(polidocanol injectable foam)
Indications, Safety and Warnings
|Important Safety Information
The use of Varithena® is contraindicated in patients with known allergy to polidocanol and those with acute thromboembolic disease. Severe allergic reactions have been reported following administration of liquid polidocanol, including anaphylactic reactions, some of them fatal. Observe patients for at least 10 minutes following injection and be prepared to treat anaphylaxis appropriately. Intra-arterial injection or extravasation of polidocanol can cause severe necrosis, ischemia or gangrene. Patients with underlying arterial disease may be at increased risk for tissue ischemia. If intra-arterial injection of polidocanol occurs, consult a vascular surgeon immediately. Varithena® can cause venous thrombosis. 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. The most common adverse events observed were pain/discomfort in extremity, retained coagulum, injection site hematoma or pain, common femoral vein thrombus extension, superficial thrombophlebitis, and deep vein thrombosis. Physicians administering Varithena® must be experienced with venous procedures, possess a detailed working knowledge of the use of the duplex ultrasound in venous disease and be trained in the administration of Varithena®.
1. INDICATIONS AND USAGE
VARITHENA (polidocanol injectable foam) is indicated for the treatment of incompetent great saphenous veins, accessory saphenous veins, and visible varicosities of the great saphenous vein (GSV) system above and below the knee. VARITHENA improves the symptoms of superficial venous incompetence and the appearance of visible varicosities.
2. DOSAGE AND ADMINISTRATION
For intravenous use only.
VARITHENA is intended for intravenous injection using ultrasound guidance, dministered via a single cannula into the lumen of the target incompetent trunk veins or by direct injection into varicosities. Use up to 5 mL per injection and no more than 15 mL per session.
Physicians administering VARITHENA must be experienced with venous procedures and be trained in the administration of VARITHENA.
Activate VARITHENA using the VARITHENA oxygen canister and polidocanol canister (see Instructions for Use). Once a VARITHENA transfer unit is in place, foam can be generated and transferred to a syringe. Discard the syringe contents if there are any visible bubbles. Administer the injectable foam within 75 seconds of extraction from the canister to maintain injectable foam properties. Use a new sterile syringe after each injection. Use a new VARITHENA transfer unit for each treatment session.
Local anesthetic may be administered prior to cannula insertion but neither tumescent anesthesia nor patient sedation is required. Cannulate the vein to be treated using ultrasound guidance to confirm venousaccess.
Inject freshly generated VARITHENA injectable foam slowly (approximately 1mL/second in the GSV and 0.5mL/second in accessory veins or varicosities) while monitoring using ultrasound. Confirm venospasm of the treated vein using ultrasound.
When treating the proximal GSV, stop the injection when VARITHENA is 3-5 cm distal to the saphenofemoral junction (SFJ).
Apply compression bandaging and stockings and have the patient walk for at least 10 minutes, while being monitored. Maintain compression for 2 weeks after treatment.
Repeat treatment may be necessary if the size and extent of the veins to be treated require more than 15 mL of VARITHENA. Separate treatment sessions by a minimum of 5 days. Retained coagulum may be removed by aspiration (microthrombectomy) to improve comfort and reduce skin staining.
3. DOSAGE FORMS AND STRENGTHS
VARITHENA is available in the following presentations:
- 180 mg/18 mL (10 mg/mL)
- 77.5 mg/7.75 mL (10 mg/mL)
Once activated, VARITHENA is a white, injectable foam delivering a 1% polidocanol solution.Each mL of VARITHENA injectable foam contains 1.3 mg of polidocanol.
The use of VARITHENA is contraindicated in patients with:
- known allergy to polidocanol [see Warnings and Precautions (5.1)]
- acute thromboembolic disease
5. WARNINGS AND PRECAUTIONS
Severe allergic reactions have been reported following administration of liquid polidocanol, including anaphylactic reactions, some of them fatal. Observe patients for at least 10 minutes following injection and be prepared to treat anaphylaxis appropriately.
5.2 Tissue Ischemia and Necrosis
Intra-arterial injection or extravasation of polidocanol can cause severe necrosis, ischemia or gangrene.Patients with underlying arterial disease, such as marked peripheral arteriosclerosis or thromboangiitis obliterans (Buerger’s Disease) may be at increased risk for tissue ischemia. If intra-arterial injection of polidocanol occurs, consult a vascular surgeon immediately.
5.3 Venous Thrombosis
VARITHENA can cause venous thrombosis [see Adverse Reactions (6)]. 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.
6. ADVERSE REACTIONS
6.1 Clinical Trials Experience
Because clinical trials are conducted under controlled but widely varying conditions, adverse reaction rates observed in clinical trials of VARITHENA cannot be directly compared to rates in the clinical trials of other drugs or procedures and may not reflect the rates observed in practice. A total of 1333 patients with GSVI in 12 clinical trials were evaluated for safety when treated with VARITHENA at dose concentrations of 0.125%, 0.5%, 1.0%, or 2.0%, including 437 patients treated with VARITHENA in placebo-controlled clinical trials.Adverse reactions occurring in 3% more patients receiving VARITHENA 1% than receiving placebo are shown in Table 1.
|Pain in extremity||14 (9.3)||25 (16.8)|
|Infusion site thrombosis(a)||0||24 (16.1)|
|Contusion/injection site hematoma||9 (6.0)||23 (15.4)|
|Limb discomfort||5 (3.3)||18 (12.1)|
|Tenderness/injection site pain||5 (3.3)||16 (10.7)|
|Venous thrombosis limb(b)||0||12 (8.1)|
|Thrombophlebitis superficial||2 (1.3)||8 (5.4)|
|Deep vein thrombosis||0||7 (4.7)|
a Retained coagulum.
b Common femoral vein thrombus extension (non-occlusive thrombi starting in the superficial vein and extending into the common femoral vein).
In VARITHENA-treated patients, 80% of pain events in the treated extremity resolved within 1 week.
Proximal symptomatic venous thrombi occurred in <1% of patients treated with VARITHENA. Approximately half of patients with thrombi received treatment with anticoagulants.
Since VARITHENA induces thrombosis in the treated superficial veins, D-dimer is commonly elevated post-treatment and is not useful diagnostically to assess patients for venous thrombus following treatment with VARITHENA.
Neurologic adverse events (cerebrovascular accident, migraines) have been reported in patients following administration of physician compounded foam sclerosants. None of the 1333 patients in the VARITHENA trials experienced clinically important neurological or visual adverse events suggestive of cerebral gas embolism. The incidence of neurologic and visual adverse events within 1 day of treatment in the placebo-controlled studies was 2.7% in the pooled VARITHENA group and 4.0% in the placebo groups.
Skin discoloration adverse events were reported in 1.1% of the pooled VARITHENA group and 0.7% of the placebo group in the placebo-controlled studies.
7 DRUG INTERACTIONS
No specific drug interaction studies have been performed. There are no known drug interactions with VARITHENA.
8 USE IN SPECIFIC POPULATIONS
Few published case reports with use of polidocanol-containing products, including VARITHENA, in pregnant women have not identified any drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. Although no risks have been identified, there is minimal benefit in treating lower extremity varicosities during pregnancy and lower extremity varicosities that develop during pregnancy as they may spontaneously regress postpartum. In animal reproduction studies, no adverse developmental effects were observed with intravenous administration of polidocanol to pregnant rats and rabbits during organogenesis at dose levels up to approximately 13.5 and 12 times, respectively, the proposed maximum human dose of 15 mL of 1% VARITHENA based on body surface area (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.
Developmental reproductive toxicity testing was performed in rats and rabbits using intravenous administration of polidocanol solution. In rabbits, dose levels up to and including 10 mg/kg/day (approximately 12 times the proposed maximum human dose of 15 mL of 1% VARITHENA based on body surface area) did not produceany indication of adverse effects on embryo-fetal mortality, fetal weight, or the incidences of fetal abnormalities and variants. In rats administered 27 mg/kg/day of polidocanol solution (approximately 13.5 times the human dose based on body surface area), there were no adverse effects on pregnancy performance or fetal development. In a peri-natal and post-natal study in rats, dose levels of polidocanol up to 9 mg/kg/day (approximately 4.5 times the human dose based on body surface area) were without effects on the developmentof the conceptus and offspring, and at a dose level of 27 mg/kg/day of polidocanol solution (approximately 13.5 times the human dose based on body surface area), effects were confined to an equivocal reduction in body weights of first-generation males, and an associated equivocal delay in the age of preputial separation.
There are no data on the presence of polidocanol in human milk, the effects on the breastfed infant, or the effects on milk production. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk up to 8 hours after VARITHENA administration in order to minimize exposure to a breastfed infant.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Of the 1333 subjects in clinical studies treated with VARITHENA, 9.1% (n=121) were ≥65 years of age. No clinically important differences in safety or efficacy were observed between older and younger patients in all studies.
There are no known cases of overdosage with VARITHENA. In clinical studies, total volumes of up to 60mL of VARITHENA per treatment session have been administered.