DEBO-METHYL-40 40MG/ML STERILE AQUEOUS SUSPENSION

Indications

• Suppression of inflammatory and allergic disorders
• Cerebral oedema associated with malignancy
• Management of graft rejection reactions
• Treatment of autoimmune diseases
• Severe allergic reactions

Dosage

Children: For paediatric dosing, refer to the BNF for Children for specific guidance.

Adults: Initially 10-500 mg by intravenous infusion, or 2-40 mg orally daily, depending on the condition being treated.

Mechanism of action

Methylprednisolone exerts its effects primarily through binding to the glucocorticoid receptor, leading to decreased vasodilation and permeability of capillaries, as well as suppression of leukocyte migration to sites of inflammation. It inhibits phospholipase A2, reducing the formation of arachidonic acid derivatives, and inhibits inflammatory transcription factors such as NF-kappa B. This results in a net anti-inflammatory effect, promoting the expression of anti-inflammatory genes like interleukin-10, while higher doses can impart immunosuppressive effects.

Pharmacodynamics

As a glucocorticoid, methylprednisolone influences various physiological processes, including the modulation of the immune response and inflammation. It has a wide therapeutic window, allowing for flexibility in dosing. Long-term use can lead to suppression of the hypothalamic-pituitary-adrenal axis, increasing the risk of infections and other side effects associated with corticosteroid therapy.

Pharmacokinetics

Methylprednisolone is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within one to two hours after oral administration. It has a half-life of approximately 18 to 36 hours, with its effects lasting longer than its plasma concentration due to its mechanism of action. The drug is primarily metabolized in the liver and excreted in the urine. It binds significantly to plasma proteins, which affects its distribution in the body.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to methylprednisolone or any component of the formulation
• Live vaccines in patients receiving immunosuppressive doses
• Untreated bacterial infections

Adverse effects

• Increased susceptibility to infections
• Gastrointestinal disturbances
• Elevated blood glucose levels
• Cushing's syndrome
• Fluid retention
• Hypertension
• Osteoporosis
• Mood changes and psychiatric effects

Interactions

• Dronedarone increases exposure to methylprednisolone
• Miconazole increases concentration of methylprednisolone
• Azole antifungals increase exposure to methylprednisolone
• Crizotinib increases exposure to methylprednisolone
• Imatinib increases exposure to methylprednisolone
• Letermovir increases exposure to methylprednisolone
• Lumacaftor decreases exposure to methylprednisolone
• Mitotane decreases exposure to methylprednisolone
• Monoclonal antibodies decrease exposure to methylprednisolone

Precautions

• Use with caution in patients with a history of peptic ulcer disease
• Monitor for signs of infection and elevated blood glucose levels
• Consider dose adjustments in patients with renal or hepatic impairment
• Gradual withdrawal recommended to avoid adrenal insufficiency

Pregnancy

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus. Caution is advised.

Breast-feeding

Methylprednisolone is excreted in breast milk. Caution should be exercised when administering to a nursing mother.

Storage

Store in a cool, dry place, protected from light. Keep out of reach of children.

Formulations

• Oral tablets
• Oral suspension
• Solution for injection
• Modified-release tablets

Indications

• Hydration therapy
• Solvent for intravenous medications
• Diluent for oral medications
• Rehydration in cases of fluid loss
• Topical applications for wound care

Dosage

Children: Refer to specific drug formulations for appropriate dosing, as the dosage will vary depending on the active ingredient in the aqueous solution.

Adults: Refer to specific drug formulations for appropriate dosing, as the dosage will vary depending on the active ingredient in the aqueous solution.

Mechanism of action

Aqueous solutions serve primarily as a medium for drug solubility and absorption. The mechanism of action depends on the active ingredient dissolved within the aqueous solution. For many drugs, the aqueous environment enhances bioavailability by allowing the active ingredients to dissolve and interact with biological membranes, facilitating their transport across cell barriers.

Pharmacodynamics

The pharmacodynamics of aqueous solutions are influenced by the solutes they contain. Generally, the dissolution of drugs in an aqueous medium can enhance their effectiveness by improving absorption rates, increasing peak plasma concentrations, and allowing for more predictable pharmacological effects. The specific pharmacodynamic response will depend on the nature of the solute and its interaction with the body’s receptors or enzymes.

Pharmacokinetics

The pharmacokinetics of aqueous solutions largely pertain to the dissolved substances. They are absorbed through various routes, such as gastrointestinal tract, intravenous administration, or topical application, depending on the formulation. The rate of absorption can vary based on the solute’s properties, such as molecular weight, lipophilicity, and the presence of other excipients. Distribution, metabolism, and excretion will also depend on the active ingredient within the aqueous solution.

Pregnancy

Aqueous solutions are generally regarded as safe for use during pregnancy, but the specific context and formulation should be considered.

Breast-feeding

Aqueous solutions are typically considered safe during breastfeeding, but caution is advised depending on the specific formulation.

Storage

Store at room temperature, away from direct sunlight and moisture. Ensure containers are tightly sealed.

Formulations

• Aqueous solution
• Aqueous gel
• Aqueous suspension

Indications

• Surgical procedures
• Injection of medications
• Preparation of sterile pharmaceutical products
• Management of open wounds
• Use in controlled environments such as hospitals and laboratories

Dosage

Children: Refer to specific drug monographs for dosage information as sterile itself is not a pharmacological agent.

Adults: Refer to specific drug monographs for dosage information as sterile itself is not a pharmacological agent.

Mechanism of action

Sterility itself does not have a mechanism of action as it is a state of cleanliness and does not interact with biological systems. However, the methods used to achieve sterility, such as heat or chemical agents, act by denaturing proteins, disrupting cellular structures, or damaging nucleic acids in microorganisms, leading to their inactivation or destruction.

Pharmacodynamics

The pharmacodynamics of sterile techniques primarily involves the prevention of microbial infection and contamination when administering medications. By ensuring that products are sterile, the risk of adverse effects related to infections is minimized. The effectiveness of sterilization methods can be influenced by factors such as temperature, duration of exposure, and the type of microorganisms present.

Pharmacokinetics

As sterility does not pertain to a specific drug, pharmacokinetics is not applicable. However, the pharmacokinetics of a drug will depend on its formulation, route of administration, and the presence of preservatives or stabilizers that may be used alongside sterile preparations.

Pregnancy

Sterile preparations are generally considered safe during pregnancy as they are used to provide hydration, nutrition, or medications in a controlled manner, but specific formulations should be assessed individually.

Breast-feeding

Sterile solutions used for hydration or nutritional support are typically safe during breastfeeding, but any specific additives or medications within the solutions should be evaluated for safety.

Storage

Sterile solutions should be stored in a cool, dry place, protected from light, and should be used before the expiration date. Once opened, they may have specific storage requirements based on the formulation.

Formulations

• Sterile saline solution
• Sterile water for injection
• Sterile dextrose solution
• Sterile electrolyte solutions

Mechanism of action

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days. Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10. Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels. Glucocorticoids are capable of suppressing the inflammatory process through numerous pathways. They interact with specific intracellular receptor proteins in target tissues to alter the expression of corticosteroid-responsive genes. Glucocorticoid-specific receptors in the cell cytoplasm bind with steroid ligands to form hormone-receptor complexes that eventually translocate to the cell nucleus. There these complexes bind to specific DNA sequences and alter their expression. The complexes may induce the transcription of mRNA leading to synthesis of new proteins. Such proteins include lipocortin, a protein known to inhibit PLA2a and thereby block the synthesis of prostaglandins, leukotrienes, and PAF. Glucocorticoids also inhibit the production of other mediators including AA metabolites such as COX, cytokines, the interleukins, adhesion molecules, and enzymes such as collagenase. /Glucocorticoids/

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.