Prednisolone

S01B - Antiinflammatory agents ATC H02AB06 Small molecule approved 1955 Oral Topical Natural product

JFDA label: Prednisolone Tablets

Mechanism of Action

Agonist of Glucocorticoid receptor — Glucocorticoid receptor agonist

Target	Action	Gene / class
Glucocorticoid receptor efficacy	AGONIST	NR3C1

Indications

Approved

Addison Disease — primary adrenal insufficiency
Adrenal Hyperplasia, Congenital — classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency
Anemia, Aplastic — Aplastic anemia
Anemia, Hemolytic — hemolytic anemia
Arthritis, Gouty — gout
Arthritis, Juvenile — juvenile idiopathic arthritis
Arthritis, Psoriatic — psoriatic arthritis
Arthritis, Rheumatoid — rheumatoid arthritis
Asthma — asthma
Bursitis — frozen shoulder
Chorioretinitis — Chorioretinitis
Choroiditis — choroiditis
Colitis, Ulcerative — ulcerative colitis
Conjunctivitis, Allergic — allergic conjunctivitis
Crohn Disease — Crohn's disease
Dermatitis Herpetiformis — dermatitis herpetiformis
Dermatitis, Atopic — atopic eczema
Dermatitis, Contact — contact dermatitis
Dermatitis, Exfoliative — exfoliative dermatitis
Dermatitis, Seborrheic — seborrheic dermatitis
Dermatomyositis — dermatomyositis
Erythema Multiforme — erythema multiforme
Eye Diseases — eye inflammation
Hemorrhoids — hemorrhoid
Herpes Zoster Ophthalmicus — ophthalmic herpes zoster
Hypercalcemia — Hypercalcemia
Iridocyclitis — Iridocyclitis
Iritis — iritis
Keratitis — keratitis
Leukemia — leukemia
Lupus Erythematosus, Systemic — systemic lupus erythematosus
Lymphoma — lymphoma
Multiple Sclerosis — multiple sclerosis
Mycosis Fungoides — mycosis fungoides
Myocarditis — myocarditis
Nasal Obstruction — Nasal congestion
Nephrotic Syndrome — nephrotic syndrome
Ophthalmia, Sympathetic — sympathetic ophthalmia
Optic Neuritis — optic neuritis
Osteoarthritis — osteoarthritis
Peptic Ulcer — Peptic ulcer
Pneumonia — pneumonia
Psoriasis — psoriasis
Pulmonary Eosinophilia — eosinophilic pneumonia
Rhinitis, Allergic, Seasonal — allergic rhinitis
Sarcoidosis — sarcoidosis
Serum Sickness — type III hypersensitivity reaction disease
Spondylitis, Ankylosing — ankylosing spondylitis
Synovitis — synovitis
Tennis Elbow — epicondylitis
Tenosynovitis — tenosynovitis
Thrombocytopenia — Thrombocytopenia
Thyroiditis, Subacute — subacute thyroiditis
Trichinellosis — trichinosis
Tuberculosis, Meningeal — meningeal tuberculosis
Tuberculosis, Pulmonary — pulmonary tuberculosis
Uveitis, Posterior — posterior uveitis

Off-label

Abortion, Habitual
Adrenal Insufficiency
Alveolitis, Extrinsic Allergic
Anemia, Hemolytic, Autoimmune
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Aspergillosis, Allergic Bronchopulmonary
Biliary Atresia
Breast Neoplasms
Bronchiolitis Obliterans Syndrome
Carcinoma, Hepatocellular
Cardiomyopathies
Cataract
Celiac Disease
Churg-Strauss Syndrome
Colitis
Croup
Diabetes Mellitus, Type 2
Eczema
Endocardial Cushion Defects
Eye Infections
Giant Cell Arteritis
Glaucoma
Glaucoma, Open-Angle
Glomerulonephritis
Glomerulonephritis, IGA
Glomerulonephritis, Membranous
Glomerulosclerosis, Focal Segmental
Graft vs Host Disease
Granulomatosis with Polyangiitis
Graves Disease
HIV Infections
Headache
Hearing Loss, Sensorineural
Hemangioma
Hepatitis, Alcoholic
Hodgkin Disease
Hypereosinophilic Syndrome
Hyperlipoproteinemia Type I
Hypersensitivity
Hyperthyroidism
Idiopathic Pulmonary Fibrosis
Immunoblastic Lymphadenopathy
Infections
Infertility
Inflammation
Kidney Diseases
Leprosy
Leukemia, Biphenotypic, Acute
Leukemia, Lymphoid
Lichen Planus
Liver Diseases, Alcoholic
Lupus Nephritis
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Non-Hodgkin
Lymphoma, T-Cell, Peripheral
Melanoma
Microscopic Polyangiitis
Mucocutaneous Lymph Node Syndrome
Multiple Myeloma
Multiple Sclerosis, Chronic Progressive
Muscular Dystrophy, Duchenne
Neoplasms, Plasma Cell
Ocular Hypertension
Orbital Pseudotumor
Osteoarthritis, Knee
Pemphigoid, Benign Mucous Membrane
Pemphigus
Pericarditis
Pituitary ACTH Hypersecretion
Polymyalgia Rheumatica
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Prostatic Neoplasms
Prostatic Neoplasms, Castration-Resistant
Pulmonary Disease, Chronic Obstructive
Pulpitis
Purpura, Thrombocytopenic, Idiopathic
Purpura, Thrombotic Thrombocytopenic
Red-Cell Aplasia, Pure
Renal Insufficiency, Chronic
Sarcoma
Schizophrenia
Scleroderma, Systemic
Severe Acute Respiratory Syndrome
Sinusitis
Sjogren's Syndrome
Spasms, Infantile
Stomatitis, Aphthous
Stroke
Takayasu Arteritis
Uveitis

Contraindications

Source: openFDA

Systemic fungal infections Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Vascular disorders (1)

Common Hypertension

Endocrine disorders (2)

Very Common Adrenal suppression (long-term) · Cushingoid features (moon face, buffalo hump)

Metabolism and nutrition disorders (3)

Very Common Hyperglycaemia · Weight gain

Common Hypokalaemia

Gastrointestinal disorders (1)

Uncommon Peptic ulcer / GI bleeding

Skin and subcutaneous tissue disorders (1)

Very Common Skin thinning / bruising

Musculoskeletal and connective tissue disorders (2)

Common Osteoporosis (long-term)

Rare Avascular necrosis of femoral head

Psychiatric disorders (1)

Common Psychiatric effects (mood lability, mania, psychosis)

Eye disorders (1)

Common Cataracts (posterior subcapsular)

Infections and infestations (1)

Common Opportunistic infections

Dosing

Source: openFDA

The initial dosage of prednisolone tablets may vary from 5 mg to 60 mg 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, prednisolone 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 increments 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 prednisolone 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. Alternate-Day Therapy Alternate-Day Therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticoid is administered every other morning. The purpose of this mode of therapy is to provide the patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms, and growth suppression in children. The rationale for this treatment schedule is based on two major premises: (a) the anti-inflammatory or therapeutic effect of corticoids persists longer than their physical presence and metabolic effects and (b) administration of the corticosteroid every other morning allows for re-establishment of more nearly normal hypothalamic-pituitary-adrenal (HPA) activity on the off-steroid day. A brief review of the HPA physiology may be helpful in understanding this rationale. Acting primarily through the hypothalamus a fall in free cortisol stimulates the pituitary gland to produce increasing amounts of corticotropin (ACTH) while a rise in free cortisol inhibits ACTH secretion. Normally the HPA system is characterized by diurnal (circadian) rhythm. Serum levels of ACTH rise from a low point about 10 p.m. to a peak level about 6 a.m. Increasing levels of ACTH stimulate adrenocortical activity resulting in a rise in plasma cortisol with maximal levels occurring between 2 a.m. and 8 a.m. This rise in cortisol dampens ACTH production and in turn adrenocortical activity. There is a gradual fall in plasma corticoids during the day, the lowest levels occurring about midnight. The diurnal rhythm of the HPA axis is lost in Cushing’s disease, a syndrome of adrenocortical hyperfunction characterized by obesity with centripetal fat distribution, thinning of the skin with easy bruisability, muscle wasting with weakness, hypertension, latent diabetes, osteoporosis, electrolyte imbalance, etc. The same clinical findings of hyperadrenocorticism may be noted during the longterm pharmacologic dose corticoid therapy administered in conventional daily divided doses. It would appear, then, that a disturbance in the diurnal cycle with maintenance of elevated corticoid values during the night may play a significant role in the development of und

Warnings & Precautions

Source: openFDA

Warnings & Precautions

In patients on corticosteroid therapy subjected to unusual stress increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Immunosuppression and Increased Risk of Infection Corticosteroids, including prednisolone, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can: Reduce resistance to new infections Exacerbate existing infections Increase the risk of disseminated infections Increase the risk of reactivation or exacerbation of latent infections Mask some signs of infection Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages. Monitor for the development of infection and consider prednisolone withdrawal or dosage reduction as needed. Do not administer prednisolone by an intraarticular, intrabursal, intratendinous, or intralesional route in the presence of acute local infection. Tuberculosis If prednisolone is used to treat a condition in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged prednisolone therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis. Varicella Zoster and Measles Viral Infections Varicella and measles can have a serious or even fatal course in non-immune patients taking corticosteroids, including prednisolone. In corticosteroid-treated patients who have not had these diseases or are nonimmune, particular care should be taken to avoid exposure to varicella and measles: If a prednisolone-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered. If a prednisolone-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated. Hepatitis B Virus Reactivation Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids, including prednisolone. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treat

Pregnancy & Lactation

Pregnancy

FDA category C Teratogenic

Caution

Benefits in controlling auto-immune disease usually outweigh small oral cleft risk. Hydrocortisone preferred for physiological replacement (prednisolone does not cross placenta well). Betamethasone/dexamethasone used for fetal lung maturation (they cross placenta)

Lactation

Probably Unsafe Hale L4 RID 0.35%

Although it is often recommended to avoid breastfeeding for 4 hours after a dose this maneuver is not necessary because prednisolone milk levels are very low.

Chemistry & Properties

Formula	C21H28O5
Molecular weight	360.45 g/mol
IUPAC name	(8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-3-one
CAS	50-24-8
PubChem CID	5755
InChIKey	`OIGNJSKKLXVSLS-VWUMJDOOSA-N`
logP	1.56 (XLogP 1.6)
Polar surface area	94.83 Å²
H-bond acceptors / donors	5 / 3
Drug-likeness (QED)	0.69
Lipinski violations	0

SMILES

C[C@]12C=CC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)CO

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrant	Yes (logBB -0.18)

Enzyme interactions

Enzyme	Role	Detail
CYP2C8	Inhibitor	—
CYP3A4	Substrate	—

Receptor binding (top 4)

Target	Action	Affinity
Glucocorticoid receptor (NR3C1)	Agonist	pKi 8.6
Mineralocorticoid receptor (NR3C2)	Agonist	pIC50 8.0
Glucocorticoid receptor (NR3C1)	Agonist	pIC50 7.8
Mineralocorticoid receptor (NR3C2)	Agonist	pKi 7.4

Transporters

BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)NTCP (Inhibitor)OATP1A2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)MRP2 (Substrate)OAT3 (Substrate)P-gp (Substrate)

Drug–drug interactions (100+, DDInter)

Interacting drug	Severity	Management
Adalimumab	major
Bacillus calmette-guerin substrain tice live antigen	major
Baricitinib	major
Bempedoic acid	major
Brexucabtagene autoleucel	major
Bupropion	major
Certolizumab pegol	major
Cinoxacin	major
Ciprofloxacin	major
Cladribine	major
Deferasirox	major
Delafloxacin	major
Desirudin	major
Desmopressin	major
Dinutuximab	major
Enoxacin	major
Etanercept	major
Fingolimod	major
Gatifloxacin	major
Gemifloxacin	major
Golimumab	major
Grepafloxacin	major
Infliximab	major
Iohexol	major
Iopamidol	major
Leflunomide	major
Levofloxacin	major
Lomefloxacin	major
Measles virus vaccine live attenuated	major
Mifepristone	major
Moxifloxacin	major
Mumps virus strain B level jeryl lynn live antigen	major
Nalidixic acid	major
Natalizumab	major
Norfloxacin	major
Ofloxacin	major
Ozanimod	major
Rotavirus vaccine	major
Rubella virus vaccine	major
Siponimod	major

Showing 40 of 100+.

Registered Products (20)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Apicort eye drops	Ophthalmic Solution 1.2 mg/ml	5 ml pack varies	Amman Pharmaceutical Indusries	0.870
Nucort Forte	Solution 1 %	5 ml pack varies	Amman Pharmaceutical Indusries	0.980
Apicort eye drops	Ophthalmic Solution 1.2 mg/ml	10 ml pack varies	Amman Pharmaceutical Indusries	1.650
Neopred-P eye ear drops	Ophthalmic Solution 10000 IU, 5 mg, 5 mg	10 ml	Amman Pharmaceutical Industries Co	1.800
Nucort Forte	Solution 1 %	10 ml pack varies	Amman Pharmaceutical Indusries	1.850
Pred Mild Ophthalmic Suspension	Ophthalmic Solution 0.12 %	5 ml pack varies	Arab Company for Medical & Agricultural Products	1.870
Prednisolone Tablets	Tablet 5 mg	100 tab pack varies	The Arab Pharmaceutical Manufacturing PSC/Salt	2.100
Pred forte	Solution 1 %	5 ml pack varies	Arab Company for Medical & Agricultural Products	2.120
Pred Mild	Solution 0.12 %	10 ml pack varies	Arab Company for Medical & Agricultural Products	2.580
Pred forte E/D	Ophthalmic Solution 1 %	10 ml pack varies	Arab Company for Medical & Agricultural Products	2.750
Prednisolon 20	Tablet 20 mg	20 tab	AL THARAA FOR PHARMACEUTICALS AND MEDICINE TRADING CO(BEIT LEHEM DRUG STORE))	2.880
COROTROPE 5 TABS	Tablet 5 mg	100 tab	JAWEDA INT. DRUD STORE	3.290
Prenzo Oral Syrup	Syrup 15 mg/5 ml	100 ml pack varies	JORDAN SWEDEN MEDICAL&STERILE.CO(JOSWE)/JORDAN	4.390
Minims Prednisolone Na 0.5% e/d	Ophthalmic Solution 0.5 %	0.5 ml	Petra Drug Store	4.620
Nucort Syrup	Syrup 15 mg/5 ml	120 ml	Amman Pharmaceutical Industries Co	5.270
Prenzo Oral Syrup	Syrup 15 mg/5 ml	120 ml pack varies	JORDAN SWEDEN MEDICAL&STERILE.CO(JOSWE)/JORDAN	5.270
Orexon syrup	Syrup 0.30 %	120 ml	PHILADELPHIA PHAEMACEUTICALS.COMP/JORDAN	5.850
Predone Syrup	Syrup 15 mg/5 ml	120 ml	Hikma Pharmaceuticals Co.Ltd/Jordan	5.850
Prednisolon 50	Tablet 50 mg	20 tab	AL THARAA FOR PHARMACEUTICALS AND MEDICINE TRADING CO(BEIT LEHEM DRUG STORE))	8.080
Prednisolone Tablets	Tablet 5 mg	1000 tab pack varies	The Arab Pharmaceutical Manufacturing PSC/Salt	18.900