PRAMLINTIDE Drug Interactions: What You Need to Know

INTERACTIONS

7.1 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 <span class="opacity-50 text-xs">[see Dosage and Administration (2.4) , Warnings and Precautions (5.4) , and Clinical Pharmacology (12.3) ]</span>.

7.2 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.5) and Clinical Pharmacology (12.3) ]</span>.

7.3 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 <span class="opacity-50 text-xs">[see Warnings and Precautions (5.6) ]</span>.

7.4 Drugs Affecting Glucose Metabolism The following are examples of medications that may increase the susceptibility to hypoglycemia when administered with SYMLIN: anti-diabetic products, angiotensin converting enzyme (ACE) inhibitors, disopyramide, fibrates, fluoxetine, monoamine oxidase inhibitors, pentoxifylline, salicylates, somatostatin analogs, and sulfonamide antibiotics. SYMLIN and these drugs should be coadministered with caution.

SYMLIN is contraindicated in patients with any of the following:

• serious hypersensitivity reaction to SYMLIN or to any of its product components.
• hypoglycemia unawareness.
• confirmed gastroparesis.
• Prior serious hypersensitivity reaction to SYMLIN or its ingredients (4)
• Hypoglycemia unawareness (4)
• Confirmed gastroparesis (4)

AND PRECAUTIONS

• Severe hypoglycemia: Increased risk particularly for type 1 diabetes. Upon initiation of SYMLIN, reduce mealtime insulin dose by 50% and frequently monitor blood glucoses (5.2) .
• Never share a SymlinPen between patients, even if the needle is changed (5.3) .
• Do not mix SYMLIN and insulin: Mixing can alter the pharmacokinetics of both products. Administer as separate injections (5.4 , 7.1) .
• Slows gastric emptying: Administer concomitant oral medications at least 1 hour before or 2 hours after SYMLIN if rapid onset or threshold concentration is critical (5.6 , 7.2) .

5.1 Patient Selection Proper patient selection is critical to the safe and effective use of SYMLIN. Before initiating SYMLIN, the patient&apos;s HbA1c, recent blood glucose monitoring data, history of insulin-induced hypoglycemia, current insulin regimen, and body weight should be reviewed. SYMLIN therapy should only be considered in patients with type 1 diabetes or patients with type 2 diabetes using mealtime insulin who fulfill the following criteria:

• have failed to achieve adequate glycemic control despite individualized insulin management.
• are receiving ongoing care under the guidance of a healthcare professional skilled in the use of insulin and supported by the services of diabetes educator(s). Patients meeting any of the following criteria should NOT be considered for SYMLIN therapy:
• poor compliance with current insulin regimen.
• poor compliance with prescribed self blood glucose monitoring.
• have a HbA1c >9%.
• recurrent severe hypoglycemia requiring assistance during the past 6 months.
• presence of hypoglycemia unawareness.
• confirmed diagnosis of gastroparesis.
• require the use of drugs that stimulate gastrointestinal motility.
• pediatric patients. SYMLIN should be prescribed with caution to persons with visual or dexterity impairment.

5.2 Hypoglycemia SYMLIN alone does not cause hypoglycemia. However, SYMLIN is indicated to be coadministered with mealtime insulin therapy, and in this setting there is an increased risk of severe hypoglycemia, particularly in patients with type 1 diabetes. If severe hypoglycemia associated with SYMLIN occurs, it is usually seen within the first 2 to 3 hours following a SYMLIN injection. If severe hypoglycemia occurs while operating a motor vehicle, heavy machinery, or while engaging in other high-risk activities, serious injuries or death may occur. Therefore, when introducing SYMLIN therapy, appropriate precautions need to be taken to avoid increasing the risk for severe hypoglycemia. These precautions include frequent monitoring of pre- and post-meal glucose combined with an initial 50% reduction in doses of mealtime insulin <span class="opacity-50 text-xs">[see Dosage and Administration (2.1 , 2.2 ) ]</span>. Early warning symptoms of hypoglycemia may be different or less pronounced under certain conditions, such as longstanding diabetes; diabetic neuropathy; use of medications such as beta-blockers, clonidine, guanethidine, or reserpine; or intensified glycemic control. The addition of any anti-diabetic medication, such as SYMLIN, to an existing regimen of one or more anti-diabetic medications (e.g., sulfonylurea), or other medications that can increase the risk of hypoglycemia may necessitate further insulin dose adjustments and particularly close monitoring of blood glucose.

5.3 Never Share a SymlinPen Between Patients SymlinPen must never be shared between patients, even if the needle is changed. Pen-sharing poses a risk for transmission of blood-borne pathogens.

5.4 Never Mix SYMLIN and Insulin Mixing SYMLIN and insulin can alter the pharmacokinetics of both products which may result in inadequate glucose control or hypoglycemia. Therefore, SYMLIN and insulin must always be administered as separate injections and should never be mixed <span class="opacity-50 text-xs">[see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]</span>.

5.5 Concomitantly Administered Oral Medications SYMLIN slows gastric emptying, which may delay the absorption of concomitantly administered oral medications. Administer the concomitant oral medication at least 1 hour prior to SYMLIN injection or 2 hours after SYMLIN injection if the rapid onset or threshold concentration of the concomitant medication is a critical determinant of its effectiveness (such as with analgesics, antibiotics, and oral contraceptives) <span class="opacity-50 text-xs">[see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ]</span>.

5.6 Medications that Affect Gastrointestinal Motility SYMLIN slows gastric emptying. SYMLIN is not recommended for patients taking other medications that alter gastrointestinal motility <span class="opacity-50 text-xs">[see Drug Interactions (7.3) ]</span>.

5.7 Allergy Local Allergy Patients may experience erythema, edema, or pruritus at the site of injection. These minor reactions usually resolve in a few days to a few weeks. In some instances, these reactions may be related to factors other than SYMLIN, such as irritants in a skin cleansing agent or improper injection technique.