Pramlintide Acetate	(PRAM-lin-tide AS-e-tate)
Trade Name(s):	Symlin   ·Solution for injection 0.6 mg/mL   ·Solution for injection 1 mg/mL Indicates Canadian Trade Name.
Class:	Amylin analog
Action:	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. Absorption: 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.
	Distribution: 40% of drug is unbound in plasma. Does not bind extensively to blood cells or albumin.
	Metabolism: 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 Populations: Renal 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:	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.
Contraindications:	Confirmed diagnosis of gastroparesis; hypoglycemia unawareness; hypersensitivity to any component of the product.
Interactions:
	Drugs 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.
Lab Test Interferences:	None well documented.
Adverse Reactions:	The following adverse reactions were reported with combined use of pramlintide with insulin. Adverse reactions occurred at a frequency of at least 5%.
	cns: Headache (13%); fatigue (7%); dizziness (6%).
	eent: Pharyngitis (5%).
	gi: Nausea (48%); anorexia (17%); vomiting (11%); abdominal pain, vomiting (8%).
	musculoskeletal: Arthralgia (7%).
	respiratory: Coughing (6%).
	miscellaneous: Inflicted injury (14%).
Precautions:
Warning:	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.
	Monitoring: 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.
	Pregnancy: Category C .
	Lactation: Unknown.
	Children: Safety and efficacy have not been established.
	Special risk patients: Use with caution in patients with visual or dexterity impairment.
	Allergy 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.
	Hypoglycemia 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.
	Missed dose If pramlintide dose is missed, do not administer an additional injection.
	Patient selection 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.
Overdosage:	Signs & symptoms Diarrhea, dizziness, severe nausea, vasodilation, vomiting.
Patient/Family Education:	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.