Levemir Side Effects Center

Last updated on RxList: 12/20/2022
Levemir Side Effects Center

What Is Levemir?

Levemir (insulin detemir [rDNA origin] injection) is a man-made form of a hormone that is produced in the body used to treat diabetes in adults and children.

What Are Side Effects of Levemir?

Levemir may cause serious side effects including:

  • redness or swelling where the injection was given,
  • itchy skin rash over the entire body,
  • trouble breathing,
  • fast heartbeats,
  • lightheadedness,
  • swelling in your tongue or throat,
  • weight gain,
  • swelling in your hands or feet,
  • shortness of breath,
  • leg cramps,
  • constipation,
  • irregular heartbeats,
  • fluttering in your chest,
  • increased thirst or urination,
  • numbness or tingling, and
  • muscle weakness or limp feeling

Get medical help right away, if you have any of the symptoms listed above.

Common side effects of Levemir include:

  • injection site reactions (e.g., pain, redness, irritation),
  • swelling of the hands/feet,
  • thickening of the skin where you inject Levemir,
  • weight gain,
  • headache,
  • back pain,
  • stomach pain,
  • flu symptoms, or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

Tell your doctor if you experience serious side effects of Levemir including:

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Levemir

Levemir is for once- or twice-daily subcutaneous (under the skin) administration. Patients treated with Levemir once-daily should administer the dose with the evening meal or at bedtime. Patients requiring twice-daily dosing can administer the evening dose with the evening meal, at bedtime, or 12 hours after the morning dose.

What Drugs, Substances, or Supplements Interact with Levemir?

Levemir may interact with albuterol, clonidine, reserpine, guanethidine, or beta-blockers. Other medicines can increase or decrease the effects of insulin Levemir on lowering your blood sugar. Tell your doctor all prescription and over-the-counter medications you use.

Levemir During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant before using Levemir. Discuss a plan for managing your blood sugars with your doctor before you become pregnant. Your doctor may switch the type of insulin you use during pregnancy. It is not known if this medication passes into breast milk. Consult your doctor before breastfeeding. Insulin needs may change while breastfeeding.

Additional Information

Our Levemir (insulin detemir [rDNA origin] injection) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Diabetes: What Raises and Lowers Your Blood Sugar Level? See Slideshow
Levemir Consumer Information

Get emergency medical help if you have signs of insulin allergy: redness or swelling where an injection was given, itchy skin rash over the entire body, trouble breathing, fast heartbeats, feeling like you might pass out, or swelling in your tongue or throat.

Call your doctor at once if you have:

  • fluid retention--weight gain, swelling in your hands or feet, feeling short of breath; or
  • low potassium--leg cramps, constipation, irregular heartbeats, fluttering in your chest, increased thirst or urination, numbness or tingling, muscle weakness or limp feeling.

Common side effects may include:

  • low blood sugar;
  • weight gain;
  • swelling in your hands and feet;
  • rash, itching; or
  • thickening or hollowing of the skin where you injected the medicine.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

Diabetes is defined best as... See Answer
Levemir Professional Information

SIDE EFFECTS

The following adverse reactions are discussed elsewhere:

  • Hypoglycemia [see WARNINGS AND PRECAUTIONS]
  • Hypoglycemia Due to Medication errors [see WARNINGS AND PRECAUTIONS]
  • Hypersensitivity Reactions [see WARNINGS AND PRECAUTIONS]
  • Hypokalemia [see WARNINGS AND PRECAUTIONS]

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 reactions (excluding hypoglycemia) reported during LEVEMIR clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in Tables 1-4 below. See Tables 5 and 6 for the hypoglycemia findings.

In two pooled trials, adults with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=767) or NPH (n=388). The mean duration of exposure to LEVEMIR was 153 days, and the total exposure to LEVEMIR was 321 patient-years. The most common adverse reactions are summarized in Table 1.

Table 1: Adverse Reactions Occurring in ≥ 5% of LEVEMIR-Treated Adult Patients with Type 1 Diabetes Mellitus in Two Trials of 16 Weeks and 24 Weeks Duration

LEVEMIR, %
(n = 767)
Upper respiratory tract infection 26. 1
Headache 22.6
Pharyngitis 9.5
Influenza-like illness 7.8
Abdominal Pain 6.0

Adults with type 1 diabetes were exposed to LEVEMIR (n=161) or insulin glargine (n=159). The mean duration of exposure to LEVEMIR was 176 days, and the total exposure to LEVEMIR was 78 patient-years. The most common adverse reactions are summarized in Table 2.

Table 2: Adverse Reactions Occurring in ≥ 5% of LEVEMIR-Treated Adult Patients with Type 1 Diabetes Mellitus in a 26-week Trial

LEVEMIR, %
(n = 161)
Upper respiratory tract infection 26.7
Headache 14.3
Back pain 8.1
Influenza-like illness 6.2
Gastroenteritis 5.6
Bronchitis 5.0

In two pooled trials, adults with type 2 diabetes were exposed to LEVEMIR (n=432) or NPH (n=437). The mean duration of exposure to LEVEMIR was 157 days, and the total exposure to LEVEMIR was 186 patient-years. The most common adverse reactions were comparable to that observed in adult patients with type 1 diabetes mellitus; see Table 1.

Pediatric patients with type 1 diabetes were exposed to individualized doses of LEVEMIR (n=232) or NPH (n=115). The mean duration of exposure to LEVEMIR was 180 days, and the total exposure to LEVEMIR was 114 patient-years. The most common adverse reactions are summarized in Table 3.

Table 3: Adverse Reactions Occurring in ≥ 5% of LEVEMIR-Treated Pediatric Patients with Type 1 Diabetes Mellitus in a 26-week Trial

LEVEMIR, %
(n = 232)
Upper respiratory tract infection 35.8
Headache 31.0
Pharyngitis 17.2
Gastroenteritis 16.8
Influenza-like illness 13.8
Abdominal pain 13.4
Pyrexia 10.3
Cough 8.2
Viral infection 7.3
Nausea 6.5
Rhinitis 6.5
Vomiting 6.5

Hypoglycemia

Hypoglycemia was the most commonly observed adverse reaction in patients treated with LEVEMIR. The rates of reported hypoglycemia depend on the definition of hypoglycemia used, diabetes type, insulin dose, intensity of glucose control, background therapies, and other intrinsic and extrinsic patient factors. For these reasons, comparing rates of hypoglycemia in clinical trials for LEVEMIR with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that will occur in clinical practice.

Table 4 (type 1 diabetes) and Table 5 (type 2 diabetes) summarize the incidence of severe and non-severe hypoglycemia in the LEVEMIR clinical trials.

For the adult trials and one of the pediatric trials (Study D), severe hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring assistance of another person and associated with either a plasma glucose value below 56 mg/dL (blood glucose below 50 mg/dL) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. For the other pediatric trial (Study I), severe hypoglycemia was defined as an event with semi-consciousness, unconsciousness, coma and/or convulsions in a patient who could not assist in the treatment and who may have required glucagon or intravenous glucose.

For the adult trials and pediatric trial (Study D), non-severe hypoglycemia was defined as an asymptomatic or symptomatic plasma glucose <56 mg/dL (or equivalently blood glucose <50 mg/dL as used in Study A and C) that was self-treated by the patient. For pediatric Study I, non-severe hypoglycemia included asymptomatic events with plasma glucose <65 mg/dL as well as symptomatic events that the patient could self-treat or treat by taking oral therapy provided by the caregiver.

Table 4: Hypoglycemia in Patients with Type 1 Diabetes

Severe Hypoglycemia Non-Severe Hypoglycemia
Percent of patients with at least 1 event
(n/total N)
Event/patient/ year Percent of patients
(n/total N)
Event/patient/ year
Study A Type 1 Diabetes Adults 16 weeks In combination with insulin aspart Twice-Daily LEVEMIR 8.7 (24/276) 0.52 88.0 (243/276) 26.4
Study B Type 1 Diabetes Adults 26 weeks In combination with insulin aspart Twice-Daily LEVEMIR 5.0 (8/161) 0.13 82.0 (132/161) 20.2
Study C Type 1 Diabetes Adults 24 weeks In combination with regular insulin Once-Daily LEVEMIR 7.5 (37/491) 0.35 88.4 (434/491) 31.1
Study D Type 1 Diabetes Pediatrics 26 weeks In combination with insulin aspart Once-or Twice Daily LEVEMIR 15.9 (37/232) 0.91 93.1 (216/232) 31.6
Study I Type 1 Diabetes Pediatrics 52 weeks In combination with insulin aspart Once-or Twice Daily LEVEMIR 1.7 (3/177) 0.02 94.9 (168/177) 56.1

Table 5: Hypoglycemia in Patients with Type 2 Diabetes

Study E Type 2 Diabetes Adults 24 weeks In combination with oral agents Study F Type 2 Diabetes Adults 22 weeks In combination with insulin aspart Study H Type 2 Diabetes Adults 26 weeks in combination with Liraglutide and Metformin
Twice-Daily LEVEMIR Once-or Twice Daily LEVEMIR Once Daily LEVEMIR + Liraglutide + Metformin
Severe hypoglycemia Percent of patients with at least 1 event (n/total N) 0.4 (1/237) 1.5 (3/195) 0
Event/patient/year 0.01 0.04 0
Non-severe hypoglycemia Percent of patients (n/total N) 40.5 (96/237) 32.3 (63/195) 9.2 (15/163)
Event/patient/year 3.5 1.6 0.29

Hypersensitivity Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock have occurred with insulin, including LEVEMIR, and may be life-threatening.

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 LEVEMIR, can cause lipodystrophy at the site of repeated insulin injections. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption [see DOSAGE AND ADMINISTRATION].

Weight Gain

Weight gain can occur with insulin therapy, including LEVEMIR, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria [see Clinical Studies]. In the clinical program, the mean change in body weight from baseline in adult patients with type 1 diabetes (Study A, B, and C) treated with LEVEMIR ranged from -0.3 kg to 0.5 kg. The mean change in body weight from baseline in adult patients with type 2 diabetes (Study E, F, and H) treated with LEVEMIR ranged from 0.5 kg to 1.2 kg.

Peripheral Edema

Insulin, including LEVEMIR, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

Injection Site Reactions

Patients taking LEVEMIR may experience injection site reactions, including localized erythema, pain, pruritus, urticaria, edema, and inflammation. In clinical studies in adults, three patients treated with LEVEMIR reported injection site pain (0.25%).

Immunogenicity

All insulin products can elicit the formation of insulin antibodies. These insulin antibodies may increase or decrease the efficacy of insulin and may require adjustment of the insulin dose. In clinical trials of LEVEMIR, antibody development has been observed with no apparent impact on glycemic control.

Postmarketing Experience

The following adverse reactions have been identified during post approval use of LEVEMIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Medication errors have been reported in which rapid-acting or short-acting insulins and other insulins, have been accidentally administered instead of LEVEMIR.

Localized cutaneous amyloidosis at the injection site has occurred. Hyperglycemia has been reported with repeated insulin injections into areas of localized cutaneous amyloidosis; hypoglycemia has been reported with a sudden change to an unaffected injection site.

DRUG INTERACTIONS

Table 6 includes clinically significant drug interactions with LEVEMIR.

Table 6: Clinically Significant Drug Interactions with LEVEMIR

Drugs That May Increase the Risk of Hypoglycemia
Drugs: Antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, salicylates, somatostatin analogs (e.g., octreotide), and sulfonamide antibiotics, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors.
Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs.
Drugs That May Decrease the Blood Glucose Lowering Effect of LEVEMIR
Drugs: Atypical antipsychotics (e.g., olanzapine and clozapine), corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens (e.g., in oral contraceptives), protease inhibitors, somatropin, sympathomimetic agents (e.g., albuterol, epinephrine, terbutaline), and thyroid hormones.
Intervention: Dosage increases and increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs.
Drugs That May Increase or Decrease the Blood Glucose Lowering Effect of LEVEMIR
Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia.
Intervention: Dosage adjustment and increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs.
Drugs That May Blunt Signs and Symptoms of Hypoglycemia
Drugs: Beta-blockers, clonidine, guanethidine, and reserpine
Intervention: Increased frequency of glucose monitoring may be required when LEVEMIR is co-administered with these drugs.

Read the entire FDA prescribing information for Levemir (Insulin Detemir)

© Levemir Patient Information is supplied by Cerner Multum, Inc. and Levemir Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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