ZEDFOS

Indications

• Suppression of inflammatory disorders
• Management of allergic conditions
• Congenital adrenal hyperplasia
• Inflammatory and allergic eye conditions

Dosage

Children: For children aged 1–11 months: Initially 1 mg, repeated up to 4 times in 24 hours according to response. Aged 1–5 years: Initially 2 mg, repeated up to 4 times in 24 hours according to response. Aged 6–11 years: Initially 4 mg, repeated up to 4 times in 24 hours according to response. Aged 12–17 years: 4–20 mg, repeated up to 4 times in 24 hours according to response.

Adults: Dosage varies based on condition; typically, initial doses are adjusted according to the patient's response and severity of condition.

Mechanism of action

Betamethasone exerts its effects by binding to glucocorticoid receptors, leading to modulation of gene expression and suppression of inflammatory cytokines and mediators.

Pharmacodynamics

Betamethasone reduces inflammation and immune response, which is beneficial in managing various inflammatory and allergic disorders.

Pharmacokinetics

Betamethasone is rapidly absorbed after administration, with a long half-life allowing for once-daily dosing in many cases. It is metabolized in the liver and excreted primarily in urine.

Adverse effects

• Hiccups
• Oedema
• Mood and behaviour changes
• Vision disorders
• Serious gastro-intestinal effects
• Musculoskeletal effects
• Ophthalmic effects
• Stevens-Johnson syndrome
• Myocardial rupture (following recent myocardial infarction)

Interactions

• Cobicistat + betamethasone: Unknown (increases exposure)
• Idelalisib + betamethasone: Unknown (increases exposure)
• Clarithromycin + betamethasone: Unknown (increases exposure)

Precautions

• Immunosuppression due to prolonged corticosteroid treatment
• Adrenal suppression if given for longer than 3 weeks
• Increased susceptibility to infections, including chickenpox and measles

Pregnancy

Readily crosses the placenta. Transient effect on fetal movements and heart rate.

Storage

Store at room temperature, protect from light.

Formulations

• Betamethasone sodium phosphate 4 mg per 1 ml solution for injection ampoules

Indications

• Eczema
• Psoriasis
• Contact dermatitis
• Seborrheic dermatitis
• Atopic dermatitis

Dosage

Children: Refer to the BNF for Children for appropriate dosing information.

Adults: Refer to relevant clinical guidelines or product information for specific dosing instructions.

Mechanism of action

Betamethasone dipropionate exerts its effects by binding to the glucocorticoid receptor, leading to the modulation of gene expression. This interaction results in the inhibition of pro-inflammatory cytokines, chemokines, and adhesion molecules, which reduces inflammation, suppresses the immune response, and promotes vasoconstriction in the affected tissues.

Pharmacodynamics

The pharmacodynamic effects of betamethasone dipropionate include a significant reduction in inflammation and immune response due to the inhibition of leukocyte infiltration at the site of inflammation. The drug also inhibits the release of arachidonic acid, subsequently decreasing the production of inflammatory mediators such as prostaglandins and leukotrienes. Its efficacy is enhanced by its high lipid solubility, allowing for better penetration through the skin layers.

Pharmacokinetics

Betamethasone dipropionate is well absorbed through the skin when applied topically. Its bioavailability is influenced by the formulation and the condition of the skin. The drug is metabolized primarily in the liver to inactive metabolites, which are excreted in the urine. The systemic absorption and effects are minimal when used as directed, but caution is advised in extensive applications or occlusive dressings, which may increase absorption.

Adverse effects

• Local skin atrophy
• Striae
• Telangiectasia
• Hypopigmentation
• Allergic contact dermatitis
• Systemic effects with prolonged use

Precautions

• Use with caution in patients with a history of diabetes mellitus
• Monitor for potential adrenal suppression with prolonged use
• Avoid application to infected areas unless treated

Pregnancy

Betamethasone dipropionate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data suggest that topical corticosteroids have low systemic absorption.

Breast-feeding

Caution is advised when using betamethasone dipropionate during breastfeeding, as it is unknown whether it is excreted in breast milk. Topical corticosteroids should be applied sparingly and avoided on the breast area to minimize ingestion by the infant.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Topical cream
• Topical ointment
• Topical lotion

Indications

• Allergic reactions
• Dermatologic conditions
• Endocrine disorders (such as adrenal insufficiency)
• Gastrointestinal diseases (such as Crohn's disease)
• Hematologic disorders (such as thrombocytopenic purpura)
• Neoplastic diseases (as part of cancer therapy)
• Nervous system disorders (such as multiple sclerosis exacerbations)
• Ocular diseases (such as uveitis)

Mechanism of action

Bethamethasone exerts its effects by binding to the glucocorticoid receptor, which is a type of nuclear receptor. Upon binding, the receptor-ligand complex translocates to the nucleus and influences gene expression. This leads to the upregulation of anti-inflammatory proteins and the downregulation of pro-inflammatory cytokines. As a result, bethamethasone reduces inflammation and modulates the immune response.

Pharmacodynamics

The pharmacodynamic effects of bethamethasone include significant anti-inflammatory, immunosuppressive, and anti-proliferative actions. It decreases the production of inflammatory mediators such as prostaglandins and leukotrienes, thereby alleviating symptoms associated with inflammation. The drug also inhibits the migration of leukocytes to sites of inflammation, which further contributes to its anti-inflammatory effects.

Pharmacokinetics

Bethamethasone is well-absorbed following oral administration, with a bioavailability that can vary based on the route of administration. It is extensively metabolized in the liver, primarily through conjugation with glucuronic acid, and has an elimination half-life of several hours to a day. The drug is excreted predominantly in the urine as metabolites. Its effects can last longer than the half-life due to the sustained action within tissues.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to bethamethasone or any component of the formulation
• Administration of live vaccines in immunocompromised patients

Adverse effects

• Increased susceptibility to infections
• Weight gain
• Fluid retention
• Hypertension
• Hyperglycemia
• Osteoporosis
• Gastrointestinal perforation
• Mood changes
• Cushing's syndrome

Interactions

• Non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of gastrointestinal adverse effects
• Antidiabetic agents may require adjustment due to altered glucose metabolism
• Live vaccines may be less effective or cause disease in immunocompromised patients

Precautions

• Use with caution in patients with diabetes, hypertension, or peptic ulcer disease
• Monitor for signs of infection due to immunosuppression
• Gradual withdrawal is necessary to avoid adrenal insufficiency after long-term therapy

Pregnancy

Bethamethasone is categorized as a pregnancy category C drug. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Bethamethasone is excreted in breast milk. Caution should be exercised when administered to a nursing mother.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets
• Injectable solution
• Topical cream
• Topical ointment
• Topical lotion

Indications

• Atopic dermatitis
• Psoriasis
• Contact dermatitis
• Seborrheic dermatitis
• Lichen planus

Dosage

Children: Refer to specific pediatric dosing guidelines in the BNF for Children, as it varies based on the formulation and condition treated.

Adults: Refer to specific prescribing information for dosing guidelines, as it varies based on the formulation and condition treated.

Mechanism of action

Dipropionate works by binding to glucocorticoid receptors in target tissues. This interaction modulates the transcription of specific genes, resulting in decreased production of pro-inflammatory cytokines and other mediators of inflammation. The drug also inhibits the migration of leukocytes to sites of inflammation and stabilizes lysosomal membranes, which contributes to its anti-inflammatory effects.

Pharmacodynamics

The pharmacodynamic effects of dipropionate include significant reduction in inflammation and immune responses. It enhances the synthesis of anti-inflammatory proteins while suppressing the production of inflammatory mediators. Its potency and efficacy vary based on the formulation and route of administration, with topical applications providing localized effects and systemic absorption leading to broader actions.

Pharmacokinetics

Dipropionate is absorbed through the skin when applied topically, with systemic absorption varying depending on the formulation and the condition of the skin (e.g., compromised barriers may enhance absorption). Its metabolism primarily occurs in the liver, with excretion predominantly via urine. The half-life can vary, but it is generally short, necessitating multiple daily applications for sustained effects.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when administered to nursing mothers, as it is unknown if it is excreted in human milk.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.

Mechanism of action

Glucocorticoids inhibit neutrophil apoptosis and demargination, and inhibit NF-Kappa B and other inflammatory transcription factors. They also inhibit phospholipase A2, leading to decreased formation of arachidonic acid derivatives. In addition, glucocorticoids promote anti-inflammatory genes like interleukin-10. Corticosteroids like betamethasone can act through nongenomic and genomic pathways. The genomic pathway is slower and occurs when glucocorticoids activate glucocorticoid receptors and initiate downstream effects that promote transcription of anti-inflammatory genes including phosphoenolpyruvate carboxykinase (PEPCK), IL-1-receptor antagonist, and tyrosine amino transferase (TAT). On the other hand, the nongenomic pathway is able to elicit a quicker response by modulating T-cell, platelet and monocyte activity through the use of existing membrane-bound receptors and second messengers. Corticosteroids interact with specific receptor proteins in target tissues to regulate the expression of corticosteroid responsive genes, thereby changing the levels and array of proteins synthesized by the various target tissues. As a consequence of the time required for changes in gene expression and protein synthesis, most effects of corticosteroids are not immediate, but become apparent after several hours. ... Although corticosteroids predominantly act to increase expression of target genes, there are well documented examples where glucocorticoids decrease transcription of target genes ... In contrast to these genomic effects, recent studies have raised the possibility that some actions of corticosteroids are immediate and are mediated by membrane-bound receptors. /Adrenocorticosteroids/ The mechanisms by which glucocorticoids inhibit glucose utilization in peripheral tissues are not fully understood. Glucocorticoids decrease glucose uptake in adipose tissue, skin, fibroblasts, thymocytes, and polymorphonuclear leukocytes; these effects are postulated to result from translocation of the glucose transporters from the plasma membrane to an intracellular location. These peripheral effects are associated with a number of catabolic actions, including atrophy of lymphoid tissue, decreased muscle mass, negative nitrogen balance, and thinning of the skin. /Adrenocorticalsteroids/ The mechanisms by which the glucocorticoids promote gluconeogenesis are not fully defined. Amino acids mobilized from a number of tissues in response to glucocorticoids reach the liver and provide substrate for the production of glucose and glycogen. In the liver, glucocorticoids induce the transcription of a number of enzymes involved in gluconeogenesis and amino acid metabolism, including phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and fructose-2,6-bisphosphatase. Analyses of the molecular basis for regulation of phosphoenolpyruvate carboxykinase gene expression have identified complex regulatory influences involving an interplay among glucocorticoids, insulin, glucagon, and catecholamine. The effects of these hormones and amines on phosphoenolpyruvate carboxykinase gene expression mirror the complex regulation of gluconeogenesis in the intact organism. /Adrenocorticalsteroids/ ... /A/ major action of corticosteroids on the cardiovascular system is to enhance vascular reactivity to other vasoactive substances. Hypoadrenalism generally is associated with hypotension and reduced response to vasoconstrictors such as norepinephrine and angiotensin II. This diminished pressor response is explained partly by recent studies in experimental systems showing that glucocorticoids increase expression of adrenergic receptors in the vascular wall. Conversely, hypertension is seen in patients with excessive glucocorticoid secretion, occurring in most patients with Cushing's syndrome and in a subset of patients treated with synthetic glucocorticoids (even those lacking any significant mineralocorticoid action). /Adrenocorticosteroids/ For more Mechanism of Action (

Pharmacodynamics

Corticosteroids bind to the glucocorticoid receptor inhibiting pro-inflammatory signals, while 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 who require long-term treatment with a corticosteroid should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.