Tapros Depot

Tapros Depot

leuprorelin

Manufacturer:

Takeda
Full Prescribing Info
Contents
Leuprorelin acetate.
Description
Each depot vial also contains the following: Powder: Leuprorelin 3.75 mg, copolymer (DL-Lactic acid/glycolic acid) 75/25 mol% 33.75 mg, mannitol 6.6 mg. Solvent: Sodium carboxymethylcellulose 10 mg, mannitol 100 mg, polysorbate 80 2 mg, water for injection sufficient quantity for 2 mL.
Action
Pharmacology: Leuprorelin is a synthetic nonapeptide analogue of natural Gn-RH. The studies performed in humans as well as in animals 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.
Through some studies in animals, another mechanism of action has been evoked: A direct effect by the decrease of sensitivity of the gonadotropin receptors.
In humans, after administration of the 1st dose, an increase in circulating levels of LH and FSH is induced, leading to an initial 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.
Indications/Uses
Treatment of prostatic cancer with metastase.
Treatment of endometriosis at genital and extragenital localization (from stage I-IV). The clinical knowledge concerning the endometriosis treatment is limited to women >18 years. The duration of treatment is limited to 6 months.
Pre-operative management of uterine myoma (fibroid) to reduce their size and associated bleeding.
Treatment of central precocious puberty.
Breast cancer in pre-menopausal women, provided endocrine treatment is indicated. It is not recommended to start a 2nd treatment period with Tapros or with another Gn-RH analogue.
Dosage/Direction for Use
Prostatic Cancer and Breast Cancer: 1 SC inj which will be renewed every 4 weeks.
Endometriosis: Adults: 1 SC/IM inj once every 4 weeks for a period of 6 months only; <50 kg: 1.88 mcg SC/IM inj. The treatment should start during the 5 days of menstrual cycle.
Uterine Myoma (Fibroid): 1 SC/IM inj will be renewed every 4 weeks. The treatment should start during the 5 days of menstrual cycle.
Central Precocious Puberty: 30 mcg/kg SC once every 4 weeks, may be increased to 90 mcg/kg.
Contraindications
Hypersensitivity to Gn-RH, Gn-RH analogues or to any of the components of Tapros Depot. Vaginal bleedings of undetermined origin.
Use in pregnancy & lactation: Do not use when pregnant. Nonpregnancy must be confirmed before the start of treatment.
Because of the lack of data regarding Tapros Depot's excretion in milk and its potential effects on nursing babies, it should not be used in breastfeeding.
Warnings
Since Tapros Depot is a sustained-release preparation with its action lasting 4 weeks, administration at an interval exceeding 4 weeks may lead to the recurrence of an increase in the serum level of gonadotropic hormone due to the pituitary-gonad system stimulating effect of this drug, resulting in a transient aggravation of the clinical condition. Therefore, the method of administering once every 4 weeks should be observed.
Endometriosis, Uterine Myoma (Fibroid): The incidence of adverse reaction generally tends to increase with an increase in dose. Thus, in setting the dose, careful attention should be paid to the body weight.
Before any prescription of Tapros Depot, it is mandatory to verify that the patient is not pregnant. During the period of the treatment, the patient should be instructed to prevent conception with the use of nonhormonal methods.
It is advised, as for every other Gn-RH analogues, to monitor the patients suffering from osteoporosis during prolonged use.
A decrease in bone mass may occur owing to estrogen reducing effect of Tapros Depot. Therefore, as a rule, it should not be administered to patients with endometriosis or uterine myoma for >6 months. (The safety of administration for >6 months has not been established). When it is inevitable to administer Tapros Depot for a long period or to resume its administration, it should be carefully administered after the bone mass is examined as far as possible.
Breast Cancer: When starting treatment with Tapros Depot, absence/presence of hormone receptor expression should be confirmed as a rule. When hormone receptor expression is confirm to be negative, Tapros Depot should not be used.
Before starting the treatment, it should be confirmed that the patient is not pregnant. During the period of treatment with Tapros Depot, the patient should be instructed to prevent conception with the use of a nonhormonal method. A decrease in bone mass may occur owing to estrogen reducing effect of Tapros Depot. Therefore, when administered for a long period, Tapros Depot should be carefully administered after bone mass is examined as far as possible.
Uterine Myoma (Fibroid): It should be noted that the treatment of uterine myoma with Tapros Depot is not radical treatment. Therefore, it should be used as a means of providing conservative treatment until operation or providing premenopausal conservative treatment. For hypogastralgia and low back pain, the effect is not observed at the early period after administration. During such a period, therefore, appropriate symptomatic treatment should be given.
Prostate Cancer: Patient who have already had renal dysfunction due to spinal cord compression or urethral obstruction or those may be risk of developing of such manifestation. There is a possibility that the symptoms or underlying diseases are aggravated with the elevation of serum testosterone level in the early period after the first administration.
Special Precautions
For All Indications: It has been reported that the benign pituitary adenoma was observed in rats in a study in which Tapros Depot was administered SC in dose of 0.8, 3.6 and 16 mg (as leuporelin acetate)/kg at 4 week intervals for 1 year, and another study in which an aqueous injectable solution of leuprorelin acetate was similarly administered in doses 0.6, 1.5, 4 mg/kg daily for 2 years.
Endometriosis, Uterine Myoma (Fibroid): In administration of Tapros Depot, care should be taken to differentiate a similar disease (malignant tumor) from endometriosis, uterine myoma. If during administration, any growing phyma is found or no improvement is seen in the clinical symptom, the administration should be discontinued.
In the early period after the first administration of Tapros Depot, a transient elevation of the serum level of estrogen may occur owing to the stimulating effect, as a highly active LH-RH derivative on the pituitary-gonad system, resulting in a transient aggravation of clinical condition. However, such an aggravation usually disappears in the course of continued administration.
Since depressed state like climateric disturbance may occur, the patient's condition should be closely observed.
In administration of Tapros Depot to patients with submucous myoma, bleeding symptom may worsen. Therefore, close observation should be made. The patient should be instructed to contact the attending physician in case of any aggravation of the bleeding symptom.
Central Percocious Puberty: In the early period after the first administration of Tapros Depot, a transient elevation of the serum level of gonadropin hormone may occur owing to the stimulating effect, as a highly active LH-RH derivative on the pituitary-gonad system, resulting in a transient aggravation of clinical condition. However, such an aggravation usually disappears in the course of continued administration.
LH-RH test should be performed at regular intervals. When suppression of the action of LH and FSH in blood is not achieved. In the administration of Tapros Depot should be discontinued.
Prostate Cancer and Breast Cancer: Since Tapros Depot is an agent for endocrine therapy, use for prostate/premenopausal breast cancer should be limited to patients for whom treatment is considered appropriate under the supervision of a physician who has adequate knowledge and experience in medication for cancer.
In the early period after the first administration of Tapros Depot, a transient elevation of the serum level of estrogen may occur owing to the stimulating effect, as a highly active LH-RH derivative on the pituitary-gonad system, resulting in a transient aggravation of clinical condition. However, such an aggravation usually disappears in the course of continued administration.
Since depressed state like climateric disturbance may occur, the patient's condition should be closely observed.
Endometriosis, Uterine Myoma (Fibroid), Central Precocious Puberty, Breast Cancer: It has been reported that the administration of Tapros Depot brought about venous thrombosis or pulmonary embolism.
Prostate Cancer: It has been reported that the administration of Tapros Depot brought about cerebral infarction, venous thrombosis or pulmonary embolism.
Use in children: The safety of Tapros Depot in prematures, newborns and nursing infants has not been established.
Use In Pregnancy & Lactation
Do not use when pregnant. Nonpregnancy must be confirmed before the start of treatment.
Because of the lack of data regarding Tapros Depot's excretion in milk and its potential effects on nursing babies, it should not be used in breastfeeding.
Adverse Reactions
Clinically Significant Adverse Reactions: Since interstitial pneumonia, accompanied by fever, coughing, dyspnea, abnormal chest X-ray may occur (<0.1%), the patient's condition should be closely observed. If any abnormality is observed, appropriate measures eg, treatment with adrenal cortical hormones should be taken.
Since anaphylactoid symptoms may occur (<0.1%), careful inquiry should be made and close observation should be made after the administration of Tapros Depot. If any abnormality is observed, appropriate measures should be taken.
Hepatid dysfunction or jaundice, with increased AST (GOT), ALT (GPT) may occur (frequency unknown). Development or aggravation of diabetes may occur (frequency unknown). Therefore, close observation should be made and if any abnormality is observed, appropriate measures should be taken.
Pituitary apoplexy has been reported in patients with pituitary adenoma (frequency unknown). Therefore, if headache, vision impairment, visual field disorder are observed immediately after the first dose of Tapros Depot, appropriate measures eg, surgical treatment should be taken after conducting examination.
Prostatic Cancer: At the beginning of the treatment (see Warnings and Precautions); the starting treatment can be sometimes accompanies by some aggravations of clinical signs and symptoms (flare phenomenon): Bone pain, hematuria, urinary obstruction and weakness of the lower limbs or paresthesia has been reported. These manifestations of the symptoms are usually transitory disappearing within 1-2 weeks during the pursuit of treatment. However, the possibility of potential exacerbation of these symptoms during the 1st few weeks of treatment has to be taken into consideration in patients with neurological disorders or with urinary obstruction.
Hepatic (Close Observation Should be Made): ≥5%: Increased LDH; 0.1 to <5%: Jaundice or increased AST (GOT), ALT (GPT), γ-GTP or ALP.
Endocrine: ≥5%: Hot flushes, feeling of warmth; 0.1 to <5%: Headache, facial hot flushes, dizziness, decreased libido, erectile disturbance, gynecomastia, testicular atrophy or discomfort in the perineal region.
Musculoskeletal: 0.1 to <5%: Arthralgia, bone pain in the shoulder, low back or limbs or difficulty in walking; <0.1%: Muscle ache or decreased bone mass.
Dermatologic: 0.1 to <5%: Dermatitis or hair growth on the head.
Urinary: 0.1 to <5%: Pollakiuria, dysuria or increased blood urea nitrogen (BUN).
Cardiovascular: 0.1 to <5%: ECG abnormalities or increased cardiothoracic ratio.
Hematologic: 0.1 to <5%: Anemia or decreased platelet count.
Gastrointestinal: 0.1 to <5%: Nausea, vomiting, anorexia; <0.1%: Diarrhea.
Hypersensitivity: 0.1 to <5%: Rash of pruritus.
Administration Site: 0.1 to <5%: Reactions at the injection site eg, pain, induration and redness; <0.1%: Abscess.
Others: 0.1 to <5%: Edema, pressure sensation of chest, rigor, malaise, numbness of lips or limbs, increased weight, paresthesia, deafness, tinnitus, fever, increased total cholesterol, triglyceride or uric acid, hyperkalemia or increased blood sugar level; <0.1%: Weakness.
Endometriosis, Uterine Myoma (Fibroid), Central Precocious Puberty, Breast Cancer: Symptoms Resulting from Decreased Estrogen: ≥5%: Hot flushes, feeling of warmth, feeling of hot flushes, shoulder stiffness, headache, insomnia, dizziness or diaphoresis; 0.1 to <5%: Decreased libido, coldness, visual disturbance or emotional lability.
Female Reproductive: 0.1 to <5%: Metrorrhagia, vaginal dryness, coital pain, vaginitis, increased fluor, ovarian hyperstimulation syndrome, or pain, swelling or atrophy of the breast.
Musculoskeletal: ≥5%: Pains eg, arthralgia and bone pain; 0.1 to <5%: Joint stiffness, lumbar pain, muscle ache, muscular spasm, decreased bone mass, increased serum phosphorus or hypercalcemia.
Dermatologic: 0.1 to <5%: Acne, dry skin, alopecia, hypertrichosis or nail abnormality.
Psychoneurologic: 0.1 to <5%: Sleepiness, irritated feeling, hypomnesia, decreased attentiveness or paresthesia.
Hypersensitivity: 0.1 to <5%: Rash of pruritus.
Hepatic (Close Observation Should be Made): 0.1 to <5%: Increased AST (GOT), ALT (GPT), ALP, LDH, γ-GTP or bilirubin; <0.1%: Jaundice.
Gastrointestinal: 0.1 to <5%: Nausea, vomiting, anorexia, abdominal pain, feeling of enlarged abdomen, diarrhea, constipation, stomatitis or thirst.
Cardiovascular: 0.1 to <5%: Palpitation or increased blood pressure.
Hematologic: 0.1 to <5%: Increased red blood cell count, anemia, decreased white blood cell, decreased platelet count or prolonged partial thromboplastin time.
Urinary: 0.1 to <5%: Pollakiuria, dysuria or increased BUN.
Administration Site: 0.1 to <5%: Reactions at the injection site eg, pain, induration and redness; <0.1%: Abscess.
Others: 0.1 to <5%: Fatigue, malaise, weakness, numbness of lips or limbs, carpal tunnel syndrome, tinnitus, deafness, chest discomfort, edema, increased weight, pain of lower extremities, respiratory distress, fever, increased total function cholesterol, LDL-cholesterol or triglyceride, or hyperkalemia; <0.1%: Decreased, taste abnomiality or abnormal thyroid function.
It has been reported that the administration of leuprorelin acetate brought about cerebral infarction, venous thrombosis or pulmonary embolism.
Drug Interactions
Tapros should be administered with care when co-administered with sex hormone preparations.
Caution For Usage
Route of Administration: Tapros should be used only by SC or IM route (IV injection of Tapros may induce thrombosis).
Method of Administration: For SC Injection: The site for SC injection should be brachial, abdominal or gluteal region.
The injection site should be changed each time. The repeated injection should not be given at the same time.
The check should be made to see that the needle is not piercing a blood vessel.
The patients should be instructed not to massage the injection site.
Preparation: The injectable solution should be prepared at the time of use and be used immediately after suspending. If any sedimentation is noticed in the suspension vial product, such suspension should be used after swirling gently, avoiding formation of bubbles, to resuspend the particles uniformly. Use immediately after reconstitution.
Storage
Store at temperature below 25°C, avoiding heat. No refrigeration necessary.
ATC Classification
L02AE02 - leuprorelin ; Belongs to the class of gonadotropin releasing hormone analogues. Used in endocrine therapy.
Presentation/Packing
Depot inj (vial) 3.75 mg x 1's.
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