SIDE EFFECTS

Loratadine; Pseudoephedrine Sulfate 12 Hour Extended Release Tablets

Experience from controlled and uncontrolled clinical studies involving approximately 10,000 patients who received the combination of loratadine; 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 (16%) and dry mouth (14%).

TABLE 2 Reported Adverse Events with an Incidence of ³ 2% in Loratadine; Pseudoephedrine Sulfate 12 Hour Extended Release Tablets in Placebo-Controlled Clinical Trials Percent of Patients Reporting Loratadine; Pseudoephedrine Sulfate 12 Hour Loratadine Pseudoephedrine Placebo n=1023 n=543 n=548 n=922 Headache 19 18 17 19 Insomnia 16 4 19 3 Dry Mouth 14 4 9 3 Somnolence 7 8 5 4 Nervousness 5 3 7 2 Dizziness 4 1 5 2 Fatigue 4 6 3 3 Dyspepsia 3 2 3 1 Nausea 3 2 3 2 Pharyngitis 3 3 2 3 Anorexia 2 1 2 1 Thirst 2 1 2 1





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 ( ³ 2%), the following less frequent adverse events have been reported in at least one patient treated with loratadine; pseudoephedrine sulfate 12 hour extended release tablets.

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.

24 Hour Extended Release Tablets

Information on adverse reactions is provided from placebo-controlled studies involving over 2000 patients, 605 of whom received loratadine; pseudoephedrine sulfate 24 hour extended release tablets once daily for up to 2 weeks. In these studies, the incidence of adverse events reported with loratadine; pseudoephedrine sulfate 24 hour extended release tablets was similar to those reported with twice-daily (q12h) 120 mg sustained-release pseudoephedrine alone.

TABLE 3 Reported Adverse Events With an Incidence of ³ 2% in Loratadine; Pseudoephedrine Sulfate 24 Hour Extended Release Tablets Treatment Group in Double-Blind, Randomized, Placebo-Controlled Clinical Trials Percent of Patients Reporting Loratadine; phedrine Sulfate 24 Hour Loratadine 10 mg Pseudoephedrine 120 mg q12h Placebo (n = 605) (n = 449) (n = 220) (n = 605) Dry Mouth 8 2 7 2 Somnolence 6 4 5 4 Insomnia 5 1 9 1 Pharyngitis 5 5 5 5 Dizziness 4 2 3 2 Coughing 3 2 3 1 Fatigue 3 4 1 2 Nausea 3 2 4 2 Nervousness 3 1 4 1 Anorexia 2 <1 2 Dysmenorrhea 2 2 2 1





Adverse events occurring in greater than or equal to 2% of loratadine; pseudoephedrine sulfate 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 nonwhites 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 loratadine; pseudoephedrine sulfate 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.

There have been postmarketing reports of mechanical upper gastrointestinal tract obstruction and esophageal perforation in patients taking a previously marketing formulation of loratadine; pseudoephedrine sulfate 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 loratadine; pseudoephedrine sulfate 24 hour extended release tablets has the potential for this adverse event (see PRECAUTIONS and DOSAGE AND ADMINISTRATION).

12 and 24 Hour Extended Release Tablets

The Following Additional Adverse Events Have Been Reported With Loratadine; Pseudoephedrine Sulfate Tablets: Alopecia, altered salivation, amnesia, anaphylaxis, angioneurotic edema, blepharospasm, breast enlargement, breast pain, dermatitis, dry hair, erythema multiforme, laryngitis, menorrhagia, nasal dryness, photosensitivity reaction, purpura, seizures, sneezing, supraventricular tachyarrhythmias, urinary discoloration. Additional Adverse Events for 24 Hour Extended Release Tablets Only: Abdominal distress, altered micturition, bronchitis, decreased libido, dry skin, hypoesthesia, impaired concentration, impotence, increased appetite, peripheral edema, rash, and upper respiratory infection.

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.

DRUG ABUSE AND DEPENDENCE

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.

Read the entire FDA prescribing information for Claritin D (Loratadine and Pseudoephedrine)