Each mL of CELESTONE SOLUSPAN* Injectable Suspension contains: 3.0 mg betamethasone as betamethasone sodium phosphate; 3.0 mg betamethasone acetate; 7.1 mg dibasic sodium phosphate; 3.4 mg monobasic sodium phosphate; 0.1 mg edetate disodium; and 0.2 mg benzalkonium chloride. It is a sterile, aqueous suspension with a pH between 6.8 and 7.2.
The formula for betamethasone sodium phosphate is C 22 H 28 FNa 2 0 8 P with a molecular weight of 516.41. Chemically, it is 9-Fluoro-11(beta),17,21-trihydroxy-16(beta)-methylpregna-1,4-diene-3,20-dione 21-(disodium phosphate).
The formula for betamethasone acetate is C 24 H 31 FO 6 with a molecular weight of 434.50. Chemically, it is 9-Fluoro-11(beta),17,21-trihydroxy-16(beta)-methylpregna-1,4-diene-3,20-dione 21-acetate.
The chemical structures for betamethasone sodium phosphate and betamethasone acetate are as follows:
Betamethasone sodium phosphate is a white to practically white, odorless powder, and is hygroscopic. It is freely soluble in water and in methanol, but is practically insoluble in acetone and in chloroform.
Betamethasone acetate is a white to creamy white, odorless powder that sinters and resolidifies at about 165°C, and remelts at about 200°C to 220°C with decomposition. It is practically insoluble in water, but freely soluble in acetone, and is soluble in alcohol and in chloroform.
Naturally occurring glucocorticoids (hydrocortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems.
Betamethasone sodium phosphate, a soluble ester, provides prompt activity, while betamethasone acetate is only slightly soluble and affords sustained activity.
Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body' immune responses to diverse stimuli.
When oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend the preparation to the treatment of the condition, CELESTONE SOLUSPAN Injectable Suspension for intramuscular use is indicated as follows:
Endocrine disorders: primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; synthetic analogs may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance).
Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice; mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used); preoperatively and in the event of serious trauma or illness, in patients with known adrenal insufficiency or when adrenocortical reserve is doubtful; shock unresponsive to conventional therapy if adrenocortical insufficiency exists or is suspected; congenital adrenal hyperplasia; nonsuppurative thyroiditis; hypercalcemia associated with cancer.
Rheumatic disorders: as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: post-traumatic osteoarthritis; synovitis of osteoarthritis; rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low-dose maintenance therapy); acute and subacute bursitis; epicondylitis; acute nonspecific tenosynovitis; acute gouty arthritis; psoriatic arthritis; ankylosing spondylitis.
Collagen diseases: during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus, acute rheumatic carditis.
Dermatologic diseases: pemphigus, severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, bullous dermatitis herpetiformis, severe seborrheic dermatitis, severe psoriasis, mycosis fungoides.
Allergic states: control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in: bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, drug hypersensitivity reactions, urticarial transfusion reactions, acute noninfectious laryngeal edema (epinephrine is the drug of first choice).
Ophthalmic diseases: severe acute and chronic allergic and inflammatory processes involving the eye, such as: herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, allergic corneal marginal ulcers, keratitis.
Gastrointestinal diseases: to tide the patient over a critical period of disease in: ulcerative colitis (systemic therapy), regional enteritis (systemic therapy).
Respiratory diseases: symptomatic sarcoidosis, berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, Loeffler' syndrome not manageable by other means, aspiration pneumonitis.
Hematologic disorders: acquired (autoimmune) hemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia (RBC anemia), congenital (erythroid) hypoplastic anemia.
Neoplastic diseases: for palliative management of: leukemias and lymphomas in adults, acute leukemia of childhood.
Edematous states: to induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.
Miscellaneous: tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy, trichinosis with neurologic or myocardial involvement.
When the strength and dosage form of the drug lend the preparation to the treatment of the condition, the intra-articular or soft tissue administration of CELESTONE SOLUSPAN Injectable Suspension is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: synovitis of osteoarthritis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, post-traumatic osteoarthritis.
When the strength and dosage form of the drug lend the preparation to the treatment of the condition, the intralesional administration of CELESTONE SOLUSPAN Injectable Suspension is indicated for: keloids; localized hypertrophic, infiltrated, inflammatory lesions of: lichen planus, psoriatic plaques, granuloma annulare, and lichen simplex chronicus (neurodermatitis); discoid lupus erythematosus; necrobiosis lipoidica diabeticorum; alopecia areata.
CELESTONE SOLUSPAN Injectable Suspension may also be useful in cystic tumors of an aponeurosis or tendon (ganglia).
CELESTONE SOLUSPAN Injectable Suspension is contraindicated in systemic fungal infections.
CELESTONE SOLUSPAN Injectable Suspension should not be administered intravenously.
In patients on corticosteroid therapy subjected to any unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.
Corticosteroids may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.
CELESTONE SOLUSPAN Injectable Suspension contains two betamethasone esters, one of which, betamethasone sodium phosphate, disappears rapidly from the injection site. The potential for systemic effect produced by the soluble portion of CELESTONE SOLUSPAN Injectable Suspension should therefore be taken into account by the physician when using the drug.
Average and large doses of cortisone or hydrocortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives, except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.
While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially in high doses, because of possible hazards of neurological complications and lack of antibody response.
Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in nonimmune children or adults on corticosteroids. In such children, or adults who have not had these diseases, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affects the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If exposed to chickenpox, prophylaxis with varicella-zoster immune globulin (VZIG) may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the respective package inserts for complete VZIG and IG prescribing information.) If chickenpox develops, treatment with antiviral agents may be considered.
Similarly, corticosteroids should be used with great care in patients with known or suspected Strongyloides (threadworm) infestation. In such patients, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
The use of CELESTONE SOLUSPAN Injectable Suspension in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with appropriate antituberculous regimen.
If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.
Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.
Usage in pregnancy: Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers, or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.
Information for Patients: Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles. Patients should also be advised that if they are exposed, medical advice should be sought without delay.
General: Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.
There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.
Corticosteroids should be used cautiously in patients with ocular herpes simplex for fear of corneal perforation.
The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction must be gradual.
Psychic derangements may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
Steroids should be used with caution in nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer; renal insufficiency; hypertension; osteoporosis; and myasthenia gravis.
Growth and development of infants and children on prolonged corticosteroid therapy should be carefully followed.
The following additional precautions also apply for parenteral corticosteroids. Intra-articular injection of a corticosteroid may produce systemic as well as local effects.
Appropriate examination of any joint fluid present is necessary to exclude a septic process.
A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.
Local injection of a steroid into a previously infected joint is to be avoided.
Corticosteroids should not be injected into unstable joints.
The slower rate of absorption by intramuscular administration should be recognized.
Fluid and electrolyte disturbances: sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, hypokalemic alkalosis, hypertension.
Musculoskeletal: muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones.
Gastrointestinal peptic ulcer with possible subsequent perforation and hemorrhage, pancreatitis, abdominal distention, ulcerative esophagitis, hiccups.
Dermatologic: impaired wound healing; thin, fragile skin; petechiae and ecchymoses; facial erythema; increased sweating; may suppress reactions to skin tests.
Neurological: convulsions, increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment, vertigo, headache.
Endocrine: menstrual irregularities; development of cushingoid state; suppression of growth in children; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery, or illness; decreased carbohydrate tolerance; manifestations of latent diabetes mellitus; increased requirements for insulin or oral hypoglycemic agents in diabetics.
Ophthalmic posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmos.
Metabolic: negative nitrogen balance due to protein catabolism.
The following additional adverse reactions are related to parenteral corticosteroid therapy: rare instances of blindness associated with intralesional therapy around the face and head, hyperpigmentation or hypopigmentation, subcutaneous and cutaneous atrophy, sterile abscess, postinjection flare (following intra-articular use), charcot-like arthropathy, anaphylactoid or hypersensitivity and hypotensive and shock-like reactions.
The initial dosage of CELESTONE SOLUSPAN Injectable Suspension may vary from 0.5 to 9.0 mg per day depending on the specific disease entity being treated. In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. Usually the parenteral dosage ranges are 1 / 3 to 1 / 2 the oral dose given every 12 hours. However, in certain overwhelming, acute, life-threatening situations, administration in dosages exceeding the usual dosages may be justified and may be in multiples of the oral dosages.
The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, CELESTONE SOLUSPAN Injectable Suspension should be discontinued and the patient transferred to other appropriate therapy. It Should Be Emphasized That Dosage Requirements Are Variable and Must Be Individualized on the Basis of the Disease Under Treatment and the Response of the Patient. After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached. It should be kept in mind that constant monitoring is needed in regard to drug dosage. Included in the situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient' individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment. In this latter situation it may be necessary to increase the dosage of CELESTONE SOLUSPAN Injectable Suspension for a period of time consistent with the patient' condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly.
If coadministration of a local anesthetic is desired,CELESTONE SOLUSPAN Injectable Suspension may be mixed with 1% or 2% lidocaine hydrochloride, using the formulations which do not contain parabens. Similar local anesthetics may also be used. Diluents containing methylparaben, propylparaben, phenol, etc., should be avoided since these compounds may cause flocculation of the steroid. The required dose of CELESTONE SOLUSPAN Injectable Suspension is first withdrawn from the vial into the syringe. The local anesthetic is then drawn in, and the syringe shaken briefly. Do not inject local anesthetics into the vial of CELESTONE SOLUSPAN Injectable Suspension.
Bursitis, tenosynovitis, peritendinitis: In acute subdeltoid, subacromial, olecranon, and prepatellar bursitis, one intrabursal injection of 1.0 mL CELESTONE SOLUSPAN Injectable Suspension can relieve pain and restore full range of movement. Several intrabursal injections of corticosteroids are usually required in recurrent acute bursitis and in acute exacerbations of chronic bursitis. Partial relief of pain and some increase in mobility can be expected in both conditions after one or two injections. Chronic bursitis may be treated with reduced dosage once the acute condition is controlled. In tenosynovitis and tendinitis, three or four local injections at intervals of 1 to 2 weeks between injections are given in most cases. Injections should be made into the affected tendon sheaths rather than into the tendons themselves. In ganglions of joint capsules and tendon sheaths, injection of 0.5 mL directly into the ganglion cysts has produced marked reduction in the size of the lesions.
Rheumatoid arthritis and osteoarthritis: Following intra-articular administration of 0.5 to 2.0 mL of CELESTONE SOLUSPAN Injectable Suspension, relief of pain, soreness, and stiffness may be experienced. Duration of relief varies widely in both diseases. Intra-articular Injection--CELESTONE SOLUSPAN Injectable Suspension is well tolerated in joints and periarticular tissues. There is virtually no pain on injection, and the "secondary flare" that sometimes occurs a few hours after intra-articular injection of corticosteroids has not been reported with CELESTONE SOLUSPAN Injectable Suspension. Using sterile technique, a 20- to 24-gauge needle on an empty syringe is inserted into the synovial cavity and a few drops of synovial fluid are withdrawn to confirm that the needle is in the joint. The aspirating syringe is replaced by a syringe containing CELESTONE SOLUSPAN Injectable Suspension and injection is then made into the joint.
A portion of the administered dose of CELESTONE SOLUSPAN Injectable Suspension is absorbed systemically following intra-articular injection. In patients being treated concomitantly with oral or parenteral corticosteroids, especially those receiving large doses, the systemic absorption of the drug should be considered in determining intra-articular dosage.
Dermatologic conditions: In intralesional treatment, 0.2 mL/sq cm of CELESTONE SOLUSPAN Injectable Suspension is injected intradermally (not subcutaneously) using a tuberculin syringe with a 25-gauge, 1 / 2 -inch needle. Care should be taken to deposit a uniform depot of medication intradermally. A total of no more than 1.0 mL at weekly intervals is recommended.
Disorders of the foot: A tuberculin syringe with a 25-gauge, 3 / 4 -inch needle is suitable for most injections into the foot. The following doses are recommended at intervals of 3 days to a week.
CELESTONE SOLUSPAN Injectable Suspension, 5-mL multiple-dose vial; box of one (NDC 0085-0566-05).
Shake well before using.
Store between 2° and 25°C (36° and 77°F).
Protect from light.
Kenilworth, NJ 07033 USA
Copyright © 1969, 1996, Schering Corporation.
All rights reserved.
Rev. 10/99 23504804