Insulin Lispro Protamine and Insulin Lispro

14-24 hours

Note: Lispro protamine is an intermediate-acting insulin and lispro is a rapid-acting insulin administered by SubQ injection. Insulin lispro protamine and insulin lispro combination products are approximately equipotent to insulin NPH and insulin regular combination products with a similar duration of activity but a more rapid onset. With combination insulin products, the proportion of rapid-acting to long-acting insulin is fixed; basal vs prandial dose adjustments cannot be made. Fixed ratio insulins (such as insulin lispro protamine and insulin lispro combination) are typically administered as 2 daily doses with each dose intended to cover two meals and a snack. Because of variability in the peak effect and individual patient variability in activities, meals, etc, it may be more difficult to achieve complete glycemic control using fixed combinations of insulins; frequent monitoring and close medical supervision may be necessary.

Diabetes mellitus, type 1: SubQ:

General insulin dosing:

Note: Multiple daily doses are utilized and guided by blood glucose monitoring. Combinations of different insulin formulations are commonly used. The daily doses presented below are expressed as the total units/kg/day of all insulin formulations combined. Insulin lispro protamine and insulin lispro combination product is not intended for initial therapy; basal insulin requirements should be established first to direct dosing of combination insulin products.

Usual maintenance range: SubQ: 0.5 to 1 units/kg/day in divided doses. An estimate of anticipated needs may be based on body weight and/or activity factors as follows:

Nonobese: 0.4 to 0.6 units/kg/day

Obese: 0.8 to 1.2 units/kg/day

Pubescent Children and Adolescents: During puberty, requirements may substantially increase to >1 unit/kg/day and in some cases up to 2 units/kg/day (IDF-ISPAD, 2011).

Division of daily insulin requirement ("conventional therapy"): Generally, 50% to 75% of the daily insulin dose is given as an intermediate- or long-acting form of insulin (in 1 to 2 daily injections). The remaining portion of the 24-hour insulin requirement is divided and administered as either regular insulin or a rapid-acting form of insulin at the same time before breakfast and dinner.

Adjustment of dose: Dosage must be titrated to achieve glucose control and avoid hypoglycemia. Since combinations of agents are frequently used, dosage adjustment must address the individual component of the insulin regimen which most directly influences the blood glucose value in question, based on the known onset and duration of the insulin component. Treatment and monitoring regimens must be individualized. Also see Additional Information or Pharmacotherapy Pearls.

Diabetes mellitus, type 2: SubQ: Note: Insulin lispro protamine and insulin lispro combination product is not intended for initial therapy; basal insulin requirements should be established first to direct dosing of combination insulin products. Dosage must be carefully adjusted.

General considerations for insulin use in type 2 diabetes:

Timing of initiation: The goal of therapy is to achieve an HbA1c <7%. According to a position statement by the ADA and European Association for the Study of Diabetes (EASD), dual therapy (metformin + a second antihyperglycemic agent) is recommended in patients with type 2 diabetes who fail to achieve glycemic goals after ~3 months with lifestyle interventions and metformin monotherapy (unless contraindications to metformin exist). Preference is not given for adding insulin or a noninsulin agent as the second antihyperglycemic agent (drug choice should be individualized based on patient characteristics). However, insulin should be considered as part of a combination regimen when hyperglycemia is severe, particularly if patient is symptomatic or has catabolic features (eg, weight loss, ketosis). If insulin is selected, the addition of basal insulin (ie, a long-acting insulin such as glargine or detemir) is recommended. If HbA1c target not achieved after ~3 months of dual therapy, may proceed to triple therapy (Inzucchi 2015).

Intensification of therapy: If HbA1c target has not been met, despite titrating basal insulin (ie, long-acting insulin) to provide acceptable fasting blood glucose concentrations, intensification of therapy should be considered to cover postprandial glucose excursions. Options include adding a mealtime insulin (1 to 3 injections of a rapid-acting insulin analog [lispro, aspart, glulisine]) or adding a GLP-1 receptor agonist (eg, exenatide, liraglutide). Alternatively, although less studied, may transition from basal insulin (ie, long-acting insulin) to a twice daily premixed (or biphasic) insulin analog (70/30 aspart mix, 75/25 or 50/50 lispro mix) (Inzucchi 2015).

There are no dosage adjustments provided in the manufacturer's labeling; dose reduction may be necessary as insulin requirements may be reduced due to changes in insulin clearance or metabolism; monitor blood glucose closely.

Refer to indication-specific dosing for obesity-related information (may not be available for all indications).

For SubQ administration only (do not administer intravenously): In order to properly resuspend the insulin, vials should be carefully shaken or rolled several times and prefilled pens should be rolled between the palms ten times and inverted 180° ten times. Properly resuspended insulin should look uniformly cloudy or milky; do not use if any white insulin substance remains at the bottom of the container, if any clumps are present, if the insulin remains clear after adequate mixing, or if white particles are stuck to the bottom or wall of the container. Cold injections should be avoided. Insulin lispro protamine and insulin lispro combination products should be administered within 15 minutes before a meal; typically given once or twice daily. SubQ administration is usually made into the thighs, arms, buttocks, or abdomen; rotate injection sites within the same region to avoid lipodystrophy. Do not dilute or mix with any other insulin formulation or solution; not recommended for use in external SubQ insulin infusion pump.

Individualized medical nutrition therapy (MNT) based on ADA recommendations is an integral part of therapy.

Also see insulin lispro for additional reactions.

Dermatologic: Pruritus, skin rash

Endocrine & metabolic: Hypoglycemia, lipodystrophy

Hypersensitivity: Hypersensitivity reaction

Local: Injection site reaction, lipotrophy at injection site

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Have patient report immediately to prescriber signs of low blood sugar (dizziness, headache, fatigue, feeling weak, shaking, a fast heartbeat, confusion, hunger, or sweating), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), severe injection site irritation, vision changes, chills, severe dizziness, passing out, mood changes, seizures, slurred speech, shortness of breath, excessive weight gain, swelling of arms of legs, or change in skin to thick or thin at injection site (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.