Endrolin

Each depot vial contains 3.75 mg leuprolide and ampoule 2 ml of solvent

Leuprolide is a synthetic nonapeptide analogue of natural Gn-RH.
Leuprolide acetate acts as a potent inhibitor of gonadotropin secretion when given continuously and in therapeutic doses.

A single monthly injection of Leuprolide acetate 3.75 mg results in an initial stimulation followed by a prolonged suppression of pituitary gonadotropins.
The studies performed in humans have demonstrated that, after an initial stimulation, the prolonged administration of leuprorelin induces a decrease of gonadotropin secretion, consequently suppressing the testicular function in men and inducing an atrophy of the uterine and ectopic endometrial tissue in women. This effect is reversible upon discontinuation of drug therapy.

After administration of the 1st dose, an increase in circulating levels of LH and FSH is induced, leading to an increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in men and oestradiol in women). The pursuit of the treatment leads to a decrease in LH and FSH levels, inducing within 3-4 weeks, to androgen or oestrogen levels equivalent to those obtained after castration or menopause, as long as drug administration continues.

Leuprolide acetate is a polypeptide natural, which will be destroyed in the GI tract. Therefore, usually is administered parenterally.
Following IM or SC administration of leuprolide acetate suspension, the drug is released slowly and gradually, thus providing a prolonged duration of action.

Bioavailability after IM injection is estimated to be about 90%.
Half life: approximately 3 hours following a 1-mg IV dose in healthy male volunteers.
Time to peak concentration: 4 hours
Elimination: < 5% of a 3.75 mg leuprolide acetate was recovered in the urine as parent drug and metabolite I (a pentapeptide).
 

1. Treatment of prostatic cancer with metastases
2. Treatment of endometriosis at genital and extragenital localization (from stage I to stage IV).
   To clinical knowledge concerning the endometriosis treatment is limited to women over 18 years old, the treatment duration is limited to 6 months (see Side Effects section). It is not recommended to start a second treatment period with Enantone or with another Gn-RH analogue.
    

1. Hypersensitivity to any of the ingredients of this drug
2. Vaginal bleedings of undetermined origin
3. Pregnancy
4. Use in women who are breast-feeding
    

1. A worsening of signs and/or symptoms of hormone-dependent disease (e.g., endometriosis, prostatic carcinoma) has occasionally occurred during the first 1-2 weeks of Endrolin therapy (secondary to the Endrolin-induced stimulation release of gonadotropins and resultant ovarian and testicular steroidogenesis) and those signs and/or symptoms will be subside if the therapy is discontinued.
2. Since menstruation should stop with effective doses of Endrolin, the patient should notify her physician if regular menstruation persists. Patients missing successive doses of Endrolin may experience breakthrough bleeding.
3. Because safety in women has not been established beyond 6 months and because of concerns about potential long-term effect on bone density, Endrolin therapy extending beyond this period or additional courses of therapy with this or another GnRH analog currently are not recommended in women.
4. Endrolin should be used with caution, carefully weighing the risks and benefits, in women with known major risk factors for decreased bone mineral content.
5. Patients should not use this drug if they are have undiagnosed abnormal vaginal bleeding, or are allergic to any of the ingredients of this drug.
6. Patients should not use hormonal methods of contraception and should be advised to see their physician if they believe they may be pregnant. If a patient becomes pregnant during treatment, the drug must be discontinued and the patient must be apprised of the potential risk to the fetus.
7. A report of an anaphylactic reaction to synthetic Gn-RH (Gonadorelin HCl) has been reported in the medical literature.
    

Many of the side effects of Endrolin are related to hypoestrogenism in females and hypotestosteronism in males.
There is a risk of increased loss of vertebral trabecular bone density during treatment for endometriosis or for anemia due to uterine leiomyomas: this loss may be irreversible. However, the loss usually is small when the treatment period is limited to 3 months (for uterine leiomyomas) or 6 months (for endometriosis), except in patients with existing risk factors (e.g., history of osteoporosis).

In adult females and males : hot flushes, blurred vision, decreased libido, dizziness, edema, headache, injection site reaction, nausea or vomiting, breasts tenderness, insomnia, weight gain, cardiac arrhythmias or palpitations, anaphylaxis, paresthesias, syncope.

In adult females only : amenorrhea, endometriotic disease flare with a transient increase in symptoms (pelvic pain, dysmenorrhea, dyspareunia), vaginitis, androgenic effects (deepening of voice, increased hair growth), personality or behavioral changes (anxiety, depression, mood changes, nervousness).

In adults males only : constipation, decreased size of testicles, increases the clinical signs and symptoms of prostatic carcinoma (these manifestations are usually transitory), impotence, angina or myocardial infarction, pulmonary embolism, thrombophlebitis.

In pediatric females : uterine bleeding, vaginal discharge.
 

1. Prostatic cancer : one sub-cutaneous injection which will be renewed every 4 weeks.
2. Endrometriosis : The treatment should start during the 5 first days of the menstrual cycle. One subcutaneous or intamuscular injection will be renewed every 4 weeks.
   Duration : Endometriosis will be treated during no more than 6 months whatever is the stage.
    

1. Verify that all of the dissolvent in the ampoule is in the ampoule’s bottom. Break the ampoule's neck to open it. (A)
2. Extract 1 ml of the dissolvent using the needle and the syringe, which are provided in the kit. Discard the rest of the dissolvent. (B)
3. Remove the cover of the vial and inject the dissolvent into the vial. (C)
4. Shake the vial to obtain a uniform milky suspension. (D)
5. Extract all of the vial’s content slowly and put the needle's bevel in the bottom. Do not invert the vial. (E)
6. Disinfect the injection area and inject the content of the syringe using the second needle, which is provided in the kit.
    

No drug interaction studies have been conducted with Endrolin. However, because Endrolin is a peptide that is mainly degraded by peptidase and not by cytochrome P-450 and because of the drug’s low degree of protein binding (46%), drug interactions would not be expected to occur.

Endrolin 3.75 mg is presented in a kit including the vial, one ampoule of dissolvent, one disposable syringe of 3 ml, and one disposable 22G needle.

Store below 250C. Protect from light. Do not freeze.

On medical prescription only
 

Manufactured by :
ERIOCHEM SA., Argentina
Imported and repacked by :
PT KALBE FARMA Tbk.
Bekasi - Indonesia