Tolterodine Tartrate 1 mg Tablet, 60-count — NDC 29300-239-16 (Billing 29300-0239-16)
This is a package of 60 tablets of Tolterodine Tartrate 1 mg Tablet from Unichem Pharmaceuticals (USA), Inc., marketed since Aug 2020 and currently FDA-listed; retail pharmacies pay about $0.2039 per tablet (NADAC). It is the main listing for this product, which comes in 2 package sizes.
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 039138
- GCN: 37061
- GPI-14 (Medi-Span): 54100060200320
- HICL (First Databank): 018047
- AHFS class code: 86:12.04.00
- RxCUI (RxNorm): 855178
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Cholinergic Muscarinic Antagonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
- It treats overactive bladder, meaning sudden urges to urinate, leaking with those urges, and going very often. It helps calm the bladder muscle.
- It is taken by mouth. If you have the extended-release capsule, such as Detrol LA, take it once daily with water and swallow it whole. Follow your label and prescriber for your exa...
- Dry mouth is the most common. Headache, constipation, dizziness, stomach pain and dry or blurry eyes can also happen. Tell me if any of them bother you.
- Get emergency help for swelling of the face, lips or throat, or trouble breathing. Call your doctor if you cannot pass urine, or if you notice confusion, hallucinations, or a fast...
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.204 | $12.23 / 60 tablets |
| Medicaid paysCMS SDUD · 12 mo | $0.3639 | $21.83 / 60 tablets |
| Medicare drug plans payPart D · Q2 2026 | $0.5958 | $35.75 / 60 tablets |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q1 2026
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 29300-0239-05 29300-239-05 | 500 TABLET in 1 BOTTLE, PLASTIC | — | — | 2020-08-05 | — | Active |
| 29300-0239-16 You're viewing this Main listing | 60 TABLET in 1 BOTTLE, PLASTIC | $0.2039 / ea | $12.23 | 2020-08-05 | — | Active |
You're viewing the smallest of 2 pack sizes for this product.
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in this package?
How does this package differ from NDC 29300-0239-05?
What NDC number is used to bill for this package of Tolterodine Tartrate 1 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Tolterodine Tartrate 1 mg 59762-0170-01 | Mylan | 500 tablets | $0.204 | AB | Discontinued | +0% |
| Tolterodine Tartrate 1 mg 00093-0010-06 | Teva | 60 tablets | $0.204 | AB | Availability likely | — |
| Tolterodine Tartrate 1 mgthis 29300-0239-16 | Unichem | 60 tablets | $0.204 | AB | Availability likely | — |
| Tolterodine tartrate 1 mg 33342-0097-09 | Macleods | 60 tablets | $0.204 | AB | Availability likely | — |
| Tolterodine Tartrate 1 mg 16571-0126-01 | Rising | 100 tablets | — | AB | FDA listed | — |
| Tolterodine Tartrate 1 mg 31722-0805-01 | Camber | 10 tablets | — | AB | FDA listed | — |
| Detrol 1 mg 58151-0098-91 | Viatris | 60 tablets | — | AB | Discontinued | — |
| Tolterodine Tartrate 1 mg 71205-0319-30 | Proficient | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Sep 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Sep 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 1, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII O7TSZ97GEP
A mineral compound that serves as a filler and binding agent in tablets and capsules. It adds bulk to the medicine and helps hold ingredients together during manufacturing.
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UNII 0WZ8WG20P6
Hypromellose 2910 is a plant-based cellulose derivative that acts as a thickener, binder, and film-coating agent. It helps control how quickly the medicine dissolves and protects the tablet or capsule from moisture and light.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 27NA468985
A starch derivative made from potatoes that helps tablets and capsules break down quickly in the stomach. It absorbs water and swells, causing the medication to disintegrate so it can be absorbed properly.
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UNII 4ELV7Z65AP
Stearic acid is a fatty acid derived from plant or animal sources. It acts as a binder and lubricant in tablets and capsules, helping them hold together and flow smoothly during manufacturing.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
8 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 1, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
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Manufacturer & labeler
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Tolterodine tartrate tablets are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION The initial recommended dose of tolterodine tartrate tablets is 2 mg twice daily. The dose may be lowered to 1 mg twice daily based on individual response and tolerability. For patients with significantly reduced hepatic or renal function or who are currently taking drugs that are potent inhibitors of CYP3A4, the recommended dose of tolterodine tartrate tablets is 1 mg twice daily (see PRECAUTIONS, General , PRECAUTIONS, Reduced Hepatic and Renal Function , and PRECAUTIONS, Drug Interactions ).
⛔ Contraindications ▾
CONTRAINDICATIONS Tolterodine tartrate tablets are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tartrate is also contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tartrate, are metabolized to 5-hydroxymethyl tolterodine.
⚠️ Warnings ▾
WARNINGS Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of tolterodine tartrate. In the event of difficulty in breathing, upper airway obstruction, or fall in blood pressure, tolterodine tartrate should be discontinued and appropriate therapy promptly provided.
🤒 Adverse Reactions ▾
ADVERSE REACTIONS The Phase 2 and 3 clinical trial program for tolterodine tartrate tablets included 3071 patients who were treated with tolterodine tartrate (N=2133) or placebo (N=938). The patients were treated with 1, 2, 4, or 8 mg/day for up to 12 months. No differences in the safety profile of tolterodine were identified based on age, gender, race, or metabolism.
The data described below reflect exposure to tolterodine tartrate 2 mg bid in 986 patients and to placebo in 683 patients exposed for 12 weeks in five Phase 3, controlled clinical studies. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and approximating rates.
Sixty-six percent of patients receiving tolterodine tartrate 2 mg bid reported adverse events versus 56% of placebo patients. The most common adverse events reported by patients receiving tolterodine tartrate were dry mouth, headache, constipation, vertigo/dizziness, and abdominal pain. Dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, and xerophthalmia are expected side effects of antimuscarinic agents.
Dry mouth was the most frequently reported adverse event for patients treated with tolterodine tartrate 2 mg bid in the Phase 3 clinical studies, occurring in 34.8% of patients treated with tolterodine tartrate and 9.8% of placebo-treated patients. One percent of patients treated with tolterodine tartrate discontinued treatment due to dry mouth. The frequency of discontinuation due to adverse events was highest during the first 4 weeks of treatment.
Seven percent of patients treated with tolterodine tartrate 2 mg bid discontinued treatment due to adverse events versus 6% of placebo patients. The most common adverse events leading to discontinuation of tolterodine tartrate were dizziness and headache. Three percent of patients treated with tolterodine tartrate 2 mg bid reported a serious adverse event versus 4% of placebo patients.
Significant ECG changes in QT and QTc have not been demonstrated in clinical-study patients treated with tolterodine tartrate 2 mg bid. Table 5 lists the adverse events reported in 1% or more of the patients treated with tolterodine tartrate 2 mg bid in the 12-week studies. The adverse events are reported regardless of causality.
Table 5. Incidence in nearest integer. (%) of Adverse Events Exceeding Placebo Rate and Reported in >1% of Patients Treated with Tolterodine Tartrate Tablets (2 mg bid) in 12-week, Phase 3 Clinical Studies Body System Adverse Event % Tolterodine Tartrate N = 986 % Placebo N = 683 Autonomic Nervous accommodation abnormal dry mouth 2 35 1 10 General chest pain fatigue headache influenza-like symptoms 2 4 7 3 1 3 5 2 Central/Peripheral Nervous vertigo/dizziness 5 3 Gastrointestinal abdominal pain constipation diarrhea dyspepsia 5 7 4 4 3 4 3 1 Urinary dysuria 2 1 Skin/Appendages dry skin 1 0 Musculoskeletal arthralgia 2 1 Vision xerophthalmia 3 2 Psychiatric somnolence 3 2 Metabolic/Nutritional weight gain 1 0 Resistance Mechanism infection 1 0 Post-marketing Surveillance The following events have been reported in association with tolterodine use in worldwide post-marketing experience: General: anaphylaxis and angioedema; Cardiovascular: tachycardia, palpitations, peripheral edema; Central/Peripheral Nervous: confusion, disorientation, memory impairment, hallucinations.
Reports of aggravation of symptoms of dementia (e.g., confusion, disorientation, delusion) have been reported after tolterodine therapy was initiated in patients taking cholinesterase inhibitors for the treatment of dementia. Because these spontaneously reported events are from the wo… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
Drug Interactions CYP3A4 Inhibitors: Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see CLINICAL PHARMACOLOGY, Variability in Metabolism and Drug-Drug Interactions ). For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as other azole antifungals (e.g., itraconazole, miconazole) or macrolide antibiotics (e.g., erythromycin, clarithromycin) or cyclosporine or vinblastine, the recommended dose of tolterodine tartrate is 1 mg twice daily (see DOSAGE AND ADMINISTRATION ).
🤰 Pregnancy ▾
Pregnancy Pregnancy Category C. At oral doses of 20 mg/kg/day (approximately 14 times the human exposure), no anomalies or malformations were observed in mice. When given at doses of 30 to 40 mg/kg/day, tolterodine has been shown to be embryolethal, reduce fetal weight, and increase the incidence of fetal abnormalities (cleft palate, digital abnormalities, intra-abdominal hemorrhage, and various skeletal abnormalities, primarily reduced ossification) in mice.
At these doses, the AUC values were about 20- to 25-fold higher than in humans. Rabbits treated subcutaneously at a dose of 0.8 mg/kg/day achieved an AUC of 100 μg h/L, which is about 3-fold higher than that resulting from the human dose. This dose did not result in any embryotoxicity or teratogenicity.
There are no studies of tolterodine in pregnant women. Therefore, tolterodine tartrate should be used during pregnancy only if the potential benefit for the mother justifies the potential risk to the fetus.
🧒 Pediatric Use ▾
Pediatric Use Efficacy in the pediatric population has not been demonstrated. Two pediatric phase 3 randomized, placebo-controlled, double-blind, 12-week studies were conducted using tolterodine extended release capsules. A total of 710 pediatric patients (486 on tolterodine tartrate extended release capsules and 224 on placebo) aged 5–10 years with urinary frequency and urge urinary incontinence were studied.
The percentage of patients with urinary tract infections was higher in patients treated with tolterodine tartrate extended release capsules (6.6%) compared to patients who received placebo (4.5%). Aggressive, abnormal, and hyperactive behavior and attention disorders occurred in 2.9% of children treated with tolterodine tartrate extended release capsules compared to 0.9% of children treated with placebo.
🧓 Geriatric Use ▾
Geriatric Use Of the 1120 patients who were treated in the four Phase 3, 12-week clinical studies of tolterodine tartrate, 474 (42%) were 65 to 91 years of age. No overall differences in safety were observed between the older and younger patients (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Special Populations ).
🆘 Overdosage ▾
OVERDOSAGE A 27-month-old child who ingested 5 to 7 tolterodine tartrate tablets 2 mg was treated with a suspension of activated charcoal and was hospitalized overnight with symptoms of dry mouth. The child fully recovered. Management of Overdosage Overdosage with tolterodine tartrate can potentially result in severe central anticholinergic effects and should be treated accordingly.
ECG monitoring is recommended in the event of overdosage. In dogs, changes in the QT interval (slight prolongation of 10% to 20%) were observed at a suprapharmacologic dose of 4.5 mg/kg, which is about 68 times higher than the recommended human dose. In clinical trials of normal volunteers and patients, QT interval prolongation was observed with tolterodine immediate release at doses up to 8 mg (4 mg bid) and higher doses were not evaluated (see PRECAUTIONS, Patients with Congenital or Acquired QT Prolongation ).
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Tolterodine is a competitive muscarinic receptor antagonist. Both urinary bladder contraction and salivation are mediated via cholinergic muscarinic receptors. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative, a major pharmacologically active metabolite.
The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic activity similar to that of tolterodine, contributes significantly to the therapeutic effect. Both tolterodine and the 5-hydroxymethyl metabolite exhibit a high specificity for muscarinic receptors, since both show negligible activity or affinity for other neurotransmitter receptors and other potential cellular targets, such as calcium channels. Tolterodine has a pronounced effect on bladder function.
Effects on urodynamic parameters before and 1 and 5 hours after a single 6.4 mg dose of tolterodine immediate release were determined in healthy volunteers. The main effects of tolterodine at 1 and 5 hours were an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure. These findings are consistent with an antimuscarinic action on the lower urinary tract.
Pharmacokinetics Absorption: In a study with 14 C-tolterodine solution in healthy volunteers who received a 5 mg oral dose, at least 77% of the radiolabeled dose was absorbed. Tolterodine immediate release is rapidly absorbed, and maximum serum concentrations (C max ) typically occur within 1 to 2 hours after dose administration. C max and area under the concentration-time curve (AUC) determined after dosage of tolterodine immediate release are dose-proportional over the range of 1 to 4 mg.
Effect of Food: Food intake increases the bioavailability of tolterodine (average increase 53%), but does not affect the levels of the 5-hydroxymethyl metabolite in extensive metabolizers. This change is not expected to be a safety concern and adjustment of dose is not needed. Distribution: Tolterodine is highly bound to plasma proteins, primarily α 1 -acid glycoprotein.
Unbound concentrations of tolterodine average 3.7% ± 0.13% over the concentration range achieved in clinical studies. The 5-hydroxymethyl metabolite is not extensively protein bound, with unbound fraction concentrations averaging 36% ± 4.0%. The blood to serum ratio of tolterodine and the 5-hydroxymethyl metabolite averages 0.6 and 0.8, respectively, indicating that these compounds do not distribute extensively into erythrocytes.
The volume of distribution of tolterodine following administration of a 1.28 mg intravenous dose is 113 ±
26.7L. Metabolism: Tolterodine is extensively metabolized by the liver following oral dosing. The primary metabolic route involves the oxidation of the 5-methyl group and is mediated by the cytochrome P450 2D6 (CYP2D6) and leads to the formation of a pharmacologically active 5-hydroxymethyl metabolite.
Further metabolism leads to formation of the 5-carboxylic acid and N -dealkylated 5-carboxylic acid metabolites, which account for 51% ± 14% and 29% ± 6.3% of the metabolites recovered in the urine, respectively. Variability in Metabolism : A subset (about 7%) of the population is devoid of CYP2D6, the enzyme responsible for the formation of the 5-hydroxymethyl metabolite of tolterodine. The identified pathway of metabolism for these individuals ("poor metabolizers") is dealkylation via cytochrome P450 3A4 (CYP3A4) to N -dealkylated tolterodine.
The remainder of the population is referred to as "extensive metabolizers." Pharmacokinetic studies revealed that tolterodine is metabolized at a slower rate in poor metabolizers than in extensive metabolizers; this results in significantly higher serum concentrations of tolterodine and in negligible concentrations of the 5-hydroxymethyl metabolite. Excretion: Following administration of a 5 mg oral dose of 14 C-tolterodine solution to healthy volunteers, 77% of radioactivity was reco… [Excerpted — this section continues on DailyMed.]
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED Tolterodine tartrate tablets are supplied as 1 mg Tablets: White to off white colored, circular, biconvex, film coated tablets with "U" debossed on one side and "239" on other side. Bottles of 60: NDC 29300-239-16 Bottles of 500: NDC 29300-239-05 2 mg Tablets: White to off white colored, circular, biconvex, film coated tablets with "U" debossed on one side and "240" on other side. Bottles of 30: NDC 29300-240-13 Bottles of 60: NDC 29300-240-16 Bottles of 90: NDC 29300-240-19 Bottles of 100: NDC 29300-240-01 Bottles of 500: NDC 29300-240-05 Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].
Manufactured by: UNICHEM LABORATORIES LTD. Pilerne Ind. Estate, Pilerne, Bardez, Goa 403 511, India.
Manufactured for: East Brunswick, NJ 08816 02-R-11/2019 13012096 Revised: November 2019 Company logo
📋 Description ▾
DESCRIPTION Tolterodine tartrate tablets contain tolterodine tartrate USP. The active moiety, tolterodine, is a muscarinic receptor antagonist. The chemical name of tolterodine tartrate is (R)-2-[3-[bis(1-methylethyl)-amino]1-phenylpropyl]-4-methylphenol [R-(R*,R*)]-2,3dihydroxybutanedioate (1:1) (salt).
The empirical formula of tolterodine tartrate is C 26 H 37 NO 7 , and its molecular weight is 475.6. The structural formula of tolterodine tartrate is represented below: Tolterodine tartrate is a white, crystalline powder. The pKa value is 9.87 and the solubility in water is 14.7657 mg/mL.
It is sparingly soluble in water, slightly soluble in anhydrous ethanol, practically insoluble in heptane. The partition coefficient (Log D) between n-octanol and water is 1.83 at pH 7.3. Tolterodine tartrate tablets for oral administration contain 1 or 2 mg of tolterodine tartrate.
The inactive ingredients are microcrystalline cellulose, dibasic calcium phosphate dihydrate, sodium starch glycolate type B (pH 3.0 to 5.0), colloidal silicon dioxide, magnesium stearate, hypromellose, stearic acid, and titanium dioxide. Structure
💬 Information for Patients ▾
Information for Patients Patients should be informed that antimuscarinic agents such as tolterodine tartrate may produce the following effects: blurred vision, dizziness, or drowsiness. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's effects have been determined.
⚠️ Precautions ▾
PRECAUTIONS General Risk of Urinary Retention and Gastric Retention: Tolterodine tartrate tablets should be administered with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention and to patients with gastrointestinal obstructive disorders, such as pyloric stenosis, because of the risk of gastric retention (see CONTRAINDICATIONS ). Decreased Gastrointestinal Motility: Tolterodine tartrate, like other antimuscarinic drugs, should be used with caution in patients with decreased gastrointestinal motility.
Controlled Narrow-Angle Glaucoma : Tolterodine tartrate should be used with caution in patients being treated for narrow-angle glaucoma. Central Nervous System (CNS) Effects : Tolterodine tartrate is associated with anticholinergic central nervous system (CNS) effects including dizziness and somnolence (see Adverse Reactions). Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose.
Advise patients not to drive or operate heavy machinery until the drug's effects have been determined. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Reduced Hepatic and Renal Function: For patients with significantly reduced hepatic function or renal function, the recommended dose of tolterodine tartrate is 1 mg twice daily (see CLINICAL PHARMACOLOGY, Pharmacokinetics in Special Populations ).
Myasthenia Gravis: Tolterodine tartrate should be used with caution in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction. Patients with Congenital or Acquired QT Prolongation In a study of the effect of tolterodine immediate release tablets on the QT interval (see CLINICAL PHARMACOLOGY, Cardiac Electrophysiology ), the effect on the QT interval appeared greater for 8 mg/day (two times the therapeutic dose) compared to 4 mg/day and was more pronounced in CYP2D6 poor metabolizers (PM) than extensive metabolizers (EMs).
The effect of tolterodine 8 mg/day was not as large as that observed after four days of therapeutic dosing with the active control moxifloxacin. However, the confidence intervals overlapped. These observations should be considered in clinical decisions to prescribe tolterodine tartrate for patients with a known history of QT prolongation or patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications (see PRECAUTIONS, Drug Interactions ).
There has been no association of Torsade de Pointes in the international post-marketing experience with tolterodine tartrate tablets or tolterodine tartrate extended release capsules. Information for Patients Patients should be informed that antimuscarinic agents such as tolterodine tartrate may produce the following effects: blurred vision, dizziness, or drowsiness. Patients should be advised to exercise caution in decisions to engage in potentially dangerous activities until the drug's effects have been determined.
Drug Interactions CYP3A4 Inhibitors: Ketoconazole, an inhibitor of the drug metabolizing enzyme CYP3A4, significantly increased plasma concentrations of tolterodine when coadministered to subjects who were poor metabolizers (see CLINICAL PHARMACOLOGY, Variability in Metabolism and Drug-Drug Interactions ). For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as other azole antifungals (e.g., itraconazole, miconazole) or macrolide antibiotics (e.g., erythromycin, clarithromycin) or cyclosporine or vinblastine, the recommended dose of tolterodine tartrate is 1 mg twice daily (see DOSAGE AND ADMINISTRATION ).
Drug-Laboratory-Test Interactions Interactions between tolterodine and laboratory tests have not been studied. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies with tolterodine were conducted in mice and… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
Nursing Mothers Tolterodine is excreted into the milk in mice. Offspring of female mice treated with tolterodine 20 mg/kg/day during the lactation period had slightly reduced body weight gain. The offspring regained the weight during the maturation phase.
It is not known whether tolterodine is excreted in human milk; therefore, tolterodine tartrate should not be administered during nursing. A decision should be made whether to discontinue nursing or to discontinue tolterodine tartrate in nursing mothers.
🧬 Pharmacokinetics ▾
Pharmacokinetics Absorption: In a study with 14 C-tolterodine solution in healthy volunteers who received a 5 mg oral dose, at least 77% of the radiolabeled dose was absorbed. Tolterodine immediate release is rapidly absorbed, and maximum serum concentrations (C max ) typically occur within 1 to 2 hours after dose administration. C max and area under the concentration-time curve (AUC) determined after dosage of tolterodine immediate release are dose-proportional over the range of 1 to 4 mg.
Effect of Food: Food intake increases the bioavailability of tolterodine (average increase 53%), but does not affect the levels of the 5-hydroxymethyl metabolite in extensive metabolizers. This change is not expected to be a safety concern and adjustment of dose is not needed. Distribution: Tolterodine is highly bound to plasma proteins, primarily α 1 -acid glycoprotein.
Unbound concentrations of tolterodine average 3.7% ± 0.13% over the concentration range achieved in clinical studies. The 5-hydroxymethyl metabolite is not extensively protein bound, with unbound fraction concentrations averaging 36% ± 4.0%. The blood to serum ratio of tolterodine and the 5-hydroxymethyl metabolite averages 0.6 and 0.8, respectively, indicating that these compounds do not distribute extensively into erythrocytes.
The volume of distribution of tolterodine following administration of a 1.28 mg intravenous dose is 113 ±
26.7L. Metabolism: Tolterodine is extensively metabolized by the liver following oral dosing. The primary metabolic route involves the oxidation of the 5-methyl group and is mediated by the cytochrome P450 2D6 (CYP2D6) and leads to the formation of a pharmacologically active 5-hydroxymethyl metabolite.
Further metabolism leads to formation of the 5-carboxylic acid and N -dealkylated 5-carboxylic acid metabolites, which account for 51% ± 14% and 29% ± 6.3% of the metabolites recovered in the urine, respectively. Variability in Metabolism : A subset (about 7%) of the population is devoid of CYP2D6, the enzyme responsible for the formation of the 5-hydroxymethyl metabolite of tolterodine. The identified pathway of metabolism for these individuals ("poor metabolizers") is dealkylation via cytochrome P450 3A4 (CYP3A4) to N -dealkylated tolterodine.
The remainder of the population is referred to as "extensive metabolizers." Pharmacokinetic studies revealed that tolterodine is metabolized at a slower rate in poor metabolizers than in extensive metabolizers; this results in significantly higher serum concentrations of tolterodine and in negligible concentrations of the 5-hydroxymethyl metabolite. Excretion: Following administration of a 5 mg oral dose of 14 C-tolterodine solution to healthy volunteers, 77% of radioactivity was recovered in urine and 17% was recovered in feces in 7 days.
Less than 1% (<2.5% in poor metabolizers) of the dose was recovered as intact tolterodine, and 5% to 14% (<1% in poor metabolizers) was recovered as the active 5-hydroxymethyl metabolite. A summary of mean (± standard deviation) pharmacokinetic parameters of tolterodine immediate release and the 5-hydroxymethyl metabolite in extensive (EM) and poor (PM) metabolizers is provided in Table 1. These data were obtained following single and multiple doses of tolterodine 4 mg administered twice daily to 16 healthy male volunteers (8 EM, 8 PM).
Table 1. Summary of Mean (±SD) Pharmacokinetic Parameters of Tolterodine and its Active Metabolite (5-hydroxymethyl metabolite) in Healthy Volunteers * Parameter was dose-normalized from 4 mg to 2 mg. † = not applicable Cmax = Maximum plasma concentration; t m a x = Time of occurrence of C m a x ; C a v g = Average plasma concentration; t 1 / 2 = Terminal elimination half-life; CL/F = Apparent oral clearance. EM = Extensive metabolizers; PM = Poor metabolizers Tolterodine 5 - Hydroxymethyl Metabolite Phenotype t m a x C m a x * C a v g * t 1 / 2 CL / F t m a x C m a x * C a v g * t 1 / 2 ( CYP2D6 ) ( h ) ( μg / L ) ( μg / L ) ( h ) ( L… [Excerpted — this section continues on DailyMed.]
🔬 Clinical Studies ▾
CLINICAL STUDIES Tolterodine tartrate tablets were evaluated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency in four randomized, double-blind, placebo-controlled, 12-week studies. A total of 853 patients received tolterodine tartrate tablets 2 mg twice daily and 685 patients received placebo. The majority of patients were Caucasian (95%) and female (78%), with a mean age of 60 years (range, 19 to 93 years).
At study entry, nearly all patients perceived they had urgency and most patients had increased frequency of micturitions and urge incontinence. These characteristics were well balanced across treatment groups for the studies. The efficacy endpoints for study 007 (see Table 3) included the change from baseline for: Number of incontinence episodes per week Number of micturitions per 24 hours (averaged over 7 days) Volume of urine voided per micturition (averaged over 2 days) The efficacy endpoints for studies 008, 009, and 010 (see Table 4) were identical to the above endpoints with the exception that the number of incontinence episodes was per 24 hours (averaged over 7 days).
Table 3. 95% Confidence Intervals (CI) for the Difference between Tolterodine Tartrate (2 mg bid) and Placebo for the Mean Change at Week 12 from Baseline in Study 007 SD = Standard Deviation. *The difference between tolterodine tartrate and placebo was statistically significant. Tolterodine Tartrate ( SD ) N = 514 Placebo ( SD ) N = 508 Difference ( 95 % CI ) Number of Incontinence Episodes per Week Mean baseline 23.2
23.3Mean change from baseline -10.6 (17) -6.9 (15) -3.7 (-5.7, -1.6) Number of Micturitions per 24 Hours Mean baseline 11.1
11.3Mean change from baseline -1.7 (3.3) -1.2 (2.9) -0.5* (-0.9, -0.1) Volume Voided per Micturition (mL) Mean baseline 137 136 Mean change from baseline 29 (47) 14(41) 15*(9, 21) Table 4. 95% Confidence Intervals (CI) for the Difference between Tolterodine Tartrate (2 mg bid) and Placebo for the Mean Change at Week 12 from Baseline in Studies 008, 009, 010 SD = Standard Deviation. *The difference between tolterodine tartrate and placebo was statistically significant. Study Tolterodine Tartrate ( SD ) Placebo ( SD ) Difference ( 95 % CI ) Number of Incontinence Episodes per 24 Hours 008 Number of patients 93 40 Mean baseline 2.9
3.3Mean change from baseline -1.3 (3.2) -0.9 (1.5) 0.5 (-1.3,0.3) 009 Number of patients 116 55 Mean baseline 3.6
3.5Mean change from baseline -1.7 (2.5) -1.3 (2.5) -0.4 (-1.0, 0.2) 010 Number of patients 90 50 Mean baseline 3.7
3.5Mean change from baseline -1.6 (2.4) -1.1 (2.1) -0.5 (-1.1,0.1) Number of Micturitions per 24 Hours 008 Number of patients 118 56 Mean baseline 11.5
11.7Mean change from baseline -2.7 (3.8) -1.6 (3.6) -1.2* (-2.0,-0.4) 009 Number of patients 128 64 Mean baseline 11.2
11.3Mean change from baseline -2.3 (2.1) -1.4 (2.8) -0.9* (-1.5,-0.3) 010 Number of patients 108 56 Mean baseline 11.6
11.6Mean change from baseline -1.7 (2.3) -1.4 (2.8) -0.38 (-1.1,0.3) Volume Voided per Micturition ( mL ) 008 Number of patients 118 56 Mean baseline 166 157 Mean change from baseline 38 (54) 6 (42) 32* (18,46) 009 Number of patients 129 64 Mean baseline 155 158 Mean change from baseline 36 (50) 10 (47) 26* (14,38) 010 Number of patients 108 56 Mean baseline 155 160 Mean change from baseline 31 (45) 13 (52) 18* (4,32)
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL Tolterodine Tartrate Tablets 1 mg 60T Tolterodine Tartrate Tablets 2 mg 30T