Drugs List

Therapeutic Indications

Uses

For the treatment of conditions requiring glucocorticoid activity including allergic and inflammatory conditions and replacement therapy in primary or secondary adrenal insufficiency.

Administration

For oral administration either as a single daily dose, a single dose on alternate days or in divided daily doses.

Contraindications

Systemic infections in the absence of anti-infective therapy

Galactosaemia
Hereditary fructose intolerance

Precautions and Warnings

The lowest effective dose should always be used for the minimum possible period. Frequent patient review is required to appropriately titrate the dose against disease activity. When reduction in dosage is possible, the reduction should be gradual.
In acute, life-threatening situations, administration of dosages exceeding the usual level may be justified.

All patients should carry a steroid treatment card containing information on precautions to be taken to minimise risks and details of the prescriber, drug, dosage and duration of treatment.

Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may be atypical, and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised. Appropriate anti-microbial therapy should accompany glucocorticoid therapy when necessary e.g. in tuberculosis and viral and fungal infections of the eye.

Patients without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster, and if exposed should seek urgent medical attention. Exposed non-immune patients who are receiving systemic corticosteroids, or who have used them within the past 3 months, should receive passive immunisation with varicella zoster immunoglobulin (VZIG) within 10 days of exposure to chicken pox. If chickenpox infection is confirmed, specialist care and urgent treatment is required. Corticosteroid therapy should not be stopped and the dose may need to be increased.

Adults and children should also take particular care to avoid exposure to measles. If exposed, prophylaxis with intramuscular pooled immunoglobulin may be indicated. Exposed patients should be advised to seek urgent medical attention.

Corticosteroids may activate latent tuberculosis, amoebiasis or strongyloidiasis or exacerbate active disease. It is recommended that these are excluded before initiating therapy, particularly in patients with unexplained diarrhoea or who have recently spent time in the tropics. For patients with latent tuberculosis, an appropriate antituberculous regimen should be taken in conjunction with the use of methylprednisolone.

Live vaccines should not be given to immunocompromised patients.
Antibody response to other vaccines may be diminished.

Treatment may result in impaired mineralocorticoid secretion, supplementation with salt or a mineralocorticoid is recommended during therapy.

Patients should be monitored for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress ( e.g. surgery, infection, trauma ). During stress it may be necessary to increase dosage temporarily. Corticosteroid therapy may need to be temporarily re-introduced if treatment has been stopped following prolonged therapy.

Corticosteroids should not be used for the management of head injury or stroke as there is unlikely to be any benefit and may be harmful.

Severe anaphylactoid reactions have occurred after administration of corticosteroids, especially in patients with a history of allergy.

Systemic corticosteroids, particularly in high doses, are linked to psychiatric reactions, both during treatment and whilst the corticosteroid is being withdrawn. A serious paranoid state or depression with risk of suicide can be induced and patients with a history of mental disorder are at particular risk. These reactions often subside on dose reduction or withdrawal of treatment but some may require specific management. Patients should be advised to seek medical advice if psychiatric symptoms occur, especially depression or ideas of suicide.

Particular caution is advised in patients with existing or history of severe affective disorders (such as depressive or manic-depressive illness or previous steroid-induced psychosis) in themselves or in their first-degree relatives.

Particular care and frequent monitoring is required when treating patients with the following conditions:
Renal impairment
Epilepsy
Hepatic cirrhosis
Hypothyroidism
Myasthenia gravis
Osteoporosis (post menopausal females are particularly at risk)
Recent myocardial infarction (left ventricular free wall rupture after MI associated with corticosteroid use)
Diabetes mellitus or a family history of diabetes mellitus
Hypertension
History of tuberculosis
Severe affective disorders or a history of severe affective disorders
Glaucoma or a family history of glaucoma.
Previous steroid-induced psychosis
Previous corticosteroid induced myopathy
Hepatic failure
Peptic ulceration
Recent intestinal anastomosis
Predisposition to thrombophlebitis
Abscess or other pyogenic infections
Ulcerative colitis (unless for treatment)
Diverticulitis
Ocular herpes simplex
Congestive cardiac failure and those patients receiving cardioactive drugs.

Kaposi's sarcoma may occur in patients on corticosteroid therapy. Discontinuation of the corticosteroid may result in remission of the sarcoma.

Prolonged use of pharmacological doses of corticosteroids can lead to hypothalamic-pituitary-adrenal (HPA) suppression. The duration and severity of adrenocortical insufficiency is dependant on dose, frequency, duration of glucocorticoid therapy and time of administration. Acute adrenal insufficiency may be fatal if glucocorticoid treatment is withdrawn too rapidly. A gradual reduction in dosage can help to minimise the effects of drug-induced secondary adrenocortical insufficiency. However, this type of relative insufficiency can persist for many months to years after treatment has been discontinued. Reinstitution of hormone therapy may be required in times of stress during this period.

Abrupt withdrawal may be acceptable if therapy has been shorter than 3 weeks and the condition is unlikely to relapse ( see also Additional dosage ).

Prolonged use of corticosteroids may produce subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Large doses of corticosteroids may mask the symptoms of gastro intestinal perforation.

Monitor linear growth in infants and children on prolonged corticosteroid therapy. Corticosteroids may cause growth retardation in infancy, childhood and adolescence.

Caution should be taken when treating elderly patients. Any serious consequences of common side effects (e.g. osteoporosis, diabetes, hypertension, hypokalaemia, susceptibility to infection and thinning of the skin) must be taken into consideration.

This medication contains lactose and sucrose and therefore patients with glucose-galactose malabsorption syndrome or those who are lactose intolerant should not take this drug.

Pregnancy and Lactation

Pregnancy

Caution is advised during pregnancy.

Methylprednisolone crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and affects on brain growth and development.

Schaefer (2007) suggests that there is inconclusive evidence that corticosteroids result in an increased incidence of congenital abnormalities however, a possible association with clefts cannot excluded. When administered for long periods or repeatedly during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation. Hypoadrenalism may occur in the neonate following prenatal exposure but usually resolves spontaneously following birth and is rarely clinically important.

Corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential, patients with normal pregnancies may be treated as though they were in a non-gravid state.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Caution is advised during lactation.

Corticosteroids are excreted in small amounts in breast milk, however doses up to 40mg daily of methylprednisolone are unlikely to cause systemic effects in the infant.

Infants of mothers taking higher doses may have a degree of adrenal suppression, but the benefits of breastfeeding are likely to outweigh any theoretical risk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - yes in small amounts

Considered suitable or recommended by manufacturer? - Yes

UK Drugs in Lactation Advisory Service Classification - Gives very low levels in infant with no apparent effects.

Drug substance licensed in infants? - From 1 month of age

Side Effects

Hypertension
Fluid retention
Osteoporosis
Euphoria
Cushing's syndrome
Cushingoid facies
Growth retardation (children)
Proximal myopathy
Dyspepsia
Peptic ulceration with perforation and haemorrhage
Abdominal distension
Oesophageal ulceration
Oesophageal candidiasis
Acute pancreatitis
Bowel perforation
Altered liver function tests
Suppression of clinical signs of infection
Increased susceptibility and severity of infections
Vertebral and long bone fractures
Avascular osteonecrosis
Tendon damage
Muscle weakness
Hypokalaemia
Congestive cardiac failure
Impaired healing
Thinning of skin
Bruising
Striae
Telangiectasia
Acne
Petechiae
Ecchymosis
Suppression of the hypothalamic-pituitary-adrenal axis
Menstrual disturbances
Amenorrhoea
Hirsutism
Weight gain
Decreased glucose tolerance
Increased appetite
Mood changes
Personality change
Psychosis
Increased I.C.P. with papilloedema in children (pseudotumour cerebri)
Seizures
Increased intra-ocular pressure
Glaucoma
Papilloedema
Cataracts
Optic nerve damage
Corneal changes
Leucocytosis
Hypersensitivity reactions
Anaphylaxis
Thromboembolism
Nausea
Malaise
Depression of hypothalamus, pituitary and adrenal function on withdrawal
Suppression of reactions to skin tests
Aggravation of schizophrenia
Recurrence of dormant tuberculosis
Exacerbation of ophthalmic viral disease
Exacerbation of ophthalmic fungal disease
Myocardial rupture following recent myocardial infarction
Withdrawal syndrome - see product information
Hiccups
Kaposi's Sarcoma
Psychological dependence
Gastro-intestinal haemorrhage
Opportunistic infections
Sodium retention
Skin atrophy
Suicidal tendencies
Mania
Delusions
Hallucinations
Irritability
Anxiety
Sleep disturbances
Cognitive impairment
Confusion
Amnesia
Scleral thinning
Musculoskeletal disturbances
Metabolic acidosis
Mental status changes
Behavioural disturbances
Headache
Dizziness
Exophthalmos
Hypokalaemic alkalosis
Rash
Diarrhoea
Erythema
Angioedema
Urticaria
Hyperhidrosis
Vertigo

Presentation

Tablets containing 2mg methylprednisolone
Tablets containing 4mg methylprednisolone
Tablets containing 16mg methylprednisolone
Tablets containing 100mg methylprednisolone

Drugs List

Therapeutic Indications

Uses

For the treatment of conditions requiring glucocorticoid activity including allergic and inflammatory conditions and replacement therapy in primary or secondary adrenal insufficiency.

Dosage

Undesirable effects may be minimised by using the lowest effective dose for the minimum period.

Dosage should be individualised and depends on condition being treated and its severity. Frequent patient review is needed to titrate dose against disease activity.

Adults

Elderly

Children

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Administration

For oral administration either as a single daily dose, a single dose on alternate days or in divided daily doses.

Contraindications

Systemic infections in the absence of anti-infective therapy

Galactosaemia
Hereditary fructose intolerance

Precautions and Warnings

The lowest effective dose should always be used for the minimum possible period. Frequent patient review is required to appropriately titrate the dose against disease activity. When reduction in dosage is possible, the reduction should be gradual.
In acute, life-threatening situations, administration of dosages exceeding the usual level may be justified.

All patients should carry a steroid treatment card containing information on precautions to be taken to minimise risks and details of the prescriber, drug, dosage and duration of treatment.

Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. The clinical presentation may be atypical, and serious infections such as septicaemia and tuberculosis may be masked and may reach an advanced stage before being recognised. Appropriate anti-microbial therapy should accompany glucocorticoid therapy when necessary e.g. in tuberculosis and viral and fungal infections of the eye.

Patients without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster, and if exposed should seek urgent medical attention. Exposed non-immune patients who are receiving systemic corticosteroids, or who have used them within the past 3 months, should receive passive immunisation with varicella zoster immunoglobulin (VZIG) within 10 days of exposure to chicken pox. If chickenpox infection is confirmed, specialist care and urgent treatment is required. Corticosteroid therapy should not be stopped and the dose may need to be increased.

Adults and children should also take particular care to avoid exposure to measles. If exposed, prophylaxis with intramuscular pooled immunoglobulin may be indicated. Exposed patients should be advised to seek urgent medical attention.

Corticosteroids may activate latent tuberculosis, amoebiasis or strongyloidiasis or exacerbate active disease. It is recommended that these are excluded before initiating therapy, particularly in patients with unexplained diarrhoea or who have recently spent time in the tropics. For patients with latent tuberculosis, an appropriate antituberculous regimen should be taken in conjunction with the use of methylprednisolone.

Live vaccines should not be given to immunocompromised patients.
Antibody response to other vaccines may be diminished.

Treatment may result in impaired mineralocorticoid secretion, supplementation with salt or a mineralocorticoid is recommended during therapy.

Patients should be monitored for signs that might require dosage adjustment, including changes in clinical status resulting from remissions or exacerbations of the disease, individual drug responsiveness, and the effect of stress ( e.g. surgery, infection, trauma ). During stress it may be necessary to increase dosage temporarily. Corticosteroid therapy may need to be temporarily re-introduced if treatment has been stopped following prolonged therapy.

Corticosteroids should not be used for the management of head injury or stroke as there is unlikely to be any benefit and may be harmful.

Severe anaphylactoid reactions have occurred after administration of corticosteroids, especially in patients with a history of allergy.

Systemic corticosteroids, particularly in high doses, are linked to psychiatric reactions, both during treatment and whilst the corticosteroid is being withdrawn. A serious paranoid state or depression with risk of suicide can be induced and patients with a history of mental disorder are at particular risk. These reactions often subside on dose reduction or withdrawal of treatment but some may require specific management. Patients should be advised to seek medical advice if psychiatric symptoms occur, especially depression or ideas of suicide.

Particular caution is advised in patients with existing or history of severe affective disorders (such as depressive or manic-depressive illness or previous steroid-induced psychosis) in themselves or in their first-degree relatives.

Particular care and frequent monitoring is required when treating patients with the following conditions:
Renal impairment
Epilepsy
Hepatic cirrhosis
Hypothyroidism
Myasthenia gravis
Osteoporosis (post menopausal females are particularly at risk)
Recent myocardial infarction (left ventricular free wall rupture after MI associated with corticosteroid use)
Diabetes mellitus or a family history of diabetes mellitus
Hypertension
History of tuberculosis
Severe affective disorders or a history of severe affective disorders
Glaucoma or a family history of glaucoma.
Previous steroid-induced psychosis
Previous corticosteroid induced myopathy
Hepatic failure
Peptic ulceration
Recent intestinal anastomosis
Predisposition to thrombophlebitis
Abscess or other pyogenic infections
Ulcerative colitis (unless for treatment)
Diverticulitis
Ocular herpes simplex
Congestive cardiac failure and those patients receiving cardioactive drugs.

Kaposi's sarcoma may occur in patients on corticosteroid therapy. Discontinuation of the corticosteroid may result in remission of the sarcoma.

Prolonged use of pharmacological doses of corticosteroids can lead to hypothalamic-pituitary-adrenal (HPA) suppression. The duration and severity of adrenocortical insufficiency is dependant on dose, frequency, duration of glucocorticoid therapy and time of administration. Acute adrenal insufficiency may be fatal if glucocorticoid treatment is withdrawn too rapidly. A gradual reduction in dosage can help to minimise the effects of drug-induced secondary adrenocortical insufficiency. However, this type of relative insufficiency can persist for many months to years after treatment has been discontinued. Reinstitution of hormone therapy may be required in times of stress during this period.

Abrupt withdrawal may be acceptable if therapy has been shorter than 3 weeks and the condition is unlikely to relapse ( see also Additional dosage ).

Prolonged use of corticosteroids may produce subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses.

Large doses of corticosteroids may mask the symptoms of gastro intestinal perforation.

Monitor linear growth in infants and children on prolonged corticosteroid therapy. Corticosteroids may cause growth retardation in infancy, childhood and adolescence.

Caution should be taken when treating elderly patients. Any serious consequences of common side effects (e.g. osteoporosis, diabetes, hypertension, hypokalaemia, susceptibility to infection and thinning of the skin) must be taken into consideration.

This medication contains lactose and sucrose and therefore patients with glucose-galactose malabsorption syndrome or those who are lactose intolerant should not take this drug.

Pregnancy and Lactation

Pregnancy

Caution is advised during pregnancy.

Methylprednisolone crosses the placenta. Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and affects on brain growth and development.

Schaefer (2007) suggests that there is inconclusive evidence that corticosteroids result in an increased incidence of congenital abnormalities however, a possible association with clefts cannot excluded. When administered for long periods or repeatedly during pregnancy, corticosteroids may increase the risk of intrauterine growth retardation. Hypoadrenalism may occur in the neonate following prenatal exposure but usually resolves spontaneously following birth and is rarely clinically important.

Corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential, patients with normal pregnancies may be treated as though they were in a non-gravid state.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Caution is advised during lactation.

Corticosteroids are excreted in small amounts in breast milk, however doses up to 40mg daily of methylprednisolone are unlikely to cause systemic effects in the infant.

Infants of mothers taking higher doses may have a degree of adrenal suppression, but the benefits of breastfeeding are likely to outweigh any theoretical risk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Drug excreted in breast milk? - yes in small amounts

Considered suitable or recommended by manufacturer? - Yes

UK Drugs in Lactation Advisory Service Classification - Gives very low levels in infant with no apparent effects.

Drug substance licensed in infants? - From 1 month of age

Effects on Ability to Drive and Operate Machinery

None known.

Counselling

All patients should carry a steroid treatment card containing information on precautions to be taken to minimise risks and details of the prescriber, drug, dosage and duration of treatment.

Patients should be advised to avoid exposure to measles, chickenpox and herpes zoster. If exposure occurs, patients should be advised to seek urgent medical attention.

Side Effects

Hypertension
Fluid retention
Osteoporosis
Euphoria
Cushing's syndrome
Cushingoid facies
Growth retardation (children)
Proximal myopathy
Dyspepsia
Peptic ulceration with perforation and haemorrhage
Abdominal distension
Oesophageal ulceration
Oesophageal candidiasis
Acute pancreatitis
Bowel perforation
Altered liver function tests
Suppression of clinical signs of infection
Increased susceptibility and severity of infections
Vertebral and long bone fractures
Avascular osteonecrosis
Tendon damage
Muscle weakness
Hypokalaemia
Congestive cardiac failure
Impaired healing
Thinning of skin
Bruising
Striae
Telangiectasia
Acne
Petechiae
Ecchymosis
Suppression of the hypothalamic-pituitary-adrenal axis
Menstrual disturbances
Amenorrhoea
Hirsutism
Weight gain
Decreased glucose tolerance
Increased appetite
Mood changes
Personality change
Psychosis
Increased I.C.P. with papilloedema in children (pseudotumour cerebri)
Seizures
Increased intra-ocular pressure
Glaucoma
Papilloedema
Cataracts
Optic nerve damage
Corneal changes
Leucocytosis
Hypersensitivity reactions
Anaphylaxis
Thromboembolism
Nausea
Malaise
Depression of hypothalamus, pituitary and adrenal function on withdrawal
Suppression of reactions to skin tests
Aggravation of schizophrenia
Recurrence of dormant tuberculosis
Exacerbation of ophthalmic viral disease
Exacerbation of ophthalmic fungal disease
Myocardial rupture following recent myocardial infarction
Withdrawal syndrome - see product information
Hiccups
Kaposi's Sarcoma
Psychological dependence
Gastro-intestinal haemorrhage
Opportunistic infections
Sodium retention
Skin atrophy
Suicidal tendencies
Mania
Delusions
Hallucinations
Irritability
Anxiety
Sleep disturbances
Cognitive impairment
Confusion
Amnesia
Scleral thinning
Musculoskeletal disturbances
Metabolic acidosis
Mental status changes
Behavioural disturbances
Headache
Dizziness
Exophthalmos
Hypokalaemic alkalosis
Rash
Diarrhoea
Erythema
Angioedema
Urticaria
Hyperhidrosis
Vertigo

Withdrawal Symptoms and Signs

A withdrawal syndrome may occur symptoms may present as:
Fever
Myalgia
Arthralgia
Rhinitis
Conjunctivitis,
Painful itchy skin nodules
Weight loss.

Withdrawal symptoms due to a rapid reduction of corticosteroid doses may lead to adrenal insufficiency, hypotension and death.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store below 25 degrees C

Further Information

Last Full Review Date: April 2012

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Summary of product characteristics: Medrone tablets 2mg, 4mg. Pharmacia Ltd. August 2011.
Summary of product characteristics: Medrone tablets 16mg. Pharmacia Ltd. September 2011.
Summary of product characteristics: Medrone tablets 100mg. Pharmacia Ltd. August 2011.

NICE Evidence Services Available at: www.nice.org.uk Last accessed: 23 August 2017