Side Effects of Symlin (pramlintide), Drug Interactions

What is Symlin (pramlintide)?

Symlin (pramlintide) is an anti-diabetic medication that lowers the level of sugar (glucose) in blood used to treat type 1 and type 2 diabetes. Symlin is a synthetic (man-made) hormone that resembles human amylin. Amylin is a hormone that is produced by the pancreas and released into the blood after meals where it helps the body to regulate levels of blood glucose. Amylin acts in several ways to control blood glucose. It slows the rate at which food (including glucose) is absorbed from the intestine. Amylin reduces the production of glucose by the liver by inhibiting the action of glucagon, a hormone produced by the pancreas that stimulates the production of glucose by the liver. Amylin also reduces appetite. In studies, Symlin-treated patients achieved lower blood glucose levels and experienced weight loss. Drug interactions of Symlin include other drugs that slow down the intestine (for example, atropine) or slow the absorption of food (for example, acarbose).

• Symlin may slow the absorption of orally administered drugs.
• To avoid this interaction, orally administered drugs that require rapid absorption should be administered 1 hour before or 2 hours after injections of Symlin.
• Insulin alters the chemical properties of Symlin. Therefore, Symlin and insulin should not be mixed in the same syringe.

There are no adequate studies of Symlin in pregnant women. There are no adequate studies of Symlin in nursing mothers, and it is unknown if Symlin is excreted in human breast milk. Consult your doctor before breastfeeding.

What are the side effects of Symlin?

What are the common side effects of Symlin?

Common side effects of Symlin include

• nausea,
• low blood sugar (hypoglycemia),
• vomiting,
• headache,
• abdominal pain,
• weight loss, and
• fatigue.

What are the serious side effects of Symlin?

Serious side effects of Symlin include severe hypoglycemia when used with insulin. Nausea decreases with continued administration of pramlintide and is less severe when pramlintide is slowly increased to the desired dose. When used with insulin, especially in patients with type 1 diabetes, severe hypoglycemia may occur. If severe hypoglycemia occurs, it usually manifests within 3 hours after receiving pramlintide.

What drugs interact with Symlin?

Insulin

The pharmacokinetic parameters of pramlintide are altered when Symlin is mixed in the same syringe with regular, NPH, and 70/30 premixed formulations of recombinant human insulin. Symlin and insulin must not be mixed and must be administered as separate injections.

Oral Medications

Symlin has the potential to delay the absorption of concomitantly administered oral medications. 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.

Drugs Affecting Gastrointestinal Motility

Due to its effects on gastric emptying, Symlin should not be considered for patients taking medications that alter gastrointestinal motility (e.g., anticholinergic agents such as atropine) or medications that slow the intestinal absorption of nutrients (e.g., alpha-glucosidase inhibitors). Patients using these medications have not been studied in Symlin clinical trials.

Drugs Affecting Glucose Metabolism

The following are examples of medications that may increase the susceptibility to hypoglycemia when administered with Symlin:

• oral anti-diabetic products,
• angiotensin converting enzyme (ACE) inhibitors,
• disopyramide,
• fibrates,
• fluoxetine,
• monoamine oxidase inhibitors,
• pentoxifylline,
• propoxyphene,
• salicylates,
• somatostatin analogs, and
• sulfonamide antibiotics.

Symlin and these drugs should be coadministered with caution.

Symlin side effects list for healthcare professionals

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Clinical Trial Experience

Adverse Reactions (Excluding Hypoglycemia)

Adverse reactions (excluding hypoglycemia, which is discussed separately below) commonly associated with Symlin when coadministered with a fixed dose of insulin in the 26- to 52-week, placebo-controlled trials in patients with type 1 diabetes and patients with type 2 diabetes on mealtimeinsulin are presented in Table 1 and Table 2, respectively.

Table 1: Patients with Type 1 Diabetes: Common Adverse Reactions (Incidence ≥5% and Greater Incidence with Symlin Compared to Placebo) in 3 Pooled Placebo-Controlled Trials

Long-Term, Placebo-Controlled Studies Symlin 30 or 60 mcg 3 Times Daily + Insulin

(N=716) %

Placebo + Insulin

(N=538) %

Nausea 48 17 Anorexia 17 2 Inflicted Injury1 14 10 Vomiting 11 7 Arthralgia 7 5 Fatigue 7 4 Allergic Reaction 6 5 Dizziness 5 4 1 Examples of inflicted injury included among others, abrasions, bruises, burns, fractures, lacerations, and muscle strains.

Table 2: Patients with Type 2 Diabetes on Insulin: Common Adverse Reactions (Incidence ≥5% and Greater Incidence with Symlin Compared to Placebo) in 2 Pooled Placebo-Controlled Trials

Long-Term, Placebo-Controlled Studies Symlin 120 mcg 2 Times Daily + Insulin

(N=292) %

Placebo + Insulin

(N=284) %

Nausea 28 12 Headache 13 7 Anorexia 9 2 Vomiting 8 4 Abdominal pain 8 7 Fatigue 7 4 Dizziness 6 4 Cough 6 4 Pharyngitis 5 2

Most adverse reactions were gastrointestinal in nature. The incidence of nausea is higher at the beginning of Symlin treatment and decreases with time in most patients. Gradual titration of the Symlin dose minimizes the incidence and severity of nausea.

Severe Hypoglycemia

Coadministration of Symlin with mealtime insulin increases the risk of severe hypoglycemia, particularly in patients with type 1 diabetes.

Two definitions of severe hypoglycemia were used in the Symlin clinical trials.

• Patient-ascertained severe hypoglycemia was defined as an episode of hypoglycemia requiring the assistance of another individual (including help administering oral carbohydrate) or requiring the administration of glucagon, intravenous glucose, or other medical intervention.
• Medically-assisted severe hypoglycemia was defined as an episode of hypoglycemia that was classified as a serious event by the investigator or that required glucagon, intravenous glucose, hospitalization, paramedic assistance or an emergency room visit.

The incidence of severe hypoglycemia during the Symlin clinical development program is summarized in Table 3 and Table 4.

Table 3: Incidence and Event Rate of Severe Hypoglycemia in Six-Month, Placebo-Controlled Trials and Dose Titration Trial in Patients with Type 1 Diabetes

Severe Hypoglycemia Long-Term, Placebo-Controlled Studies (No Insulin Dose-Reduction During Initiation) Placebo-Controlled Dose Titration Study Symlin + Insulin Placebo + Insulin Symlin + Insulin Placebo+Insulin 0 to 3 Months

(n=716)

>3 to 6 Months

(n=576)

0 to 3 Months

(n=538)

>3 to 6 Months

(n=470)

0 to 3 Months

(n=148)

>3 to 6 Months

(n=133)

0 to 3 Months

(n=147)

>3 to 6 Months

(n=138)

Patient- Ascertained1 Event Rate (events/ patient-year) 1.55 0.82 1.33 1.06 0.69 0.49 0.28 0.3 Subject Incidence (%) 16.8 11.1 10.8 8.7 13.5 10.5 6.1 5.8 Medically- Assisted2 Event Rate (events/ patient-year) 0.50 0.27 0.19 0.24 0.14 0.20 0.08 0.15 Subject Incidence (%) 7.3 5.2 3.3 4.3 3.4 4.5 2.0 2.9 1 Patient-ascertained severe hypoglycemia: Requiring the assistance of another individual (including help ingesting oral carbohydrate) and/or requiring the administration of glucagon injection, intravenous glucose, or other medical intervention.

2 Medically-assisted severe hypoglycemia: Requiring glucagon, intravenous glucose, hospitalization, paramedic assistance, emergency room visit, and/or assessed as a serious adverse event by the investigator.

Table 4: Incidence and Event Rate of Severe Hypoglycemia in Six-Month, Placebo-Controlled Trials in Patients with Type 2 Diabetes Using Insulin

Severe Hypoglycemia Long-Term, Placebo-Controlled Studies (No Insulin Dose-Reduction During Initiation) Symlin + Insulin Placebo + Insulin 0 to 3 Months

(n=292)

>3 to 6 Months

(n=255)

0 to 3 Months

(n=284)

>3 to 6 Months

(n=251)

Patient-Ascertained1 Event Rate (events/patient-year) 0.45 0.39 0.24 0.13 Subject Incidence (%) 8.2 4.7 2.1 2.4 Medically-Assisted2 Event Rate (events/patient-year) 0.09 0.02 0.06 0.07 Subject Incidence (%) 1.7 0.4 0.7 1.2 1 Patient-ascertained severe hypoglycemia: Requiring the assistance of another individual (including help ingesting oral carbohydrate) and/or requiring the administration of glucagon injection, intravenous glucose, or other medical intervention.

2 Medically-assisted severe hypoglycemia: Requiring glucagon, intravenous glucose, hospitalization, paramedic assistance, emergency room visit, and/or assessed as a serious adverse event by the investigator.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Symlin. 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.

• Injection site reactions
• Pancreatitis

Summary

Symlin (pramlintide) is an anti-diabetic medication that lowers the level of sugar (glucose) in blood used to treat type 1 and type 2 diabetes. Symlin is a synthetic (man-made) hormone that resembles human amylin. Common side effects of Symlin include nausea, low blood sugar (hypoglycemia), vomiting, headache, abdominal pain, weight loss, and fatigue. There are no adequate studies of Symlin in pregnant or breastfeeding women.

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Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.