Flumethasone

Overview

Flumethasone (Flucort®) is a long-acting glucocorticoid used in veterinary medicine for its anti-inflammatory and immunosuppressive effects. It has been supplied in both injectable and oral formulations, Used as ear drops in combination products
although tablets are no longer marketed in the United States and it is no longer commonly used in small animal practice.

Flumethasone has a prolonged duration of action (approximately 36–48 hours) and is significantly more potent than hydrocortisone, with minimal mineralocorticoid activity. It’s used as much as is required for short an amount of time as possible, The primary adverse effects are Cushingoid in nature with sustained use.

In dogs it may be used for musculoskeletal inflammation, dermatoses, allergic states and certain acute reactions, while labeled use in cats is limited to acute and chronic dermatoses. However, its use should follow the general principle of glucocorticoid therapy: use the lowest effective dose for the shortest possible duration.

Mechanism of Action (MOA): Flumethasone’s anti-inflammatory effects are complex but occur primarily through inhibition of inflammatory cells and suppression of inflammatory mediator expression.
The major use of flumethasone is for treatment of inflammatory and immune-mediated disease.”

Indications

Flumethasone is used in dogs for inflammatory, allergic and dermatologic conditions; labeled use in cats is for acute and chronic dermatoses. It may be administered via multiple routes depending on the clinical indication.

• Musculoskeletal inflammation (dogs): Used for conditions involving inflammation in muscles, joints, and associated structures without permanent structural changes (e.g., arthritis, osteoarthritis, intervertebral disc disease, myositis).
• Dermatologic conditions: Indicated for acute and chronic dermatoses to control pruritus, inflammation, and irritation in both dogs and cats.
• Allergic conditions (dogs): Includes hypersensitivity reactions such as urticaria and insect bite reactions.
• Otitis externa (dogs): Used as an adjunct to topical therapy to reduce inflammation and irritation.
• Acute inflammatory reactions: May be given IM or IV for acute reactions such as insect-bite hypersensitivity or vaccine reactions, although it does not act as rapidly as phosphate or succinate corticosteroid esters.
• Shock and shock-like states (dogs): Given intravenously in dogs for shock and shock-like states, at the systemic parenteral dose shown in the dog dose table.

Dosage (Reference)

Dog

In dogs, flumethasone dosing is individualized based on disease severity, response, and route of administration. Importantly, the labeled doses are expressed per animal (mg/dog), not per kg; note that some references instead give an anti-inflammatory range of 0.15 to 0.3 mg/kg every 12 to 24 hours and regard the labeled dose as low for some conditions.

Cat

In cats, flumethasone is used primarily for dermatologic conditions ,as indicated for certain acute and chronic dermatoses Dosing is individualized and expressed per animal rather than body weight; note that some references instead give an anti-inflammatory range of 0.15 to 0.3 mg/kg every 12 to 24 hours and regard the labeled dose as low for some conditions.

Warnings & Precautions

Flumethasone, like other systemic glucocorticoids, requires careful use due to its potent and long-acting effects on multiple body systems.

• Pregnancy: Contraindicated during the last trimester: corticosteroids may induce the first stage of parturition and precipitate premature parturition followed by dystocia, fetal death, retained placenta and metritis.
• Lactation: Use cautiously in nursing dams: glucocorticoid unbound to plasma proteins can enter milk, and high doses or prolonged administration may inhibit growth or interfere with endogenous corticosteroid production in nursing offspring.
• Reproductive safety: Because reproductive safety has not been established in animals, this drug should only be used when the maternal benefits outweigh the potential risks to offspring.
• Systemic infections: Generally contraindicated in animals with systemic fungal infections unless used for replacement therapy.
  Use of sustained-release, injectable glucocorticoids is contraindicated for chronic corticosteroid therapy of systemic diseases.”
• Hypersensitivity: Do not use in animals with known hypersensitivity to flumethasone.
• Idiopathic thrombocytopenia: Avoid IM administration in these patients
• Chronic therapy limitation: Sustained-release injectable glucocorticoids should not be used for long-term management of systemic diseases.
• Tapering required: Animals receiving glucocorticoids systemically and prolonged therapy must be gradually tapered to avoid adrenal insufficiency.
• Stress response: Additional glucocorticoids may be required during periods of stress (e.g., surgery, illness) while tapering or until normal adrenal function returns.
• Labeled contraindications: Do not use in viral infections. Except for emergency therapy, do not use in patients with tuberculosis, chronic nephritis, cushingoid syndrome or peptic ulcers; congestive heart failure, diabetes and osteoporosis are relative contraindications. Use cautiously where wound healing is required.
• Septic arthritis: In septic arthritis, appropriate antibacterial therapy should be administered concurrently.
• Congenital anomalies: In dogs, rabbits and rodents, corticosteroid administration during pregnancy has produced congenital anomalies including cleft palate, deformed forelegs, phocomelia and anasarca.
• Gastrointestinal warning signs: In dogs, stomach or intestinal ulceration, perforation or bleeding can occur; anorexia, high fever, black tarry stools or bloody vomit resembling coffee grounds require immediate veterinary assessment.

Drug Interactions

Flumethasone has multiple clinically relevant interactions, primarily related to its glucocorticoid effects on metabolism, electrolytes, and immune function. Weigh the potential risks and perform additional monitoring when appropriate.

• Amphotericin B: Increased risk of hypokalemia when used concurrently.
• Anticholinesterase agents (e.g., pyridostigmine, neostigmine): May cause profound muscle weakness in patients with myasthenia gravis; if possible, discontinue the anticholinesterase medication at least 24 hours before corticosteroid administration.
• Aspirin: May reduce salicylate levels and increase the risk of gastrointestinal ulceration and bleeding.
• Azole antifungals (e.g., ketoconazole): May decrease glucocorticoid metabolism and increase flumethasone concentrations; ketoconazole may induce adrenal insufficiency when glucocorticoids are withdrawn by inhibiting adrenal corticosteroid synthesis.”
• Cyclophosphamide: Glucocorticoids may inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required.
• Cyclosporine: May increase blood concentrations of both drugs through mutual inhibition of hepatic metabolism, although the clinical significance is unclear.
• Diazepam: Flumethasone may decrease diazepam concentrations.
• Potassium-depleting diuretics (e.g., furosemide, thiazides): Increased risk of hypokalemia.
• Ephedrine: May increase glucocorticoid metabolism, reducing drug blood concentration .
• Estrogens: May potentiate glucocorticoid effects.
• Insulin: May increase insulin requirements.
• Macrolide antibiotics (e.g., erythromycin, clarithromycin): May decrease metabolism and increase flumethasone levels.
• Mitotane: May alter steroid metabolism; higher-than-usual glucocorticoid doses may be required to treat mitotane-induced adrenal insufficiency.
• NSAIDs (e.g., carprofen, meloxicam): Increased risk of gastrointestinal ulceration.
• Rifampin: May increase glucocorticoid metabolism, decreasing drug blood concentration .
• Phenobarbital, Primidone: May increase metabolism and reduce drug levels.
• Live vaccines: Patients receiving immunosuppressive corticosteroid doses should generally not receive live attenuated-virus vaccines as virus replication may be augmented; immune responses to vaccines, toxoids and bacterins may be diminished.

Side Effects & Overdose

Side Effects

Adverse effects of flumethasone are primarily associated with prolonged or high-dose glucocorticoid therapy and are typically Cushingoid in nature.

• Endocrine/metabolic effects: Polyuria, polydipsia, polyphagia, weight gain, and potential worsening or activation of diabetes mellitus.
• Gastrointestinal effects (dogs): Vomiting, diarrhea, and risk of gastrointestinal ulceration, pancreatitis, increase liver enzymes even with short-term use.
• Dermatologic effects: A dull, dry haircoat and delayed wound healing may occur, and chronic corticosteroid therapy can decrease protein synthesis.
• Musculoskeletal effects: Muscle wasting and delayed growth in young animals.
• Behavioral changes: Depression, lethargy, or behavioral alterations.
• Other effects: Panting, increased liver enzymes, pancreatitis, and dyslipidemia.
• Cats: Generally fewer adverse effects, but may show PU/PD/PP, weight gain, diarrhea, or depression; long-term use can lead to Cushingoid changes.
• Immunosuppression and secondary infection: Immunosuppression may allow secondary infections, including demodicosis, toxoplasmosis, fungal infections and urinary tract infections; delayed wound healing and decreased thyroid hormone concentrations also occur.

Overdose

Acute overdose of glucocorticoids is unlikely to cause severe toxicity. Harmful effects are unlikely even after massive doses given short-term.

• Acute exposure: One case of acute CNS effects have been reported in a dog after accidental ingestion of glucocorticoids.
• Chronic overdose: Prolonged high-dose exposure may produce clinical signs of hyperadrenocorticism.
  When administered to young, growing animals, glucocorticoids can retard growth.”
• Management: Supportive treatment as required if clinical signs occur.
• Poison control: For a suspected or confirmed overdose, consult a 24-hour poison control centre that provides veterinary-specific advice.

Key Notes

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

• Long-acting profile: a long-acting glucocorticoid agent with a duration of effect of 36 to 48 hours.
• High potency: Reported glucocorticoid potency varies among veterinary references, ranging from approximately 15 to 30 times that of hydrocortisone (cortisol).
• No mineralocorticoid activity: Flumethasone has no appreciable mineralocorticoid activity.
• Not suitable for alternate-day therapy: Due to its long duration and pharmacologic profile.
  is not suitable for every-other-day dosing
• Slower onset compared to some steroids: Does not act as rapidly as phosphate or succinate ester corticosteroids in acute situations.
• Formulation considerations: Tablets are no longer marketed in the United States, while a prescription 0.5 mg/mL injection is supplied in 100 mL multidose vials flucort solution
  2 mg/mL; Fluosmin® Suspension; (Rx). FDA-approved for use in dogs.
• Storage: Store the injection and the tablets at room temperature; do not freeze the injection.
  protected from light
• Administration with food: Doses are best given with food, though they may be given without; if vomiting or nausea follows a dose given on an empty stomach, give subsequent doses with food or a small treat, and seek advice if vomiting continues.
• Steroid dose equivalence: 1.3 mg of flumethasone is equivalent to 5 mg of prednisone, and it is roughly 6 to 7 times as potent as prednisolone.
• Monitoring: Individualize monitoring according to the reason for use, dose, schedule, treatment duration, and the animal’s age and condition. Depending on the patient this may include weight, appetite and signs of oedema, serum and urine electrolytes, total plasma proteins and albumin, blood glucose, urine culture, growth in young animals, liver enzymes, renal function and watching for secondary infection; an ACTH stimulation test is used where adrenal function must be assessed.
• Laboratory test interference: Glucocorticoids may increase serum cholesterol and urine glucose, decrease serum potassium, suppress TSH release with lower T3 and T4 values, reduce thyroid radioiodine uptake and suppress intradermal skin-test reactions, and may cause false-negative nitroblue tetrazolium tests for systemic bacterial infection. Thyroid gland atrophy has been reported after chronic administration. Neutrophilia may occur within 4 to 8 hours of dosing and returns to baseline 24 to 48 hours after discontinuation; in dogs, lymphopenia can persist for weeks.