Dutasteride/ Tamsulosin

Registered South African indications:

• Moderate to severe symptoms of benign prostatic hyperplasia (BPH)

Contraindications

• Patients with hypersensitivity to dutasteride, other 5-alpha reductase inhibitors, tamsulosin or any excipients
• Pregnancy
• Breastfeeding
• Women
• Children
• Adolescents
• Tamsulosin induced angio-edema
• History of orthostatic hypotension
• Severe hepatic impairment
• Soya or peanut allergies
• Allergy to FD&C yellow 6

Cautions

• Patients with risk factors to develop cardiac failure
• Patients with high risk factors for prostate cancer
• Cataract surgery
• Severe renal impairment
• Mild to moderate hepatic impairment
• Contact made with leaking capsules
• Sulfonamide allergy
• Severely diminished urinary flow
• Obstructive uropathy
• Changes in breast tissue of men (such as lumps or nipple discharge)
• May impair the ability to drive or operate machinery

Forms avail. in SA and covered in this monograph: cap

• Oral (cap): 1 cap (0.5mg/ 0.4mg), dly

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Taken approximately 30 minutes after the same meal each day

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Capsules should be swallowed whole and not chewed or opened

Not established for use in children below 18 years

Pregnancy

• Contraindicated
• As with other 5-alpha reductase inhibitors, dutasteride inhibits the conversion of testosterone to dihydrotestosterone and may, if administered to a woman carrying a male foetus, inhibit the development of the external genitalia of the foetus
• Small amounts of dutasteride have been recovered from the semen in subjects receiving dutasteride. It is not known whether a male foetus will be adversely affected if his mother is exposed to the semen of a patient being treated with dutasteride (the risk of which is greatest during the first 16 weeks of pregnancy)
• As with all 5 alpha reductase inhibitors, when the patient's partner is or may potentially be pregnant, it is recommended that the patient avoids exposure of his partner to semen by use of a condom
• Dutasteride is absorbed through the skin, therefore, women, children and adolescents must avoid contact with leaking capsules. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water
• Administration of tamsulosin hydrochloride to pregnant female rats and rabbits showed no evidence of foetal harm

Breastfeeding

• Contraindicated
• It is not known whether dutasteride or tamsulosin are excreted in breast milk

Fertility

• Dutasteride has been reported to affect semen characteristics (reduction in sperm count, semen volume, and sperm motility) in healthy men. The possibility of reduced male fertility cannot be excluded
• Effects of tamsulosin hydrochloride on sperm counts or sperm function have not been evaluated
• Male patients on treatment with dutasteride/ tamsulosin are advised to use condoms

Renal impairment

• Caution; no information available

Hepatic impairment

• Mild to moderate: Caution; no dose adjustment recommended (tamsulosin)
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Adverse reactions reported in dutasteride & tamsulosin combination therapy

Central Nervous System Disorders

• Dizziness
• Depressed mood

Cardiovascular Disorders

• Congestive cardiac failure
• Left ventricular failure
• Acute cardiac failure
• Cardiogenic shock
• Acute left ventricular failure
• Right ventricular failure
• Acute right ventricular failure
• Ventricular failure
• Cardiopulmonary failure
• Congestive cardiomyopathy
• Cardiac failure
• Palpitations
• Atrial fibrillation

Respiratory Disorders 

• Shortness of breath
• Epistaxis

Gastrointestinal Disorders 

• Constipation
• Diarrhoea
• Vomiting

Genitourinary Disorders

• Impotence
• Altered (decreased) libido
• Ejaculation disorders
• Priapism
• Testicular pain
• Testicular swelling
• Prostate cancer

Skin and Subcutaneous Tissue Disorders

• Rash
• Pruritis
• Urticaria
• Aloplecia (primarily body hair loss)
• Hypertrichosis
• Steven-Johnson Syndrome

Immune, Blood and Lymphatic System Disorders

• Allergic reactions

Sensory Disorders

• Intra-operative Floppy Iris Syndrome (IRIS)
• Changes in vision

Others

• Breast disorders, including breast tenderness and breast enlargement
• Localised oedema
• Angioedema
• Decreased PSA levels

Adverse reactions reported in dutasteride monotherapy

Central Nervous System Disorders

• Dizziness
• Depression

Cardiovascular Disorders

• Congestive cardiac failure
• Left ventricular failure
• Acute cardiac failure
• Cardiogenic shock
• Acute left ventricular failure
• Right ventricular failure
• Acute right ventricular failure
• Ventricular failure
• Cardiopulmonary failure
• Congestive cardiomyopathy
• Cardiac failure

Genitourinary Disorders

• Impotence
• Altered (decreased) libido
• Ejaculation disorders
• Testicular pain
• Testicular swelling

Skin and Subcutaneous Tissue Disorders

• Alopecia (primarily body hair loss)
• Hypertrichosis

Immune, Blood and Lymphatic System Disorders 

• Allergic reactions

Others

• Breast disorders, including breast tenderness and breast enlargement
• Breast cancer in men

Adverse reactions reported in tamsulosin monotherapy

Central Nervous System Disorders

• Dizziness
• Syncope
• Headache

Cardiovascular Disorders

• Palpitations
• Atrial fibrillation
• Dysrhythmia
• Tachycardia
• Dyspnoea

Respiratory Disorders 

• Rhinitis
• Epistaxis

Gastrointestinal Disorders 

• Constipation
• Diarrhoea
• Nausea
• Vomiting

Genitourinary Disorders

• Priapism
• Ejaculation disorders

Skin and Subcutaneous Tissue Disorders

• Angioedema
• Steven-Johnson syndrome
• Urticaria
• Rash
• Pruritis
• Erythema multiforme
• Dermatitis exfoliative

Immune, Blood and Lymphatic System Disorders 

• Orthostatic hypotension

Sensory Disorders

• Intra-operative Floppy Iris Syndrome (IRIS)
• Blurred vision
• Visual impairment

Others

• Asthenia
• Dry mouth

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Dutasteride

• CYP3A4 inhibitors (e.g. ritonavir, indinavir, nefazodone, itraconazole, ketoconazole)
• P-glycoprotein inhibitors 
• Verapamil 
• Diltiazem 

Tamsulosin

• CYP3A4 inhibitors (e.g. ritonavir, indinavir, nefazodone, itraconazole)
• Ketoconazole
• Paroxetine
• CYP2D6 inhibitors
• Medicines that reduce blood pressure 
• Anaesthetic agents
• PDE5 inhibitors
• Other alpha-adrenoceptor antagonists
• Cimetidine
• Warfarin
• Diclofenac

• Prostate specific antigen (PSA) levels at baseline, then after 6 months of treatment, and periodically thereafter
• Digital rectal exam

Effects on prostate specific antigen (PSA) and prostate cancer detection

• Dutasteride/ tamsulosin causes a decrease in mean blood PSA levels by approximately 50%, after 6 months of treatment
• Patients receiving dutasteride/ tamsulosin should have a new PSA baseline established after 6 months of treatment with dutasteride/ tamsulosin. It is recommended to monitor PSA values regularly thereafter
• Any confirmed increase from lowest PSA level while on dutasteride/ tamsulosin may signal the presence of prostate cancer or noncompliance to therapy with dutasteride/ tamsulosin and should be carefully evaluated, even if those values are still within the normal range for men not taking a 5-alpha reductase inhibitor
• In the interpretation of a PSA value for a patient taking dutasteride, previous PSA values should be sought for comparison
• Treatment with dutasteride/ tamsulosin does not interfere with the use of PSA as a tool to assist in the diagnosis of prostate cancer after a new baseline has been established
• Total blood PSA level return to baseline within 6 months of discontinuing treatment. The ratio of free to total PSA remains constant even under the influence of dutasteride/ tamsulosin. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing dutasteride/ tamsulosin therapy, no adjustment to its value appears necessary
• Digital rectal examination, as well as other evaluations for prostate cancer or other conditions which can cause the same symptoms as BPH, must be performed on patients prior to initiating therapy with dutasteride/ tamsulosin and periodically thereafter 

Breast neoplasia

• There have been rare reports of breast cancer in men taking dutasteride in clinical trials and during the post marketing period
• However, epidemiological studies showed no increase in the risk of developing male breast cancer with the use of 5-alpha reductase inhibitors
• Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps or nipple discharge

Leaking capsules

• Dutasteride is absorbed through the skin, therefore, women, children and adolescents must avoid contact with leaking capsules
• If contact is made with leaking capsules, the contact area should be washed immediately with soap and water
• Pregnant women or women trying to conceive should not handle dutasteride/ tamsulosin

Dutasteride-tamsulosin is a combination of two medicines: dutasteride, a dual 5 α-reductase inhibitor (5 ARI) and tamsulosin hydrochloride, an antagonist of α and α adrenoreceptors. These medicines have complementary mechanisms of action that rapidly improve symptoms, urinary flow and reduce the risk of acute urinary retention (AUR) and the need for BPH related surgery

Dutasteride

Dutasteride inhibits both type 1 and type 2, 5 alpha-reductase isoenzymes, which are responsible for the conversion of testosterone to dihydrotestosterone (DHT). DHT is the androgen primarily responsible for prostate growth and BPH development

Tamsulosin

Tamsulosin inhibits α and α adrenergic receptors in the stromal prostatic smooth muscle and bladder neck. Approximately 75% of the α-receptors in the prostate are of the α subtype

COMBINATION PREPARATIONS

Dutasteride/Tamsulosin

Capsule 0.5mg/0.4mg

• Duodart (GSK) originator
• Uromax Co (Cipla Medpro)