Side Effects of Orapred (prednisolone)

Orapred ODT (prednisolone orally disintegrating tablets) are a corticosteroid used to treat inflammation due to inflammatory and allergic conditions, for example,

• rheumatoid arthritis,
• lupus,
• gout,
• ulcerative colitis,
• Crohn's disease,
• hay fever,
• types of dermatitis,
• asthma,
• bronchitis,
• allergic or inflammatory conditions of the nose and eyes, and
• many others.

Corticosteroids are natural substances produced by the adrenal glands located adjacent to the kidneys. 

Common side effects of Orapred ODT include

• fluid retention,
• weight gain,
• high blood pressure,
• potassium loss,
• headache,
• muscle weakness,
• puffiness of face,
• hair growth on the face,
• thinning and easy bruising of the skin, and
• irregular menstrual periods.

Serious side effects of Orapred ODT include

• glaucoma,
• cataracts,
• peptic ulcers,
• worsening of diabetes,
• growth retardation in children,
• convulsions, and
• psychic disturbances (such as depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior).

Drug interactions of Orapred ODT include rifampin, which decreases blood levels of Orapred ODT by increasing its breakdown in the liver.

• Corticosteroids have variable effects of warfarin therapy.
• Estrogens may increase the levels of Orapred ODT by decreasing its breakdown.
• Steroids such as Orapred ODT increase blood sugar (glucose) levels and, therefore, reduce the effect of drugs used for treating diabetes.
• Activity of cyclosporine and corticosteroids increase when both drugs are combined. Seizures have been reported.
• Combining aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) and Orapred ODT increases the risk of gastrointestinal side effects.
• Combining Orapred ODT with potassium-depleting agents (for example, diuretics) increases the risk of low blood potassium (hypokalemia).
• Vaccines are less effective in patients on prolonged corticosteroid treatment because corticosteroids suppress the immune system.

Orapred ODT can cause fetal harm when administered to a pregnant woman. Use of corticosteroids during the first trimester of pregnancy is associated with an increased risk of orofacial clefts, intrauterine growth restriction and decreased birth weight.

Orapred ODT is secreted in breast milk. Caution should be exercised when prednisolone is Orapred ODT to a breastfeeding woman. 

Prednisolone side effects depend on the dose, the duration and the frequency of administration.

• Short courses of prednisolone - days to a week or two - are usually well tolerated with few and mild side effects.
• Long-term, high doses of prednisolone will usually produce predictable and potentially serious side effects.
• Whenever possible, the lowest effective doses of prednisolone should be used for the shortest length of time to minimize side effects. Alternate day dosing can also help reduce side effects.

Side effects of prednisolone and other corticosteroids range from mild annoyances to serious irreversible damage. Side effects include

• fluid retention,
• weight gain,
• high blood pressure,
• potassium loss,
• headache,
• muscle weakness,
• puffiness of and hair growth on the face,
• thinning and easy bruising of the skin,
• glaucoma,
• cataracts,
• peptic ulceration,
• worsening of diabetes,
• irregular menses,
• growth retardation in children,
• convulsions, and
• psychic disturbances. (Psychic disturbances can include depression, euphoria, insomnia, mood swings, personality changes, and even psychotic behavior.)

Prolonged use of prednisolone can depress the ability of body's adrenal glands to produce corticosteroids.

• Abruptly stopping prednisolone can cause symptoms of corticosteroid insufficiency, with accompanying nausea, vomiting, and even shock.
• Therefore, withdrawal of prednisolone is usually accomplished by gradual tapering.
• Gradually tapering prednisolone not only minimizes the symptoms of corticosteroid insufficiency, but it also reduces the risk of an abrupt flare of the disease under treatment.

Prednisolone and other corticosteroids can mask signs of infection and impair the body's natural immune response to infection. Patients on corticosteroids are more susceptible to infections and can develop more serious infections than healthy individuals.

• For instance, chickenpox and measles viruses can produce serious and even fatal illnesses in patients on high doses of prednisolone.
• Live virus vaccines, such as smallpox vaccine, should be avoided in patients taking high doses of prednisolone, since even vaccine viruses may cause disease in patients taking prednisolone.
• Some infectious organisms, such as tuberculosis (TB) and malaria, can remain dormant in a patient for years.
• Prednisolone and other corticosteroids can reactivate dormant infections in these patients and cause serious illnesses.
• Patients with dormant TB may require anti-TB medications while undergoing prolonged corticosteroid treatment.

By interfering with the patient's immune response, prednisolone can impede the effectiveness of vaccinations. Prednisolone can also interfere with the tuberculin skin test and cause false negative results in patients with tuberculosis infection.

• Prednisolone impairs calcium absorption and new bone formation.
• Patients on prolonged treatment with prednisolone and other corticosteroids can develop thinning of bone (osteoporosis) and an increased risk of bone fractures.
• Supplemental calcium and vitamin D are encouraged to slow this process of bone thinning.

In some patients, medications used to treat osteoporosis may be prescribed. In rare individuals, destruction of large joints (osteonecrosis) can occur while undergoing treatment with prednisolone or other corticosteroids.

These patients experience severe pain in the involved joints, and can require replacement of joints. The reason behind such destruction is not clear.

Common adverse reactions for corticosteroids include

• fluid retention,
• alteration in glucose tolerance,
• elevation in blood pressure,
• behavioral and mood changes,
• increased appetite and
• weight gain.

Allergic Reactions: Anaphylactoid reaction, anaphylaxis, angioedema

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis

Dermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scalp, edema, facial erythema, hyper or hypo-pigmentation, impaired wound healing, increased sweating, petechiae and ecchymoses, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria

Endocrine: Abnormal fat deposits, decreased carbohydrate tolerance, development of Cushingoid state, hirsutism, manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics, menstrual irregularities, moon facies, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness), suppression of growth in children

Fluid and Electrolyte Disturbances: Fluid retention, potassium loss, hypertension, hypokalemic alkalosis, sodium retention

Gastrointestinal: Abdominal distention; elevation in serum liver enzyme levels (usually reversible upon discontinuation); hepatomegaly, hiccups, malaise, nausea, pancreatitis; peptic ulcer with possible perforation and hemorrhage; ulcerative esophagitis

General: Increased appetite and weight gain

Metabolic: Negative nitrogen balance due to protein catabolism

Musculoskeletal: Aseptic necrosis of femoral and humeral heads; charcot-like arthropathy, loss of muscle mass; muscle weakness; osteoporosis; pathologic fracture of long bones; steroid myopathy; tendon rupture; vertebral compression fractures

Neurological: Arachnoiditis, convulsions; depression, emotional instability, euphoria, headache; increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment; insomnia, meningitis, mood swings, neuritis, neuropathy, paraparesis/ paraplegia, paresthesia, personality changes, sensory disturbances, vertigo

Ophthalmic: Exophthalmos; glaucoma; increased intraocular pressure; posterior subcapsular cataracts

Reproductive: Alteration in motility and number of spermatozoa

Postmarketing Experience

Adverse reactions have been identified during post approval use of Orapred ODT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The postmarketing experience has not raised new safety concerns beyond those already established for immediate-release prednisolone.

Aminoglutethimide

Aminoglutethimide may lead to loss of corticosteroid-induced adrenal suppression.

Amphotericin B

There have been cases reported in which concomitant use of Amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure (see also Potassium depleting agents).

Anticholinesterase agents

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.

Anticoagulant Agents

Co-administration 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.

Antidiabetic Agents

Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.

Antitubercular Drugs

Serum concentrations of isoniazid may be decreased.

CYP 3A4 Inducers (E.g. Barbiturates, Phenytoin, Carbamazepine, And Rifampin)

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.

CYP 3A4 Inhibitors (E.g., Ketoconazole, Macrolide Antibiotics)

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

Cholestyramine

Cholestyramine may increase the clearance of corticosteroids.

Cyclosporine

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

Digitalis

Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia.

Estrogens, Including Oral Contraceptives

Estrogens may decrease the hepatic metabolism of certain corticosteroids thereby increasing their effect.

NSAIDS, Including Aspirin And Salicylates

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.

Potassium-Depleting Agents (E.g., Diuretics, Amphotericin B)

When corticosteroids are administered concomitantly with potassium-depleting agents, patients should be observed closely for development of hypokalemia.

Skin Tests

Corticosteroids may suppress reactions to skin tests.

Toxoids And Live Or Inactivated Vaccines

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.