IMPULSE is rapidly absorbed after oral administration. Cmax is reached as early as 15 minutes (median 60 minutes) of oral dosing in the fasted state.

Due to a considerable first-pass effect, the mean absolute oral bioavailability is about 15%.

After oral dosing of IMPULSE AUC and Cmax increase almost dose-proportionally over the recommended dose range(60-120 mg).

When IMPULSE 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%. IMPULSE AUC was not affected. After a normal meal (containing 30% fat) IMPULSE pharmacokinetic parameter(Cmax, Tmax, and AUC) were not affected at all.

Based on these results IMPULSE can be taken with of without food.

Description: The mean steady state volume of distribution (Vss) for IMPULSE is 208 L, indicating distribution into the tissues.

IMUPULSE and its major circulating metabolite (M1) are highly bound 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 IMPULSE 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.

IMPULSE is metabolized predominantly by hepatic enzymes via CYP3A4, with some contribution from CYP2A5 and CYP2C9 isoforms.

Mean elimination half life (t1/2) is about 4-5 hours.

In humans, the major circulating metabolite (M1) results from desethylation at the piperazine moiety of IMPULSE, 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 M1 are in form of its glucuronide-conjugate (glucuonic acid) in systemic circulation.

The plasma concentration of non-glucuronidated M1 is about 26% that of the parent compound. The metabolite M1 show a phosphodiesterase Selectivity Profile Similar to that of IMPULSE and an in vitro inhibitory potency for PDE5 of approximately 28% compared to IMPULSE, resulting in an efficacy contribution of about 7%.

The total boby clearance of IMPULSE is 56 l/h with a resultant terminal half life of about 4-5 hours.

After oral administration, IMPULSE 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).

Elderly:

IMPULSE 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 52% 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, IMPULSE 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 IMPULSE plasma exposure (AUC and Cmax) was observed.

The Pharmacokinetics of IMPULSE has not been studied in patients requiring dialysis.

Hepatic insufficiency:

In patients with mild to moderate hepatic impairment (Child-Pugh A and B), IMPULSE clearance was reduced in proportion to the degree of hepatic impairment.

In patients with mild hepatic impairment (Chil-pugh A), IMPULSE 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), IMPULSE AUC was increased 2.6-fold (160%) and Cmax was increased 2.3-fold (130%), compared to healthy control subjects.

The pharmacokinetics of IMPULSE has not been studied in patents with severe hepatic impairment (Child-Pugh C).

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 Single doses of Maalox (antacid; magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability (AUC) or the maximum concentraton (Cmax) of IMPULSE.

IMPULSE (60 mg) did not influence the bleeding time when taken alone or in combination with low dose Acetylsalicylic Acid (2*81 mg tablets)

IMPULSE (120 mg) did not potentiate the hypotensive effects of Alcohol (0.5 g/kg bw.) The pharmacokinetics of IMPULSE where not altered.

Population pharmacokinetic investigations of phase III data revealed no significant effect of Acetysalicylic Acid, ACE-inhibitors, beta-blockers, weak CYP 3A4-inhibitors, diuretics and metformin) on the pharmacokinetics of IMPULSE.

Food and dietary products: when IMPULSE is taken with a high fat meal (containg 57% fat), the rate of absorption is reduced with an increase in the median time of maximal plasma concentration of 60 minutes and a mean reduction in peak plasma concentration of 20%. IMPULSE bioavailability was not affected. After a normal meal (containing 30% fat) IMPULSE pharmacokinetic parameter were not affected at all. Based on these results IMPULSE can be taken with or without food.

Pregnancy and lactation:

Is not indicated for use in newborns, children or women.

IMPULSE was administered to over 7800 patients during clinical trials worldwide.

IMPULSE was generally very well tolerated.

Adverse events were generally transient and mild to moderate in nature

For adverse reactions reported in <1% of patients, only those which warrant special attention, because of their possible association with serious disease states of otherwise clinical relevance, and which have been reported in > 2 cases are listed. In a phase I study with 40 mg (twice the maximum recommended dose) priapism was observed in 2 cases as ADR.

Myocardial infarction (M) has been reported in temporal association with the use of IMPULSE and sexual activity, but it is not possible to determine whether MI is related directly to IMPULSE, or to sexual activity, to the patient’s underlying cardiovascular disease, or to a combination of these factors.

STORAGE: Stored at 25â„?or below as directed by doctors, moisture proofing.

USAGE: Orally taken one granule 40 minutes before your need, each granule will retain in the body for about 72 hours.

CONTENT: 120mg*7 grain*12boxes/pack

NOTES: Kept all drugs beyond the touch of children.

WARNING: The retail prescription to be sold is only available for urologist, psychiatrist, endocrine and venereal doctors.

MANUFACTURING LICENSE: BOC11511020