GLUCAGON Drug Interactions: What You Need to Know

INTERACTIONS Table 4: Clinically Significant Drug Interaction with GVOKE and GVOKE VialDx Beta-Blockers Clincial Impact: Patients taking beta-blockers may have a transient increase in pulse and blood pressure when given GVOKE or GVOKE VialDx.

Intervention

The increase in blood pressure and heart rate may require therapy in patients with coronary artery disease.

Insulin Clincial

Impact: Insulin acts antagonistically to glucagon.

Intervention

Monitor blood glucose when GVOKE VialDx is used as a diagnostic aid in patients receiving insulin.

Indomethacin Clincial

Impact: In patients taking indomethacin, GVOKE may lose its ability to raise blood glucose or may even produce hypoglycemia.

Intervention

Monitor blood glucose levels during glucagon treatment of patients taking indomethacin.

Anticholinergic Drugs Clincial

Impact: The concomitant use of anticholinergic drugs and GVOKE VialDx increases the risk of gastrointestinal adverse reactions due to additive effects on inhibition of gastrointestinal motility.

Intervention

Concomitant use of anticholinergic drugs with GVOKE VialDx is not recommended.

Warfarin Clincial

Impact: GVOKE and GVOKE Vial Dx may increase the anticoagulant effect of warfarin.

Intervention

Monitor patients for unusual bruising or bleeding, as adjustments in warfarin dosage may be required. Beta-blockers: GVOKE- or GVOKE VialDx-treated patients taking concomitant beta-blockers may have a transient increase in pulse and blood pressure. ( 7 ) Indomethacin: In patients taking concomitant indomethacin, GVOKE may lose its ability to raise glucose or may produce hypoglycemia. ( 7 ) Anticholinergic drugs: Concomitant use of anticholinergic drugs with GVOKE VialDx for use as a diagnostic aid is not recommended. ( 7 ) Warfarin: GVOKE and GVOKE VialDx may increase the anticoagulant effect of warfarin. ( 7 ) Insulin: Monitor blood glucose when GVOKE VialDx is used as a diagnostic aid in patients receiving insulin. ( 7 )

See

17 for PATIENT COUNSELING INFORMATION and FDA ‑ approved patient labeling for GVOKE.

GVOKE and GVOKE VialDx are contraindicated in patients with:

• Pheochromocytoma because of the risk of substantial increase in blood pressure [see Warnings and Precautions ( 5.1 )]
• Insulinoma because of the risk of hypoglycemia [see Warnings and Precautions ( 5.2 )]
• Prior hypersensitivity reaction to glucagon or to any of the excipients in GVOKE or GVOKE VialDx. Serious hypersensitivity reactions have been reported with glucagon and include anaphylactic shock with breathing difficulties and hypotension [see Warnings and Precautions ( 5.3 )] .

Gvoke

VialDx for use as a diagnostic aid is also contraindicated in patients with glucagonoma because of risk of hypoglycemia [see Warnings and Precautions ( 5.8 )]

• Pheochromocytoma ( 4 )
• Insulinoma ( 4 )
• Prior hypersensitivity reaction to glucagon or to any of the excipients ( 4 )
• Glucagonoma when used as a diagnostic aid ( 4 )

AND PRECAUTIONS Substantial Increase in Blood Pressure in Patients with Pheochromocytoma: Contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor. ( 5.1 )

• Hypoglycemia in Patients with Insulinoma: In patients with insulinoma, administration may produce an initial increase in blood glucose; however, glucagon may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. If a patient develops symptoms of hypoglycemia after a dose of GVOKE or GVOKE VialDx, give glucose orally or intravenously. ( 5.2 )
• Serious Hypersensitivity Reactions: Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash, and in some cases anaphylactic shock with breathing difficulties, and hypotension.( 5.3 )
• Lack of Efficacy with Subcutaneous Use for Severe Hypoglycemia in Patients with Decreased Hepatic Glycogen: Patients with insufficient hepatic stores of glycogen may not respond to GVOKE for subcutaneous use for the treatment of severe hypoglycemia. Insufficient hepatic stores of glycogen may be present in conditions such as states of starvation, or in patients with adrenal insufficiency or chronic hypoglycemia. ( 5.4 )
• Necrolytic Migratory Erythema (NME): a skin rash, has been reported postmarketing following continuous glucagon infusion and resolved with discontinuation of the glucagon. GVOKE and GVOKE VialDx are not approved for continuous infusion. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks. ( 5.5 )
• Hyperglycemia with Intravenous Use as a Diagnostic Aid in Patients with Diabetes Mellitus: GVOKE VialDx in patients with diabetes mellitus may cause hyperglycemia. Monitor patients with diabetes for changes in blood glucose levels during treatment and treat hyperglycemia if indicated. ( 5.6 )
• Blood Pressure and Heart Rate Increases with Intravenous Use as a Diagnostic Aid in Patients with Cardiac Disease: GVOKE VialDx may increase myocardial oxygen demand, blood pressure, and pulse rate. Cardiac monitoring is recommended in patients with cardiac disease during use of GVOKE VialDx as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy. ( 5.7 )
• Hypoglycemia in Patients with Glucagonoma with Intravenous Use as a Diagnostic Aid: GVOKE VialDx administered to patients with glucagonoma may cause secondary hypoglycemia. Test patients suspected of having glucagonoma for blood levels of glucagon prior to treatment and monitor for changes in blood glucose levels during treatment. ( 5.8 )

5.1 Substantial Increase in Blood Pressure in Patients with Pheochromocytoma GVOKE and GVOKE VialDx are contraindicated in patients with pheochromocytoma because glucagon may stimulate the release of catecholamines from the tumor <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . If the patient develops a substantial increase in blood pressure and a previously undiagnosed pheochromocytoma is suspected, 5 to 10 mg of phentolamine mesylate, administered intravenously, has been shown to be effective in lowering blood pressure.

5.2 Hypoglycemia in Patients with Insulinoma In patients with insulinoma, administration of glucagon may produce an initial increase in blood glucose; however, glucagon administration may directly or indirectly (through an initial rise in blood glucose) stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. GVOKE and GVOKE VialDx are contraindicated in patients with insulinoma <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> . If a patient develops symptoms of hypoglycemia after a dose of GVOKE or GVOKE VialDx, give glucose orally or intravenously.

5.3 Serious Hypersensitivity Reactions Serious hypersensitivity reactions have been reported with glucagon products, including generalized rash, and in some cases anaphylactic shock with breathing difficulties and hypotension. Discontinue GVOKE or GVOKE VialDx if symptoms of serious hypersensitivity reactions occur. Advise patients and/or caregivers to seek immediate medical attention if the patient experiences any symptoms of serious hypersensitivity reactions.GVOKE and GVOKE VialDx are contraindicated in patients with a prior hypersensitivity reaction to glucagon, or any of the excipients in GVOKE and GVOKE VialDx <span class="opacity-50 text-xs">[see Contraindications ( 4 )]</span> .

5.4 Lack of Efficacy with Subcutaneous Use for Severe Hypoglycemia in Patients with Decreased Hepatic Glycogen Patients with insufficient hepatic stores of glycogen may not respond to GVOKE for the treatment of severe hypoglycemia <span class="opacity-50 text-xs">[see Clinical Pharmacology ( 12.2 )]</span> . Insufficient hepatic stores of glycogen may be present in conditions such as states of starvation, or in patients with adrenal insufficiency or chronic hypoglycemia.

5.5 Necrolytic Migratory Erythema Necrolytic migratory erythema (NME), a skin rash commonly associated with glucagonomas (glucagon-producing tumors) and characterized by scaly, pruritic erythematous plaques, bullae, and erosions, has been reported postmarketing following continuous glucagon infusion.GVOKE and GVOKE VialDx are not approved for continuous infusion. NME lesions may affect the face, groin, perineum and legs or be more widespread. In the reported cases NME resolved with discontinuation of the glucagon, and treatment with corticosteroids was not effective. Should NME occur, consider whether the benefits of continuous glucagon infusion outweigh the risks.

5.6 Hyperglycemia with Intravenous Use as a Diagnostic Aid in Patients with Diabetes Mellitus GVOKE VialDx in patients with diabetes mellitus may cause hyperglycemia. Monitor patients with diabetes for changes in blood glucose levels during treatment with GVOKE VialDx and treat hyperglycemia, if indicated.

5.7 Blood Pressure and Heart Rate Increases with Intravenous Use as a Diagnostic Aid in Patients with Cardiac Disease GVOKE VialDx may increase myocardial oxygen demand, blood pressure, and pulse rate which may be life threatening in patients with cardiac disease. Cardiac monitoring is recommended in patients with cardiac disease during use of GVOKE VialDx as a diagnostic aid, and an increase in blood pressure and pulse rate may require therapy.

5.8 Hypoglycemia in Patients with Glucagonoma with Intravenous Use as a Diagnostic Aid Use of GVOKE VialDx in patients with glucagonoma may cause secondary hypoglycemia.

Gvoke

VialDx is contraindicated in patients with glucagonoma when used as a diagnostic aid [see Contraindications ( 4 )]. Test patients suspected of having glucagonoma for blood levels of glucagon prior to administration of GVOKE VialDx, and monitor for changes in blood glucose levels during treatment. If a patient develops symptoms of hypoglycemia after administration of GVOKE VialDx, administer glucose orally or intravenously.