Cortef Oral Suspension

Cortef Oral Suspension contains hydrocortisone cypionate which is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic, which are readily absorbed from the gastrointestinal tract. Hydrocortisone cypionate is the water-insoluble cypionate ester of hydrocortisone. It is both tasteless and odorless, and by the oral route and in equimolar doses, is equivalent to hydrocortisone free alcohol in biologic activity (rat liver-glycogen assay). Determinations of plasma and urinary 17-hydroxycorticoid levels in man following oral administration indicate that this ester is as efficiently absorbed and metabolized as the free alcohol.

The chemical name for hydrocortisone cypionate is pregn-4-ene-3,20-dione,21-(3-cyclopentyl-1-oxopropoxy)-11,17-dihydroxy-,(11β)- and the molecular weight is 486.65. The structural formula is represented below:

CORTEF, a preparation for oral use, contains 13.4 mg hydrocortisone cypionate (equivalent to 10 mg hydrocortisone) in each 5 mL. CORTEF also contains the following inactive ingredients: benzoic acid, citric acid, FD&C yellow #6 as a color additive, flavors, glycerin, methylparaben, propylparaben, sucrose, xanthan gum NF food grade, and purified water. CORTEF is stable at room temperature. The pH is within a range of 2.8 to 3.2.

Systemic fungal infections and known hypersensitivity to components.

In patients on corticosteroid therapy subjected to 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. Infections with any pathogen including viral, bacterial, fungal, protozoan or helminthic infections, in any location of the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function.1

These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.2

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.

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.

Average and large doses of hydrocortisone or cortisone 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.

Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids.

The use of Cortef Oral 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 an 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.

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune 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 chicken pox, 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 chicken pox 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.

100 mg rectally (retention enema) nightly for 21 days or until both clinical and protological remission occurs
-Difficult cases may require 2 or 3 months of treatment

Comments:
-Clinical symptoms should subside within 3 to 5 days; improvement in appearance of the mucosa (as viewed by sigmoidoscopic exam) may lag behind; discontinue use if no improvement observed within 2 to 3 weeks.
-Some patients may require 2 to 3 months of therapy; if therapy lasts more than 21 days, do not stop abruptly
-Therapy has shown to benefit distal forms of ulcerative colitis including ulcerative proctitis, ulcerative proctosigmoiditis, and left-sided ulcerative colitis; it has been useful in some cases involving the transverse and ascending colons.

Use: As adjunctive therapy in the treatment of ulcerative colitis, especially distal forms.

Acute exacerbation: 800 mg oral/IV/IM once a day for 1 week followed by 320 mg oral/IV/IM every other day for 1 month

Comments:
-Short-term high-dose corticosteroids are an accepted standard of care for treating relapses of multiple sclerosis; chronic daily corticosteroids are not recommended.
-IV methylprednisolone, oral prednisone and prednisolone are the corticosteroids most studied and cited in clinical guidelines; while this drug has been used, efficacy studies and comparative data are lacking.

Use: For the treatment of acute exacerbations of multiple sclerosis.

Dosing should be individualized on the basis of disease and patient response

-Initial dose: 0.56 to 8 mg/kg/day oral or IV in 3 or 4 divided doses (20 to 240 mg/m2/day)

Maintenance dose: After a favorable initial response, dose should be decreased in small amounts to the lowest dose that maintains an adequate clinical response; if a positive response is not achieved after a reasonable period of time, alternative therapy should be sought.

Comments:
-Lower doses, including doses lower than recommended doses, may suffice in less severe disease; doses in excess of recommended doses may be required in severe disease; in life-threatening situations, doses exceeding multiples of the oral dose may be justified.
-Patients should be closely monitored for signs requiring dose adjustments; if therapy is to be stopped after more than a few days, it should be gradually withdrawn.

Uses: For use as a potent anti-inflammatory agent in managing disorders, diseases, and conditions affecting many organ systems including endocrine, dermatologic, ophthalmic, nervous, gastrointestinal, respiratory, musculoskeletal, and hematologic.

Use with caution; no dose adjustments recommended

Consult WARNINGS section for additional precautions.

Safety and efficacy of rectal products have not been established in patients younger than 18 years.