Betamethasone (Systemic)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Kit, Injection:

Pod-Care 100C: Betamethasone sodium phosphate 3 mg and betamethasone acetate 3 mg per 1 mL [contains benzalkonium chloride, disodium edta]

ReadySharp Betamethasone: Betamethasone sodium phosphate 3 mg and betamethasone acetate 3 mg per 1 mL [contains benzalkonium chloride, disodium edta]

Suspension, Injection:

Celestone Soluspan: Betamethasone sodium phosphate 3 mg and betamethasone acetate 3 mg per 1 mL (5 mL) [contains benzalkonium chloride, edetate disodium]

Generic: Betamethasone sodium phosphate 3 mg and betamethasone acetate 3 mg per 1 mL (5 mL)

Pharmacology

Mechanism of Action

Controls the rate of protein synthesis; depresses the migration of polymorphonuclear leukocytes, fibroblasts; reverses capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation

Pharmacokinetics/Pharmacodynamics

Metabolism

Hepatic (Peterson 1983)

Excretion

Urine (<5% as unchanged drug) (Peterson 1983)

Time to Peak

Serum: IV: 10 to 36 minutes (Peterson 1983)

Half-Life Elimination

6.5 hours (Peterson 1983)

Protein Binding

64% (Peterson 1983)

Use: Labeled Indications

Intramuscular:

Allergic states: Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in asthma, atopic dermatitis, contact dermatitis, drug hypersensitivity reactions, perennial or seasonal allergic rhinitis, serum sickness, transfusion reactions

Dermatologic diseases: Bullous dermatitis herpetiformis, exfoliative erythroderma, mycosis fungoides, pemphigus, severe erythema multiforme (Stevens-Johnson syndrome)

Endocrine disorders: Congenital adrenal hyperplasia, hypercalcemia associated with cancer, nonsuppurative thyroiditis. Note: Hydrocortisone or cortisone is the drug of choice in primary or secondary adrenocortical insufficiency. Synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance

Gastrointestinal diseases: During acute episodes in regional enteritis and ulcerative colitis

Hematologic disorders: Acquired (autoimmune) hemolytic anemia, Diamond-Blackfan anemia, pure red cell aplasia, selected cases of secondary thrombocytopenia

Neoplastic diseases: Palliative management of leukemias and lymphomas

Nervous system: Acute exacerbations of multiple sclerosis; cerebral edema associated with primary or metastatic brain tumor or craniotomy. Note: Treatment guidelines recommend the use of high-dose IV or oral methylprednisolone for acute exacerbations of multiple sclerosis (AAN [Scott 2011]; NICE 2014).

Ophthalmic diseases: Sympathetic ophthalmia, temporal arteritis, uveitis and ocular inflammatory conditions unresponsive to topical corticosteroids

Renal diseases: To induce diuresis or remission of proteinuria in idiopathic nephrotic syndrome or that due to lupus erythematosus

Respiratory diseases: Berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, idiopathic eosinophilic pneumonias, symptomatic sarcoidosis

Rheumatic disorders: Adjunctive therapy for short-term administration in acute gout flares; acute rheumatic carditis; ankylosing spondylitis; psoriatic arthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); treatment of dermatomyositis, polymyositis, and systemic lupus erythematosus.

Miscellaneous: Trichinosis with neurologic or myocardial involvement, tuberculous meningitis with subarachnoid block or impending block when used with appropriate antituberculous chemotherapy

Intra-articular or soft tissue administration:

Adjunctive therapy for short-term administration in acute gout flares, acute and subacute bursitis, acute nonspecific tenosynovitis, epicondylitis, rheumatoid arthritis, synovitis of osteoarthritis

Intralesional:

Treatment of alopecia areata; discoid lupus erythematosus; keloids; localized hypertrophic, infiltrated, inflammatory lesions of granuloma annulare, lichen planus, lichen simplex chronicus (neurodermatitis), and psoriatic plaques; necrobiosis lipoidica diabeticorum

Use: Off Label

Accelerate fetal lung maturationbyes

According to systematic reviews of randomized controlled trials using betamethasone or dexamethasone, evidence supports the use of a single course of antenatal corticosteroids to accelerate fetal lung maturation in women at risk for preterm delivery, with no clear advantages found regarding use of one corticosteroid over another Brownfoot 2013, Roberts 2017.

Based on the American Congress of Obstetricians and Gynecologists (ACOG) practice bulletin for the management of premature rupture of membranes or preterm labor, the antenatal use of corticosteroids (eg, betamethasone) to accelerate fetal lung maturation is effective and recommended

Contraindications

Hypersensitivity to any component of the formulation; IM administration contraindicated in immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura).

Canadian labeling: Additional contraindications (not in US labeling): Herpes simplex of the eye; systemic fungal infections; vaccinia; cerebral malaria; use in areas with local infection.

Documentation of allergenic cross-reactivity for glucocorticoids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Note: Dosages expressed as combined amount of betamethasone sodium phosphate and betamethasone acetate; 1 mg is equivalent to betamethasone sodium phosphate 0.5 mg and betamethasone acetate 0.5 mg.

Usual dosage range: IM: Initial: 0.25 to 9 mg/day (based on severity of disease and patient response).

Indication-specific dosing:

Antenatal fetal maturation (off-label use): IM: 12 mg every 24 hours for a total of 2 doses (ACOG 171 2016). A single course of betamethasone is recommended for women between 24 and 34 weeks of gestation, including those with ruptured membranes or multiple gestations, who are at risk of delivering within 7 days. A single course may be appropriate in some women beginning at 23 weeks gestation or late preterm (between 34 0/7 weeks and 36 6/7 weeks gestation). A single repeat course may be considered in some women with pregnancies less than 34 weeks gestation at risk for delivery within 7 days and who had a course of antenatal corticosteroids >14 days prior (ACOG 171 2016; ACOG 713 2017, ACOG 188 2018).

Bursitis (other than of foot): Intra-articular: 3 to 6 mg (0.5 to 1 mL) for one dose; additional injections may be required for acute exacerbations or chronic conditions; generally, injections should be separated by a minimum of 4 to 6 weeks and limited to ≤4 injections per year. If symptoms are not improved after 1 or 2 injections, additional injections are unlikely to provide benefit (Cardone 2002); following resolution of acute episodes, reduced doses may be warranted for chronic conditions.

Dermatologic conditions: Intradermal: 1.2 mg/cm² (0.2 mL/cm²) into lesion for one dose (maximum: 6 mg [1 mL] weekly).

Foot disorders: Intra-articular: 1.5 mg to 6 mg (0.25 to 1 mL) per dose. Dose is based upon condition; additional injections (when required) should generally be separated by a minimum of 4 to 6 weeks and limited to ≤4 injections per year. If symptoms are not improved after 1 or 2 injections, additional injections are unlikely to provide benefit (Cardone 2002):

Bursitis: 1.5 mg to 3 mg (0.25 to 0.5 mL).

Tenosynovitis: 3 mg (0.5 mL).

Acute gouty arthritis: 3 mg to 6 mg (0.5 to 1 mL).

Multiple sclerosis: Note: Treatment guidelines recommend the use of high-dose IV or oral methylprednisolone for acute exacerbations of multiple sclerosis (AAN [Scott 2011]; NICE 2014).

IM: 30 mg daily for 1 week, followed by 12 mg every other day for 4 weeks.

Rheumatoid and osteoarthritis: Intra-articular: 3 mg to 12 mg (0.5 to 2 mL) for one dose. Dose is based upon the joint size:

Very large (eg, hip): 6 to 12 mg (1 to 2 mL).

Large (eg, knee, ankle, shoulder): 6 mg (1 mL).

Medium (eg, elbow, wrist): 3 mg to 6 mg (0.5 to 1 mL).

Small (eg, inter- or metacarpophalangeal, sternoclavicular): 1.5 mg to 3 mg (0.25 to 0.5 mL).

Tenosynovitis (other than of foot), peritendinitis: Intra-articular: 1.5 to 6 mg (0.25 to 1 mL) depending on joint size for one dose (Cardone 2002; Churgay 2009; Waryasz 2017; manufacturer labeling); additional injections (when required) should generally be separated by a minimum of 4 to 6 weeks and limited to ≤4 injections per year. If symptoms are not improved after 1 or 2 injections, additional injections are unlikely to provide benefit (Cardone 2002; Waryasz 2017).

Dosing: Geriatric

Refer to adult dosing. Use the lowest effective dose.

Dosing: Pediatric

Note: Dosages expressed as combined amount of betamethasone sodium phosphate and betamethasone acetate; 1 mg is equivalent to betamethasone sodium phosphate 0.5 mg and betamethasone acetate 0.5 mg. Dosage should be based on severity of disease and patient response; use lowest effective dose for shortest period of time to avoid HPA axis suppression

General dosing, treatment of inflammatory and allergic conditions: Infants, Children, and Adolescents: IM: Initial: 0.02 to 0.3 mg/kg/day (0.6 to 9 mg/m²/day) in 3 or 4 divided doses

Infantile hemangioma, severe: Limited data available: Infants and Children: Intralesional: Dosage dependent upon size of lesion: Commonly reported: 6 mg administered as a 6 mg/mL (in combination with triamcinolone injection) divided into multiple injections along the lesion perimeter; reported range: 1.5 to 18 mg/dose; doses usually administered every 8 to 14 weeks; reported range: 6 to 25 weeks (Buckmiller, 2008; Chowdri, 1994; Kushner, 1985; Praseyono, 2011). Dosing based on small trials and case-series, mostly reported in infants and children ≤4 years of age. The largest experience (n=70, age range: 2 months to 12 years) prospectively used a betamethasone/triamcinolone combination injection (1.5 to 18 mg betamethasone acetate) and showed that 89.23% of lesions with an initial volume <20 cc³ regressed by more than 50%, but only 22.2% of lesions with an initial volume >20 cc³ displayed a good or excellent response (Chowdri, 1994). Another trial (n=25, age range: 7 weeks to 2 years) used lower doses of 3 to 12 mg (in combination with triamcinolone); 16 patients experienced a marked response (Kushner, 1985).

Reconstitution

If suspension is coadministered with a local anesthetic, it may be mixed in syringe with 1% or 2% lidocaine HCl (without parabens) or similar parabens-free local anesthetic. Withdraw the dose of betamethasone suspension from the vial into the syringe, then draw up the local anesthetic into the syringe and shake the syringe briefly. Do not inject the local anesthetic directly into the suspension vial.

Administration

Note: Shake well prior to use.

IM: May be administered intramuscularly.

Intra-articular: Needle size requirements vary based on the size of the joint to be treated (eg, <25 gauge [hip, knee, shoulder], 25 gauge [wrist, ankle, elbow]) and/or method of administration (Rastogi 2016).

Bursitis: Inject into affected bursa.

Rheumatoid or osteoarthritis: Inject into synovial cavity.

Tendinitis/tenosynovitis: Inject into affected tendon sheaths (not directly into tendons).

Intradermal: Inject a uniform depot using a 1 mL (eg, tuberculin) syringe with ¹/₂-inch needle (typically 26 or 27 gauge) (Love 2006). Do not inject subcutaneously.

Storage

Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). Protect from light.

Drug Interactions

Acetylcholinesterase Inhibitors: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Acetylcholinesterase Inhibitors. Increased muscular weakness may occur. Monitor therapy

Aldesleukin: Corticosteroids may diminish the antineoplastic effect of Aldesleukin. Avoid combination

Amphotericin B: Corticosteroids (Systemic) may enhance the hypokalemic effect of Amphotericin B. Monitor therapy

Androgens: Corticosteroids (Systemic) may enhance the fluid-retaining effect of Androgens. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Aprepitant: May increase the serum concentration of Corticosteroids (Systemic). Management: No dose adjustment is needed for single 40 mg aprepitant doses. For other regimens, reduce oral dexamethasone or methylprednisolone doses by 50%, and IV methylprednisolone doses by 25%. Antiemetic regimens containing dexamethasone reflect this adjustment. Consider therapy modification

Axicabtagene Ciloleucel: Corticosteroids (Systemic) may diminish the therapeutic effect of Axicabtagene Ciloleucel. Management: Avoid use of corticosteroids as premedication before axicabtagene ciloleucel. Corticosteroids may, however, be required for treatment of cytokine release syndrome or neurologic toxicity. Consider therapy modification

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Calcitriol (Systemic): Corticosteroids (Systemic) may diminish the therapeutic effect of Calcitriol (Systemic). Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Corticorelin: Corticosteroids may diminish the therapeutic effect of Corticorelin. Specifically, the plasma ACTH response to corticorelin may be blunted by recent or current corticosteroid therapy. Monitor therapy

Cosyntropin: Corticosteroids (Systemic) may diminish the diagnostic effect of Cosyntropin. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Corticosteroids (Systemic). Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Deferasirox: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Deferasirox: Corticosteroids may enhance the adverse/toxic effect of Deferasirox. Specifically, the risk for GI ulceration/irritation or GI bleeding may be increased. Monitor therapy

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Desirudin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Desirudin. More specifically, corticosteroids may increase hemorrhagic risk during desirudin treatment. Management: Discontinue treatment with systemic corticosteroids prior to desirudin initiation. If concomitant use cannot be avoided, monitor patients receiving these combinations closely for clinical and laboratory evidence of excessive anticoagulation. Consider therapy modification

Desmopressin: Corticosteroids (Systemic) may enhance the hyponatremic effect of Desmopressin. Avoid combination

DilTIAZem: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Estrogen Derivatives: May increase the serum concentration of Corticosteroids (Systemic). Monitor therapy

Fexinidazole [INT]: Corticosteroids (Systemic) may enhance the arrhythmogenic effect of Fexinidazole [INT]. Avoid combination

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of Corticosteroids (Systemic). The active metabolite aprepitant is likely responsible for this effect. Consider therapy modification

Hyaluronidase: Corticosteroids may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving corticosteroids (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Indacaterol: May enhance the hypokalemic effect of Corticosteroids (Systemic). Monitor therapy

Indium 111 Capromab Pendetide: Corticosteroids (Systemic) may diminish the diagnostic effect of Indium 111 Capromab Pendetide. Avoid combination

Isoniazid: Corticosteroids (Systemic) may decrease the serum concentration of Isoniazid. Monitor therapy

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Loop Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Macimorelin: Corticosteroids (Systemic) may diminish the diagnostic effect of Macimorelin. Avoid combination

Mifamurtide: Corticosteroids (Systemic) may diminish the therapeutic effect of Mifamurtide. Avoid combination

MiFEPRIStone: May diminish the therapeutic effect of Corticosteroids (Systemic). MiFEPRIStone may increase the serum concentration of Corticosteroids (Systemic). Management: Avoid mifepristone in patients who require long-term corticosteroid treatment of serious illnesses or conditions (e.g., for immunosuppression following transplantation). Corticosteroid effects may be reduced by mifepristone treatment. Avoid combination

Mitotane: May decrease the serum concentration of Corticosteroids (Systemic). Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Neuromuscular-Blocking Agents (Nondepolarizing): May enhance the adverse neuromuscular effect of Corticosteroids (Systemic). Increased muscle weakness, possibly progressing to polyneuropathies and myopathies, may occur. Consider therapy modification

Nicorandil: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nicorandil. Gastrointestinal perforation has been reported in association with this combination. Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (COX-2 Selective). Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Nonselective): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Monitor therapy

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Quinolones: Corticosteroids (Systemic) may enhance the adverse/toxic effect of Quinolones. Specifically, the risk of tendonitis and tendon rupture may be increased. Monitor therapy

Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Salicylates: May enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Monitor therapy

Sargramostim: Corticosteroids (Systemic) may enhance the therapeutic effect of Sargramostim. Specifically, corticosteroids may enhance the myeloproliferative effects of sargramostim. Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Somatropin: Corticosteroids (Systemic) may diminish the therapeutic effect of Somatropin. Monitor therapy

Tacrolimus (Systemic): Corticosteroids (Systemic) may decrease the serum concentration of Tacrolimus (Systemic). Conversely, when discontinuing corticosteroid therapy, tacrolimus concentrations may increase. Monitor therapy

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Corticosteroids (Systemic) may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tisagenlecleucel: Corticosteroids (Systemic) may diminish the therapeutic effect of Tisagenlecleucel. Management: Avoid use of corticosteroids as premedication or at any time during treatment with tisagenlecleucel, except in the case of life-threatening emergency (such as resistant cytokine release syndrome). Consider therapy modification

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Urea Cycle Disorder Agents: Corticosteroids (Systemic) may diminish the therapeutic effect of Urea Cycle Disorder Agents. More specifically, Corticosteroids (Systemic) may increase protein catabolism and plasma ammonia concentrations, thereby increasing the doses of Urea Cycle Disorder Agents needed to maintain these concentrations in the target range. Monitor therapy

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Corticosteroids (Systemic) may enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Consider therapy modification

Warfarin: Corticosteroids (Systemic) may enhance the anticoagulant effect of Warfarin. Monitor therapy

Test Interactions

May suppress the wheal and flare reactions to skin test antigens

Adverse Reactions

Frequency not defined:

Cardiovascular: Bradycardia, cardiac arrhythmia, cardiomegaly, circulatory shock, edema, embolism (fat), hypertension, hypertrophic cardiomyopathy, myocardial rupture (following recent MI), syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Central nervous system: Abnormal sensory symptoms, arachnoiditis, depression, emotional lability, euphoria, headache, increased intracranial pressure, insomnia, malaise, meningitis, myasthenia, neuritis, neuropathy, paraplegia, paresthesia, personality changes, pseudotumor cerebri, psychic disorder, seizure, spinal cord compression, vertigo

Dermatologic: Acne vulgaris, allergic dermatitis, atrophic striae, diaphoresis, ecchymoses, erythema, exfoliation of skin, fragile skin, hyperpigmentation, hypertrichosis, hypopigmentation, skin atrophy, skin rash, subcutaneous atrophy, suppression of skin test reaction, thinning hair, urticaria, xeroderma

Endocrine & metabolic: Amenorrhea, calcinosis, cushingoid state, decreased glucose tolerance, decreased serum potassium, fluid retention, glycosuria, growth suppression (pediatric), hirsutism, HPA-axis suppression, hypokalemic alkalosis, impaired glucose tolerance/prediabetes, insulin resistance (increased requirements for insulin or oral hyperglycemic agents), moon face, negative nitrogen balance, protein catabolism, sodium retention, weight gain

Gastrointestinal: Abdominal distention, change in bowel habits, hiccups, increased appetite, intestinal perforation, nausea, pancreatitis, peptic ulcer, ulcerative esophagitis

Genitourinary: Bladder dysfunction, spermatozoa disorder (decreased motility and number)

Hematologic & oncologic: Petechia

Hepatic: Hepatomegaly, increased liver enzymes

Hypersensitivity: Anaphylactoid reaction, anaphylaxis, angioedema

Infection: Infection (decreased resistance), sterile abscess

Local: Injection site reaction (intra-articular use). postinjection flare (intra-articular use)

Neuromuscular & skeletal: Amyotrophy, aseptic necrosis of femoral head, aseptic necrosis of humeral head, bone fracture, Charcot arthropathy, lipotrophy, myopathy, osteoporosis, rupture of tendon, steroid myopathy

Ophthalmic: Blindness, blurred vision, cataract, exophthalmos, glaucoma, increased intraocular pressure, papilledema

Respiratory: Pulmonary edema

Miscellaneous: Wound healing impairment

Warnings/Precautions

Concerns related to adverse effects:

• Adrenal suppression: May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections. In stressful situations, HPA axis-suppressed patients should receive adequate supplementation with natural glucocorticoids (hydrocortisone or cortisone) rather than betamethasone (due to lack of mineralocorticoid activity).
• Anaphylactoid reactions: Rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.
• Immunosuppression: Prolonged use of corticosteroids may increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate infections, or limit response to killed or inactivated vaccines. Special pathogens (Amoeba, Candida, Cryptococcus, Mycobacterium, Nocardia, Pneumocystis, Strongyloides, or Toxoplasma) may be activated or an infection exacerbation may occur (may be fatal). Amebiasis or Strongyloides infections should be particularly ruled out. Exposure to chickenpox or measles should be avoided; corticosteroids should not be used to treat ocular herpes simplex. Corticosteroids should not be used for cerebral malaria, fungal infections, or viral hepatitis. Close observation is required in patients with latent tuberculosis and/or TB reactivity; restrict use in active TB (only fulminating or disseminated TB in conjunction with antituberculosis treatment). Amebiasis should be ruled out in any patient with recent travel to tropic climates or unexplained diarrhea prior to initiation of corticosteroids.
• Kaposi sarcoma: Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered.
• Myopathy: Acute myopathy has been reported with high-dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.
• Psychiatric disturbances: Corticosteroid use may cause psychiatric disturbances, including depression, euphoria, insomnia, mood swings, and personality changes. Preexisting psychiatric conditions may be exacerbated by corticosteroid use.

Disease-related issues:

• Cardiovascular disease: Use with caution in patients with HF and/or hypertension; use has been associated with electrolyte disturbances, fluid retention, and hypertension. Dietary modifications may be necessary. Use with caution in patients with a recent history of myocardial infarction (MI); left ventricular free wall rupture has been reported after the use of corticosteroids.
• Diabetes: Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.
• Gastrointestinal disease: Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, peptic ulcer, ulcerative colitis) due to perforation risk. Avoid ethanol may enhance gastric mucosal irritation.
• Head injury: Increased mortality was observed in patients receiving high-dose IV methylprednisolone; high-dose corticosteroids should not be used for the management of head injury.
• Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.
• Myasthenia gravis: Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.
• Ocular disease: Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Not recommended for the treatment of optic neuritis; may increase frequency of new episodes. Consider routine eye exams in chronic users.
• Osteoporosis: Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.
• Renal impairment: Use with caution in patients with renal impairment; fluid retention may occur.
• Seizure disorders: Use with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.
• Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroidism and decreases in hypothyroidism.

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.

Special populations:

• Elderly: Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly in the smallest possible effective dose for the shortest duration.
• Pediatric: May affect growth velocity; growth should be routinely monitored in pediatric patients.

Other warnings/precautions:

• Appropriate use: For intramuscular, intra-articular or intralesional use only, do not administer intravenously or epidurally (see Epidural injection).
• Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.
• Epidural injection: Corticosteroids are not approved for epidural injection. Serious neurologic events (eg, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke), some resulting in death, have been reported with epidural injection of corticosteroids, with and without use of fluoroscopy.
• Intra-articular injection: May produce systemic as well as local effects. Appropriate examination of any joint fluid present is necessary to exclude a septic process. Avoid injection into an infected site. Do not inject into unstable joints. Intra-articular injection may result in damage to joint tissues.

Monitoring Parameters

Growth in children; injection site reactions, risk of infection

Pregnancy

Pregnancy Considerations

Betamethasone crosses the placenta (Brownfoot 2013) and is partially metabolized by placental enzymes to an inactive metabolite (Murphy 2007). Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts or decreased birth weight; however, information is conflicting and may be influenced by maternal dose/indication for use (Lunghi 2010; Park-Wyllie 2000; Pradat 2003). Hypoadrenalism may occur in newborns following maternal use of corticosteroids during pregnancy; monitor.

Because antenatal corticosteroid administration may reduce the incidence of intraventricular hemorrhage, necrotizing enterocolitis, neonatal mortality, and respiratory distress syndrome, the injection is often used for antenatal fetal lung maturation in patients with preterm premature rupture of membranes or preterm labor who are at risk of preterm delivery. A single course of betamethasone is recommended for women between 24 and 34 weeks gestation who are at risk of delivering within 7 days, including those with ruptured membranes or multiple gestations. A single course of betamethasone may be considered for women beginning at 23 weeks gestation, who are at risk of delivering within 7 days, in consultation with the family. In addition, a single course of betamethasone may be given to women between 34 0/7 weeks and 36 6/7 weeks who are at risk of preterm delivery within 7 days and who have not previously received corticosteroids; use of concomitant tocolytics is not currently recommended and administration of late preterm corticosteroids has not been evaluated in women with intrauterine infection, multiple gestations, pregestational diabetes, or women who delivered previously by cesarean section at term. Multiple repeat courses are not recommended. However, in women with pregnancies less than 34 weeks gestation at risk for delivery within 7 days and who had a course of antenatal corticosteroids >14 days prior, a single repeat course may be considered; use of a repeat course in women with preterm prelabor rupture of membranes is controversial (ACOG 171 2016; ACOG 713 2017, ACOG 188 2018).

When systemic corticosteroids are needed in pregnancy for rheumatic disorders, it is generally recommended to use the lowest effective dose for the shortest duration of time, avoiding high doses during the first trimester. Intra-articular dosing may also be used during pregnancy (Götestam Skorpen 2016; Makol 2011; Østensen 2009).

Patient Education

What is this drug used for?

• It is used for many health problems like allergy signs, asthma, adrenal gland problems, blood problems, skin rashes, or swelling problems.
• This is not a list of all health problems that this drug may be used for. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea
• Vomiting
• Agitation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• High blood sugar like confusion, fatigue, increased thirst, increased hunger, passing a lot of urine, flushing, fast breathing, or breath that smells like fruit
• Cushing syndrome like weight gain in upper back or abdomen; moon face; severe headache; or slow healing
• Skin changes like pimples, stretch marks, slow healing, or hair growth
• Infection
• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat
• Pancreatitis like severe abdominal pain, severe back pain, severe nausea, or vomiting
• Bleeding like vomiting blood or vomit that looks like coffee grounds, coughing up blood, blood in the urine, black, red, or tarry stools, bleeding from the gums, abnormal vaginal bleeding, bruises without a reason or that get bigger, or any severe or persistent bleeding
• Adrenal gland problems like severe nausea, vomiting, severe dizziness, passing out, muscle weakness, severe fatigue, mood changes, lack of appetite, or weight loss
• Severe cerebrovascular disease like change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes
• DVT like edema, warmth, numbness, change in color, or pain in the extremities
• Severe loss of strength and energy
• Tremors
• Irritability
• Fast heartbeat
• Confusion
• Sweating a lot
• Severe dizziness
• Paralysis
• Blindness
• Shortness of breath
• Excessive weight gain
• Swelling of arms or legs
• Slow heartbeat
• Chest pain
• Menstrual changes
• Joint pain
• Bone pain
• Behavioral changes
• Seizures
• Depression
• Burning or numbness feeling
• Vision changes
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.