Tolterodine
Tolerin®
Antisposmodic (Urinary bladder) (USPDI)
Chemistry
(+)-(R)-2-{ -[(Diisopropylamino)ethyl]benzyl}-p-cresol tartrate C22H31NO,C4 H6O6 = 475.6 (Martindale)
Mechanism of action / Pharmacokinetics
Tolterodine is a competitive muscarinic receptor antagonist for overactive bladder. Infact it is a tertiary antimuscarinic with actions similar to those of atropine and have a greater selectivity for muscarinic receptors of the bladder. After oral administration, tolterodine is metabolized in the liver, resulting in the formation of the 5-hydroxymethyl derivative which exhibits antimuscarinic
activity similar to tolterodine. (Facts,PDR,Martindale,USPDI)
Pharmacokinetics properties
(USPDI,Facts) Indications
Bladder hyperactivity (USPDI)
Contraindication
Tolterodine Tablets are contraindicated in patients with urinary retention, gastric retention, uncontrolled narrow-angle glucoma
and hypersensitivity to the drug or its ingredients. (Facts,PDR)
Warning and precaution
- Patients with significantly reduced hepatic function should not receive doses>1mg twice daily.
- Treat patients with renal impairment with caution.
- Administer with caution to patients with clinically significant bladder outflow obstruction because of the risk of urinary retention. - Administer with caution to patients with GI obstructive disorders, such as pyloric stenosis, because of the risk of gastric retention.
- Use with caution in patients being treated for narrow-angle glaucoma. (Facts)
pregnancy
Category C
Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. (Facts)
Breast - Feeding
Tolterodine is excreted into the milk of mice. It is not known whether tolterodine is excreted in human breast milk, therefore,
discontinue administration during nursing . (Facts,PDR)
Drug Interaction
- Fluoxetine a SSRI and cytochrome P450 2D6 inhibitor, significantly inhibits the metabolism of tolterodine in extensive metabolizers,
however, no dosage adjustment is necessary.
- Patients receiving cytochrome P450 3A4 inhibitors, such as macrolide antibiotics(erythromycin and clarithromycim), antifungal agents(ketoconazole, itraconazole and miconazole), or cyclosporine or vinblastine should not receive doses of tolterodine > 1mg bid.
- Tolterodine is not expected to influence the pharmacokinetics of drugs that are metabolized by cytochrome P450 2D6, such as
flecainide, vinblastine, carbamazepine and TCAs.
- Tolterodine can prolong the QT interval and should be used with caution in patients receiving other drugs known to have this effect, particularly class Ia and class III antiarrhythmics.
- Coadministration of tolterodine immediate release up to 8mg for up to 12 weeks with diuretic agents such as indapamide,
hydrochlorothiazide,triamterene,bendroflumethiazide,chlorothiazide,methylchlorothiazide or furosemide, did not cause any adverse ECG effects.
- Tolterodine immediate release 4 mg had no effect on the pharmacokinetics of an oral contraceptive.
- A few cases of agitation, anxiety, confusion, aggression and delusion precipitated by tolterodine in patients who had been stable on donepezil. (USPDI,PDR,Martindale,Facts)
Adverse reaction
Accommodation abnormal; dry mouth; chest pain; fatigue; headache; influenza-like symptoms; vertigo; dizziness; abdominal pain; constipation; diarrhea; dyspepsia; dysuria; dry skin; arthralgia; xerophthalmia; somnolence; weight gain; infection; hypertension; flatulence; anaphylactoid reactions; including angioedema;
tachycardia; palpations; peripheral edema; hallucinations. (Facts -PDR-USPDI)
Overdosage
A 27-month-old child who ingested 5-7 tablets of 2mg tolterodine was treated with a suspension of activated charcoal and was hospitalized avernight with symptoms of dry mouth. The child fully recoverd . (Facts)
Dosage and Administration
To treat bladder problems:
Adults - 1 to 2 mg two times a day .
Children - use and dose must be determined by doctor. (USPDI) Storage
Store below 30 and away from heat & direct light. (USPDI)
How Supplied
Tolterodine tablets are available containing 1,2 mg tolterodine.The 1mg tablets are white, biconvex & film coated tablet . The 2mg
tablets are white, biconvex, film coated and scored tablets.
Reference
1- PDR 2006 2-USPDI 2006 3-USPDI 204
4- Martindale 2007 5- Drug Facts ne-Tedaphar