Biotin capsule 10 boxes

Description:

Biotin

Pharmacokinetic properties
Absorption:

Biotin is rapidly absorbed after oral administration. Cmax is reached as early as 15 minutes,in 90% of the time Cmax is reached within 30 tp 120 minutes (median 60minutes) of oral dosing in the fasted state.
Due to a considerable first-pass effect, the mean absolute oral bioavailability is abut 15%.
After oral dosing of Biotin AUC and Cmax increase almos dose-proportionally over the recommended dose range (60-120mg).

When Biotin is taken with a high fat meal(containing 57% fat),the rate of absorption is reduced with an increase in the median Tmax of 60 minutes and a mean reduction in Cmax of 20%. Biotin AUC was not affected.After a normal meal (containing 30%fat) Biotin pharmacokinetic parameter(Cmax,Tmax,and AUC)were not affected at all. Based on tese results Biotin can be taken with or without food.

Distrbution:

The mean steady state volume of distribution(Vss)for Biotin is 208 L,indicating distribution into the tissues. Biotin and its major circulating metabolite (M1)are highly bond to plasma proteins (about 95%for parent frug or M1).This protein binding is reversible and independent of total drug concentrations.
Based upon measurements of Biotin in semen of healthy subjects 90 minutes after dosing,not more than 0.00012% of the administered dose may appear in the semen of patients.

Metabolism:

Biotin is metabolized predominantly by hepatic enzymes via CYP3A4, with some contribution from CYP3A5 and CYP29 isoforms.
Mean elimination half life(t1/2)is about 4-5hours.
In humans, the major circulating metabolite (M1) results from desethylation at the piperazine moiety of Biotin. and is subject to further metabolism. The plasma elimination half life of the metabolite M1 is approximately 4 h, comparable to the parent drug.

Parts of M1are in form of its glucuronide-conjugate(glucuronic acid)in systemic circulation.

The plasma concentration of non-glucuronidated M1 is about 26% that of the paren compound. The metabolite M1 show a phosphodiesterase selectivity profile similar to that of Biotin and an in vitro inhibitory potency for PDE5 of approximately 28%compared to Biotin,resulting in an efficacy contribution of about 7%.

Excretion:

The total boby clearance of Biotin is 56 1/h with a resultant terminal half lfe of about 4-5 hours.
After oral administration,Biotin is excreted as metabolites predominantly in the faeces )approximately 91-95%of administered oral dose) and to a lesser extent in the urine (approximately 2-6%of administered oral dose).

Pharmacokinetics in special populations:

Elderly:

Biotin hepatic clearance in healthy elderly volunteers(60 years or over) was reduced as compared to volunteers of younger age(45 years and below).On average , elderly males had a 50% higher AUC than younger males which is within the variability observed in clinical trials. No overall differences in safety or effectiveness were observed between elderly and younger subjects in placebo controlled clinical trials.

Renal insufficiency:

In patients with mild (CLcr>50-80 ml/min)to moderate (CLcr>30-50 ml/min) renal impairment,Biotin pharmacokinetics Were similar to that of a normal renal function control group. In volunteers with severe renal impairment (CLcr>30 ml/min)the mean AUC was increased by 21% and the mean Cmax decreased by 23%,compared to volunteers with no renal impairment. No statistically significant correlation between creatinine clearance and Biotin Plasma exposure (AUC and Cmax)was observed.
The pharmacokinetics of Biotin has not been studied in patients requiring dialysis.

Hepatic insufficiency:

In patients with mild to moderate hepatic impairment (Child –Pugh A and B),Biotin clearance was reduced in proportion to the degree of hepatic impairment.
Proportion to the degree of hepatic impairment.
In patients with mild hepatic impairment (Chil-Pugh A),Biotin AUC and Cmax were increased 1.2-fold (AUC by 17%,and Cmax by 22%).compared to healthy.
Control subjects.
In patients with moderate hepatic impairment (Child-Pugh B),Biotin AUC was increased 2.6-fold (160%)and Cmax was increased 2.3-fold (130%),compared to healthy control subjects.
The phamacokinetics of Biotin has not been studied in patents with severe hepatic impairment (Child –Pugh C) Indications.
Treatment of erectile dysfunction (inability to achieve of maintain penile erection sufficient for satisfactory sexual performance).
In order for Biotin to be effective ,sexual stimulation is required.
Posology and method of administration.
Recommended usual dose.
The recommended starting dose is 50mg taken as needed app. oximately 25-60 minutes before sexual activity. In chinical trials

Biotin was shown to be efficacious when taken up tp 4-5hours before sexual activity. The maximum recommended dose frequency is once per day .BIOTIN can be taken with or without food. The onset of activity may be delayed if taken with a high fat meal. Sexual stimulation is required for a natural response to treatment.(see ,Interaction with other medicaments and other forms of interaction).

Range of dose:

Based on efficacy and tolerability ,the dose may be increased to 120mg once daily. A maximum dose of 30mg should not be exceeded when used in combination with the potent cytochrome P450(CYP) 3A4 inhibitor erythromycin (increased AUC by 4 fold )

Concomitant use with ketoconazole ,itraconazole, indinavir or ritonavir, should be avoided as Biotin AUC is increased by 10-16 fold if the drugs are combined (se”Special warnings and special precautions for use”).

Method of administration:

For oral use.

Elderly (above 56 years):

Hepatic clearance of healthy elderly volunteers was reduced. The AUC and Cmax in the elderly are higher by 52% and 34%as compared to young male volunteers (18-45years).
Therefore,a slarting dose of 30mg is recommended.(see”Contraindications”)

Children(from birth to 16 years):

BIOTIN is no indicated for use in children.

Hepatic impairment:

No dose adjustment needed in patients with mild hepatic impairment (Child -Pugh A).
Biotin clearance is reduced in patients with moderate hepatic impairment (Dhild –Pugh B).Therefore a starting dose of 30mg is recommended .(see”Contraindications”)
The pharmacokinetics has not been studied in patients with severe hepatic impairment (Child –Pugh C)

Renal impairment:

No dose adjustment is needed in patients with mild (CLcr>50-80 ml/min)and moderate(CLcr>30-50 ml/min)renal impairment.
In patients with severe renal impairment (CLor<30 ml/min),a starting dose of 30mg should be considered .
Use in Women.

Biotin is not indicated for use in women.

Concomitant Medications:

Consistent with vasodilatory effects of alpha–blockers and Biotin. The concomitant use of Biotin with alpha-blockers may lead to symptomatic hypotension in some patients Until further data are available,a maximum dose of 30mg Biotin with alpha –blockers must not be exceeded. Biotin 30mg should not be taken within 6 h of an alpha-blocker(see interaction with Other Medicaments and Other Forms of Interaction).Concomitant treatment should only be initiated if the patient is stable on his alpha-blocker therapy.
A maximum dose of 30mg should not be exceeded when use in combination with the potent Cytochrome P450(CYP)3A4 inhibitor erythromycin.
A maximum dose of 30mg should not be exceeded when used in combination with the potent Cytochrome P450(CYP)3A4 inhibitors ketoconazole and itraconazole. Biotin must not be taken with dosages of ketoconazole and itraconazole higher than 200mg.
Concomitant use with HLV protease Inhibitors such as indinavir and ritonavir, which are very potent inhibitors of CPY3A4, is contraindicated.

Contraindications

Contraindicated in patients with hypersensitivity to any of the drug’s components (active or inactive ingredients).
Consistent with the effects of PDE inhibition on the nitric oxide /cGMP-pathway ,PDE5 inhibitors may potentiate the hypotensive effects of nitrates. BIOTIN is thus contraindicated in patients who are concomitantly treated with nitrates or nitric oxide donors.
He safety of BIOTIN nas not been studied in the following sub-groups of patients and its use is therefore contraindicated until further information is available:severe hepatic impairment (Child –Pugh C).endstage renal disease requiring dialysis. hypotension(resting systolic blood pressure of <90 mmHg).recent history of stoke or myocardial infarction (within last 5 months).unstable angina ,and known hereditary.
Degenerative retinal disorders xuch as retinitis pigmentosa.
In men for whom sexual activity is not recommended because of their underlying cardiovascular status,agents for the treatment of erectile dysfunction should not be used.
Concomitant use of Biotin with potent CYP3A4 inhibitors such as ketoconazole and itraconazole (oralform) is contraindicated in men older than 75 years.
Concomitant use of Biotin with HIV protease inhibitors such as indinavir of ritonavir is contraindicated. as they are potent inhibitors of CYP 3A4.
Special warmings and special precautions for use .
Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of Cardiac risk associated with sexual activity. Biotin has vasodilator properties which may result in mild and transient decreases in blood.
Pressure,Patients with left ventricular outflow obstruction e .g. aortic stenosis and idiopathic hypertrophic subarctic stenosis ,can be sensitive to the.
Action of vasodilators including Type 5 phosphodiesterase inhibitors.
A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before pharmacological treatment is considered.

Others

Biotin(120mg),when co-administered with Glibenclamide (Glyburide,3.5mg). did not affect the relative bioavailability of Glibenclamide (no effect on AUC and Cmax of Glibenclamide).There was no evidence that Biotin phamacokinetics were altered by coadministration of Glibenclamide.
No pharmacokinetic and pharmacodynamic (prothrombin time and clotting factor 11, Vll and X) interaction was shown when Warfarin (20mg) was co-administered with Biotin (120mg). Biotin pharmacokinetics was not affected by co-administration of Warfarin.
No relevant pharmacokinetic interaction was shown when Biotin (120mg)f, was co-administered with Nifedipine(30 of 60mg). The combined treatment of Biotin and Nifedipine did not lead to pharmacodnamic interaction(as compared to placebo. Biotin produced mean additional blood pressure reductions of 5.9 mmHg and 5.25 mmHg for supine systolic and diastolic blood pressure respectively) Since alpha-blocker monotherapy can cause marked lowering of blood pressure, especially postural hypotension and syncope, interaction studies were conducted with Biotin. Following shor –term alpha blockade with terazosin 60mg or tamsulosin 0.4mg daily in normotensive volunteers ,the addition of Biotin 60mg and 120mg dosed with the alpha-blocker to achieve simultaneous Cmax with both drugs, resulted in a number of cases of standing systolic BP<85 mmHg, reduction in standing systolic BP>30 mmHg and cases of symptomatic postural hypotension When dosed to produce a 6 hour separation in Cmax ther were fewer cases with a reduction in standing systolic BP and of systolic standing BFP<85 mmHg, particularly with tamsulosin. Mean maximum reductions of up to 8 mmHg for standing systolic BP and up to 7 mmHg for standing diastolic BP were observed for tamsulosin regardless of the dosing interval.

A further study of Biotin 30mg on the background of stable chronic alpha-blocker therapy (tamsulosin 0.4mg or terazosin 30mg and 60 mg) in patients with benign prostatic hypertrophy (BPH)was performed .Dosing of the alpha-blocker and Biotin 30mg was simultaneous or separated by 6hours. Mean maximum reductions of up to 6 mmHg for standing systolic BFP and up to 3 mmHg for standing diastolic BP were observed regardless of the dosing interval or the alpha-blocker. Three tamsulosin-treated subjects had transient standing systolic BP<85 mmHg following Biotin treatment on at least one occasion, however none of these subjects had symptoms of hypotension. For the terazosin-treated subjects dosed simultaneously with Biotin 30mg ,5 had a reduction in standing systolic BP of >30 mmGg (compared tp 2 on placebo) and one subject exhibited exhibited standing systolic BP<82 mmHg with dizziness. A 6 hours separation of terazosin and Biotin 30 mg did not result in any reductions in standing systolic BP of >30 mmHg or and cases of standing systolic BP<85 mmHg or of symptoms of hypotension.

Lack of pharmacokinetic interaction was shown when Digoxin (0.375mg) in steady-state was co –administered with Biotin f(120mg)over 14 days every other day. There was no evidence that Biotin phamacokinetics were altered by co-administration of Digoxin.

Bioavailability of Biotin was not affected by co-administration of the H2-antagonists Ranitidine(150mg b.i .d.)and Cimetidine (400mg b.i.d.).
Single doses of Maalox (antacid; magnesium hydroxide / aluminium ) did not affect the bioavailability (AUC)or the maximum concentration(Cmax)of Biotin.
Biotin(60mg)did not influence the bleeding time when taken alone or in combination with low dose Acetylsalicylic Acid(2*81 mg tablets)
Biotin (120mg)did not potentiate the hypotensive effects of Alcohol(0.5g/kg bw).The phamacokinetics of Biotin where not altered.
Population pharmacokinetic investigations of phase lll data revealed no significant effect of Acetysalicylic Acid, Ace –inhibitors ,beta-blockers,weak CYP 3A4-inhibitors, diuretics and medications for the treatment o diabetes(sulfonylureas and metformin)on the pharmacokinetics of Biotin.
Food and dietary products:when Biotin is taken with a high fat meal (containing 57% fat)the rate of absorption is reduced with an increase in the median time of maxima plasma concentration of 60minutes and a mean reduction in peak plasma concentration of 20%.Biotin bioavailability was not affected .After a normal meal (containing 30% fat f)biotin pharmacokinetic parameter were not affected at all. Based on these results Biotin can be taken with or without food .

Pregnancy and lactation:

Is not indicated for us in newborns,children or women.
Undesirable effects
BLOTIN was administered to over 7800 patients during dlinical trials worldwide.
BIOTIN was generally very well tolerated.
Adverse events were generally transient and mild to moderate in nature IN a study evaluating visual function with twice the maximum recommended dose of Biotin ,some patients were found to have mild and transient impairment of colour discrimination in the blue/green range and in the purple range one hour after dosing.
These changes had improved by six hours and no changes were present at 24 hours.
The majority of these patients had no subjective visual symptoms.
*Fo adverse reactions reported in <1% of patients. only those which warrant special attention because of their possible association with serious disease states or of otherwise clinical relevance. and which have been reported in >2 cases are listed.
In a phase 1 study with 40mg (twice the maximum recommended dose )priapism was observed in 2 cases as ADR.

Post-Marketing

Myocardial infarction(M)has been reported in temporal association with the use of Biotin and sexual activity ,but it is not possible to determine whether M1 is related directly to Biotin,or to sexual activity. to the patient’s underlying cardiovascular disease ,or to a combination of these factors.
STORAGE:Stored at 25℃.or below as directed by doctors. moisture proofing.
USAGE:Orally taken one granule 60 minutes before your need ,each granule will retain in the body for about 72 hours.
CONENT:120mg.
NOES:Kept All Drugs Beyond The Touch Of Children.
WARNING :The retail prescription to be sole is only available for urologist, psychiatrist,endocrine and venereal doctors.