Data Sheet
Zyplast
Cross-linked bovine dermal collagen 35mg/mL and lignocaine 3mg/mL collagen implant
NAME OF MEDICINE
ZYPLAST™ collagen implant is a sterile device composed of highly purified bovine dermal collagen that is lightly cross-linked with glutaraldehyde and dispersed in phosphate-buffered physiological saline.
ZYPLAST™ contains cross-linked purified bovine dermal collagen 35mg/mL and lignocaine 3mg/mL.
Presentation
ZYPLAST™ collagen implants have 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. ZYPLAST™ collagen implant is supplied sterile in syringes, ready for implantation.
Uses
Actions
ZYPLAST™ is introduced into mid to deep dermal tissues for the correction of contour deficiencies. 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. 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
ZYPLAST™ collagen implant is indicated for the correction of contour deformities of the dermis in non-weight bearing areas; and particularly for deeper depressions and more pronounced contour problems. 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. Best results with ZYPLAST™ are achieved in defects requiring mid to deep dermal implant placement.
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 contains 35mg/mL purified bovine dermal collagen and 3mg/mL lignocaine.
- 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.
- ZYPLAST™ is implanted via a fine-gauge needle (30 gauge). The needle is
introduced intradermally into the plane(s) of apparent deformity. The lesion
should not be overcorrected. Best results with ZYPLAST™ are achieved in
defects requiring mid to deep dermal implant placement. The rate and degree
of subsidence of correction in the implanted area varies with patient,
treatment site, and plane of implant placement. Correction should be
conservative during initial treatment. Results of in vitro and in vivo
studies suggest that ZYPLAST™ Implant, because it is cross-linked, may
persist in tissue to a greater extent than the non-cross-linked ZYDERM™ 1 or
ZYDERM™ 2 collagen implants. Therefore, it is recommended that during
treatment, correction should be limited to no more than 100% of the dermal
defect.
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. Hence, ZYPLAST™ is not recommended for use in the periorbital area. Caution is advised when using ZYPLAST™ around the vermilion border of the lip. ZYPLAST™ is not recommended for use in the glabellar area. - Vigorous massage of the treated areas is recommended following ZYPLAST™ implantation.
- Severely indurated lesions which initially resist distension often require several treatment sessions before desired correction is obtained.
- 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 ZYPLAST™ 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 ZYPLAST™ 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
ZYPLAST™ collagen implant therapy must not be initiated if the patient has an untoward response to the required test implantation (see Dosage and Administration).
ZYPLAST™ must not be used in patients with severe allergies manifested by a history of anaphylaxis, or history or presence of multiple severe allergies.
ZYPLAST™ contains lignocaine and must not be used in patients with known lignocaine hypersensitivity.
ZYPLAST™ must not be used in patients with a history of allergies to any bovine collagen product, including but not limited to collagen injectables, collagen implants, haemostatic sponges and collagen-based sutures, because these patients are likely to have hypersensitivity to ZYPLAST™.
ZYPLAST™ must not be used in patients undergoing or planning to undergo desensitisation injections to meat products, as these injections can contain bovine collagen.
ZYPLAST™ is contraindicated for use in breast augmentation, and for implantation into bone, tendon, ligament or muscle.
ZYPLAST™ should not be used in patients previously treated with other injectable materials intended for soft tissue augmentation (silicone fluid), since potential risks due to interaction with such materials have not yet been determined.
Warnings and Precautions
A test implantation must be administered and evaluated prior to soft tissue deficiency correction with ZYPLAST™ (see Dosage and Administration). Note: The collagen test implant (ZYDERM™ Test Dose) is non-cross-linked collagen, while ZYPLAST™ is cross-linked collagen. If the test implantation response is positive, the patient must not be treated with ZYPLAST™. If the test implantation response is equivocal, it is recommended that a second test implantation be administered in the opposite arm and evaluated prior to the initiation of treatment. 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.
ZYPLAST™ must not be implanted into blood vessels. Collagen can initiate platelet aggregation and implantation of ZYPLAST™ into dermal vessels may cause vascular occlusion, infarction or embolic phenomena.
Use of ZYPLAST™ collagen implant in an individual patient should be limited to 30mL over a one-year period. 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 in an individual patient should be limited to 30mL over a one-year period.
Use of ZYPLAST™ at specific sites in which an active inflammatory process (skin eruptions such as cysts, pimples, rashes or hives) or infection is present should be deferred until the underlying process has been controlled.
The safety of ZYPLAST™ for use during pregnancy or in infants and children has not been established.
ZYPLAST™ should be used with caution in patients on immuno-suppressive therapy.
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 ZYPLAST™ 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 ZYPLAST™ collagen implant corrections, although they may persist throughout the life of the implant.
Persistent swelling and scarring associated with ZYPLAST™ implantation may occur despite a four week problem-free interval after the test dose. Patients treated intradermally with ZYPLAST™ have reported temporary palpable lumpiness or visible material (milia-like yellow or white papules) at injection sites. Both of these types of treatment-associated responses resolved spontaneously without squeal, and are believed to reflect reduced shrinkage of cross-linked implants due to water resorption, compared with non-cross-linked collagen implants.
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™ than with 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.
The antigenic specificity of cross-linked ZYPLAST™ has been determined to be identical to that of non-cross-linked ZYDERM™ 1 and ZYDERM™ 2. During clinical trials and post-marketing surveillance, the overall incidence of hypersensitivity responses to ZYPLAST™ has been significantly lower than to ZYDERM™ 1 or ZYDERM™ 2. However, because of the potential for prolonged local availability of antigen, it is possible that the long-term rate of response to ZYPLAST™ may exceed the low rate experienced to date.
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 squeal.
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, 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, particularly when ZYPLAST™ was injected into glabellar frown lines (see Precautions). 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 avoiding implantation into blood vessels.
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
ZYPLAST™ 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. ZYPLAST™ collagen implants have 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.
ZYPLAST™ collagen implant: 6 x 0.5mL, 6 x 1.0mL, 6 x 1.5mL
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