Prednisone

K K Jain MD†

Neuropharmacology & Neurotherapeutics

Updated 03.10.2021
Released 02.23.1999
Expires For CME 03.10.2024

Prednisone

Author: K K Jain MD†

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Prednisone

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Introduction

Historical note and terminology

Adrenocortical steroids were introduced in medicine more than 50 years ago. Prednisone, a glucocorticoid, is one of the most widely used drugs. It is used as an anti-inflammatory agent in disorders of several systems including the CNS. Although oral prednisone is often prescribed for multiple sclerosis patients, a related compound, methylprednisolone, which can be given parenterally, is used for managing acute exacerbations of multiple sclerosis. Another related compound, dexamethasone, is used for the treatment of acute spinal cord injury and control of cerebral edema due to trauma and neoplastic disease. The description in this article focuses on oral prednisone.

Pharmacology

The chemical name for prednisone is pregna-1,4-diene-3,11,20-trione, 17,21-dihydroxy.

Pharmacodynamics. Prednisone is a glucocorticoid. Glucocorticoids are adrenocortical steroids, both naturally occurring and synthetic. Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. Metabolic effects include glycogenolysis and neoglycogenesis as well as protein catabolism. Their synthetic analogs, such as prednisone, are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. These effects are:

• Decreased production of prostaglandins, cytokines, and interleukins.
• Decreased proliferation and migration of lymphocytes and macrophages.

Pharmacokinetics. Important pharmacokinetic features of prednisone are as follows:

• Rapidly and promptly absorbed from the gastrointestinal tract due to its lipophilic character.
• Half-life varies between 2 to 5 hours.
• Highly bound to plasma proteins.
• Prednisone is metabolized in the liver to its active form, prednisolone.
• Liver and kidneys are the major sites of inactivation.
• Inducers of hepatic drug metabolism such as phenytoin may accelerate biotransformation of prednisone in the liver and higher doses of prednisone may be required.

Special preparations. Injectable glutathione PEGylated liposomal methylprednisolone (2B3-201) is an alternative to intravenous high-dose free prednisone injection for neuroinflammatory conditions, such as multiple sclerosis. It is a slow-release preparation with enhanced delivery to the brain, which requires one tenth the dose of free prednisone and avoids the acute psychiatric side effects associated with injection of high doses of free prednisone leading to high peak concentrations of the drug. A phase 1 clinical trial showed that 2B3-201 is safe, with no clinically relevant changes in central nervous system safety parameters and no serious adverse events (08). In addition, 2B3-201 shows a long plasma half-life and prolonged immunosuppressive effects.

A 26-week feasibility study showed that modified-release prednisone was a safe and effective treatment for newly diagnosed cases of giant cell arteritis with an outcome profile that was like standard immediate-release prednisolone (15).

Indications

There is no official list of approved indications. Some of the conditions for which prednisone is used, both neurologic as well as non-neurologic, are listed below.

Neurologic disorders

	• Multiple sclerosis. Results of a retrospective analysis suggest that oral prednisone taper, often used for the treatment of relapses in multiple sclerosis following treatment with intravenous methylprednisolone for a relapse, does not lead to improved neurologic outcome after 12 months compared with treatment with intravenous methylprednisolone only (14).
	• Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy.
	• Trichinosis with neurologic involvement.
	• Concomitant with albendazole treatment of neurocysticercosis.
	• Neurosarcoidosis.
	• Susac syndrome.
	• Cerebral vasculitis.
	• Optic neuritis.
	• Duchenne muscular dystrophy. Of all the therapeutic drugs studied in Duchenne muscular dystrophy, only prednisone seems to have the potential for providing interim functional improvement for patients with this disease and delaying the progression while they wait for a cure with gene or cell therapy. A retrospective analysis of data of patients with Duchenne muscular dystrophy who were treated with prednisone 0.75 mg/kg per day intermittently (10 days on, then 10 days off) showed that this approach has few side effects and extends the period of improvement by 1 year compared to historical controls (17). A double-blind, randomized study has provided Class I evidence that weekend prednisone dosing is as safe and effective as daily prednisone in preserving muscle strength and preventing increase of body mass index in boys with Duchenne muscular dystrophy over a 1-year period (06). Alternating prednisone regimen (10 days on/10 days off) has no apparent adverse effects on weight and height in children with Duchenne muscular dystrophy who are ambulant (19).
	• Low-dose prednisone with gradual dose escalation was shown to be safe, well-tolerated, and effective in treating ocular myasthenia gravis in a randomized clinical trial (03).
	• Treatment of myelopathy in Sjögren syndrome with a combination of prednisone and cyclophosphamide.
	• Prednisone therapy is considered a safe and effective adjunctive treatment for epilepsy for older children with intractable generalized epilepsy who have failed conventional antiepileptic therapy.
	• In a comparative study on children with intractable epilepsy, intravenous immune globulin was more effective than prednisone and had less adverse effects. This response was independent of epilepsy type, etiology, and duration, suggesting different mechanisms of action between intravenous immune globulin and prednisone despite a common, reversible, immune-mediated pathway to intractability of epilepsy (18).
	• Temporal arteritis.
	• Polyneuropathy and myositis in idiopathic hypereosinophilic syndrome.
	• Vestibular neuritis
	• Intratympanic dexamethasone is effective in preventing the progression of sensorineural hearing loss in Ménière disease (13). This is preferable to the use of oral high-dose prednisone for the recovery of hearing loss, which can have adverse effects.
	• Episodic cluster headache
	• High-dose prednisone has been used successfully in the treatment of infantile spasms in China (20). There is immune dysfunction in infantile spasms as evidenced by the rise in serum levels of inflammatory cytokines such as interleukin-8 and tumor necrosis factor alfa. Prednisone can control seizures in children with infantile spasms, possibly by regulating and improving immune dysfunction as evidenced by lowering levels of cytokines (04).
	• In a patient with post-stroke central pain in whom first-line agents were contraindicated due to comorbidities, the choice was limited to low-dose gabapentin, but prednisone taper as adjunct medication led to significant pain relief with eventual resolution (02).
	• Bell palsy. Several studies have reported significant improvement in recovery of function in complete idiopathic facial nerve palsy following treatment with corticosteroids. It is usually used in combination with acyclovir or valacyclovir.
	• Pain associated with herpes zoster

Disorders of other systems

	• Endocrine disorders: primary or secondary adrenocortical insufficiency. Hydrocortisone or cortisone is the first choice, but synthetic analogs may be used in conjunction with mineralocorticoids where applicable.
	• Rheumatic disorders: as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation).
	• Collagen diseases: eg, during an exacerbation or as maintenance therapy in selected cases of systemic lupus erythematosus.
	• Skin disorders such as severe erythema multiforme.
	• Allergic states: eg, allergic rhinitis, bronchial asthma, and drug hypersensitivity reactions.
	• Respiratory diseases: eg, aspiration pneumonitis.
	• Hematological disorders: eg, idiopathic thrombocytopenic purpura in adults.
	• Neoplastic diseases: eg, palliative management of leukemia and lymphoma in adults.

Special considerations

General precautions for prednisone use include the following:

	• Patients on corticosteroid therapy subjected to unusual stress. Increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated.
	• Corticosteroids may mask some signs of infection.
	• Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Because mineralocorticoid secretion may be impaired, salt or a mineralocorticoid or both should be administered concurrently.
	• Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to COVID-19.
	• There is an enhanced effect of corticosteroids in patients with hypothyroidism and in those with cirrhosis.
	• Steroids should be used with caution in myasthenia gravis. Patients at risk of developing treatment-resistant myasthenia-associated ophthalmoplegia may have inadequate endogenous levels of complement regulatory protein protection in their extraocular muscle in response to prednisone, which increases their susceptibility to complement-mediated damage (01). In patients with generalized myasthenia, adjuvant therapy with intravenous immunoglobulin when starting prednisone for the first time is safe and effective in preventing prednisone-induced exacerbation (05). A clinical trial has shown that thymectomy is useful for patients with myasthenia gravis by increasing the likelihood of achieving sustained minimal manifestation status with complete withdrawal of prednisone (10).

Pregnancy. Because adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnant women, nursing mothers, or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. A case of neonatal acute adrenal insufficiency manifesting as hypoglycemia and seizures has been reported following maternal exposure to moderate doses of corticosteroids during pregnancy (16). Little prednisone is excreted in breast milk.

Pediatric. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed.

Adverse effects

Long-term therapeutic administration of prednisone is limited by major adverse effects as follows:

	• Psychic disorders: These may appear when corticosteroids are used and range from euphoria, insomnia, mood swings, personality changes, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids. Switching from a regimen of intravenous methylprednisolone in an inpatient to outpatient setting is without problems in patients with multiple sclerosis, but rare psychotic reactions to treatment are unpredictable (12).
	• Neurologic: increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment; convulsions, vertigo, or headache.
	• Musculoskeletal: muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fracture of long bones
	• Gastrointestinal: peptic ulcer with possible perforation and hemorrhage.
	• Cardiovascular: Patients receiving high-dose corticosteroid therapy are at increased risk of developing atrial fibrillation.
	• Impaired wound healing.
	• Fluid and electrolyte disturbances: sodium retention and hypertension.
	• Leukocytosis: The degree of leukocytosis is related to the dosage administered. It reaches maximal values within 2 weeks in most cases, after which the white blood cell count decreases, albeit not to pretreatment levels. There is predominantly a rise in the polymorphonuclear white blood cells and coincides with monocytosis, eosinopenia, and a variable degree of lymphopenia.
	• Diabetes: Manifestations of latent diabetes mellitus and increased requirements for insulin or oral hypoglycemic agents in diabetics may occur. Even low doses of prednisone for 1 week impair insulin sensitivity in a dose-dependent manner, which is clinically relevant in individuals predisposed to develop glucose intolerance (09). Patients on long-term prednisone therapy should be monitored by blood HbA1c test for detection of pre-diabetes.
	• Prolonged use of prednisone can lead to negative nitrogen balance due to protein catabolism.
	• Addison-like adrenal insufficiency may manifest if prednisone is discontinued after prolonged use. The adrenocorticotrophic hormone stimulation test is the most specific test for diagnosing adrenal insufficiency. Blood cortisol levels are measured before and after a synthetic form of adrenocorticotrophic hormone is given by injection. If the measurement of cortisol levels shows no response to adrenocorticotrophic hormone stimulation, the patient may need to remain on a low dose of prednisone for prevention of an Addisonian crisis, eg, 5 mg per day.
	• Ophthalmic: posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exophthalmos.
	• Urticaria and other allergic, anaphylactic, or hypersensitivity reactions.
	• Malignancies: Kaposi sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.
	• Miscellaneous side effects: These include skin atrophy, menstrual irregularities, osteoporosis, fatty liver, and growth inhibition in children.

Most of the adverse effects are managed with gradual tapering and discontinuation of prednisone. There is ongoing research to find alternative drugs for prednisone that are effective for suppressing inflammation by activation of glucocorticoid receptor but do not have its adverse effects, which are due to concomitant inactivation of glucocorticoid receptor. A CpdX compound has been shown to be a selective glucocorticoid receptor agonistic modulator with none of the known glucocorticoid receptor–related debilitating side effects as observed in the mouse following 3 months of treatment with CpdX (07).

References

01: Auret J, Abrahams A, Prince S, Heckmann JM. The effects of prednisone and steroid-sparing agents on decay accelerating factor (CD55) expression: implications in myasthenia gravis. Neuromuscul Disord 2014;24(6):499-508. PMID 24703255
02: Batlle L, Mattie R, Irwin R. A medication combination for the treatment of central poststroke pain via the adjuvant use of prednisone with gabapentin: a case report. PM R 2016;8(3):278-81. PMID 26409194
03: Benatar M, Mcdermott MP, Sanders DB, et al. Efficacy of prednisone for the treatment of ocular myasthenia (EPITOME): a randomized, controlled trial. Muscle Nerve 2016;53(3):363-9. PMID 26179124
04: Chen H, Zhong JM, Yi ZS, Zha J, Chen Y, Cai LY. Immunological mechanism of prednisone in the treatment of infantile spasm. [Article in Chinese] Zhongguo Dang Dai Er Ke Za Zhi 2017;19(10):1044-50. PMID 29046198
05: Díez-Porras L, Homedes C, Alberti MA, Vélez-Santamaría V, Casasnovas C. Intravenous immunoglobulins may prevent prednisone-exacerbation in myasthenia gravis. Sci Rep 2020;10(1):13497.** PMID 32782330
06: Escolar DM, Hache LP, Clemens PR, et al. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology 2011;77(5):444-52. PMID 21753160
07: Hua G, Zein N, Paulen L, Chambon P. The glucocorticoid receptor agonistic modulators CpdX and CpdX-D3 do not generate the debilitating effects of synthetic glucocorticoids. Proc Natl Acad Sci U S A 2019;116(28):14200-9. PMID 31221758
08: Kanhai KM, Zuiker RG, Stavrakaki I, et al. Glutathione-PEGylated liposomal methylprednisolone in comparison to free methylprednisolone: slow release characteristics and prolonged lymphocyte depression in a first-in-human study. Br J Clin Pharmacol 2018;84(5):1020-8. PMID 29385232
09: Kauh EA, Mixson LA, Shankar S, et al. Short-term metabolic effects of prednisone administration in healthy subjects. Diabetes Obes Metab 2011;13(11):1001-7. PMID 21635675
10: Lee I, Kuo HC, Aban IB, et al. Minimal manifestation status and prednisone withdrawal in the MGTX trial. Neurology 2020;95(6):e755-66.** PMID 32611638
11: Les I, Pijoán JI, Rodríguez-Álvarez R, Ruiz-Irastorza G, Martínez-Berriotxoa A. Effectiveness and safety of medium-dose prednisone in giant cell arteritis: a retrospective cohort study of 103 patients. Clin Exp Rheumatol 2015;33(2 Suppl 89):S-90-7. PMID 26016756
12: Lienert C, Schawalder G, Findling O, et al. Tolerance of intravenous methylprednisolone for relapse treatment in demyelinating CNS disease. Swiss Med Wkly 2013;143:w13783. PMID 23740464
13: Molnár A, Maihoub S, Tamás L, Szirmai Á. Intratympanically administered steroid for progressive sensorineural hearing loss in Ménière's disease. Acta Otolaryngol 2019;139(11):982-6. PMID 31498001
14: Perumal JS, Caon C, Hreha S, et al. Oral prednisone taper following intravenous steroids fails to improve disability or recovery from relapses in multiple sclerosis. Eur J Neurol 2008;15(7):677-80. PMID 18459972
15: Raine C, Stapleton PP, Merinopoulos D, et al. A 26-week feasibility study comparing the efficacy and safety of modified-release prednisone with immediate-release prednisolone in newly diagnosed cases of giant cell arteritis. Int J Rheum Dis 2018;21(1):285-91. PMID 28791802
16: Saulnier PJ, Piguel X, Perault-Pochat MC, Csizmadia-Bremaud C, Saulnier JP. Hypoglycaemic seizure and neonatal acute adrenal insufficiency after maternal exposure to prednisone during pregnancy: a case report. Eur J Pediatr 2010;169(6):763-5. PMID 19902248
17: Straathof CS, Overweg-Plandsoen WC, van den Burg GJ, van der Kooi AJ, Verschuuren JJ, de Groot IJ. Prednisone 10 days on/10 days off in patients with Duchenne muscular dystrophy. J Neurol 2009;256(5):768-73. PMID 19306039
18: Tang-Wai R, Mailo J, Rosenblatt B. Breaking the cycle: a comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children. Seizure 2017;47:34-41. PMID 28284046
19: ten Dam K, de Groot IJ, Noordam C, van Alfen N, Hendriks JC, Sie LT. Normal height and weight in a series of ambulant Duchenne muscular dystrophy patients using the 10 day on/10 day off prednisone regimen. Neuromuscul Disord 2012;22(6):500-4. PMID 22390890
20: Yi ZS, Wu HP, Yu XY, Chen Y, Zhong JM. Efficacy and tolerability of high-dose prednisone in Chinese children with infantile spasms. Brain Dev 2015;37(1):23-8. PMID 24657009

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Prednisone

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Prednisone

	• Drugs that induce hepatic enzymes, such as phenobarbital, phenytoin, and rifampin, may increase the clearance of corticosteroids and may require increases in corticosteroid dose to achieve the desired response.
	• Drugs such as troleandomycin and ketoconazole may inhibit the metabolism of corticosteroids and, thus, decrease their clearance. Therefore, the dose of corticosteroid should be titrated to avoid steroid toxicity.
	• Corticosteroids may increase the clearance of chronic, high-dose aspirin. This could lead to decreased salicylate serum levels or increased risk of salicylate toxicity when the corticosteroid is withdrawn. Aspirin should be used cautiously in conjunction with corticosteroids in patients suffering from hypoprothrombinemia.
	• The effect of corticosteroids on oral anticoagulants is variable. There are reports of enhanced as well as diminished effects of anticoagulants when given concurrently with corticosteroids. Therefore, coagulation indices should be monitored to maintain the desired anticoagulant effect.
	• Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Because concurrent use of these agents results in a mutual inhibition of metabolism, it is possible that adverse events associated with the individual use of either drug may be more apt to occur.

Prednisone

Prednisone

Introduction

Historical note and terminology

Pharmacology

Clinical trials

Indications

Neurologic disorders

Disorders of other systems

Contraindications

Goals and duration of treatment

Dosing

Special considerations

Interactions

Adverse effects

References

Contributors

Author

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Also in This Category

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Toxic and nutritional deficiency optic neuropathies

Third nerve palsy

Nystagmus

Brain death/death by neurologic criteria

Outpatient rehabilitation of chronic neurologic conditions

Prednisone

Introduction

Historical note and terminology

Pharmacology

Clinical trials

Indications

Neurologic disorders

Disorders of other systems

Contraindications

Goals and duration of treatment

Dosing

Special considerations

Interactions

Adverse effects

References

Contributors

Author

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Toxic and nutritional deficiency optic neuropathies

Third nerve palsy

Nystagmus

Brain death/death by neurologic criteria

Outpatient rehabilitation of chronic neurologic conditions

This is an article preview.
Start a Free Account
to access the full version.