Basaglar

• Eli Lilly and Company

Serious side effects have been reported with Basaglar, including:

• transmission of diseases transmitted through blood when sharing the same Basaglar Kwikpen between patients. Never share a Basaglar KwikPen between patients.
• hyperglycemia (high blood sugar) with changes in insulin regimen. Tell your healthcare provider right away if you have some or all of the following symptoms of hyperglycemia:
  • excessive thirst
  • excessive urination
  • increased urination at night
  • blurry vision
  • sores that won’t heal
  • fatigue
  • difficulty concentrating
  • frequent urination
  • headaches
  • high blood glucose
  • high levels of sugar in the urine
  • increased fatigue
  • increased thirst
  • weight loss
• hypoglycemia (low blood sugar). Tell your healthcare provider right away if you have some or all of the following symptoms of hypoglycemia:
  • shakiness
  • nervousness or anxiety
  • sweating, chills and clamminess
  • irritability or impatience
  • confusion, including delirium
  • rapid/fast heartbeat
  • lightheadedness or dizziness
  • hunger and nausea
  • sleepiness
  • blurred/impaired vision
  • tingling or numbness in the lips or tongue
  • headaches
  • weakness or fatigue
  • anger, stubbornness, or sadness
  • lack of coordination
  • nightmares or crying out during sleep
  • seizures
  • unconsciousness
• medication errors. Take extra precautions against mixing up Basaglar with other insulin products.
• allergic reaction. Tell your healthcare provider right away if you have some or all of the following symptoms of an allergic reaction:
• hypokalemia (low potassium in the blood). Tell your healthcare provider right away if you have some or all of the following symptoms of hypokalemia:
  • constipation
  • feeling of skipped heart beats or palpitations
  • fatigue
  • muscle damage
  • muscle weakness or spasms
  • tingling or numbness
• fluid retention and heart failure when taken with PPAR-gamma Agonists. Tell your healthcare provider right away if you have some or all of the following symptoms of fluid retention or heart failure:
  • swollen ankles, legs, abdomen and weight gain.
  • increased need to urinate during the night.
  • loss of appetite or nausea
  • shortness of breath with exercise
  • difficulty breathing at rest or when lying flat in bed
  • dizziness, fatigue, and weakness
  • rapid or irregular heartbeats

Do not use Basaglar if you: 

• are having an episode of low blood sugar (hypoglycemia).
• have an allergy to insulin glargine or any of the ingredients in Basaglar. See the end of this Patient Information leaflet for a complete list of ingredients in Basaglar.

While using Basaglar do not: 

• drive or operate heavy machinery, until you know how Basaglar affects you.
• drink alcohol or use over-the-counter medicines that contain alcohol.

In the U.S.

• Basaglar
• Lantus
• Lantus SoloStar
• Toujeo

Available Dosage Forms:

• Solution

Therapeutic Class: Antidiabetic

Pharmacologic Class: Insulin, Long Acting

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Anxiety
• behavior change similar to being drunk
• blurred vision
• chills
• cold sweats
• confusion
• convulsions (seizures)
• cool, pale skin
• difficulty with thinking
• dizziness or lightheadedness
• drowsiness
• excessive hunger
• fast heartbeat
• headache
• nausea
• nervousness
• nightmares
• restless sleep
• shakiness
• slurred speech
• tingling in the hands, feet, lips, or tongue
• unusual tiredness or weakness

• Fast pulse
• skin rash or itching over the entire body
• sweating
• trouble breathing

• Bloating or swelling of the face, hands, lower legs, or feet
• cough
• decreased urine
• difficulty with swallowing
• dry mouth
• hives
• increased thirst
• irregular heartbeat
• muscle pain or cramps
• numbness or tingling in the hands, feet, or lips
• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
• rapid weight gain
• vomiting

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Fever
• sore throat
• stuffy or runny nose

• Depression of the skin at the injection site
• itching, pain, redness, or swelling at the injection site
• thickening of the skin at injection site

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Available as a clear, colorless, sterile solution for injection: 100 units per mL (U-100) in a 3 mL prefilled delivery device (Basaglar® KwikPen®)

Mechanism of Action

The primary activity of insulin, including insulin glargine, is regulation of glucose metabolism. Insulin and its analog lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis.

Pharmacodynamics

The pharmacodynamic profile for Basaglar was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 91 healthy subjects. The median time to maximum effect of Basaglar (measured by the peak rate of glucose infusion) was approximately 12.0 hours. The pharmacodynamic profile of Basaglar following subcutaneous injection demonstrated sustained glucose lowering activity over 24 hours with no pronounced peak. The mean area under the glucose infusion rate curves (measure of overall pharmacodynamic effect) and maximum glucose infusion rate were 1670 mg/kg and 2.12 mg/kg/min, respectively.

A euglycemic clamp study in 20 patients with type 1 diabetes showed a similar pharmacodynamic profile with a sustained glucose lowering activity over 24 hours following a single 0.3 U/kg subcutaneous dose of Basaglar.

After subcutaneous injection of 0.3 units/kg of another insulin glargine product, 100 units/mL, in patients with type 1 diabetes, the duration of action after abdominal, deltoid, or thigh subcutaneous administration was similar.

The time course of action of insulins, including insulin glargine, may vary between individuals and within the same individual.

Pharmacokinetics

Absorption and Bioavailability

The pharmacokinetic profile for Basaglar was determined after subcutaneous administration of a single 0.5 U/kg dose in a euglycemic clamp study conducted in 91 healthy subjects. The insulin serum concentrations indicated a slow and prolonged absorption and a relatively constant concentration/time profile over 24 hours with no pronounced peak. The median time to maximum serum insulin concentration was 12 hours after injection. On average, serum insulin concentrations declined to baseline by approximately 24 hours. The mean observed area under the serum insulin concentration-time curve from time zero to 24 hours and peak serum insulin concentration were 1720 pmol*hr/L and 103 pmol/L, respectively.

Metabolism and Elimination

After subcutaneous injection of another insulin glargine product, 100 units/mL, in diabetic patients, insulin glargine is metabolized at the carboxyl terminus of the Beta chain with formation of two active metabolites M1 (21A-Gly-insulin) and M2 (21A-Gly-des-30B-Thr-insulin). The in vitro activity of M1 and M2 were similar to that of insulin.

Specific Populations

Age, Race, and Gender: Effect of age, race, and gender on the pharmacokinetics of Basaglar has not been evaluated.

Obesity: Effect of BMI on the pharmacokinetics of Basaglar has not been evaluated.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In mice and rats, standard two-year carcinogenicity studies with another insulin glargine product were performed at doses up to 0.455 mg/kg, which was for the rat approximately 10 times and for the mouse approximately 5 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m2. The findings in female mice were not conclusive due to excessive mortality in all dose groups during the study. Histiocytomas were found at injection sites in male rats (statistically significant) and male mice (not statistically significant) in acid vehicle containing groups. These tumors were not found in female animals, in saline control, or insulin comparator groups using a different vehicle. The relevance of these findings to humans is unknown.

Another insulin glargine product was not mutagenic in tests for detection of gene mutations in bacteria and mammalian cells (Ames- and HGPRT-test) and in tests for detection of chromosomal aberrations (cytogenetics in vitro in V79 cells and in vivo in Chinese hamsters).

In a combined fertility and prenatal and postnatal study of another insulin glargine product in male and female rats at subcutaneous doses up to 0.36 mg/kg/day, which was approximately 7 times the recommended human subcutaneous starting dose of 10 units/day (0.008 mg/kg/day), based on mg/m2, maternal toxicity due to dose-dependent hypoglycemia, including some deaths, was observed. Consequently, a reduction of the rearing rate occurred in the high-dose group only. Similar effects were observed with NPH insulin.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. Insulin overdose can cause life-threatening hypoglycemia. Symptoms include drowsiness, confusion, blurred vision, numbness or tingling in your mouth, trouble speaking, muscle weakness, clumsy or jerky movements, seizure (convulsions), or loss of consciousness.

Avoid medication errors by always checking the medicine label before injecting your insulin.

Avoid drinking alcohol. It can cause low blood sugar and may interfere with your diabetes treatment.

There are no controlled data in human pregnancy, however in more than 1000 pregnancy outcomes, no specific adverse effects of insulin glargine on pregnancy and no specific malformations nor fetal or neonatal toxicity were reported. In animal studies in rats and rabbits, the effects of insulin glargine did not differ greatly from those observed with regular human insulin, although 5 fetuses from 2 litters in the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal. Patients with diabetes or a history of gestational diabetes should maintain good metabolic control before conception and during pregnancy. Insulin requirements may decrease during the first trimester; generally increase during the second and third trimesters, and rapidly decline after delivery. Careful monitoring of glucose control is essential. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use during pregnancy only if the potential benefit justifies the potential risk to the fetus AU TGA pregnancy category: B3 US FDA pregnancy category: C