Orapred

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

Before taking prednisolone, 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 using prednisolone. The vaccine may not work as well during this time, and may not fully protect you from disease.

Do not stop using prednisolone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using prednisolone.

Wear a medical alert tag or carry an ID card stating that you take prednisolone. Any medical care provider who treats you should know that you take steroid medication.

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

Call your doctor at once if you have a serious side effect such as:

• 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.

• If you have an allergy to prednisolone 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 a herpes infection of the eye.
• If you have any of these health problems: A fungal infection or malaria infection in the brain.
• If you have nerve problems in the eye.

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

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.

Orapred Solution is a dye free, pale to light yellow solution. Each 5 mL (teaspoonful) of Orapred contains 20.2 mg prednisolone sodium phosphate (15 mg prednisolone base) in a palatable, aqueous vehicle.

Inactive Ingredients: Orapred Solution equivalent to 15 mg prednisolone per 5 mL contains the following inactive ingredients: alcohol 2%, fructose, glycerin, monoammonium glycyrrhizinate, povidone, sodium benzoate, sorbitol, and flavor. Orapred may contain citric acid and/or sodium hydroxide for pH adjustment.

Prednisolone sodium phosphate occurs as white or slightly yellow, friable granules or powder. It is freely soluble in water; soluble in methanol; slightly soluble in alcohol and in chloroform; and very slightly soluble in acetone and in dioxane. The chemical name of prednisolone sodium phosphate is pregna-1, 4-diene-3,20-dione, 11, 17-dihydroxy-21-(phosphonooxy)-, disodium salt, (11ß)-. The empirical formula is C21 H27Na2O8P; the molecular weight is 484.39. Its chemical structure is:

General:

In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during and after the stressful situation is indicated.

Cardio-renal:

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.

Endocrine:

Corticosteroids can produce reversible hypothalamicpituitary adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment.

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate adjustment in dosage.

Infections (General):

Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen including viral, bacterial, fungal, protozoan or helminthic infection, in any location of the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect humoral or cellular immunity, or neutrophil function. These infections may be mild to severe, and, with increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of infection after it has already started.

Infections (Viral):

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 affect 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 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 should be considered.

Ophthalmic:

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 bacteria, fungi or viruses. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in active ocular herpes simplex.

Special pathogens:

Latent disease may be activated or there may be an exacerbation of intercurrent infections due to pathogens, including those caused by Candida, Mycobacterium, Ameba, Toxoplasma, Pneumocystis, Cryptococcus, Nocardia, etc.

Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent or active amebiasis be ruled out before initiating corticosteroid therapy in any patient who has spent time in the tropics or in any patient with unexplained diarrhea.

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.

Corticosteroids should not be used in cerebral malaria.

Tuberculosis:

The use of prednisolone 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.

Vaccination: Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered, however, the response to such vaccines can not be predicted. Immunization procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g., for Addison's disease.

General:

The lowest possible dose of corticosteroid should be used to control the condition under treatment, and when reduction in dosage is possible, the reduction should be gradual.

Since complications of treatment with glucocorticoids are dependent on the size of the dose and the duration of treatment, a risk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whether daily or intermittent therapy should be used.

There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.

Kaposi's sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Cardio-renal:

As sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids, these agents should be used with caution in patients with hypertension, congestive heart failure, or renal insufficiency.

Endocrine:

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.

Gastrointestinal:

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.

Signs of peritoneal irritation following gastrointestinal perforation in patients receiving corticosteroids may be minimal or absent.

Musculoskeletal:

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in children and adolescents and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (i.e., postmenopausal women) before initiating corticosteroid therapy.

Neuro-psychiatric:

Although controlled clinical trials have shown corticosteroids to be effective in speeding the resolution of acute exacerbations of multiple sclerosis, they do not show that they affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect. (See DOSAGE AND ADMINISTRATION.)

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatinine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

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.

Ophthalmic:

Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

Information For Patients:

Patients should be warned not to discontinue the use of Orapred abruptly or without medical supervision, to advise any medical attendants that they are taking it and to seek medical advice at once should they develop fever or other signs of infection.

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.

Drug Interactions:

Drugs such as barbiturates, phenytoin, ephedrine, and rifampin, which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of prednisolone and require that the dosage of Orapred be increased.

Increased activity of both cyclosporin and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.

Estrogens may decrease the hepatic metabolism of certain cortico-steroids thereby increasing their effect.

Ketoconazole has been reported to decrease the metabolism of certain corticosteroids by up to 60% leading to an increased risk of corticosteroid side effects.

Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

Concomitant use of aspirin (or other non-steroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia. The clearance of salicylates may be increased with concurrent use of corticosteroids.

When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., diuretics, amphotericin-B), patients should be observed closely for development of hypokalemia. Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

Due to inhibition of antibody response, patients on prolonged corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. If possible, routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued.

Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required. Corticosteroids may suppress reactions to skin tests.

Pregnancy:

Teratogenic Effects: Pregnancy Category C. Prednisolone has been shown to be teratogenic in many species when given in doses equivalent to the human dose. Animal studies in which prednisolone has been given to pregnant mice, rats, and rabbits have yielded an increased incidence of cleft palate in the offspring. There are no adequate and well controlled studies in pregnant women. Orapred should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born to mothers who have received corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Nursing Mothers:

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when Orapred is administered to a nursing woman.

Pediatric Use:

The efficacy and safety of prednisolone in the pediatric population are based on the well-established course of effect of corticosteroids which is similar in pediatric and adult populations. Published studies provide evidence of efficacy and safety in pediatric patients for the treatment of nephrotic syndrome (>2 years of age), and aggressive lymphomas and leukemias (>1 month of age). However, some of these conclusions and other indications for pediatric use of corticosteroid, e.g., severe asthma and wheezing, are based on adequate and well-controlled trials conducted in adults, on the premises that the course of the diseases and their pathophysiology are considered to be substantially similar in both populations.

The adverse effects of prednisolone in pediatric patients are similar to those in adults (see ADVERSE REACTIONS). Like adults, pediatric patients should be carefully observed with frequent measurements of blood pressure, weight, height, intraocular pressure, and clinical evaluation for the presence of infection, psychosocial disturbances, throm-boembolism, peptic ulcers, cataracts, and osteoporosis. Children who are treated with corticosteroids by any route, including systemically administered corticosteroids, may experience a decrease in their growth velocity. This negative impact of corticosteroids on growth has been observed at low systemic doses and in the absence of laboratory evidence of HPA axis suppression (i.e., cosyntropin stimulation and basal cortisol plasma levels). Growth velocity may therefore be a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of HPA axis function. The linear growth of children treated with corticosteroids by any route should be monitored, and the potential growth effects of prolonged treatment should be weighed against clinical benefits obtained and the availability of other treatment alternatives. In order to minimize the potential growth effects of corticosteroids, children should be titrated to the lowest effective dose.

Geriatric Use:

Clinical studies of prednisolone sodium phosphate oral solution did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience with prednisolone sodium phosphate has not identified differences in responses between the elderly and younger patients. However, the incidence of corticosteroid-induced side effects may be increased in geriatric patients and appear to be dose-related. Osteoporosis is the most frequently encountered complication, which occurs at a higher incidence rate in corticosteroid-treated geriatric patients as compared to younger populations and in age-matched controls. Losses of bone mineral density appear to be greatest early on in the course of treatment and may recover over time after steroid withdrawal or use of lower doses (i.e., ≤5 mg/day). Prednisolone doses of 7.5 mg/day or higher have been associated with an increased relative risk of both vertebral and nonvertebral fractures, even in the presence of higher bone density compared to patients with involutional osteoporosis.

Routine screening of geriatric patients, including regular assessments of bone mineral density and institution of fracture prevention strategies, along with regular review of Orapred indication should be undertaken to minimize complications and keep the Orapred dose at the lowest acceptable level. Co-administration of bisphosphonates has been shown to retard the rate of bone loss in corticosteroid-treated males and post-menopausal females, and these agents are recommended in the prevention and treatment of corticosteroid-induced osteoporosis.

It has been reported that equivalent weight-based doses yield higher total and unbound prednisolone plasma concentrations and reduced renal and non-renal clearance in elderly patients compared to younger populations. However, it is not clear whether dosing reductions would be necessary in elderly patients, since these pharmacokinetic alterations may be offset by age-related differences in responsiveness of target organs and/or less pronounced suppression of adrenal release of cortisol. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function (see CLINICAL PHARMACOLOGY).

Available as:
NDC 59630-710-08 8 fl oz (237 mL) bottle
NDC 59630-710-10 10 pk of 2/3 fl oz (20 mL) bottles - Institutional Pack

Dispense in tight, light-resistant glass or PET plastic containers as defined in USP.

Store refrigerated, 2-8°C (36-46°F)

Keep tightly closed and out of the reach of children.

Rx only
ORS-PI-03 Rev. 03/11

Manufactured for Shionogi, Inc.
Florham Park, NJ 07932
by Lyne Laboratories, Inc., Brockton, MA 02301

To report SUSPECTED ADVERSE EVENTS, contact Shionogi, Inc. at 1-800-849-9707 ext. 1454 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Call your doctor for instructions if you miss a dose or forget to take your medicine.

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 using Orapred. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Avoid drinking alcohol while you are taking Orapred.

Applies to prednisolone: oral liquid, oral solution, oral suspension, oral syrup, oral tablet, oral tablet disintegrating

Along with its needed effects, prednisolone (the active ingredient contained in Orapred) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking prednisolone:

• Aggression
• agitation
• anxiety
• blurred vision
• decrease in the amount of urine
• dizziness
• fast, slow, pounding, or irregular heartbeat or pulse
• headache
• irritability
• mental depression
• mood changes
• nervousness
• noisy, rattling breathing
• numbness or tingling in the arms or legs
• pounding in the ears
• shortness of breath
• swelling of the fingers, hands, feet, or lower legs
• trouble thinking, speaking, or walking
• troubled breathing at rest
• weight gain

• Abdominal cramping and/or burning (severe)
• abdominal pain
• backache
• bloody, black, or tarry stools
• cough or hoarseness
• darkening of skin
• decrease in height
• decreased vision
• diarrhea
• dry mouth
• eye pain
• eye tearing
• facial hair growth in females
• fainting
• fatigue
• fever or chills
• flushed, dry skin
• fractures
• fruit-like breath odor
• full or round face, neck, or trunk
• heartburn and/or indigestion (severe and continuous)
• increased hunger
• increased thirst
• increased urination
• loss of appetite
• loss of sexual desire or ability
• lower back or side pain
• menstrual irregularities
• muscle pain or tenderness
• muscle wasting or weakness
• nausea
• pain in back, ribs, arms, or legs
• painful or difficult urination
• skin rash
• sleeplessness
• sweating
• trouble healing
• trouble sleeping
• unexplained weight loss
• unusual tiredness or weakness
• vision changes
• vomiting
• vomiting of material that looks like coffee grounds

Some side effects of prednisolone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Increased appetite

• Abnormal fat deposits on the face, neck, and trunk
• acne
• dry scalp
• lightening of normal skin color
• red face
• reddish purple lines on the arms, face, legs, trunk, or groin
• swelling of the stomach area
• thinning of the scalp hair