Fexofenadine + Pseudoephedrine

Uses

For the relief of symptoms associated with seasonal and perennial allergic complications 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.

It should be administered when both the antihistaminic properties of Fexofenadine Hydrochloride and the nasal decongestant properties of Pseudoephedrine Hydrochloride are desired.

Fexofenadine + Pseudoephedrine is also used to associated treatment for these conditions: Allergic Rhinitis (AR), Chronic Idiopathic Urticaria, Seasonal Allergic Rhinitis, AntihistamineAllergic Rhinitis (AR), Allergies, Common Cold, Common Cold Associated With Cough, Common Cold/Flu, Cough, Cough caused by Common Cold, Eye allergy, Fever, Flu caused by Influenza, Headache, Irritative cough, Nasal Allergies, Nasal Congestion, Nasal Congestion caused by Common Cold, Pain, Perennial Allergy, Priapism, Respiratory Allergy, Rhinorrhoea, Seasonal Allergic Rhinitis, Seasonal Allergies, Sinus Congestion, Sinusitis, Sneezing, Sore Throat, Symptoms of Acute Bronchitis Accompanied by Coughing, Throat irritation, Upper Respiratory Tract Infection, Upper respiratory tract congestion, Upper respiratory tract signs and symptoms, Dry cough, Minor aches and pains, Sinus pain, Watery itchy eyes, Airway secretion clearance therapy

How Fexofenadine + Pseudoephedrine works

The H₁ histamine receptor is responsible for mediating hypersensitivity and allergic reactions. Exposure to an allergen results in degranulation of mast cells and basophils, which then release histamine and other inflammatory mediators. Histamine binds to, and activates, H₁ receptors, which results in the further release of pro-inflammatory cytokines, such as interleukins, from basophils and mast cells. These downstream effects of histamine binding are responsible for a wide variety of allergic symptoms, such as pruritus, rhinorrhea, and watery eyes.

Fexofenadine is considered an “inverse agonist” of the H₁ receptor because it binds to and stabilizes the inactive form of the receptor, preventing its activation and subsequent downstream effects. It has a potent and selective affinity for H₁ receptors, and there is no evidence that it carries antidopaminergic, antiserotonergic, anticholinergic, sedative, or adrenergic blocking activity. Fexofenadine does not cross the blood-brain barrier and thus is unlikely to cause significant CNS effects.

Pseudoephedrine acts mainly as an agonist of alpha adrenergic receptors and less strongly as an agonist of beta adrenergic receptors.[A10896] This agonism of adrenergic receptors produces vasoconstriction which is used as a decongestant and as a treatment of priapism. Pseudoephedrine is also an inhibitor of norepinephrine, dopamine, and serotonin transporters.

The sympathomimetic effects of pseudoephedrine include an increase in mean arterial pressure, heart rate, and chronotropic response of the right atria. Pseudoephedrine is also a partial agonist of the anococcygeal muscle. Pseudoephedrine also inhibits NF-kappa-B, NFAT, and AP-1.

Dosage

Fexofenadine + Pseudoephedrine dosage

The recommended dose is one tablet twice daily administered on an empty stomach with water for adults and children 12 years of age and older. It is recommended that the administration of this Tablet with food should be avoided.

One tablet once daily is recommended as the starting dose in patients with decreased renal function. This must be swallowed whole and never crushed or chewed.

Side Effects

The reported side effects are insomnia, headache, nausea, dry mouth, dizziness, agitation, nervousness, anxiety, and palpitation etc.

Toxicity

No deaths were observed following the oral administration of up to 5000 mg/kg in both mice and rats (equivalent to approximately 100-200x the recommended human dose). Single doses of up to 800 mg and chronic exposure of up to 690 mg twice daily for 1 month in humans did not result in clinically significant adverse events. Symptoms of overdosage are consistent with fexofenadine's adverse effect profile and are likely to include dizziness, drowsiness, and dry mouth.

If overdosage occurs, employ symptomatic and supportive treatment. Hemodialysis does not effectively remove fexofenadine from the blood and is therefore of no benefit.

The oral LD₅₀ of pseudoephedrine is 2206mg/kg in rats and 726mg/kg in mice.

Patients experiencing an overdose of pseudoephedrine may present with giddiness, headache, nausea, vomiting, sweating, thirst, tachycardia, precordial pain, palpitations, difficulty urinating, muscle weakness, muscle tension, anxiety, restlessness, insomnia, toxic psychosis, cardiac arrhythmias, circulatory collapse, convulsions, coma, and respiratory failure. Treat overdose with symptomatic and supportive treatment including removal of unabsorbed drug.

Precaution

Hyperthyroidism; ischaemic heart disease, arrhythmia or tachycardia; occlusive vascular disorders e.g. arteriosclerosis, hypertension or aneurysms; DM and closed-angle glaucoma; renal impairment, prostatic enlargement. Pregnancy; lactation.

Interaction

Fexofenadine Hydrochloride and Pseudoephedrine Hydrochloride do not influence the pharmacokinetics of each other when administered concomitantly. However, co-administration of Fexofenadine Hydrochloride with either ketoconazole or Erythromycin lead to increased plasma concentrations of Fexofenadine.

Volume of Distribution

The volume of distribution is approximately 5.4-5.8 L/kg.

The apparent volume of distribution of pseudoephedrin is 2.6-3.3L/kg.

Elimination Route

Fexofenadine is rapidly absorbed following oral administration and its absolute bioavailability is approximately 33%. The T_max following oral administration is approximately 1-3 hours. The steady-state AUC_ss(0-12h) and C_max following twice daily dosing of 60mg are 1367 ng/mL.h and 299 ng/mL, respectively.

Fexofenadine AUC is decreased by >20% when coadministered with fruit juices (e.g. apple, orange, grapefruit) due to their inhibition of OATP transporters - for this reason, prescribing information recommends administering fexofenadine only with water. Similarly, coadministration of fexofenadine with a high-fat meal appears to decrease AUC and C_max by >20%.

A 240mg oral dose of pseudoephedrine reaches a C_max of 246.3±10.5ng/mL fed and 272.5±13.4ng/mL fasted, with a T_max of 6.60±1.38h fed and 11.87±0.72h fasted, with an AUC of 6862.0±334.1ng*h/mL fed and 7535.1±333.0ng*h/mL fasted.

Half Life

The terminal elimination half-life is approximately 11-15 hours.

The mean elimination half life of pseudoephedrine is 6.0h.

Clearance

The oral clearance of fexofenadine is approximately 50.6 L/h and the renal clearance is approximately 4.32 L/h.

A 60mg oral dose of pseudoephedrine has a clearance of 5.9±1.7mL/min/kg.

Elimination Route

Approximately 80% of an ingested dose is eliminated in the feces, likely largely unchanged due to fexofenadine's limited metabolism, and 11% is eliminated in the urine. The principal pathways of fexofenadine elimination are biliary and renal.

55-75% of an oral dose is detected in the urine as unchanged pseudoephedrine.

Pregnancy & Breastfeeding use

Pregnancy: Category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: Caution should be exercised when this drug is administered to nursing women.

Contraindication

This drug is contraindicated in patients with known hypersensitivity to any of its ingredients.

Special Warning

Pediatric Uses: This drug is not recommended for pediatric patients under 12 years of age.

Acute Overdose

For Fexofenadine: There is limited information, however, dizziness, drowsiness, and dry mouth etc. have been reported.

For Pseudoephedrine: headache, nausea, vomiting, sweating, thirst, tachycardia, pericardial pain, palpitations, difficulty in micturition, muscular weakness and tenseness, anxiety, restlessness, and insomnia etc have been reported.

Storage Condition

Store at a cool and dry place, protected from light & moisture. Keep out of reach of children.

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