Humalog

You should tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking.

Humalog interacts with many drugs, including:

• Beta blockers like Tenormin (atenolol), Trandate (labetalol), Toprol XL (metoprolol succinate), or Lopressor (metoprolol tartrate)
• Saxenda or Victoza (liraglutide) and repaglinide-containing drugs like Prandin or Prandimet
• Estrogen-containing drugs, including birth control and hormone replacements
• Sulfonylureas like Diabeta (glyburide), and drugs that contain glipizide, such as Glucotrol, Glucotrol XL, or Metaglip
• Other diabetes drugs like Starlix (nateglinide) and Glyset (miglitol)
• Psych drugs like Invega (paliperidone), Risperdal (risperidone), and Precose (acarbose)

Humalog and Alcohol

You should avoid or limit drinking while taking Humalog.

Serious side effects have been reported with Humalog including the following:

Low blood sugar (hypoglycemia). Low blood sugar can occur with changes in insulin regimens or dose miscalculations. Monitor blood glucose levels regularly. Signs and symptoms of low blood sugar include:

• sweating
• dizziness or lightheadedness
• shakiness
• hunger
• fast heart beat
• tingling of lips and tongue
• trouble concentrating or confusion
• blurred vision
• slurred speech
• anxiety, irritability or mood changes
• headache

Humalog may also cause the following side effects. Tell your doctor right away if you experience any of the following signs and symptoms:

• rash and itching
• difficulty breathing
• hives
• wheezing
• fast heartbeat
• sweating
• weakness
• muscle cramps
• abnormal heartbeat
• shortness of breath
• large weight gain in a short period of time
• swelling of the arms, hands, feet, ankles, or lower legs

Humalog can cause low blood sugar, which can cause dizziness and drowsiness. Do not drive or operate heavy machinery until you know how Humalog affects you.

Do not take Humalog if you:

• are allergic to Humalog or to any of its ingredients
• have low blood sugar

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of Humalog, there are no specific foods that you must exclude from your diet when receiving this medication.

If you take too much Humalog, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Humalog is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Your pharmacist can provide more information about insulin lispro.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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Observed With HUMALOG U-100

The following adverse reactions are discussed elsewhere:

• Hypoglycemia [see WARNINGS AND PRECAUTIONS].
• Hypokalemia [see WARNINGS AND PRECAUTIONS].

Clinical Trial Experience

Because clinical trials are conducted under widely varying designs, the adverse reaction rates reported in one clinical trial may not be easily compared with those rates reported in another clinical trial, and may not reflect the rates actually observed in clinical practice.

The frequencies of Treatment-Emergent Adverse Events during HUMALOG clinical trials in patients with type 1 diabetes mellitus and type 2 diabetes mellitus are listed in the tables below.

Table 1: Treatment-Emergent Adverse Events in Patients with Type 1 Diabetes Mellitus (adverse events with frequency ≥5%)

Table 2: Treatment-Emergent Adverse Events in Patients with Type 2 Diabetes Mellitus (adverse events with frequency ≥5%)

Intensification or rapid improvement in glucose control has been associated with a transitory, reversible ophthalmologic refraction disorder, worsening of diabetic retinopathy, and acute painful peripheral neuropathy. However, long-term glycemic control decreases the risk of diabetic retinopathy and neuropathy.

Long-term use of insulin, including HUMALOG, can cause lipodystrophy at the site of repeated insulin injections or infusion. Lipodystrophy includes lipohypertrophy (thickening of adipose tissue) and lipoatrophy (thinning of adipose tissue), and may affect insulin absorption. Rotate insulin injection or infusion sites within the same region to reduce the risk of lipodystrophy [see DOSAGE AND ADMINISTRATION].

Weight gain can occur with insulin therapy, including HUMALOG, and has been attributed to the anabolic effects of insulin and the decrease in glucosuria.

Insulin, including HUMALOG, may cause sodium retention and edema, particularly if previously poor metabolic control is improved by intensified insulin therapy.

In a 12-week, randomized, crossover study in adult patients with type 1 diabetes (n=39), the rates of catheter occlusions and infusion site reactions were similar for HUMALOG U-100 and regular human insulin treated patients (see Table 3).

Table 3: Catheter Occlusions and Infusion Site Reactions

In a randomized, 16-week, open-label, parallel design study of children and adolescents with type 1 diabetes, adverse event reports related to infusion-site reactions were similar for insulin lispro and insulin aspart (21% of 100 patients versus 17% of 198 patients, respectively). In both groups, the most frequently reported infusion site adverse events were infusion site erythema and infusion site reaction.

Local Allergy

As with any insulin therapy, patients taking HUMALOG may experience redness, swelling, or itching at the site of the injection. These minor reactions usually resolve in a few days to a few weeks, but in some occasions, may require discontinuation of HUMALOG. In some instances, these reactions may be related to factors other than insulin, such as irritants in a skin cleansing agent or poor injection technique.

Systemic Allergy

Severe, life-threatening, generalized allergy, including anaphylaxis, may occur with any insulin, including HUMALOG. Generalized allergy to insulin may cause whole body rash (including pruritus), dyspnea, wheezing, hypotension, tachycardia, or diaphoresis.

In controlled clinical trials, pruritus (with or without rash) was seen in 17 patients receiving regular human insulin (n=2969) and 30 patients receiving HUMALOG (n=2944).

Localized reactions and generalized myalgias have been reported with injected metacresol, which is an excipient in HUMALOG [see CONTRAINDICATIONS].

In large clinical trials with patients with type 1 (n=509) and type 2 (n=262) diabetes mellitus, anti-insulin antibody (insulin lispro-specific antibodies, insulin-specific antibodies, cross-reactive antibodies) formation was evaluated in patients receiving both regular human insulin and HUMALOG (including patients previously treated with human insulin and naive patients). As expected, the largest increase in the antibody levels occurred in patients new to insulin therapy. The antibody levels peaked by 12 months and declined over the remaining years of the study. These antibodies do not appear to cause deterioration in glycemic control or necessitate an increase in insulin dose. There was no statistically significant relationship between the change in the total daily insulin dose and the change in percent antibody binding for any of the antibody types.

Postmarketing Experience

The following additional adverse reactions have been identified during post-approval use of HUMALOG. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Medication errors in which other insulins have been accidentally substituted for HUMALOG have been identified during postapproval use [see PATIENT INFORMATION].

Read the entire FDA prescribing information for Humalog (Insulin Lispro (Human Analog))

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.

• Facilitates cellular uptake of glucose in muscle and other tissues, except the brain.c d Stimulates protein synthesis and inhibits protein catabolism.1 d

• Inhibits output of glucose from the liver.9 c d In the liver, insulin facilitates phosphorylation of glucose to glucose-6-phosphate which is converted to glycogen or further metabolized.d Promotes the conversion of excess glucose into fat.1

• Stimulates lipogenesis and inhibits lipolysis and release of free fatty acids from adipose cells.d

• Promotes an intracellular shift of potassium and thereby appears to temporarily decrease elevated blood concentrations of this ion.d

• Importance of providing the patient with a copy of the manufacturer’s patient information.1 2 23 26

• Importance of providing instructions regarding insulin storage, dosage, and proper injection technique.1 e

• Importance of strict adherence to manufacturer’s instructions regarding assembly, administration, and care of specialized delivery systems, such as insulin pens.72 144 145 e

• Importance of changing insulin preparation or dosage with caution and only under medical supervision.1 19 51 Discuss potential for alterations in insulin requirements and need for additional monitoring of blood glucose concentrations in special situations (e.g., illness, concomitant agents that alter glycemic control, travel, emotional disturbances, or other stresses).

• Advise patients of the risks and advantages of conventional and intensive insulin therapy.

• Importance of administering insulin lispro sub-Q within 15 minutes before or immediately after a meal.1

• Advise patient not to smoke within 30 minutes after insulin injection, due to potential for decreased absorption of insulin.e

• Importance of carefully advising patients of the differences in action profiles between insulin lispro and insulin human (regular) during transfer from insulin human to insulin lispro.1 74 May be necessary to adjust the consumption and/or timing of snacks or exercise to avoid hypoglycemic episodes and/or prevent preprandial hyperglycemia.1 74

• Importance of regular self monitoring of blood glucose concentrations.1 e Particular importance of frequent self monitoring of blood glucose concentrations in patients with a history of hypoglycemic unawareness or recurrent, severe hypoglycemic episodes.

• Provide instructions regarding adherence to meal planning, regular physical exercise, periodic HbA1c monitoring, and management of hypoglycemia or hyperglycemia.1 e

• Importance of wearing a medical identification bracelet or pendant, carrying ample insulin supply and syringes on trips, and having carbohydrates (sugar or candy) on hand for emergency.e

• Importance of not changing the order of mixing insulins or the model or brand of syringe or needle without medical supervision.1 e When mixing with long-acting insulin preparations, importance of drawing insulin lispro into the syringe first.e

• Importance of informing clinicians of the development of generalized hypersensitivity reactions (shortness of breath, hypotension, wheezing, whole body rash, tachycardia, diaphoresis).1

• Importance of patients being aware of symptoms of diabetic ketoacidosis and the need to monitor blood ketones if preprandial blood glucose concentrations repeatedly exceed 250–300 mg/dL or if they have an acute illness. Importance of contacting a physician if results of self-monitored blood glucose concentrations are consistently abnormal.

• Inform patient that use of marijuana may increase insulin requirements.e

• Instruct patient on the appropriate measures for safe disposal of needles.e

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs as well as any concomitant illnesses.1

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Insulin lispro is a fast-acting type of insulin. Insulin is one of many hormones that helps the body turn the food we eat into energy. This is done by using the glucose (sugar) in the blood as quick energy. Also, insulin helps us store energy that we can use for later. When you have diabetes mellitus, your body cannot make enough or does not use insulin properly. So, you must take additional insulin to regulate your blood sugar and keep your body healthy. This is very important as too much sugar in your blood can be harmful to your health.

Insulin lispro starts to work faster than some other types of insulin, and its effects do not last as long. It should act more like the insulin your body would normally produce. Because the effects of insulin lispro are short-acting, your doctor may also prescribe a longer-acting insulin for you to use.

This medicine is available only with your doctor's prescription.

Never Share a Humalog KwikPen, Cartridge, Reusable Pen Compatible with Lilly 3 mL Cartridges1, or Syringe Between Patients

Humalog KwikPens, cartridges, and reusable pens compatible with Lilly 3 mL cartridges must never be shared between patients, even if the needle is changed. Patients using Humalog vials must never share needles or syringes with another person. Sharing poses a risk for transmission of blood-borne pathogens.

Hyper- or Hypoglycemia with Changes in Insulin Regimen

Changes in insulin strength, manufacturer, type, or method of administration may affect glycemic control and predispose to hypoglycemia [see Warnings and Precautions (5.3)] or hyperglycemia. These changes should be made cautiously and under close medical supervision and the frequency of blood glucose monitoring should be increased.

Hypoglycemia

Hypoglycemia is the most common adverse reaction associated with insulins, including Humalog. 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).

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) [see Drug Interactions (7)], or in patients who experience recurrent hypoglycemia.

Risk Factors for Hypoglycemia

The risk of hypoglycemia after an injection is related to the duration of action of the insulin 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 Humalog 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 [see Clinical Pharmacology (12.2)]. 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 co-administered medication [see Drug Interactions (7)]. Patients with renal or hepatic impairment may be at higher risk of hypoglycemia [see Use in Specific Populations (8.6, 8.7)].

Risk Mitigation Strategies for Hypoglycemia

Patients and caregivers must be educated to recognize and manage hypoglycemia. Self-monitoring 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 basal insulin products and other insulins, particularly rapid-acting insulins, have been reported. To avoid medication errors between Humalog and other insulins, instruct patients to always check the insulin label before each injection.

Do not transfer Humalog U-200 from the Humalog KwikPen to a syringe. The markings on the insulin syringe will not measure the dose correctly and can result in overdosage and severe hypoglycemia [see Dosage and Administration (2.1) and Warnings and Precautions (5.3)].

Hypersensitivity Reactions

Severe, life-threatening, generalized allergy, including anaphylaxis, can occur with insulin products, including Humalog. If hypersensitivity reactions occur, discontinue Humalog; treat per standard of care and monitor until symptoms and signs resolve [see Adverse Reactions (6.1)]. Humalog is contraindicated in patients who have had hypersensitivity reactions to Humalog or any of its excipients [see Contraindications (4)].

Hypokalemia

All insulin products, including Humalog, 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 serum potassium concentrations).

Fluid Retention and Heart Failure with Concomitant Use of PPAR-gamma Agonists

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 heart failure. Patients treated with insulin, including Humalog, and a PPAR-gamma agonist should be observed for signs and symptoms of heart failure. If 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.

Hyperglycemia and Ketoacidosis Due to Insulin Pump Device Malfunction

Malfunction of the insulin pump or insulin infusion set or insulin degradation can rapidly lead to hyperglycemia and ketoacidosis. Prompt identification and correction of the cause of hyperglycemia or ketosis is necessary. Interim subcutaneous injections with Humalog may be required. Patients using continuous subcutaneous insulin infusion pump therapy must be trained to administer insulin by injection and have alternate insulin therapy available in case of pump failure [see How Supplied/Storage and Handling (16.2) and Patient Counseling Information (17.7)].

Pregnancy

Pregnancy Category B. All pregnancies have a background risk of birth defects, loss, or other adverse outcome regardless of drug exposure. This background risk is increased in pregnancies complicated by hyperglycemia and may be decreased with good metabolic control. It is essential for patients with diabetes or history of gestational diabetes to maintain good metabolic control before conception and throughout pregnancy. In patients with diabetes or gestational diabetes 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. Therefore, female patients should be advised to tell their physicians if they intend to become, or if they become pregnant while taking Humalog.

Although there are limited clinical studies of the use of Humalog in pregnancy, published studies with human insulins suggest that optimizing overall glycemic control, including postprandial control, before conception and during pregnancy improves fetal outcome.

In a combined fertility and embryo-fetal development study, female rats were given subcutaneous insulin lispro injections of 5 and 20 units/kg/day (0.8 and 3 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) from 2 weeks prior to cohabitation through Gestation Day 19. There were no adverse effects on female fertility, implantation, or fetal viability and morphology. However, fetal growth retardation was produced at the 20 units/kg/day-dose as indicated by decreased fetal weight and an increased incidence of fetal runts/litter.

In an embryo-fetal development study in pregnant rabbits, insulin lispro doses of 0.1, 0.25, and 0.75 unit/kg/day (0.03, 0.08, and 0.24 times the human subcutaneous dose of 1 unit/kg/day, based on units/body surface area, respectively) were injected subcutaneously on Gestation days 7 through 19. There were no adverse effects on fetal viability, weight, and morphology at any dose.

Nursing Mothers

It is unknown whether insulin lispro is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Humalog is administered to a nursing woman. Use of Humalog is compatible with breastfeeding, but women with diabetes who are lactating may require adjustments of their insulin doses.

Pediatric Use

Humalog is approved for use in children for subcutaneous daily injections [see Clinical Studies (14)]. Only the U-100 formulation of Humalog is approved for use in children by continuous subcutaneous infusion in insulin pumps. Humalog has not been studied in pediatric patients younger than 3 years of age. Humalog has not been studied in pediatric patients with type 2 diabetes.

As in adults, the dosage of Humalog must be individualized in pediatric patients based on metabolic needs and results of frequent monitoring of blood glucose.

Geriatric Use

Of the total number of subjects (n=2834) in eight clinical studies of Humalog, twelve percent (n=338) were 65 years of age or over. The majority of these had type 2 diabetes. HbA1c values and hypoglycemia rates did not differ by age. Pharmacokinetic/pharmacodynamic studies to assess the effect of age on the onset of Humalog action have not been performed.

Renal Impairment

Patients with renal impairment may be at increased risk of hypoglycemia and may require more frequent Humalog dose adjustment and more frequent blood glucose monitoring [see Clinical Pharmacology (12.3)].

Hepatic Impairment

Patients with hepatic impairment may be at increased risk of hypoglycemia and may require more frequent Humalog dose adjustment and more frequent blood glucose monitoring [see Clinical Pharmacology (12.3)].

Humalog (insulin lispro) is a fast-acting insulin that starts to work about 15 minutes after injection, peaks in about 1 hour, and keeps working for 2 to 4 hours. Insulin is a hormone that works by lowering levels of glucose (sugar) in the blood.

Humalog is used to improve blood sugar control in adults and children with diabetes mellitus.

Humalog is used to treat type 2 diabetes in adults.

Humalog is also used to treat type 1 diabetes in adults and children who are at least 3 years old.

Insulin can cause low blood sugar. Avoid driving or operating machinery until you know how this medicine will affect you.

Avoid medication errors by always checking the medicine label before injecting your insulin.

Avoid drinking alcohol. It can cause low blood sugar and may interfere with your diabetes treatment.