AVAMYS NASAL SPRAY

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

• Asthma
• Chronic Obstructive Pulmonary Disease (COPD)
• Acute bronchospasm
• Respiratory distress

Dosage

Children: Refer to specific drug guidelines in the BNF for Children for accurate dosing information.

Adults: Refer to specific drug guidelines in the BNF for accurate dosing information.

Mechanism of action

The mechanism of action varies depending on the specific drug being actuated, but generally involves the rapid dispersal of drug particles into the airways. For inhaled bronchodilators, they typically work by binding to adrenergic receptors in the bronchial smooth muscle leading to relaxation and dilation of the airways.

Pharmacodynamics

Pharmacodynamics of actuation primarily involves the drug's effects on the respiratory system, with the intention of relieving bronchoconstriction and improving airflow. The duration of action and peak effect can vary widely based on the specific medication used and the delivery technique.

Pharmacokinetics

Pharmacokinetics of inhaled medications generally indicates a rapid onset of action due to the direct delivery to the lungs, with peak plasma concentrations occurring within minutes. The distribution is localized, and the elimination half-life will depend on the specific pharmacological properties of the drug being actuated.

Pregnancy

Limited data on the safety of actuation during pregnancy. Consult a healthcare provider for individualized assessment.

Breast-feeding

Consult a healthcare provider as the effects on breastfed infants are not well-studied.

Storage

Store in a cool, dry place, away from light and moisture.

Indications

• Induction of labor
• Management of uterine atony
• Postpartum hemorrhage
• Cervical ripening

Dosage

Children: Dosage for paediatric patients is typically not applicable, as these medications are intended for use in laboring women.

Adults: The dosage for adult women is generally determined based on clinical guidelines and the specific medication used, with careful monitoring required during administration.

Mechanism of action

Oxytocin, a key drug in delivery, acts on the oxytocin receptors in the uterus to stimulate uterine contractions. It mimics the natural hormone released by the posterior pituitary gland during labor, promoting rhythmic contractions that help in the delivery process. Prostaglandins also play a role by softening the cervix and enhancing uterine contractions, facilitating labor.

Pharmacodynamics

The pharmacodynamics of delivery medications involve the modulation of uterine smooth muscle activity. Oxytocin enhances calcium influx into uterine myocytes, leading to increased contractility. Prostaglandins induce cervical ripening and augment uterine tone, effectively preparing the body for the labor process. The balance between contraction strength, frequency, and duration is vital for effective labor progression.

Pharmacokinetics

The pharmacokinetics of delivery medications vary by substance. Oxytocin has a rapid onset of action when administered intravenously, with a half-life of approximately 3 to 5 minutes. It is primarily metabolized in the liver and has a short duration of action, often requiring continuous infusion during labor. Prostaglandins, depending on the specific compound used, may have varied absorption and elimination profiles, often administered via vaginal or oral routes.

Pregnancy

The safety of delivers during pregnancy has not been established. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is unknown whether delivers is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Dosage

Children: Refer to specific drug monographs for paediatric dosing information, as micrograms are a measurement unit rather than a medication.

Adults: Refer to specific drug monographs for adult dosing information, as micrograms are a measurement unit rather than a medication.

Pregnancy

Safety in pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Use with caution. The effects on a nursing infant are unknown, and it may be excreted in breast milk.

Storage

Store in a cool, dry place away from light. Ensure it is kept out of reach of children.

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.