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Drug Medrol 4 mg have composition methylprednisolone 4mg, Medrol 4 mg indication for Rheumatic Disorders, Dermatologic Diseases, Allergic States, Respiratory Disease, Neoplastic Diseases,  Gastrointestinal Diseases

Alpha Choay indications enzymatic anti-oedema and anti-inflammatory : such as soft tissue injuries

SPECIAL WARNING:

Prescription only

Read the instruction thoroughly before use Do not exceed the prescnbed dosage, if encountenng with any side effects, please consult physicians.

Consuit physician for further information Do not use the expired drugs Keep out of reach of children

MEDROL 4 MG - methylprednisolone 4 mg

1. NAME OF THE MEDICINAL PRODUCT MEDROL

2. QUALITATIVE AND QUANTITATIVE COMPOSITION :

Each tablet contains 4 mg or 16 mg of methylprednisolone.

3. PHARMACEUTICAL FORM

Tablet

4. CLINICAL PARTICULARS

4.1 Therapeutic Indications of Medrol 4 mg

Endocrine Disorders

Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the first choice, synthetic analogs may be used in conjunction with mmalocorticoids where applicable, in infancy mineralocorticoid supplementation is of particular importance).

– Congenital adrenal hyperplasia

– Nonsuppurative thyroiditis

– Hypercalcemia associated with cancer

Nonendocrine Disorders

1. Rheumatic Disorders

As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in.

– psonatic arthritis

– acute gouty arthritis

– rheumatoid arthritis, including juvenile

– post-traumatic osteoarthritis rheumatoid arthntis (selected cases may require low-dose maintenance therapy)

– ankylosing spondylitis

– synovitis of osteoarthritis

– acute ana subacute bursitis

– epicondylitis

– acute nonspecific tenosynovitis

2. Collagen Deeases

Dunng an exacerbation or as maintenance therapy in selected cases of:

– systemic lupus erythematosus

– polymyalgia rheumatics

– systemcdermatomyositis (polymyositis)

– giant cell arteritis

– acute rheumatic carditis

3. Dermatologic Diseases

– pemphigus

– mycosis fungoides

– bullous dermatitis herpetiformis

– severe psoriasis

– severe erythema multitorme (Stevens- Johnson syndrome)

– severe seborrheic dermatitis

exfoliative dermatitis

4. Allergic States

Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment:

– seasonal or perennial allergic rhinitis

– drug hypersensitivity reactions

– serum sickness

– contact dermatitis

– bronchial asthma

– atopic dermatitis

5. Ophthalmic Diseases

Severe acute and chronic allergic and inflammatory processes involving the eye and its adenexa such as.

– allergic corneal marginal ulcers

– allergic conjunctivitis

– herpes zoster ophthalmicus

– keratitis

– anterior segment inflammation

– chorioretinitis

– diffuse posterior uveitis and choroiditis

– optic neuritis

– sympathetic ophthalmia

– iritis and iridocyclitis

6. Respiratory Disease

– symptomatic sarcoidosis

– fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy

– Leoffler’s syndrome not manageable

– aspiration pneumonitis by other means

– berylliosis

7. Hematologic Disorders

– idiopathic thrombocytopenic purpura

– erythroblastopenia (RBC anemia) in adults

– secondary thrombocytopenia in adults

– congenital (erythroid) hypoplastic anemia

– acquired (autoimmune) hemolytic anemia

8. Neoplastic Diseases

For palliative management of

– leukemias and lymphomas in adults

– acute leukemia of childhood

9. Edematous States

– to induce a diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, or the idiopathic type or that due to lupus erythematosus

10. Gastrointestinal Diseases

To tide the patient over a critical period of the disease in:

– ulcerative colitis

– regional enteritis

11. Nervous System

– acute exacerbations of multiple sclerosis

– management of edema associated with brain tumor

12. Organ Transplantation

13. Miscellaneous

– tuberculous meningitis with subarachnoid block or impending block when used concurrently with approphate antituberculous chemotherapy

– trichinosis with neurologic or myocardial involvement

MEDROL 16 MG - methylprednisolone 16 mg

4.2 Posology and Method of Administration

The initial dosage or methylprednisolone tablets may vary from 4 mg to 48 mg as methylprednisotone per day depending on the specific disease entity being treated In situations of less severity, lower doses will generally suffice while in selected patients higher initial doses may be required. Clinical situations in which high-dose therapy may be indicated include multiple sclerosis (200 mg/day), cerebral edema (200-1,000 mg/ day), and organ transplantation (up to 7 mg/kg/day). If after a reasonable period of time there js a Jack of satisfactory clinical response, methylprednisolone tablets should be discontinued and the patient transferred to other appropriate therapy If after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually rather than abruptly

After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response is reached It should be kept in mind that constant monitoring is needed in regard to drug dosage Included in toe situations which may make dosage adjustments necessary are changes in clinical status secondary to remissions or exacerbations in the disease process, the patient’s individual drug responsiveness, and the effect of patient exposure to stressful situations not directly related to the disease entity under treatment; in this latter situation it may be necessary to increase the dosage of methylprednisolone tablets for a period of time consistent with the patient’s condition.

It should be emphasized that dosage requirements are variable and must be i ndividualized on the basis of the disease under treatment and the response of the patient.

Alternate Dav Therapy (ADT)

Alternate day therapy is a corticosteroid dosing regimen in which twice the usual daily dose of corticosteroid is administered every other morning. The purpose of this mode of therapy is to provide a patient requiring long-term pharmacologic dose treatment with the beneficial effects of corticoids while minimizing certain undesirable effects, including pituitary-adrenal suppression, the Cushingoid state, corticoid withdrawal symptoms, and growth suppression in children,

4.3 Contraindications

Medrol 4 mg ( Methylprednisolone ) tablets are contraindicated in patients who have;

– systemic fungal infections

– known hypersensitivity to methylprednisolone tablets or to methylprednisolone. Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids,

4.4 Special Warnings and Special Precautions for Use

Immunosuppressant Effects/lncreased Susceptibility to Infections

Corticosteroids may increase susceptibility to infection, may mask some signs of infection, and new infections may appear during their use. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infections with any pathogen including viral, bacterial, fungal, protozoan or helminthic organisms, in any location in the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect cellular immunity, humoral immunity, or neutrophil function. These infections may be mild, but can be severe and at times fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.

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 fetal course in non-immune children or adults on corticosteroids. Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to such vaccines may be diminished. Indicated immunization procedures may be undertaken in patients receiving nonimmunosuppressive doses of corticosteroids.

The use of corticosteroids in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen, if corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis. Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy Discontinuation of corticosteroids may result in clinical remission The rote 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 and a systematic review concluded that short-course, high-dose corticosteroids did not support their use However, meta-analyses and a review suggest that longer courses (5-11 days) of low-dose corticosteroids might reduce mortality, especially in patients with vasopressor-dependent septic shock.

Immune System

Allergic reactions (e.g., angioedema) may occur.

Because rare instances of skin reactions and anaphylactic/anaphylactoid reactions have occurred in patients receiving corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.

Endocrine

In patients on corticosteroid therapy subjected to unusual stress, increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation is indicated. Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitaiy-adrenal (HPA) suppression (secondary adrenocortical insufficiency). The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy. This effect may be minimazed by the use of alternate-day theapy.

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. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

A steroid syndrome  seemingly initiated to adrenocortical insufficiency, may also occur Following abrupt discontinuance of glucocorticoids. This syndrome ntiudes Symptoms such as anorexia nausea vomiting, lethargy headache, fever,desquamation myalgia weigh loss and/for hypotension These effects are though to be due to toe sudden change m glucocorticoid concentration rather than to low cortcosterord levels

Because gtococortcotos can produce or aggravate Cushing’s syndrome, glucocorticoids should be avoided in patients with Cushing’s disease There is an enhanced effect of corticosteroids on patients with hypothyroidism

Metabolism and Nutrition

Including methylprednisolone. can increase blood glucose, worsen ore-exfshng diabetes and predispose those on long-term corticosteroid therapy to diabetes

Psychiatric

Psyche derangements may appear when corticosteroids are used, ranging from euphoria, reomma. mood swings personality charges, and severe depression to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids

Potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8 Undesirable Effects Psychiatric disorders) Symptoms typically emerge withm a few days or weeks of starting treatment Most reactions recover after either dose reduction or withdrawal although specific treatment may be necessary. Psychological effects have been reported upon withdrawal of corticosteroids: the frequency is unknown Patents/caregivers should be encouraged to seek medical attention if psychological symptoms develop in toe patient, especially if depressed mood or sudda) ideation is suspected Patients/caregivere should be alert to possible psydtitnc disturbances that may occur ether dunng or mmediatety after dose tapering/ withdrawal of systemic steroids

Nervous System

Corticosteroids should be used with caution in patients with seizure disorders. Corticosteroids should be used with caution m patients with myasthenia gravis (see myopathy statement in Muscutoskeletaf Effects section)

Although controlled drnreaf trials have shown corticosteroids to be effective in speeding toe resolution of acute exacerbations of mufcpfe sderosts they do not show that corticosteroids affect the ultimate outcome or natural history of the disease. The studies do show that relatively high doses of corticosteroids are necessary to demonstrate a significant effect (see section 4.2 Posdogy and Method of Administration)

There have been reports of epckirai lipomatosis in patients taking corticosteroids,

typkatiy with long-term use at high doses

Ocular

Corticosteroids should be used cautiously n patients with ocular herpes smptex because of posstie corneal perforation

Prolonged use of corticosteroids may produce posterior subcapsiiar cataracts and nudear cataracts (particularly in deldren), exophthalmos, or mcreased intraocular pressure, which may resuit m glaucoma with possible damage to toe optic nerves Establishment of secondary tagal and wrai infections of toe eye may also be enhanced in patients receiving glucocorticoids

Corticosteroid therapy has been associated with central serous chorioretinopathy, which may lead to retinal detachment

Cardiac

Adverse effects of glucocorticoids on toe cardiovascular system, such as dyslpidemia and hypertension may predispose treated patients wit existing carttiovascular nsk factors to additional cardiovascular effects, if high doses and prolonged courses are used Accordingly. corticosteroids should be employed in such patients and attention should be paid to nsk modification and additional cardiac it needed lowdose art altenute day therapy may redua tbe ncidena of complications n corticosteroid therapy

Systerrec corticosteroids should be used with caution, and only if necessary, in cases of congestive heart failure.

Vascular

Corticosteroids should be used with caution in patients with hypertension

Gastrointestinal

There is no universal agreement on whether corticosteroids per se are responsible for peptic ulcers encountered dunng therapy: however, glucocorticoid therapy may mask toe symptoms of peptic ulcer so tost perforation or hemorrhage may occur without significant par in combination with NSAIDs, toe risk of developing gastrointestinal ufcsre is increased

Corticosteroids should be used with caution in nonspecific ulcerative colitis if there is a probaotty of itnpending perforation, abscess or other pyogenic infection, diverticulitis fresh ntestinal anastomoses, or active or latent peptic ulcer

Hepatobiliary

High doses of corticosteroids may produce acute pancreatitis.

Musculoskeletal

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 grave), or in patients recerwig concomitant therapy with anticholinergics, such as neuromuscular blocking drugs fe.g. pancuronium). This acute myopathy is generafceti may involve ocular and respiratory musdes and may resuftfiquadnpa rests

Bcianons of creatine ksiase may occur. Clinical improvement or recovery after stopping require weeks to years

Osteoporosis is common but infrequently recognized adverse effect associated with a long-term of large Does

Renal and Urinary

Corteomrode should be used with caution in patients with renal insufficiency

Investigations

Average and large doses of hydrocortisone can cause elevation of blood pressure, salt and water  retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when use in large doses

Dietary salt restriction and potassium supplemention may be necessary all corticosteroids increase calcium excretion.

Injury, Poisoning and Procedural Complications

High doses of systemic corticosteroids should not be used for the treatment of traumati brain injury.

Other

Because complications of treatment with glucocorticoids are dependent on tbe size of tbe dose and tbe duration of treatment, a nsk/benefit decision must be made in each individual case as to dose and duration of treatment and as to whetber daily or intermittent therapy should be used

The lowest possible dose of corticosteroid should be used to control the condition under treatment and when reduction in dosage is possible, the reduction should be gradual Aspmn and non-steroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids.

Pheochromocytoma crisis, which can be fetal, 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 Use in Children

Growth and development of infants and children on prolonged corticosteroid therapy should be carefolty observed

Growth may be suppressed in children receiving long-term daily, divided dose glucocorticoid therapy and use of such regimen should be restricted to the most urgent indications. Alternate day glucocorticoid therapy usually avoids or minimizes this side effect (see section 4.2 Posology and Method of Administration, Alternate pay Therapy). Infants and children on prolonged corticosteroid therapy are at special risk from raised intracranial pressure

High doses of corticosteroids may produce pancreatitis in children.

4.5 Interaction with Other Medicaments and Other Forms of Interaction

Medrol 4 mg ( Methylprednisolone ) is a cytochrome P450 enzyme (CYP) substrate and is mainly metabolized by tbe CYP3A4 enzyme. CYP3A4 is tbe dominant enzyme of tbe most abundant CYP subfamily in the liver of adult humans. It catalyzes 6p-hydroxylation of steroids, tbe 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.

CYP3A4 INHIBITORS – Drugs feat inhibit CYP3A4 activity generally decrease hepatic clearance and increase the plasma concentration of CYP3A4 substrate medications, such as methylprednisolone. In tbe presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity CYP3A4 INDUCERS – 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

CYP3A4 SUBSTRATES – In the presence of another CYP3A4 substrate, tbe hepatic clearance of methylprednisolone may be affected, with corresponding dosage adjustments requited. It is possible that adverse events associated with the use of ether drug alone may be more likely to occur with co-administration.

NON-CYP3A4-MEDIATED EFFECTS – Other interactions and effects that occur with methylprednisolone are described in Table 1 below

Table 1 provides a list and descriptions of the most common and/or clinically important

drug interactions or effects with Medrol 4 mg ( methylprednisolone )

Table 1 . Important drug or substance interactions/effects with methylprednisolone

Drug Class or Type – DRUG or SUBSTANCE Interaction/Effect
Antibacterial

ISONIAZID

CYP3A4 INHIBITOR. In addition, there is a potential effect of methylprednisolone to increase the acetylation rate and clearance ofisoniazid.
Antibiotic, Antitubercular – RIFAMPIN CYP3A4 INDUCER
Anticoagulants (oral) The effect of methylprednisolone 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 anticoaaulant effects.
Anticonvulsants – CARBAMAZEPINE CYP3A4 INDUCER (and SUBSTRATE)
Anticonvulsants

– PHENOBARBITAL

– PHENYTOIN

CYP3A4 INDUCERS
Anticholinergics – NEUROMUSCULAR BLOCKERS Corticosteroids may influence the effect of anticholinergics.

1)      An acute myopathy has been reported with tbe concomitant use of high doses of corticosteroids and anticholinergics, such as neuromuscular blocking drugs (see section 4.4 Special Warnings and Special Precautions for Use, Musculoskeletal, for additional information).

2)      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.

Anticholinesterases Steroids may reduce the effects of anticholinesterases in myasthenia gravis.
Antidiabetics Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents mav be reauired
Antiemetic

–        APREPITANT

–        fosaprepitant

CYP3A4 INHIBITORS (and SUBSTRATES)

 

Antifungal

–        ITRACONAZOLE-KETOCONAZOLE

 

CYP3A4 INHIBITORS (and SUBSTRATES)

Aromatase inhibitors – AMIN OGLUTETHIMI DE Aminoglutethimide-incluced adrenal suppression may exacerbate  andocrine changes caused by prolonged glucocorticoid treatment

 

Calcium Channel Blocker

DILTIAZEM

CYP3A4 INHIBITOR (and SUBSTRATE)
Contraceptives (oral)

ETHINYLESTRADIOUlC N0RETHINDRONE

CYP3A4 INHIBITOR (and SUBSTRATE)
GRAPEFRUIT JUICE

 

CYP3A4 INHIBITOR
Immunosuppressant

–        CYCLOSPORINE

YP3A4 INHIBITOR (and SUBSTRATE)

1)      Mutual inhibition of metabolism occurs with concurrent

use of cyclosporine 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 co-admmistration

2)      Convulsions have been reported with concurrent use of methylprednisolone and cyclosporine

Immunosuppressant CYCLOPHOSPHAMIDE

tacrolimus

CYP3A4 SUBSTRATES

 

Macrolide Antibacterial

CLARITHROMYCIN

ERYTHROMYCIN

CYP3A4 INHIBITORS (and SUBSTRATES)
Macrotide Antibacterial TROLEANOOMYCIN CYP3A4 INHIBITOR
NSAIDs (non-steroidal anti-inflammatory drugs)

–        high-dose ASPIRIN (acetylsalicytic acid)

1)      There may be increased incidence of gastrointestinal bleeding and ulceration when corticosteroids are given with NSAIDs

2)      MethylprednlsoJone may increase the clearance of high- dose aspirin, 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

potassium-depleting agents When corticosteroids are administered concomitantly with potassium-depleting agents (i.e„ diuretics such as thiazides or loop diuretics), patients should be observed closely for development of hy pokalemia. There is also an increased risk of hypokalemia with concurrent use of corticosteroids with amphotericin B. xanthenes. or beta2 agonists
Antivirals

HIV-PROTEASE INHIBITORS

CYP3A4 INHIBITOR

CYP3A4 INHIBITORS (and SUBSTRATES)

1)      Protease inhibitors, such as indinavir and ritonavir, may increase plasma concentrations of corticosteroids

2)      Corticosteroids may induce the metabolism of HIV-inhibitors resulting in reduced plasma concentrations

 

4.6 Pregnancy and Lactation

Fertility

There is no evidence that corticosteroids impair fertility (see section 5.3 Preclinical Safety Data).

Pregnancy

Some animal studies have shown that corticosteroids, when administered to the mother at high doses, may cause fetal malformations, However, corticosteroids do not appear to cause congenital anomalies when given to pregnant women.

Despite animal findings, it would appear that the possibility of fetal harm is remote, if the drug is used during pregnancy. Adequate human reproductive studies have not been done with corticosteroids. Since there is inadequate evidence of safety in human pregnancy, this drug should be used in pregnancy only if dearly needed.

Some corticosteroids readily cross the placenta. One retrospective study found an increased incidence of low birth weights in infants bom of mothers receiving corticosteroids Infants born to mothers, who have received substantial doses of corticosteroids during pregnancy must be carefully observed and evaluated for signs of adrenal insufficiency, although neonatal adrenal insufficiency appears to be rare in infants who were exposed in utero to corticosteroids.

There are no known effects of corticosteroids on tabor and delivery.

Cataracts have been observed in infanls bom to mothers undergoing long-term treatment with corticosteroids during pregnancy.

Lactation

Corticoids are excreted in breast milk. Corticosteroids distributed into breast milk may suppress growth and interfere with endogenous glucocorticoid production in nursing infants Since adequate reproductive studies have not been performed in humans with glucocorticoids, these drugs should be administered to nursing mothers only if the benefits of therapy are judged to outweigh the potential risks to the infant

4.7 Effects on Ability to Drive and Use Machines

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.

4.8 Undesirable Effects

Infections and infestations: Infection, Opportunistic infection Immune system disorders: Drug hypersensitivity (including Anaphylactic reaction and Anaphylactoid reaction), suppression of reactions to skin tests Endocrine disorders: Cushingoid, Hypopituitarism, Steroid Withdrawal syndrome Metabolism and nutrition disorders: Alkalosis hypokalaemic, Fluid retention, Glucose tolerance impaired, Increased appetite (which may result in Weight increased), increased requirements for insulin or oral hypoglycemic agents in diabetics. Metabolic acidosis, Sodium retention

Psychiatric disorders: Abnormal behaviour, Affective disorder (including Affect lability, Depressed mood. Euphoric mood, psychological dependence, Suicidal ideation), Anxiety. Confusional state, Insomnia, Irritability. Mental disorder. Mood swings. Personality change. Psychotic behaviour, Psychotic disorder (including Mania, Delusion, Hallucination, and Schizophrenia [aggravation of])

Nervous system disorders: Amnesia, Cognitive disorder. Convulsions, Dizziness. Headache, Intracranial pressure increased (with Papilloedema [Benign intracranial hypertension)), Epidural lipomatosis

Eye disorders’ Cataract subcapsular. Exophthalmos, Glaucoma, Centra! serous

chorioretinopathy

Ear and labymth disorders. Vertigo

CeraEac disorders Cardiac failure congestive (in susceptible patients)

Vascular itsorders Hypertension, Hypotension

Respiratory, thoracic and mediastinal disorders Hiccups

Gastrofotest/naf disorders Abdominal distension. Abdominal pain. Diarrhoea. Dyspepse.

Gastric haemorrhage Intestinal perforation. Nausea Oesophagitis Oseophagitis

ulcerative, Pancreatitis, Peptic ulcer (with possible Peptic ulcer perforation aid Peptic

ulcer haemorrhage)

Skin and subcutaneous tissue disorders: Angoedema, Eechymosis, Erythema, Hirsutism. Hyperhidrosis, Petechiae Pruritus, Rash. Skin atrophy. Skin striae. Urticaria Musculoskeletal and connective tissue disorders. Arthralgia. Growth retardation. Musde atrophy, Muscular weakness Myalgia Myopathy, Neuropathic arthropathy, Osteonecrosis, Osteoporosis. Pathologic fracture Reproductive system and breast disorders: Menstruation irregular Genera/disorders and admimsbabon site conditions: Fatigue Impaired beating, Malaise Investigations: Alanine aminotransferase increased. Aspartate aminotransferase increased, Blood alkaline phosphatase increased. Blood potassium decreased, Carbohydrate tolerance decreased, Intraocular pressure increased. Urine calcium increased Injury, poisoning and procedural complications Spinal compression fracture. Tendon rupture (particularly of the Achilles tendon)

4.9 Overdose

There is no clinical syndrome of acute overdosage with corticosteroids. Reports of acute tenacity and/or death following overdosage of corticosteroids are rare. In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic. Medrol 4 mg ( Methylprednisolone ) is dialyzable.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic Properties

Medrol 4 mg ( Methylprednisolone ) is a potent anti-inflammatory steroid. It has greater anti-inflammatory potency than prednisolone and less tendency than prednisolone to induce sodium and water retention. The relative potency of methylprednisolone to hydrocortisone is at least four to one.

5.2 Pharmacokinetic Properties

Methylprednisolone pharmacokinetics is linear, independent of route of administration. Absorotion.

Methylprednisolone is rapidly absorbed and the maximum plasma methylprednisolone concentration is achieved around 1.5 to 2 3 hours across doses following oral administration in normal healthy adults. The absolute bioavailability of methylprednisolone in normal healthy subjects is generally high (82% to 89%) following oral administration. Distnbution

Methylprednisolone is widely distributed into toe tissues, crosses the blood-brain barrier, and is secreted in breast milk, Its apparent volume of distribution is approximately 1,4 L/kg The plasma protein binding of methylprednisolone in humans is approximately 77%. Metabolism:

In humans, methylprednisolone is metabolized in the liver to inactive metabolites; the major ones are 20a-hydroxymethylpredni$ok>ne and 20^-hydroxymethylprednisolone. Metabolism in tbe liver occurs primarily via the CYP3A4 enzyme For a list of drug interactions based on CYP3A4-mediated metabolism, see section 4.5 Interactions with Other Medicinal Products and Other Forms of Interaction Methylprednisolone. Like many CYP3A4 substrates, may also be a substrate for toe ATP- binding cassette (ABC) transport protein p-glycoprotein. influencing tissue distribution and interactions with other methanes Elimination

Tbe mean elimination half-life for total methylprednisolone is in toe range of 1.8 to 5.2 hours Total clearance is approximately 5 to 6 mL/min/kg

No dosing adjustments are necessary in renal feilure Methylprectoisotone is hemodiatyzabte.

5.3 Preclinicai Safety Data

Tbe nondmical database, m combination with evidence of safety gleaned from years of cincal experience and posi-mafketmg survetiance. supports tbe safety of methylprednisolone tablets as a potent anti inflammatory agent in shot-term inflammatory disorders.

Based on conventional studies of safety pharmacology, repeated-dose toxicity to mice, rats, rabbits, and dogs using intravenous, intraperitoneal, subcutaneous, intramuscular, and oral routes of administration. no unexpected hazards were identified Tbe toxidties seen in tbe repeated-dose studies are those expected to occur with continued exposure to exogenous adrenocortical steroids Carcinoaenic potential

Longterm studies n animals have not been performed to evaluate carcinogenic potential, as toe drug is indicated for short-term treatment only

There was no evidence of a potential for genetic and chromosome mutations when tested in limited studies performed in bacterial and mammalian cells Reproduce toaotv-

Reproductive fertility studies in animals have not been performed to evaluate specifically the potential of impairment of fertility. There is no evidence that corticosteroids cause impair of fertility.

Corticosteroids have been shown to be teratogenic in many species when given in doses equivalent to the human dose. In animal reproduction studies, glucocorticoids such as methylprednisolone have been shown to induce malformations (deft palate, skeletal malformations) and intra-utenne growth retardation.

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipients

Medrol 4 mg: Lactose, com starch, dried com starch, sucrose, calcium stearate. Medrol 16 mg: Lactose, com starch, sucrose, calcium stearate, liquid paraffin

6.2 Incompatibilities Notappticable

6.3 Shelf-life

Medrol 4 mg 36 months since manufacturing date Medrol 16 mg 24 months since manufacturing date

6.4 Special Precautions for Storage Store below 30C

6.5 Nature and Contents of Container

Medrol 4 mg Box of 3 blisters x 10 tablets Medrol 16 mg Box of 3 blisters x 10 tablets Specification: Manufacturer’s Manufacturer.

 

 

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