Varithena is a non-thermal, non-tumescent treatment for the great saphenous vein system (GSV) and associated veins of the GSV system, and is the only FDA approved foam indicated for treating venous insufficiency. Varithena’s patented Microfoam UDSS™ technology produces cohesive, low-nitrogen microfoam1 with O2:CO2 (65:35) gas mixture with <0.8% nitrogen. The cohesive microfoam fills the lumen for circumferential contact1 where it’s designed to displace blood and destroy the endothelial lining efficiently. Varithena uses no tumescent anesthesia and takes about 10 minutes to administer.

VANISH-1 and VANISH-2 Clinical Trials

Varithena was evaluated in two randomized, blinded, multi-center clinical trials to asses the efficacy and safety for Varithena with the primary endpoint as improvement in varicose vein symptoms.* Clinical trial efficacy measures also included improvement in varicose vein appearance and physiological response to treatment.

• Data demonstrates efficacy and durability of Varithena treatment in the GSV
• To measure symptom relief, the VVSymQ® instrument was developed and thoroughly tested for reliability, sensitivity, and content validity, in accordance with FDA guidelines for the development of patient-reported outcomes (PRO) tools.2 It is the first and only varicose vein symptom PRO tool to meet these requirements.
• Using the VVSymQ® electronic daily diary, study patients rated the severity of the 5 most relevant varicose vein symptoms (HASTI™ Symptoms):
• Heaviness
• Achiness
• Swelling
• Throbbing
• Itching

*Primary endpoint: Improvement in symptoms as measured by change in VVSymQ® Score from baseline to Week 8.

Conclusion

Varithena provided clinically meaningful improvement* in symptoms and appearance in patients with incompetent great saphenous veins (GSV), accessory saphenous veins, and visible varicosities of the GSV system. Improvement was measured by a patient global impression of change (PGIC) questionnaire at Week 8.

*Percent of patients who reported their symptoms (or appearance of varicose veins) had “moderately improved” or “much improved” compared with baseline.

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 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. WARNINGS AND PRECAUTIONS

1.1 Anaphylaxis

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.

1.2 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. 

1.3 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. 

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.

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.