Fexofenadine

Overview

Fexofenadine (Allegra®) is a second-generation antihistamine used in dogs and cats for the management of allergic, histamine-mediated conditions. It is considered a nonsedating antihistamine: second-generation antihistamines are more lipophobic than first-generation drugs and therefore do not readily cross into the central nervous system.

Compared with first-generation antihistamines such as diphenhydramine and chlorpheniramine, it causes little sedation and has no substantial anticholinergic effect, although sedation and CNS depression remain possible in an individual patient. However, clinical response to antihistamines in veterinary medicine is variable, and published evidence supporting consistent efficacy remains limited.

Mechanism of Action (MOA): Fexofenadine is a selective peripheral H1-receptor antagonist that blocks the effects of histamine released during allergic reactions. It may also provide additional anti-inflammatory benefits through mast cell stabilization and modulation of inflammatory mediators such as leukotrienes and prostaglandins.

Indications

Fexofenadine is used in dogs and cats for the management of histamine-mediated allergic conditions. For canine atopic dermatitis it is best used as part of combination therapy rather than alone, and it is not suitable for treating an acute flare; response varies between individual dogs.

• Allergic dermatitis (atopic dermatitis): May provide a small and limited benefit in some dogs with mild atopic dermatitis; evidence is insufficient either for or against its use in active or chronic canine atopic dermatitis. Clinical benefit is inconsistent and may require a trial period to assess response.
• Allergic pruritus: Used for itching related to hypersensitivity reactions, including seasonal or environmental allergens. Evidence of benefit against pruritus comes from dogs and is variable between individuals, and some current veterinary reviews report that second-generation antihistamines have not been shown to control pruritus in small animals.
• Allergic rhinitis: May help control clinical signs associated with allergic rhinitis.
• Preventive use in allergy-prone patients: In dogs with atopic dermatitis, benefit may improve when it is given consistently and started before allergen exposure or a flare – before the animal becomes moderately pruritic rather than after signs are established.

Dosage (Reference)

Dog

In dogs, fexofenadine is used extra-label for management of allergic conditions. Clinical response is variable and often unpredictable, so a minimum trial period of 2 weeks is recommended to assess effectiveness.

Cat

In cats, dosing is fixed per animal (not weight-based). As in dogs, response is variable and treatment should be evaluated over time.

Warnings & Precautions

Fexofenadine is generally well tolerated in dogs and cats, but clinical data in veterinary patients are limited. Select a product containing fexofenadine alone and monitor clinical response and adverse effects.

• Hypersensitivity: Do not use in animals with known hypersensitivity to fexofenadine.
• Limited veterinary evidence: Published data supporting efficacy in dogs and cats are limited; response is variable and may be unpredictable.
• Combination products (critical warning): Do not use combination products. Over-the-counter allergy preparations may contain other potentially toxic ingredients such as pseudoephedrine or acetaminophen, and acetaminophen is contraindicated in cats at any dosage. Check that fexofenadine is the only active ingredient.
• Xylitol toxicity (dogs): The human oral suspension, 30 mg/5 mL, contains xylitol and must not be used in dogs; check the excipients of any liquid preparation before dispensing.
• Renal impairment: Based on human data, adjust the dose in moderate to severe renal dysfunction, as plasma concentrations can increase by 100% or more.
• MDR1 mutation (dogs): Fexofenadine is a P-glycoprotein substrate, so exposure could theoretically be altered in dogs with the MDR1 mutation. Higher plasma concentrations were reported 4 and 8 hours after dosing in one study, but interpretation was confounded by concurrent famotidine, quinidine and loperamide; clinical significance remains unknown.
• Use in pregnancy and lactation: Safety in pregnant animals has not been established. No teratogenic effect was seen in rats or rabbits at 300 mg/kg, but rats showed dose-related reductions in implantation, more post-implantation losses, and reduced pup weights and survival at three times the recommended human dose; use only where the maternal benefit outweighs the potential risk to the offspring.
• Nursing animals: It is unknown whether fexofenadine enters milk, and it is thought unlikely to pose much risk to nursing offspring. Human guidance recommends monitoring exposed infants for irritability or drowsiness.
• Product selection: Ensure the product contains only fexofenadine as the active ingredient; avoid formulations with additional drugs or additives.
• Regulatory status: There is no veterinary-labelled fexofenadine product; all use in dogs and cats is extra-label and uses human products.

Drug Interactions

Clinically relevant interactions with fexofenadine in dogs and cats are mainly related to altered absorption or changes in drug transport (P-glycoprotein). Most interactions are not strictly contraindicated but may require dose separation or monitoring.

• Antacids (aluminum or magnesium-containing): Aluminium- or magnesium-containing antacids reduce the oral bioavailability of fexofenadine. Separate the doses by at least 1 hour; for aluminium hydroxide, another recommendation gives an interval of at least 2 hours.
• Erythromycin, ketoconazole: May increase fexofenadine plasma concentrations by enhancing absorption; usually not clinically significant due to wide safety margin.
• Fruit juices (grapefruit, apple, orange): In humans, grapefruit, apple and orange juice may reduce fexofenadine bioavailability; the recommendation is to give it with water rather than juice.
• P-glycoprotein substrates (e.g., famotidine, loperamide, quinidine) : Fexofenadine is a P-glycoprotein substrate. In one canine study, higher plasma concentrations were reported 4 and 8 hours after dosing, but interpretation was confounded by concurrent famotidine, quinidine and loperamide; clinical significance remains uncertain.

Side Effects & Overdose

Side Effects

Fexofenadine is generally well tolerated in dogs and cats, and adverse effects appear to be uncommon. When adverse effects occur, they may include sedation, central nervous system depression or gastrointestinal effects.

• Sedation: Although considered a nonsedating antihistamine, drowsiness may still occur in some animals.
• CNS depression: Listed as a possible adverse effect, although adverse effects are not common.
• Gastrointestinal effects: Vomiting or other gastrointestinal effects may occur.

Overdose

Fexofenadine has a wide margin of safety in dogs: in laboratory studies, dogs given oral doses of up to 2 g/kg – about three hundred times the maximum recommended adult human daily dose – showed no evidence of toxicity. Because combination products may contain additional drugs, determine exactly which product was ingested.

• Lethargy: One of the signs reported following overdose.
• Facial edema: Swelling of the face may occur in some cases.
• Vomiting: May be observed following overdose.
• CNS depression: May also occur following overdose.
• Combination product toxicity: Products containing additional ingredients, such as pseudoephedrine, require assessment according to the complete product ingested.
• Management: Determine exactly which product was ingested and consult a 24-hour poison control centre that provides veterinary-specific information for any actual or suspected overdose.
• Cardiac rhythm: QT intervals were not prolonged in dogs given 30 mg/kg twice daily for five days, despite plasma concentrations nine times those in humans receiving 180 mg/day.

Key Notes

Practical clinical points to optimize the use of fexofenadine in dogs and cats:

• Variable response: Not all patients respond to antihistamines; effectiveness should be judged on an individual basis.
• Trial-based therapy: Continue treatment for a minimum trial period of 2 weeks before deciding whether it is effective.
• Better as preventive therapy: In dogs that respond, benefit may improve when it is given regularly and started before allergen exposure.
• Adjunctive role: For canine atopic dermatitis it is best used as part of combination therapy and may serve as a glucocorticoid-sparing agent.
• Low sedation advantage: Preferred when minimal sedation is desired compared to first-generation antihistamines.
• Flexible administration: Can be given with or without food. If the animal vomits or seems unwell after a dose on an empty stomach, give subsequent doses with food or a small treat; if vomiting continues, reassess the patient.
• Monitoring response: Monitor two things: improvement in the allergic signs themselves, such as pruritus and rhinitis, and the appearance of adverse effects such as sedation or gastrointestinal upset.
• Allergy testing: Stop oral antihistamines 1 to 2 weeks before intradermal allergy testing in dogs and cats. If testing in a dog cannot be delayed, a minimum two-day washout may be acceptable for some antihistamines. Withdrawal before IgE serological testing is theoretically unnecessary, but this has not been proven.
• Pharmacokinetics: In humans, peak concentrations occur 2 to 3 hours after dosing, the elimination half-life is about 14.4 hours on twice-daily dosing, about 5% of the dose is cleared by hepatic metabolism and the majority of an oral dose is eliminated in the faeces.
• Relationship to terfenadine: Fexofenadine is the active metabolite of terfenadine, an earlier antihistamine withdrawn from the market secondary to concerns that it could prolong the QTc interval in people. Fexofenadine itself did not prolong the QTc interval in dogs at plasma concentrations many times those reached at recommended doses.
• Storage: Store tablets, orally disintegrating tablets and oral suspension at 20-25°C. Protect the orally disintegrating tablets from moisture and use each one immediately after opening its individual blister.