FLUTIM CREAM 15GM

Indications

• Asthma maintenance therapy
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Nasal polyps

Dosage

Adults: For asthma: 160 micrograms once daily, may be reduced to 80 micrograms once daily if control is maintained; may be increased to 320 micrograms twice daily if necessary. For allergic rhinitis:

Mechanism of action

Fluticasone propionate acts as a highly selective agonist at the human glucocorticoid receptor, exhibiting negligible activity at androgen, estrogen, or mineralocorticoid receptors. It activates glucocorticoid receptors and inhibits nuclear factor kappa B, which plays a crucial role in the inflammatory response. Additionally, fluticasone reduces the number of inflammatory mediator cells in the nasal mucosa and decreases nasal reactivity to allergens, leading to reduced release of inflammatory mediators and proteolytic enzymes.

Pharmacodynamics

Fluticasone's therapeutic effects are primarily local, resulting from the deposition of the inhaled drug on the nasal mucosa or lungs, rather than systemic effects from swallowed portions. Its anti-inflammatory action includes the inhibition of eosinophilia and other inflammatory cell types, contributing to the management of allergic conditions and symptoms of asthma. The drug is associated with vasoconstriction in the skin when used topically.

Pharmacokinetics

Fluticasone is administered via inhalation or intranasal routes, leading to low systemic absorption. Following inhalation, it is rapidly absorbed, with peak plasma concentrations occurring within one to two hours. The drug has a high protein binding rate and is extensively metabolized by the liver, primarily through cytochrome P450 enzymes. The elimination half-life is approximately 3 to 4 hours, with metabolites excreted primarily in feces and urine. Due to its significant first-pass metabolism, systemic exposure is minimized.

Contra-indications

• Hypersensitivity to fluticasone or any excipients
• Severe systemic fungal infections
• Untreated localized infections

Adverse effects

• Oral candidiasis
• Dysphonia
• Cough
• Nasal irritation
• Headache
• Throat irritation
• Nasal bleeding
• Increased risk of pneumonia in COPD patients

Interactions

• Cenobamate: Moderate interaction (decreases exposure)
• Cobicistat: Unknown interaction (increases exposure)
• Idelalisib: Unknown interaction (increases exposure)
• Mitotane: Unknown interaction (decreases exposure)
• Clarithromycin: Unknown interaction (increases exposure)
• Rifampicin: Unknown interaction (decreases exposure)

Precautions

• Caution in patients with tuberculosis, untreated systemic infections, or those with a history of severe allergies
• Monitor for signs of adrenal suppression in long-term use
• Use with caution in patients with hepatic impairment

Pregnancy

Fluticasone should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consultation with a healthcare provider is recommended.

Breast-feeding

Fluticasone is excreted in breast milk. Caution is advised when administered to breastfeeding women.

Storage

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

Formulations

• Pressurized inhalation aerosol: 320 micrograms/9 micrograms per dose
• Nasal spray: 50 micrograms per actuation
• Dry powder inhaler: 200 micrograms per dose

Indications

• Eradication of nasal carriage of Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus (MRSA)
• Treatment of skin infections caused by susceptible bacteria, including impetigo and folliculitis

Dosage

Adults: For nasal carriage eradication, apply 2-3 times a day for 5 days, with the dose applied to the inner surface of each nostril. For

Mechanism of action

Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, inhibiting the enzyme that converts isoleucine and tRNA to isoleucyl-tRNA. This inhibition leads to decreased bacterial protein and RNA synthesis, resulting in bacteriostatic effects at lower concentrations and bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over 24 hours.

Pharmacodynamics

Mupirocin is effective against susceptible aerobic gram-positive cocci, particularly Staphylococcus aureus, Staphylococcus epidermidis, and beta-hemolytic streptococci such as Streptococcus pyogenes. Its antibacterial activity is attributed to its ability to inhibit protein synthesis, which is crucial for bacterial survival. Clinical studies have shown a therapeutic response rate of 94 to 98% after one week of treatment for conditions like impetigo, with over 90% of patients demonstrating clinical improvement in primary and secondary skin infections.

Pharmacokinetics

Mupirocin is primarily used topically, resulting in minimal systemic absorption. When applied to the skin, it is rapidly absorbed and achieves high local concentrations. The drug is metabolized in the liver and excreted in urine. Its pharmacokinetic profile supports its use for localized infections with minimal risk of systemic side effects.

Adverse effects

• Skin reactions
• Nasal mucosal disorder

Interactions

• Caution in patients with sensitivity to sulfonamides
• Caution with significant hepatic impairment
• Caution with significant renal impairment

Precautions

• Monitor for leucopenia
• Use with caution in patients with G6PD deficiency due to risk of hemolysis
• Avoid use in pregnancy unless potential benefit outweighs risk due to risk of neonatal hemolysis and methaemoglobinaemia in the third trimester

Pregnancy

Manufacturer advises avoiding unless potential benefit outweighs risk-no information available.

Breast-feeding

Small risk of kernicterus in jaundiced infants and of haemolysis in G6PD-deficient infants.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Mupirocin 20 mg per 1 gram cream
• Mupirocin nasal spray

Mechanism of action

[DB08906] and [DB00588] work through an unknown mechanism to affect the action of various cell types and mediators of inflammation. In vitro experiments show [DB08906] activating glucocorticoid receptors, inhibiting nuclear factor kappa b, and inhibiting lung eosinophilia in rats. [DB00588] performs similar activity but is not stated to affect nuclear factor kappa b. Fluticasone propionate is a highly selective agonist at the human glucocorticoid receptor with negligible activity at androgen, estrogen, or mineralocorticoid receptors. In preclinical studies, fluticasone propionate reportedly exhibited weak progesterone-like activity. However, as plasma concentrations of fluticasone propionate are very low following intranasal administration of the drug in recommended doses, the clinical importance of this finding is not known. The therapeutic effects of fluticasone propionate are thought to result from local actions of the deposited inhaled dose on the nasal mucosa rather than from the systemic actions of the swallowed portion of the dose. The exact mechanism(s) of anti-inflammatory action of corticosteroids in allergic rhinitis remains unknown, but may involve reductions in the following: number of mediator cells (basophils, eosinophils, helper-inducer [CD4+, T4] T-cells, mast cells, and neutrophils) in the nasal mucosa, nasal reactivity to allergens, and release of inflammatory mediators and proteolytic enzymes. Following exposure of patients with a history of allergic rhinitis to allergen, eosinophils, basophils, mast cells, T cells, and neutrophils appear to infiltrate nasal secretions and mucosa, releasing inflammatory mediators that generate allergic responses such as pruritus, sneezing, rhinorrhea, and nasal edema. /Corticosteroids/ Other mechanisms by which corticosteroids may improve symptoms of allergic rhinitis may involve inhibition of postcapillary venule dilation and permeability and facilitation of nasomucociliary clearance of nasal secretions. Patients receiving short- and long-term treatment with intranasal fluticasone propionate have demonstrated decreases in nasal turbinate swelling and mucosal inflammation. As inflammatory changes occur during periods of increased nasal hyperresponsiveness, the degree of response to nasal secretory stimuli has been used as an indirect measure of inflammation. In patients with asymptomatic seasonal allergic rhinitis, pretreatment with intranasal fluticasone propionate for 2-6 weeks prior to challenge with allergens or inflammatory mediatorsgenerally reduced the release of tryptase, histamine, eosinophilic cationic protein, and prostaglandin D2 in nasal biopsies or nasal lavage fluid; concentrations of eosinophils or activated eosinophils, CD4+ T-cells, and basophils also were reduced. /Corticosteroids/ Like other topical corticosteroids, fluticasone propionate has anti-inflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of the topical steroids, in general, is unclear. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Pharmacodynamics

Systemically, in vitro experiments show [DB08906] activates glucocorticoid receptors, inhibits nuclear factor kappa b, and inhibits lung eosinophilia in rats. [DB00588] performs similar activity but is not stated to affect nuclear factor kappa b. [DB00588] as a topical formulation is also associated with vasoconstriction in the skin.

Mechanism of action

Mupirocin specifically and reversibly binds to bacterial isoleucyl transfer-RNA (tRNA) synthetase, which is an enzyme that promotes the conversion of isoleucine and tRNA to isoleucyl-tRNA. Inhibition of this enzyme subsequently leads to the inhibition of the bacterial protein and RNA synthesis. Mupirocin is bacteriostatic at lower concentrations but it exerts bactericidal effects with prolonged exposure, killing 90-99% of susceptible bacteria over a 24 hour period.

Pharmacodynamics

Mupirocin is reported to be active against susceptible aerobic gram-positive cocci, such as _Staphylococcus aureus_, _Staphylococcus epidermidis_, and other beta-hemolytic streptococci_Streptococcus pyogenes_. It mediates its antibacterial activity by inhibiting the bacterial protein synthesis and formation of bacterial proteins essential for survival. The minimum bactericidal concentration (MBC) against relevant pathogens is generally eight-fold to thirty-fold higher than the minimum inhibitory concentration (MIC). In one clinical study investigating the therapeutic effectiveness of topical mupirocin in impetigo, the therapeutic response rate was about 94 to 98% after one week following the end of therapy. In clinical studies of patients with primary and secondary skin infections, both elimination of the bacterial pathogen and clinical cure or improvement hav been demonstrated in over 90% of patients receiving topical mupirocin. Mupirocin resistance as high as 81% has been reported previously. Resistance to mupirocin, which occurs more frequently in methicillin-resistant than methicillin-susceptible staphylococci, may occur with the production of a modified isoleucyl-tRNA synthetase, or the acquisition of, by genetic transfer, a plasmid mediating a new isoleucyl-tRNA synthetase.