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Tamsulosin

G04C - Drugs used in benign prostatic hypertrophy ATC G04CA02 Small molecule approved 1997 Oral Natural product

JFDA label: Omnic Ocas

Mechanism of Action

Tamsulosin is an antagonist of alpha1A-adrenoreceptors in the prostate. Smooth muscle tone in the prostate is mediated by alpha1A-adrenoreceptors; blocking them leads to relaxation of smooth muscle in the bladder neck and prostate causing an improvement of urine flow and decreased symptoms of BPH. Approximately 75% of the alpha1-receptors in the prostate are of the alpha1A subtype.

Indications

Approved

  • Benign prostatic hyperplasia

Off-label

  • Bladder outlet obstruction symptoms
  • Ureteral calculi (distal)

Contraindications

Source: Lexicomp

  • Additional contraindications (not in US labeling): Concomitant use with strong CYP3A4 inhibitors (including ketoconazole) Absolute
  • Hypersensitivity (eg, angioedema, rash, urticaria, pruritus, respiratory symptoms) to tamsulosin or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Cardiac disorders (1)

Very Common Orthostatic hypotension Central nervous system: Headache, dizziness

Nervous system disorders (3)

Common Drowsiness · insomnia · vertigo

Renal and urinary disorders (1)

Very Common Ejaculation failure

Metabolism and nutrition disorders (1)

Common Loss of libido

Gastrointestinal disorders (2)

Common Diarrhea · nausea

Musculoskeletal and connective tissue disorders (2)

Common back pain · Weakness

Eye disorders (1)

Common Blurred vision

Infections and infestations (1)

Very Common Infection

Respiratory, thoracic and mediastinal disorders (4)

Very Common Rhinitis

Common cough · Pharyngitis · sinusitis

Dosing

Source: Lexicomp

Benign prostatic hyperplasia (BPH): Males: Oral: 0.4 mg once daily ~30 minutes after the same meal each day; dose may be increased after 2 to 4 weeks to 0.8 mg once daily in patients who fail to respond. If therapy is discontinued or interrupted for several days, restart with 0.4 mg once daily. Bladder outlet obstruction symptoms (off-label use): Oral: 0.4 mg once daily (Rossi, 2001) Ureteral calculi (distal) expulsion (off-label use): Oral: 0.4 mg once daily, discontinue after successful expulsion (average time to expulsion was 1 to 2 weeks) (Agrawal, 2009; Ahmed, 2010). Note: Patients with stones >10 mm were excluded from studies.
Refer to adult dosing.
CrCl ≥10 mL/minute: No dosage adjustment necessary. CrCl
Mild-to-moderate impairment: No dosage adjustment is necessary. Severe impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).

Warnings & Precautions

Source: Lexicomp

Angina

Discontinue if symptoms of angina occur or worsen.

Floppy iris syndrome

Intraoperative floppy iris syndrome (IFIS) is characterized by a combination of flaccid iris that billows with intraoperative currents, progressive intraoperative miosis despite dilation, and potential iris prolapse. IFIS has been observed in cataract and glaucoma surgery patients who were on or were previously treated with alpha1-blockers, particularly with tamsulosin use (Abdel-Aziz, 2009); in some cases, patients had discontinued the alpha1-blocker 5 weeks to 9 months prior to the surgery. The benefit of discontinuing alpha-blocker therapy prior to cataract or glaucoma surgery has not been established. IFIS may increase the risk of ocular complications during and after surgery. May require modifications to surgical technique; instruct patients to inform ophthalmologist of current or previous alpha1-blocker use when considering eye surgery. Initiation of tamsulosin therapy in patients with planned cataract or glaucoma surgery is not recommended.

Orthostatic hypotension/syncope

May cause significant orthostatic hypotension and syncope, especially with first dose; anticipate a similar effect if therapy is interrupted for a few days, if dosage is rapidly increased, or if another antihypertensive drug (particularly vasodilators) or a PDE-5 inhibitor (eg, sildenafil, tadalafil, vardenafil) is introduced. “First-dose” orthostatic hypotension may occur 4-8 hours after dosing; may be dose related. Patients should be cautioned about performing hazardous tasks, driving, or operating heavy machinery when starting new therapy or adjusting dosage upward.

Priapism

Priapism has been associated with use (rarely).

Sulfonamide allergy

Rarely, patients with a sulfa allergy have also developed an allergic reaction to tamsulosin; avoid use when previous reaction has been severe or life-threatening. Disease-related concerns:

Heart failure

In a scientific statement from the American Heart Association, tamsulosin has been determined to be an agent that may exacerbate underlying myocardial dysfunction (magnitude: moderate) (AHA [Page 2016]).

Prostate cancer

It is recommended to rule out prostatic carcinoma with screening before beginning therapy and then screen at regular intervals. Concurrent drug therapy issues:

Limitation of use

Not intended for use as an antihypertensive drug.

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events were not observed in animal reproduction studies. For pregnant women with kidney stones, other treatments such as stents or ureteroscopy, are recommended if stone removal is needed (Preminger, 2007; Tan, 2013).

Lactation

Compatible Hale L1

If tamsulosin is required by the mother, it is not a reason to discontinue breastfeeding.

Monitoring

Clinical pearlBlood pressure; urinary symptoms

Chemistry & Properties

2D structure
FormulaC20H28N2O5S
Molecular weight408.52 g/mol
IUPAC name5-[(2R)-2-[2-(2-ethoxyphenoxy)ethylamino]propyl]-2-methoxybenzenesulfonamide
CAS106133-20-4
PubChem CID129211
InChIKeyDRHKJLXJIQTDTD-OAHLLOKOSA-N
logP2.34 (XLogP 2.7)
Polar surface area99.88 Ų
H-bond acceptors / donors6 / 2
Drug-likeness (QED)0.55
Lipinski violations0
SMILESCCOc1ccccc1OCCN[C@H](C)Cc1ccc(OC)c(S(N)(=O)=O)c1

Biology & Pharmacokinetics

Pharmacokinetics

BBB penetrantNo

Enzyme interactions

EnzymeRoleDetail
CYP1A2Inhibitor
CYP2B6Inhibitor
CYP2C8Inhibitor
CYP2D6Inhibitor
CYP2D6Substrate
CYP3A4Substrate

Receptor binding (top 5)

TargetActionAffinity
alpha1A Binding pKi 10.2
adrenergic Alpha1A (ADRA1A) Binding pKi 9.9
alpha1B Binding pKi 9.9
adrenergic Alpha1D (ADRA1D) Binding pKi 9.8
adrenergic Alpha1B (ADRA1B) Binding pKi 8.8

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)MDR1 (Substrate)P-gp (Substrate)

Drug–drug interactions (73, DDInter)

Interacting drugSeverityManagement
Ceritinib major
Clarithromycin major
Cobicistat major
Idelalisib major
Ketoconazole major
Abiraterone moderate
Alimemazine moderate
Amifostine moderate
Apalutamide moderate
Aprepitant moderate
Brimonidine (ophthalmic) moderate
Brimonidine (topical) moderate
Bupropion moderate
Canagliflozin moderate
Celecoxib moderate
Chlorphenesin moderate
Cimetidine moderate
Cinacalcet moderate
Clotrimazole moderate
Codeine moderate
Crizotinib moderate
Dabrafenib moderate
Dacomitinib moderate
Dapagliflozin moderate
Dexfenfluramine moderate
Diphenhydramine moderate
Doxepin moderate
Doxepin (topical) moderate
Dronabinol moderate
Eliglustat moderate
Empagliflozin moderate
Enzalutamide moderate
Epoprostenol moderate
Ertugliflozin moderate
Erythromycin moderate
Ethanol moderate
Fedratinib moderate
Fenfluramine moderate
Fluconazole moderate
Fostamatinib moderate

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Registered Products (11)

BrandForm / strengthPackAgentCitizen (JOD)
Tamucas PR 0.4 mg Prolonged Release Film Coated Tablets Film-Coated Tablet 0.4 mg 30 tab Sukhtian Group 6.980
Prostanic XR Tablet 0.4 mg 30 tab pack varies AL-TAQADDOM PHARMACEUTICAL INDUSTRIES/JORDAN 7.060
Tamsin Tablet 0.4 mg 30 tab Hikma Pharmaceuticals Co.Ltd/Jordan 7.200
Eziflo Tablet 0.4 mg 30 tab UNITED PHARM.MFG.CO.LTD(UPM)/JORDAN 9.080
Tamzoman 0.4 mg F.C.Tablet Film-Coated Tablet 0.4 mg 30 tab SAVVY PHARMA/JORDAN 9.260
Gamcet 0.4mg F.C Tab Film-Coated Tablet 0.4 mg 30 tab Dar Al Dawa Development and Investment Co Ltd/Jordan 9.510
Prostanic Tablet 0.4 mg 30 tab pack varies Al-Taqqadom Pharmaceutical Industries 9.550
Uriflo Tablet 0.4 mg 30 tab pharma international 9.670
Omnic Ocas Tablet 0.4 mg 30 tab Ibn Rushd Drug Store 10.990
Prostanic Plus Capsule 0.4 mg, 0.5 mg 30 cap Altaqadom Pharmaceutical Industries 19.530
Gamcet Duo Capsules Capsule 0.4 mg, 0.5 mg 30 cap / Dar Al Dawa Development and Investment Co Ltd/Jordan / General 20.960