Zoladex depot amp. 3.6 mg.

The composition and dosage form:

Zoladex a sterile, white to cream colored cylindrical depot, wherein goserelin acetate (equivalent to 3.6 mg of goserelin) is dispersed in a matrix of a biodegradable lactide-glycolide copolymer. It is sold in a syringe with a single dose applicator.

Indications:
 
Prostate cancer: Zoladex is indicated for the treatment of prostate cancer suitable for hormonal therapy.
 
Breast cancer: Zoladex is indicated for the treatment of breast cancer suitable for hormonal therapy in premenopausal and perimenopausal.
 
Endometriosis in the treatment of endometriosis Zoladex relieves symptoms, including pain, and reduce the size and number of endometriotic lesions. Thinning of the endometrium: Zoladex is indicated for pre-thinning of the uterine endometrium before endometrial resection or ablatsio.
 
Uterine fibroids in the treatment of fibroids Zoladex narrowed lesions improve hematologic status of patients and reduces the symptoms, including pain. It is used as adjunctive treatment operations to facilitate the operational equipment and reduce operational loss of blood.

Assisted Reproduction: Suppression of hypothalamic-pituitary axis in preparation for ovulation induction.

Dosage and method of administration

Adults

A depot of Zoladex 3.6 mg injected subcutaneously into the anterior abdominal wall every 28 days.

Artificial insemination: Zoladex ® 3.6 mg were administered to suppress the pituitary gland, as determined by serum estradiol levels, similar to those observed in the early follicular phase (approximately 150 pmol / 1). This usually takes between 7 and 21 days.

When you achieve suppression begins superovulation (controlled ovarian stimulation) with gonadotrophin. The suppression achieved with agonist depot is stable, which implies that in some cases there may be an increased need for HCG. At the appropriate stage of follicular development is stopped and the gonadotropin is administered human chorionic gonadotrophin (hCG) for ovulation induction. Treatment follow-up, receiving the oocyte and fertilization techniques are performed according to usual practices in the clinic.

There is no need for dose adjustment in patients with renal impairment.

There is no need for dose adjustment in patients with hepatic impairment.

There is no need for dosage adjustment in elderly patients.

Endometriosis should be treated for a period of six months, as there are no clinical data for longer periods of treatment. You do not have to make repeated courses because of the risk of loss of bone mineral substance. It has been shown that in patients receiving Zoladex for the treatment of endometriosis, the addition of the hormone replacement therapy (estrogen and progesterone daily) reduces the loss of bone mineral substance and vasomotor symptoms.

For use in endometrial thinning: to be implemented two landfills every 4 weeks, the operation is scheduled between zero and the second week after the second depot.

Children

Zoladex is not indicated for use in children.

Contraindications:

Zoladex should not be used in patients with known hypersensitivity to Zoladex or other analogs of LHRH.

Zoladex should not be used during pregnancy or breastfeeding.

Precautions:

Zoladex is not indicated for use in children as safety and efficacy have not been established in this group of patients.

Men

The use of Zoladex in men at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully and patients should be monitored closely during the first month of treatment. In the presence or development of spinal cord compression or renal impairment due to obstruction of the ureter, to be specific standard treatment of these complications.

Ladies

The use of LHRH agonists in women can cause the loss of bone mineral substance. Available so far for Zoladex data show an average loss of 4.6% to bone mineral substance in the spinal cord after a six-month course of progressive recovery to an average loss of 2.6% compared to baseline six months after cessation of treatment. It has been shown that in patients receiving Zoladex for the treatment of endometriosis, the addition of the hormone replacement therapy (estrogen and progesterone daily) reduces the loss of bone mineral substance and vasomotor symptoms.

Zoladex should be used with caution in women with known metabolic bone disease.

Zoladex can cause an increase in the resistance of the cervix, which may lead to difficulties in the dilatation of the cervix.

Currently, there are no clinical data on the effect of treatment of benign gynecological conditions with Zoladex for periods exceeding six months.

Artificial insemination:

Zoladex 3.6 mg should be used only as part of a scheme for artificial insemination under the supervision of a physician experienced in this field.

As with other agonists, LHRH, there are reports of ovarian hyperstimulation syndrome (OHSS) associated with the use of Zoladex 3.6 mg in combination with HCG. It is assumed that the inhibition level observed with agonist depot, can in some cases lead to an increased need for HCG. Should be carefully monitored stimulation cycle to identify patients at risk of developing OHSS, as the severity and frequency may vary depending on the dosing regimen of HCG. Can not apply human chorionic gonadotrophin (hCG), if it is deemed necessary.

Recommended Zoladex 3.6 mg be given with caution to artificial insemination in patients with polycystic ovarian syndrome, since the receipt of follicles can be increased.

Interactions with other medicinal products and other forms of interaction:

None known.

Pregnancy and lactation:

Although reproductive toxicology studies in animals have revealed no evidence of teratological potential Zoladex should not be applied during pregnancy, since there is a theoretical risk of miscarriage and fetal malformation, LHRH agonists if used during pregnancy. Potentially fertile women should be carefully examined before treatment to exclude pregnancy. Non-hormonal contraceptive methods should be used during the treatment and in the case of endometriosis to restore menstruation.

Should exclude pregnancy before Zoladex 3.6 mg be used for artificial insemination. Clinical data on the use of these conditions are limited but available evidence it may be presumed that there is no causal link between Zoladex and any subsequent developmental abnormalities of the oocyte or pregnancy and the outcome of it.

The use of Zoladex during lactation is not recommended.

Effects on ability to drive and use machines:

There is no evidence that Zoladex leads to violation of these activities.

Adverse effects:


General

Rare cases of hypersensitivity reactions, which may include some manifestations of anaphylaxis.

There are reports of arthralgia. Reported skin rashes are usually mild and often reduced without interrupting treatment.

In patients using Zoladex, were sometimes observed changes in blood pressure, manifest as hypotension or hypertension. The changes are usually transient, resolving with continued therapy or after cessation of therapy with Zoladex. Rarely, such changes were so pronounced as to require medical intervention including withdrawal of treatment with Zoladex.

Individual local effects include pronounced bruising at the site of subcutaneous injection.

Men

Pharmacological effects in men include hot flushes and reduced libido, rarely require discontinuation of therapy. Not very often marked swelling and tenderness of the breast. In patients with early prostate cancer may experience a temporary increase in bone pain, which can be treated symptomatically. Isolated cases of ureteric obstruction and spinal cord compression.

The use of LHRH agonists in men can cause loss of bone minerals.

Ladies

Pharmacological effects in women include hot flashes, sweating, and loss of libido, which rarely require discontinuation of therapy. Not very often noted headache, mood changes, including depression, vaginal dryness and changes in breast size. In patients with early breast cancer may experience a temporary increase in signs and symptoms that can be treated symptomatically. In women with fibroids may cause degeneration of fibroids. Rarely, patients with breast cancer metastases have developed hypercalcaemia on initiation of treatment.

In vitro fertilization: As with other agonists of LHRH, there are reports of ovarian hyperstimulation syndrome (OHSS) associated with the use of Zoladex 3.6 mg in combination with HCG. It is assumed that the inhibition level observed with agonist depot, can in some cases lead to an increased need for HCG. Should be carefully monitored stimulation cycle to identify patients at risk of developing OHSS, as the severity and frequency may vary depending on the dosing regimen of HCG. Can not apply human chorionic gonadotrophin (hCG), if it is deemed necessary.

Overdose

There is no experience with overdose in humans. From animal experiments it can be assumed that, at higher doses, Zoladex can not effect other than the intended therapeutic concentrations of the sex hormones and the reproductive tract. In case of overdose, it should be treated symptomatically.

Pharmacological Properties

Pharmacodynamic properties

Mechanism of action: Zoladex (D-Ser (But) 6 Azgly10 LHRH) is a synthetic analogue of the natural LHRH. As a result of chronic administration of Zoladex inhibit pituitary secretion of luteinising hormone, resulting in a decrease in serum concentrations of testosterone in men, and in the serum concentration of estradiol in women. This effect is reversible upon discontinuation of therapy. Beginning Zoladex, and other agonists of LHRH, can transiently increased serum concentrations of testosterone in men, and serum concentrations of estradiol in women. During the early stages of treatment with Zoladex some women may experience vaginal bleeding of variable duration and intensity. Such bleeding is probably bleeding from estrogen withdrawal and is expected to stop spontaneously.

In men, about 21 days after the first depot injection, testosterone concentrations dropped to kastratni values and remained depressed at treatment every 28 days. This inhibition leads to tumor regression and symptomatic improvement in most patients.

In women, serum concentrations of estradiol inhibit about 21 days after the first depot injection and continued treatment every 28 days remain depressed at levels comparable to those observed in postmenopausal women. This inhibition has been associated with response to hormone-dependent breast cancer, endometriosis, uterine fibroids, and suppression of follicular development in the uterus. It will cause thinning of the endometrium and lead to amenorrhea in most patients.

It has been shown that in combination with Zoladex iron induces amenorrhea and enhances the concentration of hemoglobin and related hematologic parameters in women with fibroids which are anemic. The combination produced a mean hemoglobin concentration of 1 g / dl higher than that achieved with treatment with iron.

Rarely, some women may enter menopause during treatment with LHRH analogues and not recovering menses after cessation of therapy.

Pharmacokinetics

Bioavailability of Zoladex is almost complete. Administration of a depot every four weeks to ensure the maintenance of effective concentrations without accumulation in tissues. Zoladex is poorly protein bound and has a half-life of serum from two to four hours in subjects with normal renal function. The half-life is prolonged in patients with impaired renal function. In this compound, which is introduced in the form of a monthly depot, this change will have negligible effect. Therefore, no adjustment of dosage for such patients. No significant change in pharmacokinetics in patients with hepatic insufficiency.

Preclinical safety data

An increased incidence of benign pituitary tumors in male rats after long-term repeated administration of Zoladex. Although this finding is similar to results previously observed in this species following surgical castration is not detected any difference for people.

In mice, long-term repeated doses being multiples of human application produced histological changes in some regions of the digestive system, manifested by hyperplasia of the islet cells in the pancreas and benign proliferative condition in the pyloric region of the stomach, reported Spontaneous lesions as such.