SYMLIN SIDE EFFECTS

  • Generic Name: pramlintide acetate injection
  • Brand Name: Symlin
  • Drug Class: Antidiabetics, Amylinomimetics, Antidiabetics, Glucagon-like Peptide-1 Agonists
Last updated on MDtodate: 10/13/2022

SIDE EFFECTS

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

 

SRC: NLM .