Rezgovlar
(insulin glargine-aglr)Dosage & Administration
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Rezgovlar Prescribing Information
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.
Important Administration Instructions
- Always check insulin labels before administration [see Warnings and Precautions ].
- 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 , and Adverse Reactions ].
- During changes to a patient's insulin regimen, increase the frequency of blood glucose monitoring [see Warnings and Precautions ].
- 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.
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 ].
- In patients with type 1 diabetes, REZVOGLAR must be used concomitantly with short-acting insulin.
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.
Recommended Starting Dosage in Patients with Type 2 Diabetes
The recommended starting dosage of REZVOGLAR in patients with type 2 diabetes who are not currently treated with insulin is 0.2 units/kg or up to 10 units once daily.
Switching to REZVOGLAR from Other Insulin Therapies
Dosage adjustments are recommended to lower the risk of hypoglycemia when switching patients to REZVOGLAR from other insulin therapies [see Warnings and Precautions ]. When switching from:
- Once-daily insulin glargine, 300 units/mL, to once-daily REZVOGLAR (100 units/mL), the recommended starting REZVOGLAR dosage is 80% of the insulin glargine, 300 units/mL dosage that is being discontinued.
- Once-daily NPH insulin to once-daily REZVOGLAR, the recommended starting REZVOGLAR dosage is the same as the dosage of NPH that is being discontinued.
- Twice-daily NPH insulin to once-daily REZVOGLAR, the recommended starting REZVOGLAR dosage is 80% of the total NPH dosage that is being discontinued.
Injection: 100 units/mL (U-100) a clear and colorless solution available as:
- 3 mL single-patient-use REZVOGLAR KwikPen prefilled pen.
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 sample size and some lacking comparator groups.
Animal Data
Subcutaneous reproduction and teratology studies have been performed with insulin glargine and regular human insulin in rats and Himalayan rabbits. Insulin glargine was given to female rats before mating, during mating, and throughout pregnancy at doses up to 0.36 mg/kg/day, which is approximately 50 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day (0.007 mg/kg/day), on a mg/kg basis. In rabbits, doses of 0.072 mg/kg/day, which is approximately 10 times the recommended human subcutaneous starting dosage of 0.2 units/kg/day on a mg/kg basis, were administered during organogenesis. The effects of insulin glargine did not generally differ from those observed with regular human insulin in rats or rabbits. However, in rabbits, five fetuses from two litters of the high-dose group exhibited dilation of the cerebral ventricles. Fertility and early embryonic development appeared normal.
Lactation
Risk Summary
There are either no or only limited data on the presence of insulin glargine products in human milk, the effects on the breastfed infant, or the effects on milk production. Endogenous insulin is present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for REZVOGLAR and any potential adverse effects on the breastfed child from REZVOGLAR or from the underlying maternal condition.
Pediatric Use
The safety and effectiveness of REZVOGLAR to improve glycemic control in pediatric patients with diabetes mellitus have been established. Use of REZVOGLAR for this indication is supported by evidence from an adequate and well-controlled study (Study D) in 174 insulin glargine-treated pediatric patients aged 6 to 15 years with type 1 diabetes mellitus, and from adequate and well-controlled studies of insulin glargine in adults with diabetes mellitus [see Clinical Pharmacology , Clinical Studies ].
In the pediatric clinical study, pediatric patients with type 1 diabetes had a higher incidence of severe symptomatic hypoglycemia compared to the adults in studies with type 1 diabetes [see Adverse Reactions ].
Geriatric Use
Of the total number of subjects in controlled clinical studies of patients with type 1 and type 2 diabetes who were treated with insulin glargine, 15% (n=316) were ≥65 years of age and 2% (n=42) were ≥75 years of age. No overall differences in safety or effectiveness of insulin glargine have been observed between patients 65 years of age and older and younger adult patients.
Nevertheless, caution should be exercised when REZVOGLAR is administered to geriatric patients. In geriatric patients with diabetes, the initial dosing, dosage increments, and maintenance dosage should be conservative to avoid hypoglycemic reactions. Hypoglycemia may be difficult to recognize in geriatric patients.
Renal Impairment
The effect of kidney impairment on the pharmacokinetics of insulin glargine products has not been studied. Some studies with human insulin have shown increased circulating levels of insulin in patients with kidney failure. Frequent glucose monitoring and dosage adjustment may be necessary for REZVOGLAR in patients with kidney impairment [see Warnings and Precautions ].
Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of insulin glargine products has not been studied. Frequent glucose monitoring and dosage adjustment may be necessary for REZVOGLAR in patients with hepatic impairment [see Warnings and Precautions ].
REZVOGLAR is contraindicated:
- during episodes of hypoglycemia [see Warnings and Precautions ].
- in patients with hypersensitivity to insulin glargine products or any of the excipients in REZVOGLAR [see Warnings and Precautions ].
Never Share a REZVOGLAR KwikPen Prefilled Pen Between Patients
REZVOGLAR KwikPen prefilled pens must never be shared between patients, even if the needle is changed. Sharing poses a risk for transmission of blood-borne pathogens.
Hyperglycemia or Hypoglycemia with Changes in Insulin Regimen
Changes in an insulin regimen (e.g., insulin strength, manufacturer, type, injection site or method of administration) may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions ] or hyperglycemia. Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis have been reported to result in hyperglycemia; and a sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia [see Adverse Reactions ].
Make any changes to a patient's insulin regimen under close medical supervision with increased frequency of blood glucose monitoring. Advise patients who have repeatedly injected into areas of lipodystrophy or localized cutaneous amyloidosis to change the injection site to unaffected areas and closely monitor for hypoglycemia. For patients with type 2 diabetes, dosage adjustments of concomitant oral and antidiabetic products may be needed.
Hypoglycemia
Hypoglycemia is the most common adverse reaction associated with insulins, including insulin glargine products. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place the patient and others at risk in situations where these abilities are important (e.g., driving or operating other machinery).
Hypoglycemia can happen suddenly and symptoms may differ in each patient and change over time in the same patient. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic neuropathy, using drugs that block the sympathetic nervous system (e.g., beta-blockers) [see Drug Interactions ], or who experience recurrent hypoglycemia.
The long-acting effect of insulin glargine products may delay recovery from hypoglycemia.
Risk Factors for Hypoglycemia
The risk of hypoglycemia after an injection is related to the duration of action of the insulin and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulins, the glucose lowering effect time course of insulin glargine products may vary in different patients or at different times in the same patient and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature [see Clinical Pharmacology ]. Other factors which may increase the risk of hypoglycemia include changes in meal pattern (e.g., macronutrient content or timing of meals), changes in level of physical activity, or changes to concomitant drugs [see Drug Interactions ]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations ].
Risk Mitigation Strategies for Hypoglycemia
Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring of blood glucose plays an essential role in the prevention and management of hypoglycemia. In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended.
Hypoglycemia Due to Medication Errors
Accidental mix-ups among insulin products have been reported. To avoid medication errors between REZVOGLAR and other insulins, instruct patients to always check the insulin label before each injection [see Adverse Reactions ].
Hypersensitivity Reactions
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulins, including insulin glargine products [see Adverse Reactions ]. If hypersensitivity reactions occur, discontinue REZVOGLAR; treat per standard of care and monitor until symptoms and signs resolve. REZVOGLAR is contraindicated in patients who have had hypersensitivity reactions to insulin glargine products or one of the excipients in REZVOGLAR.
Hypokalemia
All insulins, including insulin glargine products, cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Monitor potassium levels in patients at risk for hypokalemia if indicated (e.g., patients using potassium-lowering medications, patients taking medications sensitive to serum potassium concentrations).
Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists
Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists, can cause dose-related fluid retention, when used in combination with insulin. Fluid retention may lead to or exacerbate heart failure. Patients treated with insulin, including REZVOGLAR, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If heart failure develops, it should be managed according to current standards of care, and discontinuation or dose reduction of the PPAR-gamma agonist must be considered.