Fexofenadine HCl and Pseudoephedrine HCl

/Fexofenadine HCl and Pseudoephedrine HCl
Fexofenadine HCl and Pseudoephedrine HCl2018-09-06T09:12:40+00:00

Prescription Drug Name:

Fexofenadine HCl and Pseudoephedrine HCl

ID:

83e76d7d-2a89-fe13-b319-56a5470a69b0

Code:

34391-3

DESCRIPTION


id: 7f71b68f-0e12-9651-81f2-eb67a0b74b80
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Fexofenadine HCl 180 mg and Pseudoephedrine HCl 240 mg Extended-Release Tablets USP(24 Hour Formulation) for oral administration contain 180 mg fexofenadine hydrochloride USP for immediate release and 240 mg pseudoephedrine hydrochloride USP for extended release. Tablets also contain as excipients: acetyltributyl citrate, colloidal silicon dioxide, copovidone, croscarmellose sodium, ethylcellulose, hydrogenated vegetable oil, hypromellose, microcrystalline cellulose, polyethylene glycol, sodium stearyl fumarate, talc and titanium dioxide.  Fexofenadine hydrochloride USP, one of the active ingredients of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets USP (24 hour formulation), is a histamine H1-receptor antagonist with the chemical name (±)-4-[1-hydroxy-4-[4- (hydroxydiphenylmethyl)-1-piperidinyl]-butyl]-α, α-dimethyl benzeneacetic acid hydrochloride and the following chemical structure: The molecular weight is 538.13 and the empirical formula is C32H39NO4•HCl. Fexofenadine hydrochloride is a white to off-white powder. It is soluble in methanol. Fexofenadine hydrochloride is a racemate and exists as a zwitterion in aqueous media at physiological pH.  Pseudoephedrine hydrochloride USP, the other active ingredient of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets USP (24 hour formulation), is an adrenergic (vasoconstrictor) agent with the chemical name [S-(R*,R*)]-α-[1- (methylamino)ethyl]-benzenemethanol hydrochloride and the following chemical structure: The molecular weight is 201.70 and the molecular formula is C10H15NO•HCl. Pseudoephedrine hydrochloride occurs as fine, white to off-white crystals or powder, having a faint characteristic odor. It is very soluble in water, freely soluble in alcohol; and sparingly soluble in chloroform.

CLINICAL PHARMACOLOGY


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displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Mechanism of Action Fexofenadine hydrochloride, the major active metabolite of terfenadine, is an antihistamine with selective peripheral H1-receptor antagonist activity. Fexofenadine hydrochloride inhibited antigen-induced bronchospasm in sensitized guinea pigs and histamine release from peritoneal mast cells in rats. In laboratory animals, no anticholinergic or alpha1-adrenergic-receptor blocking effects were observed. Moreover, no sedative or other central nervous system effects were observed. Radiolabeled tissue distribution studies in rats indicated that fexofenadine does not cross the blood-brain barrier.  Pseudoephedrine hydrochloride is an orally active sympathomimetic amine and exerts a decongestant action on the nasal mucosa. Pseudoephedrine hydrochloride 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. Pharmacokinetics The pharmacokinetics of fexofenadine hydrochloride in subjects with seasonal allergic rhinitis were similar to those in healthy volunteers.  Absorption: Fexofenadine hydrochloride and pseudoephedrine hydrochloride administered as fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) are absorbed at a similar rate and are equally available under single-dose and steady-state conditions as the separate administration of the components. Coadministration of fexofenadine and pseudoephedrine does not significantly affect the bioavailability of either component. The administration of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) 30 minutes or 1.5 hour after a high-fat meal decreased the bioavailability of fexofenadine by approximately 50% (AUC 42% and Cmax 54%). Pseudoephedrine pharmacokinetics were unaffected when coadministered with a high-fat meal. Therefore, fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) should be taken on an empty stomach with water (see DOSAGE AND ADMINISTRATION ).  A pharmacokinetic study following single and multiple oral doses over 7 days of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) in 66 healthy volunteers showed that fexofenadine, the immediate release component of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation), was rapidly absorbed with mean maximum plasma concentrations of 634 ng/mL and 674 ng/mL after single and multiple doses, respectively. The median time to maximum concentration of fexofenadine was 1.8-2.0 hours post-dose. In the same study, the mean maximum plasma concentrations of pseudoephedrine, the extended-release component of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation), were 394 ng/mL and 495 ng/mL after single and multiple doses, respectively, with median time to maximum concentration of 12 hours post-dose. Pseudoephedrine concentrations at the end of the dosing interval (mean: 172 ng/mL) at steady state were equivalent to those observed from a comparator pseudoephedrine hydrochloride 240 mg tablet. Distribution Fexofenadine hydrochloride is 60% to 70% bound to plasma proteins, primarily albumin and α1-acid glycoprotein. The protein binding of pseudoephedrine in humans is not known. Pseudoephedrine hydrochloride is extensively distributed into extravascular sites (apparent volume of distribution between 2.6 and 3.5 L/kg).  Metabolism Approximately 5% of the total dose of fexofenadine hydrochloride and less than 1% of the total oral dose of pseudoephedrine hydrochloride were eliminated by hepatic metabolism.  Elimination The mean terminal elimination half-life of fexofenadine was 14.6 hours following administration of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) in healthy volunteers, which is consistent with observations from separate administration. Human mass balance studies documented a recovery of approximately 80% and 11% of the [14C]-fexofenadine hydrochloride dose in the feces and urine, respectively. Because the absolute bioavailability of fexofenadine hydrochloride has not been established, it is unknown if the fecal component is primarily unabsorbed drug or the result of biliary excretion. The mean terminal half-life of pseudoephedrine was 7 hours following single-dose administration of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation).  Pseudoephedrine has been shown to have a mean elimination half-life of 4-6 hours which is dependent on urine pH. The elimination half-life is decreased at urine pH lower than 6 and may be increased at urine pH higher than 8.  Special Populations Pharmacokinetics in special populations (for renal, hepatic impairment, and age), obtained after a single dose of 80 mg fexofenadine hydrochloride, were compared to those from healthy volunteers in a separate study of similar design.  Effect of Age. In older subjects (≥65 years old), peak plasma levels of fexofenadine were 99% greater than those observed in younger subjects (<65 years old). Mean fexofenadine elimination half-lives were similar to those observed in younger subjects.  Renally Impaired. In subjects with mild (creatinine clearance 41-80 mL/min) to severe (creatinine clearance 11-40 mL/min) renal impairment, peak plasma levels of fexofenadine were 87% and 111% greater, respectively, and mean elimination half-lives were 59% and 72% longer, respectively, than observed in healthy volunteers. Peak plasma levels in subjects on dialysis (creatinine clearance ≤10 mL/min) were 82% greater and half-life was 31% longer than observed in healthy volunteers. No data are available on the pharmacokinetics of pseudoephedrine in renally impaired subjects. However, most of the oral dose of pseudoephedrine hydrochloride (43- 96%) is excreted unchanged in the urine. A decrease in renal function is, therefore, likely to decrease the clearance of pseudoephedrine significantly, thus prolonging the half-life and resulting in accumulation. (See PRECAUTIONS
and DOSAGE AND ADMINISTRATION.
Hepatically Impaired. The pharmacokinetics of fexofenadine hydrochloride in subjects with hepatic disease did not differ substantially from that observed in healthy volunteers. The effect on pseudoephedrine pharmacokinetics is unknown.  Effect of Gender. Across several trials, no clinically significant gender-related differences were observed in the pharmacokinetics of fexofenadine hydrochloride. 
PharmacodynamicsWheal and Flare. Human histamine skin wheal and flare studies following single and twice daily doses of 20 mg and 40 mg fexofenadine hydrochloride demonstrated that the drug exhibits an antihistamine effect by 1 hour, achieves maximum effect at 2-3 hours, and an effect is still seen at 12 hours. There was no evidence of tolerance to these effects after 28 days of dosing. The clinical significance of these observations is unknown. 
Effects on QTc. In dogs, (30 mg/kg/orally twice daily for 5 days) and rabbits (10 mg/kg, intravenously over 1 hour) fexofenadine hydrochloride did not prolong QTc at plasma concentrations that were at least 7 and 15 times, respectively, the therapeutic plasma concentrations in man (based on a 180 mg once daily fexofenadine hydrochloride dose when administered as fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation)). No effect was observed on calcium channel current, delayed K+ channel current, or action potential duration in guinea pig myocytes, Na+ current in rat neonatal myocytes, or on the delayed rectifier K+ channel cloned from human heart at concentrations up to 1 x 10-5 M of fexofenadine. This concentration was at least 8 times the therapeutic plasma concentration in man (based on a 180 mg once daily fexofenadine hydrochloride dose). No statistically significant increase in mean QTc interval compared to placebo was observed in 714 subjects with seasonal allergic rhinitis given fexofenadine hydrochloride capsules in doses of 60 mg to 240 mg twice daily for 2 weeks or in 40 healthy volunteers given fexofenadine hydrochloride as an oral solution at doses up to 400 mg twice daily for 6 days.  A 1-year study designed to evaluate safety and tolerability of 240 mg of fexofenadine hydrochloride (n=240) compared to placebo (n=237) in healthy volunteers, did not reveal a statistically significant increase in the mean QTc interval for the fexofenadine hydrochloride treated group when evaluated pretreatment and after 1, 2, 3, 6, 9, and 12 months of treatment. Administration of the 60 mg fexofenadine hydrochloride/120 mg pseudoephedrine hydrochloride combination tablet for approximately 2 weeks to 213 subjects with seasonal allergic rhinitis demonstrated no statistically significant increase in the mean QTc interval compared to fexofenadine hydrochloride administered alone (60 mg twice daily, n=215), or compared to pseudoephedrine hydrochloride (120 mg twice daily, n=215) administered alone. 

CLINICAL TRIALS


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displayName: CLINICAL STUDIES SECTION
FDA Article Code: 34092-7

Clinical StudiesClinical efficacy and safety studies were not conducted with fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation). The effectiveness of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) for the treatment of seasonal allergic rhinitis is based on an extrapolation of the demonstrated efficacy of fexofenadine hydrochloride 180 mg and the nasal decongestant properties of pseudoephedrine hydrochloride.  In one 2-week, multicenter, randomized, double-blind clinical trial in subjects 12 to 65 years of age with seasonal allergic rhinitis (n=863), fexofenadine hydrochloride 180 mg once daily significantly reduced total symptom scores (the sum of the individual scores for sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes) compared to placebo. Although the number of subjects in some of the subgroups was small, there were no significant differences in the effect of fexofenadine hydrochloride across subgroups of subjects defined by gender, age, and race.

INDICATIONS AND USAGE


id: e69f22e9-7f82-141d-da00-5c64e0662ddd
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) are indicated for the relief of symptoms associated with seasonal allergic rhinitis in adults and children 12 years of age and older. Symptoms treated effectively include sneezing, rhinorrhea, itchy nose/palate/ and/or throat, itchy/watery/red eyes, and nasal congestion.  Fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) should be administered when both the antihistaminic properties of fexofenadine hydrochloride and the nasal decongestant properties of pseudoephedrine hydrochloride are desired (see CLINICAL PHARMACOLOGY ).

CONTRAINDICATIONS


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displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) are contraindicated in patients with known hypersensitivity to any of its ingredients. Due to its pseudoephedrine component, fexofenadine HCl 180 mg and pseudoephedrine HCl  240 mg extended-release tablets (24 hour formulation) are 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 Drug Interactions section). It is also contraindicated in patients with severe hypertension, or severe coronary artery disease, and in those who have shown 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


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displayName: WARNINGS SECTION
FDA Article Code: 34071-1

Sympathomimetic amines should be used with caution in patients with hypertension, diabetes mellitus, ischemic heart disease, increased intraocular pressure, hyperthyroidism, renal impairment, or prostatic hypertrophy (see CONTRAINDICATIONS ). Sympathomimetic amines may produce central nervous system stimulation with convulsions or cardiovascular collapse with accompanying hypotension.

ADVERSE REACTIONS


id: 9678cb6f-2a9f-f5a3-2bf6-50787d6b471d
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Fexofenadine Hydrochloride In a placebo-controlled clinical study in the United States, which included 570 subjects with seasonal allergic rhinitis aged 12 years and older receiving fexofenadine hydrochloride tablets at doses of 120 or 180 mg once daily, adverse events were similar in fexofenadine hydrochloride and placebo-treated subjects. The following table lists adverse experiences that were reported by greater than 2% of subjects treated with fexofenadine hydrochloride tablets at doses of 180 mg once daily and that were more common with fexofenadine hydrochloride than placebo. 
 
                  Once daily dosing with fexofenadine hydrochloride                                  tablets
at rates of greater than 2%

Adverse experience            
Fexofenadine 180 mg            Placebo
                                                                    
                                             once daily (n=293)
                (n=283)
Headache                                    10.6%                                              7.5% Upper Respiratory                          3.2%                                              3.1% Tract Infection Back Pain                                      2.8%                                             1.4% Events that have been reported during controlled clinical trials involving subjects with seasonal allergic rhinitis at incidences less than 1% and similar to placebo and have been rarely reported during postmarketing surveillance include: insomnia, nervousness, and sleep disorders or paroniria. In rare cases, rash, urticaria, pruritus and hypersensitivity reactions with manifestations such as angioedema, chest tightness, dyspnea, flushing and systemic anaphylaxis have been reported. 
Pseudoephedrine HydrochloridePseudoephedrine hydrochloride may cause mild CNS stimulation in hypersensitive patients. Nervousness, excitability, restlessness, dizziness, weakness, or insomnia may occur. Headache, drowsiness, tachycardia, palpitation, pressor activity, cardiac arrhythmias and ischemic colitis 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


id: a602e91d-2165-09b0-d99a-4ab8431e2091
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

Most reports of fexofenadine hydrochloride overdose contain limited information. However, dizziness, drowsiness, and dry mouth have been reported. For the pseudoephedrine hydrochloride component of fexofenadine HCl and pseudoephedrine HCl extended-release tablets (24 hour formulation), information on acute overdose is limited to the marketing history of pseudoephedrine hydrochloride. Single doses of fexofenadine hydrochloride up to 800 mg (6 healthy volunteers at this dose level), and doses up to 690 mg twice daily for one month (3 healthy volunteers at this dose level), were administered without the development of clinically significant adverse events. 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. In the event of overdose, consider standard measures to remove any unabsorbed drug. Symptomatic and supportive treatment is recommended. Following administration of terfenadine, hemodialysis did not effectively remove fexofenadine, the major active metabolite of terfenadine, from blood (up to 1.7% removed). The effect of hemodialysis on the removal of pseudoephedrine is unknown.  No deaths occurred in mature mice and rats at oral doses of fexofenadine hydrochloride up to 5000 mg/kg (approximately 110 and 230 times, respectively, the maximum recommended human daily oral dose of fexofenadine HCl and pseudoephedrine HCl extended-release tablets (24 hour formulation) on a mg/m2 basis.) The median oral lethal dose in newborn rats was 438 mg/kg (approximately 20 times the maximum recommended human daily oral dose of fexofenadine HCl and pseudoephedrine HCl extended-release tablets (24 hour formulation) on a mg/m2 basis). In dogs, no evidence of toxicity was observed at oral doses up to 2000 mg/kg (approximately 300 times the maximum recommended human daily oral dose of fexofenadine HCl and pseudoephedrine HCl extended-release tablets (24 hour formulation) on a mg/m2 basis). The oral median lethal dose of pseudoephedrine hydrochloride in rats was 1674 mg/kg (approximately 55 times the maximum recommended human daily oral dose of fexofenadine HCl and pseudoephedrine HCl extended-release tablets (24 hour formulation) on a mg/m2 basis).

DOSAGE AND ADMINISTRATION


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displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

The recommended dose of fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) is one tablet once daily administered on an empty stomach with water for adults and children 12 years of age and older fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) should generally be avoided in patients with renal insufficiency. Fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets (24 hour formulation) must be swallowed whole and never crushed or chewed.

HOW SUPPLIED


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displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets USP (24 hour formulation) are off-white to white caplet shaped biconvex film coated tablets debossed with “RDY” on one side and “572” on another side and are supplied in bottles of 30, 60, 100, 500 and unit dose packages of 100 (10 x 10).  Bottles of 30                                    55111-572-30            Bottles of 60                                   55111-572-60            Bottles of 100                                 55111-572-01            Bottles of 500                                 55111-572-05            Unit dose packages of 100 (10 x 10) 55111-572-78  Store fexofenadine HCl 180 mg and pseudoephedrine HCl 240 mg extended-release tablets USP (24 hour formulation) at 20-25°C (68-77°F). (See USP Controlled Room Temperature.)  Rx Only                                                                   Manufactured by                                                    Dr. Reddy’s Laboratories Limited Bachepalli – 502 325 INDIA   Revised: 0410

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION


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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

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PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION


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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

PRINCIPAL DISPLAY PANEL Carton