GyneFix®

GPrescribing Information


 

I. Name of Product
GyneFix® Intrauterine Copper Contraceptive for interval and postabortal use (< 10 weeks)

II. Composition
Qualitative composition:
Cuprum 99.99% (high purity copper)
Quantitative composition: 420 mg (standard version); 280 mg (small version)

III. Description
GyneFix® is a new concept in intrauterine device (IUD) technology. It is fixed to the uterine fundus, is frameless and entirely flexible.
GyneFix® consists of 6 copper sleeves (standard version) or 4 copper sleeves (mini version) , each 5 mm long and 2.2 mm in diameter, threaded on a length of polypropylene suture material. The sleeves are prevented from sliding off the material by the upper and lower sleeves, being crimped onto the thread. The proximal end of the thread is provided with a knot which at insertion is placed in the fundal myometrium with an inserter for anchoring the device. The total surface of copper, including the inner and outer surfaces, is 330  mm2 for the standard version and 200 mm2 for the small version.

IV. Clinical Pharmacology
Available data indicate that the contraceptive effectiveness of copper IUDs is enhanced by a minute quantity of copper being released continuously into the uterine cavity. The exact mechanism by which copper enhances the contraceptive effect of an IUD has not been conclusively demonstrated. Various hypotheses have been advanced; the major one being that copper placed in the uterus interferes with enzymatic or other processes that regulate blastocyst implantation. In addition, recent animal studies suggest that copper may play a role in reducing sperm transport within the uterine environment.

V. Indication and Clinical Use
Indication: GyneFix® is indicated for contraception.
Clinical Use: A candidate for use of GyneFix® is any healthy, non-pregnant, female.  
Time of insertion:
Experience has shown that GyneFix® can be inserted at any time during the menstrual cycle. It is evident, however, that the physician should rule out the presence of a pregnancy if insertion of the device is planned in the second half of the menstrual cycle.
Clinical trials have shown that GyneFix® can be inserted immediately after spontaneous or induced first trimester abortion of less than 10 weeks gestational age. GyneFix® is unsuitable for use in the immediate postpartum period. A period of at least 6 weeks should be allowed until the uterus has regained its normal size or the subject has had at least one normal menstrual period. In breastfeeding women, however, a period of 8 to 12 weeks following full term delivery is recommended because of the higher risk of perforation reported in some studies with traditional IUDs.

VI. Use-Effectiveness Studies
GyneFix® has been studied since 1985 and over 15,000 women years of experience (international, multicenter, non-comparative and comparative clinical trials, including a large proportion of nulligravid/nulliparous women) have been collected.  
1. Effectiveness of GyneFix®
GyneFix® is a very effective contraceptive device. The pregnancy rates are comparable or superior when compared with the most effective currently used high-load copper devices, and to oral contraceptives and sterilization. Ectopic pregnancy rates with GyneFix® are very low in large-scale, long-term, randomized comparative clinical trials and significantly lower than with the TCu380A IUD.
Use in young parous and nulliravid/nulliparous women:
Studies suggest that young parous and nulligravid/nulliparous women using GyneFix® are no more susceptible to pregnancy than other age groups: the annual pregnancy rates being close to zero.
The low pregnancy rate with GyneFix® is attributed to the high delivery of the copper ions in the uterine cavity. The small version is more suitable for small uterine cavities.
2. Bleeding/pain with GyneFix®
Due to its design characteristics, flexibility, absence of a frame and the reduced space it occupies within the uterine cavity, GyneFix® is highly tolerated and the removal rate for pain is very low.
The removal rate for bleeding is also low with GyneFix® especially with the mini GyneFix® IUD and is ascribed to the small surface area and the characteristics of the device already described. Although abnormal bleeding still may occur, the low removal rate for bleeding/pain is probably due to the low incidence of concomitant complaints of pain, rendering abnormal bleeding, mostly spotting, more acceptable to the woman.
Recommendation: In case of spotting or heavy bleeding, the use of one of the following medications may be useful: NSAIDs, anti-fibrinolytic agents or a hormone-releasing intrauterine system may be a good alternative after having excluded intrauterine patholocical conditions.
3. Expulsion of GyneFix®
With traditional IUDs, young and nulligravid/nulliparous women are particularly prone to downward migration and expulsion of the IUD. This is not the case with the GyneFix®, if properly inserted. Long-term multicenter clinical trials with the GyneFix® showed lower expulsion rates, after the first year of use, both in parous and nulliparous women, as compared with expulsion rates of current copper IUDs.  
Duration of action
The GyneFix® is recommended for 5 years. In women over 40, GyneFix® can remain in situ until menopause.
Safety of the anchoring system

Histological studies conducted in hysterectomy specimen up to 4 years after insertion of the GyneFix®  have shown that the myometrial tissue reaction at the site of the anchor is minimal (less than 1.0 mm), or even absent, supporting both the safety of the material and the safety of the implant system. No transplanted endometrial tissue could be observed within the adjacent endometrium in any of these cases studied.
Reversibility and Return to Fertility
In depth studies have shown that there is no difference in conception rates between a group who had previously used a copper IUD and a group who had not used an IUD. Fertility studies after GyneFix® removal do not suggest any impairment of fertility.

VII. Contraindications and caution
(for IUDs in general)
Contraindications: pregnancy, abnormalities of the uterus, hypoplastic uterus (i.e. following use of injectables), current pelvic inflammatory disease (PID), sexual transmitted disease (STD), postpartum endometritis or infected abortion in the past 3 months, endometrial or cervical malignancy, unexplained genital bleeding, acute cervicitis,  bleeding disorders (eg von Willebrand’s disease), genital actinomycosis, known or suspected allergy to copper, diagnosed Wilson’s disease, leukemia, chronic corticosteroid or immunosuppressive therapy.
Caution: anemia (depending on the cause), previous ectopic pregnancy, prior uterine or tubal surgery, valvular heart disease (with antibiotic cover), heavy menstrual flow, severe menstrual cramps, fibroid uterus (physician's opinion). 

VIII. Warnings
 (for IUDs in general)  
A. Pregnancy
1. Septic abortion
Reports on traditional IUDs have indicated an increased incidence of septic abortions, associated in some instances with septicemia, septic shock and death in patients conceiving with an IUD in place. Most of these reports have been associated with mid-trimester of pregnancy. In some cases the initial symptoms have been insidious and not easily  recognized.
If pregnancy should occur with GyneFix® in situ, the device should be removed if the string is visible even though removal may increase the chances of miscarriage. If the decision is made not to remove the device, or removal proves to be difficult, or if the woman elects to continue the pregnancy, she should be warned that there may be an increased risk of abortion or preterm labor and/or sepsis and she should be followed closely. It must be noted, however, that nothing of this kind has been reported with GyneFix® so far.
2. Ectopic pregnancy
A woman who conceives while using an IUD should be carefully evaluated for the possibility of an ectopic pregnancy. Special attention should be directed to patients with delayed menses, heavy and prolonged bleeding and/or pelvic pain.    
B. Pelvic Infection
An increased risk of PID associated with the use of IUDs has been reported. The risk appears to be greatest for nulliparous women who have a multiplicity of sexual partners. Studies conducted with GyneFix® in nulligravid and nulliparous women, however, have not shown any increased risk of PID in properly selected nulligravid and nulliparous women. If salpingitis should occur, however, the infection could result in tubal damage and occlusion, thereby threatening future fertility. Therefore, it is recommended that women be advised to look for and report symptoms of pelvic inflammatory disease.
The symptoms of pelvic infection include: development of menstrual anomaly (prolonged or heavy bleeding), abnormal vaginal discharge, abdominal or pelvic pain, dyspareunia, fever. The signs and symptoms are especially significant if they occur following the first few cycles after insertion. Appropriate aerobic and anaerobic bacteriological studies should be done and antibiotic therapy initiated promptly. If the infection does not show marked clinical improvement within 24 to 48 hours, GyneFix® should be removed and treatment reassessed on the basis of the results of culture and sensitivity tests.  
C. Perforation

Partial or total perforation of the uterine wall or cervix has occurred with the use of conventional IUDs, most commonly during IUD insertion. Although perforations with GyneFix® are very rare (approximately 1/1000), the possibility of perforation must be kept in mind during insertion and at the time of any subsequent examination. If perforation occurs, the device should be removed. Laparoscopy or laparotomy may be indicated to remove the implant. Abdominal adhesions, intestinal penetration, obstruction, and local inflammatory reaction with abscess formation and erosion of adjacent viscera may result if the implant is left in the abdominal cavity. The risk of perforation can be minimized by closely following the recommendations for insertion.
D. Effects of Copper
Additional amounts of copper available to the body from a copper IUD may precipitate symptoms in women with undiagnosed Wilson’s disease. The estimated incidence of Wilson’s disease is 1 in 200,000.

IX. How Supplied and How Stored
Each GyneFix®  IUD is sterile and delivered in a blister-pack, together with an inserter unit and uterine sound. Please store dry and at room temperature.