Suprefact Depot
Suprefact Depot Medication Information:
Suprefact Depot medication comes in several different strengths; click on the strength you need to view prices from pharmacies competing to earn your business.
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Suprefact Depot 6.3mg/IMP
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Suprefact Depot 9.45mg/IMP
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Information for the Patient
Suprefact Depot
Pharmacology
Buserelin is a synthetic peptide analogue of the natural gonadotropin releasing hormone (GnRH/LH-RH). The substitution of glycine in position 6 by D-serine, and that of glycinamide in position 10 by ethylamide, leads to a nonapeptide with a greatly enhanced LH-RH effect. The effects of buserelin on follicle stimulating hormone (FSH) and luteinizing hormone (LH) release are 20 to 170 times greater than those of LH-RH. Buserelin also has a longer duration of action than natural LH-RH.
Investigations in healthy adult males and females have demonstrated that the increase in plasma LH and FSH levels persist for at least 7 hours and that a return to basal values requires about 24 hours.
Clinical inhibition of gonadotropin release, and subsequent reduction of serum testosterone or estradiol to castration level, was found when large pharmacologic doses (50 to 500 µg s.c./day or 300 to 1200 µg intranasal/day) were administered for periods greater than 1 to 3 months. Chronic administration of such doses of buserelin results in sustained inhibition of gonadotropin production, suppression of ovarian and testicular steroidogenesis and, ultimately, reduced circulating levels of gonadotropin and gonadal steroids. These effects form the basis for buserelin use in patients with hormone-dependent metastatic carcinoma of the prostate gland.
In the clinical pharmacology studies with the buserelin implant 2 months, the time-concentration curves of buserelin release from implants were reproducible and similar to those observed in preclinical studies. Maximum release on day 1 was followed by an extended plateau phase which lasted for 8 weeks. After this period, an accelerated biodegradation of the implant material was observed with a terminal half-life of release of 20 to 30 days. The single dose studies performed in healthy male subjects and in patients with benign prostatic hypertrophy showed a therapeutic release rate for 8 weeks (dosage interval); a minimum therapeutic release rate of 4.95 µg/day after 2 months was fully effective in maintaining testosterone levels in the surgical castration range by controlled release of buserelin. At the end of the dosage interval, the average fraction of the buserelin dose released from the implants based on urinary excretion data was 84% (in healthy subjects) and 92% (in patients with benign prostatic hypertrophy). Chronic administration of the implant every 2 months ensures continuous suppression of testosterone secretion with no cumulation of buserelin release after repeated dosing.
Similarly the release profile of the buserelin implant 3 months is biphasic; the initial release (Tmax <1 day) is followed by a phase with slow, steady-release lasting more than the 3-month dosing interval. A second small increase in the serum buserelin concentration was detected between weeks 12 and 16. At 16 weeks, median serum levels of buserelin were far above the detection limit (0.05 ng/mL), indicating considerable release reserve, and testosterone levels were in the surgical castration range. Sixteen weeks after single-dose administration of buserelin implant 3 months, urinary excretion of buserelin is between 2 and 31 µg/g creatinine (estimated threshold for suppression of testosterone secretion is 1 µg/g creatinine). This indicates that the release characteristics of buserelin from the implant ensure therapeutically effective systemic concentrations for at least 3 weeks after the end of the proposed dosing interval (3 months).
Indications
Palliative treatment of patients with hormone-dependent advanced carcinoma of the prostate gland (Stage D).
Precautions
Drug Interactions
During treatment with buserelin, the effect of antidiabetic agents may be attenuated (see also Adverse Effects).
Allergic Reactions
Allergic asthma with dyspnea as well as in isolated cases, anaphylactic/anaphylactoid shock have been observed in patients treated with buserelin, necessitating early treatment of such conditions. For patients experiencing anaphylactic/anaphylactoid reactions who were given buserelin implant 2 months or buserelin implant 3 months, it may be necessary to surgically remove the implant.
Supplied
Depot 3 Months
Each applicator contains 1 implant dose consisting of 3 identical cream-colored, biodegradable and biocompatible rods. Each implant dose contains a total of buserelin acetate 9.9 mg equivalent to buserelin base 9.45 mg. Nonmedicinal ingredients: poly-(D,L-lactide-co-glycolide). Sterile ready-to-use disposable applicator with an integrated safety engineered needle (internal needle diameter of 1.4 mm) for s.c. injection. Cartons supplied with 1 sterile foil bag containing 1 applicator prefilled with 1 implant dose. Consists of 3 identical rods.
Store the intact package between 15 and 30°C. Protect from excessive heat and do not use beyond the expiration date printed on the container label.
Depot 2 Months
Each applicator contains 1 implant dose consisting of 2 identical cream-colored, biodegradable and biocompatible rods. Each implant dose contains a total of buserelin acetate 6.6 mg equivalent to buserelin base 6.3 mg. Nonmedicinal ingredients: poly-(D,L-lactide-co-glycolide). Sterile ready-to-use disposable applicator with an integrated safety engineered needle (internal needle diameter of 1.4 mm) for s.c. injection. Cartons supplied with 1 sterile foil bag containing 1 applicator prefilled with 1 implant dose. Consists of 2 identical rods.
Contraindications
In patients with known hypersensitivity to buserelin or any other formulation component (see Supplied); patients who do not present with hormone-dependent carcinoma; and in patients who have undergone orchiectomy (in these patients, no further reduction of testosterone level is to be expected with buserelin therapy).
Warnings
General: Cases of early, transient exacerbation of disease signs and symptoms have been reported during treatment with LH-RH agonists (see Precautions). At the start of treatment, there is a temporary rise in male sex hormones. In a few patients, this rise may be associated with isolated cases of short-term worsening of signs and symptoms such as bone pain, urinary signs and symptoms (usually occurring in patients with a previous history of obstructive uropathy) or muscular weakness in the legs. Worsening of clinical conditions may occasionally require discontinuation of therapy and/or surgical intervention.
The majority of clinical studies demonstrating the efficacy of buserelin injection and nasal solution were completed without concomitant therapy with antiandrogens during the first weeks of treatment. For the clinical studies with buserelin implant 2 months and buserelin implant 3 months, however, an antiandrogen was administered as initial concurrent treatment for a duration of 5 weeks, starting 7 days before the start of buserelin implant therapy.
Patients with Vertebral Metastases: Due to the possibility of early, transient, lesion exacerbation, and consequent possible spinal cord compression, these patients should be closely monitored when LH-RH agonist treatment is initiated.
Patients with Genitourinary Tract Symptoms: Patients with genitourinary symptoms may experience a transient increase in such symptoms early in LH-RH agonist treatment. These patients should be particularly closely observed for events indicative of obstruction.
Reversibility of LH-RH Agonist-induced Hypogonadism: While hypogonadism is a pharmacologic consequence of long-term LH-RH agonist treatment, its reversibility has not been established in patients suffering with prostatic carcinoma.
Adverse Effects
Suprefact Depot
Listing Of Adverse Reactions (At Least Possibly Or Probably Related), Incidence ≥1%
Other adverse reactions, arranged by body system, and, at least possibly or probably related to the administration of buserelin implant 2 months or buserelin implant 3 months (individual signs/symptoms occurred at an incidence of less than 1%) were:
Digestive
changes in appetite (e.g., anorexia), increased thirst and vomiting.
Special Senses
eye dryness and irritation, feeling of pressure behind the eyes, impaired vision (e.g., blurred vision), hearing disorders and tinnitus.
Musculoskeletal System
The use of LHRH-agonists may be associated with musculoskeletal discomfort and pain (including shoulder pain/stiffness in women). It may be associated with decreased bone density and may lead to osteoporosis and an increased risk of bone fracture. The risk of skeletal fracture increases with the duration of therapy.
Miscellaneous
In the literature and in our international database, other adverse events, including events which were observed only in females (excluding female gender-specific events) or for other unlabeled indications, have been observed in patients treated with buserelin, as itemized below (not all events were considered to be related to buserelin therapy):
Skin and Appendages
articular pains, irritation of the mucosa in the nasopharynx due to nasal solution administration (which may lead to nosebleeds, hoarseness, disturbances of smell or taste), rhinorrhea and skin reaction (wheal) allergy, changes in scalp and body hair (increase or decrease).
Endocrine
exacerbation of pre-existing diabetes mellitus and hyperglycemia.
Body as a Whole
non-serious clinical flare reaction, asthenia and fever.
Respiratory
dyspnea and pharyngitis.
Laboratory Values
changes in blood lipids (e.g. hypercholesterolemia, hyperlipidemia), increase in bilirubin levels and increase in serum liver enzymes levels (e.g., transaminases).
Musculoskeletal
muscle cramps and myopathy.
Nervous System
concentration and memory disturbances, dizziness, drowsiness, emotional instability, feelings of anxiety, mood changes, nervousness and tiredness.
Urogenital
abnormal ejaculation, male genital pain and urogenital disorder.
Metabolic and Nutritional
weight gain and weight loss.
Hemic and Lymphatic
leukopenia and thrombopenia.
Cardiovascular
heart failure, tachycardia and thrombophlebitis.
Overdose
For management of a suspected drug overdose, CPhA recommends that you contact your regional Poison Control Centre. See the eCPS Directories section for a list of Poison Control Centres.
There have been no clinical reports of acute overdosage with buserelin implant 2 months or buserelin implant 3 months.
From acute studies of buserelin in rodents, neither 0.5 mg/kg/i.v. (mouse) nor 1 mg/kg/i.v. (rat) produced evidence of toxic signs.
Two groups of 6 and 4 healthy volunteers, aged 26 to 40 years and 31 to 40 years respectively, were given 1 mg buserelin or 5 mg buserelin orally as a single dose. No LH or FSH release was observed. No clinical effects were observed.
Dosage
Instructions for Using the Applicator
(See package insert for illustrations.)
Please Note: To prevent the implant rods from falling out of the injection needle, hold the applicator in a vertical position until immediately prior to puncture, with the needle pointing upwards.
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After removing the applicator from the foil wrapping, check that the implant rods are located in the window of the handle. If necessary, tap the protective cap of the needle lightly to reposition them in the window.
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Disinfect the injection site of the lateral abdominal wall and administer a local anesthetic, if desired. After removing the protective case from the plunger, remove the cap from the injection needle.
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Lift a fold of skin and insert the needle approximately 3 cm (somewhat more than 1 inch) into the subcutaneous tissue, with the tip of the needle pointed slightly upwards. Withdraw the applicator about 1 to 2 cm prior to injection of the implant rods.
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While fully depressing the plunger, inject the implant rods into the subcutaneous tissue. Compress the puncture channel while withdrawing the needle so that the implant rods are retained in the tissue.
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When the plunger is completely inserted to its final position (plunger knob is touching the body of applicator), the front end of the plunger protrudes the top of the cannula, protecting the needle and minimizing the risks of needle stick injuries.
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To ensure that the implant rods have been injected, check the tip of the plunger to see if it is visible at the tip of the needle.
