Data Sheet
ZYDERMTM 1
Purified bovine dermal collagen 35mg/mL and lignocaine 3mg/mL collagen implant
ZYDERMTM 2
Purified bovine dermal collagen 65mg/mL and lignocaine 3mg/mL collagen implant
NAME OF MEDICINE
ZYDERM™ collagen implants are sterile devices composed of highly purified bovine dermal collagen that is dispersed in phosphate-buffered physiological saline.
ZYDERM™ 1 contains purified bovine dermal collagen 35mg/mL and lignocaine 3mg/mL.
ZYDERM™ 2 contains purified bovine dermal collagen 65mg/mL and lignocaine 3mg/mL.
Presentation
ZYDERM™ collagen implant has a whitish, opaque or semi-opaque appearance. In the event that a syringe contains material that is crystal clear (like water), the syringe must not be used. The test implant to be used prior to ZYDERM™ has the same composition as ZYDERM™.
Uses
Actions
ZYDERM™ collagen implant is introduced into the dermis for correction of contour deficiencies of this soft tissue. When injected into an extravascular connective tissue space and warmed to body temperature, the implant undergoes a fibrous transformation evolving from an opalescent gel to a white opaque mass. A soft cohesive network of fibres is formed, which is responsible for restoring skin contour. Histological examination reveals infiltration of various cell types into the collagen matrix within 24 to 48 hours after implantation. This infiltration later becomes limited to the normal cell types of connective tissue, i.e. fibroblasts and adipocytes. A newly developed vascular network can also be observed in and around the implant.
Once in place, the collagen implant condenses; syneresis of the implant and the resulting absorption of the exuded saline result in a rapid (less than 24 hour) reduction of implant volume, which is followed by a further, but more gradual (two or more weeks) reduction as the implant stabilises. When established, the implant is similar in response and appearance to the surrounding soft tissue and is subject to the same stresses and ageing processes.
Indications
ZYDERM™ 1 collagen implant is indicated for the correction of contour deformities of the dermis in non-weight bearing areas. ZYDERM™ 2 is indicated particularly for deeper depressions, more pronounced contour problems, and glabellar frown lines. The aetiology and distensibility of the lesion, tissue stress at the implant site, and the tissue plane of placement of the implant will affect the degree and duration of contour restoration. ZYDERM™ collagen implant should be injected into the superficial papillary dermis.
Dosage and Administration
A test implantation using ZYDERM™ Test Dose (0.1mL) must be completed and evaluated prior to soft tissue deficiency correction with any injectable collagen implant.
ZYDERM™ Test Dose has the same composition as ZYDERM™.
- The patient's soft tissue deficiencies should be characterised with regard to aetiology, distensibility, stress at the site and depth of lesion. Pretreatment photographs are recommended.
- After ensuring that the patient has thoroughly washed the treatment area with soap and water, the area should be swabbed with alcohol or other antiseptic.
- ZYDERM™ is implanted via a fine-gauge needle (30 gauge). The needle is
introduced intradermally into the plane(s) of apparent deformity. The needle
should be placed as superficially as possible in the papillary dermis, and
the lesion should be deliberately overcorrected. If blanching is not
achieved, withdraw the needle immediately as it has probably been placed too
deep in the dermis.
To decrease the total number of treatment visits required, it is recommended that the contour deficiency be overcorrected to compensate for the loss of saline in the suspension. Overcorrection of the lesion to 1.5 to 2.0 times the initial depth of deformity is recommended.
Syneresis of the implant and the resulting absorption of the exuded saline result in a rapid (less than 24 hour) reduction of overcorrection, which is followed by a further, but more gradual (two or more weeks) reduction as the implant stabilises. Approximately 25 to 30% of the ZYDERM™ implants volume remains, although this volume varies among individual patients.
The rate and degree of subsidence of the implanted area is variable but utilisation of this technique has not resulted in any instances of permanent overcorrection. However, clinical experience has shown that overcorrection has been slow to resolve in the periorbital area and in treatment sites around the vermilion border of the lip, due to minimal tissue stresses at these sites. Hence, these areas should be treated cautiously and small amounts of ZYDERM™ should be implanted over several treatment sessions without overcorrection. - Severely indurated lesions which initially resist distension often require several treatment sessions before desired correction is obtained. In such lesions, it is preferable to implant within the scar rather than beneath it.
- Needles may become occluded or dull during a treatment session and replacement may be necessary.
- Additional implantations at intervals of 2 weeks or more are usually necessary to achieve the desired level of correction. Not more than 30mL of ZYDERM™ should be implanted in any one year.
- The physician should instruct the patient to report to her/him any evidence of adverse texture change in the surrounding tissues. Other problems possibly associated with ZYDERM™ implantation should also be promptly brought to the attention of the physician.
- Discard any unused material and the syringe after a single treatment.
Partly used syringes are to be discarded. A syringe should not be used on
more than one patient.
Long-term follow-up data indicate that "touch-up" implantations at 6-18 month intervals are usually required to maintain maximum correction. The interval at which touch-up implantations are needed depends on the nature of the lesion, the amount of implant introduced and the stresses that may exist at corrected sites. For example, ongoing mechanical stresses (such as smiling or frowning) eventually cause these defects to recur. However, correction tends to persist longer in areas in which disease processes (such as acne) have become quiescent. Nevertheless, if a stable level of correction is desired, all patients should be counselled to anticipate supplemental implantations.
Contraindications
ZYDERM™ must not be used in patients with severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies.
ZYDERM™ must not be used in patients with any bovine collagen products.
ZYDERM™ contains lignocaine and must not be used in patients with known lignocaine hypersensitivity.
ZYDERM™ is contraindicated for use in breast augmentation, and for implantation into bone, tendon, ligament or muscle.
Warnings and Precautions
A test implantation must be administered and evaluated prior to soft tissue deficiency correction with ZYDERM™ (see Dosage and Administration). If the test implantation response is positive, the patient must not be treated with ZYDERM™. Some physicians have reported the occurrence of connective tissue diseases such as rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis (DM), and polymyositis (PM) subsequent to collagen injections, in patients with no previous history of these disorders. A comparison of the observed number of cases of PM/DM in the collagen treated population with an estimate of the expected number of cases suggests an association between collagen injections and PM/DM; i.e. there appears to be a higher than expected incidence of PM/DM in the collagen treated population. However, a causal relationship between collagen injection and the onset of autoimmune disease or systemic connective tissue disease has not been established. Also, an increased incidence of cell-mediated and humoral immunity to various collagens have been found in systemic connective tissue diseases such as rheumatoid arthritis, juvenile rheumatoid arthritis, and progressive systemic sclerosis (scleroderma). Patients with these diseases may thus have an increased susceptibility to hypersensitivity responses and/or accelerated clearance of their implants when injected with bovine dermal collagen preparations.
ZYDERM™ must not be implanted into blood vessels. Collagen can initiate platelet aggregation and implantation of ZYDERM™ into dermal vessels may cause vascular occlusion, infarction or embolic phenomena.
Use of ZYDERM™ 1 collagen implant in an individual patient should be limited to 30mL over a one year period. Use of ZYDERM™ 2 collagen implant in an individual patient should be limited to 15mL over a one-year period. The combination of these products or in conjunction with ZYPLAST™ in an individual patient should be limited to 30mL over a one-year period. The safety of injecting greater amounts on an annual basis has not been established.
Injectable bovine collagen should be used with caution in patients who are atopic or have a history of allergies. This class of patient has a greater potential of ultimately exhibiting an allergic reaction to bovine collagen than do other patients.
The safety of ZYDERM™ for use during pregnancy or in infants and children has not been established.
Adverse Effects
Adverse reactions have occurred in approximately 3% of patients.
Transient or minimal swelling, mild redness and discomfort will probably occur at the implant site immediately following implantation. Increasing discomfort or swelling, or spreading redness should be brought immediately to the physician's attention.
On occasion, transient painless bruising or discolouration has been noted to develop at one or more of the implantation sites. Resolution has always been spontaneous.
Fewer than 1% of patients receiving injectable collagen implants have at some time reported an intermittent swelling response, involving moderate induration at the implant site and oedema within the surrounding tissues. In some cases, these responses have been found to be associated with antibodies to bovine collagen. At times this has been accompanied by mild pruritus or minimal transient erythema. These reactions may last only a few hours and are usually associated with causes of peripheral vasodilatation such as consumption of alcohol, prolonged exposure to sun and/or heat, exercise and flare-ups of hay fever and other causes of nasal and sinus congestion. To date, these reactions have been self-limiting and have not been shown to affect adversely the long-term success of injectable collagen implant corrections, although they may persist throughout the life of the implant.
Persistent swelling and scarring associated with injectable collagen implantation may occur despite a four week problem-free interval after the test dose.
Sensitisation reactions to injectable collagen implants have occurred in 1-2% of treated patients. Most reactions have been of a hypersensitivity nature and have consisted of erythema, swelling, induration and/or urticaria at implantation sites. Often these reactions have occurred following an unrecognised or unreported positive collagen skin test. Most of the remaining responses occurred in patients who became sensitised to injectable collagen implants at some point during their course of treatment. Approximately 80% of these reactions occur within four weeks following the sensitising dose.
Typically, allergic reactions persist between one and nine months, with an average duration of four months. These reactions may be intermittent or continuous in nature. In rare instances, reactions have resolved in one or two weeks or have persisted for more than one year. Although several forms of therapy (antihistamines; oral, topical and intralesional steroids) have been tried, they usually resulted in only temporary improvement. In most cases, time has proved to be the determining factor in the resolution of these reactions. In rare instances, patients have been left with residual firmness at the site of a resolved adverse reaction.
On rare occasions, the hypersensitivity response has progressed to a cystic reaction which may drain purulent material. The incidence and severity of this type of hypersensitivity response reported to date has been greater with ZYPLAST™ (cross-linked) collagen implant than with non-cross-linked ZYDERM™ 1 or ZYDERM™ 2. In some cases, this reaction has been associated with increased titres of anti-bovine collagen antibodies. These reactions develop weeks to months following injection and may result in induration and/or scar formation. This type of reaction can occur as multiple and/or recurrent sterile abscesses which tend to be persistent and resistant to drug therapy; careful incision and drainage has been a useful treatment.
Infections at implantation sites have occurred in fewer than 0.08% of treated patients, and reactivation of a pre-existing herpes simplex infection at implantation sites has been reported in fewer than 0.06% of treated patients. These responses resolved quickly and without sequelae.
Systemic complaints have been reported by fewer than 0.5% of patients. During clinical testing and subsequent monitoring of patient complaints following treatment with injectable collagen implants, a variety of systemic complaints have been reported. These reports have included flu-like symptoms (fever, myalgia, neuralgia, headache, nausea, malaise or dizziness); pruritus; rash; transient visual disturbances including blurred vision; tingling and numbness; transient polyarthralgia; and various systemic diseases including immune-mediated diseases. Rare anaphylactoid responses have been reported with injectable collagen implants including acute episodes of hypotension, difficulty in breathing, and tightness in chest and/or shortness of breath.
As with any injection into the head or neck, the injected material may be inadvertently implanted in a blood vessel. Localised necrosis and/or sloughing, resulting in a scab and/or scar, has occurred following interruption of blood flow through blood vessel laceration or occlusion. It is possible that over distension of tissue resulting in compromised tissue vascularity may lead to similar complications, caused by interruption of blood supply to an injection site. The extent of necrosis has varied and is in the pattern of the tissue served by the vessel involved. This phenomenon has been reported more frequently in the glabellar region of the face than in other areas. Nevertheless, the incidence of this scab or scar formation is less than 0.3% of treated patients, and may occur in conjunction with either infection and/or hypersensitivity responses. If implantation is followed by prolonged blanching or significant ecchymosis at the treatment site, gentle massage and close follow-up are recommended.
In addition, forceful injection into superficial dermal arterial branches of the face and scalp could cause retrograde movement of the implant material into retinal arteries, resulting in vascular occlusion. Such a complication has been reported with the use of injectable collagen implants in one patient and resulted in the sudden and permanent loss of vision in one eye. Similar complications have been associated with other injectable preparations including corticosteroids, local anaesthetics and angiographic agents. These findings emphasise the importance of superficial dermal implantation to avoid dermal blood vessels during implantation of ZYDERM™.
Pharmaceutical Precautions
Shelf-life is 36 months when stored at 2°C to 10°C. Refrigerate. Do not freeze.
Medicine Classification
Prescription Medicine
Package Quantities
ZYDERM™ collagen implant is supplied sterile in syringes, ready for implantation. Each syringe is packaged with a sterile fine-gauge needle. If the syringe cap is dislodged, or if the package is not intact, sterility cannot be assured and the syringe should not be used. In the event that a syringe contains material that is crystal clear (like water), the syringe must not be used.
ZYDERM™ 1 collagen implant: 6 x 0.5mL, 6 x 1.0 mL
ZYDERM™ 2 collagen implant: 6 x 0.5mL, 6 x 1.0 mL
Caution: The technique of the practitioner is essential to the success of the medical treatment. This medical device can only be used by or under the supervision of a medical doctor.
Name and Address
Allergan New Zealand Limited
Cnr Manu Tapu Drive & Joseph Hammond Place,
Auckland International Airport,
Mangere
Auckland 1
New Zealand
Toll free telephone: 0800 659 912
Date of Preparation
December 2007