Prednisone

Prednisone belongs to the pharmacological class of Corticosteroids. Prednisone appears to have anti-inflammatory Anti-neoplastic and Vasoconstrictive effects .

Prednisone had been approved for relieving symptoms as well as also for the treatment and maintenance of episodes of blood problems, arthritis, cancer, immune system problems, eye conditions, breathing problems, allergies etc.

Prednisone is completely and rapidly absorbed with oral bioavailability of 70%. Prednisone achieved a steady state volume of distribution of 29.3 L at a dose of about 0.15mg/kg and 44.2L at 0.30mg/kg dose. Prednisone can be reversibly metabolized to prednisolone and various other metabolites such as 6βhydroxy-prednisone,6α-hydroxy-prednisone, 17α,21-dihydroxy-pregnan-1,4,6-trien-3,11,30-trione, etc. Prednisone was found to be excreted in the form of urine in the form of sulfate and glucuronide conjugates.

The common side effects associated with Prednisone are irregular nausea, headache, dizziness, menstrual pain, acne, etc.

Prednisone is available in the form of oral soluble tablets and solutions. Prednisone is available in the U.S., Canada, E.U., India, Australia, and Japan.

Prednisone belongs to the pharmacological class Corticosteroids. Prednisone appears to have anti-inflammatory, Anti-neoplastic and Vasoconstrictive effects .

Prednisone binds to the glucocorticoid receptor which mediates changes in gene expression that might lead to multiple downstream effects over hours to days.

Glucocorticoids inhibit demargination and neutrophil apoptosis.They inhibit phospholipase A2, which further decreases the formation of arachidonic acid derivatives which in turn inhibits NF-Kappa B and other inflammatory transcription factors. They also promote anti-inflammatory genes like interleukin-10.

Lower doses of Prednisone provide an anti-inflammatory effect, while higher doses are said to be immunosuppressive. The High doses of glucocorticoids for an extended period binds to the mineralocorticoid receptor which in turn causes raising sodium levels and decreasing potassium levels

Prednisone had been approved for relieving symptoms as well as also for the treatment and maintenance of episodes of adrenal insufficiency ,alcoholic hepatitis,angioedema,asthma, Bell palsy ,Chronic obstructive pulmonary disease ,duchenne muscular dystrophy ,focus sedimental glomerulosclerosis, giant cell arteritis, gout, hepatitis ,immune thrombocytopenia ,inflammatory bowel disease, minimal change disease ,multiple myeloma ,myasthenia gravis ,myopathies ,pericarditis ,polymyalgia rheumatica ,prostate cancer ,takayasu arteritis ,tuberculosis ,urticaria ,warm autoimmune hemolytic anemia.

The Onset of action of Prednisone is found to be very fast within a few minutes during the acute condition and 2-20 hours during the chronic condition. and the duration of action is about 14 to 22 hrs

Prednisone can be used in the treatment of the following conditions:

• Adrenal insufficiency
• Alcoholic hepatitis
• Angioedema
• Asthma
• Bell palsy
• Chronic obstructive pulmonary disease
• Duchenne muscular dystrophy
• Focus sedimental glomerulosclerosis
• Giant cell arteritis
• Gout
• Hepatitis
• Immune thrombocytopenia
• Inflammatory bowel disease
• Minimal change disease
• Multiple myeloma
• Myasthenia gravis
• Myopathies
• Pericarditis
• Polymyalgia rheumatica
• Prostate cancer
• Takayasu arteritis
• Tuberculosis
• Urticaria
• Warm autoimmune hemolytic anemia

Prednisone is approved for use in the following clinical indications/conditions:

• Adrenal insufficiency
• Alcoholic hepatitis
• Angioedema
• Asthma
• Bell palsy
• Chronic obstructive pulmonary disease
• Duchenne muscular dystrophy
• Focus sedimental glomerulosclerosis
• Giant cell arteritis
• Gout
• Hepatitis
• Immune thrombocytopenia
• Inflammatory bowel disease
• Minimal change disease
• Multiple myeloma
• Myasthenia gravis
• Myopathies
• Pericarditis
• Polymyalgia rheumatica
• Prostate cancer
• Takayasu arteritis
• Tuberculosis
• Urticaria
• Warm autoimmune hemolytic anemia

Oral:

To be swallowed with the water as a whole as per the physician's prescription.

Oral:

Oral prednisone solution: 5 mg per 5 milliliters (mL)

Tablets: 1 mg 2.5 mg, 5 mg, 10 mg, 20 mg, 50 mg.

Delayed-release tablets: 1 mg, 2 mg, 5 mL.

Oral prednisone intensol concentrated solution: 5 mg/1 ml.

Adrenal insufficiency: 2.5 to 7.5 mg once daily

Adrenal insufficiency: Usual dosage range: 2.5 to 7.5 mg once a day.

Alcoholic hepatitis (off-label): 40 mg once a day for 28 days and then the dose is tapered down.

Angioedema: 20-60 mg once daily and then the dose is tapered down over 5 to 7 days.

Asthma: 40-60 mg once daily divided into 1 or 2 doses.

Bell palsy: (off-label use): 60 mg - 80 mg once a day for 5 days and then tapered down to 10 mg daily for 10 days.

Chronic obstructive pulmonary disease(off-label use): 40-60 mg for 5 - 14 days.

Duchenne muscular dystrophy(off-label): 0.75mg/kg/day.

Gout, treatment: 30 to 40 mg/day given once daily or in 2 divided doses.

Focal segmental glomerulosclerosis, primary (off-label use): 1 mg once daily or 2 mg every alternative day.

Hepatitis, autoimmune (off-label use): Oral: 40 to 60 mg once daily for one week followed by the tapering down of the dose to 20 mg and 10 mg.

Immune thrombocytopenia: 1 mg/kg/day for 1 or 2 weeks and then tapering down.

Inflammatory bowel disease: 40 to 60 mg once daily for seven to fourteen days, followed by a taper of up to 3 months and further tapering down to 5mg.

Minimal change disease, treatment (off-label use): Initial dose of Oral: 1 mg/kg/day a maximum: 80 mg/day once a day or 2 mg/kg alternative days

Multiple sclerosis, acute exacerbation: Oral: 625 mg to 1.25 g daily for three to seven days followed by tapering.

Myasthenia gravis, crisis (adjunctive therapy) (off-label use): 1 mg/kg/day.

Myopathies (dermatomyositis/polymyositis), treatment: 1 mg/kg/day a maximum: 80 mg/day as a single daily dose until improvement.

Pericarditis, acute or recurrent (alternative agent) (off-label use): 0.2 to 0.5 mg/kg/day until the symptoms are resolved for at least twenty-four hours and normalization of inflammatory biomarkers .

Pneumocystis pneumonia, an adjunctive therapy for moderate to severe disease (off-label use): 40 mg twice daily on days one to five beginning as early as possible,followed by tapering down the dose to 2o mg and 10 mg or 5mg.

Polymyalgia rheumatica:Initial: Usual dose of 15 mg/day in a single daily dose or in an divided doses or consider lower initial doses of about 7.5 to 10 mg/day for smaller patients having mild symptoms or at high risk for side effects.

Takayasu arteritis (off-label use): Oral: Initial dose of 40 to 60 mg daily in combination with the appropriate steroid-sparing agent followed by gradually tapering to the lowest effective dose.

Thyroiditis, subacute (off-label use): Initial dose of 40 mg/day for one to two weeks; gradually tapered eg, by 5 to 10 mg/day every five to seven days, which is based on clinical response.

Tuberculosis pulmonary (off-label): 40 mg once a day for fourteen days, followed by 20 mg once daily for fourteen days

Urticaria, chronic spontaneous, acute exacerbation (off-label use): 35 to 40 mg once a day until symptoms are controlled usually occurs after two to three days of therapy.

Warm autoimmune hemolytic anemia: Oral dose of 1 to 2 mg/kg/day until a hemoglobin response had occurred, typically within one to three weeks.

Ophthalmic, Oral.

• Dosage Adjustments in Pediatric Patients:

In infants and children who are less than 12 years of age suffering from asthma, the dose of 1 to 2 mg/kg/day PO in 2 divided doses until the peak expiratory flow is about 70% of predicted or personal best. A 3 to 5-day course is usually a sufficient maximum of about 60 mg/day. A dose of 1 mg/kg/day PO had been shown to be just as effective as a dose of 2 mg/kg/day with lesser adverse effects, and this dose might be preferable. Another source recommends the following Max doses of 20 mg/day of Prednisolone in children less than two years, 30 mg/day of Prednisolone in children aged 3 to 5 years, and 40 mg/day of Prednisolone in children aged 6 to 11 years.

In the condition of bell palsy, the dosage of 2-4mg/kg/day is to be administered three or four times a day.

In the condition of Juvenile idiopathic arthritis, 1mg/kg/day is to be administered every day along with methylprednisolone.

In the condition of Dermatomyositis, juvenile 1-2mg/kg/day is recommended every day.

Smoking cessation and maintaining health is a must.

Caffeine should be avoided or limited to use as it might lead to the risk of nausea, palpitations, nervousness, rapid heartbeat, etc.

Alcohol should be avoided in the patient, especially with an underlying liver disorder or liver dysfunction.

A diet containing food with high sugar content and carbohydrates should be restricted. This includes pies, cakes, honey, cookies, jams, candies, chips, and bread. It is also advised to reduce or limit the intake of cholesterol and saturated fat and instead chooses poultry, lean meat, or fish.

The dietary restrictions need to be individualized as per the patient's requirements.

Prednisone may be contraindicated under the following conditions:

• Hypersensitivity to the ingredients of the medication. Rare instances of anaphylactoid reactions have been found to have occurred in patients receiving corticosteroid therapy.

The treating physician should closely monitor the patients and keep pharmacovigilance as follows:

Behavioral and Mood Disturbances

Corticosteroid use might be associated with central nervous system effects ranging from personality changes, euphoria, insomnia, mood swings, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies might be aggravated by corticosteroids.

Decrease in Bone Density

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation which is decreasing absorption and increasing excretion and also by the inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone secondary to an increase in protein catabolism, as well as reduced sex hormone production, might lead to the inhibition of bone growth in children and adolescents and also the development of osteoporosis at any age. Special consideration should be given to patients who are at an increased risk of osteoporosis such as postmenopausal women before initiating corticosteroid therapy, bone density should be monitored in patients who are on long-term corticosteroid therapy.

Ophthalmic Effects

Prolonged use of corticosteroids might produce posterior subcapsular cataracts and glaucoma with possible damage to the optic nerves and might enhance the establishment of secondary ocular infections caused due to fungi or viruses. The use of oral Prednisone is not recommended in the treatment of optic neuritis and might lead to an increased risk of new episodes. Intraocular pressure might become elevated in some individuals. In case steroid therapy is continued for more than 6 weeks Herpes Simplex Corticosteroids should be used with caution in patients with ocular herpes simplex because of possible corneal perforation. Corticosteroids should not be given or used in active ocular herpes simplex.

Vaccination

The Administration of live or live attenuated vaccines is found to be contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines might be administered; however, the response to such vaccines can be predicted. Immunization procedures might be undertaken in patients who are receiving corticosteroids as replacement therapy such as for Addison's disease. While on corticosteroid therapy, it is advised that patients should not be vaccinated against smallpox. Any other immunization procedures should not be undertaken in patients who are on corticosteroids, especially those on high dose, as it might lead to possible hazards of neurological complications and a lack of antibody response.

Effect on Growth and Development

Long-term use of corticosteroids might have negative effects on growth and development in children. Hence it is advised that growth and development of pediatric patients on prolonged corticosteroid therapy should be carefully monitored.

Alterations in Endocrine Function

Cushing's syndrome, Hypothalamic-pituitary-adrenal (HPA) axis suppression, and hyperglycemia. It is advised that patients should be monitored for these conditions with chronic use. Corticosteroids might produce reversible Hypothalamic-pituitary-adrenal axis suppression with the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Drug-induced secondary adrenocortical insufficiency might be minimized by gradual reduction of dosage. This type of relative insufficiency might persist for many months after discontinuation of therapy. Therefore, in any situation of stress occurring during that period, it is advised that hormone therapy should be reinstituted.

Alterations in Cardiovascular/Renal Function

Corticosteroids can cause an increase in salt, blood pressure, and water retention, and increased excretion of potassium and calcium. These effects are found to be less likely to occur while using synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation might be necessary. Such agents should be used cautiously in patients with renal insufficiency, hypertension, congestive heart failure.Reports suggest an association between concomitant use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction.Therefore, therapy with corticosteroids should be used cautiously in these patients

Use in Patients with Gastrointestinal Disorders

There is said to be an increased risk of gastrointestinal (GI) perforation in patients suffering from certain gastrointestinal disorders. Signs of gastrointestinal perforation, including peritoneal irritation, might be masked in patients receiving corticosteroids. Corticosteroids should be used cautiously if there is a probability of abscess, impending perforation, or other fresh intestinal anastomoses; pyogenic infections; diverticulitis; active or latent peptic ulcer, etc.

Avoid alcohol usage while on Prednisone medication as alcohol can worsen the effects of any underlying disease condition, including conditions such as dizziness, blurred vision etc.

Prednisone is found to be secreted in human milk. Reports suggest that Prednisone concentrations in human milk are about 5 to 25% of maternal serum levels, and that total infant daily doses are as small, about 0.14% of the maternal daily dose. Therefore, caution should be exercised when Prednisone is administered to a nursing woman. High doses of corticosteroids for a long period could potentially produce problems in infant development and growth and interfere with endogenous corticosteroid production. If Prednisone is to be prescribed to a breastfeeding mother, the very lowest dose should be prescribed to achieve the desired clinical effect.

Pregnancy Category D

Prednisone has not been formally evaluated in clinical or nonclinical studies for its effects on pregnancy and fetal development. Multiple cohorts and case-controlled studies in humans suggested that maternal corticosteroid use during the first trimester causes an increase in the incidence of cleft lip with or without cleft palate from around 1/1000 infants to 3-5/1000 infants. 2 prospective case-control studies had shown that decreased birth weight in infants when exposed to maternal corticosteroids in the uterus. Prednisone should be prescribed and used during pregnancy only when the potential benefits outweigh the potential risks associated with the fetus. Published literature indicated that Prednisone has been shown to be teratogenic in animal studies such as hamsters, rats, rabbits, and mice with increased incidence of cleft palate in offspring have been reported in the clinical data. In teratogenicity studies, cleft palate along with an elevated fetal lethality and reductions in fetal body weight had been seen in rats at maternal doses of 30 mg/kg which is equivalent to 290 mg in a 60 kg individual based on mg/m2 body surface comparison and higher. Cleft palate had been observed in mice at a maternal dose of 20 mg/kg which is equivalent to 100 mg in a 60 kg individual based on an mg/m2 comparison. Additionally, constriction of the ductus arteriosus had been observed in the clinical studies in the fetuses of pregnant rats exposed to Prednisone.

No sufficient scientific evidence traceable regarding the use and safety of Prednisone in concurrent use with any particular food.

The adverse reactions related to Prednisone can be categorized as:

Common

• Muscle pain or weakness
• Stomach discomfort, bloating
• Changes in your menstrual periods
• Headache
• Fluid retention
• Dizziness
• Spinning sensation

Rare

• Painful or difficult urination
• Skin rash
• Sleeplessness
• Sweating
• Trouble healing
• Trouble sleeping
• Unexplained weight loss
• Unusual tiredness or weakness
• Vision changes
• Vomiting
• 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

The clinically relevant drug interactions of Prednisone is briefly summarized here:

• Aminoglutethimide: Aminoglutethimide might lead to a loss of corticosteroid-induced adrenal suppression.

• Amphotericin B: There had been cases reported in which concomitant use of Amphotericin B with Prednisone caused cardiac enlargement and congestive heart failure.

• Anticholinesterase agents: Concomitant use of anticholinesterase agents and corticosteroids might produce severe weakness in patients suffering from myasthenia gravis. It is advised that anticholinesterase agents should be withdrawn at least 24 hours before initiating the corticosteroid therapy.

• Anticoagulant agents: Co-administration of corticosteroids with warfarin usually resulted in inhibition of response to warfarin, although there had been some conflicting reports. Therefore, it is advised that coagulation indices should be monitored frequently to maintain the desired anticoagulant effect.

• Antidiabetic Agents: As corticosteroids might increase blood glucose concentrations, dosage adjustments of antidiabetic agents might be required.

• Antitubercular drugs: Serum concentrations of isoniazid might be decreased with the concomitant use of corticosteroids.

• CYP 3A4 inducers e.g.carbamazepine, barbiturates, phenytoin, and rifampin: Drugs such as ephedrine, barbiturates, phenytoin,and rifampin, which induces hepatic microsomal drug metabolizing enzyme activity might enhance metabolism of Prednisone and requires that the dosage of Prednisone be increased.

• CYP 3A4 inhibitors, e.g., macrolide antibiotics, ketoconazole: Ketoconazole had been reported to decrease the metabolism of certain corticosteroids by up to 60% causing an increased risk of corticosteroid side effects.

• Cholestyramine: Cholestyramine might cause an increase in the clearance of corticosteroids.

• Cyclosporine: An Increased activity of both cyclosporine and corticosteroids might occur when the both are used concurrently. Convulsions had been reported with this concurrent use with corticosteroids.

• Digitalis: Patients on digitalis glycosides might be at increased risk of arrhythmias due to condition called as hypokalemia.

• Estrogens, including oral contraceptives: Estrogens might decrease the hepatic metabolism of certain corticosteroids, thereby causing increase in their effect.

• NSAIDS, including aspirin and salicylates: Coadministration of use of aspirin or other non-steroidal anti-inflammatory agents with corticosteroids causes an increase in the risk of gastrointestinal side effects. Aspirin should be used cautiously along with corticosteroids in hypoprothrombinemia. The clearance of salicylates might be increased with concurrent use of corticosteroids.

• Potassium-depleting agents such as diuretics, Amphotericin B: When corticosteroids are administered along with potassium-depleting agents, patients should be observed closely for development conditions called as of hypokalemia.

• Skin Tests: Corticosteroids might suppress reactions to the skin tests.

• Toxoids as well as live or inactivated Vaccines: Due to inhibition of antibody response, the patients who are on prolonged corticosteroid therapy might exhibit a reduced response to toxoids and live or inactivated vaccines. Corticosteroids might also potentiate the replication of some organisms contained in live attenuated vaccines.

The common side effects of Prednisone include the following:

• Nausea
• Heartburn
• Headache
• Dizziness
• Menstrual period changes
• Trouble sleeping
• Increased sweating
• Acne

Pregnancy

Pregnancy Category D

Prednisone has not been formally evaluated in clinical or nonclinical studies for effects on pregnancy and fetal development. Multiple cohort as well as case controlled studies in humans suggested that maternal corticosteroid use during the first trimester causes increase in the incidence of cleft lip with or without cleft palate from around 1/1000 infants to 3-5/1000 infants. 2 prospective case control studies had shown that decreased birth weight in infants when exposed to maternal corticosteroids in uterus. Prednisone should be prescribed and used during pregnancy only when the potential benefits outweigh the potential risks associated with the fetus. Published literature indicated that Prednisone has been shown to be teratogenic in animal studies such as hamsters, rats, rabbits, and mice with increased incidence of cleft palate in offspring has been reported in the clinical data. In teratogenicity studies, the formation of cleft palate along with an elevated fetal lethality and reductions in fetal body weight had been seen in rats at maternal doses of 30 mg/kg which is equivalent to 290 mg in a 60 kg individual based on mg/m2 body surface comparison and higher. Cleft palate had been observed in mice at a maternal dose of 20 mg/kg which is equivalent to 100 mg in a 60 kg individual based on an mg/m2 comparison. Additionally, constriction of the ductus arteriosus had been observed in the clinical studies in the fetuses of pregnant rats exposed to Prednisone.

Nursing Mothers

Prednisone is found to be secreted in human milk. Reports suggest that Prednisone concentrations in human milk are about 5 to 25% of maternal serum levels as well as that total infant daily doses are as small, about 0.14% of the maternal daily dose. Therefore, caution should be exercised when Prednisone is administered to a nursing woman. High doses of corticosteroids for a long period could potentially produce problems in infant development and growth and interfere with endogenous corticosteroid production. If Prednisone is to be prescribed to a breastfeeding mother, the very lowest dose should be prescribed and used to achieve the desired clinical effect.

Pediatric Use

The safety and efficacy of Prednisone in the pediatric population are based on the well-established study of the effect of corticosteroids, which is found to be similar in pediatric and adult populations. Published studies provide evidence of safety and efficacy in pediatric patients for the treatment of nephrotic syndrome in >2 years of age, and aggressive lymphomas and leukemias in >1 month of age. The adverse effects of Prednisone in pediatric patients are found to be similar to those in adults.

Geriatric Use

Physicians should be knowledgeable and vigilant about the treatment pertaining to the treatment and identification of overdosage of Prednisone.

The adverse effects of accidental ingestion of large quantities of Prednisone in a very short period of time had not been reported, but prolonged use of the drug can produce thinning scalp hair, increased blood pressure, tachycardia, thrombophlebitis, hypertrichosis, acne, striae, ecchymosis, increased sweating, pigmentation, hypokalemia,fluid retention, excessive appetite,mental symptoms, moon face, abnormal fat deposits, weight gain, dry scaly skin,and adrenal insufficiency, etc. Hepatomegaly and abdominal distention had been observed in children.

Treatment of acute overdosage is done by immediate gastric lavage or emesis followed by a symptomatic and suppporative therapy. For chronic overdosage in the face of severe disease which requires continuous steroid therapy, the dosage of Prednisone might be reduced only temporarily, or alternate day treatment might be introduced.

Pharmacodynamics

Corticosteroids are said to bind to the glucocorticoid receptor, inhibiting the pro-inflammatory signals, and thereby promoting anti-inflammatory signals. Prednisone is said to have a short duration of action as the half life is about 2.1-3.5 hours. Corticosteroids are found to have a wide therapeutic window as patients might require doses that are multiples of what the body can produce naturally. Patients who are taking corticosteroids should be counseled regarding the risk of hypothalamic-pituitary-adrenal axis suppression as well as increased susceptibility to infections.

Pharmacokinetics

• Absorption

Oral prednisone has been found to have a Tmax of 2 hours.The delayed-release formulation has been found to have a Tmax of 6-6.5 hours. A 5mg dose of prednisone achieved an AUC of 572mL/min/1.73m2, while a 20mg dose of prednisone achieved an AUC of 1034mL/min/1.73m2, and a 50mg dose of prednisone achieved an AUC of 2271mL/min/1.73m2.5 The data reports regarding the Cmax of prednisone is not available

• Distribution

A 0.15mg/kg dose of Prednisone had been found to have achieved a volume of distribution of 29.3L, while 0.30mg/kg dose of Prednisone had been found to have achieved a volume of distribution of 44.2L.

• Metabolism

Prednisone has been reported to be metabolized mainly in the liver and is excreted in the urine as sulfate and glucuronide conjugates. Prednisone is found to be reversibly metabolized to prednisolone which is then metabolized to 6βhydroxy-prednisone (M-XII), 6α-hydroxy-prednisone (M-XIII), 17α,21-dihydroxy-pregnan-1,4,6-trien-3,11,30-trione (M-XVII), 20α-dihydro-prednisone (M-V), or 20β-dihydro-prednisone (M-IV).

• Elimination

Prednisone was found to be eliminated in the form of urine as sulfates and glucoronide conjugates.

1. https://go.drugbank.com/drugs/DB00635
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202020s000lbl.pdf
3. https://www.drugs.com/prednisone.html
4. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=10fe5a3b-84dc-4600-87c2-b80c97ce18cf
5. https://cdn.brief.vet/web-files/PVD/drupal-uploads/files/VMG-Prednisolone-Prednisone-2019-01-30-1259.pdf
6. https://docs.boehringer-ingelheim.com/Prescribing Information/PIs/Roxane/Prednisone Reformulated/PredniSONEReform.pdf
7. https://www.singlecare.com/prescription/prednisone/dosage