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Pronunciation: PRAM-lin-tide AS-e-tate
Class: Amylin analog
- Solution for injection 0.6 mg/mL
- Solution for injection 1 mg/mL
Synthetic analog of the naturally occurring neuroendocrine hormone amylin. Amylin is colocated with insulin in pancreatic beta cells and is cosecreted with insulin in response to food intake. Amylin slows gastric emptying, suppresses glucagon secretion, and regulates food intake by centrally mediated modulation of appetite.
Absolute bioavailability following subcutaneous injection is 30% to 40%. Injection into arm showed higher exposure with more variability as compared with injection in abdominal area or thigh.
40% of drug is unbound in plasma. Does not bind extensively to blood cells or albumin.
Metabolized by the kidneys to active metabolite (2-37 pramlintide). The t ½ of pramlintide and active metabolite is approximately 48 min. AUC values are relatively constant with repeated dosing.
Special PopulationsRenal Function Impairment
No changes in pharmacokinetics have been shown in patients with moderate or severe renal function impairment. Studies have not been done in dialysis patients.Hepatic Function Impairment
Studies have not been conducted.Elderly
No studies have been conducted; however, no differences have been observed in clinical trials.Gender
No studies have been conducted; however, no differences have been observed in clinical trials.Race
No studies have been conducted; however, no differences have been observed in clinical trials.
Indications and Usage
As an adjunct treatment for type 1 diabetes in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy; as an adjunct treatment for type 2 diabetes in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy, with or without concurrent sulfonylurea and/or metformin therapy.
Confirmed diagnosis of gastroparesis; hypoglycemia unawareness; hypersensitivity to any component of the product.
Dosage and AdministrationInsulin-Using Type 2 Diabetes
Subcutaneous Initiate pramlintide at dose of 60 mcg immediately prior to major meals. Reduce preprandial, rapid-acting or short-acting insulin doses, including fixed-mix insulins (eg, 70/30), by 50%. Increase dose to 120 mcg when no clinically significant nausea has occurred for 3 to 7 days. If significant nausea persists at the 120 mcg dose, decrease pramlintide dose to 60 mcg.Type 1 Diabetes
Subcutaneous Initiate pramlintide at dose of 15 mcg immediately prior to major meals. Reduce preprandial, rapid-acting or short-acting insulin doses, including fixed-mix insulins (eg, 70/30), by 50%. Increase dose in 15 mcg increments to maintenance dose of 30 or 60 mcg. Increase pramlintide dose to next increment (eg, 30, 45, or 60 mcg) when no clinically significant nausea has occurred for at least 3 days. If significant nausea persists at the 45 or 60 mcg dose level, decrease dose to 30 mcg. If 30 mcg dose is not tolerated, consider discontinuing therapy.
- Adjust insulin dose to optimize glycemic control once target dose of pramlintide is achieved and nausea (if experienced) has subsided.
- Instruct patients that dosage adjustments should be made only as directed by the health care provider.
- Administer immediately prior to each major meal (containing at least 250 kcal or 30 g of carbohydrate).
- Visually inspect solution before withdrawing dose. Do not use if particulate matter, discoloration, or cloudiness noted.
- Measure prescribed dose using 0.3 mL U-100 insulin syringe using the following guidelines: For 15 mcg dose: withdraw 0.025 mL or 2.5 units using increment line on U-100 syringe. For 30 mcg dose: withdraw 0.05 mL or 5 units using increment line on U-100 syringe. For 45 mcg dose: withdraw 0.075 mL or 7.5 units using increment line on U-100 syringe. For 60 mcg dose: withdraw 0.1 mL or 10 units using increment line on U-100 syringe. For 120 mcg dose: withdraw 0.2 mL or 20 units using increment line on U-100 syringe.
- Administer each dose into abdomen or thigh. Do not administer into arm because of variable absorption. Rotate injection sites. Make injection site distinct from the site chosen for any concomitant insulin injection.
- Always administer pramlintide and insulin as separate injections. Do not mix pramlintide with any type of insulin. Always use a new syringe and needle to give pramlintide and insulin injections.
Store unopened (not in-use) vial in refrigerator (36° to 46°F). Protect from light and freezing. Discard if vial has been frozen or overheated. Store opened (in-use) vial in refrigerator (36° to 46°F) or at room temperature not exceeding 86°F for up to 30 days. Discard after 30 days.
Drug InteractionsDrugs that alter GI motility (eg, anticholinergic agents [eg, atropine]), agents that slow intestinal absorption of nutrients (eg, alpha-glucosidase inhibitors)
Pramlintide alters gastric emptying time and slows the rate at which food is released from the stomach to the small intestine. Until studied, do not consider pramlintide for use in patients taking drugs that alter GI motility or slow intestinal absorption of nutrients.Orally coadministered drugs
Pramlintide has the potential to delay the absorption of coadministered oral drugs. When the rapid onset of the coadministered oral drug is critical for effectiveness, administer the drug at least 1 h prior to or 2 h after pramlintide injection.
Laboratory Test Interactions
None well documented.
The following adverse reactions were reported with combined use of pramlintide with insulin. Adverse reactions occurred at a frequency of at least 5%.
Headache (13%); fatigue (7%); dizziness (6%).
Nausea (48%); anorexia (17%); vomiting (11%); abdominal pain, vomiting (8%).
Inflicted injury (14%).
Pramlintide is used with insulin and has been associated with an increased risk of insulin-induced severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia associated with pramlintide use occurs, it is seen within 3 h after a pramlintide injection. If severe hypoglycemia occurs while operating a motor vehicle or heavy machinery, or while engaging in other high-risk activities, serious injuries may occur. Appropriate patient selection, careful patient instructions, and insulin dose adjustments are critical elements for reducing this risk.
Review hemoglobin A 1c (HBA 1c ), recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight before initiating pramlintide therapy. Monitor blood glucose frequently, including pre- and post-meals and at bedtime. Patient should be seen at least once a week until target dose of pramlintide is achieved and well tolerated, and blood glucose concentrations are stable.
Category C .
Safety and efficacy have not been established.
Special Risk Patients
Use with caution in patients with visual or dexterity impairment.
Redness, swelling, or itching at the site of injection may occur. Systemic allergy occurred in about 5% of patients and reactions were similar to those occurring with placebo.
Discontinuation of therapy
Discontinue pramlintide therapy if any of the following occur: recurrent unexplained hypoglycemia requiring medical assistance; persistent clinically significant nausea; noncompliance with self-monitoring of blood glucose concentrations; noncompliance with insulin dose adjustments; noncompliance with scheduled health care provider contacts or recommended follow-up.
Pramlintide alone does not cause hypoglycemia but does increase the risk of insulin-induced hypoglycemia, particularly in patients with type 1 diabetes. Severe hypoglycemia occurs within the first 3 h following pramlintide administration. Take precautions (eg, frequent pre- and post-meal glucose monitoring combined with an initial 50% reduction in pre-meal dose of short-acting insulin) to reduce the risk of insulin-induced severe hypoglycemia.
If pramlintide dose is missed, do not administer an additional injection.
Pramlintide therapy should only be considered in patients with insulin-using type 2 or type 1 diabetes who have failed to achieve adequate glycemic control despite individualized insulin management and are receiving ongoing care under the guidance of a health care provider skilled in the use of insulin and supported by the services of diabetes educator(s). Pramlintide should not be used if the patient has any of the following: poor compliance with current insulin regimen; poor compliance with prescribed self–blood glucose monitoring; HBA 1c greater than 9%; recurrent severe hypoglycemia requiring assistance during the past 6 mo; presence of hypoglycemia unawareness; confirmed diagnosis of gastroparesis; if the patient requires use of drugs that stimulate GI motility; or if the patient is a child.
Reinstituting pramlintide therapy
If pramlintide therapy is discontinued for any reason (eg, surgery, illness), follow the same initiation protocol when pramlintide therapy is reinstituted.
Diarrhea, dizziness, severe nausea, vasodilation, vomiting.
- Explain name, dose, action, potential adverse reactions of pramlintide, and the need for frequent blood sugar monitoring and follow-up visits for dosage adjustment of pramlintide and insulin.
- Ensure that patient or caregiver understands that pramlintide does not replace daily insulin but may lower the amount of insulin needed, especially before meals.
- Advise patient that pramlintide will be started at a low dose and then increased, as tolerated, to a dose that will provide max benefit.
- Advise patient that insulin dose will be reduced when pramlintide is started but the insulin dose will be periodically readjusted to achieve maximum blood sugar control.
- Advise patient or caregiver to read patient information leaflet before using the first time and with each refill.
- Ensure that patient or caregiver understands how to store, prepare, and administer the pramlintide and insulin doses and how to dispose of used equipment and supplies.
- Ensure that patient or caregiver understands that pramlintide and insulin must be administered as separate injections at separate injection sites and that pramlintide cannot be mixed with any insulin product.
- Advise patient to continuously rotate pramlintide and insulin injection sites (abdomen and thigh). Caution patient not to inject pramlintide into arm because of variable absorption and effectiveness.
- Instruct patient to administer prescribed dose of pramlintide immediately before each major meal.
- Advise patient that if a pramlintide dose is missed, to skip it and take the next dose immediately before the next major meal. Caution patient not to double the dose to catch up.
- Educate patient or caregiver regarding diabetes and its management, including target ranges for blood sugar control. Instruct patient that pramlintide and insulin are not a substitute for diet and exercise and to follow prescribed regimens.
- Instruct patients that pramlintide and insulin dosage adjustments should be made only as directed by health care provider.
- Educate patient or caregiver regarding potential long-term complications of diabetes and need for regular general physical and eye examinations.
- Ensure that patient or caregiver understands how to use home glucose monitoring system and understands the need for frequent (eg, pre- and post-meals and bedtime) monitoring and recording of blood sugar measurements. Advise patient to take blood sugar log to each visit with health care provider.
- Advise patient that dose(s) of insulin will be adjusted based on the results of home glucose monitoring.
- Ensure that patient with type 1 diabetes understands how to monitor for ketones and knows what to do if ketones are detected.
- Educate patient regarding value of periodic A 1c testing to confirm level of glucose control.
- Review symptoms of hypoglycemia and hyperglycemia and what to do if either occurs.
- Advise patient to discuss with health care provider a plan for managing each of the following situations: pramlintide and insulin dosing during intercurrent conditions (eg, vomiting, infection, trauma, stress, sick days); accidental administration of too little or too much pramlintide or insulin; missing insulin dose; inadequate food intake or a skipped meal; travel across time zones; change in physical activity.
- Advise patient to carry medical identification (eg, card, bracelet) indicating diabetes.
- Instruct patient to notify health care provider if experiencing severe, continuous, or frequent hypoglycemic episodes, recurrent nausea, hypoglycemic episodes with few or no warning symptoms, continuous or severe hyperglycemia, or injection-site reactions that do not go away or continue to recur.
- Caution patient that pramlintide may cause hypoglycemia during the first 3 h following a dose and to use caution while driving or performing other high-risk activities during that time.
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