CLASSES
Varicose Therapy, Systemic
DESCRIPTION
Injectable sclerosing agent
Used for treatment of incompetent veins and visible varicosities of the lower extremities
Can cause venous thrombosis and pulmonary embolism or other thrombotic events
COMMON BRAND NAMES
Varithena
HOW SUPPLIED
Varithena Intravenous Inj Emulsion: 18mL, 180mg
DOSAGE & INDICATIONS
For the treatment of varicose veins.
For the treatment of uncomplicated spider veins in the lower extremity (varicose veins <= 1 mm in diameter).
Intravenous dosage [injectable solution (Asclera)]
Adults
Insert the needle tangentially into the affected vein; then, with the needle still in the vein, slowly inject 0.1 to 0.3 mL of polidocanol 0.5% solution. Multiple injections may be necessary; however, do not inject more than 10 mL per session. After the needle has been removed, cover the injection site and apply compression in the form of a stocking or bandage. Encourage patients to walk for 15 to 20 minutes after each treatment session. Keep the patient under observation during this time to observe any allergic or anaphylactic reaction. Maintain compression for 2 to 3 days after treatment. Longer compression with compression bandages or a gradient compression stocking of a higher class may be necessary for more extensive varicosities. Post-treatment compression is necessary to reduce the risk of deep vein thrombosis. Repeat treatments may be necessary if the varicose vein requires more than 10 mL. Separate treatments by 1 to 2 weeks. If small intravaricose blood clots (thrombi) develop, they may be removed by stab incision and thrombus expression (thrombectomy).
For the treatment of uncomplicated reticular veins (varicose veins 1 to 3 mm in diameter).
NOTE: Asclera has not been studied in varicose veins > 3 mm in diameter.
Intravenous dosage [injectable solution (Asclera)]
Adults
Insert the needle tangentially into the affected vein; then, with the needle still in the vein, slowly inject 0.1 to 0.3 mL of polidocanol 1% solution. Multiple injections may be necessary; however, do not inject more than 10 mL per session. After the needle has been removed, cover the injection site and apply compression in the form of a stocking or bandage. Encourage patients to walk for 15 to 20 minutes after each treatment session. Keep the patient under observation during this time to observe any allergic or anaphylactic reaction. Maintain compression for 2 to 3 days after treatment. Longer compression with compression bandages or a gradient compression stocking of a higher class may be necessary for more extensive varicosities. Post-treatment compression is necessary to reduce the risk of deep vein thrombosis. Repeat treatments may be necessary if the varicose vein requires more than 10 mL. Separate treatments by 1 to 2 weeks. If small intravaricose blood clots (thrombi) develop, they may be removed by stab incision and thrombus expression (thrombectomy).
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.
Intravenous dosage [injectable foam (Varithena)]
Adults
Using ultrasound guidance, inject up to 5 mL of polidocanol 1% foam into affected vein or varicosity slowly (approximately 1 mL/second in the GSV and 0.5 mL/second in accessory veins or varicosities). Confirm venospasm of the treated vein using ultrasound. Multiple injections may be necessary; however, do not inject more than 15 mL per session. Cannulate the vein to be treated using ultrasound guidance to confirm venous access. Local anesthetic may be administered prior to cannula insertion but neither tumescent anesthesia nor patient sedation is required. Administer polidocanol via a single cannula into the lumen of the target incompetent trunk veins or by direct injection into varicosities. When treating the proximal GSV, stop the injection when polidocanol is 3 to 5 cm distal to the saphenofemoral junction. 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 polidocanol. Separate treatment sessions by a minimum of 5 days. Retained coagulum may be removed by aspiration (microthrombectomy) to improve comfort and reduce skin staining.
MAXIMUM DOSAGE
Adults
0.3 mL per injection and 10 mL per treatment session for injectable solution; 5 mL per injection and 15 mL per treatment session for injectable foam.
Geriatric
0.3 mL per injection and 10 mL per treatment session for injectable solution; 5 mL per injection and 15 mL per treatment session for injectable foam.
Adolescents
Safety and efficacy have not been established.
Children
Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
ADMINISTRATION
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
Injectable solution:
Use a fine needle syringe (typically 26- or 30-gauge).
Insert the needle tangentially into the vein and inject 0.1 to 0.3 mL of the solution slowly. Apply only gentle pressure during injection to prevent vein rupture.
After the needle has been removed and the injection site covered, apply compression in the form of a bandage or stocking.
After the treatment session, encourage the patient to walk for 15 to 20 minutes. Keep the patient under direct observation for allergic or anaphylactic reaction.
Maintain compression for 2 to 3 days for spider veins and 5 to 7 days for reticular veins. Extensive varicosities may require longer or more intense compression.
Do not inject more than 10 mL of polidocanol solution per treatment session.[40030]
Injectable foam:
Activate product using the oxygen canister and polidocanol canister as described in the Instructions for Use accompanying the product. Do not shake canisters.
With the supplied transfer unit 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.
Local anesthetic may be administered prior to insertion of cannula; however, tumescent anesthesia or patient sedation is not required.
To confirm venous access, cannulate the vein using ultrasound guidance.
Inject foam slowly (1 mL/second in the great saphenous vein and 0.5 mL/second in accessory veins or varicosities). Use ultrasound to confirm venospasm of the treated vein.
When injecting into the great saphenous vein, stop injection when polidocanol foam is 3 to 5 cm distal to the saphenofemoral junction.
Use a new sterile syringe for each injection; only use supplied low-silicone syringes. Use a new transfer unit for each treatment session.
Following the injection, 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.
Keep the patient under direct observation for at least 10 minutes following the injection for allergic or anaphylactic reaction; be prepared to treat anaphylaxis appropriately.
Do not inject more than 15 mL of polidocanol foam per treatment session. Separate treatment sessions by a minimum of 5 days.
Retained coagulum may be removed by aspiration to improve patient comfort and reduce skin staining.
Storage: Once activated, use the 77.5 mg canister within 4 hours and the 180 mg canister within 30 days. Store activated canisters upright, with the transfer unit attached under the same temperature conditions as the canister or convenience box.[56497]
STORAGE
Varithena:
- Do not use more than 30 days after opening
CONTRAINDICATIONS / PRECAUTIONS
Thromboembolic disease
Polidocanol is contraindicated for use in patients with acute thromboembolic disease. Polidocanol 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 at increased risk for developing thrombosis include those with reduced mobility, history of deep vein thrombosis or pulmonary embolism, or recent (within 3 months) major surgery, prolonged hospitalization, or pregnant females. The mechanism of action of polidocanol in the treatment of varicose veins involves the destruction of the endothelial lining of target vessels. This destruction induces subsequent endovascular fibrosis and occlusion. In addition, polidocanol appears to increase the apparent activity of clotting factors VIII, IX, XI, and XII.
Extravasation
Severe allergic reactions, including anaphylactic reactions, have occurred with polidocanol use. Some of these reactions have been fatal. Polidocanol is contraindicated for use in patients with a known allergy or anaphylactic reaction to polidocanol. Severe reactions occur more frequently with the use of larger volumes of polidocanol (more than 3 mL). The minimum effective dose of polidocanol should be used, and clinicians should be prepared to treat anaphylaxis appropriately. In addition, severe local adverse effects including tissue necrosis may occur after polidocanol extravasation. Use caution when placing the intravenous needle and administer the smallest effective volume at each injection site. After the injection session is completed, apply compression with a stocking or bandage for 15 to 20 minutes. Keep the patient under observation for allergic reaction during this time.
Arteriosclerosis, intraarterial administration, thromboangiitis obliterans (Buerger's disease)
Intraarterial administration or extravasation of polidocanol may cause severe necrosis, ischemia, or gangrene. Carefully place the intravenous needle and use the smallest effective volume at each injection site. Apply compression with a stocking or bandage and have patients walk for 15 to 20 minutes after the injection session. If polidocanol is administered intraarterially consult a vascular surgeon immediately. Patients with underlying arterial disease, such as marked peripheral arteriosclerosis or thromboangiitis obliterans (Buerger's disease) may be at increased risk for tissue ischemia.
Pregnancy
Do not use polidocanol during pregnancy. There are no adequate and well-controlled studies in pregnant women.[40030] Few published case reports have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.[56497] However, there is minimal benefit in treating lower extremity varicosities during pregnancy; lower extremity varicosities that develop during pregnancy may spontaneously regress postpartum.[56497] In animal studies, doses approximately equal to the recommended human dose (based on body surface area) resulted in embryocidal effects.[40030]
Breast-feeding
Interrupt breast-feeding and pump and discard breast milk up to 8 hours after polidocanol administration in order to minimize exposure to the breast-fed infant.[56497] There are no data on the presence of polidocanol in human milk, the effects on the breastfed infant, or the effects on milk production.[40030] [56497]
Air embolism
Avoid use of polidocanol foamed with room air. Stroke, transient ischemic attack, myocardial infarction, and impaired cardiac function have been reported in close temporal relationship with polidocanol administration. Such events may be caused by air embolism when using the product foamed with room air (high nitrogen concentration) or thromboembolism.
ADVERSE REACTIONS
Severe
anaphylactoid reactions / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
thrombosis / Delayed / Incidence not known
vasculitis / Delayed / Incidence not known
pulmonary embolism / Delayed / Incidence not known
cardiac arrest / Early / Incidence not known
stroke / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
Moderate
palpitations / Early / Incidence not known
migraine / Early / Incidence not known
confusion / Early / Incidence not known
dyspnea / Early / Incidence not known
Mild
skin discoloration / Delayed / 1.1-38.0
pruritus / Rapid / 19.0-19.0
hypertrichosis / Delayed / Incidence not known
injection site reaction / Rapid / Incidence not known
skin hyperpigmentation / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
syncope / Early / Incidence not known
dizziness / Early / Incidence not known
paresthesias / Delayed / Incidence not known
fever / Early / Incidence not known
flushing / Rapid / Incidence not known
DRUG INTERACTIONS
There are no drug interactions associated with Polidocanol products.
PREGNANCY AND LACTATION
Pregnancy
Do not use polidocanol during pregnancy. There are no adequate and well-controlled studies in pregnant women.[40030] Few published case reports have not identified a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes.[56497] However, there is minimal benefit in treating lower extremity varicosities during pregnancy; lower extremity varicosities that develop during pregnancy may spontaneously regress postpartum.[56497] In animal studies, doses approximately equal to the recommended human dose (based on body surface area) resulted in embryocidal effects.[40030]
Interrupt breast-feeding and pump and discard breast milk up to 8 hours after polidocanol administration in order to minimize exposure to the breast-fed infant.[56497] There are no data on the presence of polidocanol in human milk, the effects on the breastfed infant, or the effects on milk production.[40030] [56497]
MECHANISM OF ACTION
Polidocanol is an injectable sclerosing agent. When administered intravenously, polidocanol locally damages the endothelium of blood vessels. As a result of this damage, platelets aggregate at the site of damage and adhere to the venous wall. Platelets, cellular debris, and fibrin subsequently occlude the vessel. The occluded vein is then replaced with connective fibrous tissue. In addition, polidocanol appears to increase the apparent activities of clotting factors VIII, IX, XI, and XII and decrease the activity of protein C and protein S. Polidocanol induced endothelial damage is concentration and volume dependent.
PHARMACOKINETICS
Polidocanol is administered intravenously for the treatment of varicose veins. Polidocanol exerts its therapeutic effect by inducing local endothelial damage at the site of injection. Low systemic concentrations of polidocanol were observed in some of a subgroup of 22 patients enrolled in a clinical trial of polidocanol. The mean elimination of half-life of polidocanol was 1.5 hours, as observed in 4 evaluable patients receiving 4.5 to 18 mg.[40030]
Affected cytochrome P450 isoenzymes and drug transporters: none