Symlinpen

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.

• •Upon initiation of SYMLIN, reduce mealtime insulin dose by 50%. Monitor glucoses frequently and individualize subsequent insulin dose adjustments
  2.1 Important Considerations Pertaining to SYMLIN and Insulin Dose Adjustments

  SYMLIN dosage differs depending on whether the patient has type 1 or type 2 diabetes [see

  Dosage and Administration (2.2, 2.3)

  ].

  SYMLIN should be used only in patients who can fully understand and adhere to proper insulin adjustments and glucose monitoring.

  Insulin and SYMLIN dose adjustments should be made only as directed by a healthcare professional skilled in the use of insulin.

  When initiating SYMLIN, reduce mealtime insulin doses, including premixed insulins, by 50% to reduce the risk of hypoglycemia.

  To reduce the risk of nausea, wait at least 3 days before titrating SYMLIN to the next dose increment.

  Monitor blood glucoses frequently, including pre- and post-meals and at bedtime, particularly when initiating SYMLIN or increasing the SYMLIN dose. After the initial 50% reduction in mealtime insulin dose, individualize insulin dose adjustments based on glycemic control and tolerability (e.g., if nausea occurs it may affect the dose of insulin required). An increased frequency of mild-to-moderate hypoglycemia should be viewed as a warning sign of increased risk for severe hypoglycemia.

  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)

  ].
  .
• •Type 1 Diabetes: Start at 15 mcg subcutaneously before major meals. Increase in 15 mcg increments to a maximum premeal dose of 30 or 60 mcg; if not tolerated, reduce to 30 mcg, as tolerated
  2.2 Patients with Type 2 Diabetes Using Mealtime Insulin

  Reduce mealtime insulin doses (including premixed insulins) by 50%, then initiate SYMLIN at 60 mcg subcutaneously, injecting immediately prior to each major meal.

  Increase the SYMLIN dose from 60 to 120 mcg prior to each major meal when no clinically significant nausea has occurred for at least 3 days.

  If significant nausea persists at the 120 mcg dose, the SYMLIN dose should be decreased to 60 mcg.
  .
• •Type 2 Diabetes: Start at 60 mcg subcutaneously before major meals then increase to 120 mcg before meals, as tolerated
  2.2 Patients with Type 2 Diabetes Using Mealtime Insulin

  Reduce mealtime insulin doses (including premixed insulins) by 50%, then initiate SYMLIN at 60 mcg subcutaneously, injecting immediately prior to each major meal.

  Increase the SYMLIN dose from 60 to 120 mcg prior to each major meal when no clinically significant nausea has occurred for at least 3 days.

  If significant nausea persists at the 120 mcg dose, the SYMLIN dose should be decreased to 60 mcg.
  .
• •Wait at least 3 days between dose titrations to minimize nausea
  2.1 Important Considerations Pertaining to SYMLIN and Insulin Dose Adjustments

  SYMLIN dosage differs depending on whether the patient has type 1 or type 2 diabetes [see

  Dosage and Administration (2.2, 2.3)

  ].

  SYMLIN should be used only in patients who can fully understand and adhere to proper insulin adjustments and glucose monitoring.

  Insulin and SYMLIN dose adjustments should be made only as directed by a healthcare professional skilled in the use of insulin.

  When initiating SYMLIN, reduce mealtime insulin doses, including premixed insulins, by 50% to reduce the risk of hypoglycemia.

  To reduce the risk of nausea, wait at least 3 days before titrating SYMLIN to the next dose increment.

  Monitor blood glucoses frequently, including pre- and post-meals and at bedtime, particularly when initiating SYMLIN or increasing the SYMLIN dose. After the initial 50% reduction in mealtime insulin dose, individualize insulin dose adjustments based on glycemic control and tolerability (e.g., if nausea occurs it may affect the dose of insulin required). An increased frequency of mild-to-moderate hypoglycemia should be viewed as a warning sign of increased risk for severe hypoglycemia.

  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)

  ].
  .

SYMLIN is supplied as a sterile injection in the following dosage forms:

• •1.5 mL disposable multidose SymlinPen^® 60 pen-injector containing 1000 mcg/mL pramlintide (as acetate).
• •2.7 mL disposable multidose SymlinPen^® 120 pen-injector containing 1000 mcg/mL pramlintide (as acetate).

Available data from a small number of reports in the manufacturer’s safety database on SYMLIN use in pregnant women are not sufficient to determine a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy (

Ex-vivo studies using term perfused human, rabbit, and rat placentas indicate that SYMLIN has low potential to cross the maternal/fetal placental barrier. In animal reproduction studies, congenital abnormalities were observed in fetuses of pregnant rats but not in fetuses of pregnant rabbits exposed during organogenesis to pramlintide at 10 times the clinical dose of 360 mcg/day, based on exposure (see

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7 and has been reported to be as high as 20-25% in women with HbA1c >10. The estimated background risk of miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. Poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity.

Developmental and reproductive toxicity studies with SYMLIN were performed in pregnant rats and rabbits. Increases in congenital abnormalities (neural tube defect, cleft palate, exencephaly) were observed in fetuses of pregnant rats administered pramlintide subcutaneously during organogenesis at 0.3 and 1 mg/kg/day (10 and 47 times the human dose of 360 mcg/day based on AUC, respectively), but not at 3mg/kg/day. Administration of pramlintide to pregnant rabbits during organogenesis resulted in maternal toxicity but did not increase fetal malformations at doses up to 0.3 mg/kg/day (9 times the human dose of 360 mcg/day based on AUC).