Humulin R U-500 Kwikpen Inj 3ml
It is used to lower blood sugar in patients with high blood sugar (diabetes).
Drug Class
Antidiabetic agent
Pharmacologic Class
Insulin, concentrated; Insulin, human
Pregnancy Category
Category B
FDA Approved
Jul 2016
DEA Schedule
Not Controlled
Overview
What is this medicine?
Humulin R U-500 KwikPen is a highly concentrated form of insulin used to lower high blood sugar in people with diabetes, especially those who need very large doses of insulin. It works by helping your body use sugar for energy. Because it's so concentrated, it has a longer-lasting effect than regular U-100 insulin.
How to Use This Medicine
Proper Use of This Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue under the skin in the upper arm, thigh, buttocks, or stomach area. If you will be self-administering the injection, your doctor or nurse will instruct you on the proper technique.
Before use, wash your hands thoroughly. It is recommended to take this medication 30 minutes before meals. To minimize the risk of injection site reactions, rotate the injection site with each dose.
Important Administration Guidelines
Do not shake the medication before use.
Avoid injecting into skin that is thickened, has pits or lumps, or is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
Do not use the medication if the solution appears cloudy, is leaking, or contains particles.
If the solution changes color, do not use it.
Remove all pen needle covers before injecting a dose. If you are unsure about the type of pen needle you have or how to use it, consult your doctor.
After each injection, remove the needle and do not store the device with the needle attached.
Dispose of used needles in a designated needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow local regulations for disposal. If you have any questions, consult your doctor or pharmacist.
Special Considerations
Do not transfer this medication from the pen to a syringe or mix it with other types of insulin.
You may hear a clicking sound when preparing the dose. Do not rely on the clicks to determine the dose, as this could lead to an incorrect dose. Instead, follow the instructions provided.
Adhere to the diet and exercise plan recommended by your doctor. If you skip a meal or do not eat as much as usual, be aware of the steps to take to maintain your blood sugar control.
Storage and Disposal
Store unopened containers in the refrigerator. If necessary, unopened containers can also be stored at room temperature. Do not freeze the medication, and do not use it if it has been frozen.
Missed Dose
If you forget to take a dose, be aware of the steps to take. If you are unsure about what to do in the event of a missed dose, contact your doctor.
To use this medication correctly, follow your doctor's instructions and read all the information provided. This medication is administered via injection into the fatty tissue under the skin in the upper arm, thigh, buttocks, or stomach area. If you will be self-administering the injection, your doctor or nurse will instruct you on the proper technique.
Before use, wash your hands thoroughly. It is recommended to take this medication 30 minutes before meals. To minimize the risk of injection site reactions, rotate the injection site with each dose.
Important Administration Guidelines
Do not shake the medication before use.
Avoid injecting into skin that is thickened, has pits or lumps, or is irritated, tender, bruised, red, scaly, hard, scarred, or has stretch marks.
Do not use the medication if the solution appears cloudy, is leaking, or contains particles.
If the solution changes color, do not use it.
Remove all pen needle covers before injecting a dose. If you are unsure about the type of pen needle you have or how to use it, consult your doctor.
After each injection, remove the needle and do not store the device with the needle attached.
Dispose of used needles in a designated needle/sharp disposal box. Do not reuse needles or other items. When the box is full, follow local regulations for disposal. If you have any questions, consult your doctor or pharmacist.
Special Considerations
Do not transfer this medication from the pen to a syringe or mix it with other types of insulin.
You may hear a clicking sound when preparing the dose. Do not rely on the clicks to determine the dose, as this could lead to an incorrect dose. Instead, follow the instructions provided.
Adhere to the diet and exercise plan recommended by your doctor. If you skip a meal or do not eat as much as usual, be aware of the steps to take to maintain your blood sugar control.
Storage and Disposal
Store unopened containers in the refrigerator. If necessary, unopened containers can also be stored at room temperature. Do not freeze the medication, and do not use it if it has been frozen.
Missed Dose
If you forget to take a dose, be aware of the steps to take. If you are unsure about what to do in the event of a missed dose, contact your doctor.
Lifestyle & Tips
- Follow your prescribed diet plan and exercise regimen consistently.
- Monitor your blood glucose levels as directed by your healthcare provider.
- Never share your KwikPen with another person, even if the needle is changed, due to risk of infection.
- Always use the KwikPen as instructed; do not transfer insulin from the pen to a syringe.
- Rotate injection sites within the same general area (e.g., abdomen, thigh, upper arm) to prevent lipodystrophy.
- Carry a source of fast-acting sugar (e.g., glucose tablets, fruit juice) to treat mild to moderate hypoglycemia.
- Inform your healthcare provider about all medications, supplements, and herbal products you are taking.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Highly individualized based on patient's metabolic needs, blood glucose monitoring results, and glycemic control goals. Typically for patients requiring more than 200 units of insulin per day. Often administered 2 or 3 times daily, 30-60 minutes before meals.
Condition-Specific Dosing:
Type 1 Diabetes Mellitus:
Initial total daily dose (TDD) is typically 0.5 to 1 unit/kg/day, with U-500 used when TDD exceeds 200 units. Dose is then titrated based on blood glucose levels.
Type 2 Diabetes Mellitus:
Initial dose often 0.3 to 0.6 units/kg/day, with U-500 used when TDD exceeds 200 units. Dose is then titrated based on blood glucose levels.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Dosing is highly individualized based on metabolic needs and blood glucose. Generally, U-500 is reserved for children with severe insulin resistance requiring very high doses.
Adolescent:
Dosing is highly individualized based on metabolic needs and blood glucose. Generally, U-500 is reserved for adolescents with severe insulin resistance requiring very high doses.
Dose Adjustments
Renal Impairment:
Mild:
May require dose adjustment; monitor glucose closely.
Moderate:
Requires dose adjustment; monitor glucose closely. Increased risk of hypoglycemia.
Severe:
Requires significant dose reduction; monitor glucose closely. Increased risk of severe hypoglycemia.
Dialysis:
Requires significant dose reduction; monitor glucose closely. Insulin requirements may decrease.
Hepatic Impairment:
Mild:
May require dose adjustment; monitor glucose closely.
Moderate:
Requires dose adjustment; monitor glucose closely. Increased risk of hypoglycemia.
Severe:
Requires significant dose reduction; monitor glucose closely. Increased risk of severe hypoglycemia.
Pharmacology
Mechanism of Action
Insulin regular (human) is a short-acting insulin that lowers blood glucose by stimulating peripheral glucose uptake by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits lipolysis and proteolysis, and enhances protein synthesis. The concentrated U-500 formulation, due to its higher concentration, has a slower absorption profile and a more prolonged duration of action compared to U-100 regular insulin.
Pharmacokinetics
Absorption:
Bioavailability:
Not applicable (subcutaneous injection)
Tmax:
Approximately 4-8 hours (for U-500, due to slower absorption from concentrated formulation)
FoodEffect:
Administered 30-60 minutes before a meal; food intake is critical for managing post-prandial glucose and preventing hypoglycemia.
Distribution:
Vd:
Approximately 0.1-0.2 L/kg
ProteinBinding:
Minimal (<10%)
CnssPenetration:
Limited
Elimination:
HalfLife:
Variable, depends on absorption rate; effective half-life for U-500 is longer than U-100, contributing to its prolonged action.
Clearance:
Approximately 0.8-1.2 L/min (in healthy individuals)
ExcretionRoute:
Renal (minor amount of intact insulin)
Unchanged:
Minimal
Pharmacodynamics
OnsetOfAction:
Approximately 30-60 minutes
PeakEffect:
Approximately 4-8 hours
DurationOfAction:
Up to 24 hours (significantly longer than U-100 regular insulin)
Confidence:
Medium
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Note: In rare cases, allergic reactions can be life-threatening.
Signs of low potassium levels, including:
+ Muscle pain or weakness
+ Muscle cramps
+ An irregular heartbeat
Swelling in the arms or legs
Thick skin, pits, or lumps at the injection site
Low blood sugar, which may cause:
+ Dizziness or fainting
+ Blurred vision
+ Mood changes
+ Slurred speech
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
+ Seizures
If you experience any of these symptoms, call your doctor right away. If you have low blood sugar, follow the instructions you have been given, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only have mild ones, it's essential to discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience:
Weight gain
Irritation at the injection site
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Note: In rare cases, allergic reactions can be life-threatening.
Signs of low potassium levels, including:
+ Muscle pain or weakness
+ Muscle cramps
+ An irregular heartbeat
Swelling in the arms or legs
Thick skin, pits, or lumps at the injection site
Low blood sugar, which may cause:
+ Dizziness or fainting
+ Blurred vision
+ Mood changes
+ Slurred speech
+ Headache
+ Feeling sleepy or weak
+ Shaking
+ Fast heartbeat
+ Confusion
+ Hunger
+ Sweating
+ Seizures
If you experience any of these symptoms, call your doctor right away. If you have low blood sugar, follow the instructions you have been given, which may include taking glucose tablets, liquid glucose, or some fruit juices.
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only have mild ones, it's essential to discuss any concerns with your doctor. Contact your doctor or seek medical help if you experience:
Weight gain
Irritation at the injection site
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Symptoms of low blood sugar (hypoglycemia): sweating, shaking, dizziness, confusion, hunger, irritability, blurred vision, rapid heartbeat. Treat immediately with fast-acting sugar.
- Symptoms of high blood sugar (hyperglycemia): increased thirst, frequent urination, fatigue, blurred vision, dry mouth. Contact your doctor if persistent.
- Symptoms of serious allergic reaction: rash over the whole body, shortness of breath, wheezing, rapid heartbeat, sweating, swelling of your face or tongue, trouble breathing, extreme drowsiness, dizziness, confusion. Seek immediate medical attention.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have low blood sugar (hypoglycemia), as this may affect your treatment plan.
This is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to disclose all of the following to your doctor and pharmacist:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Your complete medical history, including any health problems you have
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm that it is safe to do so. This will help prevent any potential interactions or adverse effects.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have low blood sugar (hypoglycemia), as this may affect your treatment plan.
This is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to disclose all of the following to your doctor and pharmacist:
All prescription and over-the-counter (OTC) medications you are taking
Any natural products or vitamins you are using
* Your complete medical history, including any health problems you have
Before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm that it is safe to do so. This will help prevent any potential interactions or adverse effects.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. This particular brand of insulin is five times more concentrated than other brands, so it is crucial to exercise extra caution when measuring your dose to avoid accidental overdose, which can lead to severe side effects or life-threatening hypoglycemia (low blood sugar). Consult your doctor to ensure you understand the proper dosing and administration.
To avoid errors, verify that you have the correct insulin product, as insulin products are available in various containers such as vials, cartridges, and pens. Make sure you know how to accurately measure and prepare your dose. If you have any questions or concerns, do not hesitate to contact your doctor or pharmacist.
Hypoglycemia (low blood sugar) is a potential side effect of this medication. Severe hypoglycemia can lead to seizures, loss of consciousness, permanent brain damage, and even death. Discuss the risks and symptoms of hypoglycemia with your doctor.
Additionally, this medication may cause hypokalemia (low blood potassium), which, if left untreated, can result in abnormal heart rhythms, severe respiratory problems, and even death. Consult your doctor if you experience any symptoms.
Until you are familiar with how this medication affects you, avoid driving and other activities that require alertness. Certain diabetes medications, such as pioglitazone or rosiglitazone, may increase the risk of heart failure when used in combination with insulin. If you are taking one of these medications, discuss the potential risks with your doctor.
Your blood sugar control may be affected during periods of stress, such as illness, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
It is recommended that you wear a medical alert identification (ID) to inform others of your condition in case of an emergency. Do not drive if you have recently experienced low blood sugar, as this can increase your risk of being involved in an accident.
Monitor your blood sugar levels as directed by your doctor and undergo regular blood tests to ensure your safety while taking this medication. Consult your doctor before consuming alcohol or using products that contain alcohol.
Do not share your insulin product, including pens, cartridge devices, needles, or syringes, with anyone else, even if the needle has been changed, as this can transmit infections. If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, plan to become pregnant, or are breastfeeding, discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
To avoid errors, verify that you have the correct insulin product, as insulin products are available in various containers such as vials, cartridges, and pens. Make sure you know how to accurately measure and prepare your dose. If you have any questions or concerns, do not hesitate to contact your doctor or pharmacist.
Hypoglycemia (low blood sugar) is a potential side effect of this medication. Severe hypoglycemia can lead to seizures, loss of consciousness, permanent brain damage, and even death. Discuss the risks and symptoms of hypoglycemia with your doctor.
Additionally, this medication may cause hypokalemia (low blood potassium), which, if left untreated, can result in abnormal heart rhythms, severe respiratory problems, and even death. Consult your doctor if you experience any symptoms.
Until you are familiar with how this medication affects you, avoid driving and other activities that require alertness. Certain diabetes medications, such as pioglitazone or rosiglitazone, may increase the risk of heart failure when used in combination with insulin. If you are taking one of these medications, discuss the potential risks with your doctor.
Your blood sugar control may be affected during periods of stress, such as illness, infection, injury, or surgery. Changes in physical activity, exercise, or diet can also impact your blood sugar levels.
It is recommended that you wear a medical alert identification (ID) to inform others of your condition in case of an emergency. Do not drive if you have recently experienced low blood sugar, as this can increase your risk of being involved in an accident.
Monitor your blood sugar levels as directed by your doctor and undergo regular blood tests to ensure your safety while taking this medication. Consult your doctor before consuming alcohol or using products that contain alcohol.
Do not share your insulin product, including pens, cartridge devices, needles, or syringes, with anyone else, even if the needle has been changed, as this can transmit infections. If you are 65 years or older, use this medication with caution, as you may be more susceptible to side effects.
If you are pregnant, plan to become pregnant, or are breastfeeding, discuss the potential benefits and risks of this medication with your doctor to ensure the best possible outcome for you and your baby.
Overdose Information
Overdose Symptoms:
- Severe hypoglycemia (very low blood sugar)
- Confusion
- Seizures
- Loss of consciousness
What to Do:
For mild to moderate hypoglycemia, consume fast-acting carbohydrates (e.g., glucose tablets, fruit juice, candy). For severe hypoglycemia, administer glucagon injection if available and call emergency medical services. Call 1-800-222-1222 (Poison Control) or seek immediate medical attention.
Drug Interactions
Major Interactions
- Beta-blockers (may mask symptoms of hypoglycemia and delay recovery)
- Thiazolidinediones (TZDs) - increased risk of fluid retention and heart failure when used with insulin
- Corticosteroids (may increase blood glucose, requiring higher insulin doses)
- Diuretics (thiazide and loop) - may increase blood glucose, requiring higher insulin doses
Moderate Interactions
- ACE inhibitors (may enhance insulin's glucose-lowering effect)
- Angiotensin Receptor Blockers (ARBs) (may enhance insulin's glucose-lowering effect)
- Salicylates (e.g., aspirin, high doses) - may enhance insulin's glucose-lowering effect
- Sulfonamide antibiotics (may enhance insulin's glucose-lowering effect)
- MAO inhibitors (may enhance insulin's glucose-lowering effect)
- Alcohol (can potentiate hypoglycemic effect)
- Sympathomimetics (e.g., decongestants, asthma medications) - may increase blood glucose
- Atypical antipsychotics (may increase blood glucose)
- Growth hormone (may increase blood glucose)
- Thyroid hormones (may increase blood glucose)
Minor Interactions
- Danazol (may increase blood glucose)
- Isoniazid (may increase blood glucose)
- Phenothiazines (may increase blood glucose)
Monitoring
Baseline Monitoring
Glycated Hemoglobin (HbA1c)
Rationale: To establish baseline glycemic control and guide initial dosing.
Timing: Prior to initiation
Fasting Plasma Glucose (FPG)
Rationale: To establish baseline glucose levels.
Timing: Prior to initiation
Renal function (SCr, eGFR)
Rationale: To assess kidney function as insulin clearance can be affected.
Timing: Prior to initiation
Hepatic function (ALT, AST)
Rationale: To assess liver function as insulin metabolism occurs in the liver.
Timing: Prior to initiation
Routine Monitoring
Self-Monitoring Blood Glucose (SMBG)
Frequency: Multiple times daily (e.g., pre-meal, 2-hour post-meal, bedtime, overnight if needed)
Target: Individualized, typically 80-130 mg/dL pre-meal, <180 mg/dL post-meal
Action Threshold: Hypoglycemia (<70 mg/dL) or persistent hyperglycemia (>180-250 mg/dL)
Glycated Hemoglobin (HbA1c)
Frequency: Every 3-6 months
Target: Individualized, typically <7% for most adults
Action Threshold: Above target range indicates need for dose adjustment or therapy modification.
Signs and symptoms of hypoglycemia
Frequency: Daily, ongoing
Target: N/A
Action Threshold: Any symptoms (e.g., sweating, tremor, confusion, hunger) require immediate glucose intake.
Injection site inspection
Frequency: Regularly
Target: N/A
Action Threshold: Presence of lipodystrophy or irritation requires site rotation.
Symptom Monitoring
- Symptoms of hypoglycemia (e.g., sweating, tremor, dizziness, confusion, hunger, irritability, blurred vision, palpitations, headache, slurred speech, seizures, unconsciousness)
- Symptoms of hyperglycemia (e.g., increased thirst, increased urination, fatigue, blurred vision, dry mouth, fruity breath odor, nausea, vomiting, abdominal pain)
Special Patient Groups
Pregnancy
Insulin is the preferred treatment for diabetes in pregnancy. Humulin R U-500 can be used if high insulin doses are required, but careful monitoring is essential to avoid hypoglycemia.
Trimester-Specific Risks:
First Trimester:
Careful glycemic control is crucial to minimize congenital malformations. Insulin requirements may decrease.
Second Trimester:
Insulin requirements typically increase due to increasing insulin resistance.
Third Trimester:
Insulin requirements continue to increase until near term, then may decrease slightly.
Lactation
Insulin is compatible with breastfeeding. Insulin is a normal component of breast milk and is not orally absorbed by the infant. Insulin requirements may be lower in breastfeeding mothers.
Infant Risk:
L1 (Safest - no known risk to infant)
Pediatric Use
Humulin R U-500 is generally reserved for pediatric patients with severe insulin resistance requiring very high daily insulin doses. Dosing must be highly individualized and closely monitored due to the increased risk of hypoglycemia with concentrated insulin.
Geriatric Use
Elderly patients may be at increased risk of hypoglycemia due to impaired renal/hepatic function, reduced counter-regulatory responses, and polypharmacy. Start with lower doses and titrate cautiously. Close monitoring of blood glucose is essential.
Clinical Information
Clinical Pearls
- Humulin R U-500 is 5 times more concentrated than U-100 insulin. This high concentration leads to a slower absorption and a longer duration of action, making it behave more like an intermediate-acting insulin.
- The KwikPen delivers the dose in units, eliminating the need for a U-500 syringe. If using vials, a specific U-500 insulin syringe must be used to avoid severe dosing errors (never use a U-100 syringe for U-500 vial insulin).
- High risk of medication errors due to its concentration. Emphasize patient education on proper administration and storage.
- Patients should be advised to take U-500 approximately 30-60 minutes before meals, similar to U-100 regular insulin, but its prolonged action means it can cover subsequent meals or provide basal coverage.
- Never dilute U-500 insulin.
- Patients transitioning from U-100 to U-500 may initially use a 1:1 unit conversion, but close monitoring and titration are crucial as individual responses vary.
- Ensure patients understand the signs and symptoms of hypoglycemia and how to treat it effectively.
Alternative Therapies
- Other concentrated insulins (e.g., Toujeo U-300, Tresiba U-200)
- Other basal insulins (e.g., insulin glargine U-100, insulin detemir, insulin degludec U-100)
- Other prandial insulins (e.g., insulin aspart, insulin lispro, insulin glulisine, insulin regular U-100)
- Oral antidiabetic agents (e.g., metformin, sulfonylureas, DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 receptor agonists)
Cost & Coverage
Average Cost:
Varies widely, typically several hundred dollars per 3ml KwikPen
Insurance Coverage:
Tier 2 or 3 (Specialty/Non-preferred Brand)
General Drug Facts
If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication, including the amount taken and the time it happened, to ensure you receive the best possible care.