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CLARITIN-D® 24 HOUR (loratadine and pseudoephedrine sulfate, USP) Extended Release Tablets contain 10 mg loratadine in the tablet coating for immediate release and 240 mg pseudoephedrine sulfate, USP in the tablet core which is released slowly allowing for once-daily administration.
Loratadine is a long-acting antihistamine having the empirical formula C 22 H 23 CIN 2 O 2 ; the chemical name ethyl 4-(8-chloro-5,6-dihydro-11 H -benzo[5,6]cyclohepta[1,2- b ]pyridin-11-ylidene)-1-piperidinecarboxylate; and the following chemical structure:
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The molecular weight of loratadine is 382.89. It is a white to off-white powder, not soluble in water, but very soluble in acetone, alcohol, and chloroform.
Pseudoephedrine sulfate is the synthetic salt of one of the naturally occurring dextrorotatory diastereomers of ephedrine and is classified as an indirect sympathomimetic amine. The empirical formula for pseudoephedrine sulfate is (C 10 H 15 NO) 2 · H 2 SO 4 ; the chemical name is (alpha)-[1-(methylamino) ethyl]-[ S -( R *, R *)]-benzenemethanol sulfate (2:1)(salt); and the chemical structure is:
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The molecular weight of pseudoephedrine sulfate is 428.54. It is a white powder, freely soluble in water and methanol and sparingly soluble in chloroform.
The inactive ingredients for oval, biconvex CLARITIN-D 24 HOUR Extended Release Tablets are calcium phosphate, carnauba wax, ethylcellulose, hydroxypropyl methylcellulose, magnesium stearate, polyethylene glycol, povidone, silicon dioxide, sugar, titanium dioxide, and white wax.
The following information is based upon studies of loratadine alone or pseudoephedrine alone, except as indicated.
Loratadine is a long-acting tricyclic antihistamine with selective peripheral histamine H 1 -receptor antagonistic activity.
Human histamine skin wheal studies following single and repeated oral doses of loratadine have shown that the drug exhibits an antihistaminic effect beginning within 1 to 3 hours, reaching a maximum at 8 to 12 hours, and lasting in excess of 24 hours. There was no evidence of tolerance to this effect developing after 28 days of dosing with loratadine.
Pharmacokinetic studies following single and multiple oral doses of loratadine in 115 volunteers showed that loratadine is rapidly absorbed and extensively metabolized to an active metabolite (descarboethoxyloratadine). Approximately 80% of the total dose administered can be found equally distributed between urine and feces in the form of metabolic products after 10 days. The mean elimination half-lives found in studies in normal adult subjects (n = 54) were 8.4 hours (range = 3 to 20 hours) for loratadine and 28 hours (range = 8.8 to 92 hours) for the major active metabolite (descarboethoxyloratadine). In nearly all patients, exposure (AUC) to the metabolite is greater than exposure to parent loratadine. Loratadine and descarboethoxyloratadine reached steady state in most patients by approximately the fifth dosing day. The pharmacokinetics of loratadine and descarboethoxyloratadine are dose independent over the dose range of 10 to 40 mg and are not significantly altered by the duration of treatment.
In vitro studies with human liver microsomes indicate that loratadine is metabolized to descarboethoxyloratadine predominantly by P450 CYP3A4 and, to a lesser extent, by P450 CYP2D6. In the presence of a CYP3A4 inhibitor ketoconazole, loratadine is metabolized to descarboethoxyloratadine predominantly by CYP2D6. Concurrent administration of loratadine with either ketoconazole, erythromycin (both CYP3A4 inhibitors), or cimetidine (CYP2D6 and CYP3A4 inhibitor) to healthy volunteers was associated with significantly increased plasma concentrations of loratadine (see Drug Interactions section
In a study involving 12 healthy geriatric subjects (66 to 78 years old), the AUC and peak plasma levels (C max ) of both loratadine and descarboethoxyloratadine were significantly higher (approximately 50% increased) than in studies of younger subjects. The mean elimination half-lives for the elderly subjects were 18.2 hours (range = 6.7 to 37 hours) for loratadine and 17.5 hours (range = 11 to 38 hours) for the active metabolite.
In patients with chronic renal impairment (creatinine clearance </=30 mL/min) both the AUC and peak plasma levels (C max ) increased on average by approximately 73% for loratadine; and approximately by 120% for descarboethoxyloratadine, compared to individuals with normal renal function. The mean elimination half-lives of loratadine (7.6 hours) and descarboethoxyloratadine (23.9 hours) were not significantly different from that observed in normal subjects. Hemodialysis does not have an effect on the pharmacokinetics of loratadine or its active metabolite (descarboethoxyloratadine) in subjects with chronic renal impairment.
In patients with chronic alcoholic liver disease the AUC and peak plasma levels (C max ) of loratadine were double while the pharmacokinetic profile of the active metabolite (descarboethoxyloratadine) was not significantly changed from that in normals. The elimination half-lives for loratadine and descarboethoxyloratadine were 24 hours and 37 hours, respectively, and increased with increasing severity of liver disease.
There was considerable variability in the pharmacokinetic data in all studies of loratadine, probably due to the extensive first-pass metabolism. Individual histograms of area under the curve, clearance, and volume of distribution showed a log normal distribution with a 25-fold range in distribution in healthy subjects.
Loratadine is about 97% bound to plasma proteins at the expected plasma concentrations (2.5 to 100 ng/mL) after a therapeutic dose. Loratadine does not affect the plasma protein binding of warfarin and digoxin. The metabolite descarboethoxyloratadine is 73% to 77% bound to plasma proteins (at 0.5 to 100 ng/mL).
Whole body autoradiographic studies in rats and monkeys, radio-labeled tissue distribution studies in mice and rats, and in vivo radioligand studies in mice have shown that neither loratadine nor its metabolites readily cross the blood-brain barrier. Radioligand binding studies with guinea pig pulmonary and brain H 1 -receptors indicate that there was preferential binding to peripheral versus central nervous system H 1 -receptors.
In a study in which loratadine alone was administered at four times the clinical dose for 90 days, no clinically significant increase in the QT c was seen on ECGs.
In a single-rising dose study of loratadine alone in which doses up to 160 mg (16 times the clinical dose) were administered, no clinically significant changes on the QT c interval in the ECGs were observed.
Pseudoephedrine sulfate (d-isoephedrine sulfate) is an orally active sympathomimetic amine which exerts a decongestant action on the nasal mucosa. It is recognized as an effective agent for the relief of nasal congestion due to allergic rhinitis. Pseudoephedrine produces peripheral effects similar to those of ephedrine and central effects similar to, but less intense than, amphetamines. It has the potential for excitatory side effects.
The bioavailability of loratadine and pseudoephedrine sulfate from CLARITIN-D 24 HOUR Extended Release Tablets is similar to that achieved with separate administration of the components. Coadministration of loratadine and pseudoephedrine does not significantly affect the bioavailability of either component.
In a single-dose study, food increased the AUC of loratadine by approximately 125% and C max by approximately 80%. However, food did not significantly affect the pharmacokinetics of pseudoephedrine sulfate or descarboethoxyloratadine.
Clinical Studies: Clinical trials of CLARITIN-D 24 HOUR Extended Release Tablets involved a total of approximately 2000 patients with seasonal allergic rhinitis. One study involved 879 patients, who received either the combination product (loratadine 10 mg and pseudoephedrine sulfate 240 mg), loratadine (10 mg once daily) or pseudoephedrine sulfate (120 mg twice daily) alone, or placebo, in a double-blind randomized design. Improvement in nasal and non-nasal symptoms of seasonal allergic rhinitis including nasal congestion in patients receiving CLARITIN-D 24 HOUR Extended Release Tablets was significantly greater than in placebo recipients, and generally greater than that achieved with loratadine or pseudoephedrine sulfate alone. In this study, CLARITIN-D 24 HOUR Extended Release Tablets were well tolerated, with a frequency of sedation similar to that seen with placebo, and a frequency of nervousness and insomnia similar to that seen with pseudoephedrine sulfate given alone.
In another study of 469 patients, once-daily administration of CLARITIN-D 24 HOUR Extended Release Tablets provided effects similar to those achieved with twice-daily administration of CLARITIN-D 12 HOUR Extended Release Tablets, a combination product containing 5 mg loratadine plus 120 mg pseudoephedrine sulfate, USP, extended release.
The end of dosing interval efficacy of the pseudoephedrine component of CLARITIN-D 24 HOUR Extended Release Tablets on the symptom of nasal stuffiness was evaluated in a study of 695 patients who were randomized to receive CLARITIN-D 24 HOUR Extended Release Tablets, CLARITIN Tablets, or placebo. Patients who received CLARITIN-D 24 HOUR Extended Release Tablets had significantly more improvement in nasal stuffiness scores at the end of the dosing interval than those patients receiving CLARITIN Tablets or placebo throughout the course of the trial.
In a 6-week, placebo-controlled study of 193 patients with seasonal allergic rhinitis and concomitant mild to moderate asthma, CLARITIN-D 12 HOUR Extended Release Tablets twice daily improved seasonal allergic rhinitis signs and symptoms with no decrease in pulmonary function or adverse effect on asthma symptoms. This supports the safety of administering CLARITIN-D 24 HOUR Extended Release Tablets to seasonal allergic rhinitis patients with asthma.
CLARITIN-D 24 HOUR Extended Release Tablets are indicated for the relief of symptoms of seasonal allergic rhinitis. CLARITIN-D 24 HOUR Extended Release Tablets should be administered when both the antihistaminic properties of CLARITIN® (loratadine) and the nasal decongestant activity of pseudoephedrine sulfate are desired (see CLINICAL PHARMACOLOGY section).
CLARITIN-D 24 HOUR Extended Release 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 (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment. (See PRECAUTIONS : 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.
CLARITIN-D 24 HOUR Extended Release 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 of Age and Older: The safety and efficacy of CLARITIN-D 24 HOUR Extended Release Tablets in patients greater than 60 years old have not been investigated in placebo-controlled clinical trials. The elderly are more likely to have adverse reactions to sympathomimetic amines.
General: Because there have been reports of esophageal obstruction and perforation in patients who have taken a previously marketed formulation of CLARITIN-D 24 HOUR Extended Release Tablets, it is recommended that patients who have a history of difficulty in swallowing tablets or who have known upper gastrointestinal narrowing or abnormal esophageal peristalsis not use this product. Furthermore, since it is not known whether this formulation of CLARITIN-D 24 HOUR Extended Release Tablets has the potential for this adverse event, it is reasonable to recommend that all patients take this product with a full glass of water (see PRECAUTIONS : Information for Patients , ADVERSE REACTIONS , DOSAGE AND ADMINISTRATION ). 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 24 HOUR Extended Release Tablets should generally be avoided in patients with hepatic insufficiency. Patients with renal insufficiency (GFR <30 mL/min) should be given a lower initial dose (one tablet every other day) because they have reduced clearance of loratadine and pseudoephedrine.
Information for Patients: Patients taking CLARITIN-D 24 HOUR Extended Release Tablets should receive the following information: CLARITIN-D 24 HOUR Extended Release Tablets are prescribed for the relief of symptoms of seasonal allergic rhinitis. Patients should be instructed to take CLARITIN-D 24 HOUR Extended Release Tablets only as prescribed and not to exceed the prescribed dose. Patients should also be advised against the concurrent use of CLARITIN-D 24 HOUR Extended Release Tablets with over-the-counter antihistamines and decongestants. Patients who have a history of difficulty in swallowing tablets or who have known upper gastrointestinal narrowing or abnormal esophageal peristalsis should not use this product.
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 monamine oxidase (MAO) 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 and to take it with a full glass of water (see PRECAUTIONS : General , ADVERSE REACTIONS , DOSAGE AND ADMINISTRATION ).
Drug Interactions: No specific interaction studies have been conducted with CLARITIN-D 24 HOUR Extended Release 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 and/or descarboethoxyloratadine were observed following coadministration of loratadine with each of these drugs in normal volunteers (n = 24 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 c 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 15% 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:
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There does not appear to be an increase in adverse events in subjects who received oral contraceptives and loratadine.
CLARITIN-D 24 HOUR Extended Release 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, mecamylamine, reserpine, and veratum alkaloids may be reduced by sympathomimetics. Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis.
Drug/Laboratory 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 carcinogenicity study in mice and a 2-year study in rats loratadine was administered in the diet at doses up to 40 mg/kg (mice) and 25 mg/kg (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 mg/kg of loratadine was 3.6 (loratadine) and 18 (active metabolite) times higher than in humans given the maximum recommended daily oral dose. Exposure of rats given 25 mg/kg of loratadine was 28 (loratadine) and 67 (active metabolite) times higher than in humans given the maximum recommended daily oral dose. Male mice given 40 mg/kg 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 mg/kg and in males and females given 25 mg/kg. The clinical significance of these findings during long-term use of loratadine is not known.
Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Programs (NTP) uncovered no evidence of carcinogenic potential of ephedrine sulfate at doses up to 10 and 27 mg/kg, respectively (approximately 16% and 100% of the maximum recommended human daily oral dose of pseudoephedrine sulfate on a mg/m 2 basis
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.
Decreased fertility in male rats, shown by lower female conception rates, occurred at 64 mg/kg of loratadine (approximately 50 times the maximum recommended human daily oral dose based on mg/m 2 ) and was reversible with cessation of dosing. Loratadine had no effect on male or female fertility or reproduction in the rat at 24 mg/kg (approximately 20 times the maximum recommended daily oral dose on a mg/m 2 basis
Pregnancy Category B: The combination product loratadine and pseudoephedrine sulfate was evaluated for teratogenicity in rats and rabbits. There was no evidence of teratogenicity in reproduction studies with this combination of the same clinical ratio (1:24) at oral doses up to 150 mg/kg (approximately 5 times the maximum recommended human daily oral dose on a mg/m 2 basis) in rats, and 120 mg/kg (8 times the maximum recommended human daily oral dose on a mg/m 2 basis) in rabbits. Similarly, no evidence of animal teratogenicity in rats and rabbits was reported at oral doses up to 96 mg/kg of loratadine alone (approximately 75 and 150 times, respectively, the maximum human daily oral dose on a mg/m 2 basis). 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 24 HOUR Extended Release Tablets should be used during pregnancy only if clearly needed.
Nursing Mothers: It is not known if this combination product is excreted in human milk. However, loratadine when administered alone and its metabolite descarboethoxyloratadine pass easily into breast milk and achieve concentrations that are equivalent to plasma levels, with an AUC milk /AUC plasma 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 over 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 pseudo-ephedrine 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 24 HOUR Extended Release Tablets are administered to a nursing woman.
Pediatric Use: Safety and effectiveness in children below the age of 12 years have not been established.
Information on adverse reactions is provided from placebo-controlled studies involving over 2000 patients, 605 of whom received CLARITIN-D 24 HOUR Extended Release Tablets once daily for up to 2 weeks. In these studies, the incidence of adverse events reported with CLARITIN-D 24 HOUR Extended Release Tablets was similar to those reported with twice-daily (q12h) 120 mg sustained-release pseudoephedrine alone.
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Adverse events occurring in greater than or equal to 2% of CLARITIN-D 24 HOUR Extended Release Tablets-treated patients, but that were more common in the placebo-treated group, include headache.
Adverse events did not appear to significantly differ based on age, sex, or race, although the number of non-whites was relatively small.
In addition to those adverse events reported above, the following adverse events have been reported in fewer than 2% of patients who received CLARITIN-D 24 HOUR Extended Release Tablets:
Autonomic Nervous System: Altered lacrimation, flushing, increased sweating, mydriasis, thirst.
Body As A Whole: Abnormal vision, asthenia, back pain, chest pain, conjunctivitis, earache, eye pain, facial edema, fever, flu-like symptoms, leg cramps, lymphadenopathy, malaise, rigors, tinnitus.
Cardiovascular System: Hypertension, palpitation, tachycardia.
Central and Peripheral Nervous System: Convulsions, dysphonia, hyperkinesis, hypertonia, migraine, paresthesia, tremor.
Gastrointestinal System: Abdominal distension, altered taste, constipation, diarrhea, dyspepsia, flatulence, gastritis, stomatitis, tongue ulceration, toothache, vomiting.
Liver and Biliary System: Cholelithiasis.
Musculoskeletal System: Arthralgia, musculoskeletal pain, myalgia, tendinitis.
Psychiatric: Agitation, depression, emotional lability, irritability.
Reproductive System: Vaginitis.
Resistance Mechanism: Abscess, viral infection.
Respiratory System: Bronchospasm, dyspnea, epistaxis, hemoptysis, nasal congestion, nasal irritation, pleurisy, pneumonia, sinusitis, sputum increased, wheezing.
Skin and Appendages: Acne, pruritus.
Urinary System: Oliguria, micturition frequency, urinary retention, urinary tract infection.
Additional adverse events reported with the combination of loratadine and pseudoephedrine include abnormal hepatic function, aggressive reaction, anxiety, apathy, confusion, euphoria, paroniria, postural hypotension, syncope, urticaria, vertigo, weight gain.
The following additional adverse events have been reported with CLARITIN Tablets: abdominal distress, alopecia, altered micturition, altered salivation, amnesia, anaphylaxis, angioneurotic edema, blepharospasm, breast enlargement, breast pain, bronchitis, decreased libido, dermatitis, dry hair, dry skin, erythema multiforme, hypoesthesia, impaired concentration, impotence, increased appetite, laryngitis, menorrhagia, nasal dryness, peripheral edema, photosensitivity reaction, purpura, rash, seizures, sneezing, supraventricular tachyarrhythmias, upper respiratory infection, 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.
There have been postmarketing reports of mechanical upper gastrointestinal tract obstruction and esophageal perforation in patients taking a previously marketed formulation of CLARITIN-D 24 HOUR Extended Release Tablets. In some, but not all, of these cases, patients have had known upper gastrointestinal narrowing or abnormal esophageal peristalsis. It is not known whether this reformulation of CLARITIN-D 24 HOUR Extended Release Tablets has the potential for this adverse event (see PRECAUTIONS , DOSAGE AND ADMINISTRATION ).
There is no information to indicate that abuse or dependency occurs with loratadine. Pseudoephedrine, like other central nervous system stimulants, has been abused. At high doses, subjects commonly experience an elevation of mood, a sense of increased energy and alertness, and decreased appetite. Some individuals become anxious, irritable, and loquacious. In addition to the marked euphoria, the user experiences a sense of markedly enhanced physical strength and mental capacity. With continued use, tolerance develops, the user increases the dose, and toxic signs and symptoms appear. Depression may follow rapid withdrawal.
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.
Somnolence, tachycardia, and headache have been reported with doses of 40 to 180 mg of loratadine. 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.
The oral median lethal dose for the mixture of the two drugs was greater than 525 and 1839 mg/kg in mice and rats, respectively (approximately 10 and 58 times the maximum recommended human daily oral dose on a mg/m 2 basis). The oral median lethal dose for loratadine was greater than 5000 mg/kg in rats and mice (greater than 2000 times the maximum recommended human daily oral dose on a mg/m 2 basis). Single oral doses of loratadine showed no effects in rats, mice, and monkeys at doses as high as 10 times the maximum recommended human daily oral dose on a mg/m 2 basis
Adults and children 12 years of age and over: one tablet daily taken with a full glass of water (see PRECAUTIONS , ADVERSE REACTIONS ). 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 24 HOUR Extended Release Tablets should generally be avoided in patients with hepatic insufficiency. Patients with renal insufficiency (GFR <30 mL/min) should be given a lower initial dose (one tablet every other day) because they have reduced clearance of loratadine and pseudoephedrine. Patients who have a history of difficulty in swallowing tablets or who have known upper gastrointestinal narrowing or abnormal esophageal peristalsis should not use this product (see PRECAUTIONS : Information for Patients , and ADVERSE REACTIONS ).
CLARITIN-D 24 HOUR Extended Release Tablets contain 10 mg loratadine in the tablet coating for immediate release and 240 mg pseudoephedrine sulfate, USP in an extended-release core. CLARITIN-D 24 HOUR Extended Release Tablets are white to off-white oval, biconvex, coated tablets branded in black with "CLARITIN-D 24 HOUR"; high-density polyethylene bottles of 100 (NDC 0085-1233-01) and blister packages of 10 x 10 tablet Unit Dose-Hospital Pack (NDC 0085-1233-02).
Protect Unit Dose-Hospital Pack from light and store in a dry place. Store between 15° and 25°C (59° and 77°F).
U.S. Patent Nos. 5,314,697; 4,731,447; and 4,282,233.
CLARITIN-D® 24 HOUR
brand of loratadine and
pseudoephedrine sulfate, USP
Extended Release Tablets
Rev. 4/98 21678406
21861804T
Copyright © 1996, 1998, Schering Corporation.
Kenilworth, NJ 07033 USA. All rights reserved.
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