Prednisol (Solution) Instructions for Use

Marketing Authorization Holder

Agio Pharmaceuticals, Ltd. (India)

ATC Code

H02AB06 (Prednisolone)

Active Substance

Prednisolone (Rec.INN registered by WHO)

Dosage Form

Prednisol

Solution for intravenous and intramuscular administration 30 mg/1 ml: amp. 3, 5, 60 or 100 pcs.

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration transparent, colorless or with a greenish-yellow tint.

Excipients: disodium edetate, anhydrous disodium hydrogen phosphate, sodium dihydrogen phosphate dihydrate, propylene glycol, water for injection.

1 ml – dark glass ampoules (3) – plastic trays (1) – cardboard packs.
1 ml – dark glass ampoules (3) – blisters (1) – cardboard packs.
1 ml – dark glass ampoules (3) – blisters (20) – cardboard packs.
1 ml – dark glass ampoules (5) – blisters (1) – cardboard packs.
1 ml – dark glass ampoules (5) – blisters (20) – cardboard packs.

Clinical-Pharmacological Group

Injectable corticosteroids

Pharmacotherapeutic Group

Glucocorticosteroid

Pharmacological Action

Prednisol is a synthetic glucocorticoid drug, a dehydrogenated analogue of hydrocortisone. It has anti-inflammatory, anti-allergic, and immunosuppressive effects, and increases the sensitivity of beta-adrenergic receptors to endogenous catecholamines.

It interacts with specific cytoplasmic receptors (glucocorticosteroid (GCS) receptors are present in all tissues, especially abundant in the liver) to form a complex that induces the production of proteins (including enzymes that regulate vital processes in cells).

Protein metabolism: decreases the amount of globulins in plasma, increases the synthesis of albumins in the liver and kidneys (with an increase in the albumin/globulin ratio), reduces the synthesis and enhances the catabolism of protein in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation occurs mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract; increases the activity of glucose-6-phosphatase (increasing the release of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxykinase and the synthesis of aminotransferases (activation of gluconeogenesis); contributes to the development of hyperglycemia.

Water-electrolyte metabolism: retains Na+ and water in the body, stimulates the excretion of K+ (mineralocorticoid activity), reduces the absorption of Ca²⁺ from the gastrointestinal tract, reduces bone mineralization.

The anti-inflammatory effect is associated with the inhibition of the release of inflammatory mediators by eosinophils and mast cells; induction of lipocortin formation and reduction in the number of mast cells producing hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes (especially lysosomal) and organelle membranes. It acts on all stages of the inflammatory process: inhibits prostaglandin synthesis at the level of arachidonic acid (lipocortin inhibits phospholipase A2, suppresses the liberation of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, which contribute to inflammation, allergy, etc.), synthesis of “pro-inflammatory cytokines” (interleukin 1, tumor necrosis factor alpha, etc.); increases the resistance of the cell membrane to the action of various damaging factors.

The immunosuppressive effect is due to the induced involution of lymphoid tissue, inhibition of lymphocyte proliferation (especially T-lymphocytes), suppression of B-cell migration and interaction of T- and B-lymphocytes, inhibition of the release of cytokines (interleukin-1, 2; gamma-interferon) from lymphocytes and macrophages, and a decrease in antibody formation.

The anti-allergic effect develops as a result of a decrease in the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a reduction in the number of circulating basophils, T- and B-lymphocytes, mast cells; suppression of the development of lymphoid and connective tissue, reduction in the sensitivity of effector cells to allergy mediators, inhibition of antibody formation, and changes in the body’s immune response.

In obstructive airway diseases, the action is mainly due to the inhibition of inflammatory processes, prevention or reduction of the severity of mucosal edema, reduction of eosinophilic infiltration of the bronchial epithelial submucosal layer and deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucosa. It increases the sensitivity of beta-adrenergic receptors of small and medium caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, and reduces the viscosity of mucus by reducing its production.

It suppresses the synthesis and secretion of ACTH and, secondarily, the synthesis of endogenous GCS. It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

Pharmacokinetics

Up to 90% of the drug binds to plasma proteins: transcortin (cortisol-binding globulin) and albumin. Prednisolone is metabolized in the liver, partially in the kidneys and other tissues, mainly by conjugation with glucuronic and sulfuric acids. The metabolites are inactive. It is excreted in bile and urine by glomerular filtration and is 80-90% reabsorbed by the tubules. 20% of the dose is excreted by the kidneys unchanged. T_1/2 from plasma after intravenous administration is 2-3 hours.

Indications

Prednisol is used for emergency therapy in conditions requiring a rapid increase in the concentration of glucocorticosteroids in the body

• Shock states (burn, traumatic, surgical, toxic, cardiogenic) – when vasoconstrictors, plasma substitutes and other symptomatic therapy are ineffective;
• Allergic reactions (acute severe forms), blood transfusion shock, anaphylactic shock, anaphylactoid reactions;
• Cerebral edema (including against the background of a brain tumor or associated with surgery, radiation therapy, or head injury);
• Bronchial asthma (severe form), status asthmaticus;
• Systemic connective tissue diseases (systemic lupus erythematosus, rheumatoid arthritis);
• Acute adrenal insufficiency;
• Thyrotoxic crisis;
• Acute hepatitis, hepatic coma;
• Reduction of inflammatory phenomena and prevention of cicatricial strictures (in case of poisoning with caustic fluids).

ICD codes

Dosage Regimen

The drug dose and duration of treatment are determined by the doctor individually depending on the indications and severity of the disease. Prednisol is administered intravenously (by drip or bolus) or intramuscularly. The drug is usually administered intravenously first by bolus, then by drip.

In acute adrenal insufficiency, a single dose of the drug is 100-200 mg, the daily dose is 300-400 mg.

In severe allergic reactions, Prednisol is administered in a daily dose of 100-200 mg for 3-16 days.

In bronchial asthma, the drug is administered depending on the severity of the disease and the effectiveness of complex treatment from 75 to 675 mg per course of treatment from 3 to 16 days; in severe cases, the dose may be increased to 1400 mg per course of treatment or more with a gradual dose reduction.

In status asthmaticus, Prednisol is administered at a dose of 500-1200 mg per day with subsequent reduction to 300 mg per day and transition to maintenance doses.

In thyrotoxic crisis, the drug is administered at 100 mg per dose with a daily dose of 200-300 mg; if necessary, the daily dose can be increased to 1000 mg. The duration of administration depends on the therapeutic effect, usually up to 6 days.

In shock resistant to standard therapy, Prednisol is usually administered by bolus at the beginning of therapy, then switched to drip infusion. If blood pressure does not increase within 10-20 minutes, the bolus administration of the drug is repeated. After recovery from shock, drip infusion is continued until blood pressure stabilizes. A single dose is 50-150 mg (in severe cases – up to 400 mg). The drug is re-administered after 3-4 hours. The daily dose can be 300-1200 mg (with subsequent dose reduction).

In acute hepatic-renal insufficiency (in acute poisoning, postoperative and postpartum periods, etc.), Prednisol is administered at 25-75 mg per day; if indicated, the daily dose can be increased to 300-1500 mg per day and higher.

In rheumatoid arthritis and systemic lupus erythematosus, Prednisol is administered in addition to systemic administration of the drug at a dose of 75 -125 mg per day for no more than 7-10 days.

In acute hepatitis, Prednisol is administered at 75-100 mg per day for 7-10 days.

In poisoning with caustic fluids with burns of the digestive tract and upper respiratory tract, Prednisol is prescribed at a dose of 75-400 mg per day for 3-18 days.

If intravenous administration is impossible, Prednisol is administered intramuscularly in the same doses. After relief of the acute condition, Prednisol tablets are prescribed orally, with subsequent gradual dose reduction. With long-term use of the drug, the daily dose should be reduced gradually. Long-term therapy should not be stopped suddenly!

Adverse Reactions

The frequency and severity of side effects depend on the duration of use, the size of the dose used, and the possibility of observing the circadian rhythm of Prednisol administration.

When using Prednisol, the following may occur

From the endocrine system decreased glucose tolerance, steroid diabetes mellitus or manifestation of latent diabetes mellitus, suppression of adrenal function, Itsenko-Cushing syndrome (moon face, pituitary-type obesity, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae), delayed sexual development in children.

From the digestive system nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, gastrointestinal bleeding and perforation of the gastrointestinal tract wall, increased or decreased appetite, indigestion, flatulence, hiccups. In rare cases – increased activity of “hepatic” transaminases and alkaline phosphatase.

From the cardiovascular system arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of heart failure, ECG changes characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction – spread of the necrosis focus, slowing of scar tissue formation, which can lead to rupture of the heart muscle.

From the nervous system delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor cerebelli, headache, convulsions.

From the sensory organs posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, tendency to develop secondary bacterial, fungal or viral eye infections, trophic changes of the cornea, exophthalmos, sudden loss of vision (with parenteral administration in the head, neck, nasal conchae, scalp, deposition of drug crystals in the eye vessels is possible).

From metabolism increased calcium excretion, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Due to mineralocorticoid activity fluid and sodium retention (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the musculoskeletal system slowing of growth and ossification processes in children (premature closure of epiphyseal growth zones), osteoporosis (very rarely – pathological bone fractures, aseptic necrosis of the head of the humerus and femur), muscle tendon rupture, steroid myopathy, decrease in muscle mass (atrophy).

From the skin and mucous membranes delayed wound healing, petechiae, ecchymoses, thinning of the skin, hyper- or hypopigmentation, steroid acne, striae, tendency to develop pyoderma and candidiasis.

Allergic reactions skin rash, itching, anaphylactic shock, local allergic reactions.

Local with parenteral administration burning, numbness, pain, tingling at the injection site, infections at the injection site, rarely – necrosis of surrounding tissues, scar formation at the injection site; atrophy of the skin and subcutaneous tissue with intramuscular injection (especially dangerous injection into the deltoid muscle).

Other development or exacerbation of infections (the appearance of this side effect is facilitated by concomitantly used immunosuppressants and vaccination), leukocyturia, “withdrawal” syndrome.

Contraindications

• Hypersensitivity to prednisolone or components of the drug.

In children during the growth period, GCS should be used only for absolute indications and under the especially careful supervision of the attending physician.

With caution

• Gastrointestinal diseases – gastric and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, recently created intestinal anastomosis, ulcerative colitis with threat of perforation or abscess formation, diverticulitis;
• Parasitic and infectious diseases of viral, fungal or bacterial nature (current or recently suffered, including recent contact with a patient) – herpes simplex, herpes zoster (viremic phase), varicella, measles; amoebiasis, strongyloidosis; systemic mycosis; active and latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific therapy;
• Pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination;
• Immunodeficiency states (including AIDS or HIV infection);
• Cardiovascular system diseases (including recently suffered myocardial infarction – in patients with acute and subacute myocardial infarction, spread of the necrosis focus, slowing of scar tissue formation and, as a result, – rupture of the heart muscle is possible), severe chronic heart failure, arterial hypertension, hyperlipidemia);
• Endocrine diseases – diabetes mellitus (including impaired carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itsenko-Cushing’s disease, obesity (III-IV degree);
• Severe chronic renal and/or hepatic insufficiency, nephrourolithiasis;
• Hypoalbuminemia and conditions predisposing to its occurrence;
• Systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (except for the form of bulbar encephalitis), open-angle and closed-angle glaucoma;
• Pregnancy.

Use in Pregnancy and Lactation

During pregnancy (especially in the first trimester), it is used only for vital indications.

Since glucocorticosteroids pass into breast milk, if it is necessary to use the drug during breastfeeding, it is recommended to stop breastfeeding.

Use in Hepatic Impairment

Use with caution in severe chronic hepatic insufficiency.

Use in Renal Impairment

Use with caution in severe chronic renal insufficiency, nephrourolithiasis.

Pediatric Use

In children during the growth period, glucocorticosteroids should be used only for absolute indications and under the especially careful supervision of the attending physician.

Special Precautions

During treatment with Prednisol (especially long-term), monitoring by an ophthalmologist, control of blood pressure, water-electrolyte balance, as well as peripheral blood picture and blood glucose level is necessary.

To reduce side effects, antacids may be prescribed, and potassium (K⁺) intake may be increased (diet, potassium supplements). Food should be rich in proteins and vitamins, with limited content of fats, carbohydrates, and table salt.

The drug’s effect is enhanced in patients with hypothyroidism and liver cirrhosis. The drug may exacerbate existing emotional instability or psychotic disorders. If there is a history of psychoses, Prednisol in high doses is prescribed under strict medical supervision.

Use with caution in acute and subacute myocardial infarction – possible spread of the necrosis focus, slowing of scar tissue formation, and rupture of the heart muscle.

In stressful situations during maintenance therapy (e.g., surgical operations, trauma, or infectious diseases), the drug dose should be adjusted due to the increased need for glucocorticosteroids.

With sudden withdrawal, especially after prior use of high doses, the development of a “withdrawal” syndrome (anorexia, nausea, lethargy, generalized musculoskeletal pain, general weakness) is possible, as well as exacerbation of the disease for which Prednisol was prescribed.

Vaccination should not be performed during treatment with Prednisol due to reduced effectiveness (immune response).

When prescribing Prednisol for intercurrent infections, septic conditions, and tuberculosis, it is necessary to simultaneously conduct treatment with bactericidal antibiotics.

In children during long-term treatment with Prednisol, careful monitoring of growth and development dynamics is necessary. Children who were in contact with patients with measles or chickenpox during the treatment period are prophylactically prescribed specific immunoglobulins.

Due to the weak mineralocorticoid effect, for replacement therapy in adrenal insufficiency, Prednisol is used in combination with mineralocorticoids.

In patients with diabetes mellitus, blood glucose levels should be monitored and therapy adjusted if necessary.

Radiological monitoring of the osteoarticular system (images of the spine, hand) is recommended.

Prednisol in patients with latent infectious diseases of the kidneys and urinary tract can cause leukocyturia, which may have diagnostic significance.

Prednisol increases the content of 11- and 17-oxyketocorticosteroid metabolites.

Overdose

An intensification of the side effects described above is possible. It is necessary to reduce the dose of Prednisol. Treatment is symptomatic.

Drug Interactions

Pharmaceutical incompatibility of Prednisol with other intravenously administered drugs is possible – it is recommended to administer it separately from other drugs (IV bolus, or via another drip, as a second solution). When mixing Prednisol solution with heparin, a precipitate forms.

Concomitant administration of Prednisol with

• Inducers of “hepatic” microsomal enzymes (phenobarbital, rifampicin, phenytoin, theophylline, ephedrine) leads to a decrease in its concentration;
• Diuretics (especially “thiazide” and carbonic anhydrase inhibitors) and amphotericin B – may lead to increased excretion of K⁺ from the body and an increased risk of heart failure;
• Sodium-containing drugs – to the development of edema and increased blood pressure;
• Cardiac glycosides – their tolerability worsens and the likelihood of ventricular extrasystole increases (due to induced hypokalemia);
• Indirect anticoagulants – weakens (less often enhances) their effect (dose adjustment required);
• Anticoagulants and thrombolytics • increases the risk of bleeding from ulcers in the gastrointestinal tract;
• Ethanol and NSAIDs – the risk of erosive-ulcerative lesions in the gastrointestinal tract and bleeding development increases (in combination with NSAIDs for treating arthritis, a reduction in the dose of glucocorticosteroids is possible due to summation of the therapeutic effect);
• Paracetamol – the risk of hepatotoxicity increases (induction of liver enzymes and formation of a toxic metabolite of paracetamol);
• Acetylsalicylic acid – accelerates its excretion and reduces its concentration in the blood (upon withdrawal of Prednisol, the level of salicylates in the blood increases and the risk of side effects rises);
• Insulin and oral hypoglycemic drugs, antihypertensive agents – their effectiveness decreases;
• Vitamin D – its effect on the absorption of Ca2+ in the intestine is reduced;
• Somatotropin – reduces the effectiveness of the latter, and with praziquantel – its concentration;
• M-cholinoblockers (including antihistamines and tricyclic antidepressants) and nitrates – contributes to increased intraocular pressure;
• Isoniazid and mexiletine – increases their metabolism (especially in “fast acetylators”), leading to a decrease in their plasma concentrations.

Carbonic anhydrase inhibitors and “loop” diuretics may increase the risk of osteoporosis.

Indomethacin, displacing Prednisol from its binding with albumins, increases the risk of its side effects.

ACTH enhances the effect of Prednisol.

Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by Prednisol.

Cyclosporine and ketoconazole, by slowing the metabolism of Prednisol, can in some cases increase its toxicity.

Concomitant administration of androgens and steroidal anabolic drugs with Prednisol contributes to the development of peripheral edema and hirsutism, and the appearance of acne.

Estrogens and oral estrogen-containing contraceptives reduce the clearance of Prednisol, which may be accompanied by an increase in the severity of its action.

Mitotane and other inhibitors of adrenal cortex function may necessitate an increase in the dose of Prednisol.

When used concomitantly with live antiviral vaccines and against the background of other types of immunization, the risk of virus activation and development of infections increases.

Antipsychotic drugs (neuroleptics) and azathioprine increase the risk of cataract development when Prednisol is prescribed.

When used concomitantly with antithyroid drugs, the clearance of Prednisol decreases, and with thyroid hormones, it increases.

Hypokalemia caused by Prednisol may increase the severity and duration of muscle blockade induced by muscle relaxants.

Immunosuppressants increase the risk of developing infections and lymphoma or other lymphoproliferative disorders associated with the Epstein-Barr virus.

Tricyclic antidepressants may exacerbate depression caused by Prednisol intake (they are not indicated for the therapy of these side effects).

Storage Conditions

Store at a temperature not exceeding 25°C (77°F) in a light-protected place. Do not freeze. Keep out of reach of children.

Shelf Life

Shelf life – 2 years.

Dispensing Status

By prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.