Urofi Capsule 5 mg+5 mg
Urofi Capsule 5 mg+5 mg Uses, Dosage, Side Effects, Food Interaction and all others data.
Finasteride, a competitive inhibitor of the 5α reductase enzyme which is used in the treatment of benign prostatic hyperplasia. It is selective for 5α reductase type 2 enzyme and has no affinity for androgen receptors. The development of the prostate gland and subsequent BPH is dependent upon conversion of testosterone to dihydrotestosterone (DHT) within the prostate. Finasteride belongs to a new class of specific inhibitors of 5α reductase, an intracellular enzyme, which metabolises testosterone into the more potent androgen, DHT. Finasteride has no affinity for the androgen receptor.
Finasteride is an antiandrogenic compound that works by suppressing the production of serum and intraprostatic dihydrotestosterone (DHT) in men via inhibiting the enzyme responsible for the biosynthesis of DHT. The maximum effect of a rapid reduction in serum DHT concentration is expected to be observed 8 hours following administration of the first dose. In a single man receiving a single oral dose of 5 mg finasteride for up to 4 years, there was a reduction in the serum DHT concentrations by approximately 70% and the median circulating level of testosterone increased by approximately 10-20% within the physiologic range. In a double-blind, placebo-controlled study, finasteride reduced intraprostatic DHT level by 91.4% but finasteride is not expected to decrease the DHT levels to castrate levels since circulating testosterone is also converted to DHT by the type 1 isoenzyme expressed in other tissues. It is expected that DHT levels return to normal within 14 days upon discontinuation of the drug. In a study of male patients with benign prostatic hyperplasia prior to prostatectomy, the treatment with finasteride resulted in an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery compared to placebo. While finasteride reduces the size of the prostate gland by 20%, this may not correlate well with improvement in symptoms. The effects of finasteride are reported to be more pronounced in male patients with enlarged prostates (>25 mL) who are at the greatest risk of disease progression.
In phase III clinical studies, oral administration of finasteride in male patients with male pattern hair loss promoted hair growth and prevented further hair loss by 66% and 83% of the subjects, respectively, which lasted during two years' treatment. The incidences of these effects in treatment groups were significantly higher than that of the group receiving a placebo. Following finasteride administration, the levels of DHT in the scalp skin was shown to be reduced by more than 60%, indicating that the DHT found in scalp is derived from both local DHT production and circulating DHT. The effect of finasteride on scalp DHT is likely seen because of its effect on both local follicular DHT levels as well as serum DHT levels.. There is evidence from early clinical observations and controlled studies that finasteride may reduce bleeding of prostatic origin.
When sexual stimulation causes the local release of nitric oxide in the corpus cavernosum, then nitric oxide activates the enzyme guanylyl cyclase, which results in increased levels of cGMP. The increased levels of cGMP in the corpus cavernosum produce smooth muscle relaxation and inflow of blood into the penile tissues, thereby producing an erection. PDE5 degrades cGMP in the corpus cavernosum, and the inhibition of PDE5 by Tadalafil maintains increased levels of cGMP in the corpus cavernosum. Tadalafil has no effect on penile blood flow in absence of sexual stimulation.
Tadalafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erection involves the release of nitric oxide (NO) in the corpus cavernosum. This then activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in the corpus cavernosum, resulting in increased inflow of blood and an erection. Tadalafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum. This means that, with tadalafil on board, normal sexual stimulation leads to increased levels of cGMP in the corpus cavernosum which leads to better erections. Without sexual stimulation and no activation of the NO/cGMP system, tadalafil should not cause an erection.
| Trade Name | Urofi Capsule 5 mg+5 mg |
| Generic | Finasteride + Tadalafil |
| Weight | 5 mg+5 mg |
| Type | Capsule |
| Therapeutic Class | BPH/ Urinary retention/ Urinary incontinence |
| Manufacturer | Beximco Pharmaceuticals Ltd. |
| Available Country | Bangladesh |
| Last Updated: | October 19, 2023 at 6:27 am |
Uses
This is indicated to initiate treatment of the signs and symptoms of Benign Prostatic Hyperplasia (BPH) in men with an enlarged prostate for up to 26 weeks.Urofi Capsule 5 mg+5 mg is also used to associated treatment for these conditions: Androgenetic Alopecia, Benign Prostatic Hyperplasia (BPH), Idiopathic Hirsutism, Symptomatic Benign Prostatic HyperplasiaBenign Prostatic Hyperplasia (BPH), Erectile Dysfunction, Symptomatic pulmonary arterial hypertension (PAH)
How Urofi Capsule 5 mg+5 mg works
Finasteride acts as a competitive and specific inhibitor of Type II 5α-reductase, a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, 5α-dihydrotestosterone (DHT). DHT is considered to be the primary androgen playing a role in the development and enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland. DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation. Responsible for the production of DHT together with type I 5α-reductase, the type II 5α-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver. Although finasteride is 100-fold more selective for type II 5α-reductase than for the type I isoenzyme, chronic treatment with this drug may have some effect on type I 5α-reductase, which is predominantly expressed in sebaceous glands of most regions of skin, including the scalp, and liver. It is proposed that the type I 5α-reductase and type II 5α-reductase is responsible for the production of one-third and two-thirds of circulating DHT, respectively.
The mechanism of action of Finasteride is based on its preferential inhibition of Type II 5α-reductase through the formation of a stable complex with the enzyme in vitro and in vivo. Finasteride works selectively, where it preferentially displays a 100-fold selectivity for the human Type II 5α-reductase over type I enzyme. Inhibition of Type II 5α-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations, minimal to moderate increase in serum testosterone concentrations, and substantial increases in prostatic testosterone concentrations. As DHT appears to be the principal androgen responsible for stimulation of prostatic growth, a decrease in DHT concentrations will result in a decrease in prostatic volume (approximately 20-30% after 6-24 months of continued therapy). It is suggested that increased levels of DHT can lead to potentiated transcription of prostaglandin D2, which promotes the proliferation of prostate cancer cells. In men with androgenic alopecia, the mechanism of action has not been fully determined, but finasteride has shown to decrease scalp DHT concentration to the levels found in the hairy scalp, reduce serum DHT, increase hair regrowth, and slow hair loss. Another study suggests that finasteride may work to reduce bleeding of prostatic origin by inhibiting vascular endothelial growth factor (VEGF) in the prostate, leading to atrophy and programmed cell death. This may bestow the drug therapeutic benefits in patients idiopathic prostatic bleeding, bleeding during anticoagulation, or bleeding after instrumentation.
Penile erection during sexual stimulation is achieved by the relaxation of penile arteries and corpus cavernosal smooth muscles, leading to increased blood flow to the organ. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum, and is degraded by the cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum located around the penis. Tadalafil inhibits PDE5 and thereby enhances erectile function by increasing the amount of cGMP available.
Dosage
Urofi Capsule 5 mg+5 mg dosage
Adult use: The recommended dosage of is one capsule orally once daily at approximately the same time every day for up to 26 weeks. It is advised to take this on an empty stomach. This combination is not recommended for more than 26 weeks because the incremental benefit beyond 26 weeks is unknown. Pediatric Use: The safety and effectiveness of Finasteride and Tadalafil have not been established yet in patients less than 18 years of age. Geriatric Use: No overall differences in safety or effectiveness of Finasteride and Tadalafil have been observed between patients 65 years of age and older. Hepatic Impairment: In case of moderately impaired hepatic function, this can be given with caution. For severely impaired hepatic function, this is not recommended. Renal Impairment: Not recommended for patients having creatinine clearance less than 50 mL/min or undergoing hemodialysis.Tadalafil may be taken without regard to food.
Side Effects
Most common adverse reactions associated with finasteride monotherapy (≥1%) in a 4-year study were impotence decreased libido, decreased volume of ejaculation and rush. Most common adverse reactions (≥2%) associated with tadalafil were headache, dyspepsia, back pain, myalgia, nasal congestion, flushing, and pain in limb.Toxicity
LD50
Oral LD50 is about 418 mg/kg in rats and there have been cases of lethality in rats receiving a single oral dose of 400 mg/kg in males and 1000 mg/kg in females.
Nonclinical toxicology
In a 24-month rat study, there were no signs of the tumorigenic potential of finasteride. In a 19-month carcinogenicity study in CD-1 mice, high doses of finasteride, at 1824 times the human exposure (250 mg/kg/day), resulted in an increase in the incidence of testicular Leydig cell adenomas and an increase in serum LH levels. In vitro mutagenesis assays demonstrated no evidence of mutagenicity. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations with much higher doses of finasteride.
Overdose
There were no reported significant adverse events in clinical trials of male patients receiving single oral doses of finasteride up to 400 mg and multiple doses of finasteride up to 80 mg/day for three months. As there have been no cases of overdose or clinically significant toxicity with finasteride, there are no specific recommendations in case of an overdose.
Significant adverse events
Common reproductive adverse events seen with finasteride therapy include erectile dysfunction, ejaculatory dysfunction, and loss of libido. These adverse events tend to disappear after discontinuation or chronic use of the drug. Only causal adverse event occurring at the male reproductive system that is caused by finasteride is decreased ejaculatory volume because of the predominant action of DHT on the prostate.
Special populations
Finasteride can be safely used in elderly patients or those with renal impairment with no specific dosing adjustment recommendations. Finasteride is indicated for male patients only, and it is advised that exposure to finasteride is avoided in pregnant women carrying male fetuses as it may lead to abnormal development of external genitalia in male fetuses.
Oral, Rat LD50 = 2000 mg/kg, no deaths or toxicity.
Precaution
This combination is not recommended for the following groups of patients: Patients who have had myocardial infarction within the last 90 days. Patients with unstable angina. Patients classified with heart failure in the last 6 months. Patients with uncontrolled arrhythmias, hypotension (<90/50 mm Hg), or uncontrolled hypertension. Patients who have had stroke within the last 6 months. Hypersensitivity Reactions: It is advised to discontinue immediately if any hypersensitivity reaction occurs.Prolonged Erection: To be used with caution in patients who have anatomical deformation of the penis. Patients are advised to seek emergency treatment if an erection lasts more than 4 hours.Interaction
Nitrates: Administration of this capsule to patients who are using any form of organic nitrate, is contraindicated. In clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates.Alpha-Blockers: Caution is advised when PDE5 inhibitors are co-administered with alpha-blockers. Discontinuation of alpha-blockers is recommended at least one day prior to starting this capsule for once-daily use for the treatment of BPH. Antihypertensives: PDE5 inhibitors, including tadalafil, are mild systemic vasodilators. Small reductions in blood pressure occurred following coadministration of tadalafil with these agents (amlodipine, angiotensin II receptor blockers, bendrofluazide, enalapril, and metoprolol) compared with placebo.Volume of Distribution
The volume of distribution is 76 L at steady state, ranging from 44 to 96 L. Finasteride has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF. It is not known whether finasteride is excreted in human milk.
- 63 L
Elimination Route
Finasteride is well absorbed following oral administration and displays a slow accumulation phase after multiple dosing.[lablel] In healthy male subjects receiving oral finasteride, the mean oral bioavailability was 65% for 1 mg finasteride and 63% for 5 mg finasteride, and the values ranged from 26 to 170% for 1 mg dose and from 34 to 108% for 5 mg dose, respectively. It is reported that food intake does not affect the oral bioavailability of the drug. The peak plasma concentrations (Cmax) averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours post administration. The AUC(0-24 hr) was 53 ngxhr/mL (range, 20-154 ngxhr/mL). The plasma concentrations and AUC are reported to be higher in elderly male patients aged 70 years or older.
After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time of 2 hours). Absolute bioavailability of tadalafil following oral dosing has not been determined.
Half Life
In healthy young subjects receiving finasteride, the mean elimination half-life in plasma was 6 hours ranging from 3 to 16 hours. In elderly patients over the age of 70 years, the half-life is prolonged to 8 hours.
17.5 hours
Clearance
In healthy young subjects (n=15), the mean plasma clearance of finasteride was 165 mL/min with the range between 70 and 279 mL/min.
- oral cl=2.5 L/hr
Elimination Route
In healthy subjects, about 32-46% of total oral dose of finasteride was excreted in the urine in the form of metabolites while about 51-64% of the dose was excreted in the feces. In patients with renal impairment, the extent of urinary excretion of finasteride is expected to be decreased while the fecal excretion is increased.
Tadalafil is excreted predominantly as metabolites, mainly in the feces (approximately 61% of the dose) and to a lesser extent in the urine (approximately 36% of the dose).
Pregnancy & Breastfeeding use
This combination is contraindicated in pregnancy and not indicated for use in females. If a pregnant female comes in contact with a crushed or broken this capsule, the contact area should be washed immediately with soap and water. This capsule is not indicated for use in lactating mothers.Contraindication
Concomitant use with any form of organic nitrate, either regularly and/or intermittently. This can potentiate the hypotensive effect of nitrates.Special Warning
Renal insufficiency: Dosage adjustments are not necessary in patients with renal insufficiency since pharmacokinetic studies did not indicate any change in the disposition of Finasteride.
Hepatic insufficiency: There are no data available in patients with hepatic insufficiency.
Elderly: No dosage adjustment is required in elderly patients.
Renal Insufficiency-
For Use as Needed:
- Mild (creatinine clearance 51 to 80 mL/min): No dose adjustment is required.
- Moderate (creatinine clearance 31 to 50 mL/min): A starting dose of 5 mg not more than once per day is recommended, and the,maximum dose should be limited to 10 mg not more than once in every 48 hours.
- Severe (creatinine clearance <30 mL/min and on hemodialysis): The maximum recommended dose is 5 mg not more than once in every 72 hours.
For Once Daily Use:
- Mild (creatinine clearance 51 to 80 mL/min): No dose adjustment is required. Moderate (creatinine clearance 31 to 50 mL/min): No dose adjustment is required.
- Severe (creatinine clearance <30 mL/min and on hemodialysis): Tadalafil for once daily use is not recommended.
Hepatic Impairment-
For Use as Needed:
- Mild or moderate: The dose should not exceed 10 mg once per day.
- Severe: Not recommended
For Once Daily Use:
- Mild or moderate: Tadalafil for once daily use has not been extensively evaluated in patients with hepatic insufficiency. Therefore, caution is advised if Tadalafil for once daily use is prescribed to these patients.
- Severe: Not recommended.
Geriatrics:
No dose adjustment is required in patients >65 years of age
Acute Overdose
In cases of overdose, standard supportive measures should be adopted as required.Storage Condition
Do not store above 30°C. Keep in a dry place. Protect from light and keep out of the reach of children.Innovators Monograph
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