Betamethasone Acetate

Synthetic glucocorticoid; minimal mineralocorticoid activity.a b

Contraindications

• Systemic fungal infections.

• Concurrent administration of live virus or live, attenuated vaccines in patients receiving immunosuppressive dosages of glucocorticoids.a (See Immunosuppression under Cautions.)

• Epidural administration in patients with local or systemic infection; individuals with bleeding disorders or receiving concurrent anticoagulant therapy (e.g., warfarin, heparin, antiplatelet agents); patients with known hypersensitivity to local anesthetic agents, contrast agents, or glucocorticoids; and patients who experienced complications with prior glucocorticoid injections.

Warnings/Precautions

Warnings

May precipitate mental disturbances ranging from euphoria, insomnia, mood swings, depression, and personality changes to frank psychoses. Use may aggravate emotional instability or psychotic tendencies.

Use with caution in patients with myasthenia gravis.a

Aseptic meningitis, arachnoiditis, exacerbation of pain, spinal cord trauma, subdural injection, intracranial air injection, increased intracranial pressure, nerve injury, seizures, bladder or bowel dysfunction, paraparesis or paralysis, sensory disturbances, and brain damage reported following epidural and/or intrathecal glucocorticoid injection. Unclear whether these effects involved improper needle placement or were related to administration of the drug and/or preservatives.

Serious, potentially permanent, and sometimes fatal adverse neurologic events (e.g., spinal cord infarction, paraplegia, quadriplegia, cortical blindness, stroke, seizures, nerve injury, brain edema) reported rarely, often within minutes to 48 hours following epidural glucocorticoid injection given either with or without fluoroscopic guidance.1000 1001 1002 1003

FDA states efficacy and safety of epidural glucocorticoid administration not established; not FDA-labeled for this use.1000 1001 (See Advice to Patients.)

When given in supraphysiologic doses for prolonged periods, glucocorticoids may cause decreased secretion of endogenous corticosteroids by suppressing pituitary release of corticotropin (secondary adrenocortical insufficiency).a

The degree and duration of adrenocortical insufficiency is highly variable among patients and depends on the dose, frequency and time of administration, and duration of glucocorticoid therapy.a

Acute adrenal insufficiency (even death) may occur if the drugs are withdrawn abruptly or if patients are transferred from systemic glucocorticoid therapy to local (e.g., inhalation) therapy.a

Withdraw very gradually following long-term therapy with pharmacologic dosages.a (See Discontinuance of Therapy under Dosage and Administration.)

Adrenal suppression may persist up to 12 months in patients who receive large dosages for prolonged periods.a

Until recovery occurs, signs and symptoms of adrenal insufficiency may develop if subjected to stress (e.g., infection, surgery, trauma) and replacement therapy may be required. Since mineralocorticoid secretion may be impaired, sodium chloride and/or a mineralocorticoid should also be administered.a

If the disease flares up during withdrawal, increase dosage and follow with a more gradual withdrawal.a

Increased susceptibility to infections secondary to glucocorticoid-induced immunosuppression. Certain infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome in such patients. (See Increased Susceptibility to Infection under Cautions.)

Administration of live virus or live, attenuated vaccines, including smallpox, is contraindicated in patients receiving immunosuppressive dosages of glucocorticoids.a If inactivated vaccines are administered to such patients, the expected serum antibody response may not be obtained.a

Glucocorticoids, especially in large doses, increase susceptibility to and mask symptoms of infection.

Infections with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic infections in any organ system, may be associated with glucocorticoids alone or in combination with other immunosuppressive agents.

Infections may be mild, but they can be severe or fatal, and localized infections may disseminate.

Do not use, except in life-threatening situations, in patients with viral infections or bacterial infections not controlled by anti-infectives.a

Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children.

Children and any adult who are not likely to have been exposed to varicella or measles should avoid exposure to these infections while receiving glucocorticoids.

If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., VZIG, IG, antiviral agents).

Fatal outcome (e.g., in those developing hemorrhagic varicella) may not always be avoided even if appropriate therapy is initiated aggressively.

Immunosuppression may result in activation of latent infection or exacerbation of intercurrent infections (e.g., those caused by Candida, Mycobacterium, Toxoplasma, Strongyloides, Pneumocystis, Cryptococcus, Nocardia, Ameba).

Use with great care in patients with known or suspected Strongyloides (threadworm) infection. Immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.

Not effective and can have detrimental effects in the management of cerebral malaria.a

Can reactivate tuberculosis. Include chemoprophylaxis in patients with a history of active tuberculosis undergoing prolonged glucocorticoid therapy.a Observe closely for evidence of reactivation. Restrict use in active tuberculosis to those with fulminating or disseminated tuberculosis in which glucocorticoids are used in conjunction with appropriate chemoprophylaxis.

Can reactivate latent amebiasis.a Exclude possible amebiasis in any patient who has been in the tropics or who has unexplained diarrhea prior to initiating therapy.a

Rarely, epidural abscess reported following epidural glucocorticoid injection; infectious complications (e.g., bacterial meningitis) also reported.

Muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones are manifestations of protein catabolism that may occur during prolonged therapy with glucocorticoids.a These adverse effects may be especially serious in geriatric or debilitated patients.a A high protein diet may help to prevent adverse effects associated with protein catabolism.a

An acute, generalized myopathy can occur with the use of high doses of glucocorticoids, particularly in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) or in patients receiving concomitant therapy with neuromuscular blocking agents (e.g., pancuronium).

Tendon rupture, particularly of the Achilles tendon.

Osteoporosis and related fractures are one of the most serious adverse effects of long-term glucocorticoid therapy.

To minimize the risk of glucocorticoid-induced bone loss, the smallest possible effective dosage and duration should be used.

Before initiating glucocorticoid therapy in postmenopausal women, consider that they are especially prone to osteoporosis.a

Withdraw glucocorticoids if osteoporosis develops, unless their use is life-saving.a

Glucocorticoid-induced bone loss can be both prevented and treated. Baseline measurement of bone mineral density (BMD) at the lumbar spine and/or hip should be obtained when initiating long-term (e.g., >6 months) therapy, and appropriate preventive therapy should be initiated. Longitudinal measurements may be repeated as often as every 6 months to detect possible bone loss. Less frequent (e.g., annual) follow-up probably is sufficient in patients who are receiving therapy to prevent bone loss.

Skeletal wasting is most rapid during the initial 6 months of therapy, and trabecular bone is affected to a greater degree than is cortical bone.

Calcium and vitamin D supplementation, bisphosphonate (e.g., alendronate, risedronate), and a weight-bearing exercise program that maintains muscle mass are suitable first-line therapies aimed at reducing the risk of adverse bone effects.

Calcitonin may be considered as second-line therapy for patients who refuse or do not tolerate bisphosphonate therapy or in whom the drugs are contraindicated.

Sodium retention with resultant edema, potassium loss, and elevation of BP may occur but is less common with betamethasone than with average or large doses of cortisone or hydrocortisone. Risk is increased with high-dose synthetic glucocorticoids for prolonged periods.a Edema and CHF (in susceptible patients) may occur.a

Dietary salt restriction is advisable and potassium supplementation may be necessary.a

Increased calcium excretion and possible hypocalcemia.a

Prolonged use may result in posterior subcapsular and nuclear cataracts (particularly in children), exophthalmos, and/or increased intraocular pressure (IOP) which may result in glaucoma or may occasionally damage the optic nerve.a

May enhance the establishment of secondary fungal and viral infections of the eye.

Use cautiously in patients with active ocular herpes simplex infections since corneal perforation may develop.

Transient blindness, amblyopia, acute retinal necrosis syndrome, intraocular hemorrhage, and cortical blindness have occurred following epidural glucocorticoid injection.1001 1002 1003

Administration over a prolonged period may produce various endocrine disorders including hypercorticism (cushingoid state) and amenorrhea or other menstrual difficulties.a

Increased or decreased motility and number of sperm in some men.a

May decrease glucose tolerance, produce hyperglycemia, and aggravate or precipitate diabetes mellitus, especially in patients predisposed to diabetes mellitus.a If glucocorticoid therapy is required in patients with diabetes mellitus, changes in insulin or oral antidiabetic agent dosage or diet may be necessary.a

Administer by epidural injection with caution in patients with diabetes mellitus.

Exaggerated response to the glucocorticoids in hypothyroidism.a

Use with extreme caution in recent MI since an association between use of glucocorticoids and left ventricular free-wall rupture has been suggested.a

Administer by epidural injection with caution in patients with CHF.

Use with caution in patients with hypertension.

Sensitivity Reactions

Anaphylactic or anaphylactoid reactions with or without circulatory collapse, cardiac arrest, or bronchospasm.a Take appropriate precautionary measures prior to administration, especially in patients with a history of allergy to any drug.

Injectable suspension contains benzalkonium chloride that has been associated with neurotoxic effects in animals or humans when used epidurally or intrathecally.

General Precautions

Prior to initiation of long-term glucocorticoid therapy, perform baseline ECGs, BPs, chest and spinal radiographs, glucose tolerance tests, and evaluations of HPA-axis function in all patients.a

Perform upper GI radiographs in patients predisposed to GI disorders, including those with known or suspected peptic ulcer disease.a

During long-term therapy, perform periodic height, weight, chest and spinal radiographs, hematopoietic, electrolyte, glucose tolerance, and ocular and BP evaluations.

Increased or decreased motility and number of sperm in some men.a

Corticosteroids should be used with caution in patients with diverticulitis, nonspecific ulcerative colitis (if there is a probability of impending perforation, abscess, or other pyogenic infection), or those with recent intestinal anastomoses.

Use with caution in patients with active or latent peptic ulcer. Manifestations of peritoneal irritation following GI perforation may be minimal or absent in patients receiving corticosteroids.a Suggest concurrent administration of antacids between meals to prevent peptic ulcer formation in patients receiving high dosages.a

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Category C.

Observe neonates born from mothers receiving prolonged therapy for signs of hypoadrenalism.

Fluoroscopy (recommended for ensuring proper needle placement for epidural injections) is contraindicated in pregnant women.

Distributed into milk and could suppress growth, interfere with endogenous glucocorticoid production, or cause other adverse effects in nursing infants.a

With long-term use, may delay growth and maturation in children and adolescents.a c Monitor carefully the growth and development of pediatric patients receiving prolonged corticosteroid therapy.a Titrate dosage to the lowest effective level.a Alternate-day therapy with short-acting glucocorticoids (e.g., prednisone, prednisolone, methylprednisolone) may minimize growth suppression and should be instituted if growth suppression occurs.a

Glucocorticoid-induced osteoporosis and associated fractures are common in children and adolescents receiving long-term systemic therapy. In addition, may prevent achievement of peak bone mass during adolescence by inhibiting bone formation. Methods for monitoring bone mineralization (e.g., dual-energy x-ray absorptiometry [DXA]) in children and adolescents are similar to those in adults.

Ensure children and adolescents consistently ingest either through diet or supplementation adequate calcium and vitamin D.

With prolonged therapy, muscle wasting, muscle pain or weakness, delayed wound healing, and atrophy of the protein matrix of the bone resulting in osteoporosis, vertebral compression fractures, aseptic necrosis of femoral or humeral heads, or pathologic fractures of long bones may occur.a May be especially serious in geriatric or debilitated patients.a

Before initiating glucocorticoid therapy in postmenopausal women, consider that such women are especially prone to osteoporosis.a

Glucocorticoids should be used with caution in patients with cirrhosis because such patients often show exaggerated response to the drugs.a

Use with caution.

Common Adverse Effects

Intra-articular and soft-tissue injection: Soft-tissue atrophy, hypopigmentation or hyperpigmentation, facial erythema, thin, fragile skin.

Inhibits and is metabolized by CYP3A4.

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (decreased betamethasone clearance).a

Inducers of CYP3A4: Potential pharmacokinetic interaction (increased betamethasone clearance).a

Specific Drugs

• In patients receiving long-term therapy, importance of not discontinuing the drug abruptly.b

• Importance of notifying a clinician of any infections, signs of infections (e.g., fever, sore throat, pain during urination, muscle aches), or injuries that develop during therapy or within 12 months after therapy is discontinued.a

• Importance of carrying identification cards listing the diseases being treated, the glucocorticoid regimen, and the name and telephone number of the clinician.a

• When surgery is required, importance of informing the attending physician, dentist, or anesthesiologist of recent (within 12 months) glucocorticoid therapy.a

• In immunosuppressed patients, importance of avoiding exposure to certain infections (e.g., chickenpox, measles) and of obtaining medical advice if such exposure occurs.

• When considering epidural glucocorticoid injections for pain relief, importance of understanding potential benefits and risks of epidural injections and alternative treatments.1000 1001 Importance of immediately seeking emergency medical attention if unusual symptoms (e.g., loss of or changes in vision, tingling in extremities, sudden weakness or numbness affecting face or occurring unilaterally or bilaterally in arms or legs, dizziness, severe headache, seizures) occur after epidural injection.1001

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information.a c (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name