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Revefenacin

Medically reviewed by Drugs.com. Last updated on Aug 18, 2020.

Pronunciation

(REV e FEN a sin)

Index Terms

  • TD-4208

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Inhalation:

Yupelri: 175 mcg/3 mL (3 mL)

Brand Names: U.S.

  • Yupelri

Pharmacologic Category

  • Anticholinergic Agent
  • Anticholinergic Agent, Long-Acting

Pharmacology

Revefenacin is a long-acting muscarinic antagonist which competitively and reversibly inhibits the action of acetylcholine at type 3 muscarinic (M3) receptors in bronchial smooth muscle causing bronchodilation.

Absorption

Rapid (Quinn 2018)

Metabolism

Primarily metabolized via hydrolysis of the primary amide to carboxylic acid (to the major active metabolite)

Excretion

Feces (primarily); Urine (<1%, as revefenacin and active metabolite)

Onset of Action

Bronchodilation onset is within 45 minutes after a single dose and peak FEV1 effect is 2 to 3 hours following a single dose (Quinn 2018)

Time to Peak

14 to 41 minutes (after start of nebulization)

Duration of Action

Bronchodilation: Up to 24 hours (Quinn 2018)

Half-Life Elimination

22 to 70 hours (revefenacin and active metabolite)

Protein Binding

Revefenacin: ~71%; Active metabolite: ~42%

Special Populations: Renal Function Impairment

In patients with severe impairment (CrCl <30 mL/minute), revefenacin Cmax and AUCinf increased 1.5-fold and up to 2.3-fold respectively, and active metabolite Cmax and AUCinf increased up to 2-fold and 2.5-fold, respectively.

Special Populations: Hepatic Function Impairment

In patients with moderate impairment (Child-Pugh score of 7 to 9), AUC of revefenacin increased 1.2-fold, and Cmax and AUC of active metabolite increased 1.5-fold and up to 4.7-fold respectively.

Use: Labeled Indications

Chronic obstructive pulmonary disease: Maintenance treatment of chronic obstructive pulmonary disease (COPD)

Contraindications

Hypersensitivity to revefenacin or any component of the formulation

Dosing: Adult

Chronic obstructive pulmonary disease: Oral inhalation: Nebulization solution: 175 mcg (1 unit-dose vial) once daily.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information

Dosing: Geriatric

Refer to adult dosing.

Administration

Nebulization solution: For oral inhalation only; do not inject or swallow solution. Administer by oral inhalation via a standard jet nebulizer with a mouthpiece connected to an air compressor. Remove the unit-dose vial from foil pouch immediately before use. Revefenacin does not require dilution prior to administration. Do not mix with other medications in nebulizer. Discard any used portion.

Storage

Store in foil pouch at 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F ). Protect from direct sunlight and excessive heat. Do not remove from foil pouch until immediately before use. Use opened vials immediately.

Drug Interactions

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Anticholinergic Agents: May enhance the anticholinergic effect of Revefenacin. Avoid combination

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Methacholine: Long-acting muscarinic antagonists (LAMAs) may diminish the therapeutic effect of Methacholine. Management: Hold long-acting muscarinic antagonists (LAMAs) for at least 7 days before methacholine use. Consider therapy modification

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors: May increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination

Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Avoid combination

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Hypertension (1% to <2%)

Central nervous system: Headache (4%), dizziness (1% to <2%)

Neuromuscular & skeletal: Back pain (2%)

Respiratory: Nasopharyngitis (4%), upper respiratory tract infection (3%), bronchitis (1% to <2%), oropharyngeal pain (1% to <2%)

<1%, postmarketing, and/or case reports: Paradoxical bronchospasm

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Paradoxical bronchospasm that may be life-threatening and may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. If paradoxical bronchospasm occurs, manage with a short-acting bronchodilator, discontinue revefenacin, and institute alternative therapy.

• CNS effects: Anticholinergic agents may cause dizziness and blurred vision; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Hypersensitivity: Immediate hypersensitivity reactions may occur. Discontinue therapy immediately if an allergic reaction occurs.

Disease-related concerns:

• Glaucoma: Use with caution in patients with narrow-angle glaucoma; may increase intraocular pressure.

• Hepatic impairment: Use is not recommended in patients with hepatic impairment.

• Prostatic hyperplasia/bladder neck obstruction: Use with caution in patients with prostatic hyperplasia or bladder neck obstruction; may cause and/or worsen urinary retention.

• Renal impairment: Monitor for systemic antimuscarinic adverse effects in patients with severe renal impairment.

Other warnings/precautions:

• Appropriate use: Revefenacin is intended as a once daily maintenance treatment and is not indicated for the initial (rescue) treatment of acute episodes of bronchospasm or with acutely deteriorating or potentially life-threatening COPD; after initiation of therapy, patients should use short-acting bronchodilators only on an as needed basis for acute symptoms. COPD may deteriorate acutely (over hours) or chronically (over days or longer); if revefenacin no longer controls bronchoconstriction symptoms, short-acting beta2-agonists becomes less effective, or the more inhalations of a short-acting beta2-agonist than usual are required, these may be indicators of COPD deterioration; re-evaluate the COPD treatment regimen. Increasing the daily revefenacin dose beyond the recommended dose is not appropriate in this situation.

Monitoring Parameters

FEV1, peak flow (or other pulmonary function tests). Monitor for signs/symptoms of acute narrow angle glaucoma, hypersensitivity reactions, and urinary retention. Monitor for systemic antimuscarinic adverse effects in patients with severe renal impairment.

Reproductive Considerations

Females of reproductive potential were not included in original studies (Pudi 2017; Quinn 2017).

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Patient Education

What is this drug used for?

• It is used to treat COPD (chronic obstructive pulmonary disease).

• This drug is not to be used to treat intense flare-ups of shortness of breath. Use a rescue inhaler. Talk with the doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Runny nose

• Common cold symptoms

• Headache

• Back pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Trouble urinating

• Painful urination

• Passing a lot of urine

• Change in amount of urine passed

• Shortness of breath

• Chest pain

• Fast heartbeat

• Nausea

• Vomiting

• Vision changes

• Eye pain

• Eye redness

• Seeing halos or bright colors around lights

• Trouble breathing

• Wheezing

• Cough

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Frequently Asked Questions