Toltam

Toltam Uses, Dosage, Side Effects, Food Interaction and all others data.

Tamsulosin is an antagonist of α1A-adrenoreceptors in the prostate. It binds selectively and competitively to postsynaptic α1A-adrenoreceptors, which convey smooth muscle contraction, thereby relaxing prostatic and urethral smooth muscle.

Tamsulosin is an alpha adrenoceptor blocker with specificity for the alpha-1A and alpha-1D subtypes, which are more common in the prostate and submaxillary tissue. The final subtype, alpha-1B, are most common in the aorta and spleen. Tamsulosin binds to alpha-1A receptors 3.9-38 times more selectively than alpha-1B and 3-20 times more selectively than alpha-1D. This selectivity allows for a significant effect on urinary flow with a reduced incidence of adverse reactions like orthostatic hypotension.

Tolterodine is a competitive, specific muscarinic receptor antagonist which exhibits a selectivity for the urinary bladder over salivary glands, which have been demonstrated in non clinical pharmacological in vivo studies. Tolterodine has a high specificity for muscarinic receptors. A major active metabolite (5-hydroxymethyl derivative) of tolterodine exhibits a pharmacological profile which is similar to that of the parent compound. In extensive metabolisers this metabolite contributes significantly to the therapeutic effect of tolterodine. The effect of treatment can be expected within 4 weeks.

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. The main effects of tolterodine are an increase in residual urine, reflecting an incomplete emptying of the bladder, and a decrease in detrusor pressure, consistent with an antimuscarinic action on the lower urinary tract.

Toltam
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Toltam
Generic	Tamsulosin + Tolterodine
Weight	0.4mg
Type	Capsule
Therapeutic Class
Manufacturer	Intas Pharmaceuticals Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Tamsulosin Hydrochloride is used for the treatment of the signs and symptoms of Benign Prostatic Hyperplasia (BPH).

Tolterodine Tartrate is used for the treatment of overactive bladder with symptoms of urinary urgency, frequency, and/or urge incontinence.

Toltam is also used to associated treatment for these conditions: Benign Prostatic Hyperplasia (BPH), Benign Prostatic Hypertrophy, Bladder Outlet Obstruction, Ureteral CalculusUrinary Bladder, Overactive

How Toltam works

Tamsulosin is a blocker of alpha-1A and alpha-1D adrenoceptors. About 70% of the alpha-1 adrenoceptors in the prostate are of the alpha-1A subtype. By blocking these adrenoceptors, smooth muscle in the prostate is relaxed and urinary flow is improved. The blocking of alpha-1D adrenoceptors relaxes the detrusor muscles of the bladder which prevents storage symptoms. The specificity of tamsulosin focuses the effects to the target area while minimizing effects in other areas.

Both tolterodine and its active metabolite, 5-hydroxymethyltolterodine, act as competitive antagonists at muscarinic receptors. This antagonism results in inhibition of bladder contraction, decrease in detrusor pressure, and an incomplete emptying of the bladder.

Dosage

Toltam dosage

The recommended dose of Tamsulosinis 0.4 mg once daily. It should be administered approximately half/hour following the same meal each day. For those patients who fail to respond to the 0.4 mg dose after two to four weeks of dosing, the dose of Tamsulosin can be increased to 0.8mg once daily. If Tamsulosin administration is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the 0.4 mg once daily dose.

The recommended dose for tolterodine is 2 mg twice daily. In case of troublesome side effects the dose may be reduced from 2 mg to 1 mg twice daily.

The recommended total daily dose of tolterodine is 2 mg (1 mg b.i.d.) for patients with impaired renal function, impaired liver function, or receiving concomitant medication with potent CYP3A inhibitors, such as macrolide antibiotics (e.g. erythromycin and clarithromycin) or azole antifungal agents (e.g. ketoconazole, itraconazole and miconazole). After six months the need for further treatment should be considered.

Side Effects

The following adverse reactions have been reported during the use of Tamsulosin: dizziness, abnormal ejaculation, and less frequently (1-2%) headache, asthenia, postural hypotension, palpitations, and rhinitis.

Gastrointestinal reactions such as nausea, vomiting, diarrhoea, and constipation can occasionally occur. Hypersensitivity reactions such as rash, pruritus, and urticaria can occur occasionally. As with other alpha-blockers, drowsiness, blurred vision, dry mouth, or edema can occur. Syncope has been reported rarely, and there have been very rare reports of angioedema and priapism.

Tolterodine may cause mild to moderate antimuscarinic effects, like dryness of mouth, dyspepsia and/or reduced lacrimation.

Toxicity

In the event of overdose, patients may experience hypotension and should lie down in a supine position to maintain blood pressure and heart rate. If further measures are required intravenous fluids should be considered. If further progression is required, vasopressors may be used and renal function should be monitored. Dialysis is unlikely to assist in treating overdose because tamsulosin is extensively protein bound.

The oral LD50 in rats is 650mg/kg.

Tamsulosin is not indicated for use in women and no studies have been performed in pregnancy, though animal studies have not shown fetal harm. Tamsulosin is excreted in the milk of rats but there is no available data on what the effect of this tamsulosin exposure may be. Animal studies have shown male and female rat fertility is affected by tamsulosin due to impairment of ejaculation and fertilization. In men, tamsulosin is associated with abnormal ejaculation. Tamsulosin is not mutagenic but may be carcinogenic at levels above the maximum recommended human dose. Female rats experience a slight increase in the rates of mammary gland fibroadenomas and adenocarcinomas.

Precaution

Not indicated for use in women. Severe renal impairment (CrCl <10 mL/min). Pregnancy and lactation.

Tolterodine should be used with caution in the following patients:

at risk for urinary retention
at risk for decreased gastrointestinal motility
with impaired renal function
with impaired hepatic function

Organic reasons for urge and frequency should be considered before treatment.

Interaction

Increased plasma concentration with strong CYP3A4 inhibitors (e.g. ketoconazole). Moderate CYP3A4 inhibitors (e.g. erythromycin), strong (e.g. paroxetine) or moderate (e.g. terbinafine) CYP2D6 inhibitors may increase exposure of tamsulosin. Increased plasma concentration with cimetidine. Additive effect with other α-adrenergic blocking agents. Concomitant use with PDE5 inhibitors may lead to symptomatic hypotension. Decreased plasma concentration with furosemide.

Pharmacokinetic interactions are possible with other drugs metabolised by or inhibiting cytochrome P450 2D6 (CYP2D6) or CYP3A4. Concomitant treatment with fluoxetine does not result in a clinically significant interaction.

Ketoconazole, a potent inhibitor of CYP3A, significantly increased plasma concentrations of tolterodine when coadministered to poor metabolisers (i.e. persons devoid of CYP2D6 metabolic pathway).

Clinical studies have shown no interactions with warfarin or combined oral contraceptives (ethinyloestradiol or levonorgestrel).

Volume of Distribution

16L after intravenous administration.

113 ± 26.7 L

Elimination Route

Oral tamsulosin is 90% absorbed in fasted patients. The area under the curve is 151-199ng/mL*hr for a 0.4mg oral dose and 440-557ng/mL*hr for a 0.8mg oral dose. The maximum plasma concentration is 3.1-5.3ng/mL for a 0.4mg oral dose and 2.5-3.6ng/mL for a 0.8mg oral dose. Taking tamsulosin with food increases the time to maximum concentration from 4-5 hours to 6-7 hours but increases bioavailability by 30% and maximum plasma concentration by 40-70%.

Half Life

The half life in fasted patients is 14.9±3.9 hours. The elimination half life is 5-7 hours and the apparent half life is 9 to 13 hours in healthy subjects. In patients who require tamsulosin, the apparent half life is 14-15 hours.

1.9-3.7 hours

Clearance

2.88L/h.

Elimination Route

97% of an orally administered does is recovered in studies, which 76% in the urine and 21% in the feces after 168 hours. 8.7% of the dose is excreted as unmetabolized tamsulosin.

Following administration of a 5-mg oral dose of 14C-tolterodine solution to healthy volunteers, 77% of radioactivity was recovered in urine and 17% was recovered in feces in 7 days.

Pregnancy & Breastfeeding use

Tamsulosin Hydrochloride capsules are not indicated for use in women.

There are no studies in pregnant women. Therefore, tolterodine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use of tolterodine during lactation should be avoided since no data on excretion of the drug into breast milk in humans is available.

Contraindication

History of orthostatic hypotension. Severe hepatic impairment.

Tolterodine is contraindicated in those patients with urinary retention, uncontrolled narrow angle glaucoma, known hypersensitivity to tolterodine or any other component of the drug.

Special Warning

Tamsulosin Hydrochloride capsules are not indicated for use in pediatric populations.

Pediatric use: Safety and effectiveness of tolterodine in children have not been established.

Geriatric use: No overall differences in safety were observed between the older and younger patients treated with Tolterodine.

Acute Overdose

As overdose of Tamsulosin Hydrochloride capsules lead to hypotension, support the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in supine position. If this measure is inadequate, then administration of intravenous fuid should be considered. Measures, such as emesis, can be taken to impede absorption. When large quantities are involved, gastric lavage can be applied and activated charcoal and an osmotic laxative, such as sodium sulphate, can be administered.

Overdosage with Tolterodine Tartrate capsules can potentially result in severe central anticholinergic effects and should be treated accordingly. ECG monitoring is recommended in the event of overdosage.