Ryzodeg Penfill

What Is Ryzodeg Penfill and What Is It Used For?

Ryzodeg Penfill (insulin degludec/insulin aspart) is a co-formulation insulin used to control blood sugar in people with type 1 and type 2 diabetes mellitus. It combines an ultra-long-acting basal insulin (insulin degludec) with a rapid-acting mealtime insulin (insulin aspart) in a fixed 70/30 ratio and is injected subcutaneously once or twice daily with the main meal(s).

Ryzodeg Penfill is a prescription medicine manufactured by Novo Nordisk. The 3 mL cartridge — called a Penfill — is designed to be used with a compatible reusable insulin pen such as NovoPen 5 or NovoPen Echo. Each cartridge contains 300 units of insulin as a clear, colorless solution for subcutaneous injection.

What makes Ryzodeg pharmacologically unique is that it is a soluble co-formulation rather than a traditional premixed insulin suspension. In classical biphasic insulins (such as biphasic insulin aspart 30 or premixed NPH-containing products), the basal component is a crystalline suspension that must be resuspended by rolling or inverting the pen before each injection. Ryzodeg, by contrast, is a clear solution in which insulin degludec and insulin aspart coexist without chemical interaction. Each component retains its own pharmacokinetic and pharmacodynamic profile after injection.

Ryzodeg is indicated for the treatment of diabetes mellitus in adults, adolescents, and children aged 2 years and older. In type 1 diabetes, it can be used as part of a simplified insulin regimen when a co-formulation approach is preferred over full basal-bolus therapy. In type 2 diabetes, Ryzodeg is commonly used when patients require both basal and prandial insulin coverage, either alone or in combination with oral antidiabetic agents (such as metformin) and/or GLP-1 receptor agonists, depending on the individual treatment plan.

How does insulin degludec and insulin aspart work together?

After subcutaneous injection, insulin aspart (the rapid-acting component) is absorbed quickly, with an onset of action within 10 to 20 minutes and a peak effect around 1 to 3 hours. This covers the rise in blood glucose caused by the meal. Simultaneously, insulin degludec molecules form soluble multi-hexamers in the subcutaneous tissue; these multi-hexamers slowly dissociate, releasing insulin degludec monomers into the bloodstream over more than 42 hours. The result is a flat, consistent basal insulin concentration that overlaps between daily injections.

Because insulin degludec has a terminal half-life of approximately 25 hours — roughly twice that of insulin glargine 100 U/mL — daily doses accumulate predictably into a steady state. Clinical trials have consistently shown reduced within-subject variability and lower rates of nocturnal hypoglycemia compared with insulin glargine and biphasic insulin aspart 30.

Pharmacokinetics at a glance

The two components of Ryzodeg work on independent timelines:

• Insulin aspart (30%): onset within 10–20 minutes, peak at approximately 1–3 hours, duration 3–5 hours
• Insulin degludec (70%): onset within 1–2 hours, no pronounced peak (flat profile), duration beyond 42 hours, half-life approximately 25 hours

Both insulins are degraded similarly to endogenous human insulin, primarily by insulin-degrading enzymes in the liver, kidneys, and peripheral tissues. No active metabolites with clinically relevant glucose-lowering activity are produced. The duration of action of insulin degludec means that day-to-day fluctuations are smaller than with traditional long-acting or intermediate insulins, potentially improving glycemic stability.

What Should You Know Before Taking Ryzodeg Penfill?

Before starting Ryzodeg, tell your healthcare provider about all medical conditions, current medications, allergies, and whether you are pregnant, planning pregnancy, or breastfeeding. Ryzodeg should not be used during episodes of hypoglycemia, in diabetic ketoacidosis, or if you are allergic to insulin degludec, insulin aspart, or any of the excipients.

Your healthcare provider will evaluate several factors before prescribing Ryzodeg, including the type of diabetes, current glycemic control, HbA1c target, kidney and liver function, other medications, meal patterns, and lifestyle. Understanding the following contraindications, warnings, and precautions will help you use this medicine safely and effectively.

Contraindications

Ryzodeg must not be used in the following situations:

• Hypersensitivity: Do not use if you are allergic to insulin degludec, insulin aspart, or any of the excipients listed in section 8 (contents), such as glycerol, phenol, metacresol, or zinc
• Hypoglycemia: Do not inject Ryzodeg during an episode of low blood sugar. Treat the hypoglycemia first, then resume your insulin schedule
• Diabetic ketoacidosis (DKA): Ryzodeg is not suitable for the acute management of DKA, which requires rapid-acting insulin administered intravenously in a hospital setting
• Intravenous or intramuscular use: Ryzodeg is for subcutaneous injection only. It must not be given IV, IM, or via continuous subcutaneous insulin infusion pumps

Warnings and Precautions

Several clinical situations require additional attention and close monitoring when using Ryzodeg:

• Insulin transition: When switching from another basal or premixed insulin to Ryzodeg, the dose usually needs to be recalculated. Total daily insulin dose is typically converted at an approximately 1:1 ratio, but the distribution between daily doses and the timing may change. Close monitoring during the transition is essential
• Illness, infection, and stress: Fever, surgery, emotional stress, and acute illness can increase insulin requirements. Temporary dose adjustments may be required
• Renal or hepatic impairment: Insulin requirements may decrease in kidney or liver disease because clearance of insulin is reduced. More frequent blood glucose monitoring is advised
• Thiazolidinedione combination: Co-administration of insulin with thiazolidinediones (pioglitazone) may increase the risk of congestive heart failure, especially in patients with existing cardiac risk factors. Report any swelling, weight gain, or breathlessness to your doctor
• Hypokalemia: Insulin shifts potassium into cells, which can lower serum potassium. This is more relevant in patients taking potassium-lowering diuretics or with predisposing conditions
• Changes in meal pattern or physical activity: Skipping meals, increased exercise, or alcohol consumption can increase the risk of hypoglycemia
• Injection technique: Always rotate injection sites within the same anatomical region (abdomen, thigh, or upper arm) to reduce the risk of lipodystrophy, which can alter insulin absorption
• Pen and cartridge safety: Never share a reusable pen or Penfill cartridge with another person, even if the needle is changed. Sharing can transmit blood-borne pathogens such as hepatitis B, hepatitis C, or HIV

Pregnancy and Breastfeeding

Clinical experience with Ryzodeg during pregnancy is limited. Insulin aspart has a well-established safety profile in pregnancy, while insulin degludec has growing real-world and post-marketing data but more limited controlled trial experience compared with insulin detemir or NPH insulin. For pregnancies that are planned or already underway, most international guidelines recommend transitioning to an insulin regimen with more extensive pregnancy safety data — typically intermediate-acting or long-acting basal insulin plus a rapid-acting mealtime insulin — under specialist supervision.

Insulin requirements change considerably during pregnancy: they typically decrease during the first trimester, then increase progressively in the second and third trimesters, and usually return rapidly to pre-pregnancy levels after delivery. Frequent blood glucose monitoring and close cooperation with a diabetes team are essential throughout pregnancy and the postpartum period.

Regarding breastfeeding, insulin is a protein that is digested in the infant's gastrointestinal tract, so clinically relevant systemic absorption does not occur. Breastfeeding mothers can safely use insulin, but the mother's dose may need adjustment as metabolic demands change during lactation.

Driving and operating machinery

Hypoglycemia can impair concentration and reaction time. If you have symptoms of low blood sugar, do not drive or operate heavy machinery until the hypoglycemia has been treated and resolved. Patients with reduced or absent warning symptoms (hypoglycemia unawareness) need particular caution. Ask your diabetes team whether driving restrictions apply in your country; national regulations vary.

How Does Ryzodeg Penfill Interact with Other Drugs?

Many medicines affect blood glucose and may alter the insulin dose needed with Ryzodeg. Drugs that lower blood sugar (e.g., sulfonylureas, GLP-1 receptor agonists) increase the risk of hypoglycemia, while drugs that raise blood sugar (e.g., corticosteroids, thyroid hormones, atypical antipsychotics) may reduce Ryzodeg's effectiveness and require a higher insulin dose.

Drug interactions with insulin can be clinically significant because they may alter blood glucose levels, potentially causing hypoglycemia or loss of glycemic control. Always inform every healthcare professional about all medicines you take, including prescription drugs, over-the-counter products, herbal supplements, and recreational substances. Below are the most important interactions to be aware of.

Major Interactions – Increased Risk of Hypoglycemia

The following medicines may increase the glucose-lowering effect of Ryzodeg, meaning the insulin dose may need to be reduced:

Minor Interactions – Reduced Insulin Effect (Hyperglycemia Risk)

The following medicines may reduce the glucose-lowering effect of Ryzodeg, potentially requiring an increase in insulin dose:

What Is the Correct Dosage of Ryzodeg Penfill?

Ryzodeg dosing is individualized by your healthcare provider based on blood glucose levels. It is given once or twice daily with the main meal(s). A common starting dose in type 2 diabetes is 10 units once daily, while patients transferring from existing insulin often start at roughly their previous total daily basal insulin dose in a 1:1 ratio.

There is no universal dose of Ryzodeg. Your healthcare provider will choose an appropriate starting dose and titrate it over time based on home blood glucose readings, HbA1c results, and individual response. The information below reflects general clinical practice aligned with the Summary of Product Characteristics (SmPC) and major international guidelines.

Adults – Type 2 Diabetes

Adults – Type 1 Diabetes

Children and Adolescents (aged 2 years and older)

Elderly

Missed Dose

If you miss a dose of Ryzodeg, take it as soon as possible with your next meal, then resume your usual schedule. Do not take a double dose to make up for a missed injection. Because insulin degludec has an ultra-long duration of action, occasional missed doses have less impact on basal coverage than with shorter-acting insulins, but postprandial glucose will still rise because of the missing aspart component.

A minimum of 8 hours between injections must be observed to avoid stacking doses of insulin aspart. If you remember a missed dose less than 8 hours after a previous dose, skip the missed dose and resume at the next scheduled injection. Setting a daily reminder or linking the injection to a routine such as a specific meal can help prevent missed doses.

Overdose

An insulin overdose can cause hypoglycemia, which can range from mild (treated by eating sugar or glucose) to severe (requiring assistance from another person or emergency medical treatment). Because Ryzodeg contains a long-acting component, hypoglycemia from an overdose may be prolonged and require extended monitoring.

• Mild hypoglycemia: Eat or drink 15–20 grams of fast-acting carbohydrate (glucose tablets, fruit juice, or regular soda). Recheck blood glucose after 15 minutes and repeat if still below 4 mmol/L (72 mg/dL)
• Moderate hypoglycemia: Follow mild-hypoglycemia treatment and have a meal or snack containing complex carbohydrates (e.g., bread, crackers, milk) to prevent recurrence
• Severe hypoglycemia: If the person is unconscious, confused, or unable to swallow, do not give food or drink by mouth. Administer glucagon (injection or nasal) if available and call emergency services immediately. Place the person on their side (recovery position) to prevent aspiration

How Do You Use the Ryzodeg Penfill Cartridge?

Ryzodeg Penfill is a 3 mL cartridge for use in compatible reusable insulin pens such as NovoPen 5 and NovoPen Echo. Insulin is injected subcutaneously into the thigh, abdomen, or upper arm with the main meal. Always use a new needle for each injection and rotate injection sites to prevent lipodystrophy.

Proper injection technique is essential for accurate dosing and safe insulin delivery. Unlike a disposable FlexTouch pen, the Penfill cartridge requires a reusable pen device. The step-by-step guide below assumes use with a compatible Novo Nordisk reusable pen.

Step-by-step injection guide (Penfill cartridge)

1. Prepare the cartridge: Wash your hands thoroughly. Inspect the cartridge: the solution should be clear and colorless. Do not use if it is cloudy, discolored, or contains particles
2. Load the cartridge into the pen: Follow the instructions supplied with your reusable pen. Typically, you unscrew the pen body, insert the Ryzodeg Penfill cartridge with the metal cap toward the needle end, and screw the pen back together
3. Attach a new needle: Tear the paper tab from a new NovoFine or NovoTwist needle. Screw or push the needle straight onto the pen. Remove the outer needle cap (keep for later disposal) and the inner needle cap (discard)
4. Perform a flow check: Dial 2 units. Hold the pen with the needle pointing upward. Press the dose button fully. A drop of insulin should appear at the needle tip. Repeat if necessary. This removes air and confirms the pen is working correctly
5. Select your dose: Turn the dose selector to your prescribed number of units. The dose can be corrected up or down without wasting insulin. NovoPen 5 has a memory function showing the last dose and time since injection
6. Choose and clean the injection site: Clean the skin with an alcohol swab. Recommended sites are the abdomen (at least 5 cm from the navel), the front of the thigh, or the upper outer arm. Rotate within the chosen region to prevent lipohypertrophy
7. Inject: Insert the needle into the skin. Press the dose button all the way in. Keep the needle in the skin for at least 6 seconds after the dose counter returns to 0 to ensure the full dose is delivered
8. Remove and dispose: Pull the needle out of the skin. Place the outer needle cap back on the needle, unscrew the needle from the pen, and dispose of it in a sharps container. Replace the pen cap. Never store the pen with a needle attached

What Are the Side Effects of Ryzodeg Penfill?

The most common side effect of Ryzodeg is hypoglycemia (low blood sugar), affecting more than 1 in 10 users. Other side effects include injection site reactions, lipodystrophy, allergic reactions, and peripheral edema. Severe hypoglycemia and anaphylaxis are rare but require immediate medical attention.

Like all medicines, Ryzodeg can cause side effects, although not everyone experiences them. The frequency classifications below follow the standard MedDRA convention used across European medicines regulatory documents. Recognizing side effects early helps you manage them effectively and seek appropriate medical advice when needed.

Long-term considerations

Long-term use of Ryzodeg has been studied in pivotal clinical trials (the BOOST program) lasting up to 52 weeks and in long-term extension and real-world studies. The safety profile is consistent with that of other basal-plus-rapid insulin regimens. Weight gain is a known effect of insulin therapy in general; with Ryzodeg, weight change is typically modest and comparable to other basal-bolus regimens.

Antibodies to insulin degludec or insulin aspart can develop but have not been shown to affect glycemic control or safety in clinical practice. If you experience any side effect — even one not listed here — talk to your healthcare provider or pharmacist. You can also report side effects to your national pharmacovigilance authority (e.g., the FDA MedWatch program in the United States, the Yellow Card scheme in the United Kingdom, or the EMA in the European Union).

How Should You Store Ryzodeg Penfill?

Store unopened Ryzodeg Penfill cartridges in a refrigerator at 2–8°C. Once inserted into a reusable pen and in use, the cartridge can be kept at room temperature below 30°C for up to 4 weeks. Do not freeze. Protect from direct light, and never return an in-use cartridge to the refrigerator.

Proper storage is critical to maintaining insulin potency. Insulin that has been frozen, exposed to excessive heat, or stored incorrectly may lose potency and result in unpredictable blood glucose control.

Before first use (unopened cartridge)

• Store in the refrigerator at 2–8°C (36–46°F)
• Keep away from the freezer compartment – do not freeze
• Do not use Ryzodeg if it has been frozen, even if it has thawed; the insulin structure may be compromised
• Keep cartridges in the outer carton to protect from light
• Check the expiry date on the label – do not use after the stated date

After first use or loaded in a reusable pen

• Keep at room temperature below 30°C (86°F); do not refrigerate once in use
• Use within 4 weeks (28 days) of first use, then discard even if insulin remains
• Always keep the pen cap on when not in use to protect the cartridge from light
• Do not store the pen with a needle attached – this can allow air bubbles, contamination, and leakage of insulin
• Do not expose to direct sunlight, excessive heat (e.g., car dashboard in summer), or frost

Signs of degraded insulin

Before each injection, visually inspect the insulin in the cartridge through the pen window. Ryzodeg should be a clear, colorless solution. Do not use it if:

• The solution appears cloudy, thickened, yellowish, or discolored
• You can see particles or crystals floating in the liquid
• The cartridge or pen has been dropped or visibly damaged
• It has been stored outside the recommended temperature conditions
• It has been frozen, even once

Safe disposal

Used needles should always be disposed of in a dedicated sharps container. Do not throw them in household trash. Used Penfill cartridges and pens can be returned to your pharmacy if local regulations require this, or disposed of according to national hazardous waste guidelines. Never flush insulin down the toilet or pour it down the drain.

What Does Ryzodeg Penfill Contain?

Each milliliter of Ryzodeg contains 100 units of insulin degludec/insulin aspart (70%/30%). Each 3 mL Penfill cartridge delivers a total of 300 units. The formulation also includes excipients such as glycerol, phenol, metacresol, zinc, and water for injections.

Active ingredients

The active substances are insulin degludec and insulin aspart, both produced by recombinant DNA technology in Saccharomyces cerevisiae (baker's yeast). Each mL contains 100 units of total insulin: 70 units as insulin degludec (the basal component) and 30 units as insulin aspart (the rapid-acting component). Each 3 mL Penfill cartridge delivers 300 units of insulin in total.

Excipients (inactive ingredients)

The inactive ingredients in Ryzodeg are carefully selected to maintain stability, sterility, and correct pH of the insulin solution, and to allow both components to coexist in a clear co-formulation:

Physical description

Ryzodeg Penfill is a clear, colorless solution in a glass cartridge containing 3 mL of insulin at 100 units/mL. The cartridge is sealed with a rubber plunger at one end and a rubber septum with a metal cap at the other end. Each Penfill cartridge is designed for single-patient use with a compatible Novo Nordisk reusable pen device (NovoPen 5, NovoPen Echo, and other models listed as compatible by the manufacturer).

Ryzodeg Penfill cartridges are typically supplied in packs of 5 cartridges (1500 units total). Not all pack sizes may be available in every country. For a disposable pen option, Ryzodeg FlexTouch is available separately; the active ingredients and strength are identical.