Dutasteride + tamsulosin


Full Generic Medicine Info
Dosage/Direction for Use

Oral
Benign prostatic hyperplasia
Adult: Available preparation: Dutasteride 0.5 mg and tamsulosin 0.4 mg cap 1 cap once daily.
Child: Contraindicated.
Hepatic impairment: Severe: Contraindicated.

Special Populations: Pharmacogenomics: Tamsulosin Tamsulosin is extensively metabolised in the liver by CYP3A4 and CYP2D6 into metabolites. Genetic polymorphism of CYP2D6 gene may affect the plasma concentrations of tamsulosin. The prevalence of CYP2D6 poor metabolisers is estimated in 7% of Caucasians and 2% of African Americans. There is insufficient evidence of any benefit with genetic testing before therapy. CYP2D6 poor metabolisers Since CYP2D6 poor metabolisers cannot be readily identified and the potential increase in tamsulosin exposure exists only when co-administered with CYP3A4 inhibitors in CYP2D6 poor metabolisers, tamsulosin should not be used with strong CYP3A4 inhibitors (e.g. ketoconazole).
Administration
Should be taken with food. Take approx 30 min after meals. Swallow whole, do not crush/chew/open.
Contraindications
Hypersensitivity. History of orthostatic hypotension. Women, children and adolescents. Pregnancy and lactation. Severe hepatic impairment. Concomitant use with strong CYP3A4 inhibitors in CYP2D6 poor metabolisers.
Special Precautions
Patient with large residual urinary volume and/or severely impaired urine flow. Cataract surgery patients. Severe renal impairment (CrCl <10 mL/min) and mild to moderate hepatic impairment. Patient Counselling Women of child-bearing potential, pregnant or children should avoid handling the cap. Excreted in semen therefore use of condom is recommended. Avoid donating blood during and for at least 6 months after discontinuation of therapy. This drug may cause dizziness and vertigo, if affected, do not drive or operate machinery. Monitoring Parameters Rule out prostate cancer before initiation of therapy. Perform digital rectal examination, other assessment for prostate cancer or other conditions causing the same symptoms as BPH before and during therapy. Obtain new baseline prostate-specific antigen level after 3 months of treatment then monitor periodically thereafter. Assess for objective and subjective signs of relief of BPH (e.g. improvement in urinary flow, reduction in symptoms of urgency, relief of difficulty in micturition).
Adverse Reactions
Significant: Intraoperative floppy iris syndrome, orthostatic hypotension and syncope; rarely, priapism. Nervous system disorders: Dizziness, vertigo. Reproductive system and breast disorders: Impotence, decreased libido, ejaculation disorder, breast disorder, gynaecomastia, breast tenderness.
Overdosage
Symptoms: Tamsulosin: Acute hypotension, vomiting, diarrhoea. Management: Supportive and symptomatic treatment. CV support should be given in acute hypotension; lying the patient down may restore blood pressure and heart rate, if insufficient, volume expanders and vasopressors may be given if necessary. Inducing emesis may delay absorption. May perform gastric lavage or administer activated charcoal and an osmotic lavage (e.g. Na sulfate) for large doses.
Drug Interactions
Dutasteride: Increased serum concentration with potent CYP3A4 inhibitors (e.g. ritonavir, indinavir, nefazodone, itraconazole, oral ketoconazole). Tamsulosin: Enhanced hypotensive effect with anaesthetic agents, PDE5 inhibitors (e.g. sildenafil, tadalafil, vardenafil) and other α1-adrenoreceptor antagonists. Increased plasma concentration with strong CYP3A4 inhibitors (e.g. ketoconazole) or to a lesser extent, with strong CYP2D6 inhibitors (e.g. paroxetine) or a combination of both CYP3A4 and CYP2D6 inhibitors (e.g. amiodarone, cimetidine, imatinib). Decreased plasma concentration with furosemide. Increased elimination rate with diclofenac and warfarin.
Food Interaction
Decreased rate and extent of absorption with food (within 30 minutes of a meal).
Lab Interference
May cause decreased serum PSA levels by approx 50% within 3-6 months of use.
Action
Dutasteride, a 4-azo analogue of testosterone, is a competitive, selective inhibitor of both type 1 and type 2, 5α-reductase isoenzyme which results to the inhibition of testosterone to dihydrotestosterone conversion, thus significantly decreasing serum dihydrotestosterone levels. Tamsulosin antagonizes the α1A-adrenoreceptors, which mediate the smooth muscle tone in the prostate. This results in the relaxation of smooth muscle in the bladder neck and prostate leading to an improved urine flow and reduced symptoms of benign prostatic hyperplasia (BPH).
Absorption: Dutasteride: Absorbed from the gastrointestinal tract. Bioavailability: Approx 60%. Time to peak plasma concentration: 1-3 hours. Tamsulosin: Absorbed from the gastrointestinal tract and almost completely available. Food, decreases rate and extent of absorption. Time to peak plasma concentration: 6-7 hours (fed state); 4-5 hours (fasting).
Distribution: Dutasteride: Volume of distribution: 300-500 L. Plasma protein binding: Approx 99% to albumin; approx 97% to α1-acid glycoprotein; >96% to semen protein. Tamsulosin: Volume of distribution: Approx 16 L. Plasma protein binding: 94-99%, mainly to α1-acid glycoprotein.
Metabolism: Dutasteride: Extensively metabolised in the liver by CYP3A4 and CYP3A5 into 6-hydroxydutasteride (similar activity to parent drug), and 4-hydroxydutasteride and 1,2-dihydrodutasteride metabolites. Tamsulosin: Extensively metabolised in the liver by CYP3A4 and CYP2D6 into metabolites; further metabolised via conjugation into glucuronide or sulfate.
Excretion: Dutasteride: Via faeces (40% as metabolites, approx 5% as unchanged drug); urine (<1% as unchanged drug). Terminal elimination half-life: Approx 3-5 weeks. Tamsulosin: Mainly via urine (76%, <10% as unchanged drug); faeces (21%). Elimination half-life: Approx 10-15 hours.
Storage
Oral: Store below 30°C.
CIMS Class
Drugs for Bladder & Prostate Disorders
ATC Classification
G04CB02 - dutasteride ; Belongs to the class of testosterone-5-alpha reductase inhibitors. Used in the treatment of benign prostatic hypertrophy.
G04CA02 - tamsulosin ; Belongs to the class of alpha-adrenoreceptor antagonists. Used in the treatment of benign prostatic hypertrophy.
Disclaimer: This information is independently developed by CIMS based on dutasteride + tamsulosin from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to CIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, CIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2021 CIMS. All rights reserved. Powered by CIMSAsia.com
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