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Generic name: pramlintide systemic

Brand names: Symlin, SymlinPen 60, SymlinPen 120, Symlin Pen

Boxed Warning

Insulin/glucose-lowering agents:

Pramlintide use with insulin increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes. When severe hypoglycemia occurs, it is seen within 3 hours following a pramlintide injection. Serious injuries may occur if severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities. Appropriate patient selection, careful patient instruction, and insulin dose adjustments are critical elements for reducing this risk.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Pen-injector, Subcutaneous, as acetate:

SymlinPen 60: 1500 mcg/1.5 mL (1.5 mL) [contains metacresol]

SymlinPen 120: 2700 mcg/2.7 mL (2.7 mL) [contains metacresol]


Mechanism of Action

Synthetic analog of human amylin cosecreted with insulin by pancreatic beta cells; reduces postprandial glucose increases via the following mechanisms: 1) prolongation of gastric emptying time, 2) reduction of postprandial glucagon secretion, and 3) reduction of caloric intake through centrally-mediated appetite suppression



Primarily renal to des-lys1 pramlintide (active metabolite)


Primarily urine

Time to Peak

20 minutes

Duration of Action

~ 3 hours

Half-Life Elimination

~48 minutes

Protein Binding


Use: Labeled Indications

Diabetes mellitus, type 1 and type 2: Adjunct 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.


Serious hypersensitivity to pramlintide or any component of the formulation; confirmed diagnosis of gastroparesis; hypoglycemia unawareness

Dosage and Administration

Dosing: Adult

Note: When initiating pramlintide, reduce current mealtime insulin dose (including premixed preparations) by 50% to avoid hypoglycemia. If pramlintide is discontinued for any reason, restart therapy with same initial titration protocol. If a dose is missed, wait until the next scheduled dose and administer the usual amount.

Diabetes mellitus, type 1: SubQ: Initial: 15 mcg immediately prior to major meals; titrate in 15 mcg increments every 3 days (if no significant nausea occurs) to target dose of 30 to 60 mcg prior to major meals (consider discontinuation if intolerant of 30 mcg dose)

Diabetes mellitus, type 2: SubQ: Initial: 60 mcg immediately prior to major meals; after 3 days, increase to 120 mcg prior to each major meal if no significant nausea occurs (if nausea occurs at 120 mcg dose, reduce to 60 mcg)

Dosing: Geriatric

Refer to adult dosing.


Subcutaneous: Do not mix with insulins; administer subcutaneously into abdominal or thigh areas at sites distinct from concomitant insulin injections (do not administer into arm due to variable absorption); rotate injection sites frequently. Allow solution to reach room temperature before administering; may reduce injection site reactions. For oral medications in which a rapid onset of action is desired, administer 1 hour before, or 2 hours after pramlintide, if possible.

Dietary Considerations

Dietary modification based on ADA recommendations is a part of therapy; pramlintide to be administered prior to major meals consisting of ≥250 Kcal or ≥30 g carbohydrates


Store at 2°C to 8°C (36°F to 46°F); do not freeze. After initial use, may be kept refrigerated or at room temperature ≤30°C (≤86°F); discard after 30 days. Protect from light.

Drug Interactions

Alpha-Lipoic Acid: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Androgens: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Exceptions: Danazol. Monitor therapy

Anticholinergic Agents: Pramlintide may enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Direct Acting Antiviral Agents (HCV): May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Guanethidine: May enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Hyperglycemia-Associated Agents: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Hypoglycemia-Associated Agents: Antidiabetic Agents may enhance the hypoglycemic effect of Hypoglycemia-Associated Agents. Monitor therapy

Insulins: Pramlintide may enhance the hypoglycemic effect of Insulins. Management: Upon initiation of pramlintide, decrease mealtime insulin dose by 50% to reduce the risk of hypoglycemia. Monitor blood glucose frequently and individualize further insulin dose adjustments based on glycemic control. Consider therapy modification

Maitake: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Monoamine Oxidase Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Pegvisomant: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Prothionamide: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Quinolones: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Quinolones may diminish the therapeutic effect of Blood Glucose Lowering Agents. Specifically, if an agent is being used to treat diabetes, loss of blood sugar control may occur with quinolone use. Monitor therapy

Ritodrine: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Salicylates: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Thiazide and Thiazide-Like Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

Adverse Reactions


Central nervous system: Headache (5% to 13%)

Endocrine & metabolic: Severe hypoglycemia (type 1 diabetes ≤17%)

Gastrointestinal: Nausea (28% to 48%), anorexia (≤17%), vomiting (7% to 11%)

Miscellaneous: Accidental injury (8% to 14%)

1% to 10%:

Central nervous system: Fatigue (3% to 7%), dizziness (2% to 6%)

Endocrine & metabolic: Severe hypoglycemia (type 2 diabetes ≤8%)

Gastrointestinal: Abdominal pain (2% to 8%)

Hypersensitivity: Hypersensitivity reaction (≤6%)

Neuromuscular & skeletal: Arthralgia (2% to 7%)

Respiratory: Cough (2% to 6%), pharyngitis (3% to 5%)

Postmarketing and/or case reports: Injection site reaction, pancreatitis


Concerns related to adverse effects:

  • Allergic reactions: Injection site reactions, including erythema, edema, or pruritus, may occur; usually resolve in a few days to weeks.

Disease-related concerns:

  • Bariatric surgery: Hypoglycemia: Use an antidiabetic agent without the potential for hypoglycemia if possible; hypoglycemia may occur after gastric bypass, sleeve gastrectomy, and gastric band. Insulin secretion and sensitivity may be partially or completely restored after these procedures (gastric bypass is most effective, followed by sleeve and finally band) (Korner 2009; Peterli 2012). First-phase insulin secretion and hepatic insulin sensitivity have been shown to be significantly improved in the immediate days after gastric bypass and sleeve gastrectomy. The restorative effects of these procedures on peripheral insulin sensitivity may occur later in the 3- to 12-month period postsurgery (Mingrone 2016).
  • Gastroparesis: Avoid use in patients with conditions or concurrent medications likely to impair gastric motility (eg, anticholinergics); do not use in patients requiring medication(s) to stimulate gastric emptying.

Concurrent drug therapy issues:

  • Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
  • Insulin/glucose-lowering agents: [US Boxed Warning]: Coadministration with insulin may induce severe hypoglycemia (usually within 3 hours following administration); coadministration with insulin therapy is an approved indication, but does require an initial dosage reduction of insulin and frequent pre- and post-blood glucose monitoring to reduce risk of severe hypoglycemia. Concurrent use of other glucose-lowering agents may increase risk of hypoglycemia.

Dosage form specific issues:

  • Multiple dose injection pens: According to the manufacturer and the Centers for Disease Control and Prevention (CDC), pen-shaped injection devices should never be used for more than one person (even when the needle is changed) because of the risk of transmission of blood-borne pathogens. The injection device should be clearly labeled with individual patient information to ensure that the correct pen is used (CDC 2012).

Other warnings/precautions:

  • Appropriate use: Avoid use in patients with poor compliance with their insulin regimen and/or blood glucose monitoring. Do not use in patients with HbA1c levels more than 9%, recurrent episodes of severe hypoglycemia requiring assistance during the past 6 months, or hypoglycemia unawareness; obtain detailed history of glucose control (eg, HbA1c, incidence of hypoglycemia, glucose monitoring, and medication compliance) and body weight before initiating therapy. Use caution in patients with visual or dexterity impairment. Patients should use caution when driving or operating heavy machinery until effects on blood sugar are known.

Monitoring Parameters

Prior to initiating therapy: HbA1c, hypoglycemic history, body weight. During therapy: Pre- and postprandial and bedtime serum glucose, HbA1c (at least twice yearly in patients who have stable glycemic control and are meeting treatment goals; quarterly in patients not meeting treatment goals or with therapy change [ADA 2019]), signs and symptoms of hypoglycemia


Pregnancy Considerations

Based on in vitro data, pramlintide has a low potential to cross the placenta.

Poorly controlled diabetes during pregnancy can be associated with an increased risk of adverse maternal and fetal outcomes, including diabetic ketoacidosis, preeclampsia, spontaneous abortion, preterm delivery, delivery complications, major birth defects, stillbirth, and macrosomia (ACOG 201 2018). To prevent adverse outcomes, prior to conception and throughout pregnancy, maternal blood glucose and HbA1c should be kept as close to target goals as possible but without causing significant hypoglycemia (ADA 2020; Blumer 2013).

Agents other than pramlintide are currently recommended to treat diabetes mellitus in pregnancy (ADA 2020).

Patient Education

What is this drug used for?

  • It is used to lower blood sugar in patients with high blood sugar (diabetes).

Frequently reported side effects of this drug

  • Headache
  • Lack of appetite
  • Injection site irritation
  • Nausea
  • Vomiting
  • Abdominal pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

  • Low blood sugar like dizziness, headache, fatigue, feeling weak, shaking, fast heartbeat, confusion, increased hunger, or sweating
  • Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Source: Wolters Kluwer Health. Last updated February 5, 2020.