Betamethasone (Diprolene) Adverse Reactions
- abdominal pain
- acne vulgaris
- acneiform rash
- adrenocortical insufficiency
- alopecia
- amenorrhea
- angioedema
- anorexia
- anxiety
- appetite stimulation
- arthralgia
- arthropathy
- avascular necrosis
- bone fractures
- cataracts
- conjunctivitis
- constipation
- contact dermatitis
- Cushing’s syndrome
- depression
- diabetes mellitus
- diaphoresis
- diarrhea
- dysmenorrhea
- ecchymosis
- edema
- EEG changes
- emotional lability
- erythema
- esophageal ulceration
- esophagitis
- euphoria
- exfoliative dermatitis
- exophthalmos
- fever
- fluid retention
- folliculitis
- gastritis
- GI bleeding
- GI perforation
- growth inhibition
- headache
- heart failure
- hirsutism
- hypercholesterolemia
- hyperglycemia
- hypernatremia
- hypertension
- hypertrichosis
- hypocalcemia
- hypokalemia
- hypotension
- hypothalamic-pituitary-adrenal (HPA) suppression
- immunosuppression
- impaired wound healing
- increased intracranial pressure
- infection
- injection site reaction
- insomnia
- lethargy
- menstrual irregularity
- metabolic alkalosis
- miliaria
- myalgia
- myopathy
- nausea/vomiting
- ocular hypertension
- optic neuritis
- osteoporosis
- palpitations
- pancreatitis
- papilledema
- paresthesias
- peptic ulcer
- peripheral neuropathy
- petechiae
- phlebitis
- physiological dependence
- pruritus
- pseudotumor cerebri
- psychosis
- restlessness
- retinopathy
- seizures
- skin atrophy
- skin hyperpigmentation
- skin hypopigmentation
- skin irritation
- skin ulcer
- sodium retention
- striae
- telangiectasia
- tendon rupture
- thromboembolism
- thrombosis
- tolerance
- urinary incontinence
- urinary urgency
- urticaria
- vertigo
- visual impairment
- weakness
- weight gain
- weight loss
- withdrawal
- xerosis
Betamethasone (Diprolene) Adverse Reactions
NOTE: Prolonged systemic administration of physiologic replacement dosages of corticosteroid therapy usually does not cause adverse effects. The severity of the adverse effects associated with prolonged administration of pharmacological dosages of corticosteroids increases with duration and frequency of therapy. Short-term administration of large doses typically does not cause adverse effects, but long-term administration can lead to adrenocortical atrophy and generalized protein depletion.
Pharmacologic doses of systemic corticosteroids administered for prolonged periods can result in physiological dependence due to hypothalamic-pituitary-adrenal (HPA) suppression. Systemic absorption of topical betamethasone is minimal in adults, but theoretically could cause systemic adverse reactions, especially if applied to a large surface area and/or if occlusive dressings are used. During treatment with betamethasone dipropionate (Diprolene®AF or Diprosone®), 23-73% of pediatric patients (< 12 years) experienced adrenal suppression. The proportion of patients with adrenal suppression was progressively greater, the younger the age group. Exogenously administered corticosteroids exert a negative feedback effect on the pituitary, inhibiting the secretion of adrenocorticotropin (ACTH). This results in a decrease in ACTH-mediated synthesis of endogenous corticosteroids and androgens by the adrenal cortex. The severity of secondary adrenocortical insufficiency varies among individuals and is dependent on the dose, frequency, time of administration, and duration of therapy. Systemic administration drug on alternate days may help to alleviate this adverse effect. Patients with HPA suppression will require increased doses of corticosteroid therapy during periods of physiologic stress. Acute adrenal insufficiency and even death can occur with abrupt discontinuation of therapy. Discontinuation of prolonged oral corticosteroid therapy should be gradual, since HPA suppression can last for up to 12 months following cessation of therapy. Patients may continue to need supplemental corticosteroid treatment during periods of physiologic stress or infectious conditions, even after the drug has been discontinued. A withdrawal syndrome unrelated to adrenocortical insufficiency can occur following sudden discontinuance of corticosteroid therapy. This syndrome includes symptoms such as anorexia, lethargy, nausea/vomiting, headache, fever, arthralgia, myalgia, exfoliative dermatitis, weight loss, and hypotension. These effects are believed to be due to the sudden change in corticosteroid concentration rather than to low corticosteroid levels. HPA axis suppression and increased intracranial pressure have been reported in children receiving topical corticosteroids. Increased intracranial pressure with papilledema (i.e., pseudotumor cerebri) has also been reported with withdrawal of glucocorticoid therapy.
Prolonged corticosteroid therapy can result in manifestations of Cushing’s syndrome. Cushing’s syndrome is characterized by truncal obesity, moon face, acne vulgaris, abdominal striae, increased blood pressure, decreased carbohydrate tolerance, protein catabolism, psychiatric disturbances, and skeletal changes, menstrual irregularity including amenorrhea or dysmenorrhea, and hirsutism.
Because of retardation of bone growth, children receiving prolonged systemic corticosteroid therapy may have growth inhibition. Controlled clinical trials have shown that intranasal or orally inhaled corticosteroids may also cause growth inhibition in pediatric patients. Growth inhibition has been observed in the absence of laboratory evidence of hypothalamic-pituitary-adrenal (HPA) suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in pediatric patients. With orally inhaled corticosteroids, the mean reduction in growth velocity is approximately 1 cm/year (range 0.3-1.8 cm/year) and appears to be related to the dose and duration of exposure. The long-term effects of this reduction in growth velocity, including the impact on final adult height, are unknown. To minimize the effects of intranasal corticosteroids, each patient should be titrated to the lowest effective dose.
Glucocorticoids are responsible for protein metabolism, and prolonged therapy can result in various musculoskeletal manifestations, including: myopathy (myalgia, muscle wasting, muscle weakness), bone matrix atrophy (osteoporosis), bone fractures such as vertebral compression fractures or fractures of long bones, and avascular necrosis of femoral or humoral heads. These effects are more likely to occur in older or debilitated patients. Glucocorticoids interact with calcium metabolism at many sites, including decreasing the synthesis by osteoblasts of the principle proteins of bone matrix, malabsorption of calcium in both the nephron and the gut, and reduction of sex hormone concentrations. Although all of these actions probably contribute to glucocorticoid-induced osteoporosis, the actions on osteoblasts are the most important. Glucocorticoids do not modify vitamin D metabolism. Postmenopausal women, in particular, should be monitored for signs of osteoporosis during corticosteroid therapy. Intra-articular injections of corticosteroids can cause Charcot-like arthropathy and post-injection flare. Atrophy at the site of injection has been reported following administration of soluble glucocorticoids. Tendon rupture has also been reported.
Adverse GI effects associated with long-term oral corticosteroid administration include nausea/vomiting and anorexia with subsequent weight loss. Appetite stimulation with weight gain, diarrhea, constipation, abdominal pain, hiccups, esophageal ulceration, esophagitis, gastritis, and pancreatitis have also been reported with systemic therapy. Peptic ulcers with possible subsequent GI bleeding and GI perforation have been reported. Although it was once believed that corticosteroids contributed to the development of peptic ulcer disease, in a published review of 93 studies of corticosteroid use, the incidence of peptic ulcer disease was not found to be higher in steroid recipients compared to control groups.
Topical preparations of betamethasone may be associated with local adverse effects and skin irritation including acneiform rash, allergic contact dermatitis, erythema, folliculitis, hypertrichosis, miliaria, perioral dermatitis, pruritus, skin atrophy, skin hypopigmentation, telangiectasia, and xerosis. The most frequent adverse reactions reported with betamethasone foam were burning, itching, and stinging at the site of application. Alopecia and conjunctivitis were also reported with foam. Skin atrophy or signs of atrophy (e.g., ecchymosis (bruising), shininess, thinness, loss of skin markings) occurred in 7 of 67 (10%) pediatric patients (age from 3 months - 12 years) treated with Diprolene® AF. Cutaneous atrophy of the face occurred in 1/6 (17%) of infants, 2/9 (22%) of 2-5 year olds, and 2/6 (33%) of the 6-8 year olds treated with Diprosone® ointment; non-facial atrophy occurred in 15%, 8%, and 5-9% of 2-5 year olds, 6-8 year olds, and 9-12 year olds, respectively. Other reported adverse reactions to topical betamethasone products include paresthesias (burning), erythema, erythematous rash, and xerosis (dry skin). Various adverse dermatologic effects reported during systemic corticosteroid therapy include skin atrophy, diaphoresis, facial erythema, petechiae, ecchymosis, and easy bruising. Hypersensitivity reactions may manifest as allergic dermatitis, urticaria, and/or angioedema. Parenteral corticosteroid therapy has also produced skin hypopigmentation, skin hyperpigmentation, scarring, and other types of injection site reaction (e.g., induration, delayed pain or soreness, subcutaneous and cutaneous atrophy, and sterile abscesses). Paresthesias (burning or tingling) in the perineal area may occur following IV injection of corticosteroids.
In general, excessive use of systemic or topical corticosteroids can lead to impaired wound healing. Betamethasone should not be applied directly on or near healing wounds. Skin ulcer may develop in patients with markedly impaired circulation who use topical corticosteroids.
Corticosteroid therapy (systemic or topical) can mask the symptoms of infection resulting in secondary infections; corticosteroids should not be used with an active infection unless adequately controlled by anti-infective agents. Immunosuppression is most likely to occur in patients receiving high-dose (e.g., equivalent to 1 mg/kg or more of prednisone daily), systemic corticosteroid therapy for any period of time, particularly in conjunction with corticosteroid sparing drugs (e.g., troleandomycin) and/or concomitant immunosuppressant agents; however, patients receiving moderate dosages of systemic corticosteroids for short periods or low dosages for prolonged periods may also be at risk. Corticosteroid-induced immunosuppression may result in activation of latent viral (e.g., herpes) or bacterial (e.g., tuberculosis) infections and should not be used in patients with an active infection except when appropriate anti-infective therapy is instituted concomitantly.
Prolonged administration of glucocorticoids also can result in edema and fluid retention due to sodium retention; electrolyte disturbances (hypokalemia, hypokalemic metabolic alkalosis, hypernatremia, hypocalcemia); and hypertension. In a review of 93 studies of corticosteroid use, hypertension was found to develop 4 times as often in steroid recipients compared to control groups. Congestive heart failure can occur in susceptible patients.
Although corticosteroids are used to treat Graves’ ophthalmopathy, ocular effects, such as exophthalmos, posterior subcapsular cataracts, retinopathy, or ocular hypertension, can result from prolonged use of corticosteroids and could result in glaucoma, or ocular nerve damage including optic neuritis. Temporary or permanent visual impairment, including blindness, has been reported with corticosteroid administration by several routes of administration including intranasal. Secondary fungal and viral infections of the eye can be exacerbated by corticosteroid therapy. Inhaled corticosteroid therapy has been associated with the development of cataracts in adults. The risk of cataracts increases with long-term and high-dose inhaled corticosteroid use. The mechanism of corticosteroid-induced cataract formation is uncertain but may involve disruption of sodium-potassium pumps in the lens epithelium leading to accumulation of water in lens fibers and agglutination of lens proteins. Ocular hypertension and cataracts leading to visual impairment have also occurred following prolonged application of corticosteroids to the skin around the eye.
Prolonged corticosteroid therapy can result in hyperglycemia and aggravation of diabetes mellitus in susceptible patients. In a published review of 93 studies of corticosteroid use, the development of diabetes mellitus was determined to occur 4 times more frequently in steroid recipients compared to control groups. Insulin or oral hypoglycemic dosages may require adjustment.
Adverse neurologic effects have been reported during prolonged corticosteroid therapy including headache, insomnia, vertigo, restlessness, ischemic peripheral neuropathy, seizures, and EEG changes. Mental status changes including depression, anxiety, euphoria, personality changes, and psychosis also have been reported. Emotional lability and psychotic problems can be exacerbated by corticosteroid therapy.
Hypercholesterolemia, atherosclerosis, fat embolism, thrombosis, thromboembolism, and phlebitis have been associated with systemic corticosteroid therapy. Palpitations, sinus tachycardia, glossitis, stomatitis, urinary incontinence, and urinary urgency have been rarely reported. Corticosteroids may also decrease serum concentrations of vitamin C (ascorbic acid) and vitamin A, which may rarely produce symptoms of vitamin A deficiency or vitamin C deficiency.
Tolerance may occur with the prolonged use of topical corticosteroids. Tolerance is usually described as a decreased acute vasoconstrictive response to the agent after a period of days to weeks. This may explain the dramatic responses noted initially by patients early in topical corticosteroid treatment and an apparent diminished response with time. Tolerance is reversible and may be attenuated by interrupted or cyclic schedules of application (e.g., betamethasone is given for 2-3 weeks, followed by a 1-week intermission).
[ Last revised: 1/12/2004 11:50:00 AM ]
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