Rebreath175 mg/3 ml

Rebreath is an inhaled long-acting muscarinic antagonist (LAMA) bronchodilator. Its evidence-based indication is classified as follows:

Established / Approved Indication

• Chronic Obstructive Pulmonary Disease (COPD) - long-term maintenance treatment: Rebreath is indicated for the once-daily maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. It is administered by oral inhalation via a standard jet nebulizer.

Not Indicated / Important Limitations

• Rebreath is not indicated for the relief of acute bronchospasm or as a rescue medication for sudden shortness of breath. A short-acting bronchodilator (rescue inhaler) should be used for acute symptoms.
• Rebreath is not approved or established for the treatment of asthma.

There are no well-established off-label uses of Rebreath at this time; use should be limited to its approved COPD maintenance indication.

Each single-dose vial for nebulization contains Revefenacin 175 mcg in 3 mL of aqueous, isotonic, preservative-free solution, intended for oral inhalation using a standard jet nebulizer connected to an air compressor.

Rebreath is a long-acting muscarinic antagonist (LAMA), also called an anticholinergic bronchodilator, formulated as a ready-to-use, preservative-free solution for oral inhalation by nebulizer. It was developed specifically for once-daily nebulized dosing in patients with chronic obstructive pulmonary disease (COPD) who have difficulty using handheld inhalers effectively, such as those with limited inspiratory effort or coordination difficulties.

Rebreath works by relaxing bronchial smooth muscle, helping to keep the airways open over a full 24-hour dosing interval. It is intended for chronic, long-term maintenance therapy and is not a rescue medication for sudden breathing difficulty.

Rebreath belongs to the therapeutic class of inhaled bronchodilators, specifically the long-acting muscarinic antagonists (LAMAs), also known as long-acting anticholinergic bronchodilators, used in the management of chronic obstructive pulmonary disease (COPD).

Mechanism

Revefenacin is a long-acting muscarinic antagonist (LAMA). It competitively and reversibly inhibits the action of acetylcholine at M3 muscarinic receptors located on airway smooth muscle, blocking acetylcholine-mediated bronchoconstriction and producing sustained bronchodilation. Revefenacin shows kinetic selectivity, dissociating more slowly from M3 receptors than from M2 receptors, which supports a prolonged, once-daily duration of action while limiting some off-target effects.

Pharmacokinetics

• Absorption: Following inhalation, systemic absorption occurs, with peak plasma concentrations reached within about 15-30 minutes; steady state is achieved within about 6 days of once-daily dosing.
• Metabolism: Revefenacin is metabolized mainly via hydrolysis by esterases (including butyrylcholinesterase) to an active metabolite, with a smaller contribution from CYP3A4/CYP2D6 oxidative pathways.
• Elimination: Eliminated primarily via the hepatobiliary route (feces), with a minor renal component; terminal half-life is approximately 20-31 hours, supporting once-daily dosing.

Rebreath is administered by oral inhalation only, using a standard jet nebulizer connected to an air compressor (not an ultrasonic nebulizer, as effectiveness has not been established with such devices). The entire contents of one unit-dose vial should be emptied into the nebulizer reservoir immediately before use and inhaled with a mouthpiece until the chamber is empty, typically over 3-5 minutes. Rebreath vials should be kept in their protective pouch until immediately before use to protect the medication from light, and any vial removed from the pouch and not used should be discarded after the manufacturer-specified period.

Other Anticholinergic (Muscarinic Antagonist) Medications

Coadministration of Rebreath with other anticholinergic-containing medications, including other long-acting or short-acting muscarinic antagonists (e.g., ipratropium, tiotropium, glycopyrrolate, umeclidinium), is not recommended, as this may increase the risk and severity of anticholinergic effects such as dry mouth, urinary retention, and constipation.

Other Considerations

No clinically significant pharmacokinetic drug interactions mediated through CYP450 enzymes have been established as requiring dose adjustment. As with other anticholinergic bronchodilators, caution is advised when Rebreath is combined with other drugs that have anticholinergic properties (e.g., certain antihistamines, tricyclic antidepressants) due to additive antimuscarinic effects; see Precautions and Warnings for related cautions in patients with glaucoma or urinary retention risk.

Common Side Effects

• Cough
• Nasopharyngitis (common cold symptoms)
• Upper respiratory tract infection
• Headache
• Back pain

Less Common but Clinically Important Effects

• Dry mouth (reported post-marketing)
• Paradoxical bronchospasm - a sudden worsening of breathing immediately after use (see Precautions and Warnings)
• Hypersensitivity reactions (rash, urticaria, angioedema)
• Urinary retention or difficulty urinating, particularly in patients with prostatic hyperplasia or bladder outlet obstruction
• Blurred vision, eye pain, or visual halos suggestive of narrow-angle glaucoma worsening

Most adverse effects associated with Rebreath are related to its anticholinergic activity. Patients should report any new or worsening symptoms to their physician.

Pregnancy

There are no adequate and well-controlled studies of Rebreath in pregnant women, and human data are limited. Rebreath should be used during pregnancy only if the potential benefit to the mother clearly justifies the potential risk to the fetus, and only under medical supervision. Animal reproduction studies have not shown fetal harm at exposures substantially higher than the maximum recommended human dose, but this does not guarantee safety in humans.

Lactation

There is no information available on the presence of Rebreath in human milk, its effects on the breastfed infant, or its effects on milk production. A decision to breastfeed during treatment with Rebreath should be made in consultation with a physician, weighing the mother's clinical need for the medicine against any potential risk to the infant.

Not for Acute Symptom Relief

Rebreath is intended for long-term, once-daily maintenance treatment and is not indicated for acute deterioration of COPD or relief of acute bronchospasm. It should not be used more frequently than once daily, and additional doses do not provide added benefit.

Paradoxical Bronchospasm

As with other inhaled bronchodilators, Rebreath can cause paradoxical bronchospasm, which may be life-threatening. If this occurs, Rebreath should be discontinued immediately and an alternative therapy instituted.

Worsening of Narrow-Angle Glaucoma

Rebreath should be used with caution in patients with narrow-angle glaucoma, as anticholinergic agents may worsen this condition. Patients should be instructed to avoid spraying or allowing the nebulized solution to come into contact with the eyes, and to seek prompt medical attention if they develop eye pain, blurred vision, visual halos, or red eyes with conjunctival congestion.

Worsening of Urinary Retention

Rebreath should be used with caution in patients with prostatic hyperplasia or bladder-neck obstruction, as anticholinergic agents may worsen urinary retention.

Cardiovascular Effects

Anticholinergic bronchodilators such as Rebreath can produce cardiovascular effects; caution is advised in patients with clinically significant, unstable cardiovascular disease.

Coexisting Conditions

Rebreath should be used with caution in patients with severe hepatic impairment, as it has not been studied in this population (see Dosage and Administration).

There is limited clinical experience with Rebreath overdosage. Excessive use may be expected to produce exaggerated anticholinergic (antimuscarinic) signs and symptoms, such as dry mouth, blurred vision, constipation, urinary retention, tachycardia, and, potentially, cardiovascular effects. There is no specific antidote for Rebreath overdose.

If overdose is suspected, seek immediate medical attention or contact a poison control center / emergency services. Supportive care and monitoring, particularly of cardiovascular status, should be provided by a physician as clinically indicated. Do not attempt to manage a suspected overdose with home remedies.

Store Rebreath unit-dose vials at 20°C to 25°C (68°F to 77°F); brief excursions between 15°C to 30°C (59°F to 86°F) are permitted. Keep vials in their sealed protective foil pouch until the time of use to protect from light. Once removed from the pouch, unused vials should be discarded after the manufacturer-specified period (do not use if left out of the pouch for an extended time). Do not freeze. Keep out of reach of children.

Pediatric Use

The safety and efficacy of Rebreath in pediatric patients have not been established. Rebreath is not indicated for use in children.

Geriatric Use

No overall differences in safety or effectiveness of Rebreath have been observed between elderly patients and younger adults; no dose adjustment is required based on age alone, though anticholinergic effects (e.g., urinary retention) may warrant closer monitoring in older adults, particularly men with prostatic hyperplasia.

Renal Impairment

No dose adjustment is required in patients with mild-to-severe renal impairment. Rebreath has not been studied in patients with end-stage renal disease requiring dialysis; use with caution in this group.

Hepatic Impairment

No dose adjustment is required in patients with mild-to-moderate hepatic impairment. Rebreath has not been studied in patients with severe hepatic impairment; use with caution in this group.

Rebreath is intended for long-term, chronic maintenance therapy in COPD and is generally continued indefinitely as part of ongoing disease management, for as long as the physician determines it is providing clinical benefit. It is not intended for short-course or as-needed use. Treatment should be reassessed periodically by the prescribing physician.

Revefenacin belongs to the drug class of long-acting muscarinic antagonists (LAMAs), also referred to as long-acting anticholinergic bronchodilators or antimuscarinic bronchodilators, within the broader category of inhaled respiratory medications used in COPD management.

Revefenacin acts as a competitive, reversible antagonist at muscarinic acetylcholine receptors, with functional selectivity for the M3 receptor subtype found on airway smooth muscle. By blocking acetylcholine binding at M3 receptors, Revefenacin prevents acetylcholine-mediated contraction of bronchial smooth muscle, resulting in bronchodilation and reduced airflow obstruction. Its relatively slow dissociation from M3 receptors compared to M2 receptors contributes to a long duration of action, enabling effective once-daily dosing.

The safety and efficacy of Rebreath have not been established in pediatric patients of any age. Rebreath is approved only for use in adults with chronic obstructive pulmonary disease (COPD), a condition that does not typically occur in children, and it should not be administered to pediatric patients outside of a controlled clinical trial setting.