Glucocorticoid (Systemic Drug)
- Injectable glucocorticoid. Long acting; 25 to 40 times more potent than hydrocortisone; no mineralocorticoid activity.
- Primary use is intra-articular administration in horses.
- Betamethasone topical preparations (i.e., cream gel) are also commercially available.
- When used systemically, goal is to use as much as is required & as little as possible for as short an amount of time as possible.
- Primary adverse effects are cushingoid in nature with sustained systemic use.
- The ARCI (Association of Racing Commissioners International) has designated this drug as a class 4 substance.
- Many potential drug & laboratory interactions when used systemically (IM).1
In veterinary medicine, betamethasone for systemic or articular effects is usually administered as an injection combining betamethasone sodium phosphate (prompt effect) and betamethasone acetate (sustained effect). It can be used when an injectable glucocorticoid with both rapid- and long-acting effects is desired.1
In horses, intra-articular injection of betamethasone sodium phosphate/acetate can be useful for treating affected areas of the body in cases of pain and inflamed joints. Duration of pain relief can be up to 4 weeks after injection.2
Betamethasone injection (0.5 mg on day 55) has been shown to induce premature labor in pregnant dogs. No long term negative clinical effects in preterm puppies (delivered by cesarean section on day 58) were detected, and betamethasone appeared to enhance vital organ maturation.3 Comparing IV or PO glucocorticoid potency: A dosage of 0.75 mg of betamethasone is approximately equivalent to 5 mg of prednisone, 4 mg of methylprednisolone, or 20 mg of hydrocortisone (intra-articular or IM may be different).
Betamethasone is used to treat inflammatory ailments that present with itching, swelling and other symptoms of skin conditions in a range of species in veterinary medicine.
Betamethasone is a synthetic corticosteroid which has marked glucocorticoid effects and ispractically devoid of mineralocorticoid effects. Its chemical structure is the same as that ofdexamethasone, except for the conformation of the 16-methyl group which projects above theplane of the steroid moiety in betamethasone, the 16β-epimer, and below the plane indexamethasone, the 16α-epimer.
In veterinary medicine, betamethasone is administered to a range of species to treat inflammatory conditions, shock and circulatory collapse, acetonaemia, and to induce parturition in cattle. However the establishment of MRLs was only requested for cattle and pigs. Formulated products are based on betamethasone or betamethasone sodiumphosphate and there is a combination product which also contains antibiotics. The products areadministered by intravenous or intramuscular injection.
Usually, up to 3 doses of 0.038 mg/kg bw/day are administered at 24-hour intervals. For induction of parturition, a single dose of 0.08 mg/kg bw is normally employed.3 The pharmacological activity of betamethasone closely paralleled that of dexamethasone. The affinities of the glucocorticoid receptors in rat hepatoma tissue culture cells for dexamethasone and betamethasone (log KD) were 8.47 and 8.55, respectively. In several studies, the antirheumatic potency of the 2 substances was identical. Betamethasone produced no significant increase in tyrosine aminotransferase activity in rat liver at oral doses of up to 0.004 mg/kg bw. Higher doses produced a dose-related statistically-significant increase in tyrosineaminotransferase activity; the pharmacological NOEL was therefore 0.004 mg/kg bw.4
The pharmacokinetics of betamethasone was studied in clinical trials in humans, in pregnant and lactating rats, and in in vitro studies. Drug information indicates that betamethasone sodium phosphate was rapidly de-esterified in vivo to betamethasone. Following oral administration of 3 different tablet formulations to human volunteers at a dose of 2 mg/person, plasma Cmax values of 24 to 25 ng/ml were obtained around 2 hours after dosing. In another study, 58 to 80% of an oral dose was recovered from the urine, as a mixture of unmetabolised betamethasone and 6 metabolites, within 48 hours of dosing. Theoral bioavailability in humans was estimated to be at least 70%. In vitro studies in human, dog, rat and cow plasma showed that betamethasone was extensively bound to plasma proteins. Betamethasone was widely distributed to the tissues.
In pregnant rats given a subcutaneous doseof 1 mg betamethasone/kg bw, concentrations of radioactivity in maternal liver, kidneys and adrenals and in the foetal membrane were higher than in maternal plasma. When the same dose was administered to lactating rats, concentrations of radioactivity in the milk peaked at122.3 ng/ml, 6 hours after dosing. The metabolic pathways were similar to those of othercorticosteroids and involved oxidation of the 11β-hydroxyl group to ketone, reduction of theC-20ketone to give the alcohol, hydroxylation at the C-6 position and loss of the C-17 side chainto give 17-oxosteroids.4
Contraindications / Precautions:
Betamethasone is contraindicated in animals with acute or chronic bacterial infections unless therapeutic doses of an effective antimicrobial agent are used. Systemic use of glucocorticoids is generally considered contraindicated in systemic fungal infections (unless used for replacement therapy in Addison’s), when administered IM in patients with idiopathic thrombocytopenia, and in patients hypersensitive to a particular compound. Use of sustained-release injectable glucocorticoids is contraindicated for chronic corticosteroid therapy of systemic diseases.
Animals that have received glucocorticoids systemically, other than with “burst” therapy, should be tapered off the drugs. Patients that have received the drugs chronically should be tapered off slowly, as endogenous ACTH and endogenous corticosteroid function may return slowly. Should the animal undergo a stressor (eg, surgery, trauma, illness) during the tapering process or until normal adrenal and pituitary function resume, additional glucocorticoids should be administered. Corticosteroid therapy may induce parturition in large animal species during the latter stages of pregnancy.1
When used systemically in horses, betamethasone, like other glucocorticoids, may potentially increase the risk for laminitis. When used as an intra-articular injection in adult horses, betamethasone sodium phosphate/acetate does not appear to have deleterious effects.5 However, there is a slight risk for infection (septic arthritis) among common side effects and postcorticosteroid reactive synovitis after intra-articular injection.
Adverse effects are generally associated with long-term systemic administration of these drugs, especially if given at high dosages or not on an alternate day regimen. Effects generally manifest as clinical signs of hyperadrenocorticism. When administered to young, growing animals, glucocorticoids can retard growth.
In dogs, polydipsia (PD), polyphagia (PP), and polyuria (PU), may all be seen with short-term “burst” therapy as well as with alternate-day maintenance therapy on days when given the drug. Adverse effects in dogs associated with long-term use can include dull, dry haircoat, weight gain, panting, vomiting, diarrhea, elevated liver enzymes, pancreatitis, GI ulceration, lipidemias, activation or worsening of diabetes mellitus, muscle wasting, and behavioral changes (eg, depression, lethargy, aggression).
Discontinuation of the drug may be necessary; changing to an alternate steroid may also alleviate the problem. With the exception of PU/PD/PP, adverse effects associated with anti-inflammatory therapy are relatively uncommon. Adverse effects associated with immunosuppressive doses are more common and potentially more severe. Because of the drug’s immunosuppressive actions, increased risks for systemic infection are possible, especially with long-term use.
Cats generally require higher dosages than dogs for clinical effect but tend to develop fewer adverse effects. Occasionally, polydipsia, polyuria, and polyphagia with weight gain, diarrhea, or depression can be seen. Long-term, high-dose therapy can lead to cushingoid effects.1
The following drug interactions have either been reported or are theoretical in humans or animals receiving betamethasone systemically and may be of significance in veterinary patients.
- AMPHOTERICIN B: May cause hypokalemia when administered concomitantly with glucocorticoids.
- ANTICHOLINESTERASE AGENTS (eg, pyridostigmine, neostigmine): In patients with myasthenia gravis, concomitant glucocorticoid and anticholinesterase agent administration may lead to profound muscle weakness; if possible, discontinue anticholinesterase medication at least 24 hours before corticosteroid administration.
- ASPIRIN AND OTHER SALICYLATES: Glucocorticoids may reduce salicylate blood levels and may increase the risk of GI ulceration.
- BARBITURATES: May increase the metabolism of glucocorticoids.
- BUPROPION: May result in lowering of the seizure threshold.
- CYCLOPHOSPHAMIDE: Glucocorticoids may inhibit the hepatic metabolism of cyclophosphamide; dosage adjustments may be required.
- CYCLOSPORINE: Concomitant administration of glucocorticoids and cyclosporine may increase the blood levels of each by mutually inhibiting hepatic metabolism; clinical significance is not clear.
- DIGOXIN: When glucocorticoids are used concurrently with digitalis glycosides, an increased chance of digitalis toxicity may occur should hypokalemia develop; diligent monitoring of potassium and digitalis glycoside levels is recommended.
- DIURETICS, POTASSIUM-DEPLETING (eg, furosemide, thiazides): May cause hypokalemia when administered concomitantly with glucocorticoids.
- ESTROGENS: May decrease corticosteroid clearance.
- INSULIN: Requirements may increase in patients receiving glucocorticoids.
- ISONIAZID: May have serum levels decreased by corticosteroids.
- KETOCONAZOLE: Corticosteroid clearance may be reduced and the AUC increased.
- MITOTANE: May alter the metabolism of steroids; higher than usual doses of steroids may be necessary to treat mitotane-induced adrenal insufficiency.
- NSAIDs: May result in increased risk of GI ulcer or bleeding.
- PHENOBARBITAL: May result in decreased betamethasone efficacy.
- PHENYTOIN: May result in decreased betamethasone efficacy.
- RIFAMPIN: May increase the metabolism of glucocorticoids.
- THEOPHYLLINE: Alterations of pharmacologic effects of either drug can occur.
- ULCEROGENIC DRUGS (eg, NSAIDs): Use with glucocorticoids may increase the risk of GI ulceration.
- VACCINES: Patients receiving corticosteroids at immunosuppressive dosages should generally not receive live attenuated-virus vaccines, as virus replication may be augmented; diminished immune response may occur after vaccine, toxoid, or bacterin administration in patients receiving glucocorticoids.1
Monitoring of glucocorticoid therapy is dependent on its reason for use, dosage, agent used (amount of mineralocorticoid activity), dosage schedule (daily versus alternate day therapy), duration of therapy, and the animal’s age and condition. The following list may not be appropriate or complete for all animals; use clinical assessment and judgment should adverse effects be noted:
- Weight, appetite, signs of edema.
- Serum and/or urine electrolytes.
- Total plasma proteins, albumin.
- Blood glucose.
- Growth and development in young animals.
- ACTH stimulation test, if necessary.
In the event of accidental exposure or allergic reaction in humans, call your doctor and/or poison control center. For non-emergency medical advice, consult with your doctor, veterinarian or pharmacist.
Intra-articular Injection: Betamethasone acetate 12 mg/mL (equivalent to 10.8 mg betamethasone) & 3.9 mg/mL betamethasone disodium phosphate (equivalent to 3 mg of betamethasone); Betavet® Soluspan Suspension; (Rx). FDA-approved for use in horses.
Injectable Suspension: 6 mg/mL as 3.15 mg betamethasone sodium phosphate and 2.85 mg betamethasone acetate; BetaVet®; (Rx). FDA-approved for use in horses.
Betamethasone valerate is also found in Gentocin® Otic, Gentocin® Topical Spray, and Topagen® Ointment. There are several other otic and topical products containing betamethasone and gentamicin on the veterinary market.
NOTE: The ARCI (Association of Racing Commissioners International) has designated this drug as a class 4 substance.
Dogs: Control of pruritus: 0.25 – 0.5 mL per 20 lb body weight IM. Dose dependent on severity of condition. May repeat when necessary. Relief averages 3 weeks in duration. Do not exceed more than 4 injections.
Horses: (NOTE: ARCI UCGFS CLASS 4 DRUG) - Intra-articular administration (extra-label): Most dosage recommendations range from 3 – 18 mg per joint intra-articularly. Repeat dosages should be limited to the minimum required to achieve soundness.
1Plumb's Veterinary Drugs.
2Edwards SHR. Intra-articular drug delivery: The challenge to extend drug residence time within the joint. Vet J. 2011;190(1):15-21.
3Vannucchi CI, Regazzi FM, Barbosa MMM, et al. Cortisol profile and clinical evaluation of canine neonates exposed antenatally to maternal corticosteroid treatment. reproduction in domestic animals. Reprod Domest Anim. 2012;47:173-176.
4The European Agency for the Evaluation of Medicinal Products (EMEA) Veterinary Medicines Evaluation Unit. Betamethasone Summary Report, June 1999.
5McIlwraith CW. The use of intra-articular corticosteroids in the horse: What is known on a scientific basis? Equine Vet J. 2010;42(6):563-571.