OPHTAPRED

may be administered by intravenous (Intravenous) or intramuscular (Intramuscular) injection or by intravenous infusion.

Intravenous injection is the preferred method for initiating treatment in emergency cases.

Dosage adjustments are variable and must be individualized, taking into account the disease to be treated, its severity and the patient's response throughout the duration of treatment.

The benefit/risk ratio must be assessed in each case and on an ongoing basis.

The lowest possible dose of corticosteroids should be used to control the condition to be treated, for the shortest possible duration.

The correct maintenance dose should be determined by decreasing the initial dosage gradually and at appropriate time intervals until the lowest dosage that will maintain an appropriate clinical response is achieved.

If, after long-term treatment, the medicine must be stopped, this should be done gradually rather than abruptly.

After the initial emergency period, consideration should be given to using a longer-acting injectable preparation or an oral formulation.

As adjuvant treatment in life-threatening situations, administer 30 mg/kg of methylprednisolone sodium succinate Intravenous over a minimum period of 30 minutes.

This dose can be repeated every 4-6 hours, for up to 48 hours.

Intravenous administration of 250 mg/day or more for a few days (usually ≤ 5 days) may be appropriate in exacerbation phases and in situations not responding to conventional treatment, such as: rheumatic diseases; systemic lupus erythematosus; edematous conditions such as glomerulonephritis or lupus nephritis.

In multiple sclerosis, in situations not responding to conventional treatment (or in exacerbation phases), intermittent administration of 500 mg/day or 1,000 mg/day, for 3 or 5 days, over at least 30 minutes.

In adjuvant treatment for other pathologies, the initial dose varies from 10-500 mg Intravenous, depending on the clinical situation being treated.

Higher doses may be needed for short-term treatment of serious acute conditions.

Initial doses up to 250 mg should be administered Intravenous over a minimum period of 5 minutes and higher doses should be administered for at least 30 minutes.

Subsequent doses should be administered Intravenous or Intramuscular, at intervals dictated by the patient's response and clinical situation.

For administration of the medicine Intravenous or Intramuscular, the solution should be prepared according to the instructions.

To avoid compatibility and stability issues, it is recommended that methylprednisolone succinate be administered separately from other substances administered Intravenous.

Dosage may be reduced for infants and children, but should be guided more by the severity of the situation and response to treatment than by the age or weight of the patient.

It should not be less than 0.5 mg/kg per 24 hours.

No dosage adjustment is necessary in cases of renal insufficiency.

Methylprednisolone is hemodialysable.

No dosage adjustment is necessary in cases of hepatic impairment.

Corticosteroids may increase susceptibility to infections, may mask some signs of infection, and new infections may develop during their use.

There may be a drop in resistance and an inability to localize the infection when corticosteroids are used.

Pathogen infections of viral, bacterial, fungal, protozoal, or helminthic origin, regardless of which part of the body is affected, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents affecting cellular or humoral immunity, or neutrophil function.

These infections can be mild but can also become severe and sometimes fatal.

As the dose of corticosteroids increases, the rate of occurrence of infectious complications increases.

Subjects treated with immunosuppressants are more susceptible to infections than healthy subjects.

Chickenpox and measles, for example, can be more serious and even fatal in unimmunized children or adults who use corticosteroids.

The administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Killed or inactivated vaccines may be administered to patients receiving immunosuppressive doses of corticosteroids; however, the response to these vaccines may be less.

The indicated immunization procedures may be performed in patients receiving non-immunosuppressive doses of corticosteroids.

The use of corticosteroids in active tuberculosis should be limited to cases of fulminant or disseminated tuberculosis where corticosteroids are used for disease management in conjunction with appropriate antituberculosis therapy.

If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close monitoring is necessary as the disease may reactivate.

During prolonged treatment with corticosteroids, these patients should receive chemoprophylaxis.

Cases of

Kaposi's sarcoma have been reported in patients receiving corticosteroid therapy.

Discontinuation of corticosteroid therapy may result in clinical remission.

The role of corticosteroids in septic shock is controversial, with early studies reporting beneficial and harmful effects.

More recently, adjunctive treatment with corticosteroids has been suggested to be beneficial in patients with established septic shock and adrenal insufficiency.

However, their routine use in septic shock is not recommended.

A systematic review of short courses of high-dose corticosteroids did not support their use.

However, meta-analyses and a review suggest that longer treatment (5-11 days) with low-dose corticosteroids may reduce mortality.

Allergic reactions may occur.

Rare cases of skin reactions and anaphylactic/anaphylactoid reactions have occurred in patients receiving corticosteroid therapy, preventive measures should be implemented before administration, particularly if there is a history of allergy to any other medicinal product.

In patients on corticosteroid therapy subjected to unusual stress, an increase in the dosage of fast-acting corticosteroids is indicated before, during and after the stressful situation.

Prolonged administration of pharmacological doses of corticosteroids may result in hypothalamic-pituitary-adrenal inhibition (secondary adrenocortical insufficiency).

The extent and duration of adrenocortical insufficiency produced varies from patient to patient and depends on the dose, frequency, timing of administration and duration of glucocorticoid treatment.

This effect can be minimized by administering the treatment every other day. Additionally, abrupt discontinuation of glucocorticoids can lead to fatal acute adrenal insufficiency.

Drug-induced adrenocortical insufficiency can be limited by gradual dose reduction.

This type of relative insufficiency may persist for months after stopping treatment.

Therefore, in any stressful situation occurring during this period, hormone therapy should be reintroduced.

A steroid “withdrawal syndrome”, apparently unrelated to adrenal insufficiency, can also occur after abrupt discontinuation of glucocorticoids.

Methylprednisolone is a substrate of cytochrome

P450 (CYP) enzymes and is primarily metabolized by the CYP3A4 enzyme.

CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in the liver of adult subjects.

This enzyme catalyzes the 6β-hydroxylation of steroids, the essential step in the phase I metabolism of endogenous and synthetic corticosteroids.

Many other compounds are also

CYP3A4 substrates, some of which (as well as other drugs) alter glucocorticoid metabolism through induction or inhibition of the CYP3A4 enzyme.

CYP3A4 inhibitors.

• drugs that inhibit CYP3A4 activity generally decrease hepatic clearance and increase plasma concentrations of drugs that are CYP3A4 substrates, such as methylprednisolone.

In the presence of a

CYP3A4 inhibitor, it may be necessary to adjust the dose of methylprednisolone to avoid corticosteroid toxicity.

CYP3A4 inducers.

• drugs that induce CYP3A4 activity generally increase hepatic clearance, resulting in a decreased plasma concentration of drugs that are CYP3A4 substrates.

If administered simultaneously, the dose of methylprednisolone may need to be increased to achieve the desired effect.

CYP3A4 substrates.

• in the presence of another CYP3A4 substrate, hepatic clearance of methylprednisolone may be affected, requiring a corresponding dose adjustment.

It is possible that adverse events associated with the use of these drugs as monotherapy may occur more often when administered concurrently.

Effects not mediated by

CYP3A4 – Table 1 below describes other interactions and effects that may occur with methylprednisolone.

Table 1 provides a list and description of the most common and/or clinically significant drug interactions and effects observed with methylprednisolone.

Table 1.

Type or class of medication.

• Drug or substance Interaction/effect Antibiotic.

• Isoniazid CYP3A4 inhibitor.

Methylprednisolone may also increase the rate of acetylation and elimination of isoniazid.

Antibiotic, anti-tuberculosis.

• Rifampicin CYP3A4 inducer Anticoagulants (oral) The effect of methylprednisolone on oral anticoagulants is variable.

Cases of increased or decreased effect of anticoagulants have been reported during simultaneous administration with corticosteroids.

Coagulation parameters must therefore be controlled in order to maintain the desired anticoagulant effects.

• Carbamazepine CYP3A4 inducer (and substrate) Anticonvulsants.

• Phenytoin CYP3A4 inducer Anticholinergics.

• Neuromuscular blocking agents Corticosteroids may have an impact on the effect of anticholinergics. 1.

• Acute myopathy has been reported during the concomitant use of high doses of corticosteroids and anticholinergics, such as neuromuscular blocking agents (for more information This interaction can be expected with all competitive neuromuscular blocking agents. Anticholinesterases Corticosteroids may reduce the effects of anticholinesterases in myasthenia gravis. Antidiabetics Because corticosteroids may increase blood glucose concentrations, dose adjustments of antidiabetics may be necessary. Antiemetics - Aprepitant - Fosaprepitant CYP3A4 inhibitors (and substrates) Antifungals.

• Ketoconazole CYP3A4 inhibitors (and substrates) Antivirals.

• HIV protease inhibitors CYP3A4 inhibitors (and substrates) 1.

• Protease inhibitors, such as indinavir and ritonavir, may increase concentrations plasma corticosteroids. 2.

• Corticosteroids may have an inducing effect on the metabolism of HIV protease inhibitors, leading to a reduction in plasma concentrations.

Pharmacokinetic potentiator.

• Cobicistat CYP3A4 inhibitor Aromatase inhibitors.

• Aminoglutethimide Aminoglutethimide-induced inhibition of adrenal function may exacerbate endocrine changes caused by prolonged treatment with glucocorticoids.

Store at a temperature not exceeding 25°C. Store in the original packaging, protected from light.

For storage conditions of the medicinal product after reconstitution and dilution.

Methylprednisolone sodium succinate is indicated for the treatment of the following conditions Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone are the drugs of choice, but synthetic analogues can be used in combination with mineralocorticoids; in children, it is particularly important to administer additional mineralocorticoids).

Acute adrenocortical insufficiency (hydrocortisone or cortisone are the drugs of choice; the addition of mineralocorticoids may be necessary, particularly when synthetic analogues are used).

Before surgery and in the event of trauma or serious illness, in patients with adrenocortical insufficiency or in cases of questionable adrenal reserve: Congenital adrenal hyperplasia Non-suppurative thyroiditis; Hypercalcemia associated with cancer.

HIKMA is used as a short-term adjuvant treatment to relieve the patient in the event of an acute episode or exacerbation of the following conditions: Post-traumatic osteoarthritis

During an exacerbation or as maintenance treatment in certain cases of: Systemic lupus erythematosus (and lupus nephritis) Acute rheumatic carditis; Systemic dermatomyositis (polymyositis); Polyarteritis nodosa Goodpasture syndrome.

Pemphigus; Severe erythema multiforme (Stevens-Johnson syndrome); Exfoliative dermatitis Severe psoriasis; Bullous dermatitis herpetiformis; Severe seborrheic dermatitis Mycosis fungoides.

Control of severe or disabling allergic conditions that cannot be treated by conventional treatment: Bronchial asthma Contact dermatitis; Atopic dermatitis; Serum sickness; Drug hypersensitivity reactions Urticarial post-transfusion reactions; Non-infectious acute laryngeal edema (adrenaline is the first-line drug).

HIKMA is indicated in severe, acute and chronic eye conditions, of an allergic and inflammatory nature, such as: ophthalmic zoster, iritis, iridocyclitis, chorioretinitis, choroiditis and diffuse posterior uveitis, optic neuritis, sympathetic ophthalmia, inflammation of the anterior segment, allergic conjunctivitis, allergic marginal corneal ulcers and keratitis.

To manage a critical episode, in the event of: Ulcerative colitis; Crohn's disease.

METHYLPREDNISOLONE HIKMA is indicated in case of: Symptomatic sarcoidosis; Berylliosis Fulminant or disseminated pulmonary tuberculosis (if used concomitantly with appropriate anti-tuberculosis chemotherapy) Loeffler syndrome (which cannot be treated by other means); Aspiration pneumonia.

HIKMA is beneficial in patients with acquired immunodeficiency syndrome (AIDS) as adjuvant treatment of moderate to severe pneumonia caused by Pneumocystis jiroveci if administered within 72 hours of starting antipneumocystosis treatment.

Acquired hemolytic anemia (autoimmune), idiopathic thrombocytopenic purpura in adults (administration only by intravenous route; intramuscular route is contraindicated), secondary thrombocytopenia in adults, erythroblastopenia (erythrocyte anemia), congenital hypoplastic (erythroid) anemia.

For the palliative treatment of leukemia and lymphoma in adults and acute leukemia in children.

Hypercalcemia associated with cancer; Terminal cancer: to improve the quality of life of patients in the terminal phase of cancer Prevention of nausea and vomiting associated with cancer chemotherapy.

To induce diuresis or remission of proteinuria in cases of nephrotic syndrome, without uremia, of the idiopathic type or due to lupus erythematosus.

Cerebral edema due to a brain tumor, primary or metastatic, and/or in association with an intervention.

Prednisolone acetate is a glucocorticoid that, on the basis of weight, has to 5 times the anti-inflammatory potency of hydrocortisone.

Glucocorticoids inhibit the edema, fibrin deposition, capillary dilation, and phagocytic migration of the acute inflammatory response, as well as capillary proliferation, deposition of collagen, and scar formation.

Pharmacotherapeutic group

Corticosteroid for systemic use, ATC code: H02AB04

Methylprednisolone sodium succinate has the same metabolic and anti-inflammatory properties as methylprednisolone.

When administered parenterally in equimolar amounts, both drugs have equivalent biological activity.

The relative potency of methylprednisolone sodium succinate and hydrocortisone sodium succinate is approximately four to one, as indicated by decreased eosinophil counts following intravenous administration.

This is consistent with the relative potency of oral formulations of methylprednisolone and hydrocortisone.

Methylprednisolone sodium succinate was studied in acute spinal cord injuries in two randomized, double-blind, comparative studies: NASCIS (National Acute Spinal Cord Injury Studies) 2 and 3.

The effect of a high dose of methylprednisolone sodium succinate, initially administered as an Intravenous bolus of 30 mg/kg over 15 minutes, followed 45 minutes later by a continuous infusion of 5.4 mg/kg/hour for 24 hours, was significant in terms of neurological recovery when administered up to 8 hours after injury (NASCIS 2), and motor recovery was greater in patients who started treatment between 3 hours and up to 8 hours after injury and who were treated according to the same regimen for 48 hours (NASCIS 3).

The following adverse reactions have been reported with intrathecal and epidural routes of administration, which are contraindicated: arachnoiditis, functional gastrointestinal disorder/bladder dysfunction, headache, meningitis, paraparesis/paraplegia, seizures, sensory disturbances.

Within each system organ class, adverse reactions are classified by frequency into the following categories: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1,000); very rare (< 1/10,000); frequency not known (cannot be estimated based on available data).

Infections and infestations Common Infection (including increased susceptibility to infections and severity of infections with suppression of symptoms and clinical signs).

Not known

Opportunistic infections, peritonitis* Blood and lymphatic system disorders Not known Frequency Leukocytosis Immune system disorders Not known Drug hypersensitivity (anaphylactic reaction and anaphylactoid reaction) Endocrine disorders Common Cushingoid syndrome Not known Inhibition of the hypothalamic-pituitary-adrenal axis, drug withdrawal syndrome steroids Metabolism and nutrition disorders Common Sodium retention, fluid retention, Not known Metabolic acidosis, impaired glucose tolerance, hypokalemic alkalosis, dyslipidemia, increased insulin requirement (or oral hypoglycemic agents in diabetics), increased appetite (may cause weight gain), epidural lipomatosis Psychiatric disorders Common Wide range of psychiatric reactions, including affective disorders (such as mood irritable, euphoric, depressed and labile, drug dependence and suicidal thoughts).

The following events were more common in children: mood swings, abnormal behavior, insomnia, irritability Not known Affective disorders (including affect lability, drug dependence, suicidal ideation), psychotic disorder (including mania, delusions, hallucinations and schizophrenia ), confusional state, mental disorders, anxiety, personality changes, mood swings, abnormal behavior, insomnia, irritability Nervous system disorders Not known Increased intracranial pressure (with papilledema ), convulsions, amnesia, cognitive impairment, dizziness, headache Eye disorders Common Cataract Not known Exophthalmia, glaucoma, chorioretinopathy, blurred vision Ear and ear disorders of the labyrinth Not known Dizziness Cardiac disorders Not known Congestive heart failure (in predisposed patients), arrhythmia Vascular disorders Common Hypertension Not known Thrombosis, hypotension, thrombotic events Respiratory, thoracic and mediastinal disorders Not known Pulmonary embolism, hiccups Gastrointestinal disorders Common Peptic ulcer (with risk of perforation and haemorrhage) Not known Gastric haemorrhage, intestinal perforation, pancreatitis, ulcerative esophagitis, esophagitis, abdominal pain, abdominal distension, diarrhea, dyspepsia, nausea Hepatobiliary disorders Not known Hepatitis, increased liver enzymes Skin and subcutaneous tissue disorders Common Ecchymosis, skin atrophy (thin and fragile skin), acne Not known Angioedema, petechiae, skin streaks, skin hypopigmentation, hirsutism, rash, erythema, pruritus, urticaria, hyperhidrosis Musculoskeletal and connective tissue disorders Common Growth retardation, muscle weakness, osteoporosis Not known Osteonecrosis, pathological fractures, muscle atrophy, myopathy, neuropathic arthropathy, arthralgia, myalgia Reproductive system and breast disorders Not known Irregular menstruation General disorders and administration site conditions Common Peripheral edema, wound healing disorders Not known Injection site reaction, fatigue, malaise.

Investigations Common Blood potassium decreased Not known Alanine aminotransferase increased, aspartate aminotransferase increased, alkaline phosphatase increased blood pressure, increased intraocular pressure, decreased carbohydrate tolerance, increased urinary calcium, suppression of reactions to skin tests, increased blood urea Injury, poisoning and complications of procedures Not known Frequency rupture of a tendon (especially.

Methylprednisolone sodium succinate is contraindicated: in patients with systemic fungal infections in patients with hypersensitivity to the active substance or to one of the excipients mentioned in section 6.1 administered intrathecally; administered by epidural route.

Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

Prolonged use of corticosteroids may result in posterior subcapsular cataract formation and may increase intraocular pressure in susceptible individuals, resulting in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision.

Prolonged use may also suppress the host immune response and thus increase the hazard of secondary ocular infections.

If this product is used for 10 days or longer, intraocular pressure should be routinely monitored even though it may be difficult in children and uncooperative patients.

Steroids should be used with caution in the presence of glaucoma.

Intraocular pressure should be checked frequently.

Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning.

Use of topical corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation.

Acute purulent infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication.

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex).

Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution; frequent slit lamp microscopy is recommended.

FORTE ® suspension contains sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people.

The overall prevalence of sulfite sensitivity in the general population is unknown and probably low.

Sulfite sensitivity is seen more frequently in asthmatic than in non-asthmatic people.

® suspension is contraindicated in acute untreated purulent ocular infections, in most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures.

FORTE ® suspension is also contraindicated in individuals with known or suspected hypersensitivity to any of the ingredients of this preparation and to other corticosteroids.

Shake well before using.

Instill one to two drops into the conjunctival sac two to four times daily.

During the initial to 48 hours, the dosing frequency may be increased if necessary.

Care should be taken not to discontinue therapy prematurely.

If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated.

® (prednisolone acetate ophthalmic suspension, USP) 1% is supplied sterile in opaque white LDPE plastic bottles with droppers with pink high impact polystyrene (HIPS) caps as follows: 1 mL in 5 mL bottle.

• NDC 11980-180-01 5 mL in 10 mL bottle.

• NDC 11980-180-05 10 mL in 15 mL bottle.

• NDC 11980-180-10 15 mL in 15 mL bottle.

• NDC 11980-180-15 Storage: Store at up to 25°C (77°F).

Protect from freezing.

Store in an upright position.

Revised: 02 / 2024 Distributed by: AbbVie, Inc.

Chicago, IL 60064 © 2024 AbbVie.

All rights reserved.

Pred Forte and its design are trademarks of Allergan, Inc., an AbbVie company. v2.0USPI180 Shape Description automatically generated.

Prednisolone has been shown to be teratogenic in mice when given in doses 1-10 times the human dose.

Dexamethasone, hydrocortisone, and prednisolone were ocularly applied to both eyes of pregnant mice five times per day on days 10 through of gestation.

A significant increase in the incidence of cleft palate was observed in the fetuses of the treated mice.

There are no adequate well-controlled studies in pregnant women.

Prednisolone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.

Because of the potential for serious adverse reactions in nursing infants from prednisolone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The safety and effectiveness in pediatric patients have been established.

Use in pediatric patients is supported by evidence from adequate and well-controlled studies of prednisolone acetate ophthalmic suspension in adults with additional data in pediatric patients.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk.

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.

Because of the potential for serious adverse reactions in nursing infants from prednisolone, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

The safety and effectiveness in pediatric patients have been established.

Use in pediatric patients is supported by evidence from adequate and well-controlled studies of prednisolone acetate ophthalmic suspension in adults with additional data in pediatric patients.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.