Cortef

• Dispensing Solutions, Inc.

• Pharmacia and Upjohn Company

• Pharmacia, Inc.

You should not use this medication if you are allergic to hydrocortisone, or if you have a fungal infection anywhere in your body.

Before taking hydrocortisone, tell your doctor about all of your medical conditions, and about all other medicines you are using. There are many other diseases that can be affected by steroid use, and many other medicines that can interact with steroids.

Your steroid medication needs may change if you have any unusual stress such as a serious illness, fever or infection, or if you have surgery or a medical emergency. Tell your doctor about any such situation that affects you during treatment.

Steroid medication can weaken your immune system, making it easier for you to get an infection or worsening an infection you already have or have recently had. Tell your doctor about any illness or infection you have had within the past several weeks.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medication.

Do not receive a "live" vaccine while you are taking hydrocortisone. Vaccines may not work as well while you are taking a steroid.

Do not stop using hydrocortisone suddenly, or you could have unpleasant withdrawal symptoms. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication.

Carry an ID card or wear a medical alert bracelet stating that you are taking a steroid, in case of emergency.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

• problems with your vision;

• swelling, rapid weight gain, feeling short of breath;

• severe depression, unusual thoughts or behavior, seizure (convulsions);

• bloody or tarry stools, coughing up blood;

• pancreatitis (severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate);

• low potassium (confusion, uneven heart rate, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling); or

• dangerously high blood pressure (severe headache, blurred vision, buzzing in your ears, anxiety, confusion, chest pain, shortness of breath, uneven heartbeats, seizure).

Less serious side effects may include:

• sleep problems (insomnia), mood changes;

• acne, dry skin, thinning skin, bruising or discoloration;

• slow wound healing;

• increased sweating;

• headache, dizziness, spinning sensation;

• nausea, stomach pain, bloating; or

• changes in the shape or location of body fat (especially in your arms, legs, face, neck, breasts, and waist).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

There are many other medicines that can interact with steroids. Below is only a partial list of these medicines:

• aspirin (taken on a daily basis or at high doses);

• a diuretic (water pill);

• a blood thinner such as warfarin (Coumadin);

• cyclosporine (Gengraf, Neoral, Sandimmune);

• insulin or diabetes medications you take by mouth;

• ketoconazole (Nizoral);

• rifampin (Rifadin, Rifater, Rifamate, Rimactane); or

• seizure medications such as phenytoin (Dilantin) or phenobarbital (Luminal, Solfoton).

This list is not complete and there may be other drugs that can interact with hydrocortisone. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

• If you have an allergy to hydrocortisone or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: A fungal infection or malaria infection in the brain.
• If you have a herpes infection of the eye.
• If you have nerve problems in the eye.

This is not a list of all drugs or health problems that interact with Cortef.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Not able to sleep.
• Restlessness.
• Sweating a lot.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Naturally occurring glucocorticoids (hydrocortisone and cortisone), 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.

Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

The initial dosage of Cortef Tablets may vary from 20 mg to 240 mg of hydrocortisone 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. 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, Cortef 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's 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 Cortef for a period of time consistent with the patient's condition. If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually, rather than abruptly.

Multiple Sclerosis

In treatment of acute exacerbations of multiple sclerosis, daily doses of 200 mg of prednisolone for a week followed by 80 mg every other day for 1 month have been shown to be effective (20 mg of hydrocortisone is equivalent to 5 mg of prednisolone).

Applies to hydrocortisone: compounding powder, injectable powder for injection, injectable solution, injectable suspension, oral suspension, oral tablet, rectal foam with applicator, rectal suspension

General

Corticosteroid side effects/complications are primarily dose and duration dependent; adverse effects are infrequent with physiologic or lower pharmacologic dosages. Short-term effects have included sodium retention-related weight gain and fluid accumulation, hyperglycemia/glucose intolerance, hypokalemia, and psychic disturbances. Long-term effects have included hypothalamus-pituitary-adrenal activity suppression, Cushingoid appearance, hirsutism, impotence, menstrual irregularities, peptic ulcer disease, cataracts and increased intraocular pressure/glaucoma, myopathy, osteoporosis, and vertebral compression fractures.[Ref]

Cardiovascular

Frequency not reported: Bradycardia, cardiac arrest, cardia arrhythmias, cardiac enlargement, circulatory collapse, fat embolism, hypertension, congestive heart failure, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, thrombophlebitis, vasculitis, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis, necrotising angiitis[Ref]

Endocrine

Frequency not reported: Hypothalamus-pituitary-adrenal activity has been suppressed up to 12 months following long-term corticosteroid administration, Cushingoid appearance with chronic therapy, hirsutism, virilism, impotence, menstrual irregularities, hypertrichosis, moon face, latent hyperparathyroidism, hypoparathyroidism[Ref]

An antagonism occurs between the parathyroids and hypercorticism. Latent hyperparathyroidism may be unmasked by administration of corticosteroids; hypoparathyroidism may be manifest by phosphate retention occurring in renal failure caused by adrenal insufficiency.[Ref]

Gastrointestinal

Frequency not reported: Gastrointestinal upset, nausea, vomiting, peptic ulcer disease, pancreatitis, ulcerative esophagitis, abdominal distention, gastrointestinal perforation and hemorrhage, esophageal candidiasis[Ref]

Metabolic

Rare (0.01% to 0.1%): Hypernatremia
Frequency not reported: Decreased glucose tolerance, hyperglycemia, hypokalemia, fluid retention, negative nitrogen balance due to protein catabolism, increased blood urea nitrogen concentration, sodium retention, hypokalemic alkalosis, increased appetite, weight gain, hypertriglyceridemia[Ref]

Musculoskeletal

Aseptic necrosis has been reported most often to affect the femoral head. Corticosteroid myopathy has presented as weakness and wasting of the proximal limb and girdle muscles and generally has been reversible following cessation of therapy.

Corticosteroids inhibit intestinal absorption and increase urinary excretion of calcium leading to bone resorption and bone loss. Postmenopausal females are at risk of loss of bone density. Sixteen percent of elderly patients treated with corticosteroids for 5 years may experience vertebral compression fractures.[Ref]

Frequency not reported: Steroid myopathy, muscle weakness, loss of muscle mass, osteoporosis, vertebral compression fractures, tendon rupture (particularly the Achilles tendon), aseptic necrosis of bone, growth suppression in pediatric patients, Charcot-like arthropathy, post-injection flare (intra-articular use), osteonecrosis[Ref]

Immunologic

Frequency not reported: Impairment in cell-mediated immunity, increased susceptibility to bacterial, viral, fungal and parasitic infections, immunosuppression, opportunistic infections from mild to fatal, reactivation of tuberculosis[Ref]

Hepatic

Increases in serum transaminases and alkaline phosphatase have been observed with corticosteroid therapy; these laboratory changes are generally small, not associated with clinical symptoms, and are reversible upon discontinuation.[Ref]

Frequency not reported: Reversible increases in serum transaminase and alkaline phosphatase concentrations, hepatomegaly[Ref]

Hematologic

Corticosteroid therapy has been associated with a total increase in WBC; with an increase in neutrophils and a decrease in monocytes, lymphocytes, and eosinophils.[Ref]

Frequency not reported: Leukocytosis[Ref]

Dermatologic

Frequency not reported: Increased ease in bruising, ecchymosis, petechiae, delayed wound healing, acne, thin fragile skin, facial erythema, increased sweating, suppress reaction to skin testing, allergic dermatitis, burning or tingling in the perineal area after IV injection, cutaneous and subcutaneous atrophy, edema, hyperpigmentation, hypopigmentation, erythema, sterile abscess, striae, thinning scalp hair, urticaria[Ref]

Ocular

Frequency not reported: Increased intraocular pressure, glaucoma, posterior subcapsular cataracts, exophthalmos, central serous chorioretinopathy, corneal or scleral thinning, exacerbation of ophthalmic viral disease[Ref]

Psychiatric

In adults, the incidence of severe psychic reactions has been estimated to be around 5% to 6%. Psychological effects have been reported on withdrawal of corticosteroids, although the incidence is unknown.[Ref]

Frequency not reported: Psychoses, personality or behavioral changes, depression, emotional instability, euphoria, insomnia, mood swings, personality changes, psychic disorders, exacerbation of preexisting affect lability or psychotic behavior[Ref]

Hypersensitivity

Case reports of hypersensitivity reactions to corticosteroids have been relatively uncommon. Side effects have included bronchospasm, shock, urticaria, and angioedema. Cross-reactivity between aspirin and hydrocortisone (the active ingredient contained in Cortef) in patients with aspirin-sensitive respiratory disease has been suggested as the mechanism in patients with asthma, however data are controversial. Anaphylaxis has been most frequently associated with rapid injection or infusion of a high dose of corticosteroid. Reactions may be mediated by an immune or nonimmune mechanism.

Bronchospasm after intravenous hydrocortisone has been reported in some patients with aspirin-sensitive respiratory disease. A challenge study with oral aspirin followed with 100 mg hydrocortisone (IV) resulted in respiratory reactions to aspirin in 45 of 53 patients. These 45 patients then received a hydrocortisone challenge. No naso-ocular, dermal, or respiratory reactions were noted in 44 of 45 patients administered hydrocortisone. One aspirin-sensitive patient experienced bronchospasm and naso-ocular reactions to hydrocortisone and naso-ocular with minimal bronchospasm with methylprednisolone. Following aspirin desensitization and while on maintenance aspirin therapy, this patient again reacted with similar symptoms to hydrocortisone.[Ref]

Rare (0.01% to 0.1%): Hypersensitivity reaction (enema)
Frequency not reported: Anaphylaxis, anaphylactoid reaction, angioedema[Ref]

Other

Frequency not reported: Vertigo, abnormal fat deposits, malaise[Ref]

Genitourinary

Frequency not reported: Glycosuria, increased or decreased motility and number of spermatozoa

Nervous system

Frequency not reported: Convulsions, increased intracranial pressure with papilledema/pseudo-tumor cerebri (usually occurs after treatment), headache, neuritis, neuropathy, paresthesia, arachnoiditis, meningitis, paraparesis/paraplegia, sensory disturbances, epidural lipomatosis

Paresthesia, arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration. Intrathecal use is contraindicated and epidural administration is not recommended due to the occurrence of serious adverse events having been associated with these routes of administration.

Oncologic

Frequency not reported: Kaposi's sarcoma

Respiratory

Frequency not reported: Pulmonary edema, hiccups[Ref]

Some side effects of Cortef may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.