Cortisone

H02A - Corticosteroids for systemic use, plain ATC H02AB10 Small molecule Prodrug Natural product

Active form: Hydrocortisone.

JFDA label: Cortisone 25mg Tablets

Mechanism of Action

Decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability

Indications

Approved

Allergic states
Dermatologic diseases
Endocrine disorders
Gastrointestinal diseases
Hematologic disorders
Miscellaneous
Neoplastic diseases
Ophthalmic diseases
Renal diseases
Respiratory diseases
Rheumatic disorders

Contraindications

Source: Lexicomp

Hypersensitivity to cortisone or any component of the formulation Absolute
administration of live virus vaccines (with immunosuppressive doses of cortisone). Documentation of allergenic cross-reactivity for glucocorticoids is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty Absolute
systemic fungal infection Absolute

Adverse Reactions

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

Nervous system disorders (2)

Very Common Insomnia · nervousness

Metabolism and nutrition disorders (2)

Common Diabetes mellitus · hirsutism

Gastrointestinal disorders (2)

Very Common Dyspepsia · increased appetite

Musculoskeletal and connective tissue disorders (1)

Common Arthralgia

Eye disorders (2)

Common Cataract · glaucoma

Respiratory, thoracic and mediastinal disorders (1)

Common Epistaxis

Dosing

Source: Lexicomp

Note: Dosing depends on the condition being treated and the response of the patient. Temporary supplemental doses may be warranted during times of stress (ie, trauma, surgery, severe infection). Discontinuation of therapy requires gradual withdrawal by tapering the dose. Anti-inflammatory/immunosuppressive/endocrine disorders: Oral: Initial: 25 to 300 mg/day; adjust dose to patient response. Physiologic replacement (off-label dose): Oral: 20 to 35 mg daily in 2 to 3 divided doses. Administer the largest dose in the morning upon awakening, followed by next dose 2 hours after lunch (two-dose regimen) or next dose at lunch, followed by smallest dose in the afternoon no later than 4 to 6 hours before bedtime (three-dose regimen) (ES [Bornstein 2016])

(For additional information see "Cortisone acetate: Pediatric drug information") Note: Dosing depends on the condition being treated and the response of the patient. Temporary supplemental doses may be warranted during times of stress (ie, trauma, surgery, severe infection). Discontinuation of therapy requires gradual withdrawal by tapering the dose. Anti-inflammatory or immunosuppressive (off-label dose): Children and Adolescents: Oral: 0.7 to 10 mg/kg/day or 20 to 300 mg/m2/day in divided doses every 6 to 8 hours (Nelson 1996); usual adult daily dose range: 25 to 300 mg/day Physiologic replacement (off-label dose): Children and Adolescents: Oral: 0.5 to 0.75 mg/kg/day or 20 to 25 mg/m2/day in divided doses every 8 hours (Keenan 1990, Kliegman 2007, Moreira 2011); usual adult daily dose range: 25 to 35 mg/day. Most physiologic replacement protocols divide the daily dose equally into 3 doses every 8 hours; however, some recommend administering a slightly higher dose in the morning to attempt to mimic the normal diurnal variation of endogenous cortisol (Shulman 2007).

Refer to adult dosing.

There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.

Warnings & Precautions

Source: Lexicomp

Adrenal suppression

May cause hypercortisolism or suppression of hypothalamic-pituitary-adrenal (HPA) axis, particularly in younger children or in patients receiving high doses for prolonged periods. HPA axis suppression may lead to adrenal crisis. Withdrawal and discontinuation of a corticosteroid should be done slowly and carefully. Particular care is required when patients are transferred from systemic corticosteroids to inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including an increase in allergic symptoms. Adult patients receiving >20 mg per day of prednisone (or equivalent) may be most susceptible. Fatalities have occurred due to adrenal insufficiency in asthmatic patients during and after transfer from systemic corticosteroids to aerosol steroids; aerosol steroids do not provide the systemic steroid needed to treat patients having trauma, surgery, or infections.

Anaphylactoid reactions

Rare cases of anaphylactoid reactions have been observed in patients receiving corticosteroids.

Immunosuppression

Prolonged use of corticosteroids may also increase the incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to inactivated vaccines. Exposure to chickenpox or measles should be avoided. Corticosteroids should not be used for cerebral malaria or viral hepatitis. Close observation is required in patients with latent tuberculosis (TB) and/or TB reactivity; restrict use in active TB (only fulminating or disseminated TB in conjunction with antituberculosis treatment). Amebiasis should be ruled out in any patient with recent travel to tropical climates or unexplained diarrhea prior to initiation of corticosteroids.

Kaposi sarcoma

Prolonged treatment with corticosteroids has been associated with the development of Kaposi sarcoma (case reports); if noted, discontinuation of therapy should be considered (Goedert 2002).

Myopathy

Acute myopathy has been reported with high-dose corticosteroids, usually in patients with neuromuscular transmission disorders; may involve ocular and/or respiratory muscles; monitor creatine kinase; recovery may be delayed.

Psychiatric disturbances

Corticosteroid use may cause psychiatric disturbances, including severe depression, euphoria, insomnia, mood swings, personality changes, to frank psychotic manifestations. Preexisting psychiatric conditions may be exacerbated by corticosteroid use. Disease-related concerns:

Cardiovascular disease

Use with caution in patients with heart failure and/or hypertension; use has been associated with electrolyte disturbances, fluid retention, and hypertension. Use with caution in patients with a recent history of myocardial infarction (MI); left ventricular free wall rupture has been reported after the use of corticosteroids.

Diabetes

Use with caution in patients with diabetes mellitus; may alter glucose production/regulation leading to hyperglycemia.

Gastrointestinal disease

Use with caution in patients with GI diseases (diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, ulcerative colitis [nonspecific) due to perforation risk.

Head injury

Increased mortality was observed in patients receiving high-dose IV methylprednisolone; high-dose corticosteroids should not be used for the management of head injury.

Hepatic impairment

Use with caution in patients with hepatic impairment, including cirrhosis; long-term use has been associated with fluid retention.

Myasthenia gravis

Use with caution in patients with myasthenia gravis; exacerbation of symptoms has occurred especially during initial treatment with corticosteroids.

Ocular disease

Use with caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use. Use with caution in patients with a history of ocular herpes simplex; corneal perforation has occurred; do not use in active ocular herpes simplex. Consider routine eye exams in chronic users.

Osteoporosis

Use with caution in patients with osteoporosis; high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures.

Renal impairment

Use with caution in patients with renal impairment; fluid retention may occur.

Seizure disorders

Use with caution in patients with a history of seizure disorder; seizures have been reported with adrenal crisis.

Thyroid disease

Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones. Concurrent drug therapy issues:

Drug-drug interactions

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Elderly

Because of the risk of adverse effects, systemic corticosteroids should be used cautiously in the elderly in the smallest possible effective dose for the shortest duration.

Pediatric

May affect growth velocity; growth and development should be routinely monitored in pediatric patients. Other warnings/precautions:

Discontinuation of therapy

Withdraw therapy with gradual tapering of dose.

Pregnancy & Lactation

Pregnancy

Adverse events have been observed with corticosteroids in animal reproduction studies. Cortisone crosses the placenta (Migeon 1957). Some studies have shown an association between first trimester systemic corticosteroid use and oral clefts (Park-Wyllie 2000; Pradat 2003). Systemic corticosteroids may also influence fetal growth (decreased birth weight); however, information is conflicting (Lunghi 2010). Hypoadrenalism may occur in newborns following maternal use of corticosteroids in pregnancy (monitor). When systemic corticosteroids are needed in pregnancy, it is generally recommended to use the lowest effective dose for the shortest duration of time, avoiding high doses during the first trimester (Leachman 2006; Lunghi 2010; Makol 2011; Østensen 2009). Cortisone may be used (alternative agent) to treat primary adrenal insufficiency (PAI) in pregnant women. Pregnant women with PAI should be monitored at least once each trimester (Bornstein 2016).

Lactation

Avoid

Corticosteroids are excreted in breast milk. The manufacturer notes that when used systemically, maternal use of corticosteroids have the potential to cause adverse events in a breast-feeding infant (eg, growth suppression, interference with endogenous corticosteroid production). Breast-feeding is not recommended by the manufacturer in women taking pharmacologic doses. If there is concern about exposure to the infant, some guidelines recommend waiting 4 hours after the maternal dose of an oral s

Monitoring

Clinical pearl	Blood pressure; glucose (in diabetics); bone mineral density; growth in children; eye exams (with prolonged use); signs and symptoms of infection; signs and symptoms of hypercortisolism or adrenal suppression.

Chemistry & Properties

Formula	C21H28O5
Molecular weight	360.45 g/mol
IUPAC name	(8S,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,11-dione
CAS	53-06-5
PubChem CID	222786
InChIKey	`MFYSYFVPBJMHGN-ZPOLXVRWSA-N`
logP	1.99 (XLogP 1.5)
Polar surface area	91.67 Å²
H-bond acceptors / donors	5 / 2
Drug-likeness (QED)	0.79
Lipinski violations	0

SMILES

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

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	70.0%
Half-life	1.733 h
Volume of distribution	0.444 L/kg
Protein binding	83.8%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C19	Substrate	—
CYP2C8	Inhibitor	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MATE1 (Inhibitor)MRP1 (Inhibitor)OATP1A2 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Cortisone	Tablet 25 mg	100 tab	Hikma Pharmaceuticals Co.Ltd/Jordan	15.000