insulin regular human (Humulin R, Novolin R, Humulin R U-500)

Dosing and uses of Humulin R, Novolin R (insulin regular human)

• Adult
• Pediatric

 

Adult dosage forms and strengths

injectable solution

• OTC
  • 100units/mL (3mL vial)
  • 100units/mL (10mL vial)
• Rx
  • 500units/mL (20mL vial); prescribe with U-500 syringes to avoid conversion for U-100 tuberculin syringes
  • 500units/mL (3mL pen)

 

Type 1 Diabetes Mellitus

Initial: 0.2-0.4 units/kg/day SC divided q8hr or more frequently

Maintenance: 0.5-1 unit/kg/day SC divided q8hr or more frequently; in insulin-resistant patients (eg, due to obesity), substantially higher daily insulin may be required

Approximately 50-75% of the total daily insulin requirements are given as intermediate- or long-acting insulin administered in 1-2 injections; rapid- or short-acting insulin should be used before or at mealtimes to satisfy the remainder balance of the total daily insulin requirements

Premixed combinations are available that deliver rapid- or short-acting components at the same time as the intermediate- or long-acting component

 

Type 2 Diabetes Mellitus

Type 2 diabetes inadequately controlled by diet, exercise, or oral medication: Suggested beginning dose of 10 units/day SC (or 0.1-0.2 unit/kg/day) in evening or divided q12hr

Morning

• Give two thirds of daily insulin requirement
• Ratio of regular insulin to NPH insulin 1:2

Evening

• Give one third of daily insulin requirement
• Ratio of regular insulin to NPH insulin 1:1

 

Severe Hyperglycemia (Diabetic Ketoacidosis)

0.1 unit/kg IV bolus (some argue against bolus), THEn

0.1 unit/kg/hr IV continuous infusion; if serum glucose does not fall by 50 mg/dL in the first hour, check hydration status; if possible, double the insulin hourly until glucose levels fall at the rate of 50-75 mg/dL/hr; decrease infusion to 0.05-0.1 unit/kg/hour when blood sugar reaches 250 mg/dL

 

Hyperkalemia

5-10 units IV insulin in 50 mL D50W (25 g) infused over 15-30 min

 

Administration

Administer within 15 minutes before a meal or immediately after a meaL

 

Dosing Considerations

Dosage of human insulin, which is always expressed in USP units, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect

Dose adjustments should be based on regular blood glucose testing

Adjust to achieve appropriate glucose controL

Planning dose adjustments

• Look for consistent pattern in blood sugars for >3 days
• Same time each day: Compare blood glucose levels with previous levels found at that time of day
• For each time of day: Calculate blood glucose range
• Calculate median blood glucose
• Consider eating and activity patterns during day

Making dose adjustments

• Adjust only 1 insulin dose at a time
• Correct hypoglycemia first
• Correct highest blood sugars next
• If all blood sugars are high (within 2.75 mmol/L [50 mg/dL]): Correct morning fasting blood glucose first
• Change insulin doses in small increments: Type 1 diabetes (1-2 unit change); type 2 diabetes (2-3 unit change)

Sliding scales

• Many sliding scales exist to determine exact insulin dose based on frequent blood glucose monitoring
• Commonly written for q4hr blood glucose test
• Sliding scale coverage usually begins after blood glucose >11 mmol/L (200 mg/dL)
• If coverage is needed q4hr for 24 hr, then base insulin dose is adjusted first; sliding scale doses may be adjusted upwards as well

 

Short Bowel Syndrome (Orphan)

Orphan designation for treatment of short bowel syndrome

Sponsor

• Nutrinia, Ltd; 15 Abba Hillel Silver Rd, 7th Floor;Ramat-Gan 5252208; Israel

 

Pediatric dosage forms and strengths

injectable solution

• OTC
  • 100units/mL (3mL vial)
  • 100units/mL (10mL vial)
• Rx
  • 500units/mL (20mL vial); prescribe with U-500 syringes to avoid conversion for U-100 tuberculin syringes
  • 500units/mL (3mL pen)

 

Type 1 Diabetes Mellitus

Initial: 0.2-0.4 unit/kg/day SC divided q8hr or more frequently

Maintenance: 0.5-1 unit/kg/day SC divided q8hr or more frequently; in insulin-resistant patients (eg, due to obesity), substantially higher daily insulin may be required

Adolescents: May require up to 1.5 mg/kg/day during puberty

The average total daily insulin requirement for prepubertal children varies from 0.7-1 unit/kg/day but may be much lower

Dosing considerations

• Dosage of human insulin, which is always expressed in USP units, must be based on the results of blood and urine glucose tests and must be carefully individualized to optimal effect
• Approximately 50-75% of the total daily insulin requirements are given as intermediate- or long-acting insulin administered in 1-2 injections
• Rapid- or short-acting insulin should be used before or at mealtimes to satisfy the remainder balance of the total daily insulin requirements
• Premixed combinations are available that deliver a rapid- or short-acting component at the same time as the intermediate- or long-acting component

 

Humulin R, Novolin R (insulin regular human) adverse (side) effects

Frequency not defined

Headache

Influenza-like symptoms

Dyspepsia

Diarrhea

Back pain

Pharyngitis

Hypoglycemia

Insulin resistance

Lipodystrophy

Lipohypertrophy

Local allergic reaction

Hypokalemia

 

Warnings

Contraindications

Hypersensitivity

Hypoglycemia

 

Cautions

Never share pen between patients even if needle is changed

Use with caution in patients with decreased insulin requirements: Diarrhea, nausea/vomiting, malabsorption, hypothyroidism, renal impairment, and hepatic impairment

Use with caution in patients with increased insulin requirements: Fever, hyperthyroidism, trauma, infection, and surgery

Rapid changes in serum glucose may induce symptoms of hypoglycemia; increase monitoring with changes to insulin dosage, co-administered glucose lowering medications, meal pattern, physical activity; and in patients with renal impairment or hepatic impairment or hypoglycemia unawareness

Hypoglycemia is the most common cause of adverse reactions (headache, tachycardia, etc)

May cause a shift in potassium from extracellular to intracellular space, possibly leading to hypokalemia; caution when coadministered with potassium-lowering drugs or when administered to patients with a condition that may decrease potassium

Thiazolidinediones are peroxisome proliferator-activated receptor (PPAR)-gamma agonists and can cause dose-related fluid retention, particularly when used in combination with insulin; fluid retention may lead to or exacerbate heart failure; monitor for signs and symptoms of heart failure, treat the patient accordingly, and consider discontinuing thiazolidinediones

Change in insulin regimen should be carried out under close medical supervision and frequency of blood glucose monitoring should be increased

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur; discontinue therapy if indicated

Not for mixing with any insulin for intravenous use or with insulins other than NPH insulin for subcutaneous use

Pregnancy

Medication errors associated with U-500

• Prescribed dose should always be expressed in actual units of insulin and NOT volume
• Reports of errors resulting in hyperglycemia, hypoglycemia, or death
• Majority of errors occurred due to errors in dispensing, prescribing, or administration; confusion with corresponding markings on the syringe the patient is using (ie, a U-100 insulin syringe or tuberculin syringe)

 

Pregnancy and lactation

Pregnancy category: B

Lactation: Safe

 

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 Humulin R, Novolin R (insulin regular human)

Mechanism of action

Regulates glucose metabolism

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

Bioavailability: 55-77% (SC)

Onset: 0.5 hr (early effect); 2.5-5 hr (peak effect)

Duration: 4-12 hr (U-100); up to 24 hr (U-500)

Peak plasma time: 0.8-2 hr (SC)

 

Distribution

Vd: 0.26-0.36 L/kg

 

Metabolism

Metabolized by liver (>50%), kidney (30%), and adipose tissue/muscle (20%)

 

Elimination

Excretion: Urine