Insulin Glargine-Aglr

FDA Drug Information • Also known as: Rezvoglar Kwikpen

Brand Names: Rezvoglar Kwikpen
Drug Class: Insulin Analog [EPC]
Route: SUBCUTANEOUS
Dosage Form: INJECTION, SOLUTION
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 DESCRIPTION Insulin glargine-aglr is a long-acting human insulin analog produced by recombinant DNA technology utilizing a non-pathogenic laboratory strain of Escherichia coli (K12). Insulin glargine-aglr differs from human insulin in that the amino acid asparagine at position A21 is replaced by glycine and two arginines are added to the C-terminus of the B-chain. Insulin glargine-aglr has a molecular weight of 6063 Da. REZVOGLAR (insulin glargine-aglr) injection is a sterile, clear and colorless solution for subcutaneous use in a 3 mL single-patient use prefilled pen (REZVOGLAR KwikPen). Prefilled Pen (REZVOGLAR KwikPen): Each mL contains 100 units of insulin glargine-aglr and the inactive ingredients: glycerin (17 mg), metacresol (2.7 mg), zinc oxide (content adjusted to provide 30 mcg zinc ion), and Water for Injection, USP. The pH is adjusted by addition of aqueous solutions of hydrochloric acid 10% and/or sodium hydroxide 10%. REZVOGLAR has a pH of approximately 4.

What Is Insulin Glargine-Aglr Used For?

1 INDICATIONS AND USAGE REZVOGLAR™ is indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. Limitations of Use REZVOGLAR is not recommended for the treatment of diabetic ketoacidosis. REZVOGLAR™ is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus. ( 1 ) Limitations of Use : Not recommended for the treatment of diabetic ketoacidosis. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Individualize dosage based on metabolic needs, blood glucose monitoring, glycemic control, type of diabetes, and prior insulin use. ( 2.1 , 2.2 , 2.3 , 2.4 ) Administer subcutaneously into the abdominal area, thigh, or deltoid once daily at any time of day, but at the same time every day. ( 2.1 ) Do not dilute or mix with any other insulin or solution. ( 2.1 ) Rotate injection sites to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. ( 2.1 ) See Full Prescribing Information for the recommended starting dosage in patients with type 2 diabetes and how to change to REZVOGLAR from other insulins ( 2.3 , 2.4 ) Closely monitor glucose when switching to REZVOGLAR and during initial weeks thereafter. ( 2.4 ) 2.1 Important Administration Instructions Always check insulin labels before administration [see Warnings and Precautions ( 5.4 )] . Visually inspect REZVOGLAR KwikPen prefilled pens for particulate matter and discoloration prior to administration. Only use if the solution is clear and colorless with no visible particles. Administer REZVOGLAR subcutaneously into the abdominal area, thigh, or deltoid, and rotate injection sites within the same region from one injection to the next to reduce the risk of lipodystrophy and localized cutaneous amyloidosis. Do not inject into areas of lipodystrophy or localized cutaneous amyloidosis [see Warnings and Precautions ( 5.2 ), and Adverse Reactions ( 6 )] . During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ( 5.2 )] . Do not administer intravenously or via an insulin pump. Do not dilute or mix REZVOGLAR with any other insulin or solution. The REZVOGLAR KwikPen prefilled pen dials in 1-unit increments. Use REZVOGLAR KwikPen prefilled pen with caution in patients with visual impairment who may rely on audible clicks to dial their dose. 2.2 General Dosing Instructions Administer REZVOGLAR subcutaneously once daily at any time of day but at the same time every day. Individualize and adjust the dosage of REZVOGLAR based on the patient's metabolic needs, blood glucose monitoring results and glycemic control goal. Dosage adjustments may be needed with changes in physical activity, changes in meal patterns (i.e., macronutrient content or timing of food intake), during acute illness, or changes in renal or hepatic function. Dosage adjustments should only be made under medical supervision with appropriate glucose monitoring [see Warnings and Precautions ( 5.2 )] . In patients with type 1 diabetes, REZVOGLAR must be used concomitantly with short-acting insulin. 2.3 Initiation of REZVOGLAR Therapy Recommended Starting Dosage in Patients with Type 1 Diabetes The recommended starting dosage of REZVOGLAR in patients with type 1 diabetes is approximately one-third of the total daily insulin requirements. Use short-acting, premeal insulin to satisfy the remainder of the daily insulin requirements....

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following adverse reactions are discussed elsewhere: Hypoglycemia [see Warnings and Precautions ( 5.3 )] . Hypoglycemia Due to Medication Errors [see Warnings and Precautions ( 5.4 )] . Hypersensitivity Reactions [see Warnings and Precautions ( 5.5 )] . Hypokalemia [see Warnings and Precautions ( 5.6 )] . Adverse reactions commonly associated with insulin glargine products include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema, and weight gain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-LillyRx (1-800-545-5979) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of a drug cannot be directly compared to rates in the clinical trial of another drug and may not reflect the rates observed in practice. The data in Table 1 reflect the exposure of 2327 patients with type 1 diabetes to insulin glargine or NPH in Studies A, B, C, and D [see Clinical Studies ( 14.2 )] . The type 1 diabetes population had the following characteristics: Mean age was 39 years. Fifty-four percent were male, 97% were Caucasian, 2% were Black or African American and 3% were Hispanic. The mean BMI was 25.1 kg/m 2 . The data in Table 2 reflect the exposure of 1563 patients with type 2 diabetes to insulin glargine or NPH in Studies E, F, and G [see Clinical Studies ( 14.3 )] . The type 2 diabetes population had the following characteristics: Mean age was 59 years. Fifty-eight percent were male, 87% were Caucasian, 8% were Black or African American and 9% were Hispanic. The mean BMI was 29.2 kg/m 2 . The frequencies of adverse reactions during insulin glargine clinical studies in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below (Tables 1 , 2 , 3 , and 4 ). Table 1: Adverse Reactions Occurring ≥5% in Pooled Clinical Studies up to 28 Weeks Duration in Adults with Type 1 Diabetes * Body system not specified Insulin Glargine, % (n=1257) NPH, % (n=1070) Upper respiratory tract infection 22.4 23.1 Infection* 9.4 10.3 Accidental injury 5.7 6.4 Headache 5.5 4.7 Table 2: Adverse Reactions Occurring ≥5% in Pooled Clinical Studies up to 1 Year Duration in Adults with Type 2 Diabetes * Body system not specified Insulin Glargine, % (n=849) NPH, % (n=714) Upper respiratory tract infection 11.4 13.3 Infection* 10.4 11.6 Retinal vascular disorder 5.8 7.4 Table 3: Adverse Reactions Occurring ≥10% in a 5-Year Study of Adults with Type 2 Diabetes Insulin Glargine, % (n=514) NPH, % (n=503) Upper respiratory tract infection 29.0 33.6 Edema peripheral 20.0 22.7 Hypertension 19.6 18.9 Influenza 18.7 19.5 Sinusitis 18.5 17.9 Cataract 18.1 15.9 Bronchitis 15.2 14.1 Arthralgia 14.2 16.1 Pain in extremity 13.0 13.1 Back pain 12.8 12.3 Cough 12.1 7.4 Urinary tract infection 10.7 10.1 Diarrhea 10.7 10.3 Depression 10.5 9.7 Headache 10.3 9.3 Table 4: Adverse Reactions Occurring ≥5% in a 28-Week Clinical Study in Pediatric Patients with Type 1 Diabetes * Body system not specified Insulin Glargine,% (n=174) NPH, % (n=175) Infection* 13.8 17.7 Upper respiratory tract infection 13.8 16.0 Pharyngitis 7.5 8.6 Rhinitis 5.2 5.1 Severe Hypoglycemia Hypoglycemia was the most commonly observed adverse reaction in patients treated with insulin glargine. Tables 5 , 6 , and 7 summarize the incidence of severe hypoglycemia in insulin glargine clinical studies. Severe symptomatic hypoglycemia was defined as an event with symptoms consistent with hypoglycemia requiring the assistance of another person and associated with either a blood glucose below 50 mg/dL (≤56 mg/dL in the 5-year study and ≤36 mg/dL in the ORIGIN study) or prompt recovery after oral carbohydrate, intravenous glucose or glucagon administration. Percentages of insulin glargine-treated adult patients who experienced severe...

Drug Interactions

7 DRUG INTERACTIONS Table 8 includes clinically significant drug interactions with REZVOGLAR. Table 8: Clinically Significant Drug Interactions with REZVOGLAR 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), sulfonamide antibiotics. GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT-2 inhibitors. Intervention: Dosage reductions and increased frequency of glucose monitoring may be required when REZVOGLAR is coadministered with these drugs. Drugs that May Decrease the Blood Glucose Lowering Effect of REZVOGLAR 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 REZVOGLAR is coadministered with these drugs. Drugs that May Increase or Decrease the Blood Glucose Lowering Effect of REZVOGLAR Drugs: Alcohol, beta-blockers, clonidine, and lithium salts. Pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia. Intervention: Dose adjustment and increased frequency of glucose monitoring may be required when REZVOGLAR is coadministered 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 REZVOGLAR is coadministered with these drugs. Drugs that affect glucose metabolism: Adjustment of insulin dosage may be needed. ( 7 ) Antiadrenergic Drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine): Signs and symptoms of hypoglycemia may be reduced or absent. ( 5.3 , 7 )

Contraindications

4 CONTRAINDICATIONS REZVOGLAR is contraindicated: during episodes of hypoglycemia [see Warnings and Precautions ( 5.3 )] . in patients with hypersensitivity to insulin glargine products or any of the excipients in REZVOGLAR [see Warnings and Precautions ( 5.5 )] . During episodes of hypoglycemia. ( 4 ) Hypersensitivity to insulin glargine products or any of the excipients in REZVOGLAR. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Published studies with use of insulin glargine products during pregnancy have not reported a clear association with insulin glargine products and adverse developmental outcomes (see Data). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Rats and rabbits were exposed to insulin glargine in animal reproduction studies during organogenesis, respectively 50 times and 10 times the human subcutaneous dosage of 0.2 units/kg/day. Overall, the effects of insulin glargine did not generally differ from those observed with regular human insulin (see Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The estimated background risk of major birth defects is 6% to 10% in women with pregestational diabetes with a peri-conceptional HbA1c >7 and has been reported to be as high as 20% to 25% in women with a peri-conceptional HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. Clinical Considerations Disease-Associated Maternal and/or Embryo-fetal Risk Hypoglycemia and hyperglycemia occur more frequently during pregnancy in patients with pre-gestational diabetes. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity. Data Human Data Published data do not report a clear association with insulin glargine products and major birth defects, miscarriage, or adverse maternal or fetal outcomes when insulin glargine is used during pregnancy. However, these studies cannot definitely establish the absence of any risk because of methodological limitations including small...

Overdosage

10 OVERDOSAGE Excess insulin administration may cause hypoglycemia and hypokalemia [see Warnings and Precautions ( 5.3 , 5.6 )] . Mild episodes of hypoglycemia can usually be treated with oral carbohydrates. Lowering the insulin dosage, and adjustments in meal patterns or exercise may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with glucagon for emergency use or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid recurrence of hypoglycemia. Hypokalemia must be corrected appropriately.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Product: 50090-6439 NDC: 50090-6439-0 3 mL in a SYRINGE / 5 in a CARTON

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.