Tolterodine (Detrol, Detrusitol) belongs to the anti-muscarinic class of drugs. It inhibits primarily the M2 and M3 receptors. Tolterodine is used primarily in the treatment of overactive bladder, urinary incontinence, and urinary urgency.
Tolterodine Uses:
- Used in the treatment of patients with an overactive bladder with symptoms of urge urinary incontinence, urgency, or frequency.
Tolterodine Dose in Adults
Tolterodine Dose in the Treatment of overactive bladder:
-
Immediate-release tablet:
- 2 mg twice daily;
- The dose may be decreased to 1 mg twice daily based on individual response and tolerability
-
Dosing adjustment in patients concurrently taking strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir):
- 1 mg twice daily
-
Extended-release capsule:
- 4 mg once a day;
- The dose may be decreased to 2 mg once daily based on individual response and tolerability
-
Tolterodine Dosing adjustment in patients concurrently taking strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir):
- 2 mg once a day
Tolterodine Dose in Childrens
Safety and efficacy not established in children
Tolterodine Pregnancy Risk Category: B3
- Some adverse events were seen in animal reproduction studies.
Tolterodine use during breastfeeding:
- It is unknown if tolterodine can be found in breast milk.
- According to the manufacturer, when deciding whether to breastfeed during therapy, one should consider the risks to infants, the benefits to the infant and the benefits to the mother.
Tolterodine Dose in Kidney Disease:
-
Immediate-release tablet:
- Significantly reduced renal function (studies conducted in patients with CrCl 10 to 30 mL/minute):
- 1 mg BD;
- use cautiously.
- Significantly reduced renal function (studies conducted in patients with CrCl 10 to 30 mL/minute):
-
Extended release capsule:
-
CrCl 10 to 30 mL/minute:
- 2 mg OD
-
CrCl <10 mL/minute:
- Not recommended; has not been studied.
-
Tolterodine Dose in Liver disease:
-
Immediate-release tablet:
- Significantly reduced hepatic function:
- 1 mg BD;
- use cautiously.
- Significantly reduced hepatic function:
-
Extended-release capsule:
-
Mild to moderate impairment (Child-Pugh class A or B):
- 2 mg OD
-
Severe impairment (Child-Pugh class C):
- Not recommended (has not been studied).
-
As reported with the immediate-release tablet, unless otherwise specified.
Common Side Effects of Tolterodine:
-
Gastrointestinal:
- Xerostomia
Less Common Side Effects of Tolterodine (Detrol):
-
Cardiovascular:
- Chest Pain
-
Central Nervous System:
- Headache
- Dizziness
- Fatigue
- Drowsiness
- Anxiety
-
Dermatologic:
- Xeroderma
-
Endocrine & Metabolic:
- Weight Gain
-
Gastrointestinal:
- Constipation
- Abdominal Pain
- Diarrhea
- Dyspepsia
-
Genitourinary:
- Dysuria
-
Infection:
- Infection
-
Neuromuscular & Skeletal:
- Arthralgia
-
Ophthalmic:
- Xerophthalmia
- Visual Disturbance
-
Respiratory:
- Flu-Like Symptoms
- Bronchitis
- Sinusitis
Contraindications to Tolterodine (Detrol):
- Hypersensitivity to the drug, fesoterodine (both metabolized to 5-hydroxymethyltolterodine or any component in the formulation)
- Urinary retention
- Gastric retention
- Glaucoma with uncontrolled narrow-angle vision
Warnings and precautions
-
Angioedema
- Angioedema can be caused by a single medication.
- Stop immediately if angioedema, associated difficulty breathing, airway obstruction or hypotension occur.
-
CNS effects
- This may cause drowsiness, dizziness and/or blurred sight, which can impair physical or mental capabilities. Patients should be cautious about tasks that require mental alertness, such as driving or operating machinery.
- Dose reduction or discontinuation is recommended if there are any CNS side effects.
-
Extension of QT
- It has been linked to QTc prolongation at high (supratherapeutic doses).
- The manufacturer suggests caution when using QTc-prolonging medications (class Ia and III antiarrhythmics) concurrently with congenital prolongedQT.
- However, even at supratherapeutic doses, QTc prolongation was limited to 15 msec.
- Individuals who are CYP2D6-poor metabolizers, or have CYP3A4 inhibitors may be more susceptible to prolongation
-
Alzheimer disease
- Preliminary data from patients who received cholinesterase inhibitors suggest that anticholinergics could potentially have an adverse effect on the clinical course and progression of Alzheimer's disease.
- Patients with dementia who are receiving dual therapy (acetylcholinesterase inhibitor, bladder anticholinergic) should be monitored for any decreases in cognition or functional abilities and more problematic behavior.
-
Bladder flow obstruction
- Patients with bladder obstruction (eg benign prostatic hypertrophy) should be cautious. This could increase the chance of urinary retention.
-
GI obstructive disorders:
- Patients with decreased GI motility (i.e. pyloric stenosis) should be cautious. This may increase the likelihood of gastric retention.
-
Glaucoma:
- Patients with narrow-angle glaucoma that has been treated (controlled) should be cautious.
-
Hepatic impairment
- Patients with hepatic impairment should be cautious
- Adjustment of dosage is required.
-
Myasthenia gravis:
- Be careful.
-
Renal impairment
- Patients with hepatic impairment should be cautious
- Adjustment of dosage is required.
Tolterodine: Drug Interaction
|
Abiraterone Acetate |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. |
|
Acetylcholinesterase Inhibitors |
May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. |
|
Ajmaline |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Amantadine |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
Anticholinergic Agents |
May enhance the adverse/toxic effect of other Anticholinergic Agents. |
|
Aprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Bosentan |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Botulinum Toxin-Containing Products |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
Cannabinoid-Containing Products |
Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Exceptions: Cannabidiol. |
|
Chloral Betaine |
May enhance the adverse/toxic effect of Anticholinergic Agents. |
|
CloBAZam |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Clofazimine |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
CYP2D6 Inhibitors (Moderate) |
May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
CYP3A4 Inhibitors (Moderate) |
May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). |
|
Deferasirox |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Duvelisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Erdafitinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Erdafitinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosaprepitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Fosnetupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Gastrointestinal Agents (Prokinetic) |
Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). |
|
Glucagon |
Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. |
|
Imatinib |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Itopride |
Anticholinergic Agents may diminish the therapeutic effect of Itopride. |
|
Ivosidenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Larotrectinib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Lumefantrine |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Mianserin |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
Mirabegron |
Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. |
|
Netupitant |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
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. |
|
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. |
|
Palbociclib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Panobinostat |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Peginterferon Alfa-2b |
May decrease the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Perhexiline |
CYP2D6 Substrates (High risk with Inhibitors) may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
QuiNINE |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
Ramosetron |
Anticholinergic Agents may enhance the constipating effect of Ramosetron. |
|
Sarilumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Siltuximab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Simeprevir |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Thiazide and Thiazide-Like Diuretics |
Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. |
|
Tocilizumab |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). |
|
Topiramate |
Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. |
|
Warfarin |
Tolterodine may enhance the anticoagulant effect of Warfarin. |
|
Risk Factor D (Consider therapy modification) |
|
|
Asunaprevir |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). |
|
CYP2D6 Inhibitors (Strong) |
May decrease the metabolism of CYP2D6 Substrates (High risk with Inhibitors). |
|
CYP3A4 Inducers (Strong) |
May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
CYP3A4 Inhibitors (Strong) |
May increase the serum concentration of Tolterodine. Management: The maximum recommended adult dose of tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor. |
|
Dabrafenib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). |
|
Dacomitinib |
May increase the serum concentration of CYP2D6 Substrates (High risk with Inhibitors). Management: Avoid concurrent use of dacomitinib with CYP2D6 subtrates that have a narrow therapeutic index. |
|
Enzalutamide |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. |
|
Lorlatinib |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. |
|
MiFEPRIStone |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. |
|
Mitotane |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. |
|
Pramlintide |
May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. |
|
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. |
|
St John's Wort |
May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. |
|
Stiripentol |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. |
|
VinBLAStine |
May increase the serum concentration of Tolterodine. Management: Reduce tolterodine dose to 1 mg twice daily (regular release formulation) or 2 mg daily (extended release formulation) (adult doses) and monitor for increased levels/effects of tolterodine with initiation of vinblastine therapy. |
|
Risk Factor X (Avoid combination) |
|
|
Aclidinium |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
Cimetropium |
Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. |
|
Conivaptan |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Eluxadoline |
Anticholinergic Agents may enhance the constipating effect of Eluxadoline. |
|
Fusidic Acid (Systemic) |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Glycopyrrolate (Oral Inhalation) |
Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). |
|
Glycopyrronium (Topical) |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
Idelalisib |
May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). |
|
Ipratropium (Oral Inhalation) |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
Levosulpiride |
Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. |
|
Oxatomide |
May enhance the anticholinergic effect of Anticholinergic Agents. |
|
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. |
|
Potassium Citrate |
Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. |
|
Revefenacin |
Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. |
|
Tiotropium |
Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. |
|
Umeclidinium |
May enhance the anticholinergic effect of Anticholinergic Agents. |
Monitoring parameters:
- Anticholinergic effects (ie, dry mouth, constipation, dizziness)
- Renal function (BUN, creatinine)
- Hepatic function;
- Postvoid residual (PVR) urine volume prior to initiation of therapy.
How to administer Tolterodine (Detrusitol)?
P/O:
- Administer without regard to food
- Do not break, crush, or chew extended-release capsules.
Mechanism of action of Tolterodine (Detrol):
- It is a competitor antagonist to muscarinic receptors.
- Tolterodine shows a preference for the urinary bladder receptors in animal models over the salivary receptors.
- Muscarinic receptors control bladder contraction.
- It increases the residual urine volume and lowers the detrusor muscles pressure.
Absorption:
- Rapid release tablet: Instant i.e. >=77%
Protein binding:
- >96% (primarily due to alpha-acid glycoprotein).
Metabolism:
- Extensively hepatic, primarily via CYP2D6 to 5-hydroxymethyltolterodine (active) and 3A4 usually (minor pathway).
- Patients with a genetic defect of CYP2D6 have a higher metabolic rate via 3A4.
Bioavailability:
- Immediate release tablet: Increased 53% with food
Half-life elimination:
Immediate release tablet:
- Extensive metabolizers: ~2 hours;
- Poor metabolizers: ~10 hours
Extended-release capsule:
- Extensive metabolizers: ~7 hours
- Poor metabolizers: ~18 hours
Time to peak:
- Immediate release tablet: 1-2 hours
- Extended-release capsule: 2-6 hours
Excretion:
- Urine (77%)
- feces (17%); primarily as metabolites (<1% unchanged drug) of which the active 5-hydroxymethyl metabolite accounts for 5% to 14% (<1% in poor metabolizers); as unchanged drug (<1%; <2.5% in poor metabolizers)
International Brands of Tolterodine:
- APO-Tolterodine
- Detrol
- Detrol LA
- MINT-Tolterodine
- MYLAN-Tolterodine ER
- SANDOZ Tolterodine LA
- TEVA-Tolterodine
- TEVA-Tolterodine LA
- Bapter
- BeiKe
- Breminal
- Caristenol
- Conturine
- Defur
- Detrodin SR
- Detrusitol
- Detrusitol Retard
- Detrusitol SR
- Detrusitol XL
- Effosomyl XL
- Eltoven
- Fluserin
- Le Zai
- Mariosea XL
- Neditol XL
- Roliten
- Sedoter
- Tendrotil
- Toladine
- Toldin
- Tolevo
- Toltem
- Tolter
- Tolterox
- Toltin
- Toltrex
- Tolusitol
- Torq
- Torq SR
- Trusitev
- Uretol SR
- Urginol
- Uridin
- Uridyne
- Uritol
- Uro-Q
- Uroflow
- Urolina
- Urositol
- Urotin S SR
- Urotol
- Urotrol
Tolterodine Brand Names in Pakistan:
Tolterodine (Tartrate) 1 mg Tablets |
|
| Akodine | Akhai Pharmaceuticals. |
| Tolodin | Valor Pharmaceuticals |
Tolterodine (Tartrate) 2 mg Tablets |
|
| Akodine | Akhai Pharmaceuticals. |
| Detriflow | Mission Pharmaceuticals |
| Detrusitol | Pfizer Laboratories Ltd. |
| Hrodin | Lexicon Pharmaceuticals (Pvt) Ltd. |
| Terodine | Noa Hemis Pharmaceuticals |
| Terol | Genome Pharmaceuticals (Pvt) Ltd |
| Toldex | Ambrosia Pharmaceuticals |
| Toldin | Sante (Pvt) Limited |
| Tolodin | Valor Pharmaceuticals |
| Toltem | Rotex Medica Pakistan (Pvt) Ltd |
| Tolter | Caraway Pharmaceuticals |
| Uridyne | Mission Pharmaceuticals |
Tolterodine SR 4 mg Tablets |
|
| Detrusitol | Pfizer Laboratories Ltd. |
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