Darifenacin is a medication used to treat overactive bladder (OAB) symptoms such as frequent urination, urgency, and urinary incontinence. It belongs to a class of medications known as antimuscarinics or anticholinergics. Darifenacin works by blocking the action of acetylcholine, a neurotransmitter responsible for muscle contractions, thereby relaxing the bladder muscles and reducing urinary frequency and urgency.
Darifenacin (Enablex) is an anticholinergic drug that specifically inhibits the contraction of bladder smooth muscles. It is used in patients with signs and symptoms of over active bladder.
Darifenacin (Enablex) Uses:
- Overactive bladder:
- It is indicated for the treatment of patients with overactive bladder manifesting with signs and symptoms of urinary frequency, urgency, and urge incontinence.
Other drugs used for the treatment of overactive bladder include:
Darifenacin (Enablex) Dose in Adults
Darifenacin (Enablex) Dose in the treatment of Overactive bladder:
- Start with 7.5 mg once daily.
- If it doesn't work well after 2 weeks, the dose can be increased to 15 mg once daily.
- If you're taking strong CYP3A4 inhibitor medicines (like ketoconazole or ritonavir), the maximum dose should be 7.5 mg per day.
Use in Children:
Not indicated.
Pregnancy Risk Factor C
- Darifenacin is classified as Pregnancy Risk Factor C, which means adverse events have been observed in animal reproduction studies.
- This suggests that there may be potential risks to the fetus if darifenacin is used during pregnancy.
Darifenacin use during breastfeeding:
- It's uncertain whether darifenacin is excreted in breast milk.
- Due to this uncertainty, caution is advised when giving darifenacin to nursing mothers.
Dose in Kidney Disease:
Adjustment in the dose is not necessary.
Darifenacin (Enablex)Dose in Liver disease:
- Mild impairment (Child-Pugh class A): No need to adjust the dosage, but use darifenacin cautiously.
- Moderate impairment (Child-Pugh class B): The maximum recommended dose is 7.5 mg per day.
- Severe impairment (Child-Pugh class C): It's not recommended to use darifenacin in this case since it hasn't been studied for this group.
Side Effects of Darifenacin (Enablex):
- Gastrointestinal:
- Xerostomia
- Constipation
Less Common Side Effects of Darifenacin (Enablex):
- Cardiovascular:
- Hypertension
- Peripheral Edema
- Central Nervous System:
- Headache
- Dizziness
- Pain
- Dermatological:
- Pruritus
- Skin Rash
- Xeroderma
- Endocrine & Metabolic:
- Weight Gain
- Gastrointestinal:
- Dyspepsia
- Abdominal Pain
- Nausea
- Vomiting
- Genitourinary:
- Urinary Tract Infection
- Vaginitis
- Urinary Retention
- Neuromuscular & Skeletal:
- Weakness
- Arthralgia
- Back Pain
- Ophthalmic:
- Dry Eye Syndrome
- Visual Disturbance
- Respiratory:
- Flu-Like Symptoms
- Bronchitis
- Pharyngitis
- Rhinitis
- Sinusitis
Contraindications to Darifenacin (Enablex):
Patients with certain conditions should avoid or be cautious when using darifenacin:
- Uncontrolled narrow-angle glaucoma: Darifenacin can worsen this condition, so it's contraindicated.
- Urinary retention: Darifenacin can worsen urinary retention, so it should be avoided.
- Gastric retention: Darifenacin can exacerbate gastric retention, so it's contraindicated.
Additionally, in Canadian labeling, darifenacin should not be used if someone has a hypersensitivity to darifenacin or any component of the formulation. This is an additional contraindication not listed in US labeling.
Warnings and precautions
Angioedema
- Angioedema, which involves swelling of the face, lips, tongue, and/or larynx, has been reported with darifenacin use.
- In some cases, this swelling occurred after the first dose and can be life-threatening.
- If swelling affects the tongue, hypopharynx, or larynx, it's crucial to stop darifenacin immediately and provide supportive care.
- This condition requires prompt medical attention to prevent serious complications.
CNS effects
- Darifenacin can have effects on the central nervous system (CNS), including headaches, confusion, hallucinations, and drowsiness.
- It's important to monitor for these effects, especially when starting treatment or increasing the dose.
- If necessary, the dose may need to be reduced or darifenacin discontinued.
- Additionally, darifenacin can cause drowsiness and blurred vision, which may affect a person's ability to perform tasks requiring mental alertness, such as operating machinery or driving.
- Patients should be cautioned about these potential effects and advised to avoid such activities if they experience drowsiness or blurred vision while taking darifenacin.
Heat prostration:
- Heat prostration is a risk when using darifenacin, especially in hot weather or during exercise.
- It's important to be cautious in such situations to avoid overheating.
- Patients taking darifenacin should be advised to stay hydrated and avoid prolonged exposure to high temperatures.
- If they experience symptoms of heat prostration such as excessive sweating, weakness, dizziness, or fainting, they should seek shade, rest, and rehydrate immediately.
Bladder flow obstruction
- Darifenacin should be used with caution in patients with bladder flow obstruction because it may increase the risk of urinary retention.
- Bladder flow obstruction can occur due to various conditions such as enlarged prostate gland in men or pelvic organ prolapse in women.
- It's important to monitor patients closely for signs and symptoms of urinary retention, such as difficulty urinating or incomplete emptying of the bladder, especially when initiating darifenacin therapy or increasing the dose.
- If urinary retention occurs, darifenacin should be discontinued, and appropriate management should be provided.
Gastrointestinal Disease:
- Darifenacin should be used cautiously in patients with gastrointestinal (GI) diseases such as severe constipation, ulcerative colitis, or GI obstructive disorders like pyloric stenosis.
- These conditions can affect GI motility and increase the risk of gastric retention when taking darifenacin.
- It's essential to monitor patients closely for symptoms of gastric retention, such as bloating, abdominal discomfort, or nausea, particularly when initiating darifenacin treatment or adjusting the dose.
- If signs of gastric retention occur, darifenacin should be discontinued, and appropriate medical management should be provided.
Glaucoma:
- Darifenacin should be used cautiously in patients with controlled (treated) narrow-angle glaucoma.
- While it's not contraindicated in these patients, darifenacin can potentially worsen the condition.
- Therefore, close monitoring is necessary for any signs or symptoms of worsening glaucoma, such as increased intraocular pressure or vision changes.
- If such symptoms occur, appropriate management should be initiated promptly.
- Patients should also be advised to report any changes in their vision or eye health while taking darifenacin.
Hepatic impairment
- Darifenacin should be used cautiously in patients with hepatic impairment.
- Dosage adjustment is required in moderate hepatic impairment (Child-Pugh class B).
- However, darifenacin is not recommended for use in severe hepatic impairment (Child-Pugh class C) due to limited data on its safety and efficacy in this population.
- Close monitoring is essential for patients with hepatic impairment, and appropriate dosage adjustments should be made as needed.
Myasthenia gravis:
- Darifenacin should be used with caution in patients with myasthenia gravis.
- Myasthenia gravis is a neuromuscular disorder characterized by muscle weakness and fatigue, which may be exacerbated by medications that affect neuromuscular transmission, such as darifenacin.
- Close monitoring is essential in these patients for any signs or symptoms of worsening muscle weakness or fatigue.
- If darifenacin worsens myasthenia gravis symptoms, discontinuation of the medication may be necessary, and alternative treatment options should be considered.
Darifenacin: Drug Interaction
Note: Drug Interaction Categories:
- Risk Factor C: Monitor When Using Combination
- Risk Factor D: Consider Treatment Modification
- Risk Factor X: Avoid Concomitant Use
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Risk Factor C (Monitor therapy). |
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Acetylcholinesterase inhibitors |
Anticholinergic Agents may have a decreased therapeutic effect. Anticholinergic Agents can decrease the therapeutic effects of Acetylcholinesterase inhibitors. |
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Ajmaline |
Moderate CYP2D6 inhibitors may raise serum levels of Ajmaline. |
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Anticholinergic Agents may have an enhanced anticholinergic effect. |
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Amphetamines |
Moderate CYP2D6 inhibitors may raise serum levels of Amphetamines. |
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Anticholinergic Agents |
Other Anticholinergic Agents may have an adverse/toxic effect. |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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ARIPiprazole |
Moderate CYP2D6 inhibitors may cause a higher serum level of ARIPiprazole. Monitoring for increased aripiprazole-pharmacologic effects is important. Aripiprazole dosage adjustments may be necessary depending on the indication and/or concomitant therapy. For more information, consult the full interaction monograph. |
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Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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Botulinum Toxin-Containing Products |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
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Brexpiprazole |
CYP2D6 inhibitors (Moderate), may increase the serum level of Brexpiprazole. Management: Brexpiprazole should not be taken with a strong or moderate CYP3A4 inhibitor. |
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Cannabinoid-Containing Products |
Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Cannabidiol is an exception. |
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Chloral Betaine |
Anticholinergic Agents may have an adverse/toxic effect. |
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Clofazimine |
High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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CloZAPine |
CloZAPine serum concentrations may be increased by CYP2D6 inhibitors (Moderate). |
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Codeine |
CYP2D6 inhibitors (Moderate), may decrease the therapeutic effects of Codeine. These CYP2D6 Inhibitors (Moderate) may block the metabolic conversion of Codeine to its active metabolite morphine. |
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CYP2D6 Substrates High Risk with Inhibitors |
Moderate CYP2D6 inhibitors may reduce the metabolism of CYP2D6 substrates (High Risk with Inhibitors). Tamoxifen is an exception. |
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Moderate CYP3A4 Inducers |
Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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Moderate CYP3A4 inhibitors |
Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors). |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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CYP2D6 inhibitors may increase serum levels of active metabolites of Fesoterodine. |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Fosnetupitant |
High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Gastrointestinal Agents (Prokinetic) |
Anticholinergic Agents can reduce the therapeutic effects of Gastrointestinal Agents (Prokinetic). |
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Glucagon |
Anticholinergic agents may increase the toxic/adverse effects of Glucagon. Particularly, there may be an increase in the likelihood of gastrointestinal adverse reactions. |
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Indoramin |
Moderate CYP2D6 inhibitors may raise the serum level of Indoramin. |
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Itopride |
Itopride's therapeutic effects may be diminished by anticholinergic agents. |
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Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Moderate CYP2D6 inhibitors may raise the serum level of Metoprolol. |
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Mianserin |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
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Anticholinergic agents may increase the toxic/adverse effects of Mirabegron. |
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Moderate CYP2D6 inhibitors may raise the serum level of Nebivolol. |
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Netupitant |
High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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The absorption of Nitroglycerin may be decreased by anticholinergic agents. Anticholinergic Agents may reduce the dissolution sublingual nitroglycerin tablet, which could impair or slow down nitroglycerin absorbtion. |
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Opioid Agonists |
Opioid Agonists can have an adverse/toxic effect that may be exacerbated by anticholinergic agents. This combination may increase the likelihood of constipation or urinary retention. |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Moderate CYP2D6 inhibitors may raise the serum level of Propafenone. Management: The drug interactions monographs for drugs listed as an exception to this monograph will be discussed in greater detail. |
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Ramosetron |
Ramosetron's constipating effects may be enhanced by anticholinergic agents. |
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Sarilumab |
Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Moderate CYP2D6 inhibitors may raise the serum level of Tamsulosin. |
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Thiazide and Thiazide - Like Diuretics |
Anticholinergic Agents can increase serum Thiazide or Thiazide-Like Diuretics. |
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Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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Topiramate's toxic/adverse effects may be exacerbated by anticholinergic agents. |
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TraMADol's therapeutic effects may be diminished by CYP2D6 inhibitors (Moderate). These CYP2D6 Inhibitors (Moderate) may reduce the therapeutic effect of TraMADol. |
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Risk Factor D (Regard therapy modification) |
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Strong CYP3A4 Inducers |
May increase metabolism of CYP3A4 substrates (High Risk with Inducers). Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling. |
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Strong CYP3A4 inhibitors |
Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors). |
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Dabrafenib |
High risk of Inducers causing a decrease in serum CYP3A4 substrates. Management: If possible, seek alternatives to the CYP3A4 substrate. Concomitant therapy should be avoided if possible. Monitor the clinical effects of the substrate carefully (especially therapeutic effects). |
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Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
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DOXOrubicin (Conventional) |
CYP2D6 inhibitors (Moderate), may increase serum levels of DOXOrubicin. (Conventional). Treatment: If possible, seek alternatives to moderate CYP2D6 inhibitors for patients who have been treated with doxorubicin. These combinations should be avoided according to one U.S. manufacturer, Pfizer Inc. |
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Moderate CYP2D6 inhibitors may increase Eliglustat serum concentrations. Management: Lower the daily eliglustat dose by 84 mg. Use eliglustat only in combination with a mild CYP2D6 inhibitor or a strong/moderate CYP3A4 inhibitor. |
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High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Avoid concurrent use of enzalutamide and CYP3A4 substrates with a narrow therapeutic index. You should exercise caution when using enzalutamide or any other CYP3A4 sub-substance. |
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Lorlatinib |
High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Management: Do not use lorlatinib concurrently with any CYP3A4 Substrates. Even a slight decrease in serum concentrations could cause therapeutic failure or serious clinical consequences. |
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High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid dihydroergotamine and ergotamine. |
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High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates. Treatment: Patients receiving mitotane may require significant adjustments in the dosage of CYP3A4 Substrates. |
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Perhexiline |
Perhexiline serum concentration may be increased by CYP2D6 inhibitors. Management: If possible, consider other options. Monitor for elevated perhexiline serum levels and toxicities (eg hypoglycemia or neuropathy, liver dysfunction) if the combination is used. Perhexiline doses should be reduced. |
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High risk of Inducers causing a decrease in serum concentrations of CYP3A4 substrates Management: Avoid combining pitolisant and a CYP3A4 substrat with a low therapeutic index. Pitolisant should not be combined with other CYP3A4 sub-substances. |
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Anticholinergic Agents may have an enhanced anticholinergic effect. These effects are only for the GI tract. |
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Secretin's therapeutic effects may be diminished by anticholinergic agents. Concomitant use: Secretin and anticholinergic agents should be avoided. Stop using anticholinergic drugs for at least five half-lives before administering secretin. |
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St John's Wort |
High risk of Inducers causing a decrease in serum CYP3A4 Substrates. Management: You may consider a different drug to replace one of the interacting drugs. Some combinations might be contraindicated. Consult appropriate manufacturer labeling. |
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High risk of Inhibitors causing an increase in serum concentrations of CYP3A4 substrates. Management: Avoid stiripentol use with CYP3A4 Substrates that have a narrow therapeutic Index. This is to avoid adverse effects and toxicities. Monitoring of any CYP3A4 substrate that is used with stiripentol should be closely done. |
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CYP2D6 inhibitors (Moderate), may reduce serum levels of active metabolites of Tamoxifen. Specifically, CYP2D6 inhibits can decrease the metabolism of potent active metabolites. Management: If possible, consider alternatives that have a lower inhibitory effect on CYP2D6 activities. |
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Risk Factor X (Avoid Combination) |
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Aclidinium |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
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Cimetropium |
Cimetropium may have an anticholinergic effect that can be enhanced by the use of anticholinergic agents. |
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Conivaptan |
High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Eluxadoline may cause constipation by using anticholinergic agents. |
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Fusidic Acid (Systemic). |
High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Glycopyrrolate (Oral Inhalation) |
Anticholinergic agents may increase the anticholinergic effects of Glycopyrrolate (Oral inhalation). |
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Glycopyrronium (Topical) |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
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High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
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Oral Inhalation with Ipratropium |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
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Levosulpiride |
Anticholinergic Agents can reduce the therapeutic effects of Levosulpiride. |
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Oxatomide |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
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Potassium Chloride may have an ulcerogenic effect that can be exacerbated by anticholinergic agents. Treatment: Patients taking drugs that have significant anticholinergic effects should not consume any oral dose form of potassium chloride. |
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Potassium Citrate |
Potassium Citrate may be more ulcerogenic if it is given to anticholinergic agents. |
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Revefenacin may be enhanced by anticholinergic agents. |
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Thioridazine |
CYP2D6 inhibitors may increase Thioridazine serum concentrations. |
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Anticholinergic agents may increase the anticholinergic effects of Tiotropium. |
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Umeclidinium |
Anticholinergic Agents may have an enhanced anticholinergic effect. |
Monitoring parameters:
Anticholinergic Effects:
- CNS Effects: Darifenacin may cause headaches, confusion, hallucinations, or drowsiness.
- Vision: It can also lead to blurred vision and fixed, dilated pupils.
- Other Symptoms: Some people may experience tremors, and their skin may become dry.
Hepatic Function:
- Darifenacin may affect liver function.
- Individuals with liver problems should use darifenacin cautiously.
- Consult a doctor if there are concerns about liver function while taking darifenacin.
How to administer Darifenacin (Enablex)?
- With Water: Take darifenacin with water, regardless of whether you've eaten.
- Swallow Whole: Do not chew, crush, or break the tablet before swallowing.
- Follow these instructions carefully to ensure the medication works effectively.
Mechanism of action of Darifenacin (Enablex):
- Darifenacin is a medication that works by selectively blocking the M3 muscarinic (cholinergic) receptor subtype.
- By doing so, it reduces bladder contractions, which helps alleviate the symptoms associated with bladder irritability or overactivity.
- These symptoms include urge incontinence, urgency, and frequency of urination.
- Essentially, darifenacin helps to calm down an overactive bladder, making it easier to control urination.
Distribution:
- Volume: Approximately 163 liters (V).
- Protein Binding: About 98%, primarily to alpha-acid glycoprotein.
Metabolism:
- Hepatic Metabolism: Darifenacin undergoes hepatic metabolism primarily through enzymes CYP3A4 and CYP2D6.
Bioavailability:
- Absorption: Darifenacin has a bioavailability ranging from 15% to 19%.
Elimination:
- Half-life: The elimination half-life of darifenacin is approximately 13 to 19 hours.
- Peak Plasma Time: It takes about 7 hours to reach peak plasma levels after administration.
Excretion:
- Routes: Darifenacin is excreted mainly via urine (around 60%) and feces (about 40%) as inactive metabolites.
International Brand Names of Darifenacin:
- Enablex
- Andodaricin
- Daricont
- Darif
- Darifen ER
- Darilax
- Dariten OD
- Emselex
- Enablex
- Enablex/Emselex
- Extracta
- Frequgard
- Oralfi
- Vesigard
- Xelena
Darifenacin Brand Names in Pakistan:
Not available.
