Omnitrope

Omnitrope is part of the drug class:

• Somatropin and somatropin agonists

Somatropin is a form of human growth hormone important for the growth of bones and muscles.

Somatropin is used to treat growth failure in children and adults who lack natural growth hormone. This includes people with with chronic kidney failure, Noonan syndrome, Turner syndrome, Prader-Willi syndrome, short stature at birth with no catch-up growth, and other causes. Somatropin is also used to prevent severe weight loss in people with AIDS, or to treat short bowel syndrome.

Somatropin may also be used for purposes not listed in this medication guide.

For all patients taking Omnitrope (somatropin (rDNA origin)):

• If you have an allergy to human growth hormone or any other part of this medicine.
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have any of these health problems: Brain tumor, cancer, diabetic eye disease, illness shortly after open heart or belly surgery, many injuries from a crash, lung disease, or sleep apnea.

Children:

• If your child has Prader-Willi syndrome and is very overweight, has trouble breathing, or has sleep apnea.
• If your child's bones are no longer growing (closed epiphyses).

This is not a list of all drugs or health problems that interact with Omnitrope.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

For all patients taking Omnitrope (somatropin (rDNA origin)):

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• If you have high blood sugar (diabetes), talk with your doctor. This medicine may raise blood sugar.
• Check your blood sugar as you have been told by your doctor.
• Tell your doctor if you have signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take Omnitrope.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• Avoid drinking alcohol while taking this medicine.
• Follow the diet and workout plan that your doctor told you about.
• If you have a history of cancer or tumors, talk with your doctor. The chance of new tumors may be raised in some patients.
• If you have Turner syndrome, talk with your doctor. The chance of ear infections, high blood pressure, and very bad blood vessel problems like stroke and bleeding in the brain may be raised.
• This medicine may affect how much of some other drugs are in your body. If you are taking other drugs, talk with your doctor. You may need to have your blood work checked more closely while taking Omnitrope with your other drugs.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Omnitrope while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Children:

• Very bad and sometimes deadly lung or breathing problems have happened in some children with Prader-Willi syndrome. The chance may be higher in children who have sleep apnea, an infection in the lungs or airway, a block in the airway, and in children who are very overweight. Call the doctor right away if your child has a fever of 100.4°F (38°C) or higher, cough, sore throat, shortness of breath, chest pain or discomfort, new or worse snoring, or breathing that is not normal while asleep.
• If your child has an abnormal curve in the spine (scoliosis), talk with your doctor. This medicine could make it worse in children who are still growing.
• Some products have benzyl alcohol. Do not give a product that has benzyl alcohol in it to a newborn. Talk with the doctor to see if this product has benzyl alcohol in it.

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• Some drugs may have another patient information leaflet. Check with your pharmacist. If you have any questions about Omnitrope, please talk with your doctor, nurse, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about Omnitrope. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using Omnitrope.

Review Date: October 4, 2017

Acute Critical Illness

Increased mortality in patients with acute critical illness due to complications following open heart surgery, abdominal surgery or multiple accidental trauma, or those with acute respiratory failure has been reported after treatment with pharmacologic amounts of somatropin [see Contraindications (4)]. Two placebo-controlled clinical trials in non-growth hormone deficient adult patients (n=522) with these conditions in intensive care units revealed a significant increase in mortality (42% vs. 19%) among somatropin-treated patients (doses 5.3-8 mg/day) compared to those receiving placebo. The safety of continuing somatropin treatment in patients receiving replacement doses for approved indications who concurrently develop these illnesses has not been established. Therefore, the potential benefit of treatment continuation with somatropin in patients experiencing acute critical illnesses should be weighed against the potential risk.

Prader-Willi Syndrome in Children

There have been reports of fatalities after initiating therapy with somatropin in pediatric patients with Prader-Willi Syndrome who had one or more of the following risk factors: severe obesity, history of upper airway obstruction or sleep apnea, or unidentified respiratory infection. Male patients with one or more of these factors may be at greater risk than females. Patients with Prader-Willi Syndrome should be evaluated for signs of upper airway obstruction (including onset of or increased snoring) and sleep apnea before initiation of treatment with somatropin. If, during treatment with somatropin, patients show signs of upper airway obstruction (including onset of or increased snoring) and/or new onset sleep apnea, treatment should be interrupted. All patients with Prader-Willi Syndrome treated with somatropin should also have effective weight control and be monitored for signs of respiratory infection, which should be diagnosed as early as possible and treated aggressively [see Contraindications (4)].

Neoplasms

In childhood cancer survivors who were treated with radiation to the brain/head for their first neoplasm and who developed subsequent GHD and were treated with somatropin, an increased risk of a second neoplasm has been reported. Intracranial tumors, in particular meningiomas, were the most common of these second neoplasms. In adults, it is unknown whether there is any relationship between somatropin replacement therapy and CNS tumor recurrence [see Contraindications (4.3)]. Monitor all patients with a history of GHD secondary to an intracranial neoplasm routinely while on somatropin therapy for progression or recurrence of the tumor [see Contraindications (4)].

Because children with certain rare genetic causes of short stature have an increased risk of developing malignancies, practitioners should thoroughly consider the risks and benefits of starting somatropin in these patients. If treatment with somatropin is initiated, these patients should be carefully monitored for development of neoplasms.

Monitor patients on somatropin therapy carefully for increased growth, or potential malignant changes, of preexisting nevi.

Impaired Glucose Tolerance and Diabetes Mellitus

Treatment with somatropin may decrease insulin sensitivity, particularly at higher doses in susceptible patients. As a result, previously undiagnosed impaired glucose tolerance and overt diabetes mellitus may be unmasked, and new onset type 2 diabetes mellitus has been reported in patients taking somatropin. Therefore, glucose levels should be monitored periodically in all patients treated with somatropin, especially in those with risk factors for diabetes mellitus, such as obesity, Turner Syndrome, or a family history of diabetes mellitus. Patients with preexisting type 1 or type 2 diabetes mellitus or impaired glucose tolerance should be monitored closely during somatropin therapy. The doses of antihyperglycemic drugs (i.e., insulin or oral agents) may require adjustment when somatropin therapy is instituted in these patients. [See Drug Interactions (7.5)]

Intracranial Hypertension (IH)

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea, and/or vomiting has been reported in a small number of patients treated with somatropin products. Symptoms usually occurred within the first eight (8) weeks after the initiation of somatropin therapy. In all reported cases, IH-associated signs and symptoms rapidly resolved after cessation of therapy or a reduction of the somatropin dose.

Funduscopic examination should be performed routinely before initiating treatment with somatropin to exclude preexisting papilledema, and periodically during the course of somatropin therapy. If papilledema is observed by funduscopy during somatropin treatment, treatment should be stopped. If somatropin-induced IH is diagnosed, treatment with somatropin can be restarted at a lower dose after IH-associated signs and symptoms have resolved. Patients with Turner syndrome and Prader-Willi Syndrome may be at increased risk for the development of IH.

Hypersensitivity

Serious systemic hypersensitivity reactions includinganaphylactic reactions and antioedema have been reported with postmarketing use of somatropin products. Patients and caregivers should be informed that such reactions are possible and that prompt medical attention should be sought if an allergic reaction occurs [see Contraindications (4)].

Fluid Retention

Fluid retention during somatropin replacement therapy in adults may frequently occur. Clinical manifestations of fluid retention (e.g. edema, arthralgia, myalgia, nerve compression syndromes including carpal tunnel syndrome/paraesthesias) are usually transient and dose dependent.

Hypoadrenalism

Patients receiving somatropin therapy who have or are at risk for pituitary hormone deficiency(s) may be at risk for reduced serum cortisol levels and/or unmasking of central (secondary) hypoadrenalism. In addition, patients treated with glucocorticoid replacement for previously diagnosed hypoadrenalism may require an increase in their maintenance or stress doses following initiation of somatropin treatment [see Section 7.1, 11-β Hydroxysteroid Dehydrogenase Type 1].

Hypothyroidism

Undiagnosed/untreated hypothyroidism may prevent an optimal response to somatropin, in particular, the growth response in children. Patients with Turner syndrome have an inherently increased risk of developing autoimmune thyroid disease and primary hypothyroidism and should have their thyroid function checked prior to initiation of somatropin therapy. In patients with GHD, central (secondary) hypothyroidism may first become evident or worsen during somatropin treatment. Therefore, patients treated with somatropin should have periodic thyroid function tests and thyroid hormone replacement therapy should be initiated or appropriately adjusted when indicated.

Slipped Capital Femoral Epiphysis in Pediatric Patients

Slipped capital femoral epiphysis may occur more frequently in patients with endocrine disorders (including GHD and Turner syndrome) or in patients undergoing rapid growth. Any pediatric patient with the onset of a limp or complaints of hip or knee pain during somatropin therapy should be carefully evaluated.

Progression of Preexisting Scoliosis in Pediatric Patients

Progression of scoliosis can occur in patients who experience rapid growth. Because somatropin increases growth rate, patients with a history of scoliosis who are treated with somatropin should be monitored for progression of scoliosis. However, somatropin has not been shown to increase the occurrence of scoliosis. Skeletal abnormalities including scoliosis are commonly seen in untreated Turner syndrome patients. Scoliosis is also commonly seen in untreated patients with Prader-Willi Syndrome. Physicians should be alert to these abnormalities, which may manifest during somatropin therapy.

Confirmation of Childhood Onset Adult GHD

Patients with epiphyseal closure who were treated with somatropin replacement therapy in childhood should be reevaluated according to the criteria in Indications and Usage (1.2) before continuation of somatropin therapy at the reduced dose level recommended for GH deficient adults.

Otitis Media and Cardiovascular Disorders in Turner Syndrome

Patients with Turner syndrome should be evaluated carefully for otitis media and other ear disorders since these patients have an increased risk of ear and hearing disorders. Somatropin treatment may increase the occurrence of otitis media in patients with Turner syndrome. In addition, patients with Turner syndrome should be monitored closely for cardiovascular disorders (e.g., stroke, aortic aneurysm/dissection, hypertension) as these patients are also at risk for these conditions.

Lipoatrophy

When somatropin is administered subcutaneously at the same site over a long period of time, tissue atrophy may result. This can be avoided by rotating the injection site [see Dosage and Administration (2.3)].

Laboratory Tests

Serum levels of inorganic phosphorus, alkaline phosphatase, parathyroid hormone (PTH) and IGF-1 may increase after somatropin therapy.

Pancreatitis

Cases of pancreatitis have been reported rarely in children and adults receiving somatropin treatment, with some evidence supporting a greater risk in children compared with adults. Published literature indicates that girls who have Turner syndrome may be at greater risk than other somatropin-treated children. Pancreatitis should be considered in any somatropin treated patient, especially a child, who develops persistent severe abdominal pain.

Benzyl Alcohol

Benzyl alcohol, a component of Omnitrope Cartridge 5 mg/1.5 mL and the diluent for Omnitrope for injection 5.8 mg/vial, has been associated with serious adverse events and death, particularly in pediatric patients. The “gasping syndrome,” (characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low-birth weight neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.

The following important adverse reactions area also described elsewhere in labeling:

• Increased mortality in patients with acute critical illness [see Warnings and Precautions (5.1)] • Fatalities in children with Prader-Willi Syndrome [see Warnings and Precautions (5.2)]. • Neoplasms [see Warnings and Precautions (5.3)] • aGlucose intolerance and diabetes mellitus [Warnings and Precautions (5.4)] • Intracranial hypertension [see Warnings and Precautions (5.5)] • Severe hypersensitivity [see Warnings and Precautions (5.6)] • Fluid retention [see Warnings and Precautions (5.7)] • Hypoadrenalism [see Warnings and Precautions (5.8)] • Hypothyroidism [see Warnings and Precautions (5.9)] • Slipped capital femoral epiphysis in pediatric patients [see Warnings and Precautions (5.10)] • Progression of preexisting scoliosis in pediatric patients [see Warnings and Precautions (5.11)] • Otitis media and cardiovascular disorders in patients with Turner syndrome [see Warnings and Precautions (5.12)] • Lipoatrophy [see Warnings and Precautions (5.14)] • Pancreatitis [see Warnings and Precautions (5.16)] • Benzyl Alcohol [see Warnings and Precautions (5.17)]

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 Pediatric GHD Patients

The following events were observed during clinical studies with Omnitrope Cartridge conducted in children with GHD:

Table 1. Incidence of Adverse Reactions Reported in ≥ 5% Pediatric Patients with GHD During Treatment with Omnitrope Cartridge (N=86)

Adverse Event	n (%)
N=number of patients receiving treatment n=number of patients who reported the event during study period %=percentage of patients who reported the event during study period
Elevated HbA1c	12 (14%)
Eosinophilia	10 (12%)
Hematoma	8 (9%)

The following events were observed during clinical studies with Omnitrope for injection conducted in children with GHD:

Table 2. Incidence of Adverse Reactions Reported in ≥ 5% Pediatric Patients with GHD During Treatment with Omnitrope for Injection (N=44)

Adverse Event	n (%)
N=number of patients receiving treatment n=number of patients who reported the event during study period %= percentage of patients who reported the event during study period
Hypothyroidism	7 (16%)
Eosinophilia	5 (11%)
Elevated HbA1c	4 (9%)
Hematoma	4 (9%)
Headache	3 (7%)
Hypertriglyceridemia	2 (5%)
Leg Pain	2 (5%)

Clinical Trials in PWS

In two clinical studies in pediatric patients with Prader-Willi Syndrome carried out with another somatropin product, 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 another somatropin product, 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.

Clinical Trials in Children with Idiopathic Short Stature

In two open-label clinical studies conducted with another somatropin product in pediatric patients with ISS, the most commonly encountered adverse events were upper respiratory tract infections, influenza, tonsillitis, nasopharyngitis, gastroenteritis, headaches, increased appetite, pyrexia, fracture, altered mood, and arthralgia. In one of the two studies during treatment with this other somatropin product, 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 Children with Turner Syndrome

In two clinical studies with another somatropin product 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 Adults with GHD

In clinical trials with another somatropin product 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 3 displays the adverse events reported by 5% or more of adult GHD patients in clinical trials after various durations of treatment with another somatropin product. 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 3. Adverse Events Reported by ≥ 5% of 1,145 Adult GHD Patients During Clinical Trials of Another Somatropin Product and Placebo, Grouped by Duration of Treatment

	Double Blind Phase		Open Label Phase Another Somatropin Product
Adverse Event	Placebo 0–6 mo. (n = 572) % Patients	Another Somatropin Product 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 another somatropin product. All 12 patients had predisposing factors, e.g., elevated glycated hemoglobin levels and/or marked obesity, prior to receiving this other somatropin product. Of the 3,031 patients receiving this other somatropin product, 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.

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 Omnitrope 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.

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.

Serious systemic hypersensitivity reactions including anaphylactic reactions and angioedema have been reported with postmarketing use of somatropin products [see Warnings and Precautions (5.6)].

Leukemia has been reported in a small number of GH deficient 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) and Warnings and Precautions (5.3)].

The following additional adverse reactions have been observed during the use of somatropin: headaches (children and adults), gynecomastia (children), and pancreatitis (children and adults [see Warnings and Precautions (5.16)].

New-onset type 2 diabetes mellitus has been reported.

Mechanism of Action

Somatropin (as well as endogenous GH) binds to a dimeric GH receptor in the cell membrane of target cells resulting in intracellular signal transduction and a host of pharmacodynamic effects. Some of these pharmacodynamic effects are primarily mediated by IGF-1 produced in the liver and also locally (e.g., skeletal growth, protein synthesis), while others are primarily a consequence of the direct effects of somatropin (e.g., lipolysis) [see Pharmacodynamics (12.2)].

Pharmacodynamics

Tissue Growth

The primary and most intensively studied action of somatropin is the stimulation of linear growth. This effect is demonstrated in children with GHD and children who have PWS, were born SGA, have TS or have ISS.

Skeletal Growth

The measurable increase in bone length after administration of somatropin results from its effect on the cartilaginous growth areas of long bones. Studies in vitro have shown that the incorporation of sulfate into proteoglycans is not due to a direct effect of somatropin, but rather is mediated by the somatomedins or insulin-like growth factors (IGFs). The somatomedins, among them IGF-1, are polypeptide hormones which are synthesized in the liver, kidney, and various other tissues. IGF-1 levels are low in the serum of hypopituitary dwarfs and hypophysectomized humans or animals, and increase after treatment with somatropin.

Cell Growth

It has been shown that the total number of skeletal muscle cells is markedly decreased in children with short stature lacking endogenous GH compared with normal children, and that treatment with somatropin results in an increase in both the number and size of muscle cells.

Organ Growth

Somatropin influences the size of internal organs, and it also increases red cell mass.

Protein Metabolism

Linear growth is facilitated in part by increased cellular protein synthesis. This synthesis and growth are reflected by nitrogen retention which can be quantitated by observing the decline in urinary nitrogen excretion and blood urea nitrogen following the initiation of somatropin therapy.

Carbohydrate Metabolism

Hypopituitary children sometimes experience fasting hypoglycemia that may be improved by treatment with somatropin. In healthy subjects, large doses of somatropin may impair glucose tolerance. Although the precise mechanism of the diabetogenic effect of somatropin is not known, it is attributed to blocking the action of insulin rather than blocking insulin secretion. Insulin levels in serum actually increase as somatropin levels increase. Administration of human growth hormone to normal adults and patients with growth hormone deficiency results in increases in mean serum fasting and postprandial insulin levels, although mean values remain in the normal range. In addition, mean fasting and postprandial glucose and hemoglobin A1C levels remain in the normal range.

Lipid Metabolism

Somatropin stimulates intracellular lipolysis, and administration of somatropin leads to an increase in plasma free fatty acids and triglycerides. Untreated GHD is associated with increased body fat stores, including increased abdominal visceral and subcutaneous adipose tissue. Treatment of growth hormone deficient patients with somatropin results in a general reduction of fat stores, and decreased serum levels of low density lipoprotein (LDL) cholesterol.

Mineral Metabolism

Administration of somatropin results in an increase in total body potassium and phosphorus and to a lesser extent sodium. This retention is thought to be the result of cell growth. Serum levels of phosphate increase in children with GHD after somatropin therapy due to metabolic activity associated with bone growth. Serum calcium levels are not altered. Although calcium excretion in the urine is increased, there is a simultaneous increase in calcium absorption from the intestine. Negative calcium balance, however, may occasionally occur during somatropin treatment.

Connective Tissue Metabolism

Somatropin stimulates the synthesis of chondroitin sulfate and collagen, and increases the urinary excretion of hydroxyproline.

Pharmacokinetics

There are no pharmacokinetic studies using Omnitrope Cartridges in patients with growth hormone deficiency.

Absorption

Following a subcutaneous injection of single dose of 5 mg Omnitrope 5 mg/1.5 mL Cartridge or 5 mg Omnitrope 10 mg/1.5 mL Cartridge in healthy male and female adults, the peak concentration (Cmax) was 72-74 mcg/L. The time to reach Cmax (tmax) for Omnitrope was 4.0 hours.

The aqueous formulations of 5 mg/1.5 mL Omnitrope cartridge and 10 mg/mL Omnitrope cartridge are bioequivalent to the lyophilized 5.8 mg/vial Omnitrope formulation.

Metabolism

Somatropin is metabolized in both the liver and kidneys by proteolytic degradation. In renal cells, at least a portion of the breakdown products are returned to the systemic circulation.

Excretion

The mean terminal half-life of somatropin after subcutaneous administration of Omnitrope Cartridge in healthy adults is 2.5-2.8 hours. The mean clearance of subcutaneously administered Omnitrope Cartridge in healthy adults was about 0.14 L/hr/kg.

SpecificPopulations

Pediatric: No pharmacokinetic studies of Omnitrope have been conducted in pediatric patients.

Gender: The effect of gender on pharmacokinetics of Omnitrope has not been evaluated in pediatric patients.

Race: No studies have been conducted with Omnitrope to assess pharmacokinetic differences among races.

Renal or hepatic impairment: No pharmacokinetic studies have been conducted with Omnitrope in patients with renal or hepatic impairment.

Omnitrope® PEN 5

For use with Omnitrope® (om-KNEE-trope)

(somatropin) injection 5 mg/1.5 mL cartridges

TABLE OF CONTENTS

Important Safety Information

DOs and DON’Ts

Pen Parts

Auto-positioning Feature

Pen Components

How to Use Your Omnitrope Pen 5

Loading the Cartridge into the Pen

Attaching the Pen Needle

Priming

Dose Dialing

Making the Injection

Removing the Pen Needle

Trouble Shooting

Care and Storage

Guarantee

Important Personal Notes

READ FIRST: Important Safety Information

1. Read the following instructions before using the Omnitrope Pen 5. Ask your healthcare professional if there is something you do not understand. 2. The Omnitrope Pen 5 is a pen injector. It is for use with Omnitrope cartridges 5 mg/1.5 mL and BD® pen needles (29G x 12.7 mm or 31G x 8 mm or 31G x 5 mm). 3. People with very poor vision should not use the Omnitrope Pen 5 unless someone with good eyesight is able to help.

DOS AND DON’TS

DOs

1. Always keep Omnitrope cartridges refrigerated. 2. Cartridges should be handled with care at all times. 3. After taking a cartridge out of the refrigerator, allow it to reach room temperature (about 30 minutes) before injecting the medicine. 4. When starting a new cartridge, always ready (prime) the pen. 5. When making an injection, insert the pen needle into the skin in the way that your healthcare professional teaches you. After pen needle insertion, push the injection button in as far as it will go and continue to press firmly for at least five seconds, before you remove the pen needle from the skin. If medicine continues to drip from the pen needle after injection, hold the pen needle in the skin longer the next time you inject. 6. This device must not be shared with other patients even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection. However, if you are giving an injection to another person, be careful when removing the pen needle. Accidental pen needle sticks can transmit infections. 7. For safety and injection comfort, use a new, sterile pen needle with each injection.

DON’Ts

1. Do not share the Omnitrope Pen 5 even if the needle is changed. It is made for only one person to use. 2. The pen needle unit is sterile. To avoid contaminating the pen needle after opening, do not place it on a surface or touch exposed parts. 3. Never dial your dose or attempt to correct a dialing error with the pen needle in your skin. This may result in a wrong dose. 4. Never store or carry your Omnitrope Pen 5 with a pen needle attached.

Never recap pen with pen needle on.

Storing or carrying your Omnitrope Pen 5 with a pen needle attached may lead to needle pricks and leaves an open passage for:

• Air to enter the cartridge • medicine to leak out

Both of these conditions can affect the dose of the injection.

5. Do not use your Omnitrope Pen 5 if the cap or other parts are missing.

PEN PARTS

AUTO-POSITIONING FEATURE

The Omnitrope Pen 5 has a black rod with an auto-positioning feature. This auto-positioning feature makes priming easier (fewer steps), especially when a new cartridge is used.

How it works

(Pictures are included only to demonstrate the auto-positioning feature. These steps are not necessary to operate pen).

Notice that the black rod moves into the pen easily and returns to the fully extended position automatically. This automatic extension of the black rod positions it correctly against the cartridge plunger.

PEN PARTS

	PEN CAP 1. Clip
	CARTRIDGE HOLDER
	PEN BODY 2. Black rod 3. Dose window with arrow indicator 4. White dose knob 5. Red injection button
	PEN NEEDLE UNIT 6. Outer pen needle shield 7. Inner pen needle shield 8. Pen needle 9. Hub 10. Paper tab

Note – Pen Needle Unit is supplied assembled and sterile. Do not disassemble at this point.

CARTRIDGE 11. Rubber septum 12. Metal Cap 13. Cartridge plunger

HOW TO USE YOUR Omnitrope PEN 5

LOADING THE CARTRIDGE INTO THE PEN

1. Remove the pen cap by pulling it off the pen. 2. Unscrew the cartridge holder from the pen body 3. Insert the cartridge, metal cap first, into the cartridge holder 4. Lower the pen body onto the cartridge holder so that the black rod presses against the cartridge plunger. Screw the cartridge holder onto the pen body until no gap remains. One of the blue arrows must line-up with the yellow line mark on the pen body.

Note – Do not overtighten.

ATTACHING THE PEN NEEDLE

5. Remove the paper tab from the back of a new pen needle.   6a. Holding the cartridge holder, push the pen needle unit onto the pen. Then screw the threaded hub of the pen needle onto the cartridge holder as shown.   6b. With a gentle pull, remove the outer pen needle shield. Save the outer shield. You will use it to remove the pen needle from the pen after your injection is finished.   6c. Do not remove the inner pen needle shield at this time.   6d. Check that the cartridge holder is attached to the pen body, with the blue arrow lined-up with the yellow mark on the pen body before each injection.   PRIMING

Important – Before using a new cartridge, you must prime the Omnitrope Pen 5.

For a New Cartridge Only

7. Hold the pen with the needle pointing upwards. Gently tap the cartridge holder with your finger to help air bubbles rise to the top of the cartridge. Set the dose to 0.05 mg (one click) by turning the dose knob. 8. Remove the inner pen needle shield. With the pen needle pointing up, firmly turn the dose knob back to the “0” position and hold for at least 5 seconds. At least 2 drops of medicine must flow out of the pen needle for the pen to be properly primed. If at least 2 drops do not flow out, set the dose to 0.05 mg and repeat the steps until at least 2 drops of medicine appear at the tip of the pen needle. When medicine appears, the Omnitrope Pen 5 is properly primed for injection and ready to use.

For a previously used Cartridge

No priming is needed. Remove the inner pen needle shield and continue with dose dialing.

DOSE DIALING

9. To set your dose, turn the dose knob until you see the number of mg for your dose in the middle of the dose window lined-up with the arrow. You will hear a click for each dose increment you dial. However, do not rely on counting these clicks to measure the right dose.

Important – Dose Correction

If you turn the dose knob past your dose, do not dial backwards.

Hold the pen body and turn the dose knob until it is fully extended as shown in picture 9a. You will see a bent arrow () in the dose dialing window. The injection button can now be fully pressed, resetting the dial to “0” without giving medicine. The right dose can now be redialed as described in step 9.

Note – Check that the cartridge holder is still attached to the pen body, with the blue arrow lined-up with the yellow mark on the pen body.

MAKING THE INJECTION

10. Insert the pen needle into the skin as instructed by your healthcare professional. 11. After inserting the pen needle, push the injection button in as far in as it will go and press firmly. A clicking sound will be heard while your dose is injecting. Continue to press firmly for at least 5 seconds, before you remove the pen needle from the skin.

If medicine continues to drip from the pen needle after injection, hold the pen needle in your skin for a longer time the next time you inject.

If you cannot push the Injection button in as far in as it goes and the dose window does not read “0”, the cartridge is empty and the full dose of medicine has not been injected. The dose indicator window will show the amount of medicine still needed. Remove the pen needle from the skin and note the number. Reset the dose knob to “0” by holding the pen and turning the dose knob until it is fully extended as shown in picture 9a. The dose injection button can now be fully pressed to “0”. Remove the pen needle from the pen (see step 12 below) and remove the empty cartridge by unscrewing the cartridge holder. Insert a new cartridge and prime the pen as described in steps 7 and 8. Set the dose, which you noted, and inject. This completes your dose.

Important – Before replacing a cartridge, be sure that the pen needle unit is NOT attached to the Omnitrope Pen 5.

REMOVING THE PEN NEEDLE

12. Carefully replace the outer pen needle shield. Hold the pen by the cartridge holder and unscrew the pen needle from the cartridge holder. Recap the pen. 13. Store your Omnitrope Pen 5 with attached Omnitrope cartridge in its pouch or refrigerator storage box. Store in a refrigerator between 36 and 46°F (2 and 8°C). 14. Dispose of used pen needles in a special container called a “sharps” container. Your healthcare professional can give you a sharps container or tell you how to make one. Do not dispose of used pen needles in the trash.

TROUBLESHOOTING

PROBLEM	POSSIBLE CAUSE	HOW TO FIX
Dial unit does not turn easily.	Dust or dirt	Turn the dial beyond the highest setting on the scale. Wipe all exposed surfaces with a clean, damp cloth. Please also refer to the chapter “Care and Storage”.
You have dialed a higher dose than needed.		Correct dose as described in step 9, “Dose correction”.
The injection button cannot be pushed or stops during injection. (Dose knob does not return to “0”).	Cartridge is empty and full dose has not been dispensed.	Remove the pen needle as per step 12 and replace the empty cartridge with a new cartridge. Refer to step 11, “If the injection button stops”.
	Clogged pen needle.	Remove the pen needle as per step 12 and replace it with a new needle as described in step 5.
No clicking is heard during the injection (Dose knob moves freely).	Pen is in dose correction mode.	Remove pen needle from skin. Press injection button all the way in so the dial returns to zero and repeat from step 9 to make the injection.
Medicine continues to drip from the pen needle after injection.	Pen needle was removed from the skin too early.	Hold the pen needle in your skin longer next time you inject.
	Cartridge holder is not properly attached to the pen body.	Line-up blue arrow on cartridge holder with yellow mark on pen body.

CARE AND STORAGE

Once your Omnitrope Pen 5 contains a somatropin cartridge, it has to be stored in the refrigerator between 36 and 46°F (2 and 8°C).

Do not remove the cartridge between injections.

Protect your Omnitrope Pen 5 and cartridge from light by storing in its pouch or refrigerator storage box.

The Omnitrope cartridge must be discarded 28 days after the first injection. The Omnitrope Pen 5 can be reloaded with a new cartridge and be used multiple times.

Your Omnitrope Pen 5 must be properly cared for.

• Only a clean, damp cloth should be used for routine cleaning. Never wash the pen in water or with strong surgical disinfectants. • Avoid exposure to dust, moisture and temperature extremes. Do not expose to heat or freeze.

If your Omnitrope Pen 5 is damaged or you cannot get it to work, contact the pharmacy that provided you the Omnitrope Pen 5 or, if OmniSource provided you with your Omnitrope Pen 5, call 1-877-456-6794. For other questions or additional information please call OmniSource at 1-877-456-6794. Do not attempt to repair the pen yourself.

GUARANTEE

Your Omnitrope Pen 5 is covered by a 2 year guarantee. Contact your Omnitrope Pen 5 provider after you have used the pen for 2 years to have it replaced by a new one.

If your Omnitrope Pen 5 is defective in materials or workmanship within the period of the guarantee, the provider of your Omnitrope Pen 5 will replace your pen and/or rectify the fault at its own cost. If OmniSource provided your Omnitrope Pen 5, call 1-877-456-6794. Otherwise call the pharmacy that provided the Omnitrope Pen 5.

In case of complaints, please contact your Omnitrope Pen 5 provider to report a complaint.

This guarantee is invalid if your Omnitrope Pen 5 has not been used in accordance with the manufacturer`s instruction leaflet or if the defect has been caused by neglect, misuse or accident.

IMPORTANT PERSONAL NOTES

Date I first used the Omnitrope Pen 5:

____________________________________(dd/mm/yy)

Pen log no:

______________________________________

Additional Comments:

______________________________________

______________________________________

______________________________________

______________________________________

Omnitrope Pen 5

Manufactured for

Sandoz GmbH, Kundl, Austria

Product of Taiwan

Distributed by

Sandoz Inc., Princeton, NJ 08540

09-2016M

CE0344

Omnitrope® is a trademark of Novartis.

BD and BD Logo are trademarks of Becton, Dickinson and Company.

OP5.ifU.06.1

46193261

Omnitrope® PEN 10
INSTRUCTIONS FOR USE

For use with Omnitrope® (somatropin) injection 10 mg/1.5 mL cartridges

TABLE OF CONTENTS

Important Safety Information

DOs and DON’Ts

Pen Parts

Auto-positioning Feature

Pen Components

How to Use Your Omnitrope Pen 10

Loading the Cartridge into the Pen

Attaching the Pen Needle

Priming

Dose Dialing

Making the Injection

Removing the Pen Needle

Trouble Shooting

Care and Storage

Guarantee

Important Personal Notes

READ FIRST: Important Safety Information

1. Read the following instructions before using the Omnitrope Pen 10. Ask your healthcare professional if there is something you do not understand. 2. The Omnitrope Pen 10 is a pen injector. It is for use with Omnitrope cartridges 10 mg/1.5 mL and BD® pen needles (29G x 12.7 mm or 31G x 8 mm or 31G x 5 mm). 3. People with very poor vision should not use the Omnitrope Pen 10 unless someone with good eyesight is able to help.

DOS AND DON’TS

DOs

1. Always keep Omnitrope cartridges refrigerated. 2. Cartridges should be handled with care at all times. 3. After taking a cartridge out of the refrigerator, allow it to reach room temperature (about 30 minutes) before injecting the medicine. 4. When starting a new cartridge, always ready (prime) the pen. 5. When making an injection, insert the pen needle into the skin in the way that your healthcare professional teaches you. After pen needle insertion, push the injection button in as far as it will go and continue to press firmly for at least five seconds, before you remove the pen needle from the skin. If medicine continues to drip from the pen needle after injection, hold the pen needle in the skin longer the next time you inject. 6. This device must not be shared with other patients even if the needle is changed. Sharing of the pen between patients may pose a risk of transmission of infection. However, if you are giving an injection to another person, be careful when removing the pen needle. Accidental pen needle sticks can transmit infections. 7. For safety and injection comfort, use a new, sterile pen needle with each injection.

DON’Ts

1. Do not share the Omnitrope Pen 10 even if the needle is changed. It is made for only one person to use. 2. The pen needle unit is sterile. To avoid contaminating the pen needle after opening, do not place it on a surface or touch exposed parts. 3. Never dial your dose or attempt to correct a dialing error with the pen needle in your skin. This may result in a wrong dose. 4. Never store or carry your Omnitrope Pen 10 with a pen needle attached.

Never recap pen with pen needle on.

Storing or carrying your Omnitrope Pen 10 with a pen needle attached may lead to needle pricks and leaves an open passage for:

• Air to enter the cartridge • medicine to leak out

Both of these conditions can affect the dose of the injection.

5. Do not use your Omnitrope Pen 10 if the cap or other parts are missing.

PEN PARTS

AUTO-POSITIONING FEATURE

The Omnitrope Pen 10 has a black rod with an auto-positioning feature. This auto-positioning feature makes priming easier (fewer steps), especially when a new cartridge is used.

How it works

(Pictures are included only to demonstrate the auto-positioning feature. These steps are not necessary to operate pen).

Notice that the black rod moves into the pen easily and returns to the fully extended position automatically. This automatic extension of the black rod positions it correctly against the cartridge plunger.

PEN PARTS

	PEN CAP 1. Clip
	CARTRIDGE HOLDER
	PEN BODY 2. Black rod 3. Dose window with arrow indicator 4. White dose knob 5. Red injection button
	PEN NEEDLE UNIT 6. Outer pen needle shield 7. Inner pen needle shield 8. Pen needle 9. Hub 10. Paper tab

Note – Pen Needle Unit is supplied assembled and sterile. Do not disassemble at this point.

CARTRIDGE 11. Rubber septum 12. Metal Cap 13. Cartridge plunger

HOW TO USE YOUR Omnitrope PEN 10

LOADING THE CARTRIDGE INTO THE PEN

1. Remove the pen cap by pulling it off the pen. 2. Unscrew the cartridge holder from the pen body 3. Insert the cartridge, metal cap first, into the cartridge holder 4. Lower the pen body onto the cartridge holder so that the black rod presses against the cartridge plunger. Screw the cartridge holder onto the pen body until no gap remains. One of the blue arrows must line-up with the white line mark on the pen body.

Note – Do not overtighten.

ATTACHING THE PEN NEEDLE

5. Remove the paper tab from the back of a new pen needle.   6a. Holding the cartridge holder, push the pen needle unit onto the pen. Then screw the threaded hub of the pen needle onto the cartridge holder as shown.   6b. With a gentle pull, remove the outer pen needle shield. Save the outer shield. You will use it to remove the pen needle from the pen after your injection is finished.   6c. Do not remove the inner pen needle shield at this time.   6d. Check that the cartridge holder is attached to the pen body, with the blue arrow lined-up with the white mark on the pen body before each injection.   PRIMING

Important – Before using a new cartridge, you must prime the Omnitrope Pen 10.

For a New Cartridge Only

7. Hold the pen with the needle pointing upwards. Gently tap the cartridge holder with your finger to help air bubbles rise to the top of the cartridge. Set the dose to 0.1 mg (one click) by turning the dose knob. 8. Remove the inner pen needle shield. With the pen needle pointing up, firmly turn the dose knob back to the “0” position and hold for at least 5 seconds. At least 2 drops of medicine must flow out of the pen needle for the pen to be properly primed. If at least 2 drops do not flow out, set the dose to 0.1 mg and repeat the steps until at least 2 drops of medicine appear at the tip of the pen needle. When medicine appears, the Omnitrope Pen 10 is properly primed for injection and ready to use.

For a previously used Cartridge

No priming is needed. Remove the inner pen needle shield and continue with dose dialing.

DOSE DIALING

9. To set your dose, turn the dose knob until you see the number of mg for your dose in the middle of the dose window lined-up with the arrow. You will hear a click for each dose increment you dial. However, do not rely on counting these clicks to measure the right dose.

Important – Dose Correction

If you turn the dose knob past your dose, do not dial backwards.

Hold the pen body and turn the dose knob until it is fully extended as shown in picture 9a. You will see a bent arrow () in the dose dialing window. The injection button can now be fully pressed, resetting the dial to “0” without giving medicine. The right dose can now be redialed as described in step 9.

Note – Check that the cartridge holder is still attached to the pen body, with the blue arrow lined-up with the white mark on the pen body.

MAKING THE INJECTION

10. Insert the pen needle into the skin as instructed by your healthcare professional. 11. After inserting the pen needle, push the injection button in as far in as it will go and press firmly. A clicking sound will be heard while your dose is injecting. Continue to press firmly for at least 5 seconds, before you remove the pen needle from the skin.

If medicine continues to drip from the pen needle after injection, hold the pen needle in your skin for a longer time the next time you inject.

If you cannot push the Injection button in as far in as it goes and the dose window does not read “0”, the cartridge is empty and the full dose of medicine has not been injected. The dose indicator window will show the amount of medicine still needed. Remove the pen needle from the skin and note the number. Reset the dose knob to “0” by holding the pen and turning the dose knob until it is fully extended as shown in picture 9a. The dose injection button can now be fully pressed to “0”. Remove the pen needle from the pen (see step 12 below) and remove the empty cartridge by unscrewing the cartridge holder. Insert a new cartridge and prime the pen as described in steps 7 and 8. Set the dose, which you noted, and inject. This completes your dose.

Important – Before replacing a cartridge, be sure that the pen needle unit is NOT attached to the Omnitrope Pen 10.

REMOVING THE PEN NEEDLE

12. Carefully replace the outer pen needle shield. Hold the pen by the cartridge holder and unscrew the pen needle from the cartridge holder. Recap the pen. 13. Store your Omnitrope Pen 10 with attached Omnitrope cartridge in its pouch or refrigerator storage box. Store in a refrigerator between 36 and 46°F (2 and 8°C). 14. Dispose of used pen needles in a special container called a “sharps” container. Your healthcare professional can give you a sharps container or tell you how to make one. Do not dispose of used pen needles in the trash.

TROUBLESHOOTING

PROBLEM	POSSIBLE CAUSE	HOW TO FIX
Dial unit does not turn easily.	Dust or dirt	Turn the dial beyond the highest setting on the scale. Wipe all exposed surfaces with a clean, damp cloth. Please also refer to the chapter “Care and Storage”.
You have dialed a higher dose than needed.		Correct dose as described in step 9, “Dose correction”.
The injection button cannot be pushed or stops during injection. (Dose knob does not return to “0”).	Cartridge is empty and full dose has not been dispensed.	Remove the pen needle as per step 12 and replace the empty cartridge with a new cartridge. Refer to step 11, “If the injection button stops”.
	Clogged pen needle.	Remove the pen needle as per step 12 and replace it with a new needle as described in step 5.
No clicking is heard during the injection (Dose knob moves freely).	Pen is in dose correction mode.	Remove pen needle from skin. Press injection button all the way in so the dial returns to zero and repeat from step 9 to make the injection.
Medicine continues to drip from the pen needle after injection.	Pen needle was removed from the skin too early.	Hold the pen needle in your skin longer next time you inject.
	Cartridge holder is not properly attached to the pen body.	Line-up blue arrow on cartridge holder with white mark on pen body.

CARE AND STORAGE

Once your Omnitrope Pen 10 contains a somatropin cartridge, it has to be stored in the refrigerator between 36 and 46°F (2 and 8°C).

Do not remove the cartridge between injections.

Protect your Omnitrope Pen 10 and cartridge from light by storing in its pouch or refrigerator storage box.

The Omnitrope cartridge must be discarded 28 days after the first injection. The Omnitrope Pen 10 can be reloaded with a new cartridge and be used multiple times.

Your Omnitrope Pen 10 must be properly cared for.

• Only a clean, damp cloth should be used for routine cleaning. Never wash the pen in water or with strong surgical disinfectants. • Avoid exposure to dust, moisture and temperature extremes. Do not expose to heat or freeze.

If your Omnitrope Pen 10 is damaged or you cannot get it to work, contact the pharmacy that provided you the Omnitrope Pen 10 or, if OmniSource provided you with your Omnitrope Pen 10, call 1-877-456-6794. For other questions or additional information please call OmniSource at 1-877-456-6794. Do not attempt to repair the pen yourself.

GUARANTEE

Your Omnitrope Pen 10 is covered by a 2 year guarantee. Contact your Omnitrope Pen 10 provider after you have used the pen for 2 years to have it replaced by a new one.

If your Omnitrope Pen 10 is defective in materials or workmanship within the period of the guarantee, the provider of your Omnitrope Pen 10 will replace your pen and/or rectify the fault at its own cost. If OmniSource provided your Omnitrope Pen 10, call 1-877-456-6794. Otherwise call the pharmacy that provided the Omnitrope Pen 10.

In case of complaints, please contact your Omnitrope Pen 10 provider to report a complaint.

This guarantee is invalid if your Omnitrope Pen 10 has not been used in accordance with the manufacturer`s instruction leaflet or if the defect has been caused by neglect, misuse or accident.

IMPORTANT PERSONAL NOTES

Date I first used the Omnitrope Pen 10:

____________________________________(dd/mm/yy)

Pen log no:

______________________________________

Additional Comments:

______________________________________

______________________________________

______________________________________

______________________________________

Omnitrope Pen 10

Manufactured for

Sandoz GmbH, Kundl, Austria

Product of Taiwan

Distributed by

Sandoz Inc., Princeton, NJ 08540

09-2016M

CE0344

Omnitrope® is a trademark of Novartis.

BD and BD Logo are trademarks of Becton, Dickinson and Company.

OP10.ifU.07.1

46193263

INSTRUCTIONS FOR Omnitrope® 5.8 MG/VIAL

The following instructions explain how to inject Omnitrope® 5.8 mg. Do not inject Omnitrope® yourself until your healthcare provider has taught you and you understand the instructions. Ask your healthcare provider or pharmacist if you have any questions about injecting Omnitrope®.

• Omnitrope® 5.8 mg is for multiple uses. • The concentration of Omnitrope® after mixing is 5 mg/mL. • After mixing, Omnitrope® 5.8 mg contains a preservative and should not be used in newborns.

Preparation

Collect necessary items before you begin:

• a vial with Omnitrope® 5.8 mg • a vial with diluent (mixing liquid - Bacteriostatic Water for Injection containing benzyl alcohol as preservative) for Omnitrope® 5.8 mg • a sterile, disposable 3 mL syringe and needle for withdrawing the diluent from the vial (not supplied in the pack) • sterile disposable 1 mL syringes and needles for under the skin (subcutaneous) injection (not supplied in the pack) • 2 alcohol swabs (not supplied in the pack)

Wash your hands before you start with the next steps.

Mixing Omnitrope® 5.8 mg

• Remove the protective caps from the two vials. With one alcohol swab, clean both the rubber top of the vial that contains the powder and the rubber top of the vial that contains diluent. • Use next the sterile diluent vial, the disposal 3 mL syringe and a needle. • Attach the needle to the syringe (if not attached already). Pull back the syringe plunger and fill the syringe with air. Push the needle fitted to the syringe through the rubber top of the diluent vial, push all the air from the syringe into the vial, turn the vial upside down, and withdraw all the diluent from the vial into the syringe. Remove the syringe and needle. • Next take the syringe with the diluent in it and push the needle through the rubber stopper of the vial that contains the white powder. Inject the diluent slowly. Aim the stream of liquid against the glass wall in order to avoid foam. Remove the syringe and needle and dispose of them. • Gently swirl the vial until the content is completely dissolved. Do not shake. • If the medicine is cloudy or contains particles, it should not be used. The medicine must be clear and colorless after mixing. • After mixing the medicine, the medicine in the vial must be used within 3 weeks. Store the vial in a refrigerator at 2° to 8°C (36° to 46°F) after mixing and using it each time.

Measuring the Dose of Omnitrope® 5.8 mg to Be Injected

• Next use the sterile, disposable 1 mL (or similar) syringe and needle for subcutaneous injection. Push the needle through the rubber top of the vial that contains the medicine that you have just mixed. • Turn the vial and the syringe upside down. • Be sure the tip of the syringe is in the Omnitrope® mixed medicine. • Pull back on the plunger slowly and withdraw the dose prescribed by your doctor into the syringe. • Hold the syringe with the needle in the vial pointing up and remove the syringe from the vial. • Check for air bubbles in the syringe. If you see any bubbles, pull the plunger slightly back; tap the syringe gently, with the needle pointing upwards, until the bubble disappears. Push the plunger slowly back up to the correct dose. If there is not enough medicine in the syringe after removing the air bubbles, draw more medicine into the syringe from the mixed medicine vial and repeat checking for bubbles. • Look at the mixed medicine in the syringe before using. Do not use if discolored or particles are present. You are now ready to inject the dose.

Injecting Omnitrope® 5.8 mg

• Choose the site of injection on your body. The best sites for injection are tissues with a layer of fat between skin and muscle such as the upper leg (thigh), buttocks, or stomach area (abdomen) as in the picture shown below. Do not inject near your belly button (navel) or waistline. • Make sure you rotate the injection sites on your body. Inject at least 1/2 inch from the last injection. Change the places on your body where you inject, as you have been taught. • Before you make an injection, clean your skin well with an alcohol swab. Wait for the area to air dry. • With one hand, pinch a fold of loose skin at the injection site. With your other hand, hold the syringe as you would a pencil. Insert the needle into the pinched skin straight in or at a slight angle (an angle of 45° to 90°). After the needle is in, remove the hand used to pinch the skin and use it to hold the syringe barrel. Pull back the plunger very slightly with one hand. If blood comes into the syringe, the needle has entered a blood vessel. Do not inject into this site; withdraw the needle and repeat the procedure at a different site. If no blood comes into the syringe, inject the solution by pushing the plunger all the way down gently. • Pull the needle straight out of the skin. After injection, press the injection site with a small bandage or sterile gauze if needed for bleeding, for several seconds. Do not massage or rub the injection site.

After Injecting Omnitrope® 5.8 mg

• Discard the injection materials. • Dispose the syringes safely in a closed container. You can ask your healthcare provider or pharmacist for a “sharps” container. A sharps container is a special container to put used needles and syringes in. You can return a full sharps container to your pharmacist or healthcare provider for disposal. • The vial of mixed medicine must be stored in the refrigerator in its carton at 2° to 8°C (36° to 46°F) and used within 3 weeks. • The solution should be clear after removal from the refrigerator. If the solution is cloudy or contains particles, discard the vial. Do not inject the medicine from this vial. Start over with a new vial of Omnitrope® 5.8 mg. Call your pharmacist if you need a replacement. • Before each use disinfect the rubber top of the reconstituted vial with an alcohol swab. You must use a new disposable 1 mL syringe and needle for each injection.

Omnitrope® is a trademark of Novartis.

Manufactured in Austria by Sandoz GmbH

Distributed by Sandoz Inc., Princeton, NJ 08540

02-2016M

46170948

46170949

46171070

Get emergency medical help if you have signs of an allergic reaction to Omnitrope: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Serious breathing problems may occur in patients with Prader-Willi syndrome who use Omnitrope. If you have Prader-Willi syndrome, call your doctor promptly if you develop signs of lung or breathing problems such as shortness of breath, coughing, or new or increased snoring.

Also call your doctor at once if you have:

• vision changes with sudden and severe pain behind your eyes and nausea or vomiting;

• pain in your knees or hips, or walking with a limp;

• ear pain, swelling, warmth, or drainage;

• numbness or tingling in your wrist, hand, or fingers;

• severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate; or

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss.

Common Omnitrope side effects may include:

• swelling, rapid weight gain;

• muscle or joint pain;

• headache; or

• pain, itching, or skin changes where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Tell your doctor about all your current medicines, and those you start or stop using during your treatment with Omnitrope, especially:

• birth control pills or hormone replacement therapy

• insulin or oral diabetes medicine; or

• steroid medicine (prednisone, dexamethasone, methylprednisolone, and others).

This list is not complete. Other drugs may interact with somatropin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.