Allegra–D 24 Hour

ALLEGRA–D 24 HOUR — fexofenadine hydrochloride and pseudoephedrine hydrochloride tablet, film coated, extended release
Physicians Total Care, Inc.

DESCRIPTION

ALLEGRA-D® 24 HOUR (fexofenadine hydrochloride and pseudoephedrine hydrochloride) Extended-Release Tablets for oral administration contain 180 mg fexofenadine hydrochloride for immediate release and 240 mg pseudoephedrine hydrochloride for extended release. Tablets also contain as excipients: microcrystalline cellulose, sodium chloride, cellulose acetate, polyethylene glycol, opadry white, povidone, talc, hypromellose, croscarmellose sodium, copovidone, titanium dioxide, magnesium stearate, colloidal silicon dioxide, brilliant blue aluminum lake, acetone, isopropyl alcohol, methyl alcohol, methylene chloride, water, and black ink.

Fexofenadine hydrochloride, one of the active ingredients of ALLEGRA-D 24 HOUR, 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:

Chemical Structure
(click image for full-size original)

The molecular weight is 538.13 and the empirical formula is C32 H39 NO4 •HCl. Fexofenadine hydrochloride is a white to off-white crystalline powder. It is freely soluble in methanol and ethanol, slightly soluble in chloroform and water, and insoluble in hexane. Fexofenadine hydrochloride is a racemate and exists as a zwitterion in aqueous media at physiological pH.

Pseudoephedrine hydrochloride, the other active ingredient of ALLEGRA-D 24 HOUR, is an adrenergic (vasoconstrictor) agent with the chemical name [S-(R*,R*)]-α-[1-(methylamino)ethyl]-benzenemethanol hydrochloride and the following chemical structure:

Chemical Structure

The molecular weight is 201.70 and the molecular formula is C10 H15 NO•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

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 ALLEGRA-D 24 HOUR tablets 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 ALLEGRA-D 24 HOUR tablets 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, ALLEGRA-D 24 HOUR 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 ALLEGRA-D 24 HOUR in 66 healthy volunteers showed that fexofenadine, the immediate release component of ALLEGRA-D 24 HOUR, 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 ALLEGRA-D 24 HOUR, 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 ALLEGRA-D 24 HOUR tablets 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 [14 C]-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 ALLEGRA-D 24 HOUR tablets.

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.

Pharmacodynamics

Wheal 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.

Page 1 of 4 1 2 3 4

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.