Dosing and uses of Ryzodeg (insulin degludec/insulin aspart)
Adult dosage forms and strengths
prefilled pen
- insulin degludec 70 units/insulin aspart 30 units per mL (ie, 100 units/mL for combination)
Diabetes Mellitus Types 1 & 2
Indicated to improve glycemic control in adults with diabetes mellitus
Starting dose in insulin naïve patients
- Type 1 diabetes mellitus: ~One third to one half of the total daily insulin dose; as a general rule; the remainder of the total daily insulin dose should be administered as a short- or rapid-acting insulin divided between each daily meal; 0.2-0.4 units/kg can be used to calculate the initial total daily insulin dose in insulin-naïve patients with type 1 diabetes
- Type 2 diabetes mellitus: 10 units SC once daily
Starting dose in patients with types 1 or 2 diabetes on a once or twice daily premix or self-mix insulin alone or as part of a regimen of multiple daily injections
- Start insulin degludec/insulin aspart 70/30 at the same unit dose and injection schedule as the premix or self-mix insulin
- In patients also using short- or rapid-acting insulin at mealtimes, continue the short- or rapid-acting insulin at the same dose for meals NOT covered by degludec/insulin aspart 70/30
Starting dose in patients with types 1 or 2 diabetes on a once or twice daily basal insulin alone or as part of a regimen of multiple daily injections
- Patients with T2DM switching from regimen that includes only a once- or twice-daily basal insulin, start insulin degludec/insulin aspart 70/30 at the same unit dose and injection schedule
- For patients switching from once-daily basal insulin to once-daily insulin degludec/insulin aspart 70/30, monitor blood glucose after starting therapy due to the rapid-acting insulin component
- In patients switching from a multiple daily injections regimen that includes a basal and short- or rapid-acting insulin at mealtimes, start insulin degludec/insulin aspart 70/30 once daily with the main meal at the same unit dose as the basal insulin; continue the short- or rapid-acting insulin at the same dose for meals NOT covered by insulin degludec/insulin aspart 70/30
Dosing Considerations
Not recommended for treatment of diabetic ketoacidosis
Pediatric dosage forms and strengths
Safety and efficacy not established
Ryzodeg (insulin degludec/insulin aspart) adverse (side) effects
>10%
Nasopharyngitis (11.1-24.6%)
Severe hypoglycemia (0.4-13.3%)
1-10%
Headache (5.6-9.7%)
URT infection (5.7-9.1%)
Influenza (6.9%)
Peripheral edema (1.8-2.2%)
Injection site reaction (2%)
<1%
Allergic reaction
Lipodystrophy
Warnings
Contraindications
During episodes of hypoglycemia
Documented hypersensitivity
Cautions
Do not share, even if the needle is changed; sharing poses a risk for transmission of blood-borne pathogens
Changes in insulin, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia or hyperglycemia; these changes should be made cautiously and only under medical supervision, and the frequency of blood glucose monitoring should be increased
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur
All insulin products cause a shift in potassium from the extracellular to intracellular space, possibly leading to hypokalemia; monitor potassium levels in patients at risk for hypokalemia including patients using potassium-lowering medications or those taking medications sensitive to serum potassium concentrations; treat if indicated
Thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR)-gamma agonists can cause dose-related fluid retention, particularly when used in combination with insulin; this may lead to or exacerbate heart failure
Hypoglycemia
- Hypoglycemia is the most common adverse effect and can happen suddenly; severe hypoglycemia can cause seizures, may be life-threatening, or cause death
- Hypoglycemia can impair concentration ability and reaction time and place an individual and others at risk in situations where these abilities are important (eg, driving or operating other machinery)
- Risk increases with intensity of glycemic control and is related to the duration of action of the insulin
- Other factors that may increase the risk of hypoglycemia include changes in meal pattern (eg, macronutrient content or timing of meals), changes in level of physical activity, or changes to coadministered medication
- Renal or hepatic impairment may increase hypoglycemia risk
- In patients at higher risk for hypoglycemia and patients who have reduced symptomatic awareness of hypoglycemia, increased frequency of blood glucose monitoring is recommended
- Accidental mix-ups between basal insulin products and other insulins, particularly rapid-insulins, have been reported
- Do not transfer insulin degludec from the prefilled pen to a syringe; the markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia
Pregnancy
Pregnancy
Pregnancy category: C
Animal studies
- The effect of insulin degludec was consistent with those observed with human insulin as both caused preimplantation and postimplantation losses and visceral/skeletal abnormalities in rats at an insulin degludec dose of 21 U/kg/day (~5 times the human exposure [AUC] at a human SC dose of 0.75 U/kg/day) and in rabbits at a dose of 3.3 U/kg/day (~10 times the AUC at a human SC dose of 0.75 U/kg/day)
- The effects are probably secondary to maternal hypoglycemia
Lactation
Unknown if distributed in human breast milk
Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Ryzodeg (insulin degludec/insulin aspart)
Mechanism of action
Insulin degludec: Long-acting basal insulin
Insulin aspart: Rapid-acting insulin
Insulin and its analogues 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; targets include skeletal muscle, liver, and adipose tissue
Absorption
Onset of action (insulin aspart): 14 min
Peak plasma time: 9 hr insulin degludec; 72 min insulin aspart
Steady state (insulin degludec): 3-4 days
Distribution
Protein bound: >99% to albumin insulin degludec; <10% insulin aspart
Metabolism
Metabolites: Inactive
Elimination
Half-life: ~25 hr insulin degludec
Administration
Preparation
Inspect visually for particulate matter and discoloration; only use if the solution appears clear and colorless
Do not dilute or mix with any other insulin products or solutions
Do not transfer drug from the insulin degludec pen into a syringe for administration
SC Administration
Inject SC once or twice daily with any main meaL
Administer a rapid- or a short-acting insulin at other meals if needed
Patients with type 1 diabetes, will generally require a rapid- or short-acting insulin at meals when insulin degludec/insulin aspart 70/30 is not administered for optimal glucose controL
Individualize and titrate the dose based on the patient’s metabolic needs, blood glucose monitoring results, and glycemic control goaL
Adjust dose according to blood glucose measurements before breakfast (fasting)
Inject SC into the thigh, upper arm, or abdomen
The recommended days between dose increases is 3-4 days
Dose adjustments may be needed with changes in physical activity, changes in meal patterns (ie, macronutrient content or timing of food intake), changes in renal or hepatic function, or during acute illness to minimize the risk of hypoglycemia or hyperglycemia
If a dose of insulin degludec/insulin aspart 70/30 is missed, the next dose should be taken with the next main meal of that day and thereafter resume the usual dosing schedule; patients should not take an extra dose to make up for a missed dose
Storage
Unopened (not in-use) prefilled pen
- Refrigerate at 36-46°F (2-8°C)
- Do not store in the freezer or directly adjacent to the refrigerator cooling element
- Do not freeze
- Do not use if it has been frozen
Open (in-use) prefilled pen
- Should NOT be refrigerated but should be kept at room temperature (<86°F [30°C])
- Keep away from direct heat and light
- The opened pen may be used for up to 28 days (4 wk) after being opened, if it is kept at room temperature
