Pramlintide

Last Updated

Medications listed in the tables and non-FDA approved indications included in these retrospective criteria are not indicative of Texas Vendor Drug Program formulary coverage.

  • Revision history
    • Oct. 21, 2022; Sept. 2020; Sept. 2018; Sept. 2016; May 2015; Oct. 2013; Dec. 2011; Jan. 2010; May 2006.
  • Initially developed
    • Feb. 2006

1. Dosage

Adults

Pramlintide (Symlin®), a synthetic analog of human amylin, is FDA-approved for use as adjunct therapy in patients with type 1 or type 2 diabetes using mealtime insulin who are not adequately controlled with optimal insulin therapy. Amylin is a neuroendocrine hormone secreted concurrently with insulin in response to food intake to decrease hepatic glucose output and slow gastric emptying, which results in reduced carbohydrate absorption and lower postprandial glucose levels. Similarly, pramlintide works by delaying gastric emptying, decreasing postprandial increases in glucagon levels, and causing satiety, which promotes decreased caloric intake and potential weight loss.1-3 Pramlintide is available as a 1.5 ml disposable, multidose 60-pen injector or a 2.7 ml disposable, multidose 120-pen injector containing pramlintide 1000 mcg/ml. The 60-pen injector provides doses of 15 mcg, 30 mcg, 45 mcg, or 60 mcg while the 120-pen injector provides pramlintide doses of 60 mcg or 120 mcg1,3. Recommended pramlintide dosages are summarized in Table 1.

Table 1. Adult Recommended Dosages
Treatment Indication Dosage Form/Strength Initial Dose Dosage Titration Maximum Recommended Dosage 
type 1 diabetes mellitus SymlinPen® 60 solution pen-injector (1000 mcg/mL, 1.5 mL) 15 mcg subcutaneously immediately prior to each major meal 15 mcg increments 60 mcg subcutaneously immediately prior to each major meal
type 2 diabetes mellitus (insulin-using) SymlinPen® 120 solution pen-injector (1000 mcg/mL, 2.7 mL) 60 mcg subcutaneously immediately prior to each major meal 60 mcg increments 120 mcg subcutaneously immediately prior to each major meal

In patients with type 1 diabetes, dosage titrations should be initiated when clinically significant nausea has been absent for at least 3 days. If nausea persists with the 45 mcg or 60 mcg dose, the dosage may be reduced to 30 mcg. If patients do not tolerate the 30 mcg dose, discontinuing therapy may be necessary. In insulin-using patients with type 2 diabetes, dosage titrations may be initiated when significant nausea is absent for at least 3 days. If the 120 mcg dose is not tolerated, the dosage may be decreased to 60 mcg. For patients with type 1 or type 2 diabetes receiving pre-prandial rapid or short-acting insulin therapy, including fixed-mixed insulin, dose should be decreased by 50% when adjunctive pramlintide therapy is initiated to minimize hypoglycemic episodes. Insulin doses may be titrated upward as needed when a maintenance pramlintide dose is established1,3. Patient profiles containing pramlintide prescription quantities of greater than 2 x 60-pen injectors or 1 x 120-pen injector per 30 days for patients with type 1 diabetes will be reviewed. Likewise, patient profiles containing pramlintide prescription quantities of greater than 2 x 120-pen injectors per 30 days for patients with type 2 diabetes will be reviewed.

Pramlintide should not be administered to patients who1,3:

  • have been diagnosed with gastroparesis
  • have recurrent episodes of hypoglycemia requiring intervention in the last 6 months and/or hypoglycemia unawareness
  • have an HbA1c greater than 9%
  • require therapy with medications that stimulate gastrointestinal motility
  • are poorly compliant with insulin regimens and/or self-monitoring of blood glucose serum concentrations

Pediatrics

Safety and efficacy of pramlintide injections in pediatric patients have not been established. However, a few small, short-term studies have evaluated pramlintide use in adolescents with type 1 diabetes and demonstrated significant reductions in postprandial hyperglycemia. Further long-term studies are necessary to solidify results4-7.

2. Duration of Therapy

Pramlintide is indicated for the management of diabetes mellitus and may be continued indefinitely based on patient need to achieve desired glucose control.

3. Drug-Drug Interactions

Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically relevant for pramlintide are summarized in Table 2. Only those drug-drug interactions identified as clinical significance level 1 or those considered life-threatening which have not yet been classified will be reviewed.

Table 2. Pramlintide Drug-Drug Interactions1,2
Target Drug Interacting Drug Interaction Recommendation Clinical Significance Level*
antidiabetic agents fluoroquinolones adjunctive administration may result in blood glucose disturbances and increased risk for hyper- or hypoglycemia due to an unknown mechanism closely monitor blood glucose levels and adjust antidiabetic doses as needed; doses may also require adjustments with fluoroquinolone discontinuation major (DrugReax) 3-moderate (CP)
antidiabetic agents somatostatin analogues (SAs) (e.g., octreotide, pasireotide) concurrent use may impair glucose regulation as SAs inhibit insulin and glucagon secretion; substantially increased blood glucose levels may result monitor closely for changes in blood glucose control before and throughout SA therapy; adjust antidiabetic doses as needed major (DrugReax) 2-major (CP)
pramlintide alpha glucosidase inhibitors (e.g., acarbose, miglitol) alpha glucosidase inhibitors slow nutritive absorption; adjunctive administration may potentiate pramlintide pharmacologic effects, increasing potential for additional blood glucose reductions and risk of hypoglycemia concurrent administration not recommended by manufacturer 3-moderate (CP)
pramlintide gastric stimulants (e.g., metoclopramide, tegaserod) concurrent administration may attenuate pharmacologic effects of both agents manufacturer states that pramlintide/gastric stimulant combination should be avoided 2-major (CP)
pramlintide medications that slow gastrointestinal motility (e.g., tricyclic antidepressants, opiates, antimuscarinics, diphenoxylate) adjunctive administration may enhance pramlintide pharmacologic effects, increasing potential for additional blood glucose reductions and risk of hypoglycemia concurrent administration not recommended by manufacturer 2-major (CP)
pramlintide insulin adjunctive use may increase hypoglycemia risk; pramlintide pharmacokinetic parameters altered if mixed in same syringe with insulins reduce mealtime insulin doses to minimize hypoglycemia; do not mix together; give as separate injections 2-major (CP)
pramlintide oral medications with hypoglycemic effects (e.g., oral antidiabetic agents, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, disopyramide, fibric acid derivatives, salicylates, sulfonamide antibiotics) concomitant administration may result in enhanced hypoglycemic pharmacologic and adverse effects monitor blood glucose levels closely and adjust dosages as necessary if drug combination required to minimize excessive hypoglycemia and associated adverse events moderate (DrugReax) 3-moderate (CP)
pramlintide oral medications with rapid gastrointestinal (GI) absorption, or narrow therapeutic index pramlintide delays gastric emptying; combined use may reduce serum levels of drugs with narrow therapeutic index, or those requiring rapid GI absorption use cautiously together 4-minor (CP)
pramlintide oral medications requiring threshold concentrations for effect (e.g., acetaminophen, oral contraceptives) concurrent administration may reduce serum levels of drugs with threshold concentrations as pramlintide delays gastric emptying use cautiously together; administer medications having threshold concentrations for effect at least 1 hour before or 2 hours after pramlintide 4-minor (CP)

4. References

  1. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2022. Available at:  http://clinicalpharmacology-ip.com.ezproxy.lib.utexas.edu/. Accessed August 17th, 2022.
  2. IMB Micromedex® DRUGDEX® (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com.libproxy.uthscsa.edu. Accessed August 17th, 2022.
  3. Pramlintide (Symlin®) package insert. AstraZeneca, December 2019.
  4. Kishiyama CM, Burdick PL, Cobry EC, et al. A pilot trial of pramlintide home usage in adolescents with type 1 diabetes. Pediatrics. 2009;124(5):1344-7.
  5. Chase HP, Lutz K, Pencek R, Zhang B, Porter L. Pramlintide lowered glucose excursions and was well-tolerated in adolescents with type 1 diabetes: results from a randomized, single-blind, placebo-controlled, crossover study.  J Pediatr. 2009;155(3):369-73.
  6. Hassan K, Heptulla RA. Reducing postprandial hyperglycemia with adjuvant premeal pramlintide and postmeal insulin in children with type 1 diabetes mellitus. Pediatr Diabetes. 2009;10(4):264-8.
  7. Weinzimer SA, Sherr JL, Cengiz E, et al. Effect of pramlintide on prandial glycemic excursions during closed-loop control in adolescents and young adults with type 1 diabetes. Diabetes Care. 2012;35(10):1994-9.