How is byetta package

Some of these events occurred in patients receiving one or more pharmacologic agents known to affect renal function or hydration status, such as angiotensin converting enzyme inhibitors, nonsteroidal anti-inflammatory drugs, or diuretics. Some events occurred in patients who had been experiencing nausea, vomiting, or diarrhea, with or without dehydration. Reversibility of altered renal function has been observed in many cases with supportive treatment and discontinuation of potentially causative agents, including BYETTA.

Exenatide has not been found to be directly nephrotoxic in preclinical or clinical studies. If a hypersensitivity reaction occurs, the patient should discontinue BYETTA and other suspect medications and promptly seek medical advice. Drug-induced thrombocytopenia is an immune-mediated reaction, with exenatide-dependent anti-platelet antibodies.

In the presence of exenatide, these antibodies cause platelet destruction. Nausea usually decreases over time. See Table 9 for insulin dose titration algorithm.

No treatment-emergent cross-reactive antibodies were observed across the range of titers. No placebo-treated patients withdrew due to adverse reactions. Nausea was the most frequently reported adverse reaction and occurred in a dose-dependent fashion. With continued therapy, the frequency and severity decreased over time in most of the patients who initially experienced nausea. Patients in the long-term uncontrolled open-label extension studies at 52 weeks reported no new types of adverse reactions than those observed in the week controlled trials.

The two patients who reported an injection-site reaction had high titers of antibodies to exenatide. No serious adverse events were reported in the placebo arm.

No placebo-treated patients withdrew due to nausea or vomiting. Because these events are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. For oral medications that are dependent on threshold concentrations for efficacy, such as contraceptives and antibiotics, patients should be advised to take those drugs at least 1 hour before BYETTA injection.

In patients taking warfarin, prothrombin time should be monitored more frequently after initiation or alteration of BYETTA therapy. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on warfarin. BYETTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The estimated background risk of miscarriage for the indicated population is unknown. In the U. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. Exenatide was present in the milk of lactating mice. BYETTA was studied in patients 65 years of age or older and in 16 patients 75 years of age or older. No differences in safety or effectiveness were observed between these patients and younger patients.

Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function. In patients with end-stage renal disease receiving dialysis, single doses of BYETTA 5 mcg were not well-tolerated due to gastrointestinal side effects. Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations. One of the three patients experienced severe hypoglycemia requiring parenteral glucose administration.

The three patients recovered without complication. In the event of overdose, appropriate supportive treatment should be initiated according to the patient's clinical signs and symptoms. The amino acid sequence for exenatide is shown below. Each milliliter mL contains micrograms mcg synthetic exenatide, 2. Two prefilled pens are available to deliver unit doses of 5 mcg or 10 mcg.

Each prefilled pen will deliver 60 doses to provide for 30 days of twice daily administration BID. BYETTA is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia. This secretion, known as the "first-phase insulin response," is characteristically absent in patients with type 2 diabetes.

The loss of the first-phase insulin response is an early beta-cell defect in type 2 diabetes. Administration of BYETTA at therapeutic plasma concentrations restored first-phase insulin response to an IV bolus of glucose in patients with type 2 diabetes Figure 1. Lower glucagon concentrations lead to decreased hepatic glucose output and decreased insulin demand. Exenatide exposure AUC increased proportionally over the therapeutic dose range of 5 to 10 mcg.

The mean apparent clearance of exenatide in humans is 9. These pharmacokinetic characteristics of exenatide are independent of the dose. In most individuals, exenatide concentrations are measurable for approximately 10 hours post-dose. There were no changes in hour mean systolic and diastolic blood pressure.

BYETTA did not alter the mean trough concentrations of levonorgestrel after repeated daily dosing of the oral contraceptive for both regimens. However, in subjects with end-stage renal disease receiving dialysis, mean exenatide exposure increased by 3. Benign thyroid C-cell adenomas were observed in female rats at all exenatide doses. Patients assigned to placebo received placebo BID throughout the trial. In addition, a week, placebo-controlled trial was conducted where BYETTA was added to existing thiazolidinedione pioglitazone or rosiglitazone treatment, with or without metformin, in patients with type 2 diabetes with inadequate glycemic control.

Patients assigned to placebo received placebo BID throughout the study. Table 7 summarizes the study results for the and week clinical trials. In this pooled subset of patients, BYETTA reduced postprandial plasma glucose concentrations in a dose-dependent manner. Five weeks after initiating randomized treatment, insulin doses were titrated with guidance from the investigator toward predefined fasting glucose targets according to the dose titration algorithm provided in Table 9.

After four weeks, their dose was increased to 10 mcg BID. The insulin lispro dose was titrated based on preprandial glucose values. Do not reuse or share needles. If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment.

You may give other people a serious infection or get a serious infection from them. You may feel the pain from your abdomen to your back. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on warfarin.

Limited data with BYETTA in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy see Clinical Considerations. BYETTA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Animal reproduction studies identified increased adverse fetal and neonatal outcomes from exposure to exenatide during pregnancy and lactation in association with maternal effects.

The estimated background risk of miscarriage for the indicated population is unknown. In the U. Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. In studies evaluating reproduction and development in pregnant mice and rabbits, maternal animals were administered exenatide, the active ingredient in BYETTA, by subcutaneous injection twice a day.

In pregnant rabbits given 0. Exenatide was present in the milk of lactating mice. However, due to species-specific differences in lactation physiology, the clinical relevance of these data is not clear see Data. In lactating mice subcutaneously injected twice a day with exenatide, the concentration of exenatide in milk was up to 2.

Effectiveness of BYETTA was not demonstrated in a randomized, double-blind, placebo-controlled study conducted in pediatric patients 78 received BYETTA and 42 received placebo aged 10 to 17 years with type 2 diabetes mellitus.

Population pharmacokinetic analysis of patients ranging from 22 to 73 years of age suggests that age does not influence the pharmacokinetic properties of exenatide [see Clinical Pharmacology BYETTA was studied in patients 65 years of age or older and in 16 patients 75 years of age or older. No differences in safety or effectiveness were observed between these patients and younger patients. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly based on renal function.

In patients with end-stage renal disease receiving dialysis, single doses of BYETTA 5 mcg were not well-tolerated due to gastrointestinal side effects. No pharmacokinetic study has been performed in patients with a diagnosis of acute or chronic hepatic impairment. Because exenatide is cleared primarily by the kidney, hepatic dysfunction is not expected to affect blood concentrations of exenatide [see Clinical Pharmacology In a clinical study of BYETTA, three patients with type 2 diabetes each experienced a single overdose of mcg SC times the maximum recommended dose.

Effects of the overdoses included severe nausea, severe vomiting, and rapidly declining blood glucose concentrations. One of the three patients experienced severe hypoglycemia requiring parenteral glucose administration.

The three patients recovered without complication. In the event of overdose, appropriate supportive treatment should be initiated according to the patient's clinical signs and symptoms.

Exenatide is a amino acid peptide amide. The amino acid sequence for exenatide is shown below. BYETTA injection is supplied for subcutaneous administration as a sterile, preserved isotonic solution in a glass cartridge that has been assembled in a pen-injector pen. Each milliliter mL contains micrograms mcg synthetic exenatide, 2. Two prefilled pens are available to deliver unit doses of 5 mcg or 10 mcg. Each prefilled pen will deliver 60 doses to provide for 30 days of twice daily administration BID.

Incretins, such as glucagon-like peptide-1 GLP-1 , enhance glucose-dependent insulin secretion and exhibit other antihyperglycemic actions following their release into the circulation from the gut.

BYETTA is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. The amino acid sequence of exenatide partially overlaps that of human GLP Exenatide has been shown to bind and activate the human GLP-1 receptor in vitro.

BYETTA improves glycemic control by reducing fasting and postprandial glucose concentrations in patients with type 2 diabetes through the actions described below. BYETTA has acute effects on pancreatic beta-cell responsiveness to glucose leading to insulin release predominantly in the presence of elevated glucose concentrations. This insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia.

In healthy individuals, robust insulin secretion occurs during the first 10 minutes following intravenous IV glucose administration. This secretion, known as the "first-phase insulin response," is characteristically absent in patients with type 2 diabetes.

The loss of the first-phase insulin response is an early beta-cell defect in type 2 diabetes. Administration of BYETTA at therapeutic plasma concentrations restored first-phase insulin response to an IV bolus of glucose in patients with type 2 diabetes Figure 1.

In patients with type 2 diabetes, BYETTA moderates glucagon secretion and lowers serum glucagon concentrations during periods of hyperglycemia. Lower glucagon concentrations lead to decreased hepatic glucose output and decreased insulin demand.

BYETTA slows gastric emptying, thereby reducing the rate at which meal-derived glucose appears in the circulation. In both animals and humans, administration of exenatide has been shown to reduce food intake. In a single-dose crossover study in patients with type 2 diabetes and fasting hyperglycemia, immediate insulin release followed injection of BYETTA.

Following SC administration to patients with type 2 diabetes, exenatide reaches median peak plasma concentrations in 2. Exenatide exposure AUC increased proportionally over the therapeutic dose range of 5 to 10 mcg. The C max values increased less than proportionally over the same range.

Nonclinical studies have shown that exenatide is predominantly eliminated by glomerular filtration with subsequent proteolytic degradation. The mean apparent clearance of exenatide in humans is 9. These pharmacokinetic characteristics of exenatide are independent of the dose. In most individuals, exenatide concentrations are measurable for approximately 10 hours post-dose.

Lisinopril steady-state T max was delayed by 2 hours. There were no changes in hour mean systolic and diastolic blood pressure. The effect of BYETTA 10 mcg BID on single and on multiple doses of a combination oral contraceptive 30 mcg ethinyl estradiol plus mcg levonorgestrel was studied in healthy female subjects. BYETTA did not alter the mean trough concentrations of levonorgestrel after repeated daily dosing of the oral contraceptive for both regimens.

Pharmacokinetics of exenatide was studied in subjects with normal, mild, or moderate renal impairment and subjects with end-stage renal disease. However, in subjects with end-stage renal disease receiving dialysis, mean exenatide exposure increased by 3. No pharmacokinetic study has been performed in patients with a diagnosis of acute or chronic hepatic impairment [see Use in Specific Populations 8.

Population pharmacokinetic analysis of patients ranging from 22 to 73 years of age suggests that age does not influence the pharmacokinetic properties of exenatide [see Use in Specific Population 8.

Population pharmacokinetic analysis of male and female patients suggests that gender does not influence the distribution and elimination of exenatide. Population pharmacokinetic analysis of samples from Caucasian, Hispanic, Asian, and Black patients suggests that race has no significant influence on the pharmacokinetics of exenatide.

Benign thyroid C-cell adenomas were observed in female rats at all exenatide doses. Exenatide was not mutagenic or clastogenic, with or without metabolic activation, in the Ames bacterial mutagenicity assay or chromosomal aberration assay in Chinese hamster ovary cells.

Exenatide was negative in the in vivo mouse micronucleus assay. Patients assigned to placebo received placebo BID throughout the trial. The primary endpoint was the change in HbA 1c from baseline to Week 24 or the last value at time of early discontinuation.

Three week, double-blind, placebo-controlled trials were conducted to evaluate the safety and efficacy of BYETTA in patients with type 2 diabetes whose glycemic control was inadequate with metformin alone, a sulfonylurea alone, or metformin in combination with a sulfonylurea. In addition, a week, placebo-controlled trial was conducted where BYETTA was added to existing thiazolidinedione pioglitazone or rosiglitazone treatment, with or without metformin, in patients with type 2 diabetes with inadequate glycemic control.

Patients assigned to placebo received placebo BID throughout the study. Mean HbA 1c values at baseline for the trials ranged from 8. The mean baseline HbA 1c values were 7. The primary endpoint in each study was the mean change in HbA 1c from baseline to study end or early discontinuation. Table 7 summarizes the study results for the and week clinical trials. In Combination with Metformin and a Sulfonylurea 30 Weeks.

The addition of BYETTA to a regimen of metformin, a sulfonylurea, or both, resulted in statistically significant reductions from baseline in HbA 1c compared with patients receiving placebo added to these agents in the three controlled trials Table 7. Postprandial glucose was measured after a mixed meal tolerance test in 9. In this pooled subset of patients, BYETTA reduced postprandial plasma glucose concentrations in a dose-dependent manner.

Five weeks after initiating randomized treatment, insulin doses were titrated with guidance from the investigator toward predefined fasting glucose targets according to the dose titration algorithm provided in Table 9. The primary endpoint was the change in HbA 1c from baseline to Week After four weeks, their dose was increased to 10 mcg BID.

The insulin lispro dose was titrated based on preprandial glucose values. Advise patients that they must never share a BYETTA pen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens [see Warnings and Precautions 5. Inform patients that persistent severe abdominal pain that may radiate to the back and which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis. Instruct patients to promptly discontinue BYETTA and contact their physician if persistent severe abdominal pain occurs [see Warnings and Precautions 5.

Inform patients that the risk of hypoglycemia is increased when BYETTA is used in combination with an agent that induces hypoglycemia, such as a sulfonylurea or insulin.

Educate patients on the signs and symptoms of hypoglycemia [see Warnings and Precautions 5. Inform patients treated with BYETTA of the potential risk for worsening renal function and about associated signs and symptoms of renal dysfunction, as well as the possibility of dialysis as a medical intervention if renal failure occurs [see Warnings and Precautions 5.

Inform patients that drug-induced immune-mediated thrombocytopenia has been reported during use of exenatide. If symptoms of hypersensitivity reactions occur, instruct patients to stop taking BYETTA and seek medical advice promptly [see Warnings and Precautions 5. Instruct patients to administer BYETTA as a subcutaneous injection in the thigh, abdomen, or upper arm at any time within the minute period before the morning and evening meals or before the two main meals of the day, approximately 6 hours or more apart.

If a dose is missed, resume the treatment regimen as prescribed with the next scheduled dose. There may be new information. This Medication Guide does not take the place of talking with your healthcare provider about your medical condition or your treatment. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Talk with your healthcare provider about how to treat low blood sugar. Talk to your healthcare provider about any side effect that bothers you or that does not go away. Call your doctor for medical advice about side effects. Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

It may harm them. You can ask your healthcare provider or pharmacist for information about BYETTA that is written for health professionals. Inactive ingredients: metacresol, mannitol, glacial acetic acid, and sodium acetate trihydrate in water for injection. All other trademarks are the trademarks of their respective owners.

This Medication Guide has been approved by the U. You may give other people a serious infection or get a serious infection from them. Read this section completely before you begin. Then, move on to Section 2—Getting Started.

It is important that you use your pen correctly. Failure to follow these instructions completely may result in a wrong dose, a broken pen or an infection. These instructions do not take the place of talking with your healthcare provider about your medical condition or your treatment.

Put your used needles in a FDA-cleared sharps disposal container right away after use. Do not throw away dispose of loose needles and syringes in your household trash. If you do not have a FDA-cleared sharps disposal container, you may use a household container that is:.

When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes.

For more information, call toll free Set up your new pen just before you use it the first time. For routine use, do not repeat this one-time-only new pen setup. Note: If you cannot turn the dose knob away from you to the , see Commonly Asked Questions, number 7, in Section 4 of these Instructions for Use. Now that you have done the one-time-only new pen setup, follow Section 3 for all of your injections.

Note: Small air bubbles will not harm you or affect your dose. Note: If you cannot turn the dose knob, or if your pen leaks, your full dose has not been delivered. It is normal for a single drop to remain on the tip of your needle after your injection is complete. If you see more than one drop:. You must follow all the steps listed above to make sure your injection is complete. Inject BYETTA into your abdomen, thigh, or upper arm using the injection method explained to you by your healthcare provider.

If is in the dose window:. If is in the dose window and the dose knob will not turn:. If and part of are in the dose window and the dose knob cannot be pushed in:. If part of and part of are in the dose window and the dose knob cannot be pushed in:. Ask your healthcare provider which pen needle length and gauge is best for you Use 29 thin , 30, or 31 thinner gauge disposable pen needles. Each prefilled pen will deliver 60 subcutaneous doses, 10 mcg per dose.

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Approval: Consider other antidiabetic therapies in patients with a history of pancreatitis. Reduction in the dose of insulin secretagogues or insulin may be necessary. BYETTA should not be used in patients with severe renal impairment or end-stage renal disease and should be used with caution in patients with renal transplantation.

If there is worsening glycemic control or failure to achieve target glycemic control, consider alternative antidiabetic therapy. Nausea usually decreases over time.