Prednisolone

Registered South African indications:

• Relief of symptoms associated with inflammatory conditions, where a steroid is indicated
• All conditions where corticosteroid therapy is likely to be of benefit
  - Acute haemolytic disorders
  - Allergic disorders
  - Asthma
  - Leukaemia
  - Thrombocytopenic purpura
  - Celiac disease
  - Insulin resistance in diabetes mellitus
  - Immunosuppression
  - Liver disorders
  - Ulcerative colitis

Registered South African contraindications

Tablet

• Hypersensitivity to the active ingredient or any of its excipients
• Peptic ulcer
• Osteoporosis
• Psychoses or severe psychoneuroses
• Active tuberculosis or doubtfully quiescent tuberculosis
• Acute infection including herpes zoster and herpes simplex ulceration of the eye
• Vaccination with live vaccine (killed vaccines or toxoids may be given)

Syrup

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Osteoporosis
• Oesophagitis
• Gastritis
• Peptic ulcer
• Acute psychosis or severe psychoneuroses
• Systemic fungal infections
• Uncontrolled, systemic or local bacterial or viral infections
• Active or doubtfully latent tuberculosis (except, very rarely, as adjuncts to anti-tubercular treatment)
• Acute viral infections such as herpes zoster or ocular herpes simplex
• Patients receiving high-dose prednisolone therapy should not be immunised with live vaccines for up to 3 months after steroid therapy

Contraindications registered in other jurisdictions

Tablet

• Hypersensitivity to the active ingredient or any of its excipients
• Systemic infections unless specific anti-infective therapy is employed
• Ocular herpes simplex due to the possibility of perforation

South African recommendations

Caution and regular patient monitoring are necessary when prescribing prednisolone in patients with conditions such as:

• Pregnancy (tab)
• Breastfeeding (tab)
• Renal impairment
• Hepatic impairment
• Elderly
• Hypertension
• Congestive heart failure
• Diabetes mellitus or a family history of diabetes
• Chronic renal failure, uraemia, renal insufficiency
• Glaucoma
• Hypothyroidism
• Recent myocardial infarction
• Liver failure
• Acute and active hepatitis
• Cirrhosis
• Menopause, post-menopause
• History of severe affective disorders, especially previous history of steroid-induced psychoses
• Pre-existing emotional instability or psychotic tendencies
• Epilepsy and/or seizure disorders
• Previous steroid myopathy
• Myasthenia gravis, especially those receiving anticholinesterase therapy
• Thromboembolic disorders

Risk of bradycardia

• Bradycardia is a rare but serious adverse effect of prednisolone, which can be both symptomatic and asymptomatic. It is more likely to occur with high doses but can occur even with standard doses and is reversible with dose reduction or discontinuation
• Patients with pre-existing cardiac or renal problems or electrolyte imbalance are at higher risk. The risk may increase with the concurrent use of other medicines causing bradycardia as an adverse event

Duchenne muscular dystrophy

• Utilize the minimum effective dose of prednisolone
• Regular patient review is essential to mitigate risks

Psychiatric adverse reactions

• Monitor patients for severe psychiatric reactions, especially those with a history of affective disorders
• Seek immediate medical advice for worrying symptoms

Tumorigenicity

• Be aware that prednisolone may enhance the risk of rapid malignancy spread in immunosuppressed patients

Calciphylaxis

• Seek immediate medical advice if symptoms develop, even in patients with normal renal function and mineral levels

Adrenocortical insufficiency

• Avoid abrupt withdrawal or significant dosage change
• Gradual dosage reduction is advised to prevent potentially fatal adrenal insufficiency

Infections

• Prednisolone increases susceptibility to serious infections
• Maintain vigilance for latent or intercurrent infections due to immunosuppressive effects

Chickenpox

• Avoid close contact with chickenpox or herpes zoster if no definite history of chickenpox
• Seek urgent medical attention if exposed
• Varicella zoster immunoglobulin needed for exposed non-immune patients on corticosteroids
• Do not stop and may need to increase corticosteroid dose if chickenpox is confirmed

Measles

• Avoid exposure to measles and seek immediate medical advice if exposure occurs

Administration of live vaccines

• Avoid live vaccines for individuals on high doses of corticosteroids due to impaired immune response
• Postpone live vaccines until at least 3 months after stopping treatment

Ocular effects

• Prolonged use may cause various eye issues including cataracts, glaucoma, and secondary infections
• Contraindicated in patients with ocular herpes simplex
• Use with caution in the presence of glaucoma
• Can cause severe exacerbation of retinal detachment in some cases

Cushing’s disease

• Avoid in patients with Cushing’s disease due to the risk of aggravation
• Enhanced effect in patients with hypothyroidism
• Can cause psychic derangements ranging from mood swings to psychotic manifestations

Raised intracranial pressure

• Reported association with corticosteroid treatment, typically occurs after treatment withdrawal

Scleroderma renal crisis

• Caution required in patients with systemic sclerosis due to increased incidence of renal crisis
• Monitor blood pressure and renal function

Use in the elderly

• Plan treatment carefully due to more serious consequences of side-effects
• Use with great caution and close clinical supervision is required

Paediatric population

• Corticosteroids cause growth retardation and an increased risk of nuclear cataracts
• Irreversible effects on growth in infancy, childhood, and adolescence

HPA axis suppression

• Minimized by using the lowest effective dose for the minimum period and preferably as a single morning dose or on alternate days
• Frequent patient review is necessary for appropriate dose titration against disease activity

Kaposi's Sarcoma

• Reported in patients receiving corticosteroid treatment, discontinuation may lead to clinical remission

Chronic immunosuppression

• Associated with an increased risk of malignancy, particularly in organ transplantation cases

Pheochromocytoma crisis concerns

• Pheochromocytoma crisis can be fatal and has been linked to systemic corticosteroids like prednisolone. Administer to patients with known or suspected pheochromocytoma only after a thorough risk/benefit assessment

Excipients

Tablets

• Not suitable for patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose galactose malabsorption

Syrup

Propylene glycol

• Adverse effects possible in neonates and children less than 5 years old, especially when co-administered with ethanol
• Requires medical monitoring in patients with impaired renal or hepatic functions

Glycerol

• Glycerol present in prednisolone syrup can lead to symptoms like headache, stomach disturbances, and diarrhoea

Ethanol/Alcohol

• Contains a small percentage, generally not likely to affect adults, adolescents, or children but may affect younger children
• Co-administration with other products containing ethanol or propylene glycol may induce adverse effects, especially in young children

Sugar

• Contains invert syrup, which may be harmful to teeth
• Not suitable for patients with certain hereditary problems like fructose intolerance or glucose-galactose malabsorption
• Consideration required for patients with diabetes mellitus

Sorbitol

• Contains sorbitol, which is not suitable for patients with hereditary fructose intolerance and may cause gastrointestinal discomfort and a mild laxative effect

Benzoic acid

• Contains a small amount; may increase bilirubinemia, potentially increasing neonatal jaundice which could develop into kernicterus

Forms avail. in SA and covered in this monograph: tab, syr

South African registered indications and dosages

All conditions where corticosteroid therapy is likely to be of benefit
- Acute haemolytic disorders
- Allergic disorders
- Asthma
- Leukaemia
- Thrombocytopenic purpura
- Celiac disease
- Insulin resistance in diabetes mellitus
- Immunosuppression
- Liver disorders
- Ulcerative colitis

• Oral (tab): Up to 60mg daily in divided doses

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Withdrawal should always be gradual. The rate depends on the patient’s response, the dose, and duration of therapy

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Adrenal function should be monitored throughout withdrawal, and symptoms attributable to over rapid withdrawal should be countered by resuming a higher dose and continuing the reduction at a slower rate

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Relief of symptoms associated with inflammatory conditions, where a steroid is indicated

• Oral (syr): Usual dose: 5-60mg daily in divided doses, depending on the disease being treated; May be given as a single dose after breakfast or as a double dose on alternate days not exceeding the maximum dose; Max dose: 1-2mg/kg

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Dosing requirements may vary depending on the specific disease, its severity, and the response of the patient. Dosages should therefore be modified to suit each patient

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Some patients may require higher initial doses, while low doses should be sufficient in less severe situations. Careful adjustment of the initial dose may be required to obtain a satisfactory response, and this dose should be maintained thereafter

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Discontinuation: Gradually discontinue the treatment if spontaneous remission occurs in a chronic condition

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See link: General prescribing points for steroids

Paed. forms avail. in SA and covered in this monograph: syr

South African registered indications and dosages

Relief of symptoms associated with inflammatory conditions, where a steroid is indicated

• Oral (syr): Usual dose: 0.5-2mg per kg of body weight OR 15-60mg per square meter of body surface area, in three divided doses

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Dosing requirements may vary depending on the specific disease, its severity, and the response of the patient. Dosages should therefore be modified to suit each patient

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Some patients may require higher initial doses, while low doses should be sufficient in less severe situations. Careful adjustment of the initial dose may be required to obtain a satisfactory response, and this dose should be maintained thereafter

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Discontinuation: Gradually discontinue the treatment if spontaneous remission occurs in a chronic condition

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No information is available for the use of prednisolone tablets in the paediatric population

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See link: General prescribing points for steroids

Pregnancy 

South African recommendations

• Caution; positive evidence of risk in animals (tab)
• Contraindicated (syr)
• The safety of prednisolone in pregnancy has not been established
• The ability of corticosteroids, such as prednisolone, to cross the placenta varies between individual medicines; however, 88% of prednisolone is inactivated as it crosses the placenta
• Administration of corticosteroids, such as prednisolone, to pregnant animals can cause abnormalities of foetal development, including cleft palate, intra-uterine growth retardation, and effects on brain growth and development
• There is no evidence that corticosteroids, such as prednisolone, result in an increased incidence of congenital abnormalities, such as cleft palate/lip
• However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids, such as prednisolone, may increase the risk of intra-uterine growth retardation
• Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important
• The use of corticosteroids, such as prednisolone, during pregnancy may also result in stillbirth (tab)
• Cataracts have been observed in infants born to mothers treated with long-term prednisolone during pregnancy (tab)
• Depression of hormone levels has been described in pregnancy, but the significance of this finding is not clear (syr)

Recommendations in other jurisdictions

• Caution; positive evidence of risk in animals
• The ability of corticosteroids to cross the placenta varies between individual drugs; however, 88% of prednisolone is inactivated as it crosses the placenta
• Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development, including cleft palate, intra-uterine growth retardation, and effects on brain growth and development
• There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate/lip in man
• However, when administered for prolonged periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation
• Hypoadrenalism, in theory, may occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important
• As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks
• When corticosteroids are essential, however, patients with normal pregnancies may be treated as though they were in the non-gravid state
• Patients with pre‐eclampsia or fluid retention require close monitoring

Breastfeeding

South African recommendations

Tablet

• Caution
• The safety of prednisolone in lactation has not been established
• Corticosteroids, such as prednisolone, are excreted in small amounts in breast milk
• Corticosteroids, such as prednisolone, distributed into breast milk may suppress growth and interfere with endogenous glucocorticoid production in nursing infants
• The concentration of the steroid, such as prednisolone, in the milk can be between 5% and 25% of those in the serum, and the two roughly parallel one another after an oral dose
• There are no reports found regarding neonatal toxicity following exposure to corticosteroids during lactation; however, if maternal doses > 40 mg/day of prednisolone are prescribed, the infant should be monitored for adrenal suppression

Syrup

• Contraindicated
• The use of prednisolone is contraindicated during lactation
• Corticosteroids, such as prednisolone, are distributed into breast milk and may cause unwanted effects, such as growth suppression and inhibition of endogenous steroid production in the infant

Recommendations in other jurisdictions

• Caution
• Corticosteroids are excreted in small amounts in breast milk
• However, doses of up to 40mg daily of prednisolone are unlikely to cause systemic effects in the infant
• Infants of mothers receiving 40mg or more daily should be monitored for signs of adrenal suppression, but the benefits of breastfeeding are likely to outweigh any theoretical risk

Fertility

South African recommendations

• No information available (tab)
• Corticosteroids, such as prednisolone, may cause irregular menstruation or amenorrhea (syr)

Recommendations in other jurisdictions

• No information available

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended

Recommendations below are applicable to South Africa and other jurisdictions

• Caution; no dose adjustment recommended

Infections and Infestations

Not known

• Increases susceptibility to and severity of infections with suppression of clinical symptoms and signs
• Opportunistic infections
• Recurrence of dormant tuberculosis

Blood and Lymphatic System Disorders

Not known

• Leucocytosis

Immune System Disorders

Not known

• Hypersensitivity including anaphylaxis

Endocrine Disorders

Not known

• Cushingoid
• Impaired carbohydrate tolerance with increased requirement for antidiabetic therapy
• Manifestation of latent diabetes mellitus

Metabolism and Nutrition Disorders

Not known

• Sodium and water retention
• Increased appetite which may result in weight gain
• Hypokalaemic alkalosis
• Negative nitrogen and calcium balance

Psychiatric Disorders

Not known

• Euphoric mood
• Drug dependence
• Depression
• Insomnia
• Schizophrenia

Nervous System Disorders

Not known

• Dizziness
• Headache
• Epilepsy

Eye Disorders

Not known

• Glaucoma
• Papilloedema
• Cataract subcapsular
• Central serous chorioretinopathy
• Exophthalmos
• Corneal or scleral thinning
• Exacerbation of ophthalmic viral or fungal disease
• Blurred vision

Ear and Labyrinth Disorders

Not known

• Vertigo

Cardiac Disorders

Not known

• Congestive heart failure in susceptible patients
• Bradycardia (following high doses)

Vascular Disorders

Not known

• Thromboembolism
• Hypertension

Gastrointestinal Disorders

Not known

• Dyspepsia
• Nausea
• Peptic ulcer with perforation and haemorrhage
• Abdominal distension
• Abdominal pain
• Diarrhoea
• Oesophageal ulceration
• Oesophageal candidiasis
• Pancreatitis acute

Skin and Subcutaneous Tissue Disorders

Not known

• Hirsutism
• Skin atrophy
• Bruising
• Skin striae
• Telangiectasia
• Acne
• Hyperhidrosis
• May suppress reactions to skin tests
• Pruritis
• Rash
• Urticaria

Musculoskeletal and Connective Tissue Disorders

Not known

• Myopathy
• Osteoporosis
• Vertebral and long bone fractures
• Avascular osteonecrosis
• Myalgia

Renal and Urinary Disorders

Not known

• Scleroderma renal crisis

Reproductive System and Breast Disorders

Not known

• Menstrual irregularity and amenorrhoea

General Disorders and Administration Site Conditions

Not known

• Impaired healing
• Withdrawal symptoms
• Fatigue
• Malaise

Investigations

Not known

• Increased weight
• Increased intra-ocular pressure

Injury, Poisoning and Procedural Complications

Not known

• Tendon rupture

• CYP3A inhibitors
• Cobicistat-containing products
• Hepatic microsomal enzyme inducers
• Phenobarbital
• Phenytoin
• Rifampicin
• Rifabutin
• Carbamazepine
• Primidone
• Aminoglutethimide
• Ketoconazole
• Troleandomycin
• Antidiabetic agents
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Indomethacin
• Aspirin
• Salicylates
• Antibacterials
• Rifamycins
• Erythromycin
• Anticoagulants
• Antiepileptics
• Antifungals
• Amphotericin
• Antivirals
• Ritonavir
• Cardiac glycosides
• Ciclosporin
• Cytotoxics
• Methotrexate
• Mifepristone
• Vaccines
• Live vaccines
• Oestrogens
• Somatropin
• Sympathomimetics
• Bambuterol
• Fenoterol
• Formoterol
• Ritodrine
• Salbutamol
• Salmeterol
• Terbutaline
• Hypoglycaemic agents
• Insulin
• Antihypertensives
• Diuretics
• Acetazolamide
• Loop diuretics
• Thiazide diuretics
• Carbenoxolone
• Theophylline

None routine. Specific cases may require

• Growth (paediatric patients)
• Blood pressure
• Blood glucose
• Electrolytes
• Bone mineral density
• Intraocular pressure (prolonged use)
• Eye examination
• Haemoglobin
• Occult blood loss
• Chest x-ray (prolonged use)
• HPA axis suppression
  - ACTH stimulation
  - Morning plasma cortisol
  - Urinary free cortisol
• Presence of infection

Withdrawal

• For patients who have been on more than physiological doses of prednisolone (approximately 7.5mg or equivalent) for over three weeks, withdrawal should not be abrupt
• The method of dose reduction depends on the likelihood of disease relapse as the dose of prednisolone is reduced
• Clinical assessment may be needed during withdrawal
• If the disease is unlikely to relapse but there is uncertainty about HPA (Hypothalamic–Pituitary–Adrenal) axis suppression, the dose of prednisolone may be reduced rapidly to physiological doses
• Once a daily dose equivalent to 7.5mg of prednisolone is reached, dose reduction should be slower to allow the HPA axis to recover
• Abrupt withdrawal is appropriate if the disease is unlikely to relapse and the treatment has continued up to three weeks
• Abrupt withdrawal of doses up to 40mg daily of prednisolone for three weeks is unlikely to lead to clinically relevant HPA axis suppression in most patients
• Gradual withdrawal should be considered in certain patient groups, even after courses lasting three weeks or less:
  • Those who have had repeated courses, especially if taken for more than three weeks
  • Those prescribed a short course within one year of cessation of long-term therapy
  • Those with potential reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy
  • Those receiving doses greater than 40mg daily of prednisolone
  • Those repeatedly taking doses in the evening
• Adrenal cortical atrophy can develop during prolonged therapy and may persist for years after stopping treatment
• Withdrawal after prolonged therapy must always be gradual to avoid acute adrenal insufficiency and may be tapered off over weeks or months depending on the dose and duration of treatment
• Any intercurrent illness, trauma, or surgical procedure during prolonged therapy will require a temporary increase in dosage; if prednisolone has been stopped following prolonged therapy, it may need to be temporarily reintroduced

Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt retaining properties, are used as replacement therapy in adrenocortical deficiency states. Their synthetic analogs are primarily used for their potent anti-inflammatory effects in disorders of many organ systems. Glucocorticoids cause profound and varied metabolic effects. In addition, they modify the body's immune responses to diverse stimuli.

Syrup (per 5ml) 15mg

• Adco prednisolone (Adcock) originator
• Aspelone (Pharmacare)
• Prelone (Adcock) originator
• Prednisilone 15 Strides (Strides Pharma SA)

Tablet 5mg

• Prelone (Adcock)
• Capsoid (Caps Pharmaceuticals)
• Lenisolone (Pharmacare)

Also available in the following form: Eye drop.