长效生长激素注射粉剂—Genotropin（somatropin）获FDA批准适用于妊娠期体形偏小，并且两岁时身高仍明显低于同龄人的患儿。
批准日期：2016年9月 公司：PFIZER INC
GENOTROPIN(生长激素[somatropin]) 用于注射, 用于皮下使用
美国初步批准: 1987
最近的重大变化
contraindications:12/2016
警告和预防措施, 急性关键 illness:9/2016
警告和预防措施, 严重的 hypersensitivity:12/2016
警告和预防措施, hypoadrenalism:9/2016
作用机制
在体外、临床前、并对实验结果表明, GENOTROPIN 冻干粉对垂体源性生长激素有一定的治疗作用, 并在正常成人中达到类似的药动学特征。在患有生长激素缺乏症 (GHD) 的儿科患者中, 有普瑞德-威利综合征 (PWS), 出生于胎龄小 (SGA), 有特纳综合征 (TS), 或有特发性矮小 (ISS), 治疗与 GENOTROPIN 刺激线性增长。在 GHD 或 PWS 患者中, GENOTROPIN 的治疗还能正常化胰岛素样生长因子-i (i/Somatomedin C) 的浓度。在有 GHD 的成年人中, GENOTROPIN 治疗导致脂肪质量降低, 瘦体质量增加, 代谢改变包括脂代谢的有益变化, 以及胰岛素样生长因子 I 浓度的正常化。
此外, 还为 GENOTROPIN 和/或生长激素演示了以下操作。
适应症和用法
GENOTROPIN 是一种重组人生长激素, 表示为:
儿科:
治疗生长衰竭的儿童由于生长激素缺乏 (GHD), 普瑞德-威利综合征, 小的孕龄, 特纳综合征, 和特发性矮小。
成人: 成人发病或儿童期发病 GHD 的治疗。
剂量和管理
GENOTROPIN 应进行皮下管理。
儿科 GHD: 0.16 至0.24 毫克/千克/周。
普瑞德-威利综合征: 0.24 毫克/千克/周。
孕龄小: 可达0.48 毫克/千克/周。
特纳综合症: 0.33 毫克/千克/周。
特发性矮小: 最多0.47 毫克/千克/周。
成人 GHD: 根据治疗反应和胰岛素样生长因子浓度, 可以遵循非重量或基于重量的剂量方案。
非重量的剂量: 一个开始剂量约 0.2mg/天 (范围, 0.15–0.30 毫克/天) 可以使用, 而不考虑体重, 并逐步增加每一个时间的增量约0.1–0.2 毫克/天。
重量的剂量: 建议的初始剂量不超过0.04 毫克/千克/周;剂量可增加为耐受性不超过0.08 毫克/千克/星期在4–8week 间隔。
GENOTROPIN 墨盒的颜色编码, 以对应于特定的 GENOTROPIN 笔传递设备。
注塑部位应始终旋转以避免 lipoatrophy。
剂型和强度
GENOTROPIN 冻干粉在两室彩色编码墨盒:
5mg (绿色尖端) 和 12mg (紫色尖端) (含防腐剂)
GENOTROPIN MINIQUICK 生长激素输送装置, 含有两室墨盒 (无防腐剂):
0.2mg、0.4mg、0.6mg、0.8mg、1.0mg、1.2mg、1.4mg、1.6mg、1.8mg 和2.0mg
禁忌
急性危重症。
普瑞德-威利综合征的儿童严重肥胖或有严重的呼吸损害-报告突然死亡。
活跃的恶性肿瘤。
对生长激素或辅料过敏。
积极增生或严重的非增生性糖尿病视网膜病变。
闭骨骺的孩子们。
警告和预防措施
急性危重症: 治疗持续的潜在益处应与潜在风险权衡。
儿童普瑞德-威利综合征: 治疗前呼吸道梗阻和睡眠呼吸暂停症状的评估
如果出现这些迹象, 停止治疗。
肿瘤: 监测存在肿瘤的患者进行进展或复发。在儿童癌症幸存者中, 第二次肿瘤的风险增加, 特别是脑膜瘤患者的生长激素治疗, 其第一个肿瘤为头部放射治疗。
糖耐量受损及糖尿病: 可能被剥去
定期监测所有患者的血糖水平。糖尿病患者并发降糖药物的剂量可能需要调整。
颅内高压: 排除先前存在的 papilledema。可在停止或剂量减少后发展并通常是可逆的。
过敏: 可能发生严重的过敏反应。在发生过敏反应时, 寻求及时的医疗照顾。
液体保留 (即水肿, 关节痛, 腕管 syndrome–especially 在成人): 可能经常发生。必要时减少剂量。
Hypoadrenalism: 监测患者的血清皮质醇水平降低和/或需要的糖皮质激素剂量增加在那些已知的 Hypoadrenalism。
甲状腺功能减退: 5月1日变得明显或恶化。定期监测甲状腺功能。
滑倒资本股骨骺: 可发育。评估儿童与跛行或髋/膝疼痛的发病。
预先存在的脊柱侧凸的进展: 监测任何儿童脊柱侧凸的进展曲线。
胰腺炎: 对持续性严重腹痛患者的胰腺炎的思考
不良反应
其他常见的生长激素相关不良反应包括注射部位反应/皮疹、lipoatrophy 和头痛。
要报告可疑的不良反应, 请联系辉瑞公司1-800-438-1985 或 fda, 1-800-fda-1088 或 www.fda.gov/medwatch。
药物相互作用
抑制 11ß-Hydroxysteroid 脱氢酶1型: 可能需要启动糖皮质激素替代疗法。用糖皮质激素替代治疗以前诊断过的 hypoadrenalism 的患者可能需要增加他们的维持剂量。
糖皮质激素置换: 应仔细调整。
细胞色素 P450-Metabolized 药物: 如果与生长激素一起使用, 请仔细观察。
口服雌激素: 妇女可能需要更大剂量的生长激素。
胰岛素和/或口服/注射降血糖剂: 可能需要调整。
包装提供/存储和处理
GENOTROPIN 冻干粉可在以下包装:
5毫克二室弹药筒 (与防腐剂)
浓度5毫克/毫升
用于与 GENOTROPIN PEN®5生长激素传递装置和/或 GENOTROPIN MIXER™生长激素重组装置。
包装 1 NDC 0013-2626-81
12毫克二室弹药筒 (与防腐剂)
浓度12毫克/毫升
用于与 GENOTROPIN 笔12生长激素传递装置和/或 GENOTROPIN 混合器生长激素重组装置。
包装 1 NDC 0013-2646-81
GENOTROPIN MINIQUICK 生长激素输送装置, 含有双腔 GENOTROPIN (无防腐剂)
重组后, 每 GENOTROPIN MINIQUICK 提供0.25 毫升, 无论强度。具有以下优点, 每包 7:
0.2 毫克 NDC 0013-2649-02
0.4 毫克 NDC 0013-2650-02
0.6 毫克 NDC 0013-2651-02
0.8 毫克 NDC 0013-2652-02
1.0 毫克 NDC 0013-2653-02
1.2 毫克 NDC 0013-2654-02
1.4 毫克 NDC 0013-2655-02
1.6 毫克 NDC 0013-2656-02
1.8 毫克 NDC 0013-2657-02
2.0 毫克 NDC 0013-2658-02
存储和处理
除以下说明外, 贮存 GENOTROPIN 冻干粉冷冻在36°F到 46°F(8°C)。不要冻结。保护光线。
5毫克和12毫克的 GENOTROPIN 墨盒含有一个防腐剂的稀释剂。因此, 在重组后, 可将它们储存在冷藏中长达28天。
GENOTROPIN MINIQUICK 生长激素送药装置应在配药前冷藏, 但在配药后可贮存在77°F (25°c) 以下三月。稀释剂没有防腐剂。重组后, GENOTROPIN MINIQUICK 可以储存在冷藏24小时前使用。GENOTROPIN MINIQUICK 只应使用一次, 然后丢弃。

药品完整说明书附件：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ffebf88b-d257-4542-9808-74d9b7167765

Genotropin® (somatropin [rDNA origin] injection)
Genotropin somatropin is a bio-identical human growth hormone (HGH) treatment approved for use in the treatment of hormonal imbalance or deficiency in adults and children. Bio-identical HGH means that Genotropin is identical to growth hormone produced by the body. Anti-Aging Group physicians use only bio-identical GH in our HGH therapy.
Growth hormone injection treatment such as Genotropin is typically prescribed for patients who are found to be HGH deficient. A hormone doctor will monitor progress during HGH therapy to ensure proper dosage.
For GENOTROPIN® Growth Hormone Injection Usage
GENOTROPIN GROWTH HORMONE USAGE INSTRUCTIONS
Read more about HGH (Human Growth Hormone)
Replacement Therapy and HGH Injections – HGH Therapy
DESCRIPTION OF GENOTROPIN Somatropin:
Genotropin Lyophilized (freeze-dried) powder contains somatropin, a polypetide hormoe of rDA origin. Genotropin has 191 residues of amino acids with a molecular weight of 22,124 daltons. The amino acid sequence of Genotropin is identical to that of HGH produced by the pituitary gland in the human body.
Genotropin is synthesized in a strain of Escherichia coli modified by adding the gene for HGH. This sterile, white freeze-dried powder is designed for subcutaneous injection.
GENOTROPIN Lyophilized Powder contains somatropin [rDNA origin], which is a polypeptide hormone of recombinant DNA origin. It has 191 amino acid residues and a molecular weight of 22,124 daltons. The amino acid sequence of the product is identical to that of human growth hormone of pituitary origin (somatropin).
GENOTROPIN is synthesized in a strain of Escherichia coli that has been modified by the addition of the gene for human growth hormone. GENOTROPIN is a sterile white lyophilized powder intended for subcutaneous injection.
GENOTROPIN 1.5 mg is dispensed in a two-chamber cartridge. The front chamber contains recombinant somatropin 1.5 mg (approximately 4.5 IU), glycine 27.6 mg, sodium dihydrogen phosphate anhydrous 0.3 mg, and disodium phosphate anhydrous 0.3 mg; the rear chamber contains 1.13 mL water for injection.
GENOTROPIN 5.8 mg is dispensed in a two-chamber cartridge. The front chamber contains recombinant somatropin 5.8 mg (approximately 17.4 IU), glycine 2.2 mg, mannitol 1.8 mg, sodium dihydrogen phosphate anhydrous 0.32 mg, and disodium phosphate anhydrous 0.31 mg; the rear chamber contains 0.3% m-Cresol (as a preservative) and mannitol 45 mg in 1.14 mL water for injection.
GENOTROPIN 13.8 mg is dispensed in a two-chamber cartridge. The front chamber contains recombinant somatropin 13.8 mg (approximately 41.4 IU), glycine 2.3 mg, mannitol 14.0 mg, sodium dihydrogen phosphate anhydrous 0.47 mg, and disodium phosphate anhydrous 0.46 mg; the rear chamber contains 0.3% m-Cresol (as a preservative) and mannitol 32 mg in 1.13 mL water for injection.
GENOTROPIN MINIQUICK ! is dispensed as a single-use syringe device containing a two-chamber cartridge. GENOTROPIN MINIQUICK ! is available as individual doses of 0.2 mg to 2.0 mg in 0.2-mg increments. The front chamber contains recombinant somatropin 0.22 to 2.2 mg (approximately 0.66 to 6.6 IU), glycine 0.23 mg, mannitol 1.14 mg, sodium dihydrogen phosphate 0.05 mg, and disodium phosphate anhydrous 0.027 mg; the rear chamber contains mannitol 12.6 mg in water for injection 0.275 mL.
GENOTROPIN is a highly purified preparation. The reconstituted recombinant somatropin solution has an osmolality of approximately 300 mOsm/kg, and a pH of approximately 6.7. The concentration of the reconstituted human growth hormone solution varies by strength and presentation (see HOW HGH SUPPLIED section).
CLINICAL PHARMACOLOGY – GENOTROPIN INJECTABLE HGH
Genotropin freeze-dried powder has been shown through in vitro, clinical and pre-clinical tests as therapeutically indistinguishable to HGH produced by the human pituitary gland with similar pharmocokinetic profiles in typical adults.
Treatment of pediatric patients with growth hormone deficiency (GHD) with Genotropin stimulates linear growth while normalizing concentrations of Insulin-like Growth Factor/Somatomedin-C.
Treatment of AGHD adults with GENOTROPIN results in reduced fat mass, increased lean body mass, metabolic alterations that include beneficial changes in lipid metabolism, and normalization of IGF-I concentrations.
Genotropin and/or Somatropin has demonstrated the following actions.
Skeletal Growth
Genotropin stimulates skeletal bone growth in children with GHD. After administering Genotropin, measurable growth results from action on the epiphyseal plates of long bones, or the rounded ends of the bone. Concentrations of IGF-I, believed to affect skeletal growth, are typically low in the serum of pediatric GHD patients, although this concentration typically increases with Genotropin treatment. Genotropin typically results in elevations in mean serum alkaline phosphase concentration as well.
Cell Growth
Pediatric patients with a short height who lack naturally-produced growth hormone have fewer skeletal muscle cells compared to typical children. Treatment with somatropin produces an increase in the size and number of muscle cells.
Protein Metabolism
Linear growth is assisted by improved cellular protein synthesis. Genotropin therapy has been shown to increase nitrogen retention, with reduced excretion of nitrogen through urine.
Carbohydrate Metabolism
Genotropin has been shown to improve fasting hypoglycemia, or low blood sugar, which is common among pediatric patients with hypopituitarism. Large GH doses can effect glucose tolerance.
Metabolism of Lipids
In patients with GHD, treatment with somatropin produces lipid mobilization, reduced body fat stores and improved plasma fatty acids.
Metabolism of Minerals
Somatropin has been found to induce the retention of potassium, phosphorus and sodium. Patients with GHD experience increased serum concentrations of inorganic phosphate following Genotropin therapy. Genotropin has not been found to significantly change serum calcium. Growth hormone could increase calciuria.
Body Composition
Adult GHD patients treated with GENOTROPIN at the recommended adult dose (see GENOTROPIN HGH DOSAGE AND ADMINISTRATION ) demonstrate a decrease in fat mass and an increase in lean body mass (increased muscle mass). When these alterations are coupled with the increase in total body water, the overall effect of GENOTROPIN is to modify body composition, an effect that is maintained with continued treatment.
PHARMACOKINETICS (Body Absorption & Delivery)
Genotropin HGH Absorption
Following a 0.03 mg/kg subcutaneous (SC) injection in the thigh of 1.3 mg/mL
GENOTROPIN to adult GHD patients, approximately 80% of the dose was systemically available as compared with that available following intravenous dosing. Results were comparable in both male and female patients. Similar bioavailability has been observed in healthy adult male subjects.
In healthy adult males, following an SC injection in the thigh of 0.03 mg/kg, the extent of absorption (AUC) of a concentration of 5.3 mg/mL GENOTROPIN was 35% greater than that for 1.3 mg/mL GENOTROPIN. The mean (± standard deviation) peak (C max ) serum levels were 23.0 (± 9.4) ng/mL and 17.4 (± 9.2) ng/mL, respectively.
In a similar study involving pediatric GHD patients, 5.3 mg/mL GENOTROPIN yielded a mean AUC that was 17% greater than that for 1.3 mg/mL GENOTROPIN. The mean C max levels were 21.0 ng/mL and 16.3 ng/mL, respectively.
Adult Growth Hormone Deficient (AGHD) patients received two single SC doses of 0.03 mg/kg of GENOTROPIN at a concentration of 1.3 mg/mL, with a one- to four-week washout period between injections. Mean C max levels were 12.4 ng/mL (first injection) and 12.2 ng/mL (second injection), achieved at approximately six hours after dosing.
There are no data on the bioequivalence between the 12 mg/mL formulation and either the 1.3 mg/mL or the 5.3 mg/mL formulations.
GENOTROPIN HGH Distribution
The mean volume of distribution of GENOTROPIN following administration of GHD adults was estimated to be 1.3 (± 0.8) L/kg.
Metabolism
The metabolic fate of Genotropin involves classical protein catabolism (the breaking down of large molecules) in the kidneys and liver. Some of the breakdown products of Genotropin are released back into the systemic circulation in renal cells.
In a normal adult, the terminal half-life of intravenous Genotropin is 0.4 hours, while Genotropin subcutaneously administered has a half-life of 3.0 hous in adults with GHD. This difference is caused by slower absorption at the subcutaneous injection site.
Excretion
The mean clearance of subcutaneously administered GENOTROPIN in 16 GHD adult patients was 0.3 (± 0.11) L/hrs/kg.
Special Populations
Pediatric: The pharmacokinetics of GENOTROPIN are similar in GHD pediatric and adult patients.
Gender: No gender studies have been performed in pediatric patients; however, GHD adults, the absolute bioavailability of GENOTROPIN was similar in males and females.
Race: No studies have been conducted with GENOTROPIN to assess pharmacokinetic differences among races.
Renal or hepatic insufficiency: No studies have been completed with GENOTROPIN in these patient populations.
* The absolute bioavailability was estimated under the assumption that the log-transformed data follow a normal distribution. The mean and standard deviation of the log-transformed data were mean = 0.22 (± 0.241).
GENOTROPIN CLINICAL STUDIES IN ADULT GHD PATIENTS
GENOTROPIN Lyophilized Powder was compared with placebo in six randomized clinical trials involving a total of 172 adult GHD patients. These trials included a 6-month double-blind treatment period, during which 85 patients received GENOTROPIN and 87 patients received placebo, followed by an open-label treatment period in which participating patients received GENOTROPIN for up to a total of 24 months.
GENOTROPIN was administered as a daily SC injection at a dose of 0.04 mg/kg week for the first month of treatment and 0.08 mg/kg/week for subsequent months.
Beneficial changes in body composition were observed at the end of the 6-month treatment period for the patients receiving GENOTROPIN as compared with the placebo patients. Lean body mass, total body water, and lean/fat ratio increased while total body fat mass and waist circumference decreased. These effects on body composition were maintained when treatment was continued beyond 6 months. Bone mineral density declined after 6 months of treatment but returned to baseline values after 12 months of treatment.
INDICATIONS AND USAGE OF GENOTROPIN HGH INJECTION
Genotropin lyophilized powder is indicated for long-term treatment of pediatric patients diagnosed with growth failure caused by insufficient secretion of endogenous GH. Other causes of short stature should be excluded before use.
GENOTROPIN is indicated for long-term replacement therapy in adults with GHD of either childhood- or adult-onset etiology. GHD should be confirmed by an appropriate growth hormone stimulation test.
CONTRAINDICATIONS
Genotropin should not be used when there is any evidence of neoplastic activity. Intracranial lesions must be inactive and antitumor therapy complete prior to the institution of therapy. Genotropin should be discontinued in the presence of tumor growth. Growth hormone therapy should not be used for pediatric patients with fused epiphyses.
Growth hormone therapy should not be used to treat patients with acute critical illness due to complications after abdominal or heart surgery, accident trauma, or acute respiratory failure. Two clinical studies in non-GHD adults with these conditions found that patients receiving somatropin (5.3 – 8mg doses per day) have a greater mortality rate (41.9% versus 19.3%) compared to patients receiving placebos.
GENOTROPIN WARNINGS
The 5.8 mg and 13.8 mg presentations of GENOTROPIN Lyophilized Powder contain m-Cresol as a preservative. These products should not be used by patients with a known sensitivity to this preservative. The GENOTROPIN 1.5 mg and GENOTROPIN MINIQUICK presentations are preservative-free. (See HOW SUPPLIED section.)
Growth therapy increases the risk of mortality in patients with acute critical illnesses in ICUs due to complications after abdominal or open heart surgery, accident trauma and acute respiratory failure. The safety of continued GH therapy in patients who receive replacement doses for approved indications who develop these illnesses has not been determined. The possible advantage of continuing treatment in patients with acute critical illnesses should be considered against the risks.
GENOTROPIN PRECAUTIONS
General
Treatment with Genotropin lyophilized powder, as with other growth hormone preparations, is best directed by a physician experienced in the diagnosis and management of GHD patients.
Patients and caregivers who will administer GENOTROPIN in medically unsupervised situations should receive appropriate training and instruction on the proper use of GENOTROPIN from the physician or other suitably qualified health professional.
Patients with GHD that is secondary to intracranial lesions should be examined often for progression or recurrance of the underlying illness. Review of literature reports of pediatric use of somatropin therapy finds no link between this treatment and recurrence of central nervous system tumors. In adults, it is not known if there is a link between somatropin replacement therapy and recurrence of CNS tumors.
Patients should be monitored for malignant changes in skin lesions.
Caution should be used if GH is administered to patients with diabetes mellitus, with insulin dosage adjusted as needed. As GH may create insulin resistance, patients should be monitored for signs of glucose intolerance. Patients with glucose intolerance or diabetes should be observed during Genotropin therapy.
In patients with hypopituitarism, typical hormone replacement therapy should be closely observed while beginning treatment with Genotropin. Hypothyroidism may develop during Genotropin therapy, in which cause insufficient treatment of the hypothyroidism may lead to an inadequate response to Genotropin. Patients should receive regular thyroid function tests and be treated if necessary.
Pediatric patients with endocrine disorders, including GHD, have a higher incidence of slipped capital femoral epiphyses. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during growth hormone therapy should be evaluated.
Intracranial hypertension along with vision changes, headaches, nausea, optic disc swelling and/or vomiting has been reported in a small number of people treated with GH. Symptoms typically occur within the first eight weeks of therapy. In all cases that have been reported IH-associated symptoms resolved after therapy was discontinued or reduced. An ophthalmoscopy is recommended at the start of treatment and periodically during GH therapy.
Before continuing treatment for as an adult, post-pubertal GHD patients who received GH therapy as a child should be reevaluated with proper testing described in INDICATIONS AND USAGE. If continuing treatment is appropriate, Genotropin should be administered at the lower dose recommended for adult GHD patients.
Drug Interactions
Concomitant glucocorticoid treatment may inhibit the growth-promoting effect of growth hormone. Pediatric GHD patients with coexisting ACTH deficiency should have their glucocorticoid replacement dose carefully adjusted to avoid an inhibitory effect on growth. See also PRECAUTIONS – General.
Limited data indicates that GH treatment increases cytochrome P450 mediated antipyrine clearance in male patients. These published data suggest that GH treatment may change the clearance of compounds metabolized by the CP450 liver enzymes such as corticosteroids. Monitoring is recommended if GH will be administered along with other drugs known to be metabolized by these enzymes.
Carcinogenesis, Mutagenesis and Fertility Impairment
Carcinogenicity studies have not been conducted with rhGH. No potential mutagenicity of rhGH was revealed in a battery of tests including induction of gene mutations in bacteria (the Ames test), gene mutations in mammalian cells growth in vitro (mouse L5178Y cells), and chromosomal damage in intact animals (bone marrow cells in rats). See PREGNANCY section for effect on fertility.
Pregnancy: Pregnancy Category B
Reproduction studies carried out with GENOTROPIN at doses of 0.3, 1, and 3.3 mg/kg/day administered SC in the rat and 0.08, 0.3, and 1.3 mg/kg/day administered intramuscularly in the rabbit (highest doses approximately 24 times and 19 times the recommended human therapeutic levels, respectively, based on body surface area) resulted in decreased maternal body weight gains but were not teratogenic. In rats receiving SC doses during gametogenesis and up to 7 days of pregnancy, 3.3 mg/kg/day (approximately 24 times human dose) produced anestrus or extended estrus cycles in females and fewer and less motile sperm in males. When given to pregnant female rats (days 1 to 7 of gestation) at 3.3 mg/kg/day a very slight increase in fetal deaths was observed. At 1 mg/kg/day (approximately seven times human dose) rats showed slightly extended estrus cycles, whereas at 0.3 mg/kg/day no effects were noted.
In perinatal and postnatal studies in rats, GENOTROPIN doses of 0.3, 1, and 3.3 mg/kg/day produced growth-promoting effects in the dams but not in the fetuses. Young rats at the highest dose showed increased weight gain during suckling but the effect was not apparent by 10 weeks of age. No adverse effects were observed on gestation, morphogenesis, parturition, lactation, postnatal development, or reproductive capacity of the offsprings due to GENOTROPIN. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Women
No studies have been completed with Genotropin in nursing women. It is unknown whether Genotropin is excreted in breast milk. As many drugs can be excreted in milk, exercise caution when administered Genotropin to nursing women.
ADVERSE REACTIONS
As with all protein drugs, a small number of patients may develop antibodies to the protein. Growth hormone antibody with binding lower than 2 mg/L has not been associated with growth attenuation. In some cases when binding capacity is > 2 mg/L, interference with growth response has been observed.
In 419 pediatric patients evaluated in clinical studies with GENOTROPIN Lyophilized Powder, 244 had been treated previously with GENOTROPIN or other growth hormone preparations and 175 had received no previous growth hormone therapy. Antibodies to growth hormone (anti-hGH antibodies) were present in six previously treated patients at baseline. Three of the six became negative for anti-HGH antibodies during 6 to 12 months of treatment with GENOTROPIN. Of the remaining 413 patients, eight (1.9%) developed detectable anti-HGH antibodies during treatment with GENOTROPIN; none had an antibody binding capacity > 2 mg/L. There was no evidence that the growth response to GENOTROPIN was affected in these antibody-positive patients.
Preparations of GENOTROPIN contain a small amount of periplasmic Escherichia coli peptides (PECP). Anti-PECP antibodies are found in a small number of patients treated with GENOTROPIN, but these appear to be of no clinical significance.
In clinical studies with GENOTROPIN in pediatric GHD patients, the following events were reported infrequently: injection site reactions, including pain or burning associated with the injection, fibrosis, nodules, rash, inflammation, pigmentation, or bleeding; lipoatrophy; headache; hematuria; hypothyroidism; and mild hyperglycemia.
Leukemia has been reported in a small number of child patients treated with GH, including growth hormone originating from the pituitary gland and somatropin. The link, if one exists, between leukemia and growth hormone is unknown.
In clinical trials with GENOTROPIN in 1,145 GHD adults, the majority of the adverse events consisted of mild to moderate symptoms of fluid retention, including peripheral swelling, arthralgia, pain and stiffness of the extremities, peripheral edema, myalgia, paresthesia, and hypoesthesia. These events were found early in GH therapy and were usually temporary or responsive to a reduction in the dosage.
Table 2 displays the adverse events reported by 5% or more of adult GHD patients in clinical trials after various durations of treatment with GENOTROPIN. Also presented are the corresponding incidence rates of these adverse events in placebo patients during the 6-month double-blind portion of the clinical trials.
* increased significantly when compared to placebo, P n = number of patients receiving GH treatment during the indicated period.
% = percentage of patients who reported the event during the indicated period.
In expanded post-trial extension studies, diabetes mellitus developed in 12 of 3,031 patients (0.4%) during treatment with GENOTROPIN. All 12 patients had predisposing factors, e.g., elevated glycated hemoglobin levels and/or marked obesity, prior to receiving GENOTROPIN. Of the 3,031 patients receiving GENOTROPIN, 61 (2%) developed symptoms of carpal tunnel syndrome, which lessened after dosage reduction or treatment interruption (52) or surgery (9). Other adverse events that have been reported include generalized edema and hypoesthesia.
OVERDOSAGE
There is little information on acute or chronic overdosage with GENOTROPIN Lyophilized Powder. Intravenously administered growth hormone has been shown to result in an acute decrease in plasma glucose. Subsequently, hyperglycemia was seen. It is thought that the same effect might occur on rare occasions with a high dosage of GENOTROPIN administered SC. Long-term overdosage of growth hormone may cause symptoms of acromegaly that is in line with overproduction of GH.
DOSAGE AND ADMINISTRATION
The dosage of GENOTROPIN Lyophilized Powder must be adjusted for the individual patient. The weekly dose should be divided into 6 or 7 subcutaneous injections. GENOTROPIN may be given in the thigh, buttocks, or abdomen; the site of SC injections should be rotated daily to help prevent lipoatrophy.
Pediatric GHD Patients: Generally, a dose of 0.16 to 0.24 mg/kg body weight/week is recommended.
Adult GHD Patients: The recommended dosage at the beginning of GH therapy is not to exceed 0.04 mg/kg/week. The dose may be increased at 4- to 8-week intervals according to individual patient needs to a maximum of 0.08 mg/kg/week, depending upon patient tolerance of treatment. Clinical response, side effects, and determination of age-adjusted serum IGF-I may be used as guidance in dose titration. This approach will tend to result in weight-adjusted doses that are larger for women compared with men and smaller for older and obese patients.
GENOTROPIN HGH must not be injected intravenously.
GENOTROPIN HGH Somatropin is supplied in a two-chamber cartridge, with the lyophilized powder in the front chamber and a diluent in the rear chamber. A reconstitution device is used to mix the diluent and powder.
Follow the directions for reconstitution provided with each growth hormone injection device. Do not shake; shaking may cause denaturation of the active ingredient.
All parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. If the solution is cloudy, the contents MUST NOT be injected.
Patients and caregivers who will administer GENOTROPIN in medically unsupervised situations should receive appropriate training and instruction on the proper use of GENOTROPIN from the physician or other suitably qualified health professional.
GENOTROPIN STABILITY AND STORAGE
Except as noted below, store GENOTROPIN Lyophilized Powder under refrigeration at 2° to 8°C (36° to 46°F). Do not freeze. Protect from light.
The 1.5 mg cartridge of GENOTROPIN contains a diluent with no preservative. After reconstitution, the cartridge may be stored under refrigeration for up to 24 hours. Use once only and discard any remaining solution.
The 5.8 mg and 13.8 mg cartridges of GENOTROPIN contain a diluent with a preservative. Thus, after reconstitution, they may be stored under refrigeration for up to 21 days.
The GENOTROPIN MINIQUICK Growth Hormone Delivery Device should be refrigerated prior to dispensing, but may be stored at or below 25°C (77°F) for up to three months after dispensing. The diluent has no preservative. After reconstitution, the GENOTROPIN MINIQUICK may be stored under refrigeration for up to 24 hours before use. The GENOTROPIN MINIQUICK should be used only once and then discarded.