Asclera Injection

For intravenous use only. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter is seen or if the contents of the vial are discolored or if the vial is damaged in any way.

For spider veins (varicose veins ≤1 mm in diameter), use Asclera 0.5%. For reticular veins (varicose veins 1 to 3 mm in diameter), use Asclera 1%. Use 0.1 to 0.3 mL per injection and no more than 10 mL per session.

Use a syringe (glass or plastic) with a fine needle (typically, 26- or 30-gauge). Insert the needle tangentially into the vein and inject the solution slowly while the needle is still in the vein. Apply only gentle pressure during injection to prevent vein rupture. After the needle has been removed and the injection site has been covered, apply compression in the form of a stocking or bandage. After the treatment session, encourage the patient to walk for 15 to 20 minutes. Keep the patient under observation to detect any anaphylactic or allergic reaction (see Warnings and Precautions [5]).

Maintain compression for 2 to 3 days after treatment of spider veins and for 5 to 7 days for reticular veins. For extensive varicosities, longer compression treatment with compression bandages or a gradient compression stocking of a higher compression class is recommended. Post-treatment compression is necessary to reduce the risk of deep vein thrombosis.

Repeat treatments may be necessary if the extent of the varicose veins requires more than 10 mL. These treatments should be separated by 1 to 2 weeks.

Small intravaricose blood clots (thrombi) that develop may be removed by stab incision and thrombus expression (microthrombectomy).

Anaphylaxis

Severe allergic reactions have been reported following polidocanol use, including anaphylactic reactions, some of them fatal. Severe reactions are more frequent with use of larger volumes (> 3 mL). The dose of polidocanol should therefore be minimized. Be prepared to treat anaphylaxis appropriately.

Severe adverse local effects, including tissue necrosis, may occur following extravasation; therefore, care should be taken in intravenous needle placement and the smallest effective volume at each injection site should be used.

After the injection session is completed, apply compression with a stocking or bandage, and have the patient walk for 15-20 minutes. Keep the patient under supervision during this period to treat any anaphylactic or allergic reaction (see Dosage and Administration [2]).

Accidental Intra-arterial Injection

Intra-arterial injection can cause severe necrosis, ischemia or gangrene. If this occurs consult a vascular surgeon immediately.

Inadvertent Perivascular Injection

Inadvertent perivascular injection of Asclera can cause pain. If pain is severe, a local anesthetic (without adrenaline) may be injected.

Pregnancy

Pregnancy Category C. Polidocanol has been shown to have an embryocidal effect in rabbits when given in doses approximately equal (on the basis of body surface area) to the human dose. This effect may have been secondary to maternal toxicity. There are no adequate and well-controlled studies in pregnant women. Asclera should not be used during pregnancy.

Animal Studies

Developmental reproductive toxicity testing was performed in rats and rabbits with intravenous administration. Polidocanol induced maternal and fetal toxicity in rabbits, including reduced mean fetal weight and reduced fetal survival, when administered during gestation days 6-20 at doses of 4 and 10 mg/kg, but it did not cause skeletal or visceral abnormalities. No adverse maternal or fetal effects were observed in rabbits at a dose of 2 mg/kg. No evidence of teratogenicity or fetal toxicity was observed in rats dosed during gestation days 6-17 with doses up to 10 mg/kg. Polidocanol did not affect the ability of rats to deliver and rear pups when administered intermittently by intravenous injection from 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.

Labor and Delivery

The effects of Asclera on labor and delivery in pregnant women are unknown.

Nursing Mothers

It is not known whether polidocanol is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants, avoid administering to a nursing woman.

Pediatric Use

The safety and effectiveness of Asclera in pediatric patients have not been established.

Geriatric Use

Clinical studies of Asclera did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Mechanism of Action

The active ingredient of Asclera is polidocanol.

Polidocanol is a sclerosing agent that locally damages the endothelium of blood vessels. When injected intravenously, polidocanol induces endothelial damage. Platelets then aggregate at the site of damage and attach to the venous wall. Eventually, a dense network of platelets, cellular debris, and fibrin occludes the vessel. Finally, the occluded vein is replaced with connective fibrous tissue.

Pharmacodynamics

Polidocanol has a concentration- and volume-dependent damaging effect on the endothelium of blood vessels.

Pharmacokinetics

During the major effectiveness study (EASI-trial), scheduled blood samples were taken from a sub-group of 22 patients to measure plasma levels of polidocanol after Asclera treatment of spider and reticular veins. Low systemic blood levels of polidocanol were seen in some patients.

The mean t1/2 of polidocanol in 4 patients with evaluable data receiving 4.5 -18.0 mg was 1.5 h.

Commonly reported side effects of polidocanol include: hematoma at injection site, hematoma, pain at injection site, and skin discoloration at injection site. Other side effects include: pain. See below for a comprehensive list of adverse effects.

Data not available

Data not available

Storage requirements:
-Consult the manufacturer product information.

Reconstitution/preparation techniques:
-Consult the manufacturer product information.