Zeropecia F

Zeropecia F 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.

Minoxidil stimulates hair growth by increasing oxygen, blood and nutrients supply to the hair follicle by widening blood vessels and inhibiting androgen hormone to affect hair follicles.

Following topical application, an average of about 1.4% of the total applied dose is absorbed from the normal intact scalp. Topical Minoxidil absorption is increased by increasing the dose applied, increasing the frequency of dosing and decreasing the barrier function of the stratum corneum. Serum Minoxidil levels and systemic effects resulting from the administration of topical Minoxidil are governed by the drug’s absorption rate through the skin. Following cessation of topical dosing, approximately 95% of the systemically absorbed drug is eliminated within 4 days. Minoxidil and its metabolites are excreted principally in the urine.

Minoxidil is an orally effective direct acting peripheral vasodilator that reduces elevated systolic and diastolic blood pressure by decreasing peripheral vascular resistance. Minoxidil is also used topically to treat androgenetic alopecia. Microcirculatory blood flow in animals is enhanced or maintained in all systemic vascular beds. In man, forearm and renal vascular resistance decline; forearm blood flow increases while renal blood flow and glomerular filtration rate are preserved. The predominant site of minoxidil action is arterial. Venodilation does not occur with minoxidil; thus, postural hypotension is unusual with its administration. The antihypertensive activity of minoxidil is due to its sulphate metabolite, minoxidil sulfate.

Zeropecia F
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Zeropecia F
Generic	Finasteride + Minoxidil
Weight	5%
Type	Solution, Gel
Therapeutic Class
Manufacturer	Iceberg Healthcare Pvt Ltd
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Finasteride is used for the treatment and control of benign prostatic hyperplasia (BPH)-

To cause regression of the enlarged prostate
To improve urinary flow
To improve the symptoms associated with BPH.

Minoxidil is used for the treatment of androgenic alopecia in males and females and stabilisation of hair loss in patients with androgenic alopecia, and also of alopecia areata.

Zeropecia F is also used to associated treatment for these conditions: Androgenetic Alopecia, Benign Prostatic Hyperplasia (BPH), Idiopathic Hirsutism, Symptomatic Benign Prostatic HyperplasiaAndrogenetic Alopecia, Severe, symptomatic Hypertension

How Zeropecia F 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.

Minoxidil is thought to promote the survival of human dermal papillary cells (DPCs) or hair cells by activating both extracellular signal-regulated kinase (ERK) and Akt and by preventing cell death by increasing the ratio of BCl^-2/Bax. Minoxidil may stimulate the growth of human hairs by prolonging anagen through these proliferative and anti-apoptotic effects on DPCs. Minoxidil, when used as a vasodilator, acts by opening adenosine triphosphate-sensitive potassium channels in vascular smooth muscle cells. This vasodilation may also improve the viability of hair cells or hair follicles.

Dosage

Zeropecia F dosage

The recommended dosage is one 5 mg tablet daily. Although early improvement may be seen, treatment for at least six months may be necessary to assess whether a beneficial response has been achieved. Thereafter, treatment should be continued.

Minoxidil topical solution is for external use only and should be applied when the hair and scalp are clean and dry. Apply 1 ml (7 sprays) of Minoxidil topical solution twice daily at 12-hour intervals to the scalp, beginning at the centre of the affected area and spreading the solution out to cover the entire affected area. The total daily application dose should not exceed 2 ml.

For the best results, Minoxidil topical solution should be allowed to remain on the scalp for about 4 hours before washing. The night-time application should be done 2-4 hours before going to bed to allow the solution to dry out. Minoxidil topical solution should not be massaged into the scalp, but applied lightly. A hair dryer should not be used to speed up the drying of the solution as it may decrease the effectiveness. Minoxidil topical solution should not be mixed with any hair oil. The drug should not be used more than two times a day, or be taken orally or applied to any other part of the body to avoid the risk of adverse effects and unwanted hair growth. More frequent use or longer application time have no effect on hair growth. In case of missing any daily applications of Minoxidil topical solution, the patient should continue with the next application.

Hands should be washed immediately if Minoxidil topical solution is applied with the fingertips. Clinical experience with Minoxidil indicates that twice-daily applications for 4 months or more may be required before there is evidence of hair growth. To arresthair fall, Minoxidil topical solution should be used for not less than 45 days. Depending upon the severity of hair loss or type and extent of baldness, particular strength of Minoxidil topical solution may be selected.

Side Effects

Finasteride is well tolerated. In clinical studies, the following adverse experiences have been reported as possibly drug related in 1% of patients treated for 12 months with 5 mg Finasteride daily: impotence (3.7%), decreased libido (3.3%), and decreased volume of ejaculate (2.8%).

Commonly encountered side effects in clinical trials with Minoxidil topical solution were minor dermatological reactions. Dermatitis or hypertrichosis may occur. These incidences may occur in 0.1–5% of patients.

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 LD₅₀ in rats has ranged from 1321-3492 mg/kg; in mice, 2456-2648 mg/kg. Side effects include cardiovascular effects associated with hypotension such as sudden weight gain, rapid heart beat, faintness or dizziness.

Precaution

General: Since the beneficial response to Finasteride may not be manifested immediately, patients with large residual urine volume and/or severely diminished urinary flow should be carefully monitored for obstructive uropathy.

Prostate cancer: Digital rectal examination, as well as, other evaluations for prostate cancer, should be performed on patients with BPH prior to initiating therapy with Finasteride and periodically thereafter. Finasteride causes a decrease in serum concentration of markers of prostatic cancer such as prostate specific antigen (PSA); therefore, reduction of serum levels of these markers in patients with BPH treated with Finasteride does not rule out concomitant prostate cancer. No clinical benefit has yet been demonstrated in patients with prostate cancer treated with Finasteride.

Minoxidil topical solution is more likely to cause scalp irritation. If scalp irritation continues or worsen, use of Minoxidil topical solution should be stopped.

Interaction

No clinically important drug interactions have been identified. Finasteride does not appear to significantly affect the cytochrome P450 linked drug metabolising enzyme system. Compounds which have been tested in man include Propranolol, Digoxin, Glibenclamide, Warfarin, Theophylline, and antipyrine.

Minoxidil topical solution should not be used along with other topical agents known to alter the stratum corneum barrier such as tretinoin or dithranol, due to the enhanced absorption of Minoxidil. Although there is no clinical evidence, there exists the theoretical possibility of absorbed Minoxidil potentiating orthostatic hypotension caused by peripheral vasodilators.

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.

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.

Minoxidil is at least 90% absorbed from the GI tract in experimental animals and man.

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.

4.2 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.

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.

Pregnancy & Breastfeeding use

Finasteride is contra-indicated in women who are or may become pregnant. Finasteride is not indicated for use in women. It is not known whether finasteride is excreted in human milk.

Exposure to finasteride- risk to male fetus: Crushed or broken Finasteride Tablets should not be handled by women who are or may become pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus. Similarly, small amounts of finasteride have been recovered from the semen in subjects receiving Finasteride 5 mg/day. It is not known whether a male fetus may be adversely affected if his mother is exposed to the semen of a patient being treated with finasteride. Therefore, when the patients sexual partner is or may become pregnant, the patient should either avoid exposure of his partner to semen (e.g. by use of a condom) or discontinue Finasteride.

Minoxidil topical solution should not be used during pregnancy and lactation.

Contraindication

Hypersensitivity to any component of this medication. Finasteride use is also contraindicated in women and paediatric patient

Patients with cardiac abnormalities
Children below 18 years of age
Patients using occlusive dressings or other medicines on the scalp
Patients with red, inflamed infection, or irritated or painful scalp (including psoriasis & sunburn)

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.

Acute Overdose

Increased systemic absorption of Minoxidil may potentially occur if higher-than-recommended doses of Minoxidil are applied to larger surface areas of the body or areas other than the scalp. There are no known cases of Minoxidil overdosage resulting from topical administration of Minoxidil.

Signs and symptoms of Minoxidil overdosage would primarily be cardiovascular effects associated with sodium and water retention, and tachycardia. Fluid retention can be managed with appropriate diuretic therapy. Clinically significant tachycardia can be controlled by administration of a beta-adrenergic blocking agent.