FDA Label for Clarinex-d 12 Hour

1.1 Seasonal Allergic Rhinitis

CLARINEX-D^® 12 HOUR Extended Release Tablets is indicated for the relief of the nasal and non-nasal symptoms of seasonal allergic rhinitis, including nasal congestion, in adults and adolescents 12 years of age and older. CLARINEX-D 12 HOUR Extended Release Tablets should be administered when the antihistaminic properties of desloratadine and the nasal decongestant properties of pseudoephedrine are desired [see Clinical Pharmacology (12)].

2 Dosage And Administration

Administer CLARINEX-D 12 HOUR Extended Release Tablet by the oral route only. Do not break, chew, or crush the tablet. Swallow the tablet whole.

2.1 Adults And Adolescents 12 Years Of Age And Over

The recommended dose of CLARINEX-D 12 HOUR Extended Release Tablets is 1 tablet twice a day, administered approximately 12 hours apart and with or without a meal. Higher doses or increased dosing frequency of CLARINEX-D 12 HOUR Extended Release Tablets have not demonstrated increased effectiveness. Do not exceed the recommended dose as desloratadine and pseudoephedrine, the active components of CLARINEX-D 12 HOUR Extended Release Tablets have been associated with adverse effects at higher doses [see Overdosage (10.1) and (10.2)].

3 Dosage Forms And Strengths

CLARINEX-D 12 HOUR Extended Release Tablets are oval shaped, blue and white bilayer tablets with "D12" embossed in the blue layer. Each tablet contains 2.5 mg desloratadine in the blue immediate-release layer and 120 mg of pseudoephedrine sulfate USP in the white extended-release layer.

4 Contraindications

CLARINEX-D 12 HOUR Extended Release Tablets are contraindicated in:

• Patients with hypersensitivity to any of its ingredients, or to loratadine [see Warnings and Precautions (5.4) and Adverse Reactions (6.2)]
• Patients with narrow-angle glaucoma
• Patients with urinary retention
• Patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment [see Drug Interactions (7.1)]
• Patients with severe hypertension or severe coronary artery disease

5.1 Cardiovascular And Central Nervous System Effects

The pseudoephedrine sulfate contained in CLARINEX-D 12 HOUR Extended Release Tablets, like other sympathomimetic amines, can produce cardiovascular and central nervous system (CNS) effects in some patients such as insomnia, dizziness, weakness, tremor, or arrhythmias. In addition, central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension has been reported. Therefore, CLARINEX-D 12 HOUR Extended Release Tablets should be used with caution in patients with cardiovascular disorders, and should not be used in patients with severe hypertension or severe coronary artery disease.

5.2 Coexisting Conditions

CLARINEX-D 12 HOUR Extended Release Tablets contain pseudoephedrine sulfate, a sympathomimetic amine, and therefore should be used with caution in patients with diabetes and hyperthyroidism. Also use with caution in patients with prostatic hypertrophy or increased intraocular pressure, as urinary retention and narrow-angle glaucoma may occur [see Contraindications (4)].

5.3 Co-Administration With Monoamine Oxidase (Mao) Inhibitors

CLARINEX-D 12 HOUR Extended Release Tablets should not be used in patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment as an increase in blood pressure or hypertensive crisis, may occur [see Contraindications (4) and Drug Interactions (7.1)].

5.4 Hypersensitivity Reactions

Hypersensitivity reactions including rash, pruritus, urticaria, edema, dyspnea, and anaphylaxis have been reported after administration of desloratadine a component of CLARINEX-D 12 HOUR Extended Release Tablets. If such a reaction occurs, therapy with CLARINEX-D 12 HOUR Extended Release Tablets should be stopped and alternative treatment should be considered [see Adverse Reactions (6.2)].

5.5 Renal Impairment

CLARINEX-D 12 HOUR Extended Release Tablets should generally be avoided in patients with renal impairment [see Clinical Pharmacology (12.3)].

5.6 Hepatic Impairment

CLARINEX-D 12 HOUR Extended Release Tablets should generally be avoided in patients with hepatic impairment [see Clinical Pharmacology (12.3)].

6 Adverse Reactions

The following adverse reactions are discussed in greater detail in other sections of the label:

• Cardiovascular and Central Nervous System effects [see Warnings and Precautions (5.1)]
• Increased intraocular pressure [see Warnings and Precautions (5.2)]
• Urinary retention in patients with prostatic hypertrophy [see Warnings and Precautions (5.2)]
• Hypersensitivity reactions [see Warnings and Precautions (5.4)]
• Severe Skin Reactions

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety data described below are from 2 clinical trials with CLARINEX-D 12 HOUR Extended Release Tablets that included 1248 patients with seasonal allergic rhinitis, of which 414 patients received CLARINEX-D 12 HOUR Extended Release Tablets twice daily for up to 2 weeks. The majority of patients were between 18 and <65 years of age with a mean age of 35.8 years and were predominantly women (64%). Patient ethnicity was 82% Caucasian, 9% Black, 6% Hispanic and 3% Asian/other ethnicity. The percentage of subjects receiving CLARINEX-D 12 HOUR Extended Release Tablets and who discontinued from the clinical trials because of an adverse event was 3.6%. Adverse reactions that were reported by ≥2% of subjects receiving CLARINEX-D 12 HOUR Extended Release Tablets are shown in Table 1.

There were no relevant differences in adverse reactions for subgroups of patients as defined by gender, age, or race.

6.2 Post-Marketing Experience

In addition to the adverse reactions reported during clinical trials and listed above, adverse events have been identified during post approval use of CLARINEX-D 12 HOUR Extended Release Tablets. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Adverse events identified from post-marketing surveillance on the use of CLARINEX-D 12 HOUR Extended Release Tablets include:
Cardiac disorders: tachycardia, palpitations
Respiratory, thoracic and mediastinal disorders: dyspnea
Skin and subcutaneous tissue disorders: rash, pruritus

In addition to these events, the following spontaneous adverse events have been reported during the marketing of desloratadine as a single ingredient product:
Nervous system disorders: headache, somnolence, dizziness, psychomotor hyperactivity, movement disorders (including dystonia, tics, and extrapyramidal symptoms), seizures (reported in patients with and without a known seizure disorder)
Immune system disorders: hypersensitivity reactions (such as urticaria, edema and anaphylaxis)
Investigations: elevated liver enzymes including bilirubin
Hepatobiliary disorders: hepatitis
Metabolism and nutrition disorders: increased appetite

Cases of severe skin reactions such as acute generalized exanthematous pustulosis (AGEP) have been reported with pseudoephedrine-containing products.

7 Drug Interactions

No specific interaction studies have been conducted with CLARINEX-D 12 HOUR Extended Release Tablets.

7.1 Monoamine Oxidase Inhibitors

CLARINEX-D 12 HOUR Extended Release Tablets should not be used in patients receiving monoamine oxidase (MAO) inhibitor therapy or within fourteen (14) days of stopping such treatment because the action of pseudoephedrine a component of CLARINEX-D 12 HOUR Extended Release tablets on the vascular system may be potentiated by these agents [see Contraindications (4) and Warnings and Precautions (5.3)].

7.2 Beta-Adrenergic Blocking Agents

The antihypertensive effects of beta-adrenergic blocking agents, methyldopa, and reserpine, may be reduced by sympathomimetics such as pseudoephedrine. Exercise caution when using CLARINEX-D 12 HOUR Extended Release Tablets with these agents.

7.3 Digitalis

Increased ectopic pacemaker activity can occur when pseudoephedrine is used concomitantly with digitalis. Exercise caution when using CLARINEX-D 12 HOUR Extended Release Tablets with these agents.

7.4 Inhibitors Of Cytochrome P450 3A4

In controlled clinical studies co-administration of desloratadine with ketoconazole, erythromycin, or azithromycin resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine but there were no clinically relevant changes in the safety profile of desloratadine [see Clinical Pharmacology (12.3)].

7.5 Fluoxetine

In controlled clinical studies co-administration of desloratadine with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine but there were no clinically relevant changes in the safety profile of desloratadine [see Clinical Pharmacology (12.3)].

7.6 Cimetidine

In controlled clinical studies co-administration of desloratadine with cimetidine a histamine H₂-receptor antagonist resulted in increased plasma concentrations of desloratadine and 3-hydroxydesloratadine but there were no clinically relevant changes in the safety profile of desloratadine [see Clinical Pharmacology (12.3)].

Other

Risk Summary

The limited available data with CLARINEX-D 12 HOUR in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. There are no adequate and well-controlled studies of desloratadine and pseudoephedrine in combination in pregnant women. Neither are there animal reproduction studies conducted with the combination of desloratadine and pseudoephedrine or pseudoephedrine alone. Desloratadine given during organogenesis to pregnant rats was not teratogenic at the summed area under the concentration-time curve (AUC)-based exposures of desloratadine and its metabolite approximately 320 times that at the recommended human daily oral dose (RHD) of 5 mg/day. Desloratadine given during organogenesis to pregnant rabbits was not teratogenic at the AUC-based exposures of desloratadine approximately 230 times that at the RHD. Desloratadine given to pregnant rats during organogenesis through lactation resulted in reduced body weight and slow righting reflex of F₁ pups at the summed AUC-based exposures of desloratadine and its metabolite approximately 70 times or greater than that at the RHD [see Data].

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Human Data

Pseudoephedrine

The majority of studies examining the use of pseudoephedrine in pregnancy did not find an association with an increased risk of congenital anomalies. A few case-control studies conducted reported potential associations with isolated congenital disorders. However, several similar studies did not find statistically significant associations. Methodological limitations of these studies included small sample size, selection bias, recall bias, inadequate adjustment for risk factors, residual confounding, exposure misclassification, and lack of information regarding dose and timing of exposure.

Animal Data

No animal reproduction studies were conducted with the combination of desloratadine and pseudoephedrine or pseudoephedrine alone.

Desloratadine

Desloratadine was given orally during organogenesis to pregnant rats at doses of 6, 24 and 48 mg/kg/day (approximately 50, 200 and 320 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). No fetal malformations were present. Reduced fetal weights and skeletal variations noted at doses of 24 and 48 mg/kg/day were likely secondary to the maternal toxicities of reduced body weight gain and food consumption observed at the same doses. Desloratadine was also given orally during organogenesis to pregnant rabbits at doses of 15, 30 and 60 mg/kg/day (approximately 30, 70 and 230 times the AUC-based exposure of desloratadine at the RHD). No adverse effects to the fetus were noted. Reduced maternal body weight gain was noted in rabbits at 60 mg/kg/day. In a peri- and post-natal development study, desloratadine was given to rats orally during the peri-natal (Gestation Day 6) through lactation periods (Postpartum Day 21) at doses of 3, 9 and 18 mg/kg/day. Reduced body weight and slow righting reflex were reported in F₁ pups at doses of 9 mg/kg/day or greater (approximately 70 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Desloratadine had no effect on F₁ pup development at 3 mg/kg/day (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Maternal toxicities including reduced body weight gain and food consumption were noted at 18 mg/kg/day for F₀ dams. F₁ offspring were subsequently mated and there was no developmental toxicity for F₂ pups observed.

Risk Summary

Desloratadine and pseudoephedrine both pass into breast milk. There are not sufficient data on the effects of desloratadine on the breastfed infant or the effects of desloratadine on milk production. Pseudoephedrine has been reported to decrease milk production [see Data]. Pseudoephedrine has been reported to cause irritability in breastfed infants. The decision should be made whether to discontinue nursing or to discontinue CLARINEX-D 12 HOUR Extended Release Tablets, taking into account the developmental and health benefits of breastfeeding, the nursing mother's clinical need, and any potential adverse effects on the breastfed infant from desloratadine and pseudoephedrine or from the underlying maternal condition.

Data

Human Data

Pseudoephedrine

In a study of eight lactating women, who were 8 to 76 weeks postpartum and received a single dose of 60 mg of pseudoephedrine, the mean 24-hour milk production was reduced by 24%. In the same study, the estimated mean relative infant dose from breast milk (assuming mean milk consumption of 150 mL/kg/day and a maternal dosing regimen of 60 mg pseudoephedrine four times per day) was calculated to be 4.3% of the weight-adjusted maternal dose.

Infertility

There are no data available on human infertility associated with desloratadine, pseudoephedrine, or the combination. There are no animal fertility studies with the combination or pseudoephedrine alone.

There were no clinically relevant effects of desloratadine on female fertility in rats. A male specific decrease in fertility occurred at an oral desloratadine dose of 12 mg/kg or greater in rats (approximately 65 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Male fertility was unaffected at a desloratadine dose of 3 mg/kg (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). [See Nonclinical Toxicology (13.1).]

Drug Interaction: In 2 controlled crossover clinical pharmacology studies in healthy male (n=12 in each study) and female (n=12 in each study) subjects, desloratadine 7.5 mg (1.5 times the daily dose) once daily was co-administered with erythromycin 500 mg every 8 hours or ketoconazole 200 mg every 12 hours for 10 days. In 3 separate controlled, parallel group clinical pharmacology studies, desloratadine at the clinical dose of 5 mg has been co-administered with azithromycin 500 mg followed by 250 mg once daily for 4 days (n=18) or with fluoxetine 20 mg once daily for 7 days after a 23-day pretreatment period with fluoxetine (n=18) or with cimetidine 600 mg every 12 hours for 14 days (n=18) under steady state conditions to healthy male and female subjects. Although increased plasma concentrations (C_max and AUC _{0-24 hrs}) of desloratadine and 3-hydroxydesloratadine were observed (see Table 2), there were no clinically relevant changes in the safety profile of desloratadine, as assessed by electrocardiographic parameters (including the corrected QT interval), clinical laboratory tests, vital signs and adverse events.

Carcinogenicity Studies:

Desloratadine

The carcinogenic potential of desloratadine was assessed using a loratadine study in rats and a desloratadine study in mice. In a 2-year study in rats, loratadine was administered in the diet at doses up to 25 mg/kg/day (approximately 45 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD). A significantly higher incidence of hepatocellular tumors (combined adenomas and carcinomas) was observed in males given 10 mg/kg/day of loratadine (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD) and in males and females given 25 mg/kg/day of loratadine. The clinical significance of these findings during long-term use of desloratadine is not known. In a 2-year dietary study in mice, males and females given up to 16 mg/kg/day and 32 mg/kg/day desloratadine, respectively (approximately 30 and 70 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD, respectively), did not show significant increases in the incidence of any tumors.

Pseudoephedrine

The carcinogenic potential of pseudoephedrine was assessed using ephedrine sulfate studies in F344/N rats and B6C3F1 mice conducted under the National Toxicology Program (NTP). In a 2-year dietary study in rats, male and female rats given up to 9 and 11 mg/kg/day ephedrine sulfate (approximately 0.4 and 0.5 times the RHD of 240 mg/day on a mg/m² basis, respectively) did not show any evidence of tumorigenicity. In a 2-year dietary study in mice, male and female mice given up to 29 and 25 mg/kg/day ephedrine sulfate (approximately 0.7 and 0.6 times the RHD of pseudoephedrine on a mg/m² basis, respectively) did not show any evidence of tumorigenicity.

Genotoxicity Studies:

Desloratadine

In genotoxicity studies with desloratadine, there was no evidence of genotoxic potential in a reverse mutation assay (Salmonella/E. coli mammalian microsome bacterial mutagenicity assay) or in 2 assays for chromosomal aberrations (human peripheral blood lymphocyte clastogenicity assay and mouse bone marrow micronucleus assay).

Pseudoephedrine

Mutagenicity studies with pseudoephedrine have not been conducted.

Impairment of Fertility:

Desloratadine

In a female fertility study, desloratadine was given to female rats orally 14 days prior to and throughout mating until Gestation Day 7 at doses of 6, 12 and 24 mg/kg/day. An increase in preimplantation loss and a decrease in number of implantations and fetuses noted at 24 mg/kg (approximately 200 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD) was likely due to maternal toxicities including reduced body weight gain and food consumption. In a male fertility study in rats, desloratadine was given orally to male rats for 70 days prior to mating and throughout the mating period (total dosing period 106-108 days) at doses of 3, 12 and 40 mg/kg/day. Reduced body weight gain, food consumption, and absolute organ weights of testes, epididymis, and cauda epididymis were noted at 40 mg/kg/day. A male-specific decrease in fertility, demonstrated by reduced female conception rates, decreased sperm numbers and motility, and histopathologic changes in testes and epididymis, occurred at a dose of 12 mg/kg or greater (approximately 65 times or greater than the summed AUC-based exposure of desloratadine and its metabolite at the RHD). Desloratadine had no effect on male fertility in rats at 3 mg/kg/day (approximately 10 times the summed AUC-based exposure of desloratadine and its metabolite at the RHD).

Pseudoephedrine

Fertility studies with pseudoephedrine have not been conducted.

Manufactured for: Organon LLC, a subsidiary of
ORGANON & Co.,
Jersey City, NJ 07302, USA

For patent information: www.organon.com/our-solutions/patent/

The trademarks depicted herein are owned by their respective companies.

Copyright © 2021 Organon Global Inc.
All rights reserved.

Revised: 6/2021

usppi-og4117a-t-d12-2106r000

8.4 Pediatric Use

CLARINEX-D 12 HOUR Extended Release Tablets are not indicated for use in pediatric patients under 12 years of age.

8.5 Geriatric Use

The number of subjects (n=10) ≥65 years old treated with CLARINEX-D 12 HOUR Extended Release Tablets was too limited to make any formal statistical comparison regarding the efficacy or safety of this drug product in this age group, or to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences between the elderly and younger patients, although the elderly are more likely to have adverse reactions to sympathomimetic amines. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy [see Clinical Pharmacology (12.3)].

Pseudoephedrine, desloratadine, and their metabolites are known to be substantially excreted by the kidney, and the risk of adverse reactions may be greater in patients with renal impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor the patient for adverse events [see Clinical Pharmacology (12.3)].

8.6 Renal Impairment

No studies with CLARINEX-D 12 HOUR Extended Release Tablets were conducted in subjects with renal impairment.

CLARINEX-D 12 HOUR Extended Release Tablets should generally be avoided in patients with renal impairment [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)].

8.7 Hepatic Impairment

No studies with CLARINEX-D 12 HOUR Extended Release Tablets or pseudoephedrine were conducted in subjects with hepatic impairment.

CLARINEX-D 12 HOUR Extended Release Tablets should generally be avoided in patients with hepatic impairment [see Warnings and Precautions (5.6) and Clinical Pharmacology (12.3)].

8.8 Gender

No clinically significant gender-related differences were observed in the pharmacokinetic parameters of desloratadine, 3-hydroxydesloratadine or pseudoephedrine following administration of CLARINEX-D 12 HOUR Extended Release Tablets.

8.9 Race

No studies have been conducted to evaluate the effect of race on the pharmacokinetics of CLARINEX-D 12 HOUR Extended Release Tablets.

9 Drug Abuse And Dependence

There is no information to indicate that abuse or dependency occurs with CLARINEX or CLARINEX-D 12 HOUR Extended Release Tablets.

10 Overdosage

In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Desloratadine and 3-hydroxydesloratadine are not eliminated by hemodialysis.

10.1 Desloratadine

Information regarding acute overdosage with desloratadine is limited to experience from post-marketing adverse event reports and from clinical trials conducted during the development of the CLARINEX product. In the reported cases of overdose, there were no significant adverse events that were attributed to desloratadine. In a dose-ranging trial, at doses of 10 mg and 20 mg/day, somnolence was reported.

In another study, no clinically relevant adverse events were reported in normal male and female volunteers who were given single daily doses of CLARINEX 45 mg for 10 days [see Clinical Pharmacology (12.2)].

10.2 Sympathomimetics

In large doses, sympathomimetics such as pseudoephedrine may give rise to giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty in micturition, muscle 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.

11 Description

CLARINEX-D 12 HOUR Extended Release Tablets are oval-shaped blue and white bilayer tablets containing 2.5 mg desloratadine in the blue immediate-release layer and 120 mg of pseudoephedrine sulfate USP in the white extended-release layer which is released slowly, allowing for twice-daily administration.

The inactive ingredients contained in CLARINEX-D 12 HOUR Extended Release Tablets are hypromellose USP, microcrystalline cellulose NF, povidone USP, silicon dioxide NF, magnesium stearate NF, corn starch NF, edetate disodium USP, citric acid anhydrous USP, stearic acid NF, and FD&C Blue No. 2 aluminum lake dye.

Desloratadine, 1 of the 2 active ingredients of CLARINEX-D 12 HOUR Extended Release Tablets, is a white to off-white powder that is slightly soluble in water, but very soluble in ethanol and propylene glycol. It has an empirical formula: C₁₉H₁₉ClN₂ and a molecular weight of 310.8. The chemical name is 8-chloro-6,11-dihydro-11-(4-piperdinylidene)-5H-benzo[5,6] cyclohepta [1,2-b]pyridine and has the following structure:

Chemical Structure - clarinex d12 01

Pseudoephedrine sulfate, the other active ingredient of CLARINEX-D 12 HOUR Extended Release Tablets, is the synthetic salt of one of the naturally occurring dextrorotatory diastereomers of ephedrine and is classified as an indirect sympathomimetic amine. Pseudoephedrine sulfate is a colorless hygroscopic crystal or white, hygroscopic crystalline powder, practically odorless, with a bitter taste. It is very soluble in water, freely soluble in alcohol, and sparingly soluble in ether. The empirical formula for pseudoephedrine sulfate is (C₁₀H₁₅NO)₂ • H₂SO₄; the chemical name is benzenemethanol, α-[1-(methylamino) ethyl]-,[S-(R*,R*)]-, sulfate (2:1)(salt); and the chemical structure is:

12.1 Mechanism Of Action

Desloratadine is a long acting tricyclic histamine antagonist with selective H₁-receptor histamine antagonist activity. Receptor binding data indicate that at a concentration of 2 to 3 ng/mL (7 nanomolar), desloratadine shows significant interaction with the human histamine H₁ receptor. Desloratadine inhibited histamine release from human mast cells in vitro. Results of a radiolabeled tissue distribution study in rats and a radioligand H₁-receptor-binding study in guinea pigs showed that desloratadine does not readily cross the blood brain barrier. The clinical significance of this finding is unknown.

Pseudoephedrine sulfate is an orally active sympathomimetic amine and exerts a decongestant action on the nasal mucosa. Pseudoephedrine sulfate 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.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

There are no animal or laboratory studies on the combination product of desloratadine and pseudoephedrine sulfate or pseudoephedrine alone to evaluate carcinogenesis, mutagenesis, or impairment of fertility.

14.1 Seasonal Allergic Rhinitis

The clinical efficacy and safety of CLARINEX-D 12 HOUR Extended Release Tablets was evaluated in two 2-week multicenter, randomized parallel group clinical trials involving 1248 subjects 12 to 78 years of age with seasonal allergic rhinitis, 414 of whom received CLARINEX-D 12 HOUR Extended Release Tablets. In the 2 trials, subjects were randomized to receive CLARINEX-D 12 HOUR Extended Release Tablets twice daily, CLARINEX Tablets 5 mg once daily, or sustained-release pseudoephedrine tablet 120 mg twice daily for 2 weeks. The majority of patients were between 18 and <65 years of age with a mean age of 35.8 years and were predominantly women (64%). Patient ethnicity was 82% Caucasian, 9% Black, 6% Hispanic and 3% Asian/other ethnicity. Primary efficacy variable was twice-daily reflective patient scoring of 4 nasal symptoms (rhinorrhea, nasal stuffiness/congestion, nasal itching, and sneezing) and four non-nasal symptoms (itching/burning eyes, tearing/watering eyes, redness of eyes, and itching of ears/palate) on a 4 point scale (0=none, 1=mild, 2=moderate, and 3=severe). In both trials, the antihistaminic efficacy of CLARINEX-D 12 HOUR Extended Release Tablets, as measured by total symptom score excluding nasal congestion, was significantly greater than pseudoephedrine alone over the 2-week treatment period; and the decongestant efficacy of CLARINEX-D 12 HOUR Extended Release Tablets, as measured by nasal stuffiness/congestion, was significantly greater than CLARINEX (desloratadine alone) over the 2-week treatment period. Primary efficacy variable results from 1 of 2 trials are shown in Table 3.

There were no significant differences in the efficacy of CLARINEX-D 12 HOUR Extended Release Tablets across subgroups of subjects defined by gender, age, or race.

16 How Supplied/Storage And Handling

CLARINEX-D 12 HOUR Extended Release Tablets are oval-shaped, blue and white bilayer tablets with "D12" embossed in the blue layer, containing 2.5 mg desloratadine in the blue immediate-release layer and 120 mg of pseudoephedrine sulfate USP in the white extended-release layer. CLARINEX-D 12 HOUR Extended Release Tablets are supplied in high-density polyethylene bottles of 100 (NDC 78206-120-01).

17 Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (Patient Information).

17.1 Cardiovascular And Central Nervous System Effects

Patients should be informed that pseudoephedrine, one of the active ingredients in CLARINEX-D 12 HOUR Extended Release Tablets may cause cardiovascular or central nervous system effects such as insomnia, dizziness, tremor, convulsions or arrhythmia.

17.2 Dosing

Patients should be advised not to increase the dose or dosing frequency of CLARINEX-D 12 HOUR Extended Release Tablets.

17.3 Additional Antihistamines And/Or Decongestants

Patients should be advised against the concurrent use of CLARINEX-D 12 HOUR Extended Release Tablets with other antihistamines and/or decongestants.

17.4 Monoamine Oxidase (Mao) Inhibitors

Patients should be informed that due to its pseudoephedrine component, they should not use CLARINEX-D 12 HOUR with a monoamine oxidase (MAO) inhibitor or within 14 days of stopping use of an MAO inhibitor.

17.5 Coexisting Conditions

Patients with severe hypertension or severe coronary artery disease, narrow-angle glaucoma, or urinary retention should be advised not to use CLARINEX-D 12 HOUR Extended Release Tablets.

17.6 Instructions For Use

Patients should be instructed not to break, crush, or chew the tablet; the tablet should be swallowed whole, and can be taken without regard to meals.

Spl Patient Package Insert

PATIENT INFORMATION

CLARINEX-D^® (CLA-RI-NEX) 12 Hour Extended Release Tablets
(desloratadine and pseudoephedrine sulfate)

Read the Patient Information that comes with CLARINEX-D 12 Hour Extended Release Tablets before you start taking it and each time you get a refill. There may be new information. This leaflet is a summary of the information for patients. Your doctor or pharmacist can give you additional information. This leaflet does not take the place of talking to your doctor about your medical condition or treatment.

What is CLARINEX-D^® 12 Hour Extended Release Tablets?

CLARINEX-D 12 Hour Extended Release Tablets is a prescription medicine that contains the medicines desloratadine (an antihistamine) and pseudoephedrine (a nasal decongestant). CLARINEX-D 12 Hour Extended Release Tablets is used to help control the symptoms of seasonal allergic rhinitis (sneezing, stuffy nose, runny nose and itching of the nose) in adults and children 12 years and older.

CLARINEX-D 12 Hour Extended Release Tablets is not for children under 12 years of age.

Who should not take CLARINEX-D^® 12 Hour Extended Release Tablets?

Do not take CLARINEX-D 12 Hour Extended Release Tablets if you:

• are allergic to desloratadine or pseudoephedrine sulfate or any of the ingredients in CLARINEX-D 12 Hour Extended Release Tablets. See the end of this leaflet for a complete list of ingredients in CLARINEX-D 12 Hour Extended Release Tablets.
• are allergic to loratadine (Alavert, Claritin)
• have narrow-angle glaucoma
• have problems with urination (urinary retention)
• take a Monoamine Oxidase Inhibitor (MAOI) medicine to treat depression, or if you stopped taking an MAOI medicine within the last 2 weeks. Ask your doctor or pharmacist if you are not sure if you take an MAOI medicine.
• have severe high blood pressure
• have severe heart disease

Talk to your doctor before taking this medicine if you have any of these conditions.

What should I tell my doctor before taking CLARINEX-D^® 12 Hour Extended Release Tablets?

Before you take CLARINEX-D 12 Hour Extended Release Tablets, tell your doctor if you:

• have any of the conditions listed in the section "Who should not take CLARINEX-D 12 Hour Extended Release Tablets?"
• diabetes
• hyperthyroidism
• have prostate problems
• have liver or kidney problems
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if CLARINEX-D 12 Hour Extended Release Tablets will harm your unborn baby. Talk to your doctor if you are pregnant or plan to become pregnant.
• are breastfeeding or plan to breastfeed. CLARINEX-D 12 Hour Extended Release Tablets can pass into your breast milk. Talk to your doctor about the best way to feed your baby if you take CLARINEX-D 12 Hour Extended Release Tablets.

Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins and herbal supplements. CLARINEX-D^® 12 Hour Extended Release Tablets may affect the way other medicines work, and other medicines may affect how CLARINEX-D 12 Hour Extended Release Tablets works. Especially tell your doctor if you take:

• Monoamine Oxidase Inhibitors (MAOIs). You should not use CLARINEX-D 12 Hour Extended Release Tablets if you take an MAOI or within 2 weeks of stopping an MAOI.
• methyldopa
• reserpine (Serpalan)
• digitalis (Digoxin, Lanoxicaps, Lanoxin) ketoconazole (Nizoral)
• erythromycin (Ery-tab, Eryc, PCE)
• azithromycin (Zithromax, Zmax)
• antihistamines
• other decongestant medicines

Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine.

How should I take CLARINEX-D^® 12 Hour Extended Release Tablets?

Take CLARINEX-D 12 Hour Extended Release Tablets exactly as your doctor tells you to take it.

• CLARINEX-D 12 Hour Extended Release Tablets can be taken with or without food.
• Swallow CLARINEX-D 12 Hour Extended Release Tablets whole. Do not break, crush, or chew CLARINEX-D 12 Hour Extended Release Tablets before swallowing. If you cannot swallow CLARINEX-D 12 Hour Extended Release Tablets whole, tell your doctor. You may need a different medicine.
• Take 1 CLARINEX-D 12 Hour Extended Release Tablet 2 times a day (every 12 hours).

What are the possible side effects of CLARINEX-D^® 12 Hour Extended Release Tablets?

CLARINEX-D 12 Hour Extended Release Tablets may cause serious side effects, including:

• Cardiovascular and central nervous system effects, such as
  • unable to sleep (insomnia)
  • dizziness
  • weakness
  • tremor
  • irregular heart beat
  • seizure
  • low blood pressure
  • Increased sleepiness or tiredness can happen if you take more CLARINEX-D 12 Hour Extended Release Tablets than your doctor prescribed to you.
  • Allergic reactions. Stop taking CLARINEX-D 12 Hour Extended Release Tablets and call your doctor right away or get emergency help if you have any of these symptoms:
    • rash
    • itching
    • hives
    • swelling of your lips, tongue, face, and throat
    • shortness of breath or trouble breathing
    • Severe skin reactions including signs and symptoms such as fever, reddening of the skin, or many small pimples

    The most common side effects of CLARINEX-D 12 HOUR Extended Release Tablets include:

    • unable to sleep (insomnia)
    • sore throat
    • headache
    • dizziness
    • dry mouth
    • nausea
    • tiredness
    • loss of appetite
    • sleepiness

    Tell your doctor if you have any side effect that bothers you or that does not go away.

    These are not all of the possible side effects of CLARINEX-D 12 Hour Extended Release Tablets. For more information, ask your doctor or pharmacist.

    Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

    How should I store CLARINEX-D^® 12 Hour Extended Release Tablets?

    • Store CLARINEX-D 12 Hour Extended Release Tablets at 59°F to 86°F (15°C to 30°C)
    • Keep CLARINEX-D 12 Hour Extended Release Tablets dry and out of the light.

    Keep CLARINEX-D 12 Hour Extended Release Tablets and all medicines out of the reach of children.

    General information about CLARINEX-D^® 12 Hour Extended Release Tablets

    Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use CLARINEX-D 12 Hour Extended Release Tablets for a condition for which it was not prescribed. Do not give CLARINEX-D 12 Hour Extended Release Tablets to other people, even if they have the same condition you have. It may harm them.

    This patient information leaflet summarizes the most important information about CLARINEX-D 12 Hour Extended Release Tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about CLARINEX-D 12 Hour Extended Release Tablets that is written for health professionals.

    What are the ingredients in CLARINEX-D^® 12 Hour Extended Release Tablets?

    Active ingredients: desloratadine and pseudoephedrine sulfate

    Inactive ingredients: hypromellose USP, microcrystalline cellulose NF, povidone USP, silicon dioxide NF, magnesium stearate NF, corn starch NF, edetate disodium USP, citric acid anhydrous USP, stearic acid NF, and FD&C Blue No. 2 aluminum lake dye.

    
    

Principal Display Panel - 100 Tablet Bottle Label

NDC 78206-120-01
100 Tablets

CLARINEX-D^®
12 HOUR
(desloratadine 2.5 mg/
pseudoephedrine sulfate, USP 120 mg)

EXTENDED RELEASE TABLETS

Rx only

actual size
D12

PRINCIPAL DISPLAY PANEL - 100 Tablet Bottle Label - clarinex d12 03