COMPOSITION:
One vial contains Powder for injection of Dynalan R3 IGF-1 (r DNA origin) 100 mcg and other ingredients: 40mg Mannitol, 3mg sodium phosphate(0.36 monobasis-sodium phosphate and 2.64 mg biradical-sodium phosphate).

PHARMACEUTICAL FORM:
Powder for injection is prepared with water solution for subcutaneous (s.c.) administration.

PHARMACO-THERAPEUTIC GROUP:
Dynalan R3 IGF-1 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. Dynalan R3 IGF-1 promotes the patients who suffering from Alzheimer's disease, Liver cirrhosis, Heart failure or Brian injury rehabilitation. Dynalan R3 IGF-1 can also enhance the body immune function and Brain memory, promotes metabolic, improve osteoporosis and sleep.

INTRODUCTION:
Dynalan R3 IGF-1 is produced by gene recombination DNA technology. It has 13 additional amino acids to the N-terminus of IGF-1 , which force the over expressed recombinant peptide into inclusion bodies and stabilize the peptide. In addition, the amino acid in the Dynalan R3 IGF-1 corresponding to the third amino acid of human IGF-1 nature peptide is mutated from Glu to Arg, which alters the combination between Dynalan R3 IGF-1 and IGFBP and advances the combination to IGF-1 receptor. Its molecular weight is 9110 daltons. Dynalan R3 IGF-1 is an asepsis and freeze-dried powder. It can be used in subcutaneous injection diluted with water. After dilution, this substance is close to liquid state.

INDICATIONS:
When certain children are much smaller than others their own age, it can be caused by a deficiency of insulin-like growth factor-1(IGF-1), a naturally occurring hormone that is secreted from the liver and other tissues in response to growth hormone (GH).A majority of the growth-promoting effects of GH are actually due to IGF-1 acting on target cells. In some cases, young people have enough GH, but their IGF-1 levels still remain low. This creates a condition called Severe Primary IGFD deficiency or, more simply, Severe Primary IGFD. A physician may diagnose Severe Primary IGFD when a child's height is significantly different from other children, and tests show that IGF-1 levels are abnormally low when growth hormone levels are normal or elevated. It is estimated that approximately 6,000 children in the United States have this condition.

CONTRAINDICATIONS:
Dynalan R3 IGF-1 should not be used for growth promotion in patients with closed epiphyses. Dynalan R3 IGF-1 is contraindicated in the presence of active or suspected neoplasia, and therapy should be discontinued if evidence of neoplasia develops. Intravenous administration of Dynalan R3 IGF-1 is contraindicated. Dynalan R3 IGF-1 should not be used by patients who are allergic to mecasermin (IGF-1) or any of the inactive ingredients in Dynalan R3 IGF-1.

WARNINGS AND PRECAUTIONS:
If sensitivity to Dynalan R3 IGF-1 occurs, treatment should be discontinued.
Dynalan R3 IGF-1 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 Dynalan R3 IGF-1 treatment, until a well-tolerated dose of Dynalan R3 IGF-1 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 Dynalan R3 IGF-1. 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 Dynalan R3 IGF-1, 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 Dynalan R3 IGF-1 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 Dynalan R3 IGF-1 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;
The safety and effectiveness of Dynalan R3 IGF-1 in patients aged 65 and over has not been evaluated in clinical studies.

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES:
The ability to react is not influenced by Dynalan R3 IGF-1.

DOSAGE AND ADMINISTRATION:
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 Dynalan R3 IGF-1 should be individualized for each patient. The recommended starting dose of Dynalan R3 IGF-1 is 50mcg per day by subcutaneous injection. If well-tolerated for at least one week, the dose may be increased by 100mcg per day, to the maximum dose 200mcg given twice daily. 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. Dynalan R3 IGF-1 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 Dynalan R3 IGF-1 should be withheld. Subsequent doses of Dynalan R3 IGF-1 should never be increased to make up for one or more omitted dose. Dynalan R3 IGF-1 injection sites should be rotated to a different site with each injection. Dynalan R3 IGF-1 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.

OVERDOSAGE:
There is no clinical experience with overdosage of Dynalan R3 IGF-1. 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 Dynalan R3 IGF-1 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.

ADVERSE REACTIONS:
As with all protein pharmaceuticals, some patients may develop antibodies to Dynalan R3 IGF-1. 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 Dynalan R3 IGF-1 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

Special populations:
Geriatric - The pharmacokinetics of Dynalan R3 IGF-1 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 Dynalan R3 IGF-1.
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.

INCOMPATIBILITIES:
Incompatibilities have not been reported for combined use of Dynalan R3 IGF-1 with other medicines or medical solution.

STORAGE:
Before Opening - Store new unopened vials of Dynalan R3 IGF-1 in the refrigerator (not the freezer) between 35° to 46°F (2° to 8°C). Do not freeze Dynalan R3 IGF-1. Keep Dynalan R3 IGF-1 out of direct heat and bright light. If a vial freezes, throw it away.
After Opening - Once a vial of Dynalan R3 IGF-1 is opened, you can keep it in the refrigerator between 35° to 4°F (2° to 8°C) for 30 days after you start using the vial. Do not freeze Dynalan R3 IGF-1. Keep Dynalan R3 IGF-1 out of direct heat and bright light. If a vial freezes, throw it away.

INSTRUCTIONS FOR USE/HANDLING:
Vials: Add injection water to vial with powder for injection. Gently dissolve the drug with a slow, swirling motion. Do not shake vigorously, which might cause denaturation of the active ingredient.
Injection: Wipe the selected injection site with alcohol swab.
Injection angel should be 45~90 degree.
Slowly inject the injection.

EXPIRY:
2 (two) years