Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/2823
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Gonal-f RFF (Kit)
|
| dailymed-instance:descripti... |
Gonal-f' RFF (follitropin alfa for injection) is a human follicle stimulating hormone (FSH) preparation of recombinant DNA origin, which consists of two non-covalently linked, non-identical glycoproteins designated as the��- and��-subunits. The��- and��-subunits have 92 and 111 amino acids, respectively, and their primary and tertiary structure are indistinguishable from those of human follicle stimulating hormone. Recombinant FSH production occurs in genetically modified Chinese Hamster Ovary (CHO) cells cultured in bioreactors. Purification by immunochromatography using anantibody specifically binding FSH results in a highly purified preparation with a consistent FSH isoform profile, and a high specific activity. The biological activity of follitropin alfa is determined by measuring the increase in ovary weight in female rats. The in vivo biological activity of follitropin alfa has been calibrated against the first International Standard for recombinant human follicle stimulating hormone established in 1995 by the Expert Committee on Biological Standards of the World Health Organization. Gonal-f' RFF contains no luteinizing hormone (LH) activity. Based on available data derived from physico-chemical tests and bioassays, follitropin alfa and follitropin beta, another recombinant follicle stimulating hormone product, are indistinguishable. Gonal-f' RFF is a sterile, lyophilized powder intended for subcutaneous injection after reconstitution. Each Gonal-f' RFF single-dose vial is filled with 82 IU (6��g) follitropin alfa to deliver 75 IU (5.5��g and contains 30 mg sucrose, 1.11 mg dibasic sodium phosphate dihydrate, 0.45 mg monobasic sodium phosphate monohydrate, 0.1 mg methionine, and 0.05 mg polysorbate 20. Phosphoric acid and/or sodium hydroxide may be used prior to lyophilization for pH adjustment. Vials are reconstituted with Sterile Water for Injection, USP. Under current storage conditions, Gonal-f' RFF may contain up to 10% of oxidized follitropin alfa. Therapeutic Class: Infertility
|
| dailymed-instance:clinicalP... |
Gonal-f' RFF (follitropin alfa for injection) stimulates ovarian follicular growth in women who do not have primary ovarian failure. FSH, the active component of Gonal-f' RFF is the primary hormone responsible for follicular recruitment and development. In order to effect final maturation of the follicle and ovulation in the absence of an endogenous LH surge, human chorionic gonadotropin (hCG) must be given following the administration of Gonal-f' RFF when monitoring of the patient indicates that sufficient follicular development has occurred. There is interpatient variability in response to FSH administration.<br/>Pharmacokinetics: Single-dose pharmacokinetics of follitropin alfa were determined following subcutaneous administration of 300 IU Gonal-f' RFF to 21 pre-menopausal healthy female volunteers who were pituitary down-regulated with a GnRH agonist. The descriptive statistics for the pharmacokinetic parameters are presented in Table 1. Absorption The absorption rate of Gonal-f' RFF following subcutaneous administration is slower than the elimination rate. Hence, the pharmacokinetics of Gonal-f' RFF are absorption rate-limited. Distribution Human tissue or organ distribution of FSH has not been determined for Gonal-f' RFF. Metabolism/Excretion FSH metabolism and excretion following administration of Gonal-f' RFF have not been studied in humans. Special populations: Safety, efficacy, and pharmacokinetics of Gonal-f' RFF in patients with renal or hepatic insufficiency have not been established. Drug-Drug Interactions: No drug-drug interaction studies have been conducted . Clinical Studies: The safety and efficacy of Gonal-f' RFF have been examined in two clinical studies: one study (Study 22240) for ovulation induction and one study (Study 21884) for assisted reproductive technologies (ART). 1. Ovulation Induction (OI): Study 22240 was a phase III, assessor-blind, randomized, comparative, multinational, multicenter study in oligo-anovulatory infertile women undergoing ovulation induction. Patients were randomized to either Gonal-f' RFF (n=83), administered subcutaneously, or a comparator recombinant human FSH. The use of insulin-sensitizing agents was allowed during the study. Efficacy was assessed using the mean ovulation rate in the first cycle of treatment. The cycle 1 ovulation rate (primary outcome) for Gonal-f' RFF is presented in Table 2. Additionally, this table includes cumulative secondary outcome results from cycle 1 through 3. Study 22240 was not powered to demonstrate differences in these secondary outcomes. 2. Assisted Reproductive Technologies (ART): Study 21884 was a phase III, assessor-blind, randomized, comparative, multinational, multicenter study in ovulatory, infertile women undergoing stimulation of multiple follicles for Assisted Reproductive Technologies (ART) after pituitary down-regulation with a GnRH agonist. Patients were randomized to either Gonal-f' RFF (n=237), administered subcutaneously, or a comparator recombinant human FSH. Randomization was stratified by insemination technique [conventional in-vitro fertilization (IVF) vs. intra-cytoplasmic sperm injection (ICSI)]. Efficacy was assessed using the mean number of fertilized oocytes the day after insemination. The initial doses of Gonal-f' RFF were 150 IU a day for patients<35 years old and 225 IU for patients���35 years old. The maximal dose allowed for both age groups was 450 IU per day. Treatment outcomes for Gonal-f' RFF are summarized in Table 3.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Gonal-f' RFF (follitropin alfa for injection) is contraindicated in women who exhibit:
|
| dailymed-instance:supply |
Gonal-f' RFF (follitropin alfa for injection) is supplied in a sterile, lyophilized form in single-dose vials containing 82 IU with diluent (Sterile Water for Injection, USP) in a pre-filled syringe. Following reconstitution with the diluent as described, upon administration each vial will deliver a dose of 75 IU. Lyophilized vials may be stored refrigerated or at room temperature (2��-25��C/36��-77��F). Protect from light. Use immediately after reconstitution. Discard unused material. Sterile Water for Injection, USP is provided in a pre-filled syringe. Separate needles are provided for reconstitution (18 G) and administration (27 G). Note: No antimicrobial or other substance has been added to the Sterile Water for Injection for the single-dose vials. Sterile Water for Injection is not suitable for intravascular injection without its first having been made approximately isotonic by the addition of a suitable solute. The following package combinations are available: 1 vial Gonal-f' RFF 75 IU and 1 pre-filled syringe Sterile Water for Injection, USP, 1 mL, 1 reconstitution needle (18 gauge), 1 administration needle (27 gauge), NDC 44087-9005-1 10 vials Gonal-f' RFF 75 IU and 10 pre-filled syringes Sterile Water for Injection, USP, 1 mL, 10 reconstitution needles (18 gauge), 10 administration needles (27 gauge), NDC 44087-9005-6 Rx only Manufactured for: SERONO, INC., Rockland, MA 02370 U.S.A. Rev: March 2005
|
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:precautio... |
GENERAL: Careful attention should be given to the diagnosis of infertility in candidates for Gonal-f' RFF (follitropin alfa for injection) therapy (see "Indications and Usage/ Selection of Patients").<br/>INFORMATION FOR PATIENTS: Prior to therapy with Gonal-f' RFF, patients should be informed of the duration of treatment and monitoring of their condition that will be required. The risks of ovarian hyperstimulation syndrome and multiple births in women and other possible adverse reactions (see���Adverse Reactions���) should also be discussed. See���DOSAGE AND ADMINISTRATION���for���PATIENT INSTRUCTIONS FOR USE OF GONAL-F' RFF���.<br/>LABORATORY TESTS: In most instances, treatment of women with Gonal-f' RFF results only in follicular recruitment and development. In the absence of an endogenous LH surge, hCG is given when monitoring of the patient indicates that sufficient follicular development has occurred. This may be estimated by ultrasound alone or in combination with measurement of serum estradiol levels. The combination of both ultrasound and serum estradiol measurement are useful for monitoring the development of follicles, for timing of the ovulatory trigger, as well as for detecting ovarian enlargement and minimizing the risk of the Ovarian Hyperstimulation Syndrome and multiple gestation. It is recommended that the number of growing follicles be confirmed using ultrasonography because plasma estrogens do not give an indication of the size or number of follicles. The clinical confirmation of ovulation, with the exception of pregnancy, is obtained by direct and indirect indices of progesterone production. The indices most generally used are as follows: When used in conjunction with the indices of progesterone production, sonographic visualization of the ovaries will assist in determining if ovulation has occurred. Sonographic evidence of ovulation may include the following: Accurate interpretation of the indices of follicle development and maturation require a physician who is experienced in the interpretation of these tests.<br/>DRUG INTERACTIONS: No drug/drug interaction studies have been performed.<br/>CARCINOGENESIS, MUTAGENESIS, IMPAIRMENT OF FERTILITY: Long-term studies in animals have not been performed to evaluate the carcinogenic potential of Gonal-f' RFF. However, follitropin alfa showed no mutagenic activity in a series of tests performed to evaluate its potential genetic toxicity including, bacterial and mammalian cell mutation tests, a chromosomal aberration test and a micronucleus test. Impaired fertility has been reported in rats, exposed to pharmacological doses of follitropin alfa (���40 IU/kg/day) for extended periods, through reduced fecundity.<br/>PREGNANCY: Pregnancy Category X. See CONTRAINDICATIONS.<br/>NURSING MOTHERS: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in the nursing infant from Gonal-f' RFF, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.<br/>PEDIATRIC USE: Safety and effectiveness in pediatric patients have not been established.
|
| dailymed-instance:overdosag... |
Aside from possible ovarian hyperstimulation and multiple gestations (see "Warnings"), there is no information on the consequences of acute overdosage with Gonal-f' RFF (follitropin alfa for injection).
|
| dailymed-instance:genericMe... |
follitropin alfa
|
| dailymed-instance:fullName |
Gonal-f RFF (Kit)
|
| dailymed-instance:adverseRe... |
The safety of Gonal-f' RFF was examined in two clinical studies [one ovulation induction study (n=83) and one study in ART (n=237)]. Adverse events (without regard to causality assessment) occurring in at least 2.0% of patients in Study 22240 (ovulation induction) are listed in Table 4. Headache occurred in greater than 20% of patients receiving Gonal-f' RFF in this study. Adverse events (without regard to causality assessment) occurring in at least 2.0% of patients in Study 21884 (ART) are listed in Table 5. Headache and abdomen enlargement occurred in more than 10% of patients and abdominal pain occurred in more than 20% of patients. The following medical events have been reported subsequent to pregnancies resulting from Gonal-f' RFF therapy in controlled clinical studies: There are no indications that use of gonadotropins during ART is associated with an increased risk of congenital malformations. The following adverse reactions have been previously reported during Gonal-f' RFF therapy: There have been infrequent reports of ovarian neoplasms, both benign and malignant, in women who have undergone multiple drug regimens for ovulation induction; however, a causal relationship has not been established. Post Marketing Reports During post-market surveillance, reports of hypersensitivity reactions including anaphylactoid reactions have been reported with the use of Gonal-f' RFF.
|
| dailymed-instance:warning |
Gonal-f' RFF (follitropin alfa for injection) should only be used by physicians who are thoroughly familiar with infertility problems and their management. Gonal-f' RFF is a potent gonadotropic substance capable of causing Ovarian Hyperstimulation Syndrome (OHSS) in women with or without pulmonary or vascular complications. Gonadotropin therapy requires a certain time commitment by physicians and supportive health professionals, and requires the availability of appropriate monitoring facilities (see "Precautions/Laboratory Tests"). Safe and effective use of Gonal-f' RFF in women requires monitoring of ovarian response with serum estradiol and vaginal ultrasound on a regular basis. The lowest effective dose should be used. Overstimulation of the Ovary During FSH Therapy: Ovarian Enlargement: Mild to moderate uncomplicated ovarian enlargement which may be accompanied by abdominal distention and/or abdominal pain occurs in approximately 20% of those treated with urofollitropin and hCG, and generally regresses without treatment within two or three weeks. Careful monitoring of ovarian response can further minimize the risk of overstimulation. If the ovaries are abnormally enlarged on the last day of Gonal-f' RFF therapy, hCG should not be administered in this course of therapy. This will reduce the chances of development of Ovarian Hyperstimulation Syndrome. Ovarian Hyperstimulation Syndrome (OHSS): OHSS is a medical event distinct from uncomplicated ovarian enlargement. Severe OHSS may progress rapidly (within 24 hours to several days) to become a serious medical event. It is characterized by an apparent dramatic increase in vascular permeability which can result in a rapid accumulation of fluid in the peritoneal cavity, thorax, and potentially, the pericardium. Theearly warning signs of development of OHSS are severe pelvic pain, nausea, vomiting, and weight gain. The following symptomatology has been seen with cases of OHSS: abdominal pain, abdominal distension, gastrointestinal symptoms including nausea, vomiting and diarrhea, severe ovarian enlargement, weight gain, dyspnea, and oliguria. Clinical evaluation may reveal hypovolemia, hemoconcentration, electrolyte imbalances, ascites, hemoperitoneum, pleural effusions, hydrothorax, acute pulmonary distress, and thromboembolic events (see "Pulmonary and Vascular Complications"). Transient liver function test abnormalities suggestive of hepatic dysfunction, which may be accompanied by morphologic changes on liver biopsy, have been reported in association with Ovarian Hyperstimulation Syndrome (OHSS). OHSS occurred in 6of 83(7.2%) Gonal-f' RFF treated women in Study 22240 (ovulation induction); none were classified as severe. In Study 21884 (ART), OHSS occurred in 11of 237(4.6%) Gonal-f' RFF treated women and 1(0.42%) was classified as severe. OHSS may be more severe and more protracted if pregnancy occurs. OHSS develops rapidly; therefore, patients should be followed for at least two weeks after hCG administration. Most often, OHSS occurs after treatment has been discontinued and reaches its maximum at about seven to ten days following treatment. Usually, OHSS resolves spontaneously with the onset of menses. If there is evidence that OHSS may be developing prior to hCG administration (see "Precautions / Laboratory Tests"), the hCG must be withheld. If severe OHSS occurs, treatment must be stopped and the patient should be hospitalized. A physician experienced in the management of this syndrome, or who is experienced in the management of fluid and electrolyte imbalances should be consulted. Pulmonary and Vascular Complications: Serious pulmonary conditions (e.g., atelectasis, acute respiratory distress syndrome and exacerbation of asthma) have been reported. In addition, thromboembolic events both in association with, and separate from Ovarian Hyperstimulation Syndrome have been reported. Intravascular thrombosis and embolism can result in reduced blood flow to critical organs or the extremities. Sequelae of such events have included venous thrombophlebitis, pulmonary embolism, pulmonary infarction, cerebral vascular occlusion (stroke), and arterial occlusion resulting in loss of limb. In rare cases, pulmonary complications and/or thromboembolic events have resulted in death. Multiple Births: Reports of multiple births have been associated with Gonal-f' RFF treatment. In Study 22240 for women receiving Gonal-f' RFF over three treatment cycles, 20% of live births were multiple births. In Study 21884, 35.1% of live births were multiple births in women receiving Gonal-f' RFF. The rate of multiple births is dependent on the number of embryos transferred. The patient should be advised of the potential risk of multiple births before starting treatment.
|
| dailymed-instance:indicatio... |
Gonal-f' RFF (follitropin alfa for injection) is indicated for the induction of ovulation and pregnancy in the oligo-anovulatory infertile patient in whom the cause of infertility is functional and not due to primary ovarian failure. Gonal-f' RFF is also indicated for the development of multiple follicles in the ovulatory patient participating in an Assisted Reproductive Technology (ART) program. Selection of Patients:
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Gonal-f RFF
|