Ryzodeg

Last updated on RxList: 5/21/2021
Ryzodeg Side Effects Center

What Is Ryzodeg?

Ryzodeg 70/30 (insulin degludec and insulin aspart injection) is an insulin analog indicated to improve glycemic control in adults with diabetes mellitus.

What Are Side Effects of Ryzodeg?

Common side effects of Ryzodeg include:

Dosage for Ryzodeg

The dose of Ryzodeg is individualized based on type of diabetes, metabolic needs, blood glucose monitoring results, and glycemic control goal.

What Drugs, Substances, or Supplements Interact with Ryzodeg?

Ryzodeg may with other insulin products, beta-blockers, clonidine, guanethidine, reserpine, other antidiabetic agents, ACE inhibitors, angiotensin II receptor blocking agents, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, pramlintide, propoxyphene, salicylates, somatostatin analogs, sulfonamide antibiotics, GLP-1 receptor agonists, DDP-4 inhibitors, SGLT-2 inhibitors, atypical antipsychotics, corticosteroids, danazol, diuretics, estrogens, glucagon, isoniazid, niacin, oral contraceptives, phenothiazines, progestogens, protease inhibitors, somatropin, sympathomimetic agents, thyroid hormones, alcohol, lithium salts, or pentamidine. Tell your doctor all medications and supplements you use.

Ryzodeg During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant while taking Ryzodeg. During pregnancy, Ryzodeg should only be taken if prescribed. It is unknown if Ryzodeg passes into breast milk. Women with diabetes who are nursing may require adjustments in insulin dose, meal plan, or both. Consult your doctor before breastfeeding.

Additional Information

Our Ryzodeg 70/30 (insulin degludec and insulin aspart 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.

QUESTION

______________ is another term for type 2 diabetes. See Answer
Ryzodeg Professional Information

SIDE EFFECTS

The following adverse reactions are also discussed elsewhere:

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of RYZODEG 70/30 in subjects with type 1 diabetes or type 2 diabetes was evaluated in five trials of 6-12 month duration in adults and in one trial of 16 week duration in pediatric patients 1 year of age and older with type 1 diabetes [see Clinical Studies].

The data in Table 1 reflect the exposure of 362 adults with type 1 diabetes to RYZODEG 70/30, with a mean exposure duration to RYZODEG 70/30 of 43 weeks. The mean age was 41 years and 1% were older than 75 years. Fifty-two percent were male, 91% were White, 3% were Black or African American and 3% were Hispanic. The mean body mass index (BMI) was 26 kg/m2. The mean duration of diabetes was 17 years and the mean HbA1c at baseline was 8.3%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported in 19%, 25%, 6% and 4% respectively. The mean eGFR at baseline was 88 mL/min/1.73 m2 and 6% of patients had an eGFR less than 60 mL/min/1.73 m2.

The data in Table 2 reflect the exposure of 998 adults with type 2 diabetes to RYZODEG 70/30 with a mean exposure duration to RYZODEG 70/30 of 24 weeks. The mean age was 58 years and 3% were older than 75 years. Fifty-four percent were male, 44% were White, 4% were Black or African American and 6% were Hispanic. The mean BMI was 29 kg/m2. The mean duration of diabetes was 12 years and the mean HbA1c at baseline was 8.5%. A history of neuropathy, ophthalmopathy, nephropathy and cardiovascular disease at baseline was reported for 15%, 21%, 10% and 1% respectively. At baseline, the mean eGFR was 84 mL/min/1.73 m2 and 11% of patients had an eGFR less than 60 mL/min/1.73 m2.

Common adverse reactions (excluding hypoglycemia) occurring in RYZODEG 70/30-treated subjects during clinical trials in adult patients with type 1 diabetes mellitus and adults with type 2 diabetes mellitus are listed in Tables 1 and 2, respectively. Common adverse reactions were defined as reactions occurring in ≥5% of the population studied. Hypoglycemia is not shown in these tables but discussed in a dedicated subsection below.

181 pediatric patients 1 year of age and older with type 1 diabetes were exposed to RYZODEG 70/30 with a mean exposure duration to RYZODEG 70/30 of 16 weeks. The mean age was 10.5 years: 22.5% were ages 1-5 years, 33.5% were ages 6-11 years, and 44% were ages 12-17 years. 48.9% were male, 92.9% were White, 4.4% were Black or African American and 8.2% were Hispanic. The mean body mass index (BMI) was 19.2 kg/m2. The mean duration of diabetes was 4.4 years and the mean HbA1c at baseline was 8.1%. A history of neuropathy and nephropathy at baseline was reported in 2.2% and 0.5%, respectively. Common adverse reactions in RYZODEG 70/30 treated children with type 1 diabetes mellitus were similar to the adverse reactions listed in Table 1.

Table 1: Adverse Reactions Occurring in ≥5% of RYZODEG 70/30-Treated Adult Patients with Type 1 Diabetes Mellitus

Adverse Reaction RYZODEG 70/30
(N=362)
Nasopharyngitis 24.6%
Headache 9.7%
Upper respiratory tract infection 9.1%
Influenza 6.9%

Table 2: Adverse Reactions Occurring in ≥5% of RYZODEG 70/30-Treated Adult Patients with Type 2 Diabetes Mellitus

Adverse Reaction RYZODEG 70/30
(N=998)
Nasopharyngitis 11.1%
Upper respiratory tract infection 5.7%
Headache 5.6%

Hypoglycemia

Hypoglycemia is the most commonly observed adverse reaction in patients using insulin, including RYZODEG 70/30 [see WARNINGS AND PRECAUTIONS]. 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 RYZODEG 70/30 with the incidence of hypoglycemia for other products may be misleading and also, may not be representative of hypoglycemia rates that occur in clinical practice.

Rates of hypoglycemia by trial are shown in Table 3 for type 1 diabetes in adult and pediatric patients and Table 4 for type 2 diabetes in adults treated with RYZODEG 70/30 [see Clinical Studies]. Severe hypoglycemia in trials with adult patients was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Severe hypoglycemia in the pediatric trial was defined as an altered mental status where the child could not assist in his own care, was semiconscious or unconscious, or in a coma ± convulsions and may require parenteral therapy (glucagon or intravenous glucose).

A Novo Nordisk hypoglycemia episode was defined as a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms).

Table 3: Percent (%) of Patients with Type 1 Diabetes Experiencing at Least One Episode of Severe Hypoglycemia or Novo Nordisk Hypoglycemia§ on RYZODEG 70/30 in Adult and Pediatric Clinical Trials

  Study A RYZODEG 70/30 OD* + Insulin Aspart BID**, Adults 52 weeks
(N= 362)
Study F RYZODEG 70/30 OD* + Insulin Aspart TID***, Pediatrics 16 weeks
(N= 181)
Severe hypoglycemia±
Percent of patients 13.3% 6.1%
Novo Nordisk hypoglycemia§
Percent of patients 95.0% 92.8%
*OD: once daily
**BID: twice daily
***TID: three times daily
±Severe hypoglycemia in pediatric patients: an episode with altered mental status, where the child could not assist in his own care, was semiconscious or unconscious, or in a coma ± convulsions and may require parenteral therapy (glucagon or intravenous glucose).
§Novo Nordisk hypoglycemia: a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms).

Table 4: Percent (%) of Patients with Type 2 Diabetes Experiencing at Least One Episode of Severe Hypoglycemia or Novo Nordisk Hypoglycemia§ on RYZODEG 70/30 in Adult Clinical Trials

  Study B RYZODEG 70/30 OD* insulin naïve, previously on 2 or more OADs***
(N=265)
Study C RYZODEG 70/30 OD* previously on basal insulin OD and 1 or more OADs***
(N=230)
Study D RYZODEG 70/30 BID** previously on OD*/BID premix/self-mix, ±OADs***
(N=224)
Study E RYZODEG 70/30 BID** previously on OD*/BID basal/premix/self-mix, ±OADs***
(N=279)
Severe hypoglycemia
Percent of patients 0.4% 0% 3.1% 1.4%
Novo Nordisk hypoglycemia
Percent of patients 49.8% 52.6% 66.1% 73.5%
*OD: once daily
**BID: twice daily
***OAD: oral anti-diabetic agent
§Novo Nordisk hypoglycemia: a severe hypoglycemia episode or an episode where a laboratory or a self-measured glucose calibrated to plasma was less than 56 mg/dL or where a whole blood glucose was less than 50 mg/dL (i.e., with or without the presence of hypoglycemic symptoms).

Allergic Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, generalized skin reactions, angioedema, bronchospasm, hypotension, and shock may occur with any insulin, including RYZODEG 70/30 and may be life threatening [see WARNINGS AND PRECAUTIONS]. Hypersensitivity (manifested with swelling of tongue and lips, diarrhea, nausea, tiredness and itching) and urticaria were reported in 0.5% of patients treated with RYZODEG 70/30.

Lipodystrophy

Long-term use of insulin, including RYZODEG 70/30, 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. Rotate insulin injection sites within the same region to reduce the risk of lipodystrophy [see DOSAGE AND ADMINISTRATION]. In the clinical program, lipodystrophy was reported in 0.1% of patients treated with RYZODEG 70/30.

Injection Site Reactions

Patients taking RYZODEG 70/30 may experience injection site reactions, including injection site hematoma, pain, hemorrhage, erythema, nodules, swelling, discoloration, pruritus, warmth, and injection site mass. In the clinical program, injection site reactions occurred in 2.0% of patients treated with RYZODEG 70/30.

Weight Gain

Weight gain can occur with insulin therapy, including RYZODEG 70/30, and has been attributed to the anabolic effects of insulin. In the clinical program, patients with type 1 diabetes treated with RYZODEG 70/30 gained an average of 2.8 kg and patients with type 2 diabetes treated with RYZODEG 70/30 gained an average of 1.6 kg.

Peripheral Edema

Insulin, including RYZODEG 70/30, may cause sodium retention and edema. In the clinical program, peripheral edema occurred in 2.2% of patients with type 1 diabetes mellitus and 1.8% of patients with type 2 diabetes mellitus treated with RYZODEG 70/30.

Immunogenicity

As with all therapeutic proteins, insulin administration may cause anti-insulin antibodies to form. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay and may be influenced by several factors such as: assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to RYZODEG 70/30 with the incidence of antibodies in other studies or to other products, may be misleading.

Insulin Aspart Antibodies

In studies of adult insulin-experienced type 1 diabetes patients, 13% of patients who received RYZODEG 70/30 once daily were positive for anti-insulin aspart antibodies at least once during the studies, including 6.4% who were positive at baseline. In studies of adult insulin-naïve type 2 diabetes patients, 12.5% of patients who received RYZODEG 70/30 once daily were positive for anti-insulin aspart antibodies at least once during the studies, including 9.1% who were positive at baseline. In a 26-week study of adult insulin-experienced type 2 diabetes patients, 21.5% of patients who received RYZODEG 70/30 twice daily were positive for anti-insulin aspart antibodies at least once during the study, including 15.4% who were positive at baseline.

Insulin Degludec Antibodies

In a 26-week study of adult insulin-experienced type 1 diabetes patients, 63.5% of patients who received RYZODEG 70/30 once daily were positive at baseline for anti-insulin degludec antibodies and 15.4% of patients developed anti-insulin degludec antibodies at least once during the study. In a 26-week study of adult insulin-naïve type 2 diabetes patients, 5.3% of patients who received RYZODEG 70/30 once daily were positive at baseline for anti-insulin degludec antibodies and 15.5% of patients developed anti-insulin degludec antibodies at least once during the study. In a 26-week study of adult insulin-experienced type 2 diabetes patients, 52.5% of patients who received RYZODEG 70/30 twice daily were positive at baseline for anti-insulin degludec antibodies and 6.7% of patients developed anti-insulin degludec antibodies at least once during the study. In these trials, between 99.4% and 100% of patients who were positive for anti-insulin degludec antibodies were also positive for anti-human insulin antibodies.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of insulin degludec and insulin aspart components of RYZODEG 70/30. 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.

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.

Read the entire FDA prescribing information for Ryzodeg (Insulin Degludec and Insulin Aspart Injection)

SLIDESHOW

Type 2 Diabetes: Signs, Symptoms, Treatments See Slideshow

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

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