Tolterodine - Indications, Contraindications, Warnings, and Precautions

Overview

Tolterodine is a widely preferred and FDA (Food and Drug Administration) endorsed medication that tackles premature bladder muscle contractions, which necessitates the patients to urinate more repeatedly. Tolterodine is marketed as a prescription medicine that can be purchased from the pharmacy only with a doctor’s prescription. It is considered to be the hallmark treatment option for hyperactive bladder.

Drug Group:

Tolterodine falls under the class of antimuscarinic drugs, which elicit its action by impeding the functions of specific receptors in the human body. The chemical structure of Tolterodine is of the tertiary amine.

Available Doses and Dosage Forms:

• Dosage Forms: Tolterodine is marketed in three distinct forms - tablet, capsule form, and transdermal gel. Capsule form is specifically designed for prolonged release of the medicine and is marketed as extended-release capsules. Such capsules ensure consistency in the drug concentration in the body. Transdermal gels are effective in maintaining drug concentration in circulation for a period of 72 hours.

• Available Doses: It is made available in two milligrams (mg) and four mg doses.

Uses

The primary and accepted usage of Tolterodine is for tackling the manifestations associated with overactive bladder. No other therapeutic application of Tolterodine has been accepted by the FDA.

For Patients:

What Is an Overactive Bladder?

Overactive bladder is a specific illness, where the person encounters trouble with urination. The person experiences an enhanced tendency to urinate (urgency). In addition, the number of times the person urinates a day (frequency) may also rise up, making it really uncomfortable for the patients. At times, the person may even lose control over urination and unknowingly and unintentionally pass the urine (incontinence). Though it can develop in both genders, reports suggest a slight preference towards the female population. It not only impacts the quality of life but also hampers the social and interactive life of the person, which could eventually have reflections on their mental health. The symptoms can be highly distressing for the person.

There are a number of causes that can give rise to overactive bladder conditions. It may develop as a result of impact or trauma to the lower abdominal region, nerve injury, hormonal disparity, infections involving the bladder, or certain medications. Both non-surgical and surgical measures are available to tackle the distressing symptoms of an overactive bladder. In addition to medical therapy, exercises to boost the strength of the pelvic floor do help in dealing with the symptoms.

How Does Tolterodine Work?

Tolterodine works by interfering with the functions of muscarinic receptors, which largely control smooth muscle activities, especially in the bladder. It is basically a muscle relaxant that interrupts the premature tightening (contractions) of the smooth muscles that form the bladder wall, where urine is stored till the time of release. Persistent tightening of the smooth muscles in the bladder induces a frequent tendency to pass urine and precipitates manifestations of an overactive bladder. By relaxing those hyperactive smooth muscles, Tolterodine brings down the frequency, and urgency of urination, which is induced by an overactive bladder condition.

What Is the Dosage of Tolterodine?

A daily intake of four milligrams of Tolterodine is advised to be ideal for adult patients suffering from overactive bladder. For regular Tolterodine capsules, the specified dose can be administered as two divided doses, and for slow-release capsules, it can be given as a single dose. However, the dose can be altered and can be reduced to half (two milligrams a day) by taking into account the patient’s tolerability and drug response. A daily dose of two mg of Tolterodine is preferred in case of patients with impaired liver functions, specifically mild to moderate impairments. The administration of Tolterodine in patients with severely impaired liver functions is not appreciated because of the lack of reliable data concerning the efficacy and safety of the medicine in such patients. For younger patients over two years of age, the dose ranges between one milligram to four milligrams. Considerable alterations in the dosage of Tolterodine are advised when it is simultaneously administered with other medicines.

How Effective Is Tolterodine?

Tolterodine is proven to be effective in dealing with urinary manifestations of overactive bladder. Prompt therapy with Tolterodine remarkably reduces the tendency for repeated urination. Urinary incontinence is a medical condition where the person experiences trouble in controlling urine, and at times, urination occurs unintentionally. It can also be tackled with Tolterodine therapy. Hence it is claimed to be the gold-standard medicinal therapy for overactive bladder conditions. Evident improvements can be appreciated within a couple of weeks following the initiation of Tolterodine therapy.

What Are the Things to Inform the Doctor Before Taking the Drug?

• Before commencing the therapy using Tolterodine, the patients are instructed to inform the doctor about prior hyper-reactivity issues encountered with the same drug, related medicine, or any of the components in Tolterodine medicine.

• In case the person has other comorbidities or ailments, be they minor or major, that should be properly discussed with the doctor to confirm the safety of the medicine in that particular medical condition. Any history of heart problems, urinary issues, or vision loss should be notified, as Tolterodine can have a negative impact on certain health issues.

• Likewise, the doctor should be informed about all other medications, allopathic and herbal, including dietary supplements, to look for any undesired drug-to-drug associations.

• The doctor should be updated about the pregnancy and breastfeeding status of the patient before starting Tolterodine. The doctor will then consider the case and make a decision accordingly to safeguard the health of both the mother and child.

• Tolterodine can induce sleepiness following consumption. Hence it can interfere with driving and other activities that require fine motor skills. If the person is working in such sectors, then it should be discussed with the doctor before treatment commences.

How Is Tolterodine Administered?

Tolterodine is widely advised in the pill form for oral intake. It is recommended to be taken with water without manipulating the pill by fracturing or powdering it. Transdermal Tolterodine patches are also available for pharmacological purposes and are occasionally prescribed for overactive bladder.

What Are the Side Effects of Tolterodine?

• The most frequently encountered side effect of Tolterodine is dryness in the mouth and eyes. The skin also exhibits dryness and flaking. Dryness in the eyes often elicits disturbances in vision and contributes to hazy and unclear vision.

• The patient experiences sleepiness, fatigue, and occasional headache. In addition, certain patients reported an appreciable loss in body weight. Vomiting, stomach pain, constipation, or diarrhea are also precipitated following Tolterodine administration.

• Tolterodine may, at times, precipitate pain and discomfort while passing the urine. The patient develops exhausted and worn-out feelings. Joint pain and anxiety issues are often seen with Tolterodine intake.

• Some of the potential side effects associated with Tolterodine include bloody urine, elevated body temperature, chills, and sometimes the person experiences trouble voiding urine completely. However, certain adverse reactions like sudden swelling (edema) over the face, eyelids, and lips entail immediate medical care. It is often accompanied by troubled breathing.

Dietary Considerations:

There are no specific dietary instructions to be followed while on Tolterodine therapy. Studies have proven that food does not induce any remarkable change in the effect of Tolterodine.

Missed Dose:

Though the patients strictly follow the dosage regimen instructed by the doctors, at times, the patient may forget to take the medicine on time. In such cases, the medicine should be taken once the patient becomes aware of the skipped dose. In case the patient gets to know about the missed dose when it is time for the subsequent dose, it is advised to disregard the missed one. Make sure not to take double the instructed dose, just to replace the missed one.

Overdose:

Consuming more than the intended doses of Tolterodine can significantly impact the person’s health condition. There will be an appreciable amplification of certain side effects like dryness in the mouth. In severe overdose, the functioning of the heart and kidneys will be considerably affected. Upon exposure to an overdose of Tolterodine, the cardiac electrical activity of the patient should be monitored to track deviations and abnormalities.

Storage:

The recommended storage temperature for Tolterodine is 68 to 77 degrees Fahreinheit (20 to 25 degrees Celsius). However, it can be safely stored under the temperature range of 59 to 86 degree Fahreinheit (15 to 30 degrees Celsius) without inducing any compositional changes. The pills should never be exposed to high temperatures, sunlight, and moisture. Keep the pills inaccessible to small kids to check accidental intake and toxicity in children.

For Doctors:

Indications:

• Overactive bladder (manifesting enhanced urgency and frequency of urination along with urinary incontinence).

Dose:

1. Adult Dose: Dosage for adult patients is based on

• Immediate-Release Capsule: For immediate-release capsules, the recommended daily dosage is two milligrams of the Tolterodine capsule two times.

• Extended-Release Capsule: The recommended daily dosage of extended-release Tolterodine capsule is four milligrams as a single dose.

2. Pediatric Dose: In the case of pediatric patients, the dose is determined by considering the body weight to prevent the chances of overdose. For pediatric patients over the age range of one month to 15 years, 0.03 to 0.12 milligrams of the medicine per kilogram of body weight is advised.

Dosing Considerations:

The dose of Tolterodine should be restricted in case of hepatic impairment of mild to moderate degree, and the dose should not exceed 2 mg a day. Severely impaired liver functions have the potential to precipitate certain complications upon Tolterodine intake, and hence it is not recommended in such patients.

What Are the Pharmacological Aspects of Tolterodine?

• Mechanism of Action: Tolterodine works by acting on the cholinergic muscarinic receptors. Smooth muscle contractions in the urinary bladder are largely controlled by these muscarinic receptors. Tolterodine blocks acetylcholine from attaching to the muscarinic M3 receptors on the bladder detrusor muscles. The acetylcholine attachment makes the muscle contract, bringing in the tendency to pass urine. The interaction of Tolterodine with muscarinic receptors collapses bladder muscle tonicity and its contractions. At the same time, it enhances the tonicity of the urethral sphincter, thereby offering more control over urination.

• Pharmacodynamics: Tolterodine elicits direct impacts on bladder contractions and thereby tackles premature tendency to pass urine.

• Pharmacokinetics: Following Tolterodine oral consumption, it gets absorbed into the bloodstream from the intestine and attains the utmost concentration in two to six hours. Tolterodine gets distributed throughout the body with the help of plasma proteins. Only a minor proportion of Tolterodine circulates unbounded. A liver enzyme, primarily cytochrome 2D6, is responsible for metabolizing the drug molecules into 5- 5-hydroxymethyl tolterodine (5-HMT), which is the reactive form of Tolterodine. In addition to 5-HMT, N-dealkylated 5-carboxylic acid and 5-carboxylic acid byproducts are also formed as a result of Tolterodine metabolism. The elimination of Tolterodine is carried out via both the excretory routes, urinary and fecal. However, the urinary route is the major path of elimination.

Toxicity:

Non-clinical studies failed to demonstrate an appreciable impact on fertility upon exposure to Tolterodine. Similarly, it has been concluded that Tolterodine does not induce toxic changes in the cells like carcinogenesis or mutagenesis. However, there is no confirmation regarding toxicity in the human population.

Clinical Studies:

A clinical study of Tolterodine against placebo was conducted to assess the effectiveness of the drug. It reported an appreciable improvement in incontinence, along with an obvious reduction in the frequency of urination. In addition, the amount of urine that is passed out during each urination also improved in patients who received Tolterodine therapy.

What Are the Contraindications of Tolterodine?

Tolterodine is strictly not advised to be taken by individuals who suffer from the following conditions:

• Urinary retention.

• Gastric retention.

• Narrow-angle glaucoma.

• Allergy towards Tolterodine.

• Allergy towards Fesoterodine fumarate slow-release tablet.

Warnings and Precautions:

• Angioedema: Tolterodine is capable of triggering angioedema, particularly upon exposure to the first dose. Face elicits puffiness at times and may extend into the respiratory tissues, which can cause trouble in breathing. It is manifested in the form of obstructed breathing with a sudden dip in blood pressure. Angioedema requires prompt treatment, or else it can endanger the person’s life.

• Narrow-Angle Glaucoma: Patients who are simultaneously undergoing treatment for narrow-angle glaucoma should be cautiously given Tolterodine. Prior to the initiation of Tolterodine therapy, make sure that the glaucoma is under control. Untreated narrow-angle glaucoma is a potential contraindication and hence should be given special emphasis.

• Urinary Retention: Tolterodine is more likely to induce urinary retention when administered to individuals with remarkably obstructed urinary outflow from the bladder.

• Gastrointestinal Disorders: In addition to urinary retention, Tolterodine can also precipitate gastric retention by gearing down the motility of the gastrointestinal tract. Therefore individuals suffering from obstructive conditions involving the gastrointestinal tract are more likely to elicit gastric retention and other associated complications.

• Myasthenia Gravis: Certain studies have shown that Tolterodine can interfere with myasthenia gravis and aggravate the condition. Hence, it should be given cautiously to such patients.

• Renal and Hepatic Impairment: Patients with considerably impaired renal and hepatic functions require dose alteration so that the organs are not overburdened and stressed.

• Effects on the Central Nervous System: Tolterodine precipitates anticholinergic effects on the body, like sleepiness, dizziness, and fatigue. The symptoms are more pronounced during the therapy initiation period and dose modification periods.

What Are the Drug Interactions of Tolterodine?

Tolterodine is reported to have interactions with certain other medicines and thereby influence the effectiveness of either or both medicines. Some of the potential interactions of Tolterodine include the following:

• Drugs that act by inhibiting the cytochrome enzyme CYP2D6, which is responsible for the processing of Tolterodine, interfere with the blood concentration of Tolterodine when administered concurrently. The concentration of the active form of Tolterodine (5-HMT), formed by the metabolism, collapses drastically. Hence, both Tolterodine and Fluoxetine, when given together, entail special attention and monitoring.

• Simultaneous intake of Tolterodine with Ketoconazole, which is a cytochrome 3A4 inhibitor, alters the utmost concentration of Tolterodine.

Specific Considerations:

• Tolterodine During Pregnancy: The restricted knowledge regarding the influence of Tolterodine on the developing fetus makes it difficult to establish a clear and conclusive decision regarding the exposure of Tolterodine to pregnant women. Animal studies have proven its safety during pregnancy. However, its effect on pregnant women is still under discussion.

• Tolterodine During Breastfeeding: Breastfeeding carries the risk of passing the medicine to the breastfed child through the mother’s milk. In addition, certain maternal medications interfere with milk production, which can impact the child’s health. Because of the lack of sufficient data regarding the safety of Tolterodine intake while breastfeeding, it is advised only after considering the therapeutic need for maternal health.