Tolterodine is a medication primarily used to treat overactive bladder (OAB) symptoms such as frequent or urgent urination and incontinence. It belongs to a class of drugs called antimuscarinics or anticholinergics, which work by blocking certain receptors in the bladder, thereby reducing muscle spasms and controlling bladder function.
Tolterodine is available in both immediate-release and extended-release formulations. The immediate-release form is typically taken multiple times a day, while the extended-release form is usually taken once daily. The choice between the two formulations depends on factors such as the severity of symptoms and individual patient preference.
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:
- Start with 2 mg twice daily. Your doctor may lower the dose to 1 mg twice daily if needed.
- If you're taking strong CYP3A4 inhibitors (like ketoconazole), your doctor may start you on 1 mg twice daily.
Extended-release capsule:
- Typically, start with 4 mg once daily. Your doctor may reduce it to 2 mg once daily if necessary.
- If you're taking strong CYP3A4 inhibitors, your doctor may start you on 2 mg once daily.
Tolterodine Dose in Children
Safety and efficacy not established in children
Tolterodine Pregnancy Risk Category: B3
- In some studies done on animals, there were some negative effects noticed during reproduction.
Tolterodine use during breastfeeding:
- It's uncertain whether tolterodine passes into breast milk.
- The manufacturer advises considering factors like the potential risk of the baby being exposed to the medication, the advantages of breastfeeding for the infant, and the benefits of treatment for the mother when deciding whether to breastfeed while using tolterodine.
Tolterodine Dose in Kidney Disease:
For Immediate-release tablet:
- In patients with significantly reduced kidney function (as shown in studies with creatinine clearance between 10 to 30 mL/minute), the recommended dose is 1 mg twice daily, but it should be used cautiously.
For Extended-release capsule:
- In patient with creatinine clearance is between 10 to 30 mL/minute, the suggested dose is 2 mg once daily.
- If patient creatinine clearance is less than 10 mL/minute, using tolterodine isn't recommended, as it hasn't been studied in this group.
Tolterodine Dose in Liver disease:
For Immediate-release tablet:
- in patient with significantly reduced liver function, the recommended dose is 1 mg twice daily, but it should be used cautiously.
For Extended-release capsule:
- If patient have mild to moderate liver impairment (Child-Pugh class A or B), the suggested dose is 2 mg once daily.
- If patient have severe impairment (Child-Pugh class C), using tolterodine isn't recommended as it hasn't been studied in this group.
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):
- If you're allergic to tolterodine or fesoterodine, which both break down into 5-hydroxymethyl tolterodine, or if you're allergic to any ingredient in the medication, you shouldn't take it.
- It's also not suitable if you have trouble emptying your bladder or stomach, or if you have uncontrolled narrow-angle glaucoma.
Warnings and precautions
Angioedema
- Angioedema, which involves swelling under the skin, has been reported with tolterodine use, with some cases occurring after just one dose.
- If you experience angioedema along with difficulty breathing, airway blockage, or low blood pressure, stop taking the medication immediately and seek medical help.
CNS effects
- Tolterodine can cause drowsiness, dizziness, and blurred vision, which might affect your ability to think clearly or react quickly.
- It's essential to be cautious when doing activities that require mental alertness, like driving or operating machinery.
- If you experience these effects, talk to your doctor about possibly lowering your dose or stopping the medication.
Extension of QT
- Tolterodine has been linked to QT prolongation, particularly at high doses beyond what's typically prescribed.
- The manufacturer advises caution in individuals with a congenital prolonged QT interval or those taking medications known to prolong QT interval, such as certain antiarrhythmic drugs.
- However, even at higher doses, the extent of QT prolongation was generally less than 15 milliseconds.
- People who are poor metabolizers of CYP2D6, or taking medications that inhibit CYP2D6 and CYP3A4, may have a higher risk of experiencing QT prolongation.
Alzheimer disease
- Preliminary research indicates that prolonged use of anticholinergic medications, like tolterodine, might have a negative impact on the progression of Alzheimer's disease in individuals also taking cholinesterase inhibitors.
- Therefore, if someone with dementia is on both an acetylcholinesterase inhibitor and a bladder anticholinergic like tolterodine, it's advisable to monitor them closely for any decline in cognitive function, daily abilities, or an increase in problematic behaviors.
Bladder flow obstruction
- Tolterodine should be used cautiously in individuals with bladder flow obstruction, such as benign prostatic hypertrophy (BPH).
- In such cases, there's a risk that tolterodine might increase the likelihood of urinary retention.
GI obstructive disorders:
- If you have conditions that affect your gastrointestinal (GI) motility or obstructive disorders like pyloric stenosis, it's important to use tolterodine with caution.
- These conditions may increase the risk of gastric retention when taking tolterodine.
Glaucoma:
- If you have controlled (treated) narrow-angle glaucoma, it's important to use tolterodine with caution.
Hepatic impairment
- If you have hepatic impairment (problems with your liver), it's important to use tolterodine with caution, and your doctor may need to adjust your dosage accordingly.
Myasthenia gravis:
- Tolterodine should be used cautiously in individuals with myasthenia gravis.
Renal impairment
- If you have renal impairment (problems with your kidneys), it's important to use tolterodine with caution, and your doctor may need to adjust your dosage accordingly.
Tolterodine: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
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:
Important Considerations Before Starting Tolterodine Therapy:
- Anticholinergic Effects: Watch out for dry mouth, constipation, and dizziness.
- Renal Function: Monitor levels of blood urea nitrogen (BUN) and creatinine, especially in patients with kidney issues.
- Hepatic Function: Take caution and assess liver function, especially in individuals with liver problems.
- Postvoid Residual (PVR) Urine Volume: Measure this before starting therapy, as recommended by the American College of Obstetricians and Gynecologists (ACOG, 2015).
How to administer Tolterodine (Detrusitol)?
- Oral Administration: You can take it with or without food.
- Extended-Release Capsules: Swallow them whole; don't break, crush, or chew them.
Mechanism of action of Tolterodine (Detrol):
- Tolterodine works by blocking muscarinic receptors in the body.
- It's particularly selective for receptors in the urinary bladder compared to those in the salivary glands.
- Muscarinic receptors play a role in controlling bladder contractions.
- By blocking these receptors, tolterodine helps increase the amount of urine left in the bladder after urination and reduces pressure in the bladder muscle.
Absorption:
- When taken as an immediate-release tablet, it's absorbed rapidly, with at least 77% of the dose reaching the bloodstream.
- Food can increase its absorption by 53%.
Distribution:
- When administered intravenously, it has a volume of distribution of approximately 113 liters.
Protein Binding:
- More than 96% of tolterodine is bound to alpha-acid glycoprotein in the blood.
Metabolism:
- Tolterodine is primarily broken down in the liver, mainly by the enzyme CYP2D6, forming an active metabolite called 5-hydroxymethyltolterodine.
- A minor pathway involves CYP3A4.
- In individuals with a genetic deficiency of CYP2D6, metabolism occurs predominantly via CYP3A4.
Bioavailability:
- Food increases the bioavailability of the immediate-release tablet by 53%.
Half-life:
- In extensive metabolizers, the half-life of the immediate-release tablet is approximately 2 hours, while in poor metabolizers, it's around 10 hours.
- For the extended-release capsule, the half-life is approximately 7 hours in extensive metabolizers and about 18 hours in poor metabolizers.
Time to Peak:
- The immediate-release tablet reaches peak concentration in the blood within 1-2 hours, while the extended-release capsule peaks between 2-6 hours.
Excretion:
- Most of tolterodine and its metabolites are excreted in the urine (about 77%), with a smaller amount in the feces (about 17%).
- Less than 1% of the drug is excreted unchanged in the urine.
- The active metabolite accounts for 5-14% of the total metabolites in extensive metabolizers and less than 1% 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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