Directions For Use For Revanesse^® Lips^TM+

What is Revanesse® Lips™ +?

Revanesse® Lips™ + is hyaluronic acid dermal filler. Hyaluronic acid is a naturally occurring substance that is found within the body. Hyaluronic acid is produced by bacteria and purified for use as injectable soft tissue filler in order to enhance the appearance of lips. Revanesse® Lips™+ is crosslinked with 1,4-butanediol diglycidyl ether (BDDE). BDDE is a chemical used to crosslink the hyaluronic acid in the dermal filler. Crosslinking is the process of chemically joining two or more molecules to form a network. The product also contains lidocaine. The product should not be used in patients with a history of allergies or sensitivities to such material and you should not be treated with the product if you have a previous hypersensitivity to local anesthetics of the amide type, such as lidocaine. The product is approved for submucosal implantation for lip augmentation in patients 22 years of age or older.

How does Revanesse® Lips™ + work?

Revanesse® Lips™+ is a gel that is injected directly into the lips using an ultrafine needle to temporarily plump the lips for lip enhancement in adults 22 years of age or older. The lidocaine in the gel improves the comfort of the injection by reducing sensitivity to pain.

Are there any reasons why I should not (contraindications) receive the Revanesse® Lips™ + injection?

Your doctor will ask about your medical history to determine if Revanesse® Lips™ + is right for you. You should not be treated with Revanesse® Lips™ + if you:

• Have severe allergies which have resulted in anaphylaxis or have a history of multiple severe allergies
• Have heightened immune responses to common allergens, especially inhaled allergens and food allergens (atopy).
• Have an allergy to natural rubber latex.
• Have an allergy to hyaluronic acid products,
• Have a history of allergies to Streptococcal proteins or have plans to undergo administration of graded doses of allergens (desensitization therapy) during treatment with Revanesse® Lips™ +;
• Have a history of hypersensitivity to lidocaine
• Have a history of bleeding disorders
• Are pregnant or nursing. Safety of Revanesse® Lips™ + has not been established in breastfeeding or pregnant women.
• Revanesse® Lips™ + should not be used in spaces other than the lip
• Have a history of hypertrophic scarring or keloid formation
• Have evidence of scars at the intended treatment sites
• Have acne and / or other inflammatory diseases of the skin, such as rosacea, seborrheic dermatitis, and psoriasis
• Have a cold sore (herpes virus) in the area of the lips
• Have acute or chronic skin disease, such as seborrheic dermatitis or rosacea, in or near the injection sites, or any infection or unhealed wound of the face
• Are under concomitant anticoagulant therapy, antiplatelet therapy, or have a history of bleeding disorders, clotting disorders such as hemophilia or connective tissue disorders such as systemic lupus erythematosus

You should never use Revanesse® Lips™ + in conjunction with a laser treatment, intense pulsed light, chemical peeling, dermabrasion treatments or any other procedure based on active dermal response, including over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment, as there is a possible risk of inflammation at the treatment site if these procedures are performed before treatment.

Are there any warnings I should be aware of?

If you are under the age of 22 you should not be treated with Revanesse® Lips™ +.

Limited safety and effectiveness information is available for this product for injection into the lips in men. The same product has been evaluated in men for the treatment of facial wrinkles and creases, (nasolabial folds).

Warning: One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately. It is imperative that you contact your health care practitioner immediately if you have any adverse inflammatory reactions that persist for more than one week.

If you have an adverse inflammatory reaction, such as redness, pain and swelling that persist for one week or more after treatment with Revanesse® Lips™ +, you should report this immediately to your doctor.

Ask your doctor if you have questions about any of the side effects, and please tell your doctor or your doctor’s staff right away if you have any side effects. Please tell them if you have any other problems with your health or the way you feel, whether or not you think these problems are related to the products.

Revanesse® Lips™+ has the same formulation as Revanesse® Versa+ which is marketed in the US for the correction of moderate to severe facial wrinkles and folds, such as nasolabial folds. Revanesse® products are distributed in many foreign countries. The reported side effects are described in the rest of this brochure.

What are the risks?

• Bleeding and Bruising: Bleeding is usually minimal and resolves within a few minutes. It is possible to have a bleeding episode from the injection of the local anesthesia or filler that requires treatment, but it is unusual. Bruising in the area is also an expected reaction and can take up to a week to resolve.
• Swelling: Swelling is also expected and may take several days to a week to resolve. It is unusual but medical treatment may be necessary if swelling is slow to resolve.
• Pain: Some discomfort is expected with injections but usually lasts less than a day. Other risks that are less likely, but may occur, include the following:
• Acne-like skin eruptions
• Skin hypersensitivity (rash, prolonged swelling, redness, hardness)
• Skin infection
• Damage to nerves or blood vessels
• Skin lumpiness
• Skin abscess
• Scarring
• Skin necrosis (death of the skin)
• Hyperpigmentation (darkening of the skin)
• Reactivation of herpes infection (blisters or skin sores) As with using any dermal filler, there is a risk of allergic reaction. If you have a very serious allergic reaction (anaphylactic shock) you may require emergency medical help and be at risk of death. Some symptoms of allergic reactions are:
• a rash
• having a hard time breathing
• wheezing when you breathe
• sudden drop in blood pressure
• swelling of the face
• fast pulse
• sweating
• dizziness or fainting
• inability to breathe without assistance
• a feeling of dread

One of the risks with using this product is unintentional injection into a blood vessel. The chances of this happening are small, but if it does happen, the complications can be serious, and may be permanent. These complications, which have been reported for facial injections, can include vision abnormalities or blindness. These complications may include vision abnormalities, blindness, stroke, temporary scabs, or permanent scarring of the skin. If you have changes in your vision, signs of a stroke (including sudden difficulty speaking, numbness or weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion), white appearance of the skin, or unusual pain during or shortly after treatment, you should notify your health care practitioner immediately.

Ask your doctor if you have questions about any of the side effects, and please tell your doctor or your doctor’s staff right away if you have any side effects. Please tell them if you have any other problems with your health or the way you feel, whether or not you think these problems are related to the products.

What side effects have been voluntarily reported following use of Revanesse® Lips™+ in the United States?

Revanesse® Lips™+ is identical in formulation to Revanesse® Versa+. The most common reported side effects reported for Revanesse® Versa and Revanesse® Versa+ included bruising, lumps, and swelling with immediate onset or delayed onset, up to several weeks after treatment. When required, treatment for these side effects included massage, cold compresses, drugs to relieve pain (analgesics), antibiotics, drugs that relieve allergy symptoms (antihistamines), drugs that reduce inflammation (topical steroids, oral corticosteroids), and an enzyme used to help break down hyaluronic acid (hyaluronidase).

When to Call your Doctor

Call your doctor immediately if you have:

• Changes in your vision
• Signs of a stroke (including sudden difficulty speaking, numbness of weakness in your face, arms, or legs, difficulty walking, face drooping, severe headache, dizziness, or confusion)
• White appearance of the skin
• Unusual pain during or shortly after treatment

Be sure to call your doctor if you have:

• Significant pain away from the injection site
• Any Redness and/or visible swelling that lasts for more than a few days
• Any side effect that occurs weeks or months after treatment
• Any other Symptoms that cause you concern

Patient Assistance Information:

If you require immediate assistance, please contact your health care provider. For further assistance, please contact Prollenium Medical Technologies Inc. at 1-866-353-3017 (24 hours a day).

For more information about Revanesse Lips+, please see the Patient Information Sheet or speak to your health care provider.

Patents 8,450,475; 8,357,795; 8,822,676; 9,089,519; 9,238,013; 9,358,322; 10,391,202; 10,485,896

INDICATION

Revanesse® Lips™ + is indicated for submucosal implantation for lip augmentation in patients 22 years of age or older.

CONTRAINDICATIONS

• Patients who develop hypertrophic scarring or keloid formation should not be treated with Revanesse® Lips™+.
• Patients with evidence of scars at the intended treatment sites should not be treated with Revanesse® Lips™+.
• Never use Revanesse® Lips™+ in conjunction with a laser, intense pulsed light, chemical peeling or dermabrasion treatments, or with Over-the-counter (OTC) wrinkle products or prescription wrinkle treatments within 4 weeks (28 days) prior to treatment.
• Patients with acne and / or other inflammatory diseases of the skin should not be treated with Revanesse® Lips™+.
• Patients with unattainable expectations should not be treated with Revanesse® Lips™+.
• Patients with multiple severe allergies, or with allergic history including anaphylaxis, multiple severe allergies, atopy, should not be treated with Revanesse® Lips™+.
• Patients with allergies to natural rubber latex should not be treated with Revanesse® Lips™+.
• Patients with allergies to hyaluronic acid products, or Streptococcal proteins should not be treated with Revanesse® Lips™+
• Patients who have plans to undergo desensitization therapy should not be treated with Revanesse® Lips™+.
• Revanesse® Lips™ + should not be used in patients with acute or chronic skin disease in or near the injection sites, or with any infection or unhealed wound of the face.
• Patients who are under concomitant anticoagulant therapy, antiplatelet therapy, or history of bleeding disorders, coagulation defects or connective tissue disorders should not use this product.
• Revanesse® Lips™+ contains lidocaine, and is contraindicated for patients with a history of allergies or sensitivities to such material and should not be used in patients with previous hypersensitivity to local anesthetics of the amide type, such as lidocaine.
• Revanesse® Lips™+ is only intended submucosal injection into the lips or intradermal injection into the nasolabial folds and must not be injected into blood vessels. Implantation of Revanesse® Lips™+ into dermal vessels may cause vascular occlusion, infarction, or embolic phenomena.

WARNINGS

• Do not inject Revanesse® Lips™+ into eye contours. Serious adverse events have been reported related to the use of dermal fillers in the area of the eye.
• Rare, but serious, adverse events associated with the intravascular injection of soft tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures.
• Defer use of Revanesse® Lips™ + at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes, or hives) or infection is present until the process has been controlled.
• Injection site reactions (e.g., lip swelling, lip pain, and contusion) are associated with Revanesse® Lips™ +, including short-term minor or moderate inflammatory symptoms starting shortly after treatment of lips
• Revanesse® Lips™ + must not be implanted into blood vessels. Localized superficial necrosis and scarring may occur after injection in or near vessels, such as in the lips, nose, or glabellar area. It is thought to result from the injury, obstruction, or compromise of blood vessels.
• Delayed onset inflammatory papules have been reported following the use of dermal fillers. Inflammatory papules that may occur rarely should be considered and treated as a soft tissue infection.
• As with all dermal filler procedures, Revanesse® Lips™ + should not be used in vascular rich areas. Use of similar products in these areas, such as glabella and nose, has resulted in cases of vascular embolization and symptoms consistent with ocular vessel occlusion, such as blindness.
• This product has not been evaluated in pregnant women, or women during lactation, and these individuals should not be treated with Revanesse® Lips™+.
• People 21 years of age and under should not be treated with Revanesse® Lips™+.

PRECAUTIONS

• Revanesse® Lips™ + is packaged for single use. Do not reserialize. Do not use if package is opened or damaged. Do not use product beyond the expiration date printed on the package.
• The safety or effectiveness of Revanesse® Lips™ + for the treatment of anatomic regions other than lips and nasolabial folds has not been established in controlled clinical studies.
• Limited safety and effectiveness information is available for Revanesse® Lips™+ for injection into the lips in men.
• As with all transcutaneous procedures, Revanesse® Lips™ + implantation carries a risk of infection. Standard precautions associated with injectable materials should be followed.
• The safety of Revanesse® Lips™ + for use during pregnancy, in breastfeeding females or in patients under 22 years has not been established.
• The safety in patients with known susceptibility to keloid formation has not been studied. Formation of keloids may occur after dermal filler injections. In a premarket study of Revanesse® Lips™ + the incidence and severity of adverse events in 53 subjects with Fitzpatrick Skin Types IV (n=27), V (n=9), and VI (n=17) was similar to that reported in the general population and no unique adverse events associated with these patient subgroups were observed.
• Hyperpigmentation may occur after dermal filler injections including Revanesse® Lips™+. Hyperpigmentation was not observed in the Revanesse® study of 158 subjects including subjects with Fitzpatrick Skin Types IV (n=27), V (n=9), and VI (n=17). Also, hyperpigmentation was not observed in any of the three previous Revanesse® product clinical studies involving 97 injections of Fitzpatrick skin types IV through V. There were no incidences of keloid formation in any of the studies.
• The safety profile for Revanesse® Lips™ + lip augmentation in persons of color is based upon information from 53 subjects with Fitzpatrick Skin Types IV, V and VI. Within this population, the incidence of adverse events was similar to the overall study population.
• Revanesse® Lips™ + should be used with caution in patients on immunosuppressive therapy.
• Bruising or bleeding may occur at Revanesse® Lips™ + injection sites. Patients who have undergone therapy with thrombolytics, anticoagulants, or inhibitors of platelet aggregation in the 3 weeks preceding treatment with Revanesse® Lips™ + have not been studied.
• After use, syringes and needles should be handled as potential biohazards. Disposal should be in accordance with accepted medical practice and applicable local, state and federal requirements.
• The safety of Revanesse® Lips™ + with concomitant dermal therapies such as epilation, UV irradiation, or laser, mechanical or chemical peeling procedures has not been evaluated in controlled clinical trials.
• Patients should minimize exposure of the treated area to excessive sun, UV lamp exposure and extreme cold weather at least until any initial swelling and redness has resolved.
• If laser treatment, chemical peeling or any other procedure based on active dermal response is considered after treatment with Revanesse® Lips™ +, there is a possible risk of eliciting an inflammatory reaction at the implant site. This also applies if Revanesse® Lips™ + is administered before the skin has healed completely after such a procedure.
• Injection of Revanesse® Lips™ + into patients with a history of previous herpetic eruption may be associated with reactivation of the herpes.
• It is imperative that patients with adverse inflammatory reactions that persist for more than one week report this immediately to their physician.

ADVERSE EXPERIENCES

Potential adverse effects (e.g., complications) associated with the use of the device, as well as for other devices in the same category include: tenderness, swelling, firmness (induration), lumps/bumps (mass), bruising, pain, redness, discoloration, and itching.

Rare, but serious, adverse events associated with the intravascular injection of soft-tissue fillers in the face have been reported and include temporary or permanent vision impairment, blindness, cerebral ischemia or cerebral hemorrhage leading to stroke, skin necrosis, and damage to underlying facial structures.

For the specific adverse events that occurred in the clinical study, please see the Professional Instructions for Use.

POSTMARKET SURVEILLANCE DATA

Revanesse® Lips™+ is identical in formulation to Revanesse® Versa™ +. Postmarket surveillance for Revanesse® Versa™ and Revanesse® Versa™+ reported the following adverse events (AEs) with 5 or greater instances in the United States: swelling, bruising, and lumps. In some instances, patients reporting these adverse events experienced symptoms that were severe, prompting additional medical evaluation. When required, treatment included massage, cold compresses, analgesics, antibiotics, antihistamines, topical steroids, oral corticosteroids, and enzymatic degradation (with hyaluronidase) of the product. Revanesse® Kiss™ + is the lips product marketed in the rest of the world markets, and is similar in composition, though not identical. There were no incidences of more than 5 of any adverse event type for Revanesse® Kiss™+ reported to the company, nor were there any contained in the literature.

For more information about Revanesse Lips+, please see the Professional Instructions for Use.

Patents 8,450,475; 8,357,795; 8,822,676; 9,089,519; 9,238,013; 9,358,322; 10,391,202; 10,485,896