Side Effects of Rayos (prednisone)

Rayos (prednisone) is a corticosteroid used to treat a wide variety of conditions including

• arthritis,
• ulcerative colitis,
• Crohn's disease,
• systemic lupus,
• allergic reactions,
• asthma,
• severe psoriasis,
• leukemias,
• lymphomas,
• idiopathic thrombocytopenic purpura,
• autoimmune hemolytic anemia,
• bronchitis, to prevent the body from rejecting transplanted organs, and
• as replacement therapy in patients whose adrenal glands are unable to produce sufficient amounts of cortisol.

Synthetic corticosteroids mimic the action of cortisol (hydrocortisone), the naturally-occurring corticosteroid produced in the body by the adrenal glands. Corticosteroids have many effects on the body, but they most often are used for their potent anti-inflammatory effects, particularly in those diseases and conditions in which the immune system plays an important role.

Prednisone is inactive in the body and, in order to be effective, first must be converted to prednisolone by enzymes in the liver. Therefore, prednisone may not work as effectively in people with liver disease whose ability to convert prednisone to prednisolone is impaired. 

Common side effects of Rayos include

• retention of sodium and fluid,
• weight gain,
• high blood pressure,
• loss of potassium,
• headache,
• muscle weakness,
• nausea,
• vomiting,
• acne,
• thinning skin,
• restlessness, and
• problems sleeping.

Serious side effects of Rayos include

• hiccups,
• puffiness of the face (moon face),
• growth of facial hair,
• thinning and easy bruising of the skin,
• impaired wound healing,
• glaucoma,
• cataracts,
• ulcers,
• worsening of diabetes,
• irregular menses,
• rounding of the upper back ("buffalo hump"),
• obesity, growth retardation in children,
• convulsions,
• anaphylaxis (severe allergic reactions like hives, itching, skin rash, swollen lips/tongue/face),
• vision changes,
• congestive heart failure,
• heart attack,
• pulmonary edema,
• fainting,
• fast heart rate,
• thrombophlebitis,
• vasculitis,
• allergic dermatitis,
• low blood pressure,
• missed menstrual periods,
• new-onset diabetes,
• high blood sugar (hyperglycemia),
• hypothyroidism,
• pancreatitis,
• anemia,
• amnesia, and
• psychiatric disturbances (depression, euphoria, insomnia, mood swings, personality changes, and psychotic behavior).

Drug interactions of Rayos include estrogens and phenytoin.

• Estrogens may reduce the action of enzymes in the liver that break down the active form of Rayos, prednisolone. As a result, the levels of prednisolone in the body may increase and lead to more frequent side effects.
• Phenytoin increases the activity of enzymes in the liver that break down Rayos and thereby may reduce the effectiveness of Rayos.
• The risk of high potassium levels in the blood increases when corticosteroids are combined with drugs that reduce potassium levels (for example, amphotericin B, diuretics), leading to serious side effects such as heart enlargement, heart arrhythmias and congestive heart failure.
• Corticosteroids may increase or decrease the response warfarin.
• The response to diabetes drugs may be reduced because Rayos increases blood glucose.
• Rayos may increase the risk of tendon rupture in patients treated with fluoroquinolone type antibiotics.
• Combining aspirin, ibuprofen, or other nonsteroidal anti-inflammatory drugs (NSAIDs) with corticosteroids increases the risk of stomach related side effects like ulcers.
• Barbiturates, carbamazepine, rifampin and other drugs that increase the activity of liver enzymes that breakdown Rayos may reduce blood levels of prednisone.
• Conversely, ketoconazole, itraconazole, ritonavir, indinavir, macrolide antibiotics, and other drugs that reduce the activity of liver enzymes that breakdown prednisone may increase blood levels of Rayos.

Corticosteroids cross the placenta into the fetus. Compared to other corticosteroids, however, Rayos is less likely to cross the placenta. Chronic use of corticosteroids during the first trimester of pregnancy may cause cleft palate.

Corticosteroids are secreted in breast milk and can cause side effects in the nursing infant. Rayos is less likely than other corticosteroids to be secreted in breast milk, but it may still pose a risk to the infant. Consult your doctor before breastfeeding.

Side effects of prednisone and other corticosteroids range from mild annoyances to serious, irreversible organ damage, and they occur more frequently with higher doses and more prolonged treatment.

Common side effects include:

• Retention of sodium (salt) and fluid
• Weight gain
• High blood pressure
• Loss of potassium
• Headache
• Muscle weakness
• Nausea
• Vomiting
• Acne
• Thinning skin
• Restlessness
• Problems sleeping

Serious side effects include:

• Hiccups
• Puffiness of the face (moon face)
• Growth of facial hair
• Thinning and easy bruising of the skin
• Impaired wound healing
• Glaucoma
• Cataracts
• Ulcers in the stomach and duodenum
• Worsening of diabetes
• Irregular menses
• Rounding of the upper back ("buffalo hump")
• Obesity
• Retardation of growth in children
• Convulsions
• Anaphylaxis (severe allergic reactions like hives, itching, skin rash, swollen lips/tongue/face)
• Vision changes
• Congestive heart failure
• Heart attack
• Pulmonary edema
• Syncope
• Tachycardia
• Thrombophlebitis
• Vasculitis
• Allergic dermatitis
• Low blood pressure
• Amenorrhea (lack of menstruation)
• Newly onset diabetes
• Hyperglycemia
• Hypothyroidism
• Pancreatitis
• Anemia
• Amnesia

This drug also causes psychiatric disturbances, which include:

• Depression
• Euphoria
• Insomnia
• Mood swings
• Personality changes
• Psychotic behavior

Other possible serious side effects of this drug include:

Prednisone and diabetes: Prednisone is associated with new onset or manifestations of latent diabetes, and worsening of diabetes. Diabetics may require higher doses of diabetes medications while taking prednisone.

Allergic reaction: Some people may develop a severe allergic reaction (anaphylaxis) to prednisone that includes swelling of the airways (angioedema) that may result in shortness of breath or airway blockage.

Immune suppression: Prednisone suppresses the immune system and, therefore, increases the frequency or severity of infections and decreases the effectiveness of vaccines and antibiotics.

Osteoporosis: Prednisone may cause osteoporosis that results in fractures of bones. Patients taking long-term prednisone often receive supplements of calcium and vitamin D to counteract the effects on bones. Calcium and vitamin D probably are not enough, however, and treatment with bisphosphonates such as alendronate (Fosamax) and risedronate (Actonel) may be necessary. Calcitonin (Miacalcin) also is effective. The development of osteoporosis and the need for treatment can be monitored using bone density scans.

Adrenal insufficiency and weaning off prednisone: Prolonged use of prednisone and other corticosteroids causes the adrenal glands to atrophy (shrink) and stop producing the body's natural corticosteroid, cortisol.

Necrosis of hips and joints: A serious complication of long-term use of corticosteroids is aseptic necrosis of the hip joints. Aseptic necrosis is a condition in which there is death and degeneration of the hip bone. It is a painful condition that ultimately can lead to the need for surgical replacement of the hip. Aseptic necrosis also has been reported in the knee joints. The estimated incidence of aseptic necrosis among long-term users of corticosteroids is 3%-4%. Patients taking corticosteroids who develop pain in the hips or knees should report the pain to their doctors promptly.

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: 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 enzymes 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: Osteonecrosis 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 (pseudo-tumor 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, and central serous chorioretinopathy

Reproductive: Alteration in motility and number of spermatozoa

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Rayos was evaluated in 375 rheumatoid arthritis patients in two controlled trials. Patients treated with Rayos ranged in age from 20 to 80 years (median age 56 years), with 85% female, 99% Caucasian, 1% African-American, and < 1% Asian.

Patients received Rayos 3 mg to 10 mg once daily at 10 pm; the majority (84%) received ≥ 5 mg. The clinical trial experience did not raise new safety concerns beyond those already established for immediate-release prednisone.

Postmarketing Experience

Adverse reactions have been identified during post-approval use of Rayos. 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 prednisone.

Aminoglutehimide

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

Amphotericin B Injection

There have been cases reported in which concomitant use of Amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

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 the metabolism of corticosteroids and require that the dosage of the corticosteroid 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 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.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) Including Aspirin and Salicylates

Concomitant use of aspirin or other nonsteroidal anti-inflammatory drugs 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; this could lead to decreased salicylate serum levels or increase the risk of salicylate toxicity when corticosteroid is withdrawn.

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 Attenuated Vaccines

Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. Routine administration of vaccines or toxoids should be deferred until corticosteroid therapy is discontinued if possible.