Genotropin Side Effects

Generic Name: somatropin

Please note - some side effects for Genotropin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Genotropin - for the Consumer

Genotropin

All medicines may cause side effects, but many people have no, or minor side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Genotropin:

Fatigue; headache; increased appetite; mild arm or leg pain or stiffness; mild swelling (eg, of the hands or feet); muscle or joint pain; prickling sensation of the skin; redness or itching at the injection site; stuffy nose.

Seek medical attention right away if any of these SEVERE side effects occur when using Genotropin:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blood in the urine; burning, tingling, itching, or numbness in the palm of the hand, fingers, or wrist; change in appearance or size of a mole; chest pain or discomfort; confusion; ear pain, discharge, or discomfort; fast heartbeat; flu-like symptoms (chills, fever); hearing problems; hip or knee pain; limp; mental or mood changes; nausea or vomiting; new growth on the skin; one-sided weakness; persistent or severe cough or sore throat; severe or persistent stomach or back pain; severe or persistent swelling of the hands, ankles, or feet; shortness of breath; slurred speech; snoring or irregular breathing during sleep; sudden, severe, or persistent headache or dizziness; symptoms of high blood sugar (eg, increased thirst, hunger, or urination; unusual weakness); thickened or hardened skin at the injection site; trouble breathing; unusual bruising; vision changes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Top

Genotropin Side Effects - for the Professional

Genotropin

Most Serious and/or Most Frequently Observed Adverse Reactions

This list presents the most seriousb and/or most frequently observeda adverse reactions during treatment with somatropin:

• b Sudden death in pediatric patients with Prader-Willi syndrome with risk factors including severe obesity, history of upper airway obstruction or sleep apnea and unidentified respiratory infection [see Contraindications (4.2) and Warnings andPrecautions (5.2)]
• b Intracranial tumors, in particular meningiomas, in teenagers/young adults treated with radiation to the head as children for a first neoplasm and somatropin [see Contraindications (4.3) and Warnings and Precautions (5.3)]
• a, b Glucose intolerance including impaired glucose tolerance/impaired fasting glucose as well as overt diabetes mellitus [see Warnings and Precautions (5.4)]
• b Intracranial hypertension [see Warnings and Precautions (5.5)]
• b Significant diabetic retinopathy [see Contraindications (4.4)]
• b Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.8)]
• b Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.9)]
• aFluid retention manifested by edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias [see Warnings and Precautions (5.6)]
• aUnmasking of latent central hypothyroidism [see Warnings and Precautions (5.7)]
• aInjection site reactions/rashes and lipoatrophy (as well as rare generalized hypersensitivity reactions) [see Warnings andPrecautions (5.11)]
• b Pancreatitis [see Warnings and Precautions (5.14)]

Clinical Trials Experience

Because clinical trials are conducted under varying conditions, adverse reaction rates observed during the clinical trials performed with one somatropin formulation cannot always be directly compared to the rates observed during the clinical trials performed with a second somatropin formulation, and may not reflect the adverse reaction rates observed in practice.

Clinical Trials in children with GHD

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.

Clinical Trials in PWS

In two clinical studies with Genotropin in pediatric patients with Prader-Willi syndrome, the following drug-related events were reported: edema, aggressiveness, arthralgia, benign intracranial hypertension, hair loss, headache, and myalgia.

Clinical Trials in children with SGA

In clinical studies of 273 pediatric patients born small for gestational age treated with Genotropin, the following clinically significant events were reported: mild transient hyperglycemia, one patient with benign intracranial hypertension, two patients with central precocious puberty, two patients with jaw prominence, and several patients with aggravation of preexisting scoliosis, injection site reactions, and self-limited progression of pigmented nevi. Anti-hGH antibodies were not detected in any of the patients treated with Genotropin.

Clinical Trials in children with Turner Syndrome

In two clinical studies with Genotropin in pediatric patients with Turner syndrome, the most frequently reported adverse events were respiratory illnesses (influenza, tonsillitis, otitis, sinusitis), joint pain, and urinary tract infection. The only treatment-related adverse event that occurred in more than 1 patient was joint pain.

Clinical Trials in children with Idiopathic Short Stature

In two open-label clinical studies with Genotropin in pediatric patients with ISS, the most commonly encountered adverse events include upper respiratory tract infections, influenza, tonsillitis, nasopharyngitis, gastroenteritis, headaches, increased appetite, pyrexia, fracture, altered mood, and arthralgia. In one of the two studies, during Genotropin treatment, the mean IGF-1 standard deviation (SD) scores were maintained in the normal range. IGF-1 SD scores above +2 SD were observed as follows: 1 subject (3%), 10 subjects (30%) and 16 subjects (38%) in the untreated control, 0. 23 and the 0.47 mg/kg/week groups, respectively, had at least one measurement; while 0 subjects (0%), 2 subjects (7%) and 6 subjects (14%) had two or more consecutive IGF-1 measurements above +2 SD.

Clinical Trials in adults with GHD

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 reported early during therapy, and tended to be transient and/or responsive to dosage reduction.

Table 1 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.

Table 1 Adverse Events Reported by ≥ 5% of 1,145 Adult GHD Patients During Clinical Trials of Genotropin and Placebo, Grouped by Duration of Treatment

	Double Blind Phase		Open Label Phase Genotropin
Adverse Event	Placebo 0–6 mo. n = 572 % Patients	Genotropin 0–6 mo. n = 573 % Patients	6–12 mo. n = 504 % Patients	12–18 mo. n = 63 % Patients	18–24 mo. n = 60 % Patients
n = number of patients receiving treatment during the indicated period. % = percentage of patients who reported the event during the indicated period.
* Increased significantly when compared to placebo, P≤.025: Fisher's Exact Test (one-sided)
Swelling, peripheral	5.1	17.5*	5.6	0	1.7
Arthralgia	4.2	17.3*	6.9	6.3	3.3
Upper respiratory infection	14.5	15.5	13.1	15.9	13.3
Pain, extremities	5.9	14.7*	6.7	1.6	3.3
Edema, peripheral	2.6	10.8*	3.0	0	0
Paresthesia	1.9	9.6*	2.2	3.2	0
Headache	7.7	9.9	6.2	0	0
Stiffness of extremities	1.6	7.9*	2.4	1.6	0
Fatigue	3.8	5.8	4.6	6.3	1.7
Myalgia	1.6	4.9*	2.0	4.8	6.7
Back pain	4.4	2.8	3.4	4.8	5.0

Post-Trial Extension Studies in Adults

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.

Anti-hGH Antibodies

As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to Genotropin with the incidence of antibodies to other products may be misleading. In the case of growth hormone, antibodies with binding capacities lower than 2 mg/mL have not been associated with growth attenuation. In a very small number of patients treated with somatropin, when binding capacity was greater than 2 mg/mL, interference with the growth response was 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.

Periplasmic Escherichia coli Peptides

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.

Post-Marketing Experience

Because these adverse events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The adverse events reported during post-marketing surveillance do not differ from those listed/discussed above in Sections 6.1 and 6.2 in children and adults.

Leukemia has been reported in a small number of GHD children treated with somatropin, somatrem (methionylated rhGH) and GH of pituitary origin. It is uncertain whether these cases of leukemia are related to GH therapy, the pathology of GHD itself, or other associated treatments such as radiation therapy. On the basis of current evidence, experts have not been able to conclude that GH therapy per se was responsible for these cases of leukemia. The risk for children with GHD, if any, remains to be established [see Contraindications (4.3) and Warnings and Precautions (5.3)].

The following additional adverse reactions have been observed during the appropriate use of somatropin: headaches (children and adults), gynecomastia (children), and pancreatitis (children and adults, see Warnings and Precautions [5.14]).

New-onset type 2 diabetes mellitus has been reported.

Top

Side Effects by Body System - for Healthcare Professionals

General

Somatropin is generally well tolerated with minimal adverse effects.

Oncologic

Oncologic side effects have included rare reports of leukemia, however, the association with human growth hormone is uncertain.

Immunologic

Immunologic adverse reactions have included the rare development of persistent antibodies in patients treated with recombinant human growth hormone. The development of antibodies may be greater with the use of somatrem than with somatropin, although the overall incidence is very low.

An IgG antibody has been identified. No antibodies to the IgE class have been detected. Growth hormone antibody binding capacities less than 2 mg/L have not led to growth attenuation. Testing for antibodies should be carried out in any patient failing to respond to treatment.

Primate studies have failed to reveal evidence of histopathological changes due to immune complex formation.

Nervous system

Nervous system effects have included headaches, weakness, paresthesia and hypethesia.

Musculoskeletal

Musculoskeletal side effects have included localized muscle pain, carpal tunnel syndrome, aggravation of preexisting scoliosis, jaw prominence and slipped capital femoral epiphysis. Patients with Short Stature Homeobox Containing Gene (SHOX) Deficiency have reported scoliosis and arthralgia.

Endocrine

Endocrine side effects have included mild hyperglycemia, gynecomastia, and, rarely pancreatitis. New-onset type 2 diabetes mellitus in children and adults has been reported in postmarketing experience. Elevations in IGF-1 (insulin like growth factor 1) and insulin levels have occurred consistently in adults. Alterations in thyroid hormone metabolism may occur.

Serum levels of inorganic phosphorus, alkaline phosphatase and parathyroid hormone (PTH) may increase during treatment with somatropin. The mechanism is unknown. These potential changes should be considered when evaluating patient laboratory measurements.

During postmarketing surveillance, cases of new onset glucose intolerance, diabetes mellitus and exacerbations of preexisting diabetes mellitus have been reported in patients receiving the Serostim brand of somatropin. Some patients developed ketoacidosis and diabetic coma. In some patients, these conditions improved when Serostim was discontinued but not in all patients.

Cardiovascular

Edema occurs more often in adults, appears to be dose-related, and is due to the antinatriuretic effect of growth hormone.

Cardiovascular side effects have included mild, transient, peripheral edema in up to 2.5% of patients during early treatment with somatropin. Intracranial hypertension is a rare effect that may present with papilledema, visual changes, headache, nausea and vomiting. Postmarketing reports have included hypertension.

Other

Athletes using human growth hormone for doping purposes may experience cardiac, renal, and splenic hypertrophy, cardiac myopathy, fluid retention, glucose intolerance, abnormal bone growth, and an increased risk of cancers.

Chronic use of human growth hormone by athletes can lead to toxicity seen in acromegaly.

There is no risk of acquiring Creutzfeldt-Jakob disease from recombinant human growth hormone, as with the previously marketed pituitary derived human growth hormone.

Dermatologic

Dermatologic side effects have included rash, pruritus, increased sweating and increased growth of preexisting nevi (hereditary malformation of the skin). Patients with Short Stature Homeobox Containing Gene (SHOX) Deficiency have reported excessive number of cutaneous nevi.

Metabolic

Metabolic side effects have included mild transient hyperglycemia and lipolysis in adults which resulted in a statistically significant decrease in total body fat (14% to 20%) and a significant reductions in total cholesterol and/or LDL levels. No changes in HDL have been observed. Elderly patients have exhibited triglyceride elevations. The long-term effect of recombinant human growth hormone on lipid metabolism is unknown.

Local

Local side effects have included localized injection site reactions and pain.

Other

Other side effects have included an increased incidence of otitis media and other ear disorders in Turner syndrome patients. Other side effects reported in Turner syndrome patients have included influenza-like illness, upper respiratory tract infection, eczema, excessive growth of hands and feet, and exacerbation of preexisting scoliosis.

Gastrointestinal

Gastrointestinal side effects have included diarrhea, nausea and vomiting.

Hypersensitivity

Hypersensitivity side effects have included allergic reactions.

Respiratory

Respiratory side effects have included rhinitis, bronchitis and upper respiratory tract infections. Postmarketing reports have included dyspnea and sleep apnea.

Top

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.