The Wichita Eagle from Wichita, Kansas • 122

CLARITIN'-D brand of loratadine and pseudoephedrine sulfate, USP Long-Acting Release Decongestant Tablets BRIEF SUMMARY (For full Prescribing Information, see package insert.) CAUTION: Federal Law Prohibits Dispensing Without Prescription INDICATIONS AND USAGE: -D Tablets are indicated for the relief of symptoms of seasonal allergic rhinitis. CLARITIN-D Tablets should be administered when both the antihistaminic properties of CLARITIN (loratadine) and the nasal decongestant activity of pseudoephedrine are desired (see CLINICAL PHARMACOLOGY). CONTRAINDICATIONS: CLARITIN-D Tablets are contraindicated in patients who are hypersensitive to this medication or to any of its ingredients. This product, due to its pseudoephedrine component, is contraindicated in patients with narrow-angle glaucoma or urinary retention, and in patients receiving monoamine oxidase (MA0) inhibitor therapy or within fourteen (14) days of stopping such treatment (see Drug Interactions section). It is also contraindicated in patients with severe hypertension, severe coronary artery disease, and in those who have shown hypersensitivity or idiosyncrasy to its components, to adrenergic agents, or to other drugs of similar chemical structures.

Manifestations of patient idiosyncrasy to adrenergic agents include: insomnia, dizziness, weakness, tremor, or arrhythmias WARNINGS: CLARITIN-D Tablets should be used with caution in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure. hyperthyroidism, renal impairment, or prostatic hypertrophy. Central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension may be produced by sympathomimetic amines. Use in Patients Approximately 60 years and Older: The safety and efficacy of CLARITIN-D Tablets in patients greater than 60 years old have not been investigated in placebocontrolled clinical trials. The elderly are more likely to have adverse reactions to thomimetic amines PRECAUTIONS: General: Because the doses of this fixed combination product cannot be individually titrated and hepatic insufficiency results in a reduced clearance of loratadine to a much greater extent than pseudoephedrine, CLARITIN-D Tablets should generally be avoided in patients with hepatic insufticiency.

Patients with renal insufficiency (GFR 30 should be given a lower initial dose (one tablet per day) because they have reduced clearance of loratadine and pseudoephedrine. Information for Patients: Patients taking CLARITIN-D Tablets should receive the following information: CLARITIN-D Tablets are prescribed for the relief of symptoms of seasonal allergic rhinitis. Patients should be instructed to take CLARITIN-D Tablets only as prescribed and not to exceed the prescribed dose. Patients should also be advised against the concurrent use of CLARITIN-D Tablets with over-the-counter antihistamines and decongestants. This product should not be used by patients who are hypersensitive to it or to any of its ingredients.

Due to its pseudoephedrine component, this product should not be used by patients with narrow-angle glaucoma, urinary retention, or by patients receiving a monoamine oxidase (MA0) inhibitor or within 14 days of stopping use of an MAO inhibitor. It also should not be used by patients with severe hypertension or severe coronary artery disease. Patients who are or may become pregnant should be told that this product should be used in pregnancy or during lactation only if the potential benefit justifies the potential risk to the fetus or nursing infant. Patients should be instructed not to break or chew the tablet. Drug Interactions: No specific interaction studies have been conducted with CLARITIN-D Tablets.

However, loratadine (10 mg once daily) has been safely coadministered with therapeutic doses of erythromycin, cimetidine, and ketoconazole in controlled clinical pharmacology studies. Although increased plasma concentrations (AUC 0-24 hrs) of loratadine descarboethoxyloratadine were observed following coadministration of loratadine with each of these drugs in normal volunteers in each study), there were no clinically relevant changes in the safety profile of loratadine, as assessed by electrocardiographic parameters, clinical laboratory tests, vital signs, and adverse events. There were no significant effects on QT, intervals, and no reports of sedation or syncope. No effects on plasma concentrations of cimetidine or ketoconazole were observed. Plasma concentrations (AUC 0-24 hrs) of erythromycin decreased with coadministration of loratadine relative to that observed with erythromycin alone.

The clinical relevance of this difference is unknown. These above findings are summarized in the following table: Effects on Plasma Concentrations (AUC 0-24 hrs) of Loratadine and Descarboethoxvioratadine After 10 Days of Coadministration (Loratadine. 10 mg) in Normal Volunteers Loratadine Descarboethoxvioratadine Erythromycin (500 mg Q8h) Cimetidine (300 mg QID) Ketoconazole (200 mg 012h) There does not appear to be an increase in adverse events in subjects who received oral contraceptives and loratadine. CLARITIN-D Tablets (pseudoephedrine component) are contraindicated in patients taking monoamine oxidase inhibitors and for 2 weeks after stopping use of an MAO inhibitor. The antihypertensive effects of beta-adrenergic blocking agents, methyldopa, mecarnylamine, reserpine, and veratrum alkaloids may be reduced by sympathorimetics.

Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis. Test Interactions: The in vitro addition of pseudoephedrine to sera containing the cardiac isoenzyme MB of serum creatinine phosphokinase progressively inhibits the activity of the enzyme. The inhibition becomes complete over 6 hours. Carcinogenesis, Mutagenesis, Impairment of Fertility: There are no animal or laboratory studies on the combination product loratadine and pseudoephedrine sulfate to evaluate carcinogenesis, mutagenesis, or impairment of fertility. In an 18-month oncogenicity study in mice and a 2-year study in rats loratadine was administered in the diet at doses up to 40 (mice) and 25 (rats).

In the carcinogenicity studies pharmacokinetic assessments were carried out to determine animal exposure to the drug. AUC data demonstrated that the exposure of mice given 40 of loratadine was 3.6 (loratadine) and 18 (active metabolite) times higher than a human given 10 Exposure of rats given 25 of loratadine was 28 (loratadine) and 67 (active metabolite) times higher than a human given 10 Male mice given 40 had a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) than concurrent controls. In rats, a significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 and males and females given 25 The clinical significance of these findings during long-term use of loratadine is not known In mutagenicity studies with loratadine alone, there was no evidence of mutagenic potential in reverse (Ames) or forward point mutation (CHO-HGPRT) assays, or in the assay for DNA damage (Rat Primary Hepatocyte Unscheduled DNA Assay) or in two assays for chromosomal aberrations (Human Peripheral Blood Lymphocyte Clastogenesis Assay and the Mouse Bone Marrow Erythrocyte Micronucleus Assay). In the Mouse Lymphoma Assay, a positive finding occurred in the nonactivated but not the activated phase of the study Loratadine administration produced hepatic microsomal enzyme induction in the mouse at 40 and rat at 25 but not at lower doses. Decreased fertility in male rats, shown by lower female conception rates, occurred at approximately 64 of loratadine and was reversible with cessation of dosing.

Loratadine had no effect on male or female fertility or reproduction in the rat at doses approximately 24 Pregnancy Category There was no evidence of animal teratogenicity in reproduction studies performed on rats and rabbits with this combination at oral doses up to 150 (885 or 5 times the recommended daily human dosage of 250 mg or 185 and 120 (1416 or 8 times the recommended daily human dosage), respectively, There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response. CLARITIN-D Tabiets should be used during pregnancy only if clearly needed Nursing Mothers: It is not known it this combination product is excreted in human milk. However, loratadine when administered alone and its metabolite descarboethoxy- loratadine pass easily into breast milk and achieve concentrations that are equivalent to plasma levels, with an ratio of 1.17 and 0.85 for the parent and active metabolite, respectively. Following a single oral dose of 40 mg, a small amount of loratadine and metabolite was excreted into the breast milk (approximately 0.03% of 40 mg after 48 hours).

Pseudoephedrine administered alone also distributes into breast milk of the lactating human female. Pseudoephedrine concentrations in milk are consistently higher than those in plasma. The total amount of drug in milk as judged by the area under the curve (AUC) is 2 to 3 times greater than in plasma. The fraction of a pseudoephedrine dose excreted in milk is estimated to be 0.4% to 0.7%. A decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Caution should be exercised when CLARITIN-D Tablets are administered to a nursing woman. Pediatric Use: Safety and effectiveness in children below the age of 12 years have not been established. ADVERSE REACTIONS: Experience from controlled and uncontrolled clinical studies involving approximately 10,000 patients who received the combination of loratadine and pseudoephedrine sulfate for a period of up to 1 month provides information on adverse reactions. The usual dose was one tablet every 12 hours for up to 28 days In controlled clinical trials using the recommended dose of one tablet every 12 hours, the incidence of reported adverse events was similar to those reported with placebo, with the exception of insomnia and dry mouth REPORTED ADVERSE EVENTS WITH AN INCIDENCE OF ON CLARITIN-D IN PLACEBO-CONTROLLED CLINICAL TRIALS PERCENT OF PATIENTS REPORTING -D Loratadine Pseudoephedrine Placebo Headache 19 18 17 19 Insomnia 16 19 00 Dry Mouth 14 9 63 Somnolence on 8 Nervousness (7 1- Dizziness on Fatigue 3 Dyspepsia cv 3 Nausea 3 Ca Pharyngitis 3 02 cv NO Anorexia Thirst cu 2 Adverse event rates did not appear to differ significantly based on age, sex, or race. although the number of non-white subjects was relatively small.

In addition to those adverse events reported above the tollowing less frequent adverse events have been reported in at least one CLARITIN-D treated patient: Autonomic Nervous System: Abnormal lacrimation, dehydration, flushing, hypoesthesia, increased sweating, mydriasis. Body As A Whole: Asthenia, back pain, blurred vision, chest pain, conjunctivitis, earache, ear infection, eye pain, fever, flu-like symptoms, leg cramps, lymphadenopathy, malaise, photophobia, rigors, tinnitus, viral infection, weight gain. Cardiovascular System: Hypertension, hypotension, palpitations, peripheral edema. syncope, tachycardia, ventricular extrasystoles, Central and Peripheral Nervous System: Dysphonia, hyperkinesia, hypertonia. migraine, paresthesia, tremors, vertigo.

Gastrointestinal System: Abdominal distension, abdominal distress, abdominal pain altered taste, constipation, diarrhea. eructation, flatulence, gastritis, gingival bleeding, hemorrhoids, increased appetite, stomatitis, taste loss, tongue discoloration. toothache, vomiting. Liver and Biliary System: Hepatic function abnormal Musculoskeletal System: Arthralgia, myalgia, torticollis. Psychiatric: Aggressive reaction, agitation, anxiety, apathy, confusion, decreased libido, depression, emotional lability, euphoria, impaired concentration, irritability.

paroniria. Reproductive System: Dysmenorrhea, impotence, intermenstrual bleeding, vaginitis Respiratory System: Bronchitis, bronchospasm, chest congestion, coughing, dry throat, dyspnea, epistaxis, halitosis, nasal congestion, nasal irritation, sinusitis, sneezing, sputum increased, upper respiratory infection, wheezing. Skin and Appendages: Acne, bacterial skin infection, dry skin, eczema, edema, epidermal necrolysis, erythema, hematoma, pruritus, rash, urticaria. Urinary System: Dysuria, micturition frequency, nocturia, polyuria, urinary retention. The following additional adverse events have been reported with the use of CLARITIN Tablets: alopecia, altered salivation, amnesia, anaphylaxis, angioneurotic edema, blepharospasm, breast enlargement, breast pain, dermatitis, dry hair, erythema multiforme, hemoptysis, hepatic necrosis, hepatitis, jaundice, laryngitis, menorrhagia.

nasal dryness, photosensitivity reaction, purpura, seizures, supraventricular tachyarrhythmias, and urinary discoloration. Pseudoephedrine may cause mild CNS stimulation in hypersensitive patients. Nervousness, excitability, restlessness, dizziness, weakness. or insomnia may occur. Headache, drowsiness, tachycardia, palpitation, pressor activity, and cardiac arrhythmias have been reported.

Sympathomimetic drugs have also been associated with other untoward effects, such as fear, anxiety, tenseness, tremor, hallucinations, seizures, pallor, respiratory difficulty, dysuria, and cardiovascular collapse. OVERDOSAGE: Somnolence, tachycardia, and headache have been reported with doses of 40 to 180 mg of CLARITIN Tablets. In the event of overdosage, general symptomatic and supportive measures should be instituted promptly and maintained for as long as necessary. Treatment of overdosage would reasonably consist of emesis (ipecac syrup), except in patients with impaired consciousness, followed by the administration of activated charcoal to absorb any remaining drug. If vomiting is unsuccessful, or contraindicated, gastric lavage should be performed with normal saline.

Saline cathartics may also be of value for rapid dilution of bowel contents. Loratadine is not eliminated by hemodialysis. It is not known if loratadine is eliminated by peritoneal dialysis. 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 1 respiratory failure. The oral LDso values for the mixture of the two drugs were greater than 525 and 1839 in mice and rats, respectively. Oral LDs0 values for loratadine were greater than 5000 in rats and mice. Doses of loratadine as high as 10 times the recommended daily clinical dose showed no effect in rats, mice, and monkeys. Scoring: Schering Kenilworth.

NJ Corporation 07033 USA Rev. 17762605-JBS Copyright 1994 Schering Corporation All rights reserved New CLARITIN-D Nondrowsy prescription relief for runny noses; itchy, watery eyes; sneezing; and stuffy, congested noses. Clear relief from seasonal nasal allergy symptoms including nasal congestion. Clear relief that won't make you drowsy. In studies, the incidence of drowsiness, was similar to placebo (sugar pill), at the recommended dose.

Clear relief for 24 hours with convenient twice-a-day dosing (every 12 hours). Clear relief with a low occurrence of side effects. Common side effects of are sleeplessness, and dry mouth, only two side effects that occurred more often with than with placebo (sugar pill). Other side effects, including headache, sleepiness, and nervousness, occurred about as often as with placebo (sugar pill). contains pseudoephedrine sulfate, which also is in many over-the-counter (OTC) and prescription medications.

Too much pseudoephedrine sulfate can cause nervousness, sleeplessness, dizziness, and other related side effects. Therefore, be sure to tell your health-care provider if you are taking any OTC or prescription medications, including decongestants. There are some people who should not take Other people need to be especially careful using it. Therefore, be sure to tell your health-care provider if you have high blood pressure, heart disease, diabetes, glaucoma, thyroid or liver problems, or difficulty urinating, or if you are taking MAO inhibitors (prescription medicines that treat depression), or if you become pregnant or are nursing a baby. Also, must not be chewed or broken.

Available by prescription only. Call 1-800-CLARITIN for a $5.00 coupon and important FREE information about relief from seasonal nasal allergies including nasal congestion. Consult your doctor for important information concerning this product. Ask your doctor for a trial of New, twice-a-day Claritin-D (loratadine 5 sulfate, USP 120 mg) Extended Release Tablets Clear Relief Please see adjacent additional important information. Copyright 1995, Schering Corporation, Kenilworth, NJ 07033.

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