Fexofenadine and pseudoephedrine

Fexofenadine is an antihistamine that reduces the effects of natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

Fexofenadine and pseudoephedrine is a combination medicine used to treat sneezing, runny or stuffy nose, itchy or watery eyes, hives, skin rash, itching, and other symptoms of allergies and the common cold.

Fexofenadine and pseudoephedrine may also be used for purposes not listed in this medication guide.

In the U.S.

• Allegra-D
• Allegra-D 24Hour

Available Dosage Forms:

• Tablet, Extended Release, 24 HR
• Tablet, Extended Release

Therapeutic Class: Antihistamine, Less-Sedating/Decongestant Combination

Pharmacologic Class: Fexofenadine

Chemical Class: Fexofenadine

• It is used to treat nose stuffiness.
• It is used to ease allergy signs.

Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets for oral administration contain 60 mg fexofenadine hydrochloride for immediate release and 120 mg pseudoephedrine hydrochloride for extended release. Tablets also contain as excipients: microcrystalline cellulose, pregelatinized starch, croscarmellose sodium, magnesium stearate, carnauba wax, stearic acid, silicon dioxide, hypromellose and polyethylene glycol.

Fexofenadine hydrochloride, one of the active ingredients, 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 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, 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. 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.

Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets

In one clinical trial (n=651) in which 215 subjects with seasonal allergic rhinitis received the 60 mg fexofenadine hydrochloride/120 mg pseudoephedrine hydrochloride combination tablet twice daily for up to 2 weeks, adverse events were similar to those reported either in subjects receiving fexofenadine hydrochloride 60 mg alone (n=218 subjects) or in subjects receiving pseudoephedrine hydrochloride 120 mg alone (n=218). A placebo group was not included in this study.

The percent of subjects who withdrew prematurely because of adverse events was 3.7% for the fexofenadine hydrochloride/pseudoephedrine hydrochloride combination group, 0.5% for the fexofenadine hydrochloride group, and 4.1% for the pseudoephedrine hydrochloride group. All adverse events that were reported by greater than 1% of subjects who received the recommended daily dose of the fexofenadine hydrochloride/pseudoephedrine hydrochloride combination are listed in the following table.

Many of the adverse events occurring in the fexofenadine hydrochloride/pseudoephedrine hydrochloride combination group were adverse events also reported predominately in the pseudoephedrine hydrochloride group, such as insomnia, headache, nausea, dry mouth, dizziness, agitation, nervousness, anxiety, and palpitation.

Fexofenadine Hydrochloride

In placebo-controlled clinical trials, which included 2461 subjects receiving fexofenadine hydrochloride at doses of 20 mg to 240 mg twice daily, adverse events were similar in fexofenadine hydrochloride and placebo-treated subjects. The incidence of adverse events, including drowsiness, was not dose related and was similar across subgroups defined by age, gender, and race. The percent of subjects who withdrew prematurely because of adverse events was 2.2% with fexofenadine hydrochloride vs 3.3% with placebo.

Events that have been reported during controlled clinical trials involving subjects with seasonal allergic rhinitis and chronic idiopathic urticaria 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 Hydrochloride

Pseudoephedrine hydrochloride 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.

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 Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets, 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 170 and 340 times, respectively, the maximum recommended human daily oral dose of Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets on a mg/m2 basis.) The median oral lethal dose in newborn rats was 438 mg/kg (approximately 30 times the maximum recommended human daily oral dose of Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets on a mg/m2 basis). In dogs, no evidence of toxicity was observed at oral doses up to 2000 mg/kg (approximately 450 times the maximum recommended human daily oral dose 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 Hydrochloride and Pseudoephedrine Hydrochloride Extended-Release Tablets on a mg/m2 basis).

Fexofenadine: Competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract.

Pseudoephedrine: Directly stimulates alpha-adrenergic receptors of respiratory mucosa causing vasoconstriction; directly stimulates beta-adrenergic receptors causing bronchial relaxation.

Seasonal allergic rhinitis: Relief of symptoms (eg, sneezing, rhinorrhea, itchy nose/palate/throat, itchy/watery/red eyes, nasal congestion) associated with seasonal allergic rhinitis in patients ≥12 years.

Seasonal allergic rhinitis: Oral:

Fexofenadine 60 mg/pseudoephedrine 120 mg 12 Hour: One tablet twice daily.

Fexofenadine 180 mg/pseudoephedrine 240 mg 24 Hour: One tablet once daily.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease); contraindicated in severe hypertension or coronary heart disease.

• Diabetes: Use with caution in patients with diabetes mellitus.

• Increased intraocular pressure: Use with caution in patients with increased intraocular pressure.

• Prostatic hyperplasia/urinary obstruction: Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

• Renal impairment: Use with caution in patients with renal impairment.

• Seizure disorder: Use with caution in patients with seizure disorder; may produce CNS stimulation.

• Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.