Sclerosing agents
https://themeditary.com/pro/asclera-prescribing-information-13057.html

Asclera Prescribing Information

Drug Detail:Asclera (Laureth-9 (polidocanol) [ lawr-eth-9 ])

Drug Class: Sclerosing agents

Contents
Uses Warnings Before Taking Dosage Side effects Interactions

Highlights of Prescribing Information

These highlights do not include all the information needed to use Asclera® Injection safely and effectively. See full prescribing information for Asclera.

Asclera (polidocanol) Injection, for intravenous use Initial U.S. Approval: 2010

Indications and Usage for Asclera

Asclera (polidocanol) is a sclerosing agent indicated to sclerose uncomplicated spider veins (varicose veins ≤1 mm in diameter) and uncomplicated reticular veins (varicose veins 1 to 3 mm in diameter) in the lower extremity. Asclera has not been studied in varicose veins more than 3mm in diameter. (1)

Asclera Dosage and Administration

For intravenous use only. Solution strength and the volume injected depend on the size and extent of the varicose veins. Extensive varicosities may require multiple treatment sessions. (2)

Spider veins (varicose veins ≤1 mm in diameter): Use Asclera 0.5%. (2)

Reticular veins (varicose veins 1 to 3 mm in diameter): Use Asclera 1%. (2)

Use 0.1 to 0.3 mL for each injection into each varicose vein. The maximum recommended volume per treatment session is 10 mL. (2)

Dosage Forms and Strengths

0.5% and 1% solution in 2 mL glass ampules. (3)

Contraindications

Known allergies to polidocanol. (4)

Patients with acute thromboembolic diseases. (4)

Warnings and Precautions

  • Be prepared to treat anaphylaxis. (5.1)
  • Venous Thrombosis and Pulmonary Embolism. (5.2)
  • Arterial Embolism. (5.3)
  • Tissue ischemia and necrosis: Do not inject intra-arterially. (5.4)

Adverse Reactions/Side Effects

The most common adverse reactions occurring at least 3% more frequently than on placebo are mild local reactions at the site of injection. (6)


To report SUSPECTED ADVERSE REACTIONS, contact Merz North America, Inc. at 1-844-469-6379 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 9/2019

Full Prescribing Information

2. Asclera Dosage and Administration

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 (5.3)].

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 thrombi that develop may be removed by microthrombectomy.

5. Warnings and Precautions

5.2 Venous Thrombosis and Pulmonary Embolism

Asclera can cause venous thrombosis and subsequent pulmonary embolism or other thrombotic events. Follow administration instructions closely and monitor for signs of venous thrombosis after treatment. Patients with reduced mobility, history of deep vein thrombosis or pulmonary embolism, or recent (within 3 months) major surgery, prolonged hospitalization or pregnancy are at increased risk for developing thrombosis.

5.3 Arterial Embolism

Stroke, transient ischemic attack, myocardial infarction, and impaired cardiac function have been reported in close temporal relationship with polidocanol administration. These events may be caused by air embolism when using the product foamed with room air (high nitrogen concentration) or thromboembolism. The safety and efficacy of polidocanol foamed with room air has not been established and its use should be avoided.

5.4 Tissue Ischemia and Necrosis

Intra-arterial injection or extravasation of polidocanol can cause severe necrosis, ischemia or gangrene. Take care in intravenous needle placement and use the smallest effective volume at each injection site. After the injection session is completed, apply compression with a stocking or bandage and have patients walk for 15-20 minutes. If intra-arterial injection of polidocanol occurs, consult a vascular surgeon immediately.

6. Adverse Reactions/Side Effects

6.1 Clinical Study Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In 5 controlled randomized clinical trials, Asclera has been administered to 401 patients with small or very small varicose veins (reticular and spider veins) and compared with another sclerosing agent and with placebo. Patients were 18 to 70 years old. The patient population was predominately female and consisted of Caucasian and Asian patients.

Table 1 shows adverse events more common with Asclera or sodium tetradecyl sulfate (STS) 1% than with placebo by at least 3% in the placebo-controlled EASI study [see Clinical Studies (14)]. All of these were injection site reactions and most were mild.

Table 1: Adverse Reactions in EASI-study
ASCLERA (180 patients)STS 1% (105 patients)Placebo (53 patients)
Injection site haematoma42%65%19%
Injection site irritation41%73%30%
Injection site discoloration38%74%4%
Injection site pain24%31%9%
Injection site pruritus19%27%4%
Injection site warmth16%21%6%
Neovascularisation8%20%4%
Injection site thrombosis6%1%0%

Ultrasound examinations at one week (±3 days) and 12 weeks (±2 weeks) after treatment did not reveal deep vein thrombosis in any treatment group.

6.2 Post-marketing Safety Experience

The following adverse reactions have been reported during use of polidocanol in world-wide experience. Because these reactions are reported voluntarily from a population of uncertain size and without a control group, it is not possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Immune system disorders: Anaphylactic shock, angioedema, urticaria generalized, asthma

Nervous system disorders: Cerebrovascular accident, migraine, paresthesia (local), loss of consciousness, confusional state, dizziness

Cardiac disorders: Cardiac arrest, palpitations

Vascular disorders: Deep vein thrombosis, pulmonary embolism, syncope vasovagal, circulatory collapse, vasculitis

Respiratory, thoracic and mediastinal disorders: Dyspnea

Skin and subcutaneous tissue disorders: Skin hyperpigmentation, dermatitis allergic, hypertrichosis (in the area of sclerotherapy)

General disorders and injection site conditions: Injection site necrosis, pyrexia, hot flush

Injury, poisoning and procedural complications: Nerve injury

8. Use In Specific Populations

8.1 Pregnancy

Risk Summary

The available data from case reports on use of polidocanol-containing products, including ASCLERA, in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Although none of these risks have been identified, there is minimal benefit in treating uncomplicated spider veins and reticular veins in the lower extremity during pregnancy and lower extremity varicosities that develop during pregnancy as they may spontaneously regress postpartum. The animal reproduction studies were conducted in a manner to achieve systemic exposure, while the intended clinical use is local exposure at the injection site with minimal to no systemic exposure; therefore, these data are not relevant to the intended clinical use (see Data).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Data

Animal Data

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.

These studies were conducted in a manner to achieve systemic exposure, while the intended clinical use is local exposure at the injection site with minimal to no systemic exposure; therefore, these data are not relevant to the intended clinical use.

14. Clinical Studies

Asclera was evaluated in a multicenter, randomized, double-blind, placebo- and comparator-controlled trial (EASI-study) in patients with spider or reticular varicose veins. A total of 338 patients were treated with Asclera [0.5% for spider veins (n=94), 1% for reticular veins (n=86)], sodium tetradecyl sulfate (STS) 1% (n=105), or placebo (0.9% isotonic saline solution) (n=53) for either spider or reticular veins. Patients were predominately female, ranging in age from 19 to 70 years. All of them received an intravenous injection in the first treatment session; repeat injections were given three and six weeks later if the previous injection was evaluated as unsuccessful (defined as 1, 2 or 3 on a 5-point scale, see below). Patients returned at 12 and 26 weeks after the last injection for final assessments.

The primary effectiveness endpoint was improvement of veins judged by a blinded panel. Digital images of the selected treatment area were taken prior to injection, compared with those taken at 12 weeks post-treatment, and rated on a 5-point scale (1 = worse than before, 2 = same as before, 3 = moderate improvement, 4 = good improvement, 5 = complete treatment success); results are shown in Table 2.
Table 2: Improvement of veins in digital photographs after 12 weeks and 26 weeks
Treatment GroupPolidocanol (n=155)STS (n=105)Placebo (n=53)
*
p <0.0001 compared to placebo (Wilcoxon-Mann-Whitney test)
Digital Photograph Scores at 12 weeks
Mean ± SD4.5* ± 0.74.5*± 0.72.2 ± 0.7
Digital Photograph Scores at 26 weeks
Mean ± SD4.5* ± 0.74.5*± 0.82.2 ± 0.7

The secondary efficacy criterion was the rate of treatment success, pre-defined as a score of 4 or 5 with patients scoring 1, 2, or 3 considered treatment failures; results are shown in Table 3.

Table 3: Treatment success rates at 12 weeks and 26 weeks
Treatment Success*Polidocanol (n=155)STS (n=105)Placebo (n=53)
*
Treatment success: Yes= Grade 4 to 5, No= Grade 1 to 3; derived from median of evaluation;
†
p<0.0001 compared to placebo.
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%

At 12 and 26 weeks, patients' judgement of the results was assessed by showing them the digital images of their treatment area taken at baseline and asking them to rate their satisfaction with their treatment using a verbal rating scale (1 = very unsatisfied; 2 = somewhat unsatisfied; 3 = slightly satisfied; 4 = satisfied and 5 = very satisfied); results are shown in Table 4.

Table 4: Patient satisfaction after 12 weeks and 26 weeks
Polidocanol (N=155)STS (N=105)Placebo (N=53)
*
p <0.0001 compared to STS and placebo
Patient satisfaction with treatment after 12 weeks (Visit 4)
Satisfied or very satisfied87%*64%14%
Patient satisfaction with treatment after 26 weeks (Visit 5)
Satisfied or very satisfied84%*63%16%

PRINCIPAL DISPLAY PANEL - 10 mg Ampule Carton

NDC 46783-121-52

ASCLERA®
(polidocanol) Injection

10 mg per 2 mL
(5 mg per mL)

0.5%

For Intravenous Use Only
Rx Only
Single use: Discard unused portion
Contains:
5 ampules each containing 10 mg per 2 mL

PRINCIPAL DISPLAY PANEL - 10 mg Ampule Carton
ASCLERA
polidocanol injection, solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:46783-221
Route of AdministrationINTRAVENOUS
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
POLIDOCANOL (UNII: 0AWH8BFG9A) (POLIDOCANOL - UNII:0AWH8BFG9A) POLIDOCANOL0.01000 g in 1 mL
Inactive Ingredients
Ingredient NameStrength
ALCOHOL (UNII: 3K9958V90M) 0.04200 g in 1 mL
MONOBASIC POTASSIUM PHOSPHATE (UNII: 4J9FJ0HL51) 0.00085 g in 1 mL
SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM (UNII: GR686LBA74) 0.00240 g in 1 mL
WATER (UNII: 059QF0KO0R) 0.93875 g in 1 mL
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:46783-221-522 mL in 1 AMPULE; Type 0: Not a Combination Product06/01/201008/31/2022
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA02120106/01/201008/31/2022
ASCLERA
polidocanol injection, solution
Product Information
Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:46783-121
Route of AdministrationINTRAVENOUS
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
POLIDOCANOL (UNII: 0AWH8BFG9A) (POLIDOCANOL - UNII:0AWH8BFG9A) POLIDOCANOL0.00500 g in 1 mL
Inactive Ingredients
Ingredient NameStrength
ALCOHOL (UNII: 3K9958V90M) 0.04200 g in 1 mL
MONOBASIC POTASSIUM PHOSPHATE (UNII: 4J9FJ0HL51) 0.00043 g in 1 mL
SODIUM PHOSPHATE, DIBASIC, UNSPECIFIED FORM (UNII: GR686LBA74) 0.00120 g in 1 mL
WATER (UNII: 059QF0KO0R) 0.94437 g in 1 mL
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:46783-121-522 mL in 1 AMPULE; Type 0: Not a Combination Product06/01/201008/31/2022
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA02120106/01/201008/31/2022
Labeler - Merz North America, Inc (028147846)
Establishment
NameAddressID/FEIBusiness Operations
Chemische Fabrik Kreussler & Co. GmbH315568337MANUFACTURE(46783-221, 46783-121)

Share this Article
Latest News
Related Drugs