NOTIDAM

Indications

• Chronic Obstructive Pulmonary Disease (COPD)
• Bronchospasm associated with COPD

Dosage

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

Adults: The recommended dose for adults is 88 mcg once daily via inhalation.

Mechanism of action

Revefenacin functions as a competitive antagonist of muscarinic cholinergic receptors, particularly displaying a high affinity for the M3 subtype. This selective antagonism inhibits acetylcholine-induced calcium mobilization and contractile responses in airway smooth muscle, resulting in bronchodilation. The drug’s slower dissociation from the M3 receptor compared to the M2 receptor contributes to its long duration of action, making it effective in managing the cholinergic bronchoconstrictor tone associated with COPD.

Pharmacodynamics

Revefenacin provides sustained bronchodilation with a lower incidence of anti-muscarinic side effects compared to other LAMAs. Clinical studies have shown that a dose of 88 mcg effectively improves forced expiratory volume and peak expiratory flow rate in patients with COPD. It has also demonstrated a reduction in the need for rescue inhalers, indicating its effectiveness in controlling symptoms over time.

Pharmacokinetics

Revefenacin is administered via inhalation, which allows for targeted delivery to the lungs and minimizes systemic exposure. Its pharmacokinetic profile supports once-daily dosing due to its long duration of action. The drug is primarily eliminated through the lungs, with low systemic absorption contributing to its favorable side effect profile.

Adverse effects

• Dry mouth
• Constipation
• Urinary retention
• Cough
• Pharyngitis
• Sinusitis
• Headache
• Nausea

Precautions

• Use with caution in patients with narrow-angle glaucoma
• Use with caution in patients with prostatic hyperplasia or bladder neck obstruction
• Caution in patients with cardiovascular disorders

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Revefenacin should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether revefenacin is excreted in human milk. Caution should be exercised when administered to a nursing woman.

Storage

Store at room temperature, away from moisture and heat. Do not freeze.

Formulations

• Inhalation solution: 88 mcg per vial

Mechanism of action

Revefenacin is an inhaled bronchodilator muscarinic antagonist with a long-acting bronchodilation activity. It has been shown to present a high affinity and behaved as a competitive antagonist of the five muscarinic cholinergic receptors. Studies have indicated that revefenacin dissociates significantly slower from the muscarinic receptor M3 (hM3) when compared to the receptor M2 (hM2) which indicates a kinetic selectivity for this subtype. This competitive antagonism produces a suppressive action of the acetylcholine-evoked calcium mobilization and contractile responses in the airway tissue. Lastly, due to the duration of the bronchodilation, revefenacin is considered a long-acting muscarinic antagonist which allows it to be dosed once daily. This response is very important for the therapy of COPD as the main goal is the reduce the frequency and severity of exacerbations which are normally driven by the presence of elevated cholinergic bronchoconstrictor tone mediated by muscarinic receptors on parasympathetic ganglia and airway smooth muscle. Hence, the activity of revefenacin produces a potent and long-lasting protection against the bronchoconstrictor response to acetylcholine or methacholine.

Pharmacodynamics

Revefenacin has been reported to produce a sustained, long-acting bronchodilation with lower anti-muscarinic-related side effects. In clinical trials, revefenacin demonstrated to be of a long duration of action and low systemic exposure in patients with COPD. Also, it was reported that a dose of 88 mcg can produce a clinically effective bronchodilation measured by through forced expiratory volume in 1s and serial spirometric assessments. In placebo-controlled trials, revefenacin showed a decrease in the use of albuterol rescue inhalers and sustained increases in the peak expiratory flow rate that reached a steady state at a maximum in day 7. As well, there was a reported superior lung selectivity index when compared with other LAMAs such as glycopyrronium and tiotropium which produced a decreased sialagogue effect.