8-0905-26-001-2_v1-13:Layout 1 2009-08-18 6:00 AM Page 1 Length: Max 29 mm (100%) Special warnings and precautions for use
The following substances may reduce the patient's insulin
eral is the most frequently occurring undesirable effect. It may The use of dosages which are inadequate or discontinuation of requirements:
occur if the insulin dose is too high in relation to the insulin Local hypersensitivity reactions (redness, swelling and itching treatment, especially in insulindependent diabetics, may lead to Oral hypoglycaemic agents (OHAs), octreotide, monoamine oxi- requirement. Severe hypoglycaemia may lead to unconsciousness at the injection site) may occur during treatment with The individual insulin requirement in adults and children is usually hyperglycaemia and diabetic ketoacidosis; conditions which are dase inhibitors (MAOIs), non-selective beta-adrenergic blocking and/or convulsions and may result in temporary or permanent insulin. These reactions are usually transitory and normally between 0.5 and 1.0 U/kg/day. In a meal-related treatment agents, angiotensin converting enzyme (ACE) inhibitors, salicy- impairment of brain function or even death. In clinical trials and they disappear during continued treatment.
50 - 70% of this requirement may be provided by NovoRapid® Patients, whose blood glucose control is greatly improved, e.g. by lates, alcohol, anabolic steroids and sulphonamides.
during marketed use the frequency varies with patient popula- and the remainder by intermediate-acting or long-acting insulin.
General disorders and administration site conditions
intensified insulin therapy, may experience a change in their usual The following substances may increase the patient's insulin
tion and dose regimens, therefore no specific frequency can be For the use only of registered medical practitioner warning symptoms of hypoglycaemia, and should be advised requirements:
Oedema may occur upon initiation of insulin therapy. These Colour: PMS 280C
NovoRapid® is administered subcutaneously in the abdominal Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, During clinical trials the overall rates of hypoglycaemia did not symptoms are usually of transitory nature.
wall, the thigh, the deltoid region or the gluteal region. Injection A consequence of the pharmacodynamics of rapid-acting insulin differ between patients treated with insulin aspart compared to sites should be rotated within the same region. When injected analogues is that if hypoglycaemia occurs, it may occur earlier Beta-blocking agents may mask the symptoms of hypoglycaemia.
subcutaneously into the abdominal wall, the onset of action will after an injection when compared with soluble human insulin.
Alcohol may intensify and prolong the hypoglycaemic effect of Frequencies of adverse drug reactions from clinical trials, which A specific overdose for insulin cannot be defined however NovoRapid® Penfill®
occur within 10 – 20 minutes of injection. The maximum effect is NovoRapid® should be administered in immediate relation to a by an overall judgement are considered related to insulin aspart hypoglycaemia may develop over sequential stages if too Solution for injection in a cartridge for s.c. use.
exerted between 1 and 3 hours after the injection. The duration meal. The rapid onset of action should therefore be considered in Pregnancy and lactation
are listed below. The frequencies are defined as: Uncommon high doses relative to the patient’s requirement are adminis- Monocomponent, biosynthetic, (r-DNA Origin) of action is 3 to 5 hours. As with all insulins, the duration of patients with concomitant diseases or medication where a NovoRapid® (insulin aspart) can be used in pregnancy. Data from (>1/1,000, <1/100) and rare (>1/10,000, <1/1,000). Isolated action will vary according to the dose, injection site, blood flow, delayed absorption of food might be expected.
two randomised controlled clinical trials (157 and 14 insulin spontaneous cases are presented as very rare defined as • Mild hypoglycaemic episodes can be treated by oral Concomitant illness, especially infections, usually increases the (<1/10,000), including isolated reports.
administration of glucose or sugary products. It is Qualitative and quantitative composition
temperature and level of physical activity. As with all insulins, aspart-exposed pregnancies respectively) do not indicate any Within each frequency grouping, undesirable effects are pre- therefore recommended that the diabetic patient subcutaneous injection in the abdominal wall ensures a faster adverse effect of insulin aspart on pregnancy or on the health of When patients are transferred between different types of insulin sented in order of decreasing seriousness.
constantly carry sugar containing products * produced by recombinant DNA technology in absorption than other injection sites. However, the faster onset of the foetus/newborn when compared to insulin human (see Phar- products, the early warning symptoms of hypoglycaemia may • Severe hypoglycaemic episodes, where the patient has action compared to soluble human insulin is maintained regard- Immune system disorders
change or become less pronounced than those experienced with become unconscious, can be treated by glucagon (0.5 to One unit of insulin aspart corresponds to 6 nmol, 0.035 mg Intensified blood glucose control and monitoring of pregnant 1 mg) given intramuscularly or subcutaneously by a If necessary, NovoRapid® may also be administered intravenously women with diabetes (type 1 diabetes, type 2 diabetes or gesta- which should be carried out by healthcare professionals.
Transferring a patient to a new type or brand of insulin should be tional diabetes) are recommended throughout pregnancy and trained person, or glucose given intravenously by a Pharmaceutical form
Symptoms of generalised hypersensitivity may include generalised NovoRapid® may be used for Continuous Subcutaneous Insulin done under strict medical supervision. Changes in strength, when contemplating pregnancy. Insulin requirements usually fall medical professional. Glucose must also be given skin rash, itching, sweating, gastrointestinal upset, angioneurotic Infusion (CSII) in pump systems suitable for insulin infusion. CSII brand, type, species (animal, human, human insulin analogue) in the first trimester and increase subsequently during the second intravenously if the patient does not respond to glucagon NovoRapid® is a clear, colourless, aqueous, solution.
oedema, difficulties in breathing, palpitation and reduction in should be administered in the abdominal wall. Infusion sites and/or method of manufacture may result in a change in dosage.
and third trimesters. After delivery, insulin requirements return Patients taking NovoRapid® may require an increased number of blood pressure. Generalised hypersensitivity reactions are poten- Upon regaining consciousness, administration of oral Clinical particulars
When used with an insulin infusion pump NovoRapid® should daily injections or a change in dosage from that used with their There are no restrictions on treatment with NovoRapid® during carbohydrate is recommended for the patient in order to Therapeutic indications
not be mixed with any other insulin. Patients using CSII should be usual insulins. If an adjustment is needed, it may occur with the lactation. Insulin treatment of the nursing mother presents no Nervous system disorders
Treatment of patients with diabetes mellitus.
comprehensively instructed in the use of the pump system and first dose or during the first several weeks or months.
risk to the baby. However, the NovoRapid® dosage may need to Pharmacological properties
Posology and method of administration
use the correct reservoir and tubing for the pump. The infusion As with any insulin, injection site reactions may occur and include Fast improvement in blood glucose control may be associated NovoRapid® has a faster onset and a shorter duration of set (tubing and cannula) should be changed in accordance with pain, itching, hives, swelling and inflammation. Continuous rota- with a condition termed acute painful neuropathy, which is usu- Pharmacodynamic properties
Effects on ability to drive and use machines
the instructions in the product information supplied with the tion of the injection site within a given area may help to reduce Pharmacotherapeutic group: Insulins and analogues for The patient’s ability to concentrate and react may be impaired as Due to the faster onset of action, NovoRapid® should gener- infusion set. Patients administering NovoRapid® by CSII must or prevent these reactions. Reactions usually resolve in a few days injection, fast-acting. ATC code A10A B05.
a result of hypoglycaemia. This may constitute a risk in situations Eye disorders
ally be given immediately before a meal. When necessary, have alternative insulin available in case of pump system failure.
to a few weeks. On rare occasions, injection site reactions may The blood glucose lowering effect of insulin occurs when where these abilities are of special importance (e.g. driving a car NovoRapid® can be given soon after a meal. Due to the Renal or hepatic impairment may reduce the patient's insulin require discontinuation of NovoRapid®.
the molecules facilitate the uptake of glucose by binding to Refraction anomalies may occur upon initiation of insulin therapy.
shorter duration, NovoRapid® has a lower risk of causing Omission of a meal or unplanned, strenuous physical exercise insulin receptors on muscle and fat cells - and simultane- Patients should be advised to take precautions in order to avoid These symptoms are usually of transitory nature.
Careful glucose monitoring and dose adjustments of insulin ously inhibit the output of glucose from the liver.
hypoglycaemia whilst driving, this is particularly important in aspart are recommended in these patients.
Adjustment of dosage may also be necessary if patients under- NovoRapid® produces a more rapid onset of action com- those who have reduced or absent awareness of the warning Long-term improved glycaemic control decreases the risk of pro- NovoRapid® can be used in children in preference to soluble take increased physical activity or change their usual diet. Exercise pared to soluble human insulin, together with a lower glu- Dosage of NovoRapid® is individual and determined on the signs of hypoglycaemia or have frequent episodes of hypogly- gression of diabetic retinopathy. However, intensification of human insulin when a rapid onset of action might be beneficial.
taken immediately after a meal may increase the risk of hypogly- cose concentration, as assessed within the first four hours basis of the physician’s advice in accordance with the needs caemia. The advisability of driving should be considered in these insulin therapy with abrupt improvement in glycaemic control For example, in the timing of the injections in relation to meals.
after a meal. NovoRapid® has a shorter duration of action of the patient. It should normally be used in combination may be associated with worsening of diabetic retinopathy.
compared to soluble human insulin after subcutaneous with intermediate-acting or long-acting insulin given at least Contraindications
Interaction with other medicinal products and other forms
Undesirable effects
Skin and subcutaneous tissue disorders
• Hypersensitivity to the active substance or to any of the of interaction
Adverse drug reactions observed in patients using NovoRapid® A number of medicinal products are known to interact with glu- are mainly dose-dependent and due to the pharmacologic effect Lipodystrophy may occur at the injection site as a consequence of of insulin. As for other insulin products, hypoglycaemia, in gen- failure to rotate injection sites within an area.
8-0905-26-001-2_v1-13:Layout 1 2009-08-18 6:00 AM Page 2 When NovoRapid® is injected subcutaneously, the onset of ments as well as a significant improvement in post prandial glu- Renal impairment: A single dose pharmacokinetic study of insulin Special precautions for disposal and other handling
action will occur within 10-20 minutes of injection. The cose control in the insulin aspart treated group.
aspart in 18 subjects with renal function ranging from normal to NovoRapid® Penfill® should only be used in combination with maximum effect is exerted between 1 and 3 hours after Insulin aspart is equipotent to soluble human insulin on a molar severely impaired was performed. No apparent effect of creati- products that are compatible with them and allow the Penfill® to injection. The duration of action is 3 to 5 hours.
give an injection are: the front of the waist (abdomen); the but- Adults. Clinical trials in patients with Type 1 diabetes have tocks; the front of the thighs or upper arms. The insulin will work Pharmacokinetic properties
aspart was found. Data were limited in subjects with moderate NovoRapid® Penfill® is for use by one person only. The cartridge demonstrated a lower postprandial blood glucose with more quickly if injected around the waist.
In NovoRapid® substitution of the amino acid proline with aspar- and severe renal impairment. Subjects with renal failure necessi- NovoRapid® compared to soluble human insulin. In two NovoRapid® Penfill® is designed to be used with Novo Nordisk tic acid at position B28 reduces the tendency to form hexamers tating dialysis treatment were not investigated.
NovoRapid® Penfill® is designed to be used with the long-term open label trials in patients with Type 1 diabetes insulin delivery systems and NovoFine® needles. If you are treated as observed with soluble human insulin. NovoRapid® is therefore Novo Nordisk insulin delivery system and NovoFine® needles.
Preclinical safety data
comprising 1070 and 884 patients, respectively, NovoRapid® with NovoRapid® Penfill® and another insulin Penfill® cartridge, more rapidly absorbed from the subcutaneous layer compared to NovoRapid® may be used in an infusion pump system (CSII). Tub- Non-clinical data reveal no special hazard for humans based on reduced glycosylated haemoglobin by 0.12 [95% C.I. 0.03; you must use two insulin delivery systems, one for each type of ings in which the inner surface materials are made of polyethy- conventional studies of safety pharmacology, repeated dose toxi- 0.22] percentage points and by 0.15 [95% C.I. 0.05; 0.26] The time to maximum concentration is, on average, half of that lene or polyolefin have been evaluated and found compatible city, genotoxicity and toxicity to reproduction.
percentage points compared to human insulin; a difference Do not refill NovoRapid® Penfill®.
for soluble human insulin. A mean maximum plasma concentra- In in vitro tests, including binding to insulin and IGF-1 receptor As a precautionary measure, always carry a spare insulin delivery tion of 492 ± 256 pmol/l was reached 40 (interquartile range: For intravenous use, infusion systems with NovoRapid® 100 U/ml sites and effects on cell growth, insulin aspart behaved in a man- Elderly. A randomised, double-blind cross-over PK/PD trial device in case your Penfill® is lost or damaged.
30-40) minutes after a subcutaneous dose of 0.15 U/kg body- at concentrations from 0.05 U/ml to 1.0 U/ml insulin aspart in the ner that closely resembled human insulin. Studies also demon- comparing insulin aspart with soluble human insulin was weight in Type 1 diabetic patients. The insulin concentrations infusion fluids 0.9% sodium chloride, 5% dextrose or 10% dex- strate that the dissociation of binding to the insulin receptor of How to inject this insulin
performed in elderly patients with type 2 diabetes (19 returned to baseline about 4 to 6 hours after dose. The absorp- trose inclusive 40 mmol/l potassium chloride using polypropylene insulin aspart is equivalent to human insulin.
►Inject the insulin under the skin. Use the injection technique patients aged 65-83 years, mean age 70 years). The relative tion rate was somewhat slower in Type 2 diabetic patients, result- infusion bags are stable at room temperature for 24 hours.
advised by the doctor or nurse and described in the delivery differences in the pharmacodynamic properties Pharmaceutical particulars
Although stable over time, a certain amount of insulin will be ini- max (352 ± 240 pmol/l) and later tmax (60 (GIRmax,AUCGIR, 0-120 min) between insulin aspart and human (interquartile range: 50-90) minutes). The intra-individual variabil- List of excipients
tially adsorbed to the material of the infusion bag. Monitoring of ►Keep the needle under the skin for at least 6 seconds to make insulin in elderly were similar to those seen in healthy sub- ity in time to maximum concentration is significantly less for blood glucose is necessary during insulin infusion.
sure that the full dose has been delivered jects and in younger subjects with diabetes.
NovoRapid® than for soluble human insulin, whereas the intra- NovoRapid® should not be used if it does not appear clear and ►After each injection be sure to discard the needle. Otherwise, Children and adolescents. When given to children the liquid may leak out when the temperature changes.
NovoRapid® showed similar long-term glucose control com- Children and adolescents. The pharmacokinetic and pharmacody- Any unused product or waste material should be disposed of in namic properties of NovoRapid® were investigated in children (6- For use in an infusion pump system
A clinical trial comparing preprandial soluble human insulin 12 years) and adolescents (13-17 years) with Type 1 diabetes.
Instructions to be given to the patient on how to handle
NovoRapid® should never be mixed with any other insulin when with postprandial insulin aspart was performed in small chil- Insulin aspart was rapidly absorbed in both age groups, with sim- NovoRapid® Penfill®
dren (26 patients aged 2 to 6 years) and a single dose PK/PD max as in adults. However, Cmax differed between the age Follow the instructions and recommendations from the doctor trial was performed in children (6-12 years) and adolescents groups, stressing the importance of the individual titration of Before using NovoRapid®
regarding the use of NovoRapid® in a pump. Before use of (13-17 years). The pharmacodynamic profile of insulin aspart ►Check the label to make sure it is the right type of insulin NovoRapid® in the pump system a comprehensive instruction in in children was similar to that seen in adults.
Elderly: The relative differences in pharmacokinetic properties ►Always check the cartridge, including the rubber plunger the use and information about any actions to be taken in case of Clinical trials in patients with Type 1 diabetes have demon- Substances added to the insulin may cause degradation of the between insulin aspart and soluble human insulin in elderly sub- (stopper). Don’t use it if any damage is seen or if there is a gap illness, too high or too low blood sugar or failure of the pump strated a reduced risk of nocturnal hypoglycaemia with insulin, e.g. if the medicinal product contains thiol or sulphites.
jects (65-83 years, mean age 70 years) with type 2 diabetes were between the rubber plunger and the white label band. See the insulin aspart compared with soluble human insulin. The risk similar to those observed in healthy subjects and in younger sub- Special precautions for storage
delivery system manual for further instructions • Before inserting the needle, use soap and water to clean the of daytime hypoglycaemia was not significantly increased.
jects with diabetes. A decreased absorption rate was observed in Do not use NovoRapid® Penfill® after the expiry date stated on ►Disinfect the rubber membrane with a medicinal swab hands and the skin where the needle is inserted so as to avoid Pregnancy. A clinical trial comparing safety and efficacy of Imported by:
the label/carton. Keep out of the reach and sight of children.
►Always use a new needle for each injection to prevent insulin aspart vs. insulin human in the treatment of pregnant Store in a refrigerator in original package at (2°C – 8°C) not in or • When filling a new reservoir, be certain not to leave large air women with type 1 diabetes (322 exposed pregnancies younger subjects with type 2 diabetes and slightly lower than in too near the freezer section or cooling element. Do not freeze.
NovoRapid® must not be used
bubbles in either the syringe or the tubing (insulin aspart: 157; insulin human: 165)) did not indicate Keep the cartridge in the outer carton in order to protect from light.
►If the cartridge or the device containing the cartridge is • Changing of the infusion set (tubing and needle) must be any adverse effect of insulin aspart on pregnancy or on the Hepatic impairment: A single dose pharmacokinetic study of NovoRapid® Penfill® in use or carried as a spare can be kept at dropped, damaged or crushed, there is a risk of leakage of done according to the instructions in the product information insulin aspart was performed in 24 subjects with hepatic function ambient temperature (not above 30°C) for up to 4 weeks, but In addition the data from a clinical trial including 27 women Novo Nordisk Producao Farmaceutica do Brasil Ltda.
ranging from normal to severely impaired. In subjects with hep- any remainder must be discarded. Do not refrigerate.
►If it has not been stored correctly or if it has been frozen with gestational diabetes randomised to treatment with To get the benefit of insulin infusion, and to detect possible mal- atic impairment absorption rate was decreased and more vari- ►If the insulin does not appear clear and colourless.
Montes Claros, Minas Gerais, Brazil 39404004.
insulin aspart vs. insulin human (insulin aspart: 14; insulin Nature and contents of container
function of the insulin pump, it is recommended to measure the able, resulting in delayed tmax from about 50 min in subjects with NovoRapid® is for injection under the skin (subcutaneously) or for human: 13) showed similar safety profiles between treat- A glass (Type 1) cartridge which contains a piston (bromobutyl normal hepatic function to about 85 min in subjects with moder- NovoRapid®, Penfill® and NovoFine® are trademarks rubber) and is closed with a disc (bromobutyl/polyisoprene rub- continuous infusion in a pump system. NovoRapid® may also be ate and severe hepatic impairment. AUC, C owned by Novo Nordisk A/S, Denmark ber) containing 3 ml of solution. Cartons of 5 X 3ml cartridges.
given intravenously by health care professionals under close What to do in case of pump system failure
similar in subjects with reduced hepatic function compared with Always have alternative insulin available for injection under the subjects with normal hepatic function.
Always vary the sites to inject, to avoid lumps. The best places to skin in case of pump system failure.


Microsoft word - [12] unni 4-19-12.doc

[12] UNNI 4-19-12.DOC (DO NOT DELETE) 9/10/2012 3:01 PM Indian Patent Law and TRIPS: Redrawing the Flexibility Framework in the Context of Public Policy and Health Presented in March 2011 at the University of the Pacific, McGeorge School of Law Symposium on The Global Impact and Implementation of Human Rights Norms. IV. THE PATENTS (AMENDMENT) ACT, 2002 . 333 V. THE PATENTS (AMENDMENT)

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SISTEMA NACIONAL DE VIGILANCIA EN SALUD PÚBLICA DATOS BÁSICOS 1. INFORMACIÓN GENERAL REG-R02.003.0000-001 V:02 AÑO 2012 1.1 Código de la UPGD Razón social de la unidad primaria generadora del dato 1.2 Nombre del evento Código del evento 1.3 Fecha de Notificación (dd/mm/aaaa) 2. IDENTIFICACIÓN DEL PACIENTE 2.1 Tipo de Documento 2.2 Número de Identificac

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