Depot progestogen for hormonal contraception
Important information, please read carefully!
1ml Noristerat contains 200mg norethisterone enantate in oily solution.
Properties and indication
Noristerat is a depot progestogen for hormonal contraception. Protection against conception is based primarily upon an alteration of the cervical mucus. This alteration is present for the whole of the duration of action and prevents the ascent of the sperms into the uterine cavity. Radioimmunological studies have shown that, during the first 5 – 7 weeks after injection, ovulation is suppressed as a result of the high plasma level of norethisterone. In addition, Noristerat causes morphological changes in the endometrium which have the effect of rendering nidation of a fertilized egg difficult.
When Noristerat is used according to instructions, protection against pregnancy begins on the day of the first injection. In the clinical studies Noristerat was generally injected at 12-week intervals. Contraceptive reliability was lower than for the oral progestogen-estrogen preparations. Most of the pregnancies observed occurred within the first two injection intervals. The contraceptive reliability was distinctly better when the duration of use was longer. In addition, injecting Noristerat at intervals of 8 weeks at the start of treatment was found to improve its contraceptive effect.
Noristerat is particularly suitable for women who cannot take oral contraceptives regularly or who do not tolerate them well. Noristerat should only be administered to women with a history of normal cycles.
Dosage and administration
Before starting Noristerat, a thorough general medical and gynecological examination (including the breasts and a cytological smear of the cervix) should be carried out and pregnancy must be excluded.
During the use of Noristerat, it is recommended that the checks be repeated at intervals of six months in order to detect any undesired effects in good time.
Noristerat must always be administered as a deep intramuscular injection (preferably intragluteal, alternatively into the upper arm). It is advisable to place a plaster over the injection site after the injection to prevent any reflux of the Noristerat solution.
Experience shows that the short-lasting reactions (urge to cough, coughing fits, respiratory distress) which occur in rare cases during or immediately after the injection of oily solutions can be avoided by injecting the solution extremely slowly.
The first intramuscular injection is given within the first 5 days of a cycle. The next three injections are to be given at intervals of 8 weeks, after which a further injection is required every 12 weeks (84 days). If the injection interval is extended beyond this, no adequate contraceptive cover is available from the 13th week onwards.
Should technical reasons make it impossible to maintain the 84-day injection interval, a 2-mouth regimen can alternatively be adopted, as was done in an extensive WHO study.
In each case, the next injection should only be given if a menstruation-like bleeding has occurred within the preceding 10 weeks. If it has not, pregnancy must be excluded before the next injection is given.
Following discontinuation, normal ability to conceive usually returns about 4 – 5 months after the last injection. If a physiological cycle pattern fails to develop within this period of time, appropriate treatment is indicated in women who want children.
Cycle disturbances in the form of spotting, break-through bleeding and short-lasting amenorrhoea are the only relatively frequent side effects. These do not generally require treatment. With persistent bleeding, however, it may be expedient to administer progestogen-estrogen tablets for 10 days, which cause a withdrawal bleeding about 1- 4 days after the last tablet has been taken.
If the use of Noristerat has been interrupted because of the absence of bleeding, diagnostic measures are called for to clarify the cause. If pregnancy can be ruled out and the amenorrhoea still persists, special treatment is required in younger women in particular.
Isolated cases of headache, dizziness, depressive moods and short-lasting nausea have been observed as subjective side effects.
Marked weight gains are rare.
The doctor should be informed if other medicines are being taken regularly (e.g. barbiturates, phenylbutazone, hydantoins, rifampicin, ampicillin), since these may impair the action of Noristerat.
Contraindications and risks
Noristerat is not to be used in pregnancy, phlebitis or thromboembolic diseases, pathologically increased blond pressure, acute and severe chronic liver diseases with and without jaundice (particularly primary biliary liver cirrhosis), existing or treated cancer of the breast or uterus, severe diabetes with vascular changes, disturbances of lipometabolism, Dubin-johnson syndrome, Rotor syndrome, previous or existing liver tumors, a history of herpes of pregnancy, idiopathic jaundice of pregnancy or severe pruritus of pregnancy, otosclerosis with deterioration in pregnancy, 12 weeks before planned operations and during immobilization (e.g. after accidents).
In porphyria, all forms of impaired liver function, a history of phlebitis or thromboembolic disease Noristerat should be used only after careful consideration of the benefits and risks. No further injection should be given if, during treatment, migrainous headaches occur for the first time or recurrent, unusually severe headaches develop, if sudden perceptual disorders (e.g. disturbances of vision or hearing) occur, if first signs of thrombophlebitis or thromboembolic disease (e.g. unusual pain in the legs or swelling of the legs, stubbing pains on breathing, or coughing for no apparent reason) are noted, or if a feeling of pain and tightness in the chest, a significant rise in blood pressure, recurrence of earlier depression or pathological changes of liver function and hormone levels are experienced.
Noristerat has no inhibiting influence on lactation. Up to now, no unfavorable effects on breast-fed babies have been observed. However, small quantities of the steroid maybe eliminated with the milk. As with other steroids it is therefore theoretically possible that the degradation of bilirubin in neonates is impaired particularly during the first week of life. If the newborn is suffering from severe or persistent jaundice which requires medical treatment, breast-feeding must be interrupted for the time of treatment.
A reduction of glucose tolerance has been observed in some women using progestogens. Consequently, diabetics and women with a tendency to diabetes should be carefully supervised during the use of Noristerat. In the case of diabetics, it may be necessary to reassess the required doses of oral antidiabetics or insulin. In earlier years, when estrane derivatives were being used at very high dosage for the maintenance of pregnancy, individual cases of virilization of the external sex characteristics of female neonates were also described following administration of preparations containing norethisterone, this being associated with the androgenic residual effect of these substances. Since it cannot be stated unequivocally that such a situation will not occur under Noristerat, injection during pregnancy – and particularly in the sensitive phase after the first month of pregnancy – is contraindicated.
It must be added, however, that no such effect has been observed in the few pregnancies which have so far occurred during the wearing-off of the Noristerat effect.
If there is a history of extrauterine pregnancy or one tube is missing, the use of Noristerat should be decided on only after carefully weighing the benefits against the risks.
If obscure lower abdominal complaints occur together with an irregular cycle pattern (above all amenorrhoea following persistent bleeding), an extrauterine pregnancy must be considered.
According to the present state of knowledge, an association between the use of hormonal contraceptives and an increased risk of venous and arterial thromboembolic diseases cannot be ruled out.
The relative risk of arterial thromboses (e.g. stroke, myocardial infarction) appears to increase further when heavy smoking, increasing age and the use of hormonal contraceptives coincide. In sickle-cell anemia, the full status of the red blond picture must be determined before the start of treatment and checked at monthly intervals during treatment. If the status deteriorates during use, no further injection of Noristerat should be given. The use of Noristerat is contraindicated if these checks are not possible or cannot be assured.
In rare cases benign and in even rarer cases malignant liver tumors leading in isolated cases to life-threatening intraabdominal hemorrhage have been observed after the use of hormonal substances such as the one contained in Noristerat. The doctor must therefore be informed of the occurrence of unusual upper abdominal complaints which do not disappear spontaneously within a short time.
Recent investigations have confirmed that norethisterone is partly metabolized to ethinylestradiol. Since the estrogenicity of norethisterone has always been assumed and experienced in clinical practice, the recent discovery of its metabolic characteristics does not change the existing recommendations of use.
Ampuls of 1 ml
Store all drugs properly and keep them out of reach of children.
Bayer Schering Pharma