Chemical formula: C₂₂H₃₀O₅ Molecular mass: 374.471 g/mol PubChem compound: 6741
Methylprednisolone interacts in the following cases:
There is also an increased risk of hypokalaemia with concurrent use of corticosteroids with beta-2 agonists.
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly metabolized by the CYP3A4 enzyme. CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in the liver of adult humans. It catalyzes 6βhydroxylation of steroids, the essential Phase I metabolic step for both endogenous and synthetic corticosteroids. Many other compounds are also substrates of CYP3A4, some of which (as well as other drugs) have been shown to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the CYP3A4 enzyme.
Drugs that induce CYP3A4 activity generally increase hepatic clearance, resulting in decreased plasma concentration of medications that are substrates for CYP3A4. Co-administration may require an increase in methylprednisolone dosage to achieve the desired result.
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly metabolized by the CYP3A4 enzyme. CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in the liver of adult humans. It catalyzes 6β-hydroxylation of steroids, the essential Phase I metabolic step for both endogenous and synthetic corticosteroids. Many other compounds are also substrates of CYP3A4, some of which (as well as other drugs) have been shown to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the CYP3A4 enzyme.
Drugs that inhibit CYP3A4 activity generally decrease hepatic clearance and increase the plasma concentration of CYP3A4 substrate medications, such as methylprednisolone. In the presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity.
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly metabolized by the CYP3A4 enzyme. CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in the liver of adult humans. It catalyzes 6β-hydroxylation of steroids, the essential Phase I metabolic step for both endogenous and synthetic corticosteroids. Many other compounds are also substrates of CYP3A4, some of which (as well as other drugs) have been shown to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the CYP3A4 enzyme.
In the presence of another CYP3A4 substrate, the hepatic clearance of methylprednisolone may be affected, with corresponding dosage adjustments required. It is possible that adverse events associated with the use of either drug alone may be more likely to occur with co-administration.
Particular care is required when considering the use of systemic corticosteroids in patients with liver failure or cirrhosis and frequent patient monitoring is necessary.
Rarely hepatobiliary disorders were reported, in the majority of these cases, they were reversible after withdrawal of therapy. Therefore appropriate monitoring is required.
Particular care is required when considering the use of systemic corticosteroids in patients with renal insufficiency and frequent patient monitoring is necessary.
Alcohol enhances the ulcerogenic effect of corticosteroids.
Because corticosteroids may increase blood glucose concentrations, dosage adjustments of anti-diabetic agents may be required.
The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.
When corticosteroids are administered concomitantly with potassium-depleting agents (i.e. diuretics), patients should be observed closely for development of hypokalaemia.
Protease inhibitors, such as indinavir and ritonavir, may increase plasma concentrations of corticosteroids. Corticosteroids may induce the metabolism of HIV-protease inhibitors resulting in reduced plasma concentrations.
Antagonism of the neuromuscular blocking effects of pancuronium and vecuronium has been reported in patients taking corticosteroids. This interaction may be expected with all competitive neuromuscular blockers.
There is also an increased risk of hypokalaemia with concurrent use of corticosteroids with xanthenes.
Steroids may reduce the effects of anticholinesterases in myasthenia gravis.
An acute myopathy has been reported with the concomitant use of high doses of corticosteroids and anticholinergics, such as neuromuscular blocking drugs.
There may be increased incidence of gastrointestinal bleeding and ulceration when corticosteroids are given with NSAIDs.
Corticosteroids have been shown to impair fertility in animal studies. In women treatment with corticosteroids can lead to menstrual irregularities.
Methylprednisolone may increase the clearance of high-dose acetylsalicylic acid, which can lead to decreased salicylate serum levels. Discontinuation of methylprednisolone treatment can lead to raised salicylate serum levels, which could lead to an increased risk of salicylate toxicity.
Aminogluthetimide-induced adrenal suppression may exacerbate endocrine changes caused by prolonged glucocorticoid treatment.
There is an increased risk of hypokalaemia with concurrent use of corticosteroids with amphotericin B.
Mutual inhibition of metabolism occurs with concurrent use of ciclosporin and methylprednisolone, which may increase the plasma concentrations of either or both drugs. Therefore, it is possible that adverse events associated with the use of either drug alone may be more likely to occur upon coadministration.
Care should be taken for patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss.
There is a potential effect of methylprednisolone to increase the acetylation rate and clearance of isoniazid.
Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.
Corticosteroids should be used with great care in patients with known or suspected parasitic infections such as Strongyloides (threadworm) infestation, which may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
Systemic corticosteroids are not indicated for, and therefore should not be used to treat, traumatic brain injury, a multicenter study revealed an increased mortality at 2 weeks and 6 months after injury in patients administered methylprednisolone sodium succinate compared to placebo. A causal association with methylprednisolone sodium succinate treatment has not been established.
Particular care is required when considering the use of systemic corticosteroids in patients with abscess or other pyogenic infections and frequent patient monitoring is necessary.
Particular care is required when considering the use of systemic corticosteroids in patients with seizure disorders and frequent patient monitoring is necessary.
Particular care is required when considering the use of systemic corticosteroids in patients with peptic ulceration and frequent patient monitoring is necessary.
Exposure to measles should be avoided. Medical advice must be sought immediately if exposure occurs. Prophylaxis with normal intramuscular immunoglobulin may be needed.
Particular care is required when considering the use of systemic corticosteroids in patients with ocular herpes simplex as there is a fear of corneal perforation, and frequent patient monitoring is necessary.
Glucocorticoids can produce or aggravate Cushing’s syndrome, therefore glucocorticoids should be avoided in patients with Cushing’s disease.
High doses of corticosteroids may produce acute pancreatitis.
Particular care is required when considering the use of systemic corticosteroids in patients with glaucoma (or a family history of glaucoma) as there is a fear of corneal perforation, and frequent patient monitoring is necessary.
An acute myopathy has been reported with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g. myasthenia gravis), or in patients receiving concomitant therapy with anticholinergics, such as neuromuscular blocking drugs (e.g. pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevations of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos or increased intraocular pressure, which may result in glaucoma with possible damage to the optic nerves.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos or increased intraocular pressure, which may result in glaucoma with possible damage to the optic nerves.
Pheochromocytoma crisis, which can be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
Particular care is required when considering the use of systemic corticosteroids in patients with diverticulitis and frequent patient monitoring is necessary.
Secondary fungal infections of the eye may also be enhanced in patients receiving glucocorticoids.
Secondary viral infections of the eye may also be enhanced in patients receiving glucocorticoids.
Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Central serous chorioretinopathy, may lead to retinal detachment.
Thrombosis including venous thromboembolism has been reported to occur with corticosteroids. As a result corticosteroids should be used with caution in patients who have or may be predisposed to thromboembolic disorders.
Particular care is required when considering the use of systemic corticosteroids in patients with hypertension and frequent patient monitoring is necessary.
Chickenpox is of serious concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. Passive immunization with varicella/zoster immunoglobulin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.
Prolonged use of corticosteroids may produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos or increased intraocular pressure, which may result in glaucoma with possible damage to the optic nerves.
Corticosteroids may increase susceptibility to infection, may mask some signs of infection, and new infections may appear during their use. Suppression of the inflammatory response and immune function increases the susceptibility to fungal, viral and bacterial infections and their severity. The clinical presentation may often be atypical and may reach an advanced stage before being recognised.
Persons who are on drugs which suppress the immune system are more susceptible to infections than healthy individuals. Chicken pox and measles, for example, can have a more serious or even fatal course in non-immune children or adults on corticosteroids.
Particular care is required when considering the use of systemic corticosteroids in patients with hypothyroidism and frequent patient monitoring is necessary.
Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of congestive heart failure.
There have been reports of epidural lipomatosis in patients taking corticosteroids, typically with long-term use at high doses.
Particular care is required when considering the use of systemic corticosteroids in patients with recent myocardial infarction (myocardial rupture has been reported) and frequent patient monitoring is necessary.
Corticosteroids cause growth retardation in infancy, childhood and adolescence. Growth and development of infants and children on prolonged corticosteroid therapy should be carefully observed. Treatment should be limited to the minimum dosage for the shortest possible time. In order to minimise suppression of the hypothalamo-pituitary-adrenal axis and growth retardation, treatment should be administered where possible as a single dose on alternate days.
Glucocorticoid therapy may mask peritonitis or other signs or symptoms associated with gastrointestinal disorders such as perforation, obstruction or pancreatitis.
Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids. Symptoms typically emerge within a few days or weeks of starting treatment. Risks may be higher with high doses/systemic exposure, although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary.
Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.
Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.
Particular care is required when considering the use of systemic corticosteroids in patients with osteoporosis (post-menopausal females are particularly at risk) and frequent patient monitoring is necessary.
Corticosteroids, including methylprednisolone, can increase blood glucose, worsen pre-existing diabetes, and predispose those on long-term corticosteroid therapy to diabetes mellitus.
Particular care is required when considering the use of systemic corticosteroids in patients with Diabetes mellitus (or a family history of diabetes) and frequent patient monitoring is necessary.
Particular care is required when considering the use of systemic corticosteroids in patients with fresh intestinal anastomoses and frequent patient monitoring is necessary.
The role of corticosteroids in septic shock has been controversial, with early studies reporting both beneficial and detrimental effects. More recently, supplemental corticosteroids have been suggested to be beneficial in patients with established septic shock who exhibit adrenal insufficiency. However, their routine use in septic shock is not recommended. A systematic review of short-course high-dose corticosteroids did not support their use. However, meta-analyses, and a review have suggested that longer courses (5-11 days) of low-dose corticosteroids might reduce mortality.
Caution is required in patients with systemic sclerosis because an increased incidence of scleroderma renal crisis has been observed with corticosteroids, including methylprednisolone. Blood pressure and renal function (s-creatinine) should therefore be routinely checked. When renal crisis is suspected, blood pressure should be carefully controlled.
Population group: only newborns (0 - 40 days old) , infants (40 days - 1 year old) , children (1 year - 12 years old)
Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure.
The ability of corticosteroids to cross the placenta varies between individual drugs, however, methylprednisolone does cross the placenta. In humans, the risk of low birth weight appears to be dose related and may be minimized by administering lower corticosteroid doses.
Administration of corticosteroids 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 result in an increased incidence of congenital abnormalities, such as cleft palate in man, however, when administered for long periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Infants born to mothers, who have received substantial doses of corticosteroids during pregnancy must be carefully observed and evaluated for signs of adrenal insufficiency. Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important.
Since adequate human reproductive studies have not been done with methylprednisolone, this medicinal product, as with all drugs, should be used during pregnancy only after a careful assessment of the benefit-risk ratio to the mother, embryo, foetus or child. When corticosteroids are essential, however, patients with normal pregnancies may be treated as though they were in the non-gravid state.
Cataracts have been observed in infants born to mothers undergoing long-term treatment with corticosteroids during pregnancy.
Corticosteroids are excreted in small amounts in breast milk, however, doses of up to 40 mg daily of methylprednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression. This medicinal product should be used during breast feeding only after a careful assessment of the benefit-risk ratio to the mother and infant.
Corticosteroids have been shown to impair fertility in animal studies.
In women treatment with corticosteroids can lead to menstrual irregularities.
The effect of corticosteroids on the ability to drive or use machinery has not been systematically evaluated. Undesirable effects, such as dizziness, vertigo, visual disturbances and fatigue are possible after treatment with corticosteroids. If affected, patients should not drive or operate machinery.
Common: Infection (including increased susceptibility and severity of infections with suppression of clinical symptoms and signs)
Not Known: Opportunistic infection; recurrence of dormant tuberculosis, Peritonitis†
Not Known: Leukocytosis
Not Known: Drug hypersensitivity, Anaphylactic reaction, Anaphylactoid reaction
Common: Cushingoid
Not Known: Hypopituitarism
Not Known: Kaposi’s sarcoma
Common: Sodium retention; Fluid retention
Not Known: Metabolic acidosis; Alkalosis hypokalaemic; Dyslipidaemia; Glucose tolerance impaired; increased requirements for insulin (or oral hypoglycemic agents in diabetics); Lipomatosis; Increased appetite (which may result in Weight increased); Epidural lipomatosis
Common: Affective disorder (including Depressed mood and Euphoric mood)
Not Known: Psychotic disorder (including Mania, Delusion, Hallucination, and Schizophrenia; Psychotic behaviour; Affective disorder (including Affect lability, Psychological dependence, Suicidal ideation); Mental disorder; Personality change; Confusional state; Anxiety; Mood swings; Abnormal behaviour; Insomnia; Irritability
Not Known: Intracranial pressure increased (with Papilloedema [Benign intracranial hypertension]); Seizure; Amnesia; Cognitive disorder; Dizziness; Headache
Common: Cataract
Rare: Vision blurred
Not Known: Glaucoma; Exophthalmos; Corneal thinning; Scleral thinning; Chorioretinopathy
Not Known: Vertigo
Not Known: Cardiac failure congestive (in susceptible patients); Myocardial rupture following myocardial infarction
Common: Hypertension
Not Known: Hypotension; Embolism arterial; Thrombotic events
Not Known: Pulmonary embolism, Hiccups
Common: Peptic ulcer (with possible Peptic ulcer perforation and Peptic ulcer haemorrhage)
Not Known: Intestinal perforation; Gastric haemorrhage; Pancreatitis; Oesophagitis ulcerative; Oesophagitis; Abdominal distension; Abdominal pain; Diarrhoea; Dyspepsia; Nausea
Not Known: Increase of liver enzymes (e.g. alanine aminotransferase increased, aspartate aminotransferase increased)
Common: Skin atrophy; Acne
Not Known: Angioedema; Hirsutism; Petechiae; Ecchymosis; Erythema; Hyperhidrosis; Skin striae; Rash; Pruritus; Urticaria; Telangiectasia
Common: Muscular weakness; Growth retardation
Not Known: Myalgia; Myopathy; Muscle atrophy; Osteoporosis; Osteonecrosis; Pathologic fracture; Neuropathic arthropathy; Arthralgia;
Not Known: Menstruation irregular
Common: Impaired healing
Not Known: Oedema peripheral ;Fatigue; Malaise; Withdrawal symptoms – too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death
Common: Blood potassium decreased
Not Known: Intraocular pressure increased; Carbohydrate tolerance decreased; Urine calcium increased Blood alkaline phosphatase increased; Blood urea increased; Suppression of reactions to skin tests*
Not Known: Tendon rupture (particularly of the Achilles tendon); Spinal compression fracture
* Not a MedDRA PT
† Peritonitis may be the primary presenting sign or symptom of a gastrointestinal disorder such as perforation, obstruction or pancreatitis.
Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Not known (frequency cannot be estimated from the available data)
The incidence of predictable undesirable side-effects associated with the use of corticosteroids, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and duration of treatment.
The following adverse reactions have been reported with the following routes of administration: Intrathecal/Epidural: Arachnoiditis, functional gastrointestinal disorder/bladder dysfunction, headache, meningitis, paraparesis/paraplegia, seizure and sensory disturbances.
Under normal circumstances methylprednisolone therapy would be considered as short-term. However, the possibility of side-effects attributable to corticosteroid therapy should be recognised, particularly when high-dose therapy is being used. Such side-effects include:
Frequency: Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Not known (frequency cannot be estimated from the available data)
Not Known: Infection (including increased susceptibility and severity of infections with suppression of clinical symptoms and signs); Opportunistic infection; Recurrence of dormant tuberculosis; Peritonitis#
Not Known: Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy. Discontinuation of corticosteroids may result in clinical remission.
Not Known: Leukocytosis.
Not Known: Drug hypersensitivity (Anaphylactic reaction; Anaphylactoid reaction).
Not Known: Cushingoid; Hypopituitarism (including suppression of the hypothalamo-pituitary-adrenal axis); Steroid withdrawal syndrome (including, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight).
Not Known: Metabolic acidosis; Sodium retention; Fluid retention; Glucose tolerance impaired; Alkalosis hypokalaemic; Dyslipidemia; Increased insulin requirements (or oral hypoglycemic agents in diabetics); Lipomatosis; Increased appetite (which may result in weight increase); Epidural lipomatosis.
Not Known: A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, drug dependence and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations and schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported for all corticosteroids. Reactions may occur in both adults and children. In adults, the frequency of severe reactions was estimated to be 5%-6%. Psychological effects have been reported on withdrawal of corticosteroids; the frequency is unknown.
Not Known: Increased intracranial pressure with Papilloedema [Benign intracranial hypertension]; Seizure; Amnesia; Cognitive disorder; Dizziness; Headache.
Rare: Vision blurred.
Not Known: Posterior subcapsular cataracts; Exophthalmos; Glaucoma; Papilloedema with possible damage to the optic nerve; Corneal or scleral thinning; Exacerbation of ophthalmic viral or fungal disease; Chorioretinopathy.
Not Known: Vertigo.
Not Known: Congestive heart failure in susceptible patients; Arrhythmia.
Not Known: Hypertension; Hypotension; Thrombotic events.
Not Known: Hiccups; Pulmonary embolism.
Not Known: Peptic ulcer (with possible peptic ulcer perforation and peptic ulcer haemorrhage); Gastric haemorrhage; Intestinal perforation; Pancreatitis; Ulcerative oesophagitis; Oesophagitis; Oesophageal candidiasis; Abdominal pain; Abdominal distension; Diarrhoea; Dyspepsia; Nausea; Vomiting; Bad taste in mouth may occur especially with rapid administration.
Not Known: Hepatitis†; Increase of liver enzymes (e.g. alanine aminotransferase increased (ALT, SGPT), aspartate aminotransferase increased (AST, SGOT)).
Not Known: Ecchymosis; Skin atrophy (thin fragile skin); Acne; Angioedema; Petechiae; Skin striae; Telangiectasia; Skin hypopigmentation or hyperpigmentation; Hirsutism; Rash; Erythema; Pruritus; Urticaria; Hyperhidrosis.
Not Known: Growth retardation; Osteoporosis; Muscular weakness; Osteonecrosis; Pathological fracture; Muscle atrophy; Myopathy; Neuropathic arthropathy; Arthralgia; Myalgia.
Not Known: Irregular menstruation; Amenorrhoea.
Not Known: Impaired wound healing; Oedema peripheral; Injection site reaction; Fatigue; Malaise; Withdrawal symptoms – Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death. However, this is more applicable to corticosteroids with an indication where continuous therapy is given.
Not Known: Intraocular pressure increased; Carbohydrate tolerance decreased; Blood potassium decreased (potassium loss); Urine calcium increased; Blood alkaline phosphatase increased; Blood urea increased; Suppression of reactions to skin tests.
Not Known: Tendon rupture (particularly of the Achilles tendon); Spinal compression fracture (vertebral compression fractures).
† Hepatitis has been reported with IV administration.
# Peritonitis may be the primary presenting sign or symptom of a gastrointestinal disorder such as perforation, obstruction or pancreatitis.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
