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.
Overdose of Ryzodeg in details
When a dose is taken in higher dose than the recommended doses, it is called Overdose. Overdose always needs a clinical supervision. Any medicine or drug when consumed in Overdose produces untoward side effects on one or various organs in the body. A medicine is excreted in the kidney or metabolized in the liver most of the times. This process goes without any hurdles when taken in normal dose, but when taken in an overdose, the body is not able to metabolize it or send it out properly which causes the effects of anoverdose.
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An excess of insulin relative to food intake, energy expenditure, or both may lead to severe and sometimes prolonged and life-threatening hypoglycemia and hypokalemia. Mild episodes of hypoglycemia usually can be treated with oral glucose. Adjustments in drug dosage, meal patterns, or exercise may be needed. More severe episodes of hypoglycemia with coma, seizure, or neurologic impairment may be treated with intramuscular/subcutaneous glucagon or concentrated intravenous glucose. After apparent clinical recovery from hypoglycemia, continued observation and additional carbohydrate intake may be necessary to avoid reoccurrence of hypoglycemia. Hypokalemia must be corrected appropriately.
What should I avoid while taking Ryzodeg?
Warnings are a mix of Precautions. Contraindications and interactions and serious harmful effects associated with the medicine intake. A diabetic or Hypertensive patient need to be warned about few drug interactions. A known hypersensitivity patient needs to be careful about the reactions or anaphylactic shock. A pregnant woman or a breastfeeding woman should be warned of certain medications. A Hepatitis [liver disease] patient or a cardiac patient should avoid few drugs.
Do not inject this medicine into a vein or muscle.
Avoid driving or operating machinery until you know how this medicine will affect you.
Avoid drinking alcohol. It can lower your blood sugar while using this medicine.
What should I discuss with my healthcare provider before taking Ryzodeg?
In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For Ryzodeg, the following should be considered:
Allergies
Tell your doctor if you have ever had any unusual or allergic reaction to Ryzodeg or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.
Pediatric
Appropriate studies have not been performed on the relationship of age to the effects of Ryzodeg combination in the pediatric population. Safety and efficacy have not been established.
Geriatric
Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of Ryzodeg combination in the elderly. However, elderly patients are more likely to have hypoglycemia, which may require caution and an adjustment in the dose for patients receiving Ryzodeg combination.
Pregnancy
Pregnancy Category
Explanation
All Trimesters
C
Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.
Breast Feeding
There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.
Interactions with Medicines
Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking Ryzodeg, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using Ryzodeg with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Balofloxacin
Besifloxacin
Ciprofloxacin
Enoxacin
Fleroxacin
Flumequine
Gatifloxacin
Gemifloxacin
Lanreotide
Levofloxacin
Liraglutide
Lomefloxacin
Metreleptin
Moxifloxacin
Nadifloxacin
Norfloxacin
Octreotide
Ofloxacin
Pasireotide
Pazufloxacin
Pefloxacin
Pioglitazone
Pramlintide
Prulifloxacin
Rosiglitazone
Rufloxacin
Sparfloxacin
Thioctic Acid
Tosufloxacin
Using Ryzodeg with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
Acebutolol
Albiglutide
Atenolol
Betaxolol
Bisoprolol
Bitter Melon
Carteolol
Carvedilol
Celiprolol
Dulaglutide
Esmolol
Exenatide
Fenugreek
Furazolidone
Glucomannan
Guar Gum
Iproniazid
Isocarboxazid
Labetalol
Levobunolol
Linezolid
Lixisenatide
Methylene Blue
Metipranolol
Metoprolol
Moclobemide
Nadolol
Nebivolol
Nialamide
Oxprenolol
Penbutolol
Phenelzine
Pindolol
Practolol
Procarbazine
Propranolol
Psyllium
Rasagiline
Safinamide
Selegiline
Sotalol
Timolol
Tranylcypromine
Interactions with Food/Tobacco/Alcohol
Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.
Using Ryzodeg with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use Ryzodeg, or give you special instructions about the use of food, alcohol, or tobacco.
Ethanol
Other Medical Problems
The presence of other medical problems may affect the use of Ryzodeg. Make sure you tell your doctor if you have any other medical problems, especially:
Hypoglycemia (low blood sugar)—Should not be used in patients with this condition.
Hypokalemia (low potassium in the blood)—May make this condition worse and increase your chance of having serious side effects.
Kidney disease or
Liver disease—Use with caution. The effects may be increased because of the slower removal of the medicine from the body.
Ryzodeg precautions
Certain people who are very sick or very old or who are sensitive show an exacerbation of side effect of the drug which can turn dangerous at times. So, it is very important to remember the precautions while taking the medicine. Pregnancy and Breastfeeding are also special categories wherein extra care or precaution is needed when taking a drug. Few patients may have a hypersensitivity reaction to few medications, and that can be life-threatening rarely. Penicillin hypersensitivity is one example. Diarrhea, rashes are few other symptoms which need a watch. A patient with other co-existing diseases like liver disease, heart disease, kidney disease should take special precautions.
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Never Share A RYZODEG 70/30 FlexTouch Pen Between Patients
RYZODEG 70/30 FlexTouch disposable prefilled pen should 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 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. For patients with type 2 diabetes, adjustments in concomitant oral anti-diabetic treatment may be needed. When converting from other insulin therapies to RYZODEG 70/30 follow dosing recommendations.
Hypoglycemia
Hypoglycemia is the most common adverse reaction of insulin, including RYZODEG 70/30. Severe hypoglycemia can cause seizures, may be life-threatening or cause death. Hypoglycemia can impair concentration ability and reaction time; this may place an individual and others at risk in situations where these abilities are important (e.g., driving or operating other machinery). RYZODEG 70/30, or any insulin, should not be used during episodes of hypoglycemia.
Hypoglycemia can happen suddenly and symptoms may differ in each individual and change over time in the same individual. Symptomatic awareness of hypoglycemia may be less pronounced in patients with longstanding diabetes, in patients with diabetic nerve disease, in patients using medications that block the sympathetic nervous system (e.g., beta-blockers) ) and, in general, is highest when the glucose lowering effect of the insulin is maximal. As with all insulin preparations, the glucose lowering effect time course of RYZODEG 70/30 may vary in different individuals or at different times in the same individual and depends on many conditions, including the area of injection as well as the injection site blood supply and temperature.
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 coadministered medication. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia.
Risk Mitigation Strategies for Hypoglycemia
Patients and caregivers must be educated to recognize and manage hypoglycemia. Selfmonitoring 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 between insulin products have been reported. To avoid medication errors between RYZODEG 70/30 and other insulins, instruct patients to always check the insulin label before each injection.
Do not transfer RYZODEG 70/30 from the RYZODEG 70/30 pen to a syringe. The markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia.
Hypersensitivity And Allergic Reactions
Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including RYZODEG 70/30. If hypersensitivity reactions occur, discontinue RYZODEG 70/30; treat per standard of care and monitor until symptoms and signs resolve. RYZODEG 70/30 is contraindicated in patients who have had hypersensitivity reactions to Insulin Degludec (Ryzodeg), Insulin Aspart (Ryzodeg), or one of the excipients.
Hypokalemia
All insulin products, including RYZODEG 70/30, 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 potassium concentrations).
Fluid Retention And Congestive Heart Failure With Concomitant Use Of A PPAR Gamma Agonist
Thiazolidinediones (TZDs), which are peroxisome proliferator-activated receptor (PPAR)- gamma agonists can cause dose related fluid retention, particularly when used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients treated with insulin, including RYZODEG 70/30 and a PPAR-gamma agonist should be observed for signs and symptoms of congestive heart failure. If congestive 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.
Patient Counseling Information
Never Share a RYZODEG 70/30 FlexTouch Pen Device Between Patients
Advise patients that they should never share a RYZODEG 70/30 FlexTouch pen device with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens.
Hyperglycemia or Hypoglycemia
Inform patients that hypoglycemia is the most common adverse reaction with insulin. Inform patients of the symptoms of hypoglycemia. Inform patients that the ability to concentrate and react may be impaired as a result of hypoglycemia. This may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Advise patients who have frequent hypoglycemia or reduced or absent warning signs of hypoglycemia to use caution when driving or operating machinery.
Advise patients that changes in insulin regimen can predispose to hyper- or hypoglycemia. Advise patients that changes in insulin regimen should be made under close medical supervision.
Medication errors
Inform patients to always check the insulin label before each injection.
Instruct patients that when injecting RYZODEG 70/30, they must press and hold down the dose button until the dose counter shows 0 and then keep the needle in the skin and count slowly to 6. When the dose counter returns to 0, the prescribed dose is not completely delivered until 6 seconds later. If the needle is removed earlier, they may see a stream of insulin coming from the needle tip. If so, the full dose will not be delivered, (a possible under-dose may occur by as much as 20%), and they should increase the frequency of checking their blood glucose levels and possible additional insulin administration may be necessary.
If 0 does not appear in the dose counter after continuously pressing the dose button, the patient may have used a blocked needle. In this case they would not have received any insulin—even though the dose counter has moved from the original dose that was set.
If the patient did have a blocked or damaged needle, instruct them to change the needle as described in Step 15 of the Instructions for Use and repeat all steps in the IFU starting with a new needle and the section Preparing your RYZODEG 70/30 FlexTouch Pen. Make sure the patient selects the full dose needed.
If patients routinely do not hold the needle under the skin as recommended, the patient may need to slightly increase the dialed insulin dose to achieve the patient's glycemic targets.
Instruct patients to not re-use needles. A new needle must be attached before each injection. Reuse of needles increases the risk of blocked needles which may cause under-dosing or overdosing.
Instruct Patients to never use a syringe to remove RYZODEG 70/30 from the FlexTouch disposable insulin prefilled pen.
Administration
RYZODEG 70/30 must only be used if the solution is clear and colorless with no particles visible.
Patients must be advised that RYZODEG 70/30 must NOT be diluted or mixed with any other insulin or solution.
Management of Hypoglycemia and Handling of Special Situations
Patients should be instructed on self-management procedures including glucose monitoring, proper injection technique, and management of hypoglycemia and hyperglycemia. Patients must be instructed on handling of special situations such as intercurrent conditions (illness, stress, or emotional disturbances), an inadequate or skipped insulin dose, inadvertent administration of an increased insulin dose, inadequate food intake, and skipped meals.
Refer patients to the RYZODEG 70/30 “Patient Information” for additional information about the potential side effects of insulin therapy, including lipodystrophy (and the need to rotate injection sites within the same body region), weight gain, allergic reactions, and hypoglycemia.
Women of Reproductive Potential
Advise patients to inform their health care professional if they are pregnant or are contemplating pregnancy.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Standard 2-year carcinogenicity studies in animals have not been performed to evaluate the carcinogenic potential of Insulin Degludec (Ryzodeg)/aspart RYZODEG 70/30.
In a 52-week study including human insulin (NPH insulin) as comparator, Sprague-Dawley rats were dosed subcutaneously with Insulin Degludec (Ryzodeg), the basal component of Insulin Degludec (Ryzodeg)/aspart RYZODEG 70/30 at 3.3, 6.7, and 10 U/kg/day resulting in 5 times the human exposure (AUC) when compared to a human subcutaneous dose of 1.08 U/kg/day RYZODEG 70/30. Human insulin was dosed at 6.7 U/kg/day. No treatment-related increases in incidences of hyperplasia, benign or malignant tumors were recorded in female mammary glands from rats dosed with Insulin Degludec (Ryzodeg) and no treatment related changes in the female mammary gland cell proliferation were found using BrdU incorporation. Further, no treatment related changes in the occurrence of hyperplastic or neoplastic lesions were seen in other tissues in animals dosed with Insulin Degludec (Ryzodeg) when compared to vehicle or human insulin.
In 52-week studies, Sprague-Dawley rats were dosed subcutaneously with Insulin Aspart (Ryzodeg), the rapid-acting component of Insulin Degludec (Ryzodeg)/aspart RYZODEG 70/30, at 10, 50, and 200 U/kg/day (approximately 2, 8, and 32 times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area, respectively). At a dose of 200 U/kg/day, Insulin Aspart (Ryzodeg) increased the incidence of mammary gland tumors in females when compared to untreated controls. The incidence of mammary tumors found with Insulin Aspart (Ryzodeg) was not significantly different from that found with regular human insulin. The relevance of these findings to humans is not known.
Genotoxicity testing of Insulin Degludec (Ryzodeg) was not performed. Insulin Aspart (Ryzodeg) was not genotoxic in the following tests: Ames test, mouse lymphoma cell forward gene mutation test, human peripheral blood lymphocyte chromosome aberration test, in vivo micronucleus test in mice, and ex vivo UDS test in rat liver hepatocytes.
In a combined fertility and embryo-fetal study in male and female rats, treatment with Insulin Degludec (Ryzodeg) up to 21 U/kg/day (approximately 5 times the human subcutaneous dose of 0.75 U/kg/day, based on U/body surface area) prior to mating and in female rats during gestation had no effect on mating performance.
In fertility studies with Insulin Aspart (Ryzodeg) (NOVOLOG) in male and female rats, at subcutaneous doses up to 200 U/kg/day (approximately 32 times the human subcutaneous dose, based on U/body surface area), no direct adverse effects on male and female fertility, or general reproductive performance of animals was observed.
Use In Specific Populations
Pregnancy
Pregnancy Category C
There are no adequate well-controlled clinical studies of the use of Insulin Degludec (Ryzodeg)/Insulin Aspart (Ryzodeg) in pregnant women. Patients should be advised to discuss with their health care provider if they intend to or if they become pregnant. Because animal reproduction studies are not always predictive of human response, Insulin Degludec (Ryzodeg)/Insulin Aspart (Ryzodeg) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is essential for patients with diabetes or a history of gestational diabetes to maintain good metabolic control before conception and throughout 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 in these patients.
An open-label, randomized study compared the safety and efficacy of NOVOLOG (Insulin Aspart (Ryzodeg), the rapid-acting component of RYZODEG 70/30) versus human insulin in the treatment of pregnant women with Type 1 diabetes (322 exposed pregnancies (Insulin Aspart (Ryzodeg): 157, human insulin: 165). Two-thirds of the enrolled patients were already pregnant when they entered the study. Since only one-third of the patients enrolled before conception, the study was not large enough to evaluate the risk of congenital malformations. Mean HbA1c of ~ 6% was observed in both groups during pregnancy, and there was no significant difference in the incidence of maternal hypoglycemia.
Subcutaneous reproduction and teratology studies have been performed with Insulin Degludec (Ryzodeg)/Insulin Aspart (Ryzodeg), and human insulin (NPH) as a comparator in rats. In these studies, Insulin Degludec (Ryzodeg)/Insulin Aspart (Ryzodeg) was given to rats during organogenesis. The effect of Insulin Degludec (Ryzodeg)/Insulin Aspart (Ryzodeg) was consistent with those observed with human insulin as both caused visceral/skeletal abnormalities in rats at dose of 30 U/kg/day (approximately 8 times the human subcutaneous dose of 1.08 U/kg/day based on U/body surface area).
Subcutaneous reproduction and teratology studies have been performed with Insulin Degludec (Ryzodeg) (basal component of Insulin Degludec (Ryzodeg)/Insulin Aspart (Ryzodeg)), and human insulin (NPH) as a comparator in rats and rabbits. In these studies, insulin was given to female rats before mating throughout pregnancy until weaning, and to rabbits during organogenesis. The effect of Insulin Degludec (Ryzodeg) was consistent with those observed with human insulin as both caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at an Insulin Degludec (Ryzodeg) dose of 21 U/kg/day (approximately 5 times the human exposure (AUC) at a human subcutaneous dose of 0.75 U/kg/day) and in rabbits at a dose of 3.3 U/kg/day (approximately 10 times the human exposure (AUC) at a human subcutaneous dose of 0.75 U/kg/day). The effects are probably secondary to maternal hypoglycemia.
Subcutaneous reproduction and teratology studies have been performed with NOVOLOG (Insulin Aspart (Ryzodeg), the rapid-acting component of RYZODEG 70/30) and regular human insulin in rats and rabbits. In these studies, Insulin Aspart (Ryzodeg) was given to female rats before mating, during mating, and throughout pregnancy, and to rabbits during organogenesis. The effects of Insulin Aspart (Ryzodeg) did not differ from those observed with subcutaneous regular human insulin. Insulin Aspart (Ryzodeg), like human insulin, caused pre- and post-implantation losses and visceral/skeletal abnormalities in rats at a dose of 200 U/kg/day (approximately 32 times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area) and in rabbits at a dose of 10 U/kg/day (approximately three times the human subcutaneous dose of 1.0 U/kg/day, based on U/body surface area). The effects are probably secondary to maternal hypoglycemia at high doses. No significant effects were observed in rats at a dose of 50 U/kg/day and in rabbits at a dose of 3 U/kg/day. These doses are approximately 8 times the human subcutaneous dose of 1.0 U/kg/day for rats and equal to the human subcutaneous dose of 1.0 U/kg/day for rabbits, based on U/body surface area.
Nursing Mothers
It is unknown whether Insulin Degludec (Ryzodeg)/aspart is excreted in human milk. Because many drugs, including human insulin, are excreted in human milk, caution should be exercised when Insulin Degludec (Ryzodeg)/aspartis administered to a nursing mother. Women with diabetes who are lactating may require adjustments in insulin dose, meal plan, or both.
In rats, the basal component of Insulin Degludec (Ryzodeg)/aspart, Insulin Degludec (Ryzodeg), was secreted in milk and the concentration in milk was lower than in plasma.
Pediatric Use
The safety and efficacy of RYZODEG 70/30 in children and adolescents under the age of 18 years have not been established.
Geriatric Use
In clinical studies a total of 9 (2.5%) of the 362 RYZODEG 70/30- treated patients with type 1 diabetes were 65 years or older and 4 (1.1%) were 75 years and older. A total of 256 (25.7%) of the 998 RYZODEG 70/30-treated patients with type 2 diabetes were 65 years or older and 32 (3.2%) were 75 years and older. Differences in safety or effectiveness were not suggested in subgroup analyses comparing subjects older than 65 years to younger subjects.
Nevertheless, greater caution should be exercised when RYZODEG 70/30 is administered to geriatric patients since greater sensitivity of some older individuals to the effects of RYZODEG 70/30 cannot be ruled out. The initial dosing, dose increments, and maintenance dosage should be conservative to avoid hypoglycemia. Hypoglycemia may be more difficult to recognize in the elderly.
Renal Impairment
In clinical studies a total of 18 (5%) of the 362 RYZODEG 70/30- treated patients with type 1 diabetes had an eGFR less than 60 mL/min/1.73 m or less and 1(0.3%) had an eGFR less than 30 mL/min/1.73 m² or less. A total of 111 (11%) of the 998 RYZODEG 70/30-treated patients with type 2 diabetes had an eGFR less than 60 mL/min/1.73 m² and no subjects had an eGFR less than 30 mL/min/1.73 m².
No differences in the pharmacokinetics of the individual components of RYZODEG 70/30, Insulin Degludec (Ryzodeg) or Insulin Aspart (Ryzodeg), were identified in separate studies comparing healthy subjects and subjects with renal impairment. However, as with all insulin products, glucose monitoring should be intensified and the RYZODEG 70/30 dosage adjusted on an individual basis in patients with renal impairment.
Hepatic Impairment
No differences in the pharmacokinetics of the individual components of RYZODEG 70/30, Insulin Degludec (Ryzodeg) or Insulin Aspart (Ryzodeg), were identified in separate studies comparing healthy subjects and subjects with hepatic impairment (mild, moderate, and severe hepatic impairment). However, as with all insulin products, glucose monitoring should be intensified and the RYZODEG 70/30 dosage adjusted on an individual basis in patients with hepatic impairment.
What happens if I miss a dose of Ryzodeg?
When you miss a dose, you should take it as soon as you remember, but you should take care that it should be well spaced from the next dose. You should not take an extra dose at the time of the second dose as it will become a double dose. The double dose can give unwanted side effects, so be careful. In chronic conditions or when you have a serious health issue, if you miss a dose, you should inform your health care provider and ask his suggestion.
Skip the missed dose and use the medicine at your next main meal on the same day. Then continue your regular dosing schedule. Do not use extra insulin to make up the missed dose.
It is important to keep insulin on hand at all times. Get your prescription refilled before you run out of medicine completely.
