ANORO ELLIPTA

Indications

• Chronic obstructive pulmonary disease (COPD)
• Maintenance treatment of asthma (in combination with other therapies)

Dosage

Children: Refer to the BNF for Children for specific dosing information in the paediatric population.

Adults: 2 puffs once daily via inhalation.

Mechanism of action

Umeclidinium acts as a long-acting muscarinic antagonist, competitively inhibiting the M3 muscarinic receptors in the airway smooth muscle. By blocking these receptors, umeclidinium prevents acetylcholine from inducing bronchoconstriction, leading to bronchodilation. The drug demonstrates a prolonged effect, maintaining bronchodilation for over 24 hours post-administration.

Pharmacodynamics

Umeclidinium does not significantly prolong the QTc interval, even at doses higher than the recommended therapeutic dose. The M3 receptor plays a critical role in the pathophysiology of asthma and COPD; its activation leads to increased intracellular calcium levels and subsequent muscle contraction, which can exacerbate symptoms of these conditions. By antagonizing this receptor, umeclidinium mitigates such adverse effects, promoting smoother airflow.

Pharmacokinetics

Umeclidinium is primarily administered via inhalation, which allows for localized delivery to the lungs. The pharmacokinetics of umeclidinium involve a prolonged half-life that supports once-daily dosing. The drug undergoes metabolism, primarily through hepatic pathways, and exhibits minimal systemic absorption, thus reducing potential systemic side effects.

Contra-indications

• Hypersensitivity to umeclidinium or any components of the formulation
• Severe hypersensitivity to atropine or its derivatives

Adverse effects

• Bronchospasm
• Dysphagia
• Epistaxis
• Altered taste
• Dry mouth
• Urinary retention
• Nausea
• Headache
• Cough
• Pharyngitis
• Sinusitis

Interactions

• Clozapine: Unknown (additive effect)
• Second-generation antipsychotics: Unknown (additive effect)

Precautions

• Use with caution in patients with narrow-angle glaucoma
• Use with caution in patients with urinary retention
• Patients should be advised on appropriate inhaler technique
• Monitor for paradoxical bronchospasm

Pregnancy

Manufacturer advises avoiding use due to limited data available on safety.

Breast-feeding

Manufacturer advises avoiding use due to lack of information on excretion in human milk.

Storage

Store below 25°C. Protect from moisture. Do not freeze.

Formulations

• Inhalation powder capsules (18 micrograms)
• Inhalation solution (2.5 micrograms/dose)

Indications

• Leishmaniasis
• Amebiasis
• Giardiasis

Dosage

Children: Refer to the BNF for Children for recommended dosing in paediatric patients, as it differs from adult dosing.

Adults: Refer to specific clinical guidelines or drug references for appropriate adult dosing as it varies based on the condition treated.

Mechanism of action

Trifenatate works by interfering with the metabolic processes of the protozoan parasites. It is thought to inhibit specific enzymes critical to the parasite's survival and proliferation, thereby disrupting cellular functions necessary for their growth. This mechanism leads to the eventual death of the parasite.

Pharmacodynamics

The pharmacodynamic profile of trifenatate indicates a significant effect on protozoan parasites, particularly in inhibiting their replication. The drug exhibits a dose-dependent response whereby increased concentrations correlate with enhanced antiparasitic activity. The therapeutic effects generally manifest over a period, reflecting the time needed for the drug to exert its action on the parasites.

Pharmacokinetics

Trifenatate is absorbed following oral administration, with its bioavailability varying among individuals. It undergoes hepatic metabolism, primarily via the cytochrome P450 system, producing several metabolites that contribute to its pharmacological effects. The elimination half-life of trifenatate is influenced by factors such as the patient's age, liver function, and the presence of other medications. Excretion occurs mainly through the urine and feces.

Contra-indications

• Hypersensitivity to trifenatate or any of its components
• Severe liver impairment
• Active bleeding disorders

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness
• Rash
• Abdominal pain

Interactions

• May enhance the effects of anticoagulants
• Caution with concurrent use of other hepatotoxic drugs
• May interact with drugs metabolized by the liver

Precautions

• Use with caution in patients with liver disease
• Monitor liver function during treatment
• Discontinue if signs of liver dysfunction occur

Pregnancy

Trifenatate should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data on its safety in pregnancy.

Breast-feeding

It is not known if trifenatate is excreted in human breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Oral suspension

Indications

• Chronic obstructive pulmonary disease (COPD)
• Asthma

Dosage

Children: The dosing regimen for paediatric patients should be determined based on clinical guidelines and individual patient needs, please refer to the BNF for Children for specific recommendations.

Adults: The dosing regimen for adults should be determined based on clinical guidelines and individual patient needs, please refer to the BNF for specific recommendations.

Mechanism of action

Vilanterol is a selective long-acting beta2-adrenergic agonist. Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase, which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs.

Pharmacodynamics

The pharmacodynamic effects of vilanterol include prolonged bronchodilation due to its long half-life and sustained action. This results in improved airflow and reduced respiratory distress in patients with obstructive airway diseases. The drug's selective action on beta2-adrenergic receptors minimizes adverse effects typically associated with non-selective adrenergic agonists.

Pharmacokinetics

Vilanterol demonstrates a long duration of action, which allows for once-daily dosing. It has a high lipid solubility, facilitating its absorption and distribution within lung tissues. The drug undergoes hepatic metabolism and is primarily eliminated via urine. The pharmacokinetic profile supports the use of vilanterol in chronic management rather than as a rescue medication.

Pregnancy

There is limited data on the use of vilanterol in pregnant women. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether vilanterol is excreted in human breast milk. Caution should be exercised when administering to breastfeeding women.

Storage

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

Mechanism of action

Umeclidinium is a long-acting muscarinic antagonist, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, it exhibits pharmacological effects through inhibition of M3 receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of methacholine- and acetylcholine-induced bronchoconstrictive effects was dose-dependent and lasted longer than 24 hours. The clinical relevance of these findings is unknown. The bronchodilation following inhalation of umeclidinium is predominantly a site-specific effect.

Pharmacodynamics

QTc interval prolongation was studied in a double-blind, multiple-dose, placebo- and positive-controlled, crossover trial in 86 healthy subjects. Following repeat doses of umeclidinium 500 mcg once daily (8 times the recommended dosage) for 10 days, umeclidinium does not prolong QTc to any clinically relevant extent. In humans, the M3 receptor has been heavily implicated in the pathophysiology of asthma and COPD. Once the M3 receptor is activated, the phospholipase C would phosphorylate downstream targets, forming inositol 1,4,5-trisphosphate and eventually releasing intracellular Ca²⁺. Increase in intracellular Ca²⁺ results in muscle contraction, thus worsening COPD and asthma-related bronchoconstriction. Additionally, M3 receptor activation also regulates pathways involving CD38, cyclic ADP ribose (cADPR), and ryanodine receptor channels, all of which control the intracellular Ca²⁺ homeostasis that will lead to muscle contraction.

Mechanism of action

Vilanterol is a selective long-acting beta2-adrenergic agonist. Its pharmacological effect is attributable to stimulation of intracellular adenylyl cyclase which catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cAMP). Increases in cyclic AMP are associated with relaxation of bronchial smooth muscle and inhibition of release of hypersensitivity mediators from mast cells in the lungs.