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:
- Initial dosage: 7.5 mg orally once a day.
- The dose may be increased after two weeks to 15 mg once a day if the response is not adequate.
-
Dosage adjustment with concomitant potent CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, nelfinavir, clarithromycin, and nefazodone:
- Do not exceed a maximum dose of 7.5 mg/day.
Use in Children:
Not indicated.
Pregnancy Risk Factor C
- Animal reproduction studies have shown adverse outcomes for fetuses.
Darifenacin use during breastfeeding:
- It is unknown if the drug will be excreted into breastmilk.
- The manufacturer suggests that lactating mothers use the drug with caution.
Dose in Kidney Disease:
Adjustment in the dose is not necessary.
Darifenacin (Enablex)Dose in Liver disease:
-
Mild impairment (Child-Pugh class A):
- Adjustment in the dose is not necessary, however, use with caution.
-
Moderate impairment (Child-Pugh class B):
- The maximum daily dose should not exceed 7.5 mg.
-
Severe impairment (Child-Pugh class C):
- Avoid using the drug. It has not been studied in patients with severe hepatic impairment.
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 who have or are at high risk for uncontrolled narrow-angle vision impairment,
- Urinary retention
- Gastric motility disorders (gastric retention)
Canadian labeling: Additional contraindications not in US labeling
- Allergy reactions to any component of the drug or the drug itself
Warnings and precautions
-
Angioedema
- Some patients may experience allergic reactions, such as swelling of the lips, lips, tongue, and larynx.
- Angioedema can sometimes be life-threatening and can occur as soon as the first dose is completed.
- If the airway becomes compromised, treatment can be stopped immediately.
-
CNS effects
- Some patients may experience neurological symptoms such as headaches, confusion, hallucinations, or somnolence.
- These features should be observed in patients, especially when treatment begins and for the first few weeks.
- You may have to reduce the dose or stop taking the medication altogether.
- It can also cause vision blurring, drowsiness, and other impairments that could lead to mental and physical problems.
- Patients should be reminded to exercise caution when operating heavy machinery or driving, as well as mental alertness.
-
Heat prostration:
- Patients who are exposed to heat, such as athletes or laborers, should not use it.
-
Bladder flow obstruction
- Patients with bladder outflow obstruction should not take the drug as it can cause urinary retention.
-
Gastrointestinal Disease:
- Patients with gastrointestinal motility disorders, such as severe constipation, ulcerative collitis, or gastrointestinal obstructive conditions such as pyloric stasis, should not take the drug.
-
Glaucoma:
- The drug should be avoided by patients with narrow-angle glaucoma. Patients with narrow-angle glaucoma treated should be warned.
-
Hepatic impairment
- Patients with severe hepatic dysfunction should not take the drug.
- Moderately severe liver disease may require dosage adjustments. This should be done with caution.
-
Myasthenia gravis:
- Patients suffering from myasthenia gravis must be advised to take the drug with caution.
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
Risk Factor C (Monitor therapy). |
|
| Acetylcholinesterase inhibitors | Anticholinergic Agents may have a decreased therapeutic effect. Anticholinergic Agents can decrease the therapeutic effects of Acetylcholinesterase inhibitors. |
| Ajmaline | Moderate CYP2D6 inhibitors may raise serum levels of Ajmaline. |
| Amantadine | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Amphetamines | Moderate CYP2D6 inhibitors may raise serum levels of Amphetamines. |
| Anticholinergic Agents | Other Anticholinergic Agents may have an adverse/toxic effect. |
| Aprepitant | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| 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. |
| Bosentan | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Botulinum Toxin-Containing Products | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Brexpiprazole | CYP2D6 inhibitors (Moderate), may increase the serum level of Brexpiprazole. Management: Brexpiprazole should not be taken with a strong or moderate CYP3A4 inhibitor. |
| Cannabinoid-Containing Products | Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Cannabidiol is an exception. |
| Chloral Betaine | Anticholinergic Agents may have an adverse/toxic effect. |
| Clofazimine | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| CloZAPine | CloZAPine serum concentrations may be increased by CYP2D6 inhibitors (Moderate). |
| 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. |
| CYP2D6 Substrates High Risk with Inhibitors | Moderate CYP2D6 inhibitors may reduce the metabolism of CYP2D6 substrates (High Risk with Inhibitors). Tamoxifen is an exception. |
| Moderate CYP3A4 Inducers | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Moderate CYP3A4 inhibitors | Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors). |
| Duvelisib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Erdafitinib | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Erdafitinib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Fesoterodine | CYP2D6 inhibitors may increase serum levels of active metabolites of Fesoterodine. |
| Fosaprepitant | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Fosnetupitant | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Gastrointestinal Agents (Prokinetic) | Anticholinergic Agents can reduce the therapeutic effects of Gastrointestinal Agents (Prokinetic). |
| Glucagon | Anticholinergic agents may increase the toxic/adverse effects of Glucagon. Particularly, there may be an increase in the likelihood of gastrointestinal adverse reactions. |
| Indoramin | Moderate CYP2D6 inhibitors may raise the serum level of Indoramin. |
| Itopride | Itopride's therapeutic effects may be diminished by anticholinergic agents. |
| Ivosidenib | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Larotrectinib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Metoprolol | Moderate CYP2D6 inhibitors may raise the serum level of Metoprolol. |
| Mianserin | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Mirabegron | Anticholinergic agents may increase the toxic/adverse effects of Mirabegron. |
| Nebivolol | Moderate CYP2D6 inhibitors may raise the serum level of Nebivolol. |
| Netupitant | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Nitroglycerin | 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. |
| 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. |
| Palbociclib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Propafenone | 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. |
| Ramosetron | Ramosetron's constipating effects may be enhanced by anticholinergic agents. |
| Sarilumab | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Siltuximab | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Simeprevir | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Tamsulosin | Moderate CYP2D6 inhibitors may raise the serum level of Tamsulosin. |
| Thiazide and Thiazide - Like Diuretics | Anticholinergic Agents can increase serum Thiazide or Thiazide-Like Diuretics. |
| Tocilizumab | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| Topiramate | Topiramate's toxic/adverse effects may be exacerbated by anticholinergic agents. |
| TraMADol | TraMADol's therapeutic effects may be diminished by CYP2D6 inhibitors (Moderate). These CYP2D6 Inhibitors (Moderate) may reduce the therapeutic effect of TraMADol. |
Risk Factor D (Regard therapy modification) |
|
| 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. |
| Strong CYP3A4 inhibitors | Might decrease metabolism of CYP3A4 substrates (High Risk with Inhibitors). |
| 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). |
| Deferasirox | Could lower serum concentrations of CYP3A4 substrates (High Risk with Inducers). |
| 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. |
| Eliglustat | 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. |
| Enzalutamide | 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. |
| 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. |
| MiFEPRIStone | 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. |
| Mitotane | 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. |
| 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. |
| Pitolisant | 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. |
| Pramlintide | Anticholinergic Agents may have an enhanced anticholinergic effect. These effects are only for the GI tract. |
| Secretin | 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. |
| 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. |
| Stiripentol | 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. |
| Tamoxifen | 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. |
Risk Factor X (Avoid Combination) |
|
| Aclidinium | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Cimetropium | Cimetropium may have an anticholinergic effect that can be enhanced by the use of anticholinergic agents. |
| Conivaptan | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Eluxadoline | Eluxadoline may cause constipation by using anticholinergic agents. |
| Fusidic Acid (Systemic). | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Glycopyrrolate (Oral Inhalation) | Anticholinergic agents may increase the anticholinergic effects of Glycopyrrolate (Oral inhalation). |
| Glycopyrronium (Topical) | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Idelalisib | High risk of Inhibitors causing an increase in serum CYP3A4 Substrates concentrations |
| Oral Inhalation with Ipratropium | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Levosulpiride | Anticholinergic Agents can reduce the therapeutic effects of Levosulpiride. |
| Oxatomide | Anticholinergic Agents may have an enhanced anticholinergic effect. |
| Potassium Chloride | 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. |
| Potassium Citrate | Potassium Citrate may be more ulcerogenic if it is given to anticholinergic agents. |
| Revefenacin | Revefenacin may be enhanced by anticholinergic agents. |
| Thioridazine | CYP2D6 inhibitors may increase Thioridazine serum concentrations. |
| Tiotropium | Anticholinergic agents may increase the anticholinergic effects of Tiotropium. |
| Umeclidinium | Anticholinergic Agents may have an enhanced anticholinergic effect. |
Monitoring parameters:
- Anticholinergic effects such as
- headache,
- confusion,
- hallucinations,
- somnolence
- fixed and dilated pupils,
- blurred vision,
- tremors,
- dry skin
- Liver function.
How to administer Darifenacin (Enablex)?
The drug may be administered without regard to food with water. The tablets must be swallowed whole and not chewed, crushed, or divided.
Mechanism of action of Darifenacin (Enablex):
- It acts as a selective inhibitor of subtypes of the M3 cholinergic muscarinic receptors.
- These receptors are inhibited by the drug, which results in inhibition of bladder contraction.
- It reduces symptoms such as bladder overactivity or irritability, which can manifest as urgency, frequency, or urge incontinence.
Protein binding:
- 98%, primarily alpha-acid glycoprotein
Metabolism:
- Hepatic, via CYP3A4 and CYP2D6
Bioavailability:
- 15% to 19%
Half-life elimination:
- About 13 to 19 hours
Time to peak plasma concentration:
- About 7 hours
Excretion:
- Urine (~60%),
- feces (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:
No Brands Available in Pakistan.
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