These highlights do not include all the information needed to use see full prescribing information for and Initial U.S. Approval

3 DOSAGE FORMS AND STRENGTHS Asclera is available as a 0.5% and 1% solution in 2 mL glass ampules.

	Asclera (180 patients)	STS 1% (105 patients)	Placebo (53 patients)
Injection site haematoma	42%	65%	19%
Injection site irritation	41%	73%	30%
Injection site discoloration	38%	74%	4%
Injection site pain	24%	31%	9%
Injection site pruritus	19%	27%	4%
Injection site warmth	16%	21%	6%
Neovascularisation	8%	20%	4%
Injection site thrombosis	6%	1%	0%

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy PregnancyCategory C. Polidocanol has been shown to have an embryocidal effect inrabbits when given in doses approximately equal (on the basis of bodysurface area) to the human dose. This effect may have been secondary tomaternal toxicity. There are no adequate and well controlled studies inpregnant women. Asclera should not be used during pregnancy. Animal Studies

Developmentalreproductive toxicity testing was performed in rats and rabbits withintravenous administration. Polidocanol induced maternal and fetaltoxicity in rabbits, including reduced mean fetal weight and reducedfetal survival, when administered during gestation days 6-20 at doses 4and 10 mg/kg, but it did not cause skeletal or visceral abnormalities.No adverse maternal or fetal effects were observed in rabbits at a doseof 2 mg/kg. No evidence of teratogenicity or fetal toxicity wasobserved in rats dosed during gestation days 6-17 with doses up to 10mg/kg. Polidocanol did not affect the ability of rats to deliver andrear pups when administered intermittently by intravenous injectionfrom gestation day 17 to post-partum day 21 at doses up to 10 mg/kg.

Human Studies

There are no adequate and well-controlled studies on the use of Asclera in pregnant women.

11 DESCRIPTION Asclerais a sterile, nonpyrogenic, and colorless to faintly greenish-yellowsolution of polidocanol for intravenous use as a sclerosing agent. Theactive ingredient, polidocanol is a non-ionic detergent, consisting oftwo components, a polar hydrophillic (dodecyl alcohol) and an apolarhydrophobic (polyethylene oxide) chain. Polidocanol has the followingstructural formula: CH(OCHCH)OH Polyethylene glycol monododecyl ether Mean extent of polymerization (n): Approximately 9 Mean molecular weight: Approximately 600 EachmL contains 5 mg (0.5%) or 10 mg (1.0%) polidocanol in water forinjection with 5% (v/v) ethanol at pH 6.5-8.0; disodium hydrogenphosphate dihydrate, potassium dihydrogen phosphate are added for pHadjustment.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The active ingredient of Asclera is polidocanol. Polidocanolis a sclerosing agent that locally damages the endothelium of bloodvessels. When injected intravenously, polidocanol induces endothelialdamage. Platelets then aggregate at the site of damage and attach tothe venous wall. Eventually, a dense network of platelets, cellulardebris, and fibrin occludes the vessel. Finally, the occluded vein isreplaced with connective fibrous tissue. 12.2 Pharmacodynamics Polidocanol has a concentration and volume dependent damaging effect on the endothelium of blood vessels. 12.3 Pharmacokinetics Duringthe major effectiveness study (EASI-trial), scheduled blood sampleswere taken from a sub-group of 22 patients to measure plasma levels ofpolidocanol after Asclera treatment of spider and reticular veins. Lowsystemic blood levels of polidocanol were seen in some patients.

Treatment Group	Polidocanol (n=155)	STS (n=105)	Placebo (n=53)
Digital Photograph Scores at 12 Weeks
Mean + SD	4.5* + 0.7	4.5* + 0.7	2.2 + 0.7
Digital Photograph Scores at 26 Weeks
Mean + SD	4.5* + 0.7	4.5* + 0.8	2.2 + 0.7

Treatment success?*	Polidocanol (n=155)	STS (n=105)	Placebo (n=53)
At 12 weeks (Visit 4)
Yes	95%**	92%**	8%
No	5%	8%	92%
Missing	0.6%	0%	0%
At 26 weeks (Visit 5)
Yes	95%**	91%**	6%
No	5%	9%	94%

	Polidocanol (n=155)	STS (n=105)	Placebo (n=53)
Patient satisfaction with treatment after 12 weeks (Visit 4)
Satisfied or very satisfied	87%*	64%	14%
Patient satisfaction with treatment after 26 weeks (Visit 5)
Satisfied or very satisfied	84%*	63%	16%

16 HOW SUPPLIED/STORAGE AND HANDLING

Asclera is supplied in single use, preservative free ampules in the following packages:

17 PATIENT COUNSELING INFORMATION

Advise patient to wear compression stockings or support hose on the treated legs continuously for 2 to 3 days and for 2 to 3 weeks during the daytime. Compression stockings or support hose should be thigh or knee high depending on the area treated in order to provide adequate coverage.

Manufacturer

Merz Aesthetics, Inc.