In the three studies, from a mean baseline body weight of 75.3 kg, 73.3 kg, and 76.6 kg, respectively, after randomization there were corresponding mean reductions of –0.8 kg, –1.6 kg, and –1.3 kg (60 mcg TID) and –0.8 kg (60 mcg QID) in the Symlin treatment group compared to mean increases of +0.8 kg, +0.4 kg, and +0.7 kg in the placebo treatment group. ©2019 AstraZeneca. Relative bioavailability of pramlintide was not significantly different between obese and non-obese patients and based on BMI or skin fold thickness. Refer patients to the Symlin Medication Guide and Patient Instructions for Use for additional information. SYMLIN slows gastric emptying which may delay absorption of concomitantly administered oral medications. The primary metabolite, Des-lys1 pramlintide (2-37 pramlintide), is biologically active in vitro. Symlin (pramlintide) is a antihyperglycemic agent. Appropriate patient selection. It is not known if Symlin is safe and effective in children. Wilmington, DE 19850. The formulation contains 2.25 mg/mL of metacresol as a preservative, D-mannitol as a tonicity modifier, acetic acid, sodium acetate as pH modifiers, and water for injection. This effect lasts for approximately 3 hours following SYMLIN administration. Read the “Instructions for Use” and the Medication Guide and that come with your Symlin for information about the right way to use Symlin. Symlin (pramlintide) is a man-made form of a hormone that occurs naturally in the body. Symlin was initiated at a dose of 15 mcg and titrated upward at weekly intervals in 15 mcg increments to maintenance doses of 30 or 60 mcg, based on whether patients experienced nausea. AstraZeneca Pharmaceuticals LP If a Symlin dose is missed, wait until the next scheduled dose and administer the usual amount. Following meals, glucagon will be released by the liver to raise levels of glucose in the blood in order to aid digestion. Pramlintide was not mutagenic in the Ames test and did not increase chromosomal aberration in the human lymphocytes assay. Prescribe with caution in patients with visual or dexterity impairment. 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. [Brand] is a [registered] trademark of the AstraZeneca group of companies. If Symlin therapy is discontinued for any reason (e.g., surgery or illnesses), the same initiation protocol should be followed when Symlin therapy is reinstituted [see Dosage and Administration (2.2)]. US-9413; US-25931 Last Updated 1/19. This Medication Guide has been approved by the U.S. Food and Drug Administration. This mechanism of action is specific to aspirin, and is not constant for all nonsteroidal anti-inflammatory drugs (NSAIDs). Symlin slows stomach emptying and can affect medicines that need to pass through the stomach quickly. Proper patient selection is critical to the safe and effective use of Symlin. Pramlintide is sold as an acetate salt. Dosage Form: injection, pen. Pharmacokinetic profiles of pramlintide and insulins after coadministration of 30 mcg Symlin with different insulins (regular, NPH, and 70/30 premixed formulations of recombinant human insulin) as one subcutaneous injection, premixed in one syringe, were compared to those observed after the coadministration of Symlin and different insulins given as separate subcutaneous injections. There may be new information. In some instances, these reactions may be related to factors other than Symlin, such as irritants in a skin cleansing agent or improper injection technique. If the 30 mcg dose is not tolerated, discontinuation of Symlin therapy should be considered. Mixing Symlin and insulin can alter the pharmacokinetics of both products which may result in inadequate glucose control or hypoglycemia. See “What is the most important information I should know about Symlin?”. Pramlintide (trade name Symlin) is an injectable amylin analogue drug for diabetes (both type 1 and 2), developed by Amylin Pharmaceuticals (now a wholly owned subsidiary of AstraZeneca). Onset averaged approximately 63 days after initiating protease inhibitor therapy, but has occurred as early as 4 days after beginning therapy. SYMLIN® (pramlintide acetate) Injection is an antihyperglycemic drug for use in patients with diabetes treated with insulin. Figure 2: Postprandial Plasma Glucose Profiles in Patients with Type 1 Diabetes or Type 2 Diabetes Receiving Symlin and Insulin Compared to Those Receiving Insulin Alone. Injection of Symlin into the arm in obese patients with type 1 or type 2 diabetes showed higher overall exposure (20%-36%) with greater variability (% CV for AUC: 73%-106%), compared with exposure after injection of Symlin into the abdominal area or thigh. When the rapid onset or threshold concentration of a concomitant orally administered medication is a critical determinant of effectiveness (such as with analgesics, antibiotics, and oral contraceptives), the medication should be administered at least 1 hour prior to Symlin injection or 2 hours after Symlin injection [see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3)]. Kruger DF, Gatcomb PM, Owen SK. Symlin should not be mixed with any type of insulin. Only consider SYMLIN for patients who failed to achieve adequate glycemic control despite individualized insulin management, and patients who are receiving ongoing care under the guidance of a healthcare professional skilled in insulin use and are supported by a diabetes educator. Advise patients that they must never share a SymlinPen with another person, even if the needle is changed, because doing so carries a risk for transmission of blood-borne pathogens. Mechanism of Action SYMLIN, by acting as an amylinomimetic agent, has the following effects: 1) modulation of gastric emptying; 2) prevention of the postprandial rise in plasma glucagon; and 3) satiety leading to decreased caloric intake and potential weight loss. It slows the rate at which food (including glucose) is absorbed from the intestine. Edelman SV, Weyer C. Unresolved challenges with insulin therapy in type 1 and type 2 diabetes: potential benefit of replacing amylin, a second beta-cell hormone. Amylin is colocated with insulin in secretory granules and cosecreted with insulin by pancreatic beta cells in response to food intake. Symlin and these drugs should be coadministered with caution. Mechanism of action. These Instructions for Use have been approved by the U.S. Food and Drug Administration. Symlin pen-injectors in use: After first use, refrigerate or keep at a temperature not greater than 86°F (30°C) for 30 days. Injection sites should be rotated so that the same site is not used repeatedly. The term incretin was first used in 1930 to describe the enhanced glucose lowering effect that was seen when a gut extract was fed to dogs. More information, go to www.Symlin.com or call 1-800-236-9933. You should have fast-acting sugar (such as hard candy, glucose tablets, juice) or glucagon for injection with you at all times. Symlin is used when your mealtime insulin dose has not controlled your blood sugar well enough. What should I tell my healthcare provider before using Symlin? Appropriate patient selection, careful patient instruction, and insulin dose reduction are critical elements for reducing this risk. Figure 1: Secretion Profile of Amylin and Insulin in Healthy Adults. SYMLIN reduced postprandial glucose levels when administered prior to meals with mealtime insulin1,5,6. Pen needles not included. The estimated background risk of miscarriage for the indicated population is unknown. No study has been conducted to evaluate the effect of gender on pramlintide pharmacokinetics. Subtracted LSM change in HbA1c at 6 Months (%), Mean Insulin Doses at Baseline: Mealtime/Bolus (U) (SE), Mean Change in Insulin Doses (U) at 6 Months: Mealtime/Bolus (SE), Mean Insulin Doses at Baseline: Basal (U) (SE), Mean Change in Insulin Doses (U) at 6 Months: Basal (SE). The incidence of severe hypoglycemia during the Symlin clinical development program is summarized in Table 3 and Table 4. The injection site selected should also be distinct from the site chosen for any concomitant insulin injection. Appropriate patient selection, careful patient instruction, and insulin dose reduction are critical elements for reducing this risk. The time to maximum plasma concentration or Tmax increased by 72, 48, and 48 minutes, respectively. The physiological effects of endogenous amylin and the administered pramlintide are similar. The following are examples of medications that may increase the susceptibility to hypoglycemia when administered with Symlin: anti-diabetic products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics. Amylin also regulates food intake due to centrally-mediated modulation of appetite. This Medication Guide summarizes the most important information about Symlin. Use 29, 30, or 31 gauge disposable pen needles. Developmental and reproductive toxicity studies with Symlin were performed in pregnant rats and rabbits. Each Symlin dose should be administered subcutaneously into the abdomen or thigh. SD: standard deviation; LSM: least squares mean; SE: standard error; U: Units; NM: not measured; TID: 3 times a day; QID: 4 times a day. Similarly, effects of premixing on insulin pharmacokinetics varied across different insulin products with a maximum increase of 15% in insulin Cmax and up to a 20% increase in insulin AUC0-600min. SYMLIN use with insulin increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes. Weyer C, Gottlieb A, Kim DD, et al. Symlin and insulin should always be administered as separate injections. Table 7 summarizes the 6-month results for the dose-titration study. We all know that insulin, either naturally from beta cell or injected from outside, affects the level of glucose in the blood. Severe Hypoglycemia: Increased risk, particularly for type 1 diabetes. SYMLIN is indicated as an adjunctive treatment in adults with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. Symlin is formulated as a clear, isotonic, sterile solution for subcutaneous administration. Do not use Symlin for a condition for which it was not prescribed. SYMLIN use with insulin increases the risk of severe hypoglycemia, , particularly in patients with type 1 diabetes. No consistent differences in the efficacy and safety of Symlin have been observed between men and women in Symlin clinical trials (n=2799 for male and n=2085 for female). Symlin use has not been studied in patients with hepatic impairment [see Clinical Pharmacology (12.3)]. Symlin is indicated as an adjunctive treatment in patients with type 1 or type 2 diabetes who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy. Use Symlin exactly as your healthcare provider tells you to use it. Serious injuries may occur if severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities. SYMLIN slows gastric emptying which may delay absorption of concomitantly administered oral medications. Symlin should be administered subcutaneously immediately prior to each major meal (≥250 kcal or containing ≥30 grams of carbohydrate). There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (see Clinical Considerations). Symlin and insulin must not be mixed and must be administered as separate injections [see Dosage and Administration (2.4), Warnings and Precautions (5.4), and Clinical Pharmacology (12.3)]. Administration of 0.3, 1, or 3 mg/kg/day of pramlintide (up to 140 times the human dose of 360 mcg/day based on exposure) prior to and during mating had no significant effects on fertility in male or female rats. An increased frequency of mild-to-moderate hypoglycemia should be viewed as a warning sign of increased risk for severe hypoglycemia. Do not inject your dose of Symlin if you: See “Disposing of used SymlinPens and needles” at the end of these Instructions for Use. Most adverse reactions were gastrointestinal in nature. Do not repeat Step 1 through 4 before each dose. Severe Hypoglycemia: Increased risk, particularly for type 1 diabetes.