Apidra Side Effects
Please note - some side effects for Apidra may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.
Side Effects of Apidra - for the Consumer
Apidra Cartridges
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Apidra Cartridges:
Seek medical attention right away if any of these SEVERE side effects occur when using Apidra Cartridges:Redness, swelling, itching, or mild pain at the injection site.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain); changes in vision; chills; confusion; dizziness; drowsiness; fainting; fast or irregular heartbeat; headache; loss of consciousness; mood changes; seizures; slurred speech; swelling; tremor; trouble breathing; trouble concentrating; unusual hunger; unusual sweating; weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Apidra Solostar Cartridges
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Apidra Solostar Cartridges:
Seek medical attention right away if any of these SEVERE side effects occur when using Apidra Solostar Cartridges:Redness, swelling, itching, or mild pain at the injection site.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain); changes in vision; chills; confusion; fainting; fast or irregular heartbeat; loss of consciousness; mood changes; nightmares or trouble sleeping; seizures; severe or persistent dizziness, drowsiness, or lightheadedness; severe or persistent headache; slurred speech; tingling in the hands, feet, lips, or tongue; tremor; trouble breathing; trouble concentrating; trouble walking; unusual hunger; unusual sweating; weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Apidra Solostar Pens
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Apidra Solostar Pens:
Seek medical attention right away if any of these SEVERE side effects occur when using Apidra Solostar Pens:Redness, swelling, itching, or mild pain at the injection site.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain); changes in vision; chills; confusion; fainting; fast or irregular heartbeat; loss of consciousness; mood changes; nightmares or trouble sleeping; seizures; severe or persistent dizziness, drowsiness, or lightheadedness; severe or persistent headache; slurred speech; tingling in the hands, feet, lips, or tongue; tremor; trouble breathing; trouble concentrating; trouble walking; unusual hunger; unusual sweating; weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
Apidra Vials
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Apidra Vials:
Seek medical attention right away if any of these SEVERE side effects occur when using Apidra Vials:Redness, swelling, itching, or mild pain at the injection site.
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue; wheezing; muscle pain); changes in vision; chills; confusion; dizziness; drowsiness; fainting; fast or irregular heartbeat; headache; loss of consciousness; mood changes; seizures; slurred speech; swelling; tremor; trouble breathing; trouble concentrating; unusual hunger; unusual sweating; weakness.
This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.
TopApidra Side Effects - for the Professional
Apidra
The following adverse reactions are discussed elsewhere:
- Hypoglycemia [See Warnings and Precautions (5.2)]
- Hypokalemia [See Warnings and Precautions (5.4)]
Clinical trial experience
Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared to those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.
The frequencies of adverse drug reactions during Apidra clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.
| Apidra, % (n=950) |
All comparators*, % (n=641) |
|
|---|---|---|
| Nasopharyngitis | 10.6 | 12.9 |
| Hypoglycemia† | 6.8 | 6.7 |
| Upper respiratory tract infection | 6.6 | 5.6 |
| Influenza | 4.0 | 5.0 |
| Apidra, % (n=883) |
Regular human insulin, % (n=883) |
|
|---|---|---|
| Upper respiratory tract infection | 10.5 | 7.7 |
| Nasopharyngitis | 7.6 | 8.2 |
| Edema peripheral | 7.5 | 7.8 |
| Influenza | 6.2 | 4.2 |
| Arthralgia | 5.9 | 6.3 |
| Hypertension | 3.9 | 5.3 |
- Pediatrics
Table 3 summarizes the adverse reactions occurring with frequency higher than 5% in a clinical study in children and adolescents with type 1 diabetes treated with Apidra (n=277) or insulin lispro (n=295).
| Apidra, % (n=277) |
Lispro, % (n=295) |
|
|---|---|---|
| Nasopharyngitis | 9.0 | 9.5 |
| Upper respiratory tract infection | 8.3 | 10.8 |
| Headache | 6.9 | 11.2 |
| Hypoglycemic seizure | 6.1 | 4.7 |
- Severe symptomatic hypoglycemia
Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including Apidra [See Warnings and Precautions (5.2)]. The rates and incidence of severe symptomatic hypoglycemia, defined as hypoglycemia requiring intervention from a third party, were comparable for all treatment regimens. In the phase 3 clinical trial, children and adolescents with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia in the two treatment groups compared to adults with type 1 diabetes. [See Clinical Studies (14)].
| Type 1 Diabetes Adults 12 weeks with insulin glargine |
Type 1 Diabetes Adults 26 weeks with insulin glargine |
Type 2 Diabetes Adults 26 weeks with NPH human insulin |
Type 1 Diabetes Pediatrics 26 weeks |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Apidra Pre-meal |
Apidra Post-meal |
Regular Human Insulin | Apidra | Insulin Lispro | Apidra | Regular Human Insulin | Apidra | Insulin Lispro | |
|
|||||||||
| Events per month per patient | 0.05 | 0.05 | 0.13 | 0.02 | 0.02 | 0.00 | 0.00 | 0.09 | 0.08 |
| Percent of patients (n/total N) | 8.4% (24/286) | 8.4% (25/296) | 10.1% (28/278) | 4.8% (16/339) |
4.0% (13/333) |
1.4% (6/416) |
1.2% (5/420) |
16.2% (45/277) |
19.3% (57/295) |
- Insulin initiation and intensification of glucose control
Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.
- Lipodystrophy
Long-term use of insulin, including Apidra, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy. [See Dosage and Administration (2.2, 2.3)].
- Weight gain
Weight gain can occur with insulin therapy, including Apidra, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.
- Peripheral Edema
Insulin, including Apidra, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.
- Adverse Reactions with Continuous Subcutaneous Insulin Infusion (CSII)
In a 12-week randomized study in patients with type 1 diabetes (n=59), the rates of catheter occlusions and infusion site reactions were similar for Apidra and insulin aspart treated patients (Table 5).
| Apidra (n=29) |
insulin aspart (n=30) |
|
|---|---|---|
| Catheter occlusions/month | 0.08 | 0.15 |
| Infusion site reactions | 10.3% (3/29) | 13.3% (4/30) |
- Allergic Reactions
Local Allergy
As with any insulin therapy, patients taking Apidra may experience redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions may require discontinuation of Apidra. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.
Systemic Allergy
Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including Apidra. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.
In controlled clinical trials up to 12 months duration, potential systemic allergic reactions were reported in 79 of 1833 patients (4.3%) who received Apidra and 58 of 1524 patients (3.8%) who received the comparator short-acting insulins. During these trials treatment with Apidra was permanently discontinued in 1 of 1833 patients due to a potential systemic allergic reaction.
Localized reactions and generalized myalgias have been reported with the use of metacresol, which is an excipient of Apidra.
Antibody Production
In a study in patients with type 1 diabetes (n=333), the concentrations of insulin antibodies that react with both human insulin and insulin glulisine (cross-reactive insulin antibodies) remained near baseline during the first 6 months of the study in the patients treated with Apidra. A decrease in antibody concentration was observed during the following 6 months of the study. In a study in patients with type 2 diabetes (n=411), a similar increase in cross-reactive insulin antibody concentration was observed in the patients treated with Apidra and in the patients treated with human insulin during the first 9 months of the study. Thereafter the concentration of antibodies decreased in the Apidra patients and remained stable in the human insulin patients. There was no correlation between cross-reactive insulin antibody concentration and changes in HbA1c, insulin doses, or incidence of hypoglycemia. The clinical significance of these antibodies is not known.
Apidra did not elicit a significant antibody response in a study of children and adolescents with type 1 diabetes.
Postmarketing experience
The following adverse reactions have been identified during post-approval use of Apidra.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.
Medication errors have been reported in which other insulins, particularly long-acting insulins, have been accidentally administered instead of Apidra [See Patient Counseling Information (17)].
TopSide Effects by Body System - for Healthcare Professionals
Endocrine
Endocrine side effects have included hypoglycemia, which has been the most common and serious side effect of insulin, occurring in approximately 16% of type 1 and 10% of type II diabetic patients (the incidence varies greatly depending on the populations studied, types of insulin therapy, etc). Although there are counterregulatory endocrinologic responses to hypoglycemia, some responses have been decreased, inefficient, or absent in some patients. Severe hypoglycemia has usually presented first as confusion, sweating, or tachycardia, and has resulted in coma, seizures, cardiac arrhythmias, neurological deficits, and death. Blood or urine glucose monitoring is recommended in patients who are at risk of hypoglycemia or who do not recognize the signs and symptoms of hypoglycemia. The risk for developing hypoglycemia has been higher in patients receiving intensive or continuous infusion insulin therapy. The association between insulin and dyslipidemia is currently being evaluated.
Permanent neuropsychological impairment has been associated with recurrent episodes of severe hypoglycemia.
In one retrospective study of 600 randomly selected patients with insulin-treated diabetes mellitus, the only reliable predictors of severe hypoglycemia were a history of hypoglycemia, a history of hypoglycemia-related injury or convulsion, and the duration of insulin therapy. Those with a history of hypoglycemia had been treated with insulin for 17.4 years, which was significantly longer than the 14.3 years in the insulin-treated patients without a history of hypoglycemia.
Human insulin does not appear to be associated with hypoglycemic episodes more often than animal insulin. Caution is recommended when switching from animal (either bovine or pork) to purified porcine insulin or biosynthetic human insulin, however, because of increased potency or bioavailability.
Cardiovascular
Cardiovascular side effects have included hyperinsulinemia. Given the high frequency of both microvascular and macrovascular diseases in patients with diabetes and hyperinsulinemia, some experts are evaluating insulin as a possible atherogenic agent. Controversy and continued study surround the role of hyperinsulinemia as the precursor of hypertension.
Other cardiovascular risk factors that are accentuated in persons with carbohydrate intolerance and hypertension include abnormalities in platelet function, clotting factors, the fibrinolytic system, and dyslipidemia. The relationship between diabetes, insulin, and these disorders is currently under investigation.
Insulin may contribute to the pathogenesis of hypertension by stimulating the sympathetic nervous system, promoting renal sodium retention, and/or stimulating vascular smooth muscle hypertrophy. It may induce dyslipidemia by promoting hepatic synthesis of very low density lipoproteins (VLDLs).
Insulin may stimulate heart rate in the absence of hypoglycemia.
Gastrointestinal
Gastrointestinal side effects have been reported rarely. GI distress has tended to resolve after dose reduction.
Dermatologic
Dermatologic side effects of insulin have included lipohypertrophy (insulin is lipogenic) and lipoatrophy (probably immunologically-mediated). The incidence of lipoatrophy has been markedly decreased with the use of purer forms of pork insulin or biosynthetic human insulin and when injection sites were alternated. Without proper hygiene, subcutaneous insulin injections have been complicated by infection.
General
General side effects have included weight gain, sometimes presenting as edema associated with abrupt restoration of glucose control in a patient whose control was previously poor. Weight gain may have been due to more efficient use of calories during insulin therapy, suggesting additional benefits of dietary and exercise modifications. Patients on intensive insulin therapy have been more likely to experience weight gain.
Intensive insulin therapy causes an increase in body fat as a result of the elimination of glycosuria and reduction in 24-hour energy expenditure. The reduction in 24-h energy expenditure is the result of an insulin-associated decrease in triglyceride/free fatty acid cycling and nonoxidative glucose and protein metabolism.
Hematologic
The effects of insulin-induced hypoglycemia on hemostasis may explain some of the clinical observations of embolic phenomenon during treatment of diabetic ketoacidosis.
Limited data show that diabetics have a significantly lower basal concentration of tissue plasminogen activator.
Hematologic side effects have included an increase in the concentration of von Willebrand factor due to insulin-induced hypoglycemia. Increased von Willebrand factor, combined with hypoglycemia-associated decreased plasma volume and increased plasma viscosity, may have predisposed patients to reduced peripheral perfusion or embolic phenomenon. A single case of insulin-induced hemolytic anemia has been reported.
Hypersensitivity
A diabetic patient with true allergy to insulin can undergo desensitization. Desensitization kits and protocols are available from some insulin manufacturers.
Hypersensitivity side effects have included both local and systemic reactions. These reactions are becoming rare (less than 1% of patients) due to the use of purer forms of pork insulin or biosynthetic human insulin. Local reactions have presented as erythema, swelling, heat, or subcutaneous nodules. They usually occurred within the first two weeks of therapy, then disappeared. True allergy to insulin has been rare, and sensitization was usually associated with specific animal proteins in bovine and less pure forms of porcine insulins.
Immunologic
Immunologic analysis of anaphylaxis to some insulin preparations in some cases has revealed markedly elevated serum levels of lgE and lgG to protamine, but not to regular insulin.
Immunologic side effects have included the formation of anti-insulin antibodies, particularly when animal insulin formulations were used. The presence of these antibodies caused the elimination half-life of insulin to increase.
Increases in levels of anti-insulin antibodies that react with both human insulin and insulin aspart have been observed in patients treated with insulin aspart. These antibodies do not appear to cause deterioration in HbA1c or to necessitate increases in insulin dose.
Metabolic
Metabolic side effects have included reports of hypokalemia and hypomagnesemia, particularly in patients treated for diabetic ketoacidosis (DKA). Insulin increases the intracellular transport of phosphate, which often results in hypophosphatemia during treatment of DKA.
Rare cases of hypophosphatemia have been associated with the use of glucose, insulin, and potassium infusions during the treatment of myocardial infarction.
Ocular
Ocular side effects have included reports of blurry vision during the beginning of therapy. This was thought to be due to changes in the osmotic equilibrium between the lens and the ocular fluids, and was usually self-limited.
Renal
Hypoglycemia is associated with increased plasma dopamine, epinephrine, and plasma renin activity. Acute changes in renal function during insulin-induced hypoglycemia, therefore, may result from direct stimulation of the efferent sympathetic nerves to the kidney and hormonal counterregulatory mechanisms.
Renal effects have included reports of significantly decreased renal plasma flow, glomerular filtration rate, and significantly increased urinary albumin excretion rate from insulin-induced hypoglycemia. These changes were usually reversible upon resolution of hypoglycemia.
Local
Local side effects have included redness, swelling, or itching at the site of injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions may require discontinuation of insulin glulisine.
Respiratory
Respiratory side effects have included upper respiratory tract infection and nasopharyngitis.
TopMore Apidra resources
- Apidra Prescribing Information (FDA)
- Apidra Monograph (AHFS DI)
- Apidra Advanced Consumer (Micromedex) - Includes Dosage Information
- Apidra Cartridges MedFacts Consumer Leaflet (Wolters Kluwer)
- Apidra Consumer Overview
Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.
