NovoRapid

NovoRapid

insulin aspart

Manufacturer:

Novo Nordisk

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Insulin aspart.
Description
NovoRapid also contains the following excipients: Glycerol, phenol, metacresol, zinc chloride, sodium chloride, disodium phosphate dihydrate, hydrochloric acid and/or sodium hydroxide and water for injections.
Action
Pharmacotherapeutic Group: Fast acting insulins and analogues, ATC Code: A10A B05.
Pharmacology: Pharmacodynamics: The blood glucose lowering effect of insulin occurs when the molecules facilitate the uptake of glucose by binding to insulin receptors on muscle and fat cells and simultaneously inhibit the output of glucose from the liver.
NovoRapid produces a more rapid onset of action compared to soluble human insulin, together with a lower glucose concentration, as assessed within the 1st 4 hrs after a meal. NovoRapid has a shorter duration of action compared to soluble human insulin after SC injection.
When NovoRapid is injected SC, the onset of action will occur within 10-20 min of injection. The maximum effect is exerted 1-3 hrs after injection. The duration of action is 3-5 hrs.
Adults: Clinical trials in patients with type 1 diabetes have demonstrated a lower postprandial blood glucose with NovoRapid compared to soluble human insulin. In 2 long-term open label trials in patients with type 1 diabetes comprising 1070 and 884 patients, respectively, NovoRapid reduced glycosylated haemoglobin by 0.12 (95% C.I. 0.03; 0.22) percentage points and by 0.15 (95% C.I. 0.05; 0.26) percentage points compared to human insulin.
Clinical trials in patients with type 1 diabetes have demonstrated a reduced risk of nocturnal hypoglycaemia with insulin aspart compared with soluble human insulin. The risk of daytime hypoglycaemia was not significantly increased.
Children and Adolescents: A clinical trial comparing preprandial soluble human insulin with postprandial insulin aspart was performed in small children (26 patients 2-6 years) and a single dose PK/PD trial was performed in children (6-12 years) and adolescents (13-17 years). The pharmacodynamic profile of insulin aspart in children was similar to that seen in adults.
Pregnancy: The effect of pregnancy on the pharmacokinetics and pharmacodynamics of NovoRapid has not been studied (see Use in pregnancy & lactation under Precautions).
Insulin aspart is equipotent to soluble human insulin on a molar basis.
Pharmacokinetics: In NovoRapid substitution of the amino acid proline with aspartic acid at position B28 reduces the tendency to form hexamers as observed with soluble human insulin.
NovoRapid is therefore more rapidly absorbed from the SC layer compared to soluble human insulin. The time to maximum concentration is, on average, ½ of that for soluble human insulin. A mean maximum plasma concentration of 492±256 pmol/L was reached 40 (interquartile range: 30-40) mins after a SC dose of 0.15 U/kg bodyweight in type 1 diabetic patients. The insulin concentrations returned to baseline about 4-6 hrs after dose. The absorption rate was somewhat slower in type 2 diabetic patients, resulting in a lower Cmax (352±240 pmol/L) and later Tmax [60 (interquartile range: 50-90) mins]. The intra-individual variability in time to maximum concentration is significantly less for NovoRapid than for soluble human insulin, whereas the intra-individual variability in Cmax for NovoRapid is larger.
Elderly: The relative differences in pharmacokinetic properties between insulin aspart and soluble human insulin in elderly subjects (65-83 years, mean age 70 years) with type 2 diabetes were similar to those observed in healthy subjects and in younger subjects with diabetes. A decreased absorption rate was observed in elderly subjects, resulting in a later Tmax [82 (interquartile: 60-120) min], whereas Cmax was similar to that observed in younger subjects with type 2 diabetes and slightly lower than in subjects with type 1 diabetes.
Hepatic Impairment: A single dose pharmacokinetic study of insulin aspart was performed in 24 subjects with hepatic function ranging from normal to severely impaired. In subjects with hepatic impairment absorption rate was decreased and more variable resulting in delayed Tmax from about 50 min in subjects with normal hepatic function to about 85 min in subjects with moderate and severe hepatic impairment. AUC, Cmax and CL/F were similar in subjects with reduced hepatic function compared with subjects with normal hepatic function.
Renal Impairment: A single dose pharmacokinetic study of insulin aspart in 18 subjects with renal function ranging from normal to severely impaired was performed. No apparent effect of creatinine clearance values on AUC, Cmax, CL/F and Tmax of insulin aspart was found. Data were limited in subjects with moderate and severe renal impairment. Subjects with renal failure necessitating dialysis treatment were not investigated.
Children and Adolescents: The pharmacokinetic and pharmacodynamic properties of NovoRapid were investigated in children (6-12 years) and adolescents (13-17 years) with type 1 diabetes. Insulin aspart was rapidly absorbed in both age groups, with similar Tmax as in adults.
However, Cmax differed between the age groups, stressing the importance of the individual titration of NovoRapid.
Toxicology: Preclinical Safety Data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction.
In in vitro tests, including binding to insulin and IGF-1 receptor sites and effects on cell growth, insulin aspart behaved in a manner that closely resembled human insulin. Studies also demonstrate that the dissociation of binding to the insulin receptor of insulin aspart is equivalent to human insulin.
Indications/Uses
Treatment of patients with diabetes mellitus.
Dosage/Direction for Use
NovoRapid has a faster onset and a shorter duration of action than soluble human insulin.
Due to the faster onset of action, NovoRapid should generally be given immediately before a meal.
When necessary, NovoRapid can be given soon after the meal.
Dosage is individual and determined on the basis of the physician's advice in accordance with the needs of the patient. It should normally be used in combination with intermediate-acting or long-acting insulin given at least once a day.
The individual insulin requirement is usually between 0.5 and 1 unit/kg/day. In a meal-related treatment, 50-70% of this requirement may be provided by NovoRapid and the remainder by intermediate-acting or long-acting insulin.
NovoRapid is administered SC in the abdominal wall, the thigh, the deltoid region or the gluteal region. Injection sites should be rotated within the same region.
When injected SC into the abdominal wall, the onset of action will occur within 10-20 min of injection. Therefore, a meal or snack containing carbohydrate should be taken within 10 min.
The maximum effect is exerted 1-3 hrs after the injection. The duration of action is 3-5 hrs. As with all insulins, the duration of action will vary according to the dose, injection site, blood flow, temperature and level of physical activity. As with all insulins, SC injection in the abdominal wall ensures a faster absorption than other injection sites. However, the faster onset of action compared to soluble human insulin is maintained regardless of injection site.
NovoRapid may be administered IV under medical supervision. In case of emergency, use of NovoRapid from a Penfill/FlexPen, NovoRapid must first be withdrawn into an insulin syringe. No studies have been conducted in critically ill people with diabetes who are likely to require IV administration. There is no pharmacokinetic or pharmacodynamic advantage in using NovoRapid over soluble human insulin when these insulins are given IV.
NovoRapid may be used for Continuous Subcutaneous Insulin Infusion (CSII) in pump systems suitable for insulin infusion. CSII should be administered in the abdominal wall. Infusion sites should be rotated.
When used with an insulin infusion pump, NovoRapid should not be mixed with any other insulin. Patients using CSII should be comprehensively instructed in the use of the pump system and use the correct reservoir and tubing for the pump. The infusion set (tubing and cannula) should be changed in accordance with the instructions in the product information supplied with the infusion set. Patients administering NovoRapid by CSII must have alternative insulin available in case of pump system failure. Renal or hepatic impairment may reduce the patient's insulin requirements.
NovoRapid should be used in children in preference to soluble human insulin when a rapid onset of action might be beneficial. For example, in the timing of the injections in relation to meals.
Overdosage
A specific overdose for insulin cannot be defined however hypoglycaemia may develop over sequential stages if too high doses relative to the patient's requirement are administered:
Mild hypoglycaemic episodes can be treated by oral administration of glucose or sugary products. It is therefore recommended that the diabetic patient constantly carry sugar containing products.
Severe hypoglycaemic episodes, where the patient has become unconscious, can be treated by glucagon (0.5-1 mg) given IM or SC by a trained person, or glucose given IV by a medical professional. Glucose must also be given IV if the patient does not respond to glucagon within 10-15 min.
Upon regaining consciousness, administration of oral carbohydrate is recommended for the patient in order to prevent relapse.
Contraindications
Hypoglycaemia. Hypersensitivity to insulin aspart or any of the excipients of NovoRapid.
Special Precautions
Inadequate dosage or discontinuation of treatment may, especially in type 1 diabetes may lead to hyperglycaemia and diabetic ketoacidosis. Usually the first symptoms of hyperglycaemia come on gradually over a period of hours and days. They include nausea, vomiting, drowsiness, flushed dry skin, dry mouth, increased urination, thirst and loss of appetite as well as acetone odour of the breath. Untreated hyperglycaemic events are potentially lethal.
Patients whose blood glucose control is greatly improved eg, by intensified insulin therapy, may experience a change in their usual warning symptoms of hypoglycaemia and should be advised accordingly.
A consequence of the pharmacodynamics of rapid-acting insulin analogues is that if hypoglycaemia occurs, it may occur earlier after an injection when compared with soluble human insulin. NovoRapid should be administered in immediate relation to a meal. The rapid onset of action should therefore be considered in patients with concomitant diseases or medication where a delayed absorption of food might be expected.
Concomitant illness, especially infections, usually increases the patient's insulin requirements.
When patients are transferred between different types of insulin products, the early warning symptoms of hypoglycaemia may change or become less pronounced than those experienced with previous insulin.
Transferring a patient to a new type or brand of insulin should be done under strict medical supervision. Changes in strength, brand, type, species (animal, human, human insulin analogue) and/or method of manufacture may result in a change in dosage. Adjustment of dosage may also be necessary if patients undertake increased physical activity or change their usual diet. Exercise immediately after a meal may increase the risk of hypoglycaemia. Patients taking NovoRapid may require an increased number of daily injections or a change in dosage from that used with their usual insulins. If an adjustment is needed, it may occur with the 1st dose or during the 1st several weeks or months.
Omission of a meal or unplanned, strenuous physical exercise may lead to hypoglycaemia.
NovoRapid contains metacresol, which in rare cases may cause allergic reactions.
Effects on the Ability to Drive or Operate Machinery: The patient's ability to concentrate and react may be impaired as a result of hypoglycaemia. This may constitute a risk in situations where these abilities are of special importance (eg, driving a car or operating machinery).
Patients should be advised to take precautions in order to avoid hypoglycaemia while driving, this is particularly important in those who have reduced or absent awareness of the warning signs of hypoglycaemia or have frequent episodes of hypoglycaemia. The advisability of driving should be considered in these circumstances.
Use in pregnancy & lactation: There is limited clinical experience with NovoRapid in pregnancy. An open-label, randomised study compared the safety and efficacy of Novorapid versus human insulin in the treatment of pregnant women with type 1 diabetes [322 exposed pregnancies (NovoRapid: 157, human insulin: 165)]. Two-thirds of the enrolled patients were already pregnant when they entered the study. Since only 1/3 of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Mean HBA1c of ~6% was observed in both groups during pregnancy and there was no significant difference in the incidence of maternal hypoglycaemia.
Intensified blood glucose control and monitoring of pregnant women with diabetes (type 1 diabetes, type 2 diabetes or gestational diabetes) is recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall in the 1st trimester and increase subsequently during the 2nd and 3rd trimesters. After delivery, insulin requirements return rapidly to pre-pregnancy levels.
There are no restrictions on the treatment with NovoRapid during lactation. Insulin treatment of the nursing mother presents no risk to the baby. However, the NovoRapid dosage may need to be adjusted.
Use In Pregnancy & Lactation
There is limited clinical experience with NovoRapid in pregnancy. An open-label, randomised study compared the safety and efficacy of Novorapid versus human insulin in the treatment of pregnant women with type 1 diabetes [322 exposed pregnancies (NovoRapid: 157, human insulin: 165)]. Two-thirds of the enrolled patients were already pregnant when they entered the study. Since only 1/3 of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Mean HBA1c of ~6% was observed in both groups during pregnancy and there was no significant difference in the incidence of maternal hypoglycaemia.
Intensified blood glucose control and monitoring of pregnant women with diabetes (type 1 diabetes, type 2 diabetes or gestational diabetes) is recommended throughout pregnancy and when contemplating pregnancy. Insulin requirements usually fall in the 1st trimester and increase subsequently during the 2nd and 3rd trimesters. After delivery, insulin requirements return rapidly to pre-pregnancy levels.
There are no restrictions on the treatment with NovoRapid during lactation. Insulin treatment of the nursing mother presents no risk to the baby. However, the NovoRapid dosage may need to be adjusted.
Adverse Reactions
Adverse drug reactions observed in patients using NovoRapid are mainly dose-dependent and due to the pharmacologic effect of insulin. As for other insulin products, hypoglycaemia, in general is the most frequently occurring undesirable effect. It may occur if the insulin dose is too high in relation to the insulin requirement. Severe hypoglycaemia may lead to unconsciousness and/or convulsions and may result in temporary or permanent impairment of brain function or even death. In clinical trials and during marketed use, the frequency varies with patient population and dose regimens. Therefore, no specific frequency can be presented.
During clinical trials, the overall rates of hypoglycaemia did not differ between patients treated with insulin aspart compared to human insulin.
Frequencies of adverse drug reactions from clinical trials, which by an overall judgment are considered related to Novorapid are listed as follows. The frequencies are defined as: Uncommon (>1/1000, <1/100) and rare (>1/10,000, <1/1000). Isolated spontaneous cases are presented as very rare defined as (<1/10,000).
Immune System Disorders: Uncommon: Urticaria, rash, eruptions. Very rare: Anaphylactic reactions.
Symptoms of generalised hypersensitivity may include generalised skin rash, itching, sweating, GI upset, angioneurotic oedema, difficulties in breathing, palpitation and reduction in blood pressure. Generalised hypersensitivity reactions are potentially life-threatening.
Nervous System Disorders: Rare: Peripheral neuropathy. Fast improvement in blood glucose control may be associated with a condition termed acute painful neuropathy, which is usually reversible.
Eye Disorders: Uncommon: Refraction disorder. Refraction anomalies may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
Uncommon: Diabetic retinopathy. Long-term improved glycaemic control decreases the risk of progression of diabetic retinopathy. However, intensification of insulin therapy with abrupt improvement in glycaemic control may be associated with worsening of diabetic retinopathy.
Skin and Subcutaneous Tissue Disorders: Uncommon: Lipodystrophy. Lipodystrophy may occur at the injection site as a consequence of failure to rotate injection sites within an area.
Uncommon: Local hypersensitivity. Local hypersensitivity reactions (redness, swelling and itching at the injection site) may occur during treatment with insulin. These reactions are usually transitory and normally they disappear during continued treatment.
General Disorders and Administration Site Conditions: Uncommon: Oedema.
Oedema may occur upon initiation of insulin therapy. These symptoms are usually of transitory nature.
Drug Interactions
A number of medicinal products are known to interact with glucose metabolism.
The following substances may reduce the patient's insulin requirements: Oral hypoglycaemic agents (OHAs), octreotide, monoamine oxidase inhibitors (MAOIs), nonselective β-adrenergic blocking agents, angiotensin-converting enzyme (ACE) inhibitors, salicylates, alcohol, anabolic steroids and sulfonamides.
The following substances may increase the patient's insulin requirements: Oral contraceptives, thiazides, glucocorticoids, thyroid hormones, sympathomimetics and danazol. β-Blocking agents may mask the symptoms of hypoglycaemia. Alcohol may intensify and prolong the hypoglycaemic effect of insulin.
Incompatibilities: Substances added to the insulin may cause degradation of the insulin eg, if the medicinal product contains thiol or sulphites.
Caution For Usage
Instructions For Use and Handling: NovoRapid is for SC injection or for continuous infusion in a pump system. NovoRapid may also be given IV under close supervision by health care professionals.
For Pump Use: Tubings in which the inner surface materials are made by polyethylene or polyolefin have been evaluated and found compatible with pump use. Although stable over time, a certain amount of insulin will be initially adsorbed to the material of the infusion bag.
For Intravenous Use: Infusion systems with NovoRapid 100 U/mL at concentrations from 0.05-1 U/mL insulin aspart in the infusion fluids 0.9% sodium chloride, 5% dextrose or 10% dextrose inclusive 40 mmol/L potassium chloride using polypropylene infusion bags are stable at room temperature for 24 hrs. Monitoring of blood glucose is necessary during insulin infusion.
Instructions to be given to the Patient:
Penfill: Penfill cartridges are designed to be used with Novo Nordisk insulin delivery systems and NovoFine needles.
If the patient is treated with NovoRapid Penfill and another insulin Penfill cartridge, 2 insulin delivery systems should be used, one for each type of insulin.
NovoRapid Penfill is for single person use only.
Check the label to make sure it is the right type of insulin. Always check the cartridge, including the rubber plunger (stopper). Don't use it if any damage is seen or if there is a gap between the rubber plunger and the white label band. Disinfect the rubber membrane with a medicinal swab. Inject the insulin under the skin. Use the injection technique advised by the doctor or diabetes nurse and described in the delivery system manual. Keep the needle under the skin for at least 6 sec to make sure that the full dose has been delivered. After each injection, be sure to discard the needle. Otherwise, the liquid may leak out when the temperature changes.
FlexPen: FlexPen is a dial-a-dose insulin pen. Doses from 1-60 units in increments of 1 unit can be dialed. It is designed to be used with NovoFine S needles of 8 mm or shorter in length. Look for an S on the needle box. The S stands for short cap. As a precautionary measure, always carry a spare insulin delivery device in case FlexPen is lost or damaged.
Getting Started: Check the label to ensure the correct type of insulin. Take off the cap. Disinfect the rubber membrane with a medical swab. Remove the protective tab from a NovoFine S short cap needle. Screw the needle straight and tightly onto FlexPen. Pull off the big outer needle cap and the inner needle cap. Do not discard the big outer needle cap.
Priming to Expel Air Prior to each Injection: small amounts of air may collect in the needle and cartridge during normal use. To avoid injection of air and ensure proper dosing: Dial 2 units. Hold FlexPen with the needle pointing upwards and tap the cartridge gently with the finger a few times to make any air bubbles collect at the top of the cartridge. Keeping the needle upwards, press the push-button all the way in. The dose selector returns to zero. A drop of insulin should appear at the needle tip. If not, change the needle and repeat the procedure no more than 6 times. If a drop of insulin still does not appear, the device is defective and must not be used.
Setting the Dose: Check that the dose selector is set at zero. Dial the number of units needed inject. The dose can be corrected either up or down by turning the dose selector in either direction. When dialing back, be careful not to push the push button as insulin will come out. Do not use the residual scale to measure the dose of insulin. A dose larger than the number of units left in the cartridge cannot be set.
Making the Injection: Insert the needle into the skin. Use injection technique advised by the doctor. Deliver the dose by pressing the push-button all the way in. Be careful only to push the push-button when injecting. Keep the push-button fully depressed after the injection until the needle has been withdrawn from the skin. The needle should remain under the skin for at least 6 sec. Keep the push button fully depressed until the needle is withdrawn from the skin. This will ensure that the full dose has been delivered.
Removing the Needle: Replace the outer needle cap and unscrew the needle. Dispose it carefully. Use a new needle for each injection. Remove the needle after each injection. Otherwise, the liquid may leak out when the temperature changes. Dispose the used FlexPen carefully without the needle attached.
Maintenance: FlexPen is designed to work accurately and safely. It should be handled with care. Clean the exterior of FlexPen by wiping it with a medicinal swab. Do not soak, wash or lubricate it. This may damage the mechanism.
NovoRapid Should Not be Used: If the FlexPen or cartridge or the device containing the cartridge is dropped, damaged or crushed, there is a risk of leakage of insulin; if it has not been stored correctly or if it has been frozen; if the insulin does not appear clear and colourless.
Always vary the site to inject to avoid lumps. The best places to give an injection are: the front of the waist (abdomen); the buttocks; the front of the thighs or upper arms. The insulin will work more quickly if injected around the waist.
For Use in an Infusion Pump System: NovoRapid should never be mixed with any other insulin when use in a pump.
Follow the instructions and recommendations from the doctor regarding the use of NovoRapid in a pump. Before use of NovoRapid in the pump system, a comprehensive instruction in the use and information about any actions to be taken in case of illness, too high or too low blood sugar or failure of the pump system must have been received.
Before inserting the needle, use soap and water to clean the hands and the skin where the needle is inserted so as to avoid any infection at the infusion site; when filling a new reservoir, be certain not to leave large air bubbles in either the syringe or the tubing; changing of the infusion set (tubing and needle) must be done according to the instructions in the product information supplied with the infusion set. To get the benefit of insulin infusion and to detect possible malfunction of the insulin pump, it is recommended to measure the blood sugar level regularly. Always have alternative insulin available for injection under the skin in case of pump system failure.
Storage
Store NovoRapid Penfill/FlexPen which are not in use at 2-8°C in a refrigerator (not in or too near the freezer section or cooling element). Do not freeze.
NovoRapid Penfill/FlexPen in Use or Carried as a Spare: Can be kept at ambient temperature (not above 30°C) for up to 4 weeks but any remainder must be discarded. Do not refrigerate.
Penfill: Keep the container in the outer carton in order to protect from light.
FlexPen: Keep the pen cap on when NovoRapid FlexPen is not in use in order to protect from light.
ATC Classification
A10AB05 - insulin aspart ; Belongs to the class of fast-acting insulins and analogues. Used in the treatment of diabetes.
Presentation/Packing
Penfill 100 units/mL (cartridge, clear, colourless, aqueous soln) x 3 mL x 5's. FlexPen 100 units/mL (pre-filled pen, clear, colourless, aqueous soln) x 3 mL x 5's.
Exclusive offer for doctors
Register for a MIMS account and receive free medical publications worth $139 a year.
Sign up for free
Already a member? Sign in