfate (terra alba), microcrystalline cellulose, rosin, zein, oleic acid, soap, talc, titanium dioxide, white wax and carnauba wax. Blister packages of 10 and 20. Bottles of 100. Store between 2 and 25°C. Protect from exposure to excessive moisture.
CLARITIN® EXTRA Schering Loratadine – Pseudoephedrine Sulfate Histamine H1-Receptor Antagonist – Sympathomimetic Amine