HuCog-5000 HP

HuCog-5000 HP

chorionic gonadotrophin

Manufacturer:

Bharat

Distributor:

Sandoval

Marketer:

BSV Bioscience Phils
Full Prescribing Info
Contents
Human chorionic gonadotrophin.
Description
Each vial of the product contains chorionic gonadotrophin B.P. 2000 I.U./5000 I.U./10000 I.U.
The product contains highly purified chorionic gonadotrophin which is a hormonal preparation derived from urine of pregnant females. It is freeze dried for subcutaneous or intramuscular injection. Chorionic gonadotrophin is available in multiple strengths of 2000, 5000 and 10000 IU.
Chemical name: Human chorionic gonadotrophin.
IUPAC name: (2S)-2-amino-6-[(2R)-1-(carboxymethylamino)-1-oxo-3-sulfanylpropan-2- yl]amino]-6-oxohexanoic acid.
Molecular formula: C11H19N3O6S.
Molecular weight: 321.348 g/mol.
Excipients/Inactive Ingredients: Mannitol B.P., sucrose B.P., sodium ascorbate B.P., anhydrous di-sodium hydrogen phosphate B.P. and phosphoric acid B.P.
Action
Pharmacology: Mechanism of Action: Human chorionic gonadotropin (hCG) exerts its effect through various mechanisms, which depend upon the purpose for which it is being used, the sex of the patient, and the level of maturity of the patient to whom it is administered.
Human chorionic gonadotropin (hCG) is secreted by fused and differentiated syncytiotrophoblasts. In adult females with infertility, human chorionic gonadotropin acts similar to luteinizing hormone (LH). It also possesses minimal follicle-stimulating hormone (FSH) activity. Human chorionic gonadotropin promotes the development and maintenance of the corpus luteum and the production of progesterone. Subsequent to hCG administration, final luteinization or maturation of the oocytes ensues and either ovulation can ensue for timed insemination techniques, or oocyte retrieval can take place for assisted reproductive technology (ART) procedures. Once pregnancy is established, endogenous hCG is normally secreted by the placenta to assist the continued secretion of female hormones and the corpus luteum.
Further, hCG is supposed to be involved in placentation through activities such as maintaining angiogenesis of the uterine vasculature and promoting differentiation of cytotrophoblasts into syncytiotrophoblasts. Ample evidences suggest roles for regular hCG in fostering implantation, preventing fetal rejection, coordinating uterine and fetal growth, and, potentially, growth and development of fetal organs.
In adult and adolescent men with hypogonadotropic hypogonadism, hCG acts similar to LH and stimulates testosterone production in the Leydig cells and spermatogenesis in the seminiferous tubules. Stimulation of androgen synthesis by hCG causes development of secondary sex characteristics in males, and also helps in normalization of serum testosterone levels. In male infants and children with cryptorchidism, hCG acts like LH and causes the Leydig cells of the testes to elicit a testosterone surge and induce the descent of palpable testes.
Clinical Trials: Use of hCG in infertility: Ovarian stimulation is commonly used alone or with assisted reproductive techniques (ART) in patients with anovulatory infertility and other causes of infertility. Different factors are presumed to influence reproductive outcomes when ART is applied. Apart from patient's age, timing of insemination in relation to ovulation is considered the most important predictive factor for treatment success. Since the advent, human chorionic gonadotropin (hCG) has been used to trigger ovulation. A study was conducted with the aim to ascertain the impact of hCG administration and luteinizing hormone surge on treatment outcomes in ART with or without ovarian stimulation. For the study, a retrospective analysis of 2000 treatment cycles; 637 timed intercourse and 1363 intrauterine insemination cycles was performed. Clomiphene citrate or letrozole, alone or with follicle stimulating hormone were used as stimulation protocols. LH surge was considered when LH levels increased ≥200% over preceding two days. hCG was administered at a dose of 10,000 IU when required. Clinical pregnancy rate per cycle was the primary outcome of the study. LH surge was associated with better outcomes. Furthermore, it was appreciated that pregnancy rate was higher when hCG was administered.
There is no consensus on appropriate dose of urine-derived hCG for oocyte maturation before oocyte collection in in vitro fertilization. Doses of 2500 to 15000 IU have been used invariably. Hoyos and colleagues conducted a study to understand the usefulness of low dose urine-hCG for effective oocyte maturation in assisted reproductive technique regardless of the body mass index (BMI). A group of 295 females who were previously subjected to in vitro fertilization/ intracytoplasmic sperm injection cycles were recruited for the study. Therapeutic cycles were categorized into 3 groups according to BMI; <25 consisting 136 females, 25 to <30 consisting 84 females and ≥30 consisting 75 females. Patients were administered 5000, 10000 or 15000 IU of urine derived hCG for the purpose of final oocyte maturation prior to oocyte collection. The primary and secondary endpoints of the study were clinical pregnancy rates and live birth rates, respectively. It was noted that serum hCG level at 12-24 hours (increasing trend) was associated with dose of urine-derived hCG administered to trigger ovulation; the results did not vary according to the BMI. The total number of developed follicles, follicles ≥14 mm and serum estradiol level on the day urine-derived hCG was administered were remarkably higher in patients receiving 5000 IU compared to 10000 IU or 15000 IU. Similar findings were observed for the number of oocytes collected, number of mature oocytes and number of fertilized oocytes. The clinical pregnancy rates and live birth rates were alike with different doses of urine-derived hCG (Table). Further, it was noted that only maternal age had an adverse impact on clinical pregnancy and live birth rates.
It was thus concluded that low dose urine-derived hCG was effective for oocyte maturation and associated with clinical pregnancy and live birth rate similar to other doses of hCG. (see table).

Click on icon to see table/diagram/image

Human chorionic gonadotrophin in cryptorchidism: Medical therapy such as hCG has been used since long for the management of cryptorchidism. Medical therapy may have an advantage over other therapies, for instance, if patient shows partial response to medical therapy with hCG, it may be repeated to obtain complete response. Further, it has been shown that hCG is more potent than luteinizing hormone-releasing hormone therapy in treatment of cryptorchidism. A study was conducted by Christiansen and colleagues to ascertain the impact of hCG, gonadotropin releasing hormone (GnRH) and placebo in males with cryptorchidism (unilateral or bilateral maldescended testes). A group of 155 males with bilateral and 88 males with unilateral cryptorchidism were enrolled in the study. The patients enrolled aged between 1 and 13 years. Patients were administered intramuscular injections of hCG twice weekly for 3 weeks whereas GnRH and placebo were administered intranasally. It was noted that the outcomes with hCG were superior to GnRH and placebo in patients with bilateral maldescended testes. Following hCG therapy, both testes descended in 25% males and improvement in the position of testes was noted in another 25% patients. In patients with unilateral maldescended testes, 14% males attained complete testicular descent compared to 3% and 0% with placebo and GnRH therapy. It was thus inferred that 25% patients with cryptorchidism achieved testes descent with hCG therapy thus substantiating the use of this therapy. However, the study results did not support the use of GnRH therapy for this indication. In another trial, a group of 128 pre-pubertal boys with unilateral or bilateral cryptorchidism were recruited to appreciate the role of hCG treatment. Patients were randomized to receive different intramuscular doses of hCG therapy twice weekly for 5 consecutive weeks according to the age of the patient; patients aged 1-4 years received 10 doses of 250 IU, 4-7 years received 10 doses of 500 IU, and 7-12 years received 10 doses of 1000 IU. Complete clinical response (complete descend of testes into the scrotum) was noted in 25% patients, and partial response denoted as distal movement of testes towards scrotum was noted in 32% males (Figure). The baseline plasma testosterone levels were 18±9 ng/dL that increased remarkably during hCG treatment to range between 344±185 to 640±288 ng/dL. However, these values did not differ remarkably between responders and partial responders. The results thus confirmed the effectiveness of hCG for treatment of cryptorchidism with minimal effective dose being 500 IU twice weekly for five consecutive weeks.
Hypogonadotropic hypogonadal and effectiveness of hCG therapy: Hypogonadism resulting from primary testicular or secondary hypothalamic-pituitary dysfunction (hypogonadotropic) is associated with impairment in testicular function. The features of hypogonadotropic hypogonadism include androgen deficiency, and delay or termination of sexual maturation. The treatment of this disorder depends on the choice of an individual to preserve fertility. It is noted that sperm production is restored to nearly 50% of the normal level with hCG or follicle stimulating hormone (FSH) therapy and full restoration is achieved with hCG plus FSH. Gonadotropin may be initiated at a dose of 1000-2500 IU twice weekly for 8 to 12 weeks. It is noteworthy that hCG alone may be useful for inducing spermatogenesis in patients. (see figure).

Click on icon to see table/diagram/image

In a study, the importance of follicle stimulating hormone for spermatogenesis was ascertained in males with hypogonadotropic hypogonadism. Patients (n=13) with gonadotropin deficiency due to idiopathic hypogonadotropic hypogonadism, Kallmann syndrome or pituitary insufficiency were recruited in the study. Individuals were treated with GnRH or hCG for induction of spermatogenesis. When spermatogenesis was achieved individuals were treated with hCG alone for maintaining secondary sexual characteristics and to ascertain whether hCG alone could be useful to maintain sperm production. It was observed that after spermatogenesis, hCG therapy alone was continued for 3-24 months. After 12 months, sperm count started to decrease gradually but was present in all except one. On the basis of study observations, it could be inferred that once spermatogenesis is induced, it can be maintained for an extended duration with hCG alone. Furthermore, it has been elicited that hCG has a stimulatory effect on testicular steroidogenesis and penile growth. In this context, a study conducted in a cohort of males with idiopathic hypogonadotropic hypogonadism with micropenis showed that administration of intramuscular injection of hCG thrice weekly for 8 weeks is useful for improving gonadal function and penile growth. Human chorionic gonadotropin helped in increasing serum testosterone level, penile length and testicular volume in males with idiopathic hypogonadotropic hypogonadism.
Pharmacokinetics: Human chorionic gonadotropin undergoes a series of metabolic conversions before ultimately being excreted in urine. One of the initial stages in hCG degradation is proteolytic cleavage of the β subunit (probably by human leukocyte elastase), which produces a 'nicked' form of the protein. Nicked hCG rapidly dissociates into its component α and β subunits. Further, the nicked β subunit is degraded, mostly in the kidneys, resulting in a β-core fragment.
Human chorionic gonadotropin injections may be given intramuscularly (IM) or subcutaneously (SC). A large slew of studies have compared the pharmacokinetics of hCG after IM and SC administration, but the results obtained have been equivocal. A study by Saal et al revealed that compared with IM administration of hCG, peak serum drug concentration was remarkably delayed and serum half-life was prolonged after SC injection.
In another study, healthy pituitary-suppressed females were assigned to single hCG injections of 5000 and 10,000 IU IM and 10,000 IU SC. The average elimination half-life was 32-33 hours, regardless of the treatment regimen. Intramuscular and SC injections of 10,000 IU hCG were found to be bioequivalent with respect to AUC. The Cmax and Tmax were also similar between the two administration routes. Intramuscular doses of 5000 IU and 10,000 IU hCG were observed to be dose-proportional. It was thus concluded that since SC hCG is bioequivalent to IM hCG with respect to extent of absorption (its major pharmacokinetic variable) and is well tolerated, the SC administration route may be effectively and safely employed in assisted reproduction.
Indications/Uses
Anovulatory infertility in female where the cause is secondary & not due to ovarian failure & its administration would form part of recognized treatment regimen involving prior stimulation of follicular maturation & endometrial proliferation w/ menotrophin or any other medication used for stimulation in infertility. Promotion of controlled superovulation in female in medically assisted reproduction programmes in combination w/ FSH or human menopausal gonadotropin (HMG). Hypogonadotrophin hypogonadism, cryptorchism & delayed puberty associated w/ insufficient gonadotrophic pituitary function in male. Induction & maintenance of spermatogenesis in male w/ concomitant menotrophin therapy.
Dosage/Direction for Use
Anovulatory infertility 5,000-10,000 IU following last dose of menotrophin or other drugs used for stimulation in infertility. Promotion of controlled superovulation in medically assisted reproduction programmes in combination w/ FSH or HMG 5,000-10,000 IU 30-40 hr after the last FSH or HMG inj. Hypogonadotrophin hypogonadism 500-1,000 IU IM thrice a wk for 3 wk followed by same dose twice a wk for 3 wk or, 4,000 u IM thrice a wk for 6-9 mth followed by 2,000 u thrice a wk for an additional 3 mth. Deficient spermatogenesis cases Usually 3,000 IU/wk in combination w/ an FSH or HMG prep. Continued for at least 3 mth before any improvement can be expected. Suspend testosterone replacement therapy during this treatment. May sometimes be maintained by HCG monotherapy once improvement is achieved. Delayed puberty associated w/ insufficient gonadotrophic pituitary function 1,500 IU twice wkly for at least 6 mth. Cryptorchidism 4,000 u IM thrice a wk for 3 wk; or 5,000 u IM every other day for 4 inj; or 500-1,000 u IM for 15 inj over a period of 6 wk; or 500 u thrice a wk for 4-6 wk, may repeat series at 1,000-u dosage 1 mth later if not successful.
Overdosage
Overdose of human menopausal gonadotropin may lead to ovarian hyperstimulation syndrome (OHSS). OHSS comprises marked ovarian enlargement, high serum sex steroids, and an increase in vascular permeability which can lead to fluid accumulation in peritoneal, pleural and, rarely, in the pericardial cavities. Severe cases of OHSS are characterized by abdominal pain, abdominal distension, severe ovarian enlargement, weight gain, dyspnea, oliguria and gastrointestinal symptoms including nausea, vomiting and diarrhea.
Contraindications
Human chorionic gonadotropin is contraindicated for use in patients with a history of hypersensitivity to this product. It is also contraindicated in males with prostate cancer, or any patient with sex hormone dependent neoplastic disease.
Special Precautions
Stimulation of ovulation with human chorionic gonadotropin may cause superovulation and the hyperstimulation syndrome. Estrogen assays help detect this excessive response so that human chorionic gonadotropin may be withheld in that particular treatment cycle.
Human chorionic gonadotropin may induce sexual precocity in males treated for cryptorchidism, necessitating a reduced dosage regimen in such cases.
Further, in males, high dosages of human chorionic gonadotropin may result in edema and in such instances dosages should be considerably reduced.
The product should be used cautiously in patients with cardiac problems that may be aggravated by fluid retention, patients with asthma, renal disorder, seizure, or migraine.
Human chorionic gonadotropin should be used with extreme caution in patients with active thrombophlebitis or other active thromboembolic disorders. Caution is also warranted in patients having risk factors of thromboembolic events such as those with prior medical or family history.
Adverse Reactions
Adverse effects associated with human chorionic gonadotropin therapy include headache, irritability, restlessness, depression, fatigue, edema, gynecomastia, sexual precocity, and pain at injection site.
When used for infertility treatment, human chorionic gonadotropin therapy may be associated with adverse events, such as ovarian hyperstimulation syndrome, rupture of ovarian cysts with resultant hemoperitoneum, multiple births, and arterial thromboembolism.
Drug Interactions
Concomitant use of human chorionic gonadotropin with other agents used for ovulation induction (human menopausal gonadotropins, clomiphene citrate) may enhance the follicular response.
Storage
Vials of the product should be stored between 2°C - 8°C. Do not freeze. Keep protected from light.
Use the reconstituted solution immediately after preparation; any unused portion should be discarded.
ATC Classification
G03GA01 - chorionic gonadotrophin ; Belongs to the class of gonadotropins. Used as ovulation stimulants.
Presentation/Packing
Powd (lyo) for inj (vial + 1 mL amp diluent) 5,000 IU x 2 mL x 1's.
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