Veltam S Kit

Uses

Symptomatic treatment of urge incontinence and/or increased urinary frequency and urgency as may occur in patients with overactive bladder syndrome.

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

Veltam S Kit is also used to associated treatment for these conditions: Benign Prostatic Hyperplasia (BPH), Urinary Bladder, OveractiveBenign Prostatic Hyperplasia (BPH), Benign Prostatic Hypertrophy, Bladder Outlet Obstruction, Ureteral Calculus

How Veltam S Kit works

Solifenacin is a competitive muscarinic receptor antagonist. It has the highest affinity for M3, M1, and M2 muscarinic receptors. 80% of the muscarinic receptors in the bladder are M2, while 20% are M3. Solifenacin's antagonism of the M3 receptor prevents contraction of the detrusor muscle, while antagonism of the M2 receptor may prevent contraction of smooth muscle in the bladder.

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.

Dosage

Veltam S Kit dosage

Adults, including the elderly: The recommended dose is Solifenacin Succinate 5 mg once daily. If needed, the dose may be increased to Solifenacin Succinate 10 mg once daily.

Children and adolescents: Safety and effectiveness in children have not yet been established. Therefore, Solifenacin Succinate should not be used in children.

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.

Side Effects

The most common side effects are blurred vision, dry mouth, constipation & heat prostration. Other side effects include dizziness, fatigue, edema, palpitation and skin reactions. Disorientation, hallucination and convulsion may occur.

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.

Toxicity

The LD₅₀ of Solifenacin has yet to be determined.

Signs of overdose include severe anticholinergic effects, mental status changes, and decreased consciousness. In case of overdose, treat patients with gastric lavage and supportive measures. Monitor patients with an ECG.

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

Other causes of frequent urination (heart failure or renal disease) should be assessed before treatment with Solifenacin. If urinary tract infection is present, an appropriate antibacterial therapy should be started. Solifenacin Succinate should be used with caution in patients with clinically significant bladder outflow obstruction at risk of urinary retention, gastrointestinal obstructive disorders, risk of decreased gastrointestinal motility, severe renal impairment (creatinine clearance 30 ml/min), moderate hepatic impairment, concomitant use of a strong CYP3A4 inhibitor, e.g. ketoconazole

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

Interaction

Concomitant medication with other drugs with anticholinergic properties may result in more pronounced therapeutic effects and side effects. The therapeutic effect of solifenacin may be reduced by concomitant administration of cholinergic receptor agonists. Solifenacin can reduce the effect of drugs that stimulate the motility of the gastro-intestinal tract, such as metoclopramide and cisapride. Ketoconazole & other CYP3A4 inhibitors increase the plasma concentration of solifenacin.

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.

Volume of Distribution

The volume of distribution of solifenacin is 600L.

16L after intravenous administration.

Elimination Route

Solifenacin is well absorbed in the duodenum, jejunum, and ileum but not the stomach. Absorption occurs via passive diffusion and so no transporters are involved. The mean oral bioavailability of solifenacin is 88%. The T_max of solifenacin is 3-8 hours with a C_ss of 32.3ng/mL for a 5mg oral dose and 62.9ng/mL for a 10mg oral dose.

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 elimination half life of solifenacin ranges from 33-85 hours.

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.

Clearance

The clearance of solifenacin is 7-14L/h and a renal clearance of 0.67-1.51L/h.

2.88L/h.

Elimination Route

69.2±7.8% of a radiolabelled dose is recovered in the urine, 22.5±3.3% was recovered in feces, and 0.4±7.8% was recovered in exhaled air. 18% of solifenacin is eliminated as the N-oxide metabolite, 9% is eliminated as the 4R-hydroxy N-oxide metabolite, and 8% is eliminated as the 4R-hydroxy metabolite.

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.

Pregnancy & Breastfeeding use

Use in pregnancy: There are no adequate data from the use of solifenacin succinate in pregnant women. Caution should be exercised while prescribing solifenacin to pregnant women.

Use in lactating mother: No data concerning the excretion of solifenacin into breast milk are available. The use of Solifenacin is avoided in lactating mother.

Tamsulosin Hydrochloride capsules are not indicated for use in women.

Contraindication

Solifenacin is contraindicated in patients with hypersensitivity to solifenacin or to any of the excipients. It is also contraindicated in myasthenia gravis, urinary retention, uncontrolled narrow angle glaucoma, severe gastro-intestinal condition (including toxic megacolon), patients undergoing haemodialysis, patients with severe hepatic impairment, patients with severe renal impairment or moderate hepatic impairment and on treatment with a strong CYP3A4 inhibitor, e.g. ketoconazole.

History of orthostatic hypotension. Severe hepatic impairment.

Special Warning

Patients with renal impairment: No dosage adjustment is necessary for patients with mild to moderate renal impairment (creatinine clearance > 30 ml/min). Patients with severe renal impairment (creatinine clearance 30 ml/min) should be treated with caution and receive no more than 5 mg Solifenacin SuccinateTablet once daily.

Patients with hepatic impairment: No dosage adjustment is necessary for patients with mild hepatic impairment. Patients with moderate hepatic impairment should be treated with caution and receive no more than 5 mg Solifenacin SuccinateTablet once daily.

Patients taking CYP3A4 inhibitors concomitantly: The maximum dose of Solifenacin Succinateshould be limited to 5 mg when treated simultaneously with ketoconazole or other potent CYP3A4 inhibitors e.g. ritonavir, nelfinavir or itraconazole.

Use in children: Safety and efficacy of solifenacin in children have not been established.

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

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.

Storage Condition

Store between 20-25° C.

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