TAMSOLIN-S TABLETS (0.4MG+6MG)

Indications

• Benign prostatic hyperplasia
• Bladder outlet obstruction
• Urinary retention

Dosage

Children: Not established; refer to BNF for Children for any potential dosing information.

Adults: Initially 400 micrograms once daily, taken after a meal. Dosage may be adjusted based on clinical response and tolerability, typically not exceeding 800 micrograms daily.

Mechanism of action

Tamsulosin exerts its therapeutic effects through selective antagonism of the alpha-1A adrenergic receptors found predominantly in the smooth muscle of the prostate and bladder neck. This action results in relaxation of these muscles, leading to improved urinary flow and reduced bladder outlet obstruction.

Pharmacodynamics

The pharmacodynamics of Tamsulosin involve its ability to decrease urinary resistance and improve urinary flow rates. It exhibits a preferential binding affinity for the alpha-1A receptors compared to alpha-1B receptors, which minimizes cardiovascular side effects commonly associated with non-selective alpha blockers. The onset of action typically occurs within a few days of starting treatment, although maximum benefits may take several weeks.

Pharmacokinetics

Tamsulosin is well-absorbed from the gastrointestinal tract, with peak plasma concentrations occurring approximately 6 hours post-administration. It has a bioavailability of about 90% due to extensive first-pass metabolism. The drug is primarily metabolized in the liver via CYP2D6 and CYP3A4 pathways, resulting in several active metabolites. Tamsulosin has a half-life of approximately 15 hours, allowing for once-daily dosing. It is excreted mainly in urine as metabolites, with less than 10% of the drug eliminated unchanged.

Contra-indications

• History of micturition syncope
• History of postural hypotension
• Congestive heart failure (due to mechanical obstruction such as aortic stenosis)

Adverse effects

• Asthenia
• Dizziness
• Constipation
• Fatigue
• Sweating

Interactions

• Caution with concomitant antihypertensives
• Potential for additive hypotensive effects when used with other antihypertensives

Precautions

• Caution in elderly patients due to risk of first dose hypotension
• Care during cataract surgery due to risk of intra-operative floppy iris syndrome
• Monitor for symptomatic orthostatic hypotension

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if clearly needed.

Breast-feeding

It is not known whether tamsulosin is excreted in human milk. Caution is advised when administering to breastfeeding mothers.

Storage

Store below 25 degrees Celsius. Keep the container tightly closed.

Formulations

• Tamsulosin hydrochloride 400 microgram capsules
• Tamsulosin hydrochloride 500 microgram tablets
• Tamsulosin hydrochloride modified-release capsules

Indications

• Urinary frequency
• Urgency
• Incontinence associated with overactive bladder
• Incontinence associated with neurogenic bladder instability

Dosage

Children: Refer to the BNF for Children for appropriate dosing information, as specific pediatric dosing is not provided.

Adults: 15 mg once daily, increased if necessary to a maximum of 30 mg once daily for immediate-release formulations. For modified-release capsules, the usual dose is 30 mg once daily.

Mechanism of action

Solifenacin succinate selectively inhibits the M3 subtype of muscarinic acetylcholine receptors, which are primarily responsible for bladder contraction. By blocking these receptors, solifenacin reduces detrusor muscle overactivity, leading to decreased urinary frequency and urgency.

Pharmacodynamics

The pharmacodynamic effects of solifenacin include a reduction in bladder contractions, increased bladder capacity, and diminished urgency to void. Its antimuscarinic properties help alleviate the symptoms associated with overactive bladder, providing symptomatic relief in patients with urinary incontinence.

Pharmacokinetics

Solifenacin is well absorbed after oral administration, with peak plasma concentrations occurring approximately 3 to 8 hours post-dose. It has a bioavailability of around 90% and is extensively metabolized in the liver via CYP3A4. The elimination half-life is approximately 45 hours, allowing for once-daily dosing. Renal impairment can affect its clearance, necessitating dose adjustments in patients with reduced creatinine clearance.

Contra-indications

• Severe hepatic impairment
• Moderate to severe renal impairment
• Hypersensitivity to solifenacin or any of its excipients

Adverse effects

• Abdominal pain
• Fatigue
• Altered taste
• Tremor
• Restlessness
• Hallucination
• Anaphylactic reaction
• Delirium
• Dysphonia
• Muscle weakness
• QT interval prolongation

Interactions

• Anticholinergic agents may enhance effects
• CYP3A4 inhibitors (e.g., ketoconazole) may increase solifenacin levels
• CYP3A4 inducers (e.g., rifampicin) may decrease solifenacin levels
• Concurrent use of medications that prolong QT interval should be approached with caution

Precautions

• Caution in patients with gastrointestinal disorders
• Caution in elderly patients due to increased sensitivity
• Caution in patients with a history of glaucoma
• Caution in patients with urinary retention

Pregnancy

Manufacturer advises caution due to lack of information available on safety in pregnancy.

Breast-feeding

Manufacturer advises avoiding use as solifenacin is present in milk in animal studies.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Oral solution: Solifenacin succinate 1 mg per 1 ml
• Modified-release capsule: Solifenacin succinate 5 mg
• Modified-release capsule: Solifenacin succinate 30 mg

Indications

• Overactive bladder
• Urinary incontinence
• Urinary urgency
• Urinary frequency

Dosage

Children: Safety and efficacy have not been established in children; refer to BNF for Children for specific dosing recommendations.

Adults: The usual adult dose is 5 mg once daily, which may be increased to 10 mg once daily based on individual patient response and tolerability.

Mechanism of action

Solifenacin competitively inhibits muscarinic receptors, with a high affinity for M3, M1, and M2 receptors. By antagonizing the M3 receptor, it prevents detrusor muscle contraction, while antagonism of the M2 receptor may inhibit contraction of bladder smooth muscle, thereby alleviating symptoms of overactive bladder.

Pharmacodynamics

The drug effectively reduces symptoms associated with overactive bladder by blocking the muscarinic receptors. Its long duration of action allows for once-daily dosing, providing consistent symptom control. However, patients should be monitored for potential adverse reactions such as angioedema and anaphylaxis, which can occur in some individuals.

Pharmacokinetics

Solifenacin is absorbed well following oral administration, with peak plasma concentrations occurring approximately 3 to 8 hours after dosing. It undergoes hepatic metabolism primarily via cytochrome P450 enzymes, leading to various metabolites, some of which may retain pharmacological activity. The elimination half-life is around 45 to 68 hours, supporting its once-daily dosing regimen. Renal and hepatic function may influence the drug's clearance.

Adverse effects

• dry mouth
• constipation
• blurred vision
• urinary retention
• angioedema
• anaphylaxis

Interactions

• clozapine+solifenacin: Unknown (additive effect)
• cobicistat+solifenacin: Unknown (increases exposure)
• idelalisib+solifenacin: Unknown (increases exposure)
• clarithromycin+solifenacin: Unknown (increases exposure)
• mitotane+solifenacin: Unknown (decreases exposure)
• rifampicin+solifenacin: Unknown (decreases exposure)
• antipsychotics, second generation+solifenacin: Unknown (additive effect)

Pregnancy

The safety of solifenacin during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Solifenacin is excreted in breast milk. Caution is advised when administered to nursing women.

Storage

Store in a cool, dry place, away from direct sunlight and moisture. Keep out of reach of children.

Formulations

• tablets

Indications

• Benign Prostatic Hyperplasia (BPH)
• Lower urinary tract symptoms associated with BPH

Dosage

Children: null

Adults: The usual dose is 400 micrograms once daily, taken approximately 30 minutes after the same meal each day.

Mechanism of action

Tamsulosin selectively blocks alpha-1A and alpha-1D adrenoceptors, which are prevalent in the prostate and bladder respectively. This leads to relaxation of the smooth muscle in the prostate and the bladder neck, thereby enhancing urinary flow. The drug's specific action on alpha-1A receptors minimizes effects on vascular smooth muscle, resulting in a lower incidence of adverse cardiovascular effects.

Pharmacodynamics

Tamsulosin exhibits selective antagonism of alpha-1 adrenergic receptors, with a greater affinity for alpha-1A and alpha-1D subtypes compared to alpha-1B. This selectivity allows for effective relief of urinary symptoms associated with BPH while reducing the risk of orthostatic hypotension and other cardiovascular side effects. Its pharmacodynamic profile supports improved urinary flow rates without significant hemodynamic changes.

Pharmacokinetics

Tamsulosin is well absorbed after oral administration and reaches peak plasma concentrations within 4 to 6 hours. It has a high protein binding rate (approximately 99%) and is primarily metabolized by the liver via cytochrome P450 enzymes, notably CYP3A4. The elimination half-life is approximately 9 to 15 hours, allowing for once-daily dosing. The drug is excreted mainly in the urine, with both unchanged drug and metabolites found in the urine.

Adverse effects

• dizziness
• headache
• nasal congestion
• semen abnormality
• orthostatic hypotension

Interactions

• cobicistat+tamsulosin: Moderate (increases exposure)
• idelalisib+tamsulosin: Moderate (increases exposure)
• antifungals, azoles+tamsulosin: Unknown (increases exposure)
• crizotinib+tamsulosin: Unknown (increases exposure)
• imatinib+tamsulosin: Unknown (increases exposure)
• letermovir+tamsulosin: Unknown (increases exposure)
• nilotinib+tamsulosin: Unknown (increases exposure)
• dronedarone+tamsulosin: Unknown (increases exposure)
• erythromycin+tamsulosin: Unknown (increases exposure)

Pregnancy

Tamsulosin is not recommended during pregnancy due to limited data on its safety.

Breast-feeding

It is unknown whether tamsulosin is excreted in human milk; caution is advised.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Capsules 0.4 mg

Mechanism of action

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.

Pharmacodynamics

Solifenacin antagonizes the M2 and M3 muscarinic receptors in the bladder to treat an overactive bladder. It has a long duration of action as it is usually taken once daily. Patients taking solifenacin should be aware of the risks of angioedema and anaphylaxis.

Mechanism of action

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. Tamsulosin hydrochloride is a sulfamoylphenethylamine-derivative alpha1-adrenergic blocking agent. The drug is pharmacologically related to doxazosin, prazosin, and terazosin; however, unlike these drugs, tamsulosin has higher affinity and selectivity for alpha1A-adrenergic receptors, which are mainly located in nonvascular smooth muscle (eg, prostate), than for alpha1B-adrenergic receptors located in vascular smooth muscle (eg, internal iliac artery). Results of in vitro studies indicate that tamsulosin has 7-38 times greater affinity for alpha1A-adrenoceptors than for alpha1B-adrenoceptors; the drug has about 12 times greater affinity for alpha1-adrenergic receptors in the prostate than for those in the aorta. Such selectivity of tamsulosin for alpha1A-receptors may result in a reduced incidence of adverse cardiovascular effects (eg, syncope, dizziness, hypotension). On a molar basis, the alpha1-adrenergic receptor affinity of tamsulosin is about 6 times that of prazosin when tested in human prostatic tissue. Because of the prevalence of alpha-receptors on the prostate capsule, prostate adenoma, and bladder trigone and the relative absence of these receptors on the bladder body, alpha-adrenergic blocking agents decrease urinary outflow resistance in men. The symptoms associated with benign prostatic hyperplasia (BPH) are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma. However, the severity of BPH symptoms and the degree of urethral obstruction do not correlate well with the size of the prostate. The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha1 adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH. The influence of (+/-)-tamsulosin, a selective alpha 1A-adrenoceptor antagonist, on the positive inotropic effect and the accumulation of inositol phosphates that are induced via alpha 1-adrenoceptors was studied in comparison with that of another alpha 1A-adrenoceptor ligand oxymetazoline in the rabbit ventricular myocardium. Phenylephrine elicited a concentration-dependent positive inotropic effect via alpha 1-adrenoceptors in the presence of either (+/-)-bupranolol or S(-)-timolol. The mode of antagonism induced by (+/-)-tamsulosin on the effect of phenylephrine was dependent or the concentration applied: (+/-)-tamsulosin at 1 and 3 nM acted in a competitive manner, the slope of the regression line of the Schild plot being unity and the pA2 value being 9.12; at 10 nM, it shifted further the concentration-response curve to the right without affecting the maximal response but the slope became less than unity. At 100 nM and higher, it suppressed the maximal response to phenylephrine. (+/-)-Tamsulosin effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of alpha 1B-adrenoceptors by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resist

Pharmacodynamics

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.