INCRELEX® (mecasermin [rDNA origin] injection) is an aqueous solution for injection containing human insulin-like growth factor-1 (rhIGF-1) produced by recombinant DNA technology. IGF-1 consists of 70 amino acids in a single chain with three intramolecular disulfide bridges and a molecular weight of 7649 daltons. The amino acid sequence of the product is identical to that of endogenous human IGF-1. The rhIGF-1 protein is synthesized in bacteria (E. coli) that have been modified by the addition of the gene for human IGF-1.

Primary Amino Acid Sequence of rhIGF-1

INCRELEX® is a purified preparation. Biological potency is determined using a bioassay.

INCRELEX® is a sterile, aqueous, clear and colorless solution intended for subcutaneous injection. Each multi-dose vial of INCRELEX® contains 10 mg/mL mecasermin, 9 mg/mL benzyl alcohol, 5.84 mg/mL sodium chloride, 2 mg/mL polysorbate 20, and 0.05M acetate at a pH of approximately 5.4.

Last updated on RxList: 2/20/2009

INCRELEX® (mecasermin [rDNA origin] injection) is indicated for the long-term treatment of growth failure in children with severe primary IGF-1 deficiency (Primary IGFD) or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH. Severe Primary IGFD is defined by:

• height standard deviation score ≤ 3.0 and
• basal IGF-1 standard deviation score ≤ 3.0 and
• normal or elevated growth hormone (GH).

Severe Primary IGFD includes patients with mutations in the GH receptor (GHR), post-GHR signaling pathway, and IGF-1 gene defects; they are not GH deficient, and therefore, they cannot be expected to respond adequately to exogenous GH treatment.

INCRELEX® is not intended for use in subjects with secondary forms of IGF-1 deficiency, such as GH deficiency, malnutrition, hypothyroidism, or chronic treatment with pharmacologic doses of anti-inflammatory steroids. Thyroid and nutritional deficiencies should be corrected before initiating INCRELEX® treatment.

INCRELEX® is not a substitute for GH treatment.

Preprandial glucose monitoring should be considered at treatment initiation and until a well tolerated dose is established. If frequent symptoms of hypoglycemia or severe hypoglycemia occur, preprandial glucose monitoring should continue. The dosage of INCRELEX® should be individualized for each patient. The recommended starting dose of INCRELEX® is 0.04 to 0.08 mg/kg (40 to 80 μg/kg) twice daily by subcutaneous injection. If well-tolerated for at least one week, the dose may be increased by 0.04 mg/kg per dose, to the maximum dose of 0.12 mg/kg given twice daily. Doses greater than 0.12 mg/kg given twice daily have not been evaluated in children with Primary IGFD and, due to potential hypoglycemic effects, should not be used. If hypoglycemia occurs with recommended doses, despite adequate food intake, the dose should be reduced. INCRELEX® should be administered shortly before or after (±20 minutes) a meal or snack. If the patient is unable to eat shortly before or after a dose for any reason, that dose of INCRELEX® should be withheld. Subsequent doses of INCRELEX® should never be increased to make up for one or more omitted dose.

INCRELEX® injection sites should be rotated to a different site with each injection.

INCRELEX® should be administered using sterile disposable syringes and needles. The syringes should be of small enough volume that the prescribed dose can be withdrawn from the vial with reasonable accuracy.

Stability And Storage

Before Opening - Vials of INCRELEX® are stable when refrigerated [2° to 8° C (35° to 46° F)]. Avoid freezing the vials of INCRELEX®. Protect from direct light. Expiration dates are stated on the labels.

After Opening - Vials of INCRELEX® are stable for 30 days after initial vial entry when stored at 2° to 8° C (35° to 46° F). Avoid freezing the vials of INCRELEX®. Protect from direct light.

Vial contents should be clear without particulate matter. If the solution is cloudy or contains particulate matter, the contents must not be injected. INCRELEX® should not be used after its expiration date. Keep refrigerated and use within 30 days of initial vial entry. Remaining unused material should be discarded.

INCRELEX® is supplied as a 10 mg/mL sterile solution in multiple dose glass vials (40 mg/vial).

NDC-15054-1040-5

Manufactured for: Tercica, Inc., Brisbane, CA 94005 USA. By: Baxter Pharmaceutical Solutions LLC, Bloomington, IN 47402 USA. Revised: August 2007.

Last updated on RxList: 2/20/2009

As with all protein pharmaceuticals, some patients may develop antibodies to INCRELEX®. Anti-IGF-1 antibodies were present at one or more of the periodic assessments in 14 of 23 children with Primary IGFD treated for 2 years. However, no clinical consequences of these antibodies were observed (e.g., allergic reactions or attenuation of growth).

In clinical studies of 71 subjects with Primary IGFD treated for a mean duration of 3.9 years and representing 274 subject-years, no subjects withdrew from any clinical study because of adverse events. Adverse events considered related to INCRELEX® treatment that occurred in 5% or more of these study participants are listed below by organ class.

Metabolism and Nutrition Disorders:hypoglycemia

General Disorders and Administrative Site Conditions: lipohypertrophy, bruising

Infections and Infestations: otitis media, serous otitis media

Respiratory, Thoracic and Mediastinal Disorders: snoring, tonsillar hypertrophy

Nervous System Disorders: headache, dizziness, convulsions

Gastrointestinal Disorders:vomiting

Ear and Labyrinth Disorders: hypoacusis, fluid in middle ear, ear pain, abnormal tympanometry

Cardiac Disorders: cardiac murmur

Musculoskeletal and Connective Tissue Disorders: arthralgia, pain in extremity

Blood and Lymphatic System Disorders: thymus hypertrophy

Surgical and Medical Procedures: ear tube insertion

Hypoglycemia was reported by 30 subjects (42%) at least once during their course of therapy. Most cases of hypoglycemia were mild or moderate in severity. Five subjects had severe hypoglycemia (requiring assistance and treatment) on one or more occasion and 4 subjects experienced hypoglycemic seizures/loss of consciousness on one or more occasion. Of the 30 subjects reporting hypoglycemia, 14 (47%) had a history of hypoglycemia prior to treatment. The frequency of hypoglycemia was highest in the first month of treatment, and episodes were more frequent in younger children. Symptomatic hypoglycemia was generally avoided when a meal or snack was consumed either shortly (i.e., 20 minutes) before or after the administration of INCRELEX®.

Tonsillar hypertrophy was noted in 11 (15%) subjects in the first 1 to 2 years of therapy with lesser tonsillar growth in subsequent years. Tonsillectomy or tonsillectomy/adenoidectomy was performed in 7 subjects; 3 of these had obstructive sleep apnea, which resolved after the procedure in all 3 cases.

Intracranial hypertension occurred in three subjects. In two subjects the events resolved without interruption of INCRELEX® treatment. INCRELEX® treatment was discontinued in the third subject and resumed later at a lower dose without recurrence.

Mild elevations in the serum AST and LDH were found in a significant proportion of patients before and during treatment and no rise in levels of these serum enzymes led to treatment discontinuation. ALT elevations were occasionally noted during treatment. Renal and splenic lengths (measured by ultrasound) increased rapidly on INCRELEX® treatment during the first years of therapy. This lengthening slowed down subsequently; though in some patients, renal and/or splenic length reached or surpassed the 95^th percentile. Renal function (as defined by serum creatinine and calculated creatinine clearance) was normal in all patients, irrespective of renal growth. Elevations in cholesterol and triglycerides to above the upper limit of normal were observed before and during treatment. Echocardiographic evidence of cardiomegaly/valvulopathy was observed in a few individuals without associated clinical symptoms. Because of underlying disease and the lack of control group, the relation of the cardiac changes to drug treatment cannot be assessed.

Thickening of the soft tissues of the face was observed in several patients and should be monitored during INCRELEX® treatment.

No information provided.

Last updated on RxList: 2/20/2009

INCRELEX® contains benzyl alcohol as a preservative. Benzyl alcohol as a preservative has been associated with neurologic toxicity in neonates. If sensitivity to INCRELEX® occurs, treatment should be discontinued.

General

Treatment with INCRELEX® should be directed by physicians who are experienced in the diagnosis and management of patients with growth disorders.

Information for Patients

Patients and/or their parents should be instructed in the safe administration of INCRELEX®. INCRELEX® should be given shortly before or after (20 minutes on either side of) a meal or snack. INCRELEX® should not be administered when the meal or snack is omitted. The dose of INCRELEX® should never be increased to make up for one or more omitted doses. INCRELEX® therapy should be initiated at a low dose and the dose should be increased only if no hypoglycemia episodes have occurred after at least 7 days of dosing. If severe hypoglycemia or persistent hypoglycemia occurs on treatment despite adequate food intake, INCRELEX® dose reduction should be considered. Providers should educate patients and caregivers on how to recognize the signs and symptoms of hypoglycemia.

Patients and/or parents should be thoroughly instructed in the importance of proper needle disposal. A puncture-resistant container should be used for the disposal of used needles and/or syringes (consistent with applicable state requirements). Needles and syringes must not be reused. Please see PATIENT INFORMATION section for more details.

INCRELEX® has not been studied in children less than 2 years of age or in adults.

INCRELEX® should be administered shortly before or after a meal or snack, because it has insulin-like hypoglycemic effects. Special attention should be paid to small children because their oral intake may not be consistent. Patients should avoid engaging in any high-risk activities (e.g., driving, etc.) within 2-3 hours after dosing, particularly at the initiation of INCRELEX® treatment, until a well-tolerated dose of INCRELEX® has been established.

Lymphoid tissue (e.g., tonsillar) hypertrophy associated with complications, such as snoring, sleep apnea, and chronic middle-ear effusions have been reported with the use of INCRELEX®. Patients should have periodic examinations to rule out such potential complications and receive appropriate treatment if necessary.

Intracranial hypertension (IH) with papilledema, visual changes, headache, nausea and/or vomiting have been reported in patients treated with INCRELEX®, as they have been reported with therapeutic growth hormone administration. IH-associated signs and symptoms resolved after interruption of dosing. Funduscopic examination is recommended at the initiation and periodically during the course of INCRELEX® therapy.

Slipped capital femoral epiphysis and progression of scoliosis can occur in patients who experience rapid growth. These conditions and other symptoms and signs known to be associated with GH treatment in general should be monitored during INCRELEX® treatment.

As with any exogenous protein administration, local or systemic allergic reactions may occur. Parents and patients should be informed that such reactions are possible and that if an allergic reaction occurs, treatment should be interrupted and prompt medical attention should be sought.

Carcinogenesis, mutagenesis, impairment of fertility

INCRELEX® was administered subcutaneously to Sprague Dawley rats at doses of 0, 0.25, 1, 4, and 10 mg/kg/day for up to 2 years. An increased incidence of adrenal medullary hyperplasia and pheochromocytoma was observed in male rats at doses of 1 mg/kg/day and above (v 1 times the clinical exposure with the maximum recommended human dose [MRHD] based on AUC) and female rats at all dose levels ( ≥ 0.3 times the clinical exposure with the MRHD based on AUC). An increased incidence of keratoacanthoma in the skin was observed in male rats at doses of 4 and 10mg/kg/day ( ≥ 4 times the MRHD) and in female rats treated with 10 mg/kg/day (7 times the MRHD based on AUC). An increased incidence of mammary gland carcinoma in both male and female rats was observed in animals treated with 10mg/kg/day (7 times the MRHD based on AUC). Based on excess mortality secondary to IGF-1 induced hypoglycemia, these skin and mammary tumor findings were only observed at doses that exceeded the maximum tolerated dose (MTD).

Mutagenesis

INCRELEX® was not clastogenic in the in vitro chromosome aberration assay and the in vivo mouse micronucleus assay.

Impairment of fertility

INCRELEX® was administered intravenously to rats at doses of 0.25, 1, and 4 mg/day to conduct the fertility study. No effects on fertility were observed in male or female rats treated with doses up to 4 mg/kg/day (4 times the clinical exposure with the MRHD based on AUC.)

Pregnancy Category C

Embryo-fetal toxicity studies were conducted in Sprague Dawley rats with doses of 1, 4, and 16 mg/kg/day, and in New Zealand White rabbits with doses of 0.125, 0.5, and 2 mg/kg/day administered intravenously. No embryo-fetal developmental abnormalities were observed in rats with doses up to 16 mg/kg/day (20 times the MRHD based on body surface area [BSA] comparison). In the rabbit study, the NOAEL for maternal toxicity was 2 mg/kg (8 times the MRHD based on BSA) and the NOAEL for fetal toxicity was 0.5 mg/kg (2 times the MRHD based on BSA). INCRELEX® displayed no teratogenicity at doses up to 2 mg/kg (8 times the MRHD based on BSA).

The effects of INCRELEX® on an unborn child have not been studied.

Therefore, there is insufficient medical information to determine whether there are significant risks to a fetus.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when INCRELEX® is administered to a nursing woman.

Geriatric Use

The safety and effectiveness of INCRELEX® in patients aged 65 and over has not been evaluated in clinical studies.

Last updated on RxList: 2/20/2009

There is no clinical experience with overdosage of INCRELEX®. Based on known pharmacological effects, acute overdosage would be predicted to lead to hypoglycemia. Long-term overdosage may result in signs and symptoms of acromegaly. Treatment of acute overdose of INCRELEX® should be directed at reversing hypoglycemia. Oral glucose or food should be consumed. If the overdose results in loss of consciousness, intravenous glucose or parenteral glucagon may be required to reverse the hypoglycemic effects.

INCRELEX® should not be used for growth promotion in patients with closed epiphyses.

INCRELEX® is contraindicated in the presence of active or suspected neoplasia, and therapy should be discontinued if evidence of neoplasia develops.

Intravenous administration of INCRELEX® is contraindicated.

INCRELEX® should not be used by patients who are allergic to mecasermin (IGF-1) or any of the inactive ingredients in INCRELEX®.

Last updated on RxList: 2/20/2009

General

Insulin-like growth factor-1 (IGF-1) is the principal hormonal mediator of statural growth. Under normal circumstances, growth hormone (GH) binds to its receptor in the liver, and other tissues, and stimulates the synthesis/secretion of IGF-1. In target tissues, the Type 1 IGF-1 receptor, which is homologous to the insulin receptor, is activated by IGF-1, leading to intracellular signaling which stimulates multiple processes leading to statural growth. The metabolic actions of IGF-1 are in part directed at stimulating the uptake of glucose, fatty acids, and amino acids so that metabolism supports growing tissues.

The following actions have been demonstrated for endogenous human IGF-1:

Tissue Growth – 1) Skeletal growth: Occurs at the cartilage growth plates of the epiphyses of bones where stem cells divide to produce new cartilage cells or chondrocytes. The growth of chondrocytes is under the control of IGF-1 and GH. The chondrocytes become calcified so that new bone is formed allowing the length of the bones to increase. This results in skeletal growth until the cartilage growth plates fuse at the end of puberty. 2) Cell growth: IGF-1 receptors are present on most types of cells and tissues. IGF-1 has mitogenic activities that lead to an increased number of cells in the body. 3) Organ growth: Treatment of IGF-1 deficient rats with rhIGF-1 results in whole body and organ growth.

Carbohydrate Metabolism – IGF-1 suppresses hepatic glucose production and stimulates peripheral glucose utilization and therefore has a hypoglycemic potential. IGF-1 has inhibitory effects on insulin secretion.

Pharmacokinetics

Absorption

While the bioavailability of rhIGF-1 after subcutaneous administration in healthy subjects has been reported to be close to 100%, the absolute bioavailability of INCRELEX® given subcutaneously to subjects with primary insulin-like growth factor-1 deficiency (Primary IGFD) has not been determined.

Distribution

In blood, IGF-1 is bound to six IGF binding proteins, with > 80% bound as a complex with IGFBP-3 and an acid-labile subunit. IGFBP-3 is greatly reduced in subjects with severe Primary IGFD, resulting in increased clearance of IGF-1 in these subjects relative to healthy subjects. The total IGF-1 volume of distribution after subcutaneous administration in subjects with severe Primary IGFD is estimated to be 0.257 (±0.073) L/kg at an INCRELEX® dose of 0.045mg/kg, and is estimated to increase as the dose of INCRELEX® increases.

Metabolism

Both the liver and the kidney have been shown to metabolize IGF-1.

Excretion

The mean terminal t1/2 after single subcutaneous administration of 0.12 mg/kg INCRELEX® in pediatric subjects with severe Primary IGFD is estimated to be 5.8 hours. Clearance of INCRELEX® is inversely proportional to IGF binding protein-3 (IGFBP-3) levels and CL/F is estimated to be 0.04 L/hr/kg at 3 mcg/mL IGFBP-3.

Summary of INCRELEX® Single-Dose Pharmacokinetic Parameters in Children with Severe Primary IGFD (0.12 mg/kg, SC)

Mean Total IGF-1 Concentration after a Single Subcutaneous Dose of INCRELEX® in Children with Severe Primary IGFD (0.06 mg/kg and 0.12 mg/kg, n = 3 per group)

Special Populations

Geriatric

The pharmacokinetics of INCRELEX® have not been studied in subjects greater than 65 years of age.

Gender

In children with Primary IGFD and in healthy adults there were no apparent differences between males and females in the pharmacokinetics of INCRELEX®.

Race

No information is available.

Renal insufficiency

No studies have been conducted in Primary IGFD children with renal impairment.

Hepatic insufficiency

No studies have been conducted to determine the effect of hepatic impairment on the pharmacokinetics of rhIGF-1.

Clinical Trials

Effects of INCRELEX® Treatment in Children with Severe Primary Insulin-like Growth Factor-1 Deficiency (Primary IGFD)

Five clinical studies (four open-label and one double-blind, placebo-controlled), with subcutaneous (SC) doses of INCRELEX® generally ranging from 0.06 to 0.12 mg/kg (60 to 120 μg/kg) administered twice daily (BID), were conducted in 71 pediatric subjects with severe Primary IGFD. Patients were enrolled in the trials on the basis of extreme short stature, slow growth rates, low IGF-1 serum concentrations, and normal growth hormone secretion. Data from these 5 clinical studies were pooled for a global efficacy and safety analysis. Baseline characteristics for the patients evaluated in the primary and secondary efficacy analyses were (mean, SD): chronological age (years): 6.7 ±3.8; height (cm): 84.8 ±15.3 cm; height standard deviation score (SDS): -6.7 ±1.8; height velocity (cm/yr): 2.8 ±1.8; height velocity SDS: -3.3 ±1.7; IGF-1 (ng/mL): 21.6 ± 20.6; IGF-1 SDS: -4.3 ±1.6; and bone age (years): 4.2 ±2.8. Sixty-one subjects had at least one year of treatment. Fifty-three (87%) had Laron Syndrome; 7 (11%) had GH gene deletion, and 1 (2%) had neutralizing antibodies to GH. Thirty-seven (61%) of the subjects were male; forty-eight (79%) were Caucasian. Fifty-six (92%) of the subjects were pre-pubertal at baseline.

Annual results for height velocity, height velocity SDS, and height SDS are shown in Table 1. Pre-treatment height velocity data were available for 58 subjects. The height velocities at a given year of treatment were compared by paired t-tests to the pre-treatment height velocities of the same subjects completing that treatment year.

Table 1: Annual Height Results by Number of Years Treated with INCRELEX®

Forty-nine subjects were included in an analysis of the effects of INCRELEX® on bone age advancement. The mean ±SD change in chronological age was 4.9 ±3.4 years and the mean ±SD change in bone age was 5.3 ±3.4 years.

Last updated on RxList: 2/20/2009

INCRELEX®
(EENK-ruh-lex)
(mecasermin [rDNA origin] injection)

Read the Patient Information that comes with INCRELEX® before your child starts taking INCRELEX® and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your child's doctor about your child's condition or treatment.

What is INCRELEX®

INCRELEX® is a liquid that contains man-made insulin-like growth factor-1 (IGF-1), which is the same as the IGF-1 made by your body. INCRELEX® is used to treat children who are very short for their age because their bodies do not make enough IGF-1. This condition is called primary IGF-1 deficiency. IGF-1 should not be used instead of growth hormone. INCRELEX® has not been studied in children under 2 years of age.

Who Should Not Use INCRELEX®?

Your child should not take INCRELEX® if your child:

• Has finished growing (the bone growth plates are closed)
• Has cancer
• Has other causes of growth failure
• Is allergic to mecasermin or any of the inactive ingredients in INCRELEX®. Check with your child's doctor if you are not sure.

Your child should never receive INCRELEX® through a vein.

What Should I Tell My Child's Doctor Before My Child Starts INCRELEX®?

Tell your child's doctor about all of your child's health conditions, including if your child:

• Has diabetes
• Has kidney problems
• Has liver problems
• Has a curved spine (scoliosis)
• Is pregnant or breast-feeding.

Tell your child's doctor about all the medicines your child takes, including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your child's doctor if your child takes insulin or other anti-diabetes medicines. A dose adjustment may be needed for these medicines.

How Should My Child Use INCRELEX®?

• Use INCRELEX® exactly as prescribed for your child. Your doctor or nurse should teach you how to inject INCRELEX®. Do not give your child INCRELEX® unless you understand all of the instructions. See the "Instructions for Use" at the end of this leaflet.
• Inject INCRELEX® under your child's skin shortly (20 minutes) before or after a meal or snack. Skip your child's dose of INCRELEX® if your child cannot eat for any reason. Do not make up the missed dose by giving two doses the next time.
• Inject INCRELEX® just below the skin in your child's upper arm, upper leg (thigh), stomach area (abdomen), or buttocks. Never inject it into a vein or muscle. Change the injection site for each injection ("rotate the injection site").
• Only use INCRELEX® that is clear and colorless. If your child's INCRELEX® is cloudy or slightly colored, return it for a replacement.

What are the Possible Side Effects of INCRELEX®?

INCRELEX® may cause the following side effects, which can be serious:

• Low blood sugar (hypoglycemia). INCRELEX® may lower blood sugar levels like insulin. It is important to only give your child INCRELEX® right before or right after (20 minutes on either side of) a snack or meal to reduce the chances of low blood sugar. Do not give your child INCRELEX® if your child is sick or cannot eat. Signs of low blood sugar are:
  • Dizziness
  • Tiredness
  • Restlessness
  • Hunger
  • Irritability
  • Trouble concentrating
  • Sweating
  • Nausea
  • Fast or irregular heartbeat
• Severe hypoglycemia may cause unconsciousness, seizures, or death. If you take INCRELEX®, you should avoid participating in high risk activities (such as driving) within 2 to 3 hours after INCRELEX® injection, especially at the beginning of INCRELEX® treatment.
  Before beginning treatment with INCRELEX® your doctor or nurse will explain to you how to treat hypoglycemia. You/your child should always have a source of sugar such as orange juice, glucose gel, candy, or milk available in case symptoms of hypoglycemia occur. For severe hypoglycemia, if your child is not responsive and cannot drink sugar-containing fluids, you should give an injection of glucagon. Your doctor or nurse will instruct you how to give the injection. Glucagon raises the blood sugar when it is injected. It is important that your child have a well-balanced diet including protein and fat such as meat and cheese in addition to sugar-containing foods.
• Enlarged tonsils. INCRELEX® may enlarge your child's tonsils. Some signs of enlarged tonsils include: snoring, difficulty breathing or swallowing, sleep apnea (a condition where breathing stops briefly during sleep), or fluid in the middle-ear. Sleep apnea can cause excessive daytime sleepiness. Call your doctor should these symptoms bother your child. Your doctor should do regular exams to check your child's tonsils.
• Increased pressure in the brain (intracranial hypertension). INCRELEX®, like growth hormone, can sometimes cause a temporary increase in pressure within the brain. The symptoms of intracranial hypertension can include headache and nausea with vomiting. Tell your doctor if your child has headache with vomiting. Your doctor can then check to see if intracranial hypertension is present. If it is present, your doctor may decide to temporarily reduce or discontinue INCRELEX® therapy. INCRELEX® therapy may be started again after the episode is over.
• A bone problem called slipped capital femoral epiphysis. This happens when the top of the upper leg (femur) slips apart. Get medical attention for your child right away if your child develops a limp or has hip or knee pain.
• Worsened scoliosis (caused by rapid growth). If your child has scoliosis, your child will need to be checked often for an increase in the curve of the spine.
• Allergic reactions. Your child may have a mild or serious allergic reaction with INCRELEX®. Call your child's doctor right away if your child gets a rash or hives. Get medical help immediately if your child has trouble breathing or goes into shock.

INCRELEX® can cause reactions at the injection site including:

• Loss of fat (lipoatrophy)
• Increase of fat (lipohypertrophy)
• Pain, redness, or bruising

Injection site reactions can be avoided by changing the injection site at each injection ("injection site rotation").

Call your child's doctor if your child has side effects that are bothersome or that do not go away.

These are not all the side effects of INCRELEX®. Ask your child's doctor or pharmacist for more information.

How Should I Store INCRELEX®

• Before Opening - Store new unopened vials of INCRELEX® in the refrigerator (not the freezer) between 35° to 46°F (2° to 8°C). Do not freeze INCRELEX®. Keep INCRELEX® out of direct heat and bright light. If a vial freezes, throw it away.
• After Opening - Once a vial of INCRELEX® is opened, you can keep it in the refrigerator between 35° to 46°F (2° to 8°C) for 30 days after you start using the vial. Do not freeze INCRELEX®. Keep INCRELEX® out of direct heat and bright light. If a vial freezes, throw it away.

Keep INCRELEX® and all medicines out of reach of children.

General Information About INCRELEX®

Medicines are sometimes prescribed for conditions other than those described in patient information leaflets. Do not give INCRELEX® to your child for a condition for which it was not prescribed. Do not give INCRELEX® to a person other than your child. It may be harmful.

This leaflet summarizes the most important information about INCRELEX®. If you would like more information, talk to your child's doctor. You can also ask your child's doctor or pharmacist for information that is written for health professionals. More information is available at 1-866-TERCICA (1-866-837-2422).

What are the Ingredients in INCRELEX®?

Active ingredient: mecasermin

Inactive ingredients: sodium chloride, polysorbate 20, benzyl alcohol, and acetate.

INSTRUCTIONS FOR USE

INCRELEX® should be administered using sterile disposable syringes and needles. The syringes should be of small enough volume that the prescribed dose can be withdrawn from the vial with reasonable accuracy.

Preparing the Dose:

1. Wash your hands before getting INCRELEX® ready for your child's injection.
2. Use a new disposable needle and syringe every time you give a dose. Use syringes and needles only once. Throw them away properly. Never share needles and syringes.
3. Check the liquid to make sure it is clear and colorless. Do not use after the expiration date or if it is cloudy or if you see particles.
4. If you are using a new vial, remove the protective cap. Do not remove the rubber stopper.
5. Wipe the rubber stopper of the vial with an alcohol swab to prevent contamination of the vial by germs that may be introduced by repeated needle insertions (see Figure 1).
6. Before putting the needle into the vial, pull back on plunger to draw air into the syringe equal to the INCRELEX® dose. Put the needle through the rubber top of the vial and push the plunger to inject air into the vial (see Figure 2).
7. Leave the syringe in the vial and turn both upside down. Hold the syringe and vial firmly (see Figure 3).
8. Make sure the tip of the needle is in the liquid (see Figure 4). Pull the plunger to withdraw the correct dose into the syringe (see Figure 5).
9. Before you take the needle out of the vial, check the syringe for air bubbles. If bubbles are in the syringe, hold the vial and syringe with needle straight up and tap the side of the syringe until the bubbles float to the top. Push the bubbles out with the plunger and draw liquid back in until you have the correct dose (see Figure 6).
10. Remove the needle from the vial. Do not let the needle touch anything. You are now ready to inject (see Figure 7).

Injecting the Dose:

Inject INCRELEX® as instructed by your child's doctor.

Do not give the INCRELEX® injection if your child is unable to eat within 2O minutes before or after the injection.

1. Decide on an injection area - upper arm, thigh, buttock, or abdomen (see below). The injection site should be changed for each injection ("rotate the injection site").
2. Use alcohol or soap and water to clean the skin where you are going to inject your child. The injection site should be dry before you inject.
3. Lightly pinch the skin. Stick the needle in the way your child's doctor showed you. Release the skin (see Figure A).
4. Slowly push in the plunger of the syringe all the way, making sure you have injected all the liquid. Pull the needle straight out and gently press on the spot where you injected your child with gauze or a cotton ball for a few seconds. Do not rub the area (see Figure B).
5. Follow your child's doctor's instructions for throwing away the needle and syringe. Do not recap the syringe. Used needle and syringe should be placed in a sharps container (such as a red biohazard container), hard plastic container (such as a detergent bottle), or metal container (such as an empty coffee can). Such containers should be sealed and disposed of properly.

For additional information, call 1-866-TERCICA (1-866-837-2422). Revised: October 2007

Last updated on RxList: 2/20/2009