FDA

Tolterodine Tartrate

Approved 19 Aug 2019OralCapsule, extended release

The FDA lists this product in 34 strengths and forms.

Indications

1. INDICATIONS AND USAGE Tolterodine tartrate extended-release capsules, USP are indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency [see CLINICAL STUDIES (14) ] . Tolterodine tartrate extended-release capsules, USP are an antimuscarinic indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency.

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Contraindications

4. CONTRAINDICATIONS Tolterodine tartrate extended-release capsules are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tartrate extended-release capsules are also contraindicated in patients with known hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tartrate extended-release capsules, are metabolized to 5-hydroxymethyl tolterodine [see WARNINGS AND PRECAUTIONS (5.2), (5.3), (5.4) ].

Tolterodine tartrate extended-release capsules are contraindicated in patients with urinary retention, gastric retention, or uncontrolled narrow-angle glaucoma. Tolterodine tartrate extended-release capsules are also contraindicated in patients with known hypersensitivity to the drug or its ingredients, or to fesoterodine fumarate extended-release tablets which, like tolterodine tartrate extended-release capsules, are metabolized to 5-hydroxymethyl tolterodine.

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Warnings and precautions

5. WARNINGS AND PRECAUTIONS Anaphylaxis and angioedema requiring hospitalization and emergency medical treatment have occurred with the first or subsequent doses of tolterodine tartrate extended-release capsules. ( 5.1 ) Urinary Retention: use caution in patients with clinically significant bladder outflow obstruction because of the risk of urinary retention. ( 5.2 ) Gastrointestinal Disorders: use caution in patients with gastrointestinal obstructive disorders or decreased gastrointestinal motility because of the risk of gastric retention.

Indications

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Contraindications

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Warnings and precautions

Interactions

7. DRUG INTERACTIONS Potent CYP3A4 inhibitors: Coadministration may increase systemic exposure to tolterodine tartrate extended-release capsules. Reduce tolterodine tartrate extended-release capsules dose to 2 mg once daily. ( 7.2 ) Other Anticholinergics (antimuscarinics): Concomitant use with other anticholinergic agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision, and other anticholinergic pharmacological effects.

( 7.6 )

7.1Potent CYP2D6 Inhibitors Fluoxetine,

a potent inhibitor of CYP2D6 activity, significantly inhibited the metabolism of tolterodine immediate release in CYP2D6 extensive metabolizers, resulting in a 4.8-fold increase in tolterodine AUC. There was a 52% decrease in C max and a 20% decrease in AUC of 5-hydroxymethyl tolterodine (5-HMT), the pharmacologically active metabolite of tolterodine [see CLINICAL PHARMACOLOGY (12.1) ] . The sums of unbound serum concentrations of tolterodine and 5-HMT are only 25% higher during the interaction.

No dose adjustment is required when tolterodine and fluoxetine are co-administered [see CLINICAL PHARMACOLOGY (12.3) ].

7.2Potent CYP3A4 Inhibitors Ketoconazole

(200 mg daily), a potent CYP3A4 inhibitor, increased the mean C max and AUC of tolterodine by 2- and 2.5-fold, respectively in CYP2D6 poor metabolizers. For patients receiving ketoconazole or other potent CYP3A4 inhibitors such as itraconazole, clarithromycin or ritonavir, the recommended dose of tolterodine tartrate extended release capsules is 2 mg once daily [see DOSAGE AND ADMINISTRATION (2.2) and CLINICAL PHARMACOLOGY (12.3) ] .

7.3 Other interactions No clinically relevant interactions have been observed when tolterodine was co-administered with warfarin, with a combined oral contraceptive drug containing ethinyl estradiol and levonorgestrel, or with diuretics [see CLINICAL PHARMACOLOGY (12.3) ].

7.4 Other drugs metabolized by Cytochrome P450 Isoenzymes In vivo drug-interaction data show that tolterodine immediate release does not result in clinically relevant inhibition of CYP1A2, 2D6, 2C9, 2C19, or 3A4 as evidenced by lack of influence on the marker drugs caffeine, debrisoquine, S-warfarin, and omeprazole [see CLINICAL PHARMACOLOGY (12.3) ].

7.5Drug-Laboratory-Test Interactions

Interactions between tolterodine and laboratory tests have not been studied.

7.6Other Anticholinergics

The concomitant use of tolterodine tartrate extended-release capsules with other anticholinergic (antimuscarinic) agents may increase the frequency and/or severity of dry mouth, constipation, blurred vision, somnolence and other anticholienrgic pharmacological effects.

Adverse reactions

6. ADVERSE REACTIONS 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 most common adverse reactions (incidence > 4% and >placebo) were dry mouth, headache, constipation, and abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Inventia Healthcare Limited, at 1-800-270-7585 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

The efficacy and safety of tolterodine tartrate extended-release capsules was evaluated in 1073 patients (537 assigned to tolterodine tartrate extended-release capsules; 536 assigned to placebo) who were treated with 2, 4, 6, or 8 mg/day for up to 15 months. These included a total of 1012 patients (505 randomized to tolterodine tartrate extended-release capsules 4 mg once daily and 507 randomized to placebo) enrolled in a randomized, placebo-controlled, double-blind, 12-week clinical efficacy and safety study.

Adverse events were reported in 52% (n=263) of patients receiving tolterodine tartrate extended-release capsules and in 49% (n=247) of patients receiving placebo. The most common adverse events reported by patients receiving tolterodine tartrate extended-release capsules were dry mouth, headache, constipation, and abdominal pain. Dry mouth was the most frequently reported adverse event for patients treated with tolterodine tartrate extended-release capsules, occurring in 23.4% of patients treated with tolterodine tartrate extended-release capsules and 7.7% of placebo-treated patients.

Dry mouth, constipation, abnormal vision (accommodation abnormalities), urinary retention, and dry eyes are expected side effects of antimuscarinic agents. A serious adverse event was reported by 1.4% (n=7) of patients receiving tolterodine tartrate extended-release capsules and by 3.6% (n=18) of patients receiving placebo. Table 1 lists the adverse events, regardless of causality, that were reported in the randomized, double-blind, placebo-controlled 12-week study at an incidence greater than placebo and in greater than or equal to 1% of patients treated with tolterodine tartrate extended-release capsules 4 mg once daily.

Table 1. Incidence* (%) of Adverse Events Exceeding Placebo Rate and Reported in ≥1% of Patients Treated with Tolterodine Tartrate Extended-Release Capsules (4 mg daily) in a 12-week, Phase 3 Clinical Trial * in nearest integer. Body System Adverse Event % Tolterodine tartrate extended-release capsules n=505 % Placebo n=507 Autonomic Nervous dry mouth 23 8 General headache 6 5 fatigue 2 1 Central/Peripheral Nervous dizziness 2 1 Gastrointestinal constipation 6 4 abdominal pain 4 2 dyspepsia 3 1 Vision xerophthalmia 3 2 vision abnormal 1 0 Psychiatric somnolence 3 2 anxiety 1 0 Respiratory sinusitis 2 1 Urinary dysuria 1 0 The frequency of discontinuation due to adverse events was highest during the first 4 weeks of treatment.

Similar percentages of patients treated with tolterodine tartrate extended-release capsules or placebo discontinued treatment due to adverse events. Dry mouth was the most common adverse event leading to treatment discontinuation among patients receiving tolterodine tartrate extended-release capsules [n=12 (2.4%) vs. placebo n=6 (1.2%)].

6.2Post-marketing Experience

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; Gastrointestinal : diarrhea ; 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 worldwide post-marketing experience, the frequency of events and the role of tolterodine in their causation cannot be reliably determined.

Tolterodine Tartrate

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Tolterodine Tartrate

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Angioedema Anaphylaxis

5.2Urinary Retention

5.3Gastrointestinal Disorders

5.4Controlled Narrow-Angle Glaucoma

5.5Central Nervous System Effects

5.6Hepatic Impairment

5.7Renal Impairment

5.8Myasthenia Gravis

Interactions

7.1Potent CYP2D6 Inhibitors Fluoxetine,

7.2Potent CYP3A4 Inhibitors Ketoconazole

7.5Drug-Laboratory-Test Interactions

7.6Other Anticholinergics

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Post-marketing Experience

Composition

Strengths and forms

Official product information

At a glance