Indications of Combomax

Treatment of moderate to severe symptoms of benign prostatic hyperplasia with Tamsulosin Hydrochloride and Dutasteride capsules (BPH).
In individuals with moderate to severe BPH symptoms, the risk of acute urine retention and surgery is reduced.

Pharmaceutical Name of Combomax

Drug International Ltd.

Pharmacology

Tamsulosin & Dutasteride is a medication combination that improves symptoms in people with Benign Prostatic Hyperplasia by combining two medicines with complementary mechanisms of action (BPH). Dutasteride, a dual 5 alpha reductase inhibitor, and Tamsulosin Hydrochloride, an antagonist of alpha1A-adrenoreceptors (5ARI). The use of alpha1-adrenoreceptor blockers with 5ARIs to treat BPH leads to an increase in urine flow rate and a reduction in BPH symptoms.

Tamsulosin is an alpha1-adrenoreceptor blocker that works by suppressing alpha1-adrenoreceptors in the stromal prostatic smooth muscle and bladder neck, which affects the dynamic component of BPH. Smooth muscles in the bladder neck and prostate can relax if these adrenoreceptors are blocked. Tamsulosin, in particular, has a preference for alpha 1A and alpha 1D receptors over alpha1B-adrenoreceptors.

In human tissue, these three adrenoreceptor subtypes have unique distribution patterns. While nearly 70% of alpha1-receptors in the human prostate are of the alpha 1A subtype, the alpha 1D subtype predominates in the human bladder, while the alpha 1B subtype predominates in blood vessels. Blockade of the alpha 1D subtypes in the human obstructed bladder is also thought to be responsible for lowering detrusor overactivity and alleviating storage symptoms.

Dutasteride is a synthetic 4-azasteriod substance that inhibits the conversion of Testosterone to Dihydrotestosterone (DHT) by the enzyme 5 alpha-reductase. It affects the static component of BPH by blocking the conversion of Testosterone to DHT by the enzyme 5 alpha-reductase. Type I and Type II are the two isoforms of 5 alpha-reductase that are found in the prostate. The expression of both isoenzymes has been found to be higher in BPH tissue than in normal tissue. The rate of dissociation from this complex has been measured in vitro and in vivo, and it is extraordinarily slow.

Dosage & Administration

Adults (including elderly): The recommended dose is one capsule (Tamsulosin Hydrochloride 0.4 mg & Dutasteride 0.5 mg) taken orally approximately 30 minutes after the same meal each day. The capsules should be swallowed whole and not chewed or opened. Where appropriate, this capsule may be used to substitute concomitant Tamsulosin Hydrochloride and Dutasteride in existing dual therapy to simplify treatment. Where clinically appropriate, direct change from Tamsulosin Hydrochloride or Dutasteride monotherapy to this capsule may be considered.

Renal impairment: The effect of renal impairment on Tamsulosin-Dutasteride pharmacokinetics has not been studied. No adjustment in dosage is anticipated for patients with renal impairment.

Hepatic impairment: The effect of hepatic impairment on Tamsulosin-Dutasteride pharmacokinetics has not been studied so caution should be used in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the use of this capsule is contra-indicated.

Interaction of Combomax

There have been no pharmacological interaction studies for the combination of Dutasteride and Tamsulosin.

Other medicines’ effects on the pharmacokinetics of dutasteride: When used with CYP3A4 and/or P-glycoprotein inhibitors, the following results can be obtained: Dutasteride is mostly excreted through the digestive system. This metabolism is catalyzed by CYP3A4 and CYP3A5, according to in vitro investigations. With potent CYP3A4 inhibitors, no formal interaction investigations have been conducted. In a population pharmacokinetic investigation, however, Dutasteride serum concentrations were 1.6 to 1.8 times higher in a small group of patients treated concurrently with verapamil or diltiazem (moderate CYP3A4 and P-glycoprotein inhibitors) than in other patients.Long-term use of Dutasteride in combination with medicines that are potent inhibitors of the CYP3A4 enzyme (e.g., ritonavir, indinavir, nefazodone, itraconazole, ketoconazole) can raise Dutasteride serum concentrations. It is unlikely that increased Dutasteride exposure will result in further inhibition of 5-alpha reductase. If side effects are observed, however, a reduction in the frequency of Dutasteride dose may be explored. It should be emphasized that in the case of enzyme inhibition, the long half-life can be extended even further, and achieving a new steady state can require more than 6 months of concurrent medication.The pharmacokinetics of Dutasteride were unaffected by the administration of 12 g cholestyramine one hour after a 5 mg single dosage.

Contraindications

Patients with hypersensitivity to Dutasteride, other 5-alpha reductase inhibitors, Tamsulosin (including Tamsulosin-induced angioedema), soya, peanut, or any of the other excipients, patients with a history of orthostatic hypotension, and patients with severe hepatic impairment should not take Tamsulosin-Dutasteride together.

Side Effects of Combomax

Impotence, decreased libido, breast disorders (including breast growth and soreness), ejaculation abnormalities, and dizziness were the most prevalent adverse events recorded in participants undergoing combo medication. When compared to either monotherapy or combination therapy, the percentages of participants with ejaculation problems, decreased libido, and impotence were higher in the combination therapy group.

Pregnancy & Lactation

The combination of Tamsulosin and Dutasteride is not recommended for women. There have been no research on the effects of combining Tamsulosin with Dutasteride on pregnancy, breastfeeding, or fertility. The following claims are based on data from studies involving the individual components. Fertility: In healthy men, dutasteride has been shown to impact sperm parameters (such as sperm count, volume, and motility). Reduced male fertility is a risk that cannot be ruled out. Tamsulosin Hydrochloride has not been studied for its effects on sperm counts or function.

Dutasteride inhibits the conversion of testosterone to dihydrotestosterone, as do other 5 alpha reductase inhibitors, and may impair the development of the external genitalia of a male foetus if given to a mother carrying a male foetus. Dutasteride has been found in small levels in the sperm of Dutasteride-treated men. It’s unclear whether a male embryo will be harmed if his mother is exposed to Dutasteride-treated sperm. When using any of the five alpha reductase inhibitors, it is recommended that the patient use a condom to avoid exposing his partner to semen if she is or may become pregnant.There was no evidence of foetal damage after Tamsulosin Hydrochloride was given to pregnant female rats and rabbits.

Tamsulosin and Dutasteride are not known to be excreted in human milk during lactation.

Precautions & Warnings

Due to the possibility for increased risk of adverse effects (including cardiac failure), combination therapy should only be administered after careful review of other treatment options, including monotherapies.

Cardiac failure: In two 4-year clinical investigations, participants taking the combination of Dutasteride plus an alpha blocker, primarily Tamsulosin, had a greater rate of cardiac failure than those not taking the combination. The frequency of cardiac failure in these two trials was low (1%) and varied between the studies.

Prostate cancer and high-grade tumors: A clinical research in men at high risk of prostate cancer found that Dutasteride-treated men had a higher prevalence of Gleason 8-10 prostate cancers than placebo-treated men. There is no obvious link between Dutasteride and high-grade prostate cancer. Men who take the Tamsulosin-Dutasteride combo should have their prostate cancer risk assessed on a regular basis, including PSA testing.

Renal impairment: Because these individuals have not been investigated, treating severely renally impaired patients (creatinine clearance less than 10 ml/min) should be addressed with caution.

Hypotension: Orthostatic- As with other alpha-blockers, Tamsulosin can cause a drop in blood pressure, which can lead to syncope. Patients starting Tamsulosin-Dutasteride medication should be advised to sit or lie down as soon as they experience symptoms of orthostatic hypotension (dizziness, weakness) until the symptoms subside. Prior to starting PDE5 inhibitors, the patient should be hemodynamically stable on alpha-blocker medication to reduce the risk of developing postural hypotension. When alpha adrenergic blocking medications, such as Tamsulosin, are used with PDE5 inhibitors, caution is suggested.

Therapeutic Class

Urinary incontinence/BPH/ Urinary retention

Storage Conditions

Store in a cold, dry, and light-protected location.

Generic of Combomax

Tamsulosin Hydrochloride + Dutasteride