Aimovig — Erenumab-Aooe drug label

1 INDICATIONS AND USAGE AIMOVIG is indicated for the preventive treatment of migraine in adults. AIMOVIG is a calcitonin gene-related peptide receptor antagonist indicated for the preventive treatment of migraine in adults. ( 1 )

4 CONTRAINDICATIONS AIMOVIG is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. Reactions have included anaphylaxis and angioedema [see Warnings and Precautions (5.1) ] . AIMOVIG is contraindicated in patients with serious hypersensitivity to erenumab-aooe or to any of the excipients. ( 4 )

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: If a serious hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy. Hypersensitivity reactions can occur within hours to more than one week after administration. ( 5.1 ) Constipation with Serious Complications: Serious complications of constipation may occur. ( 5.2 ) Hypertension: New-onset or worsening of pre-existing hypertension may occur. ( 5.3 ) Raynaud's Phenomenon: New-onset or worsening of pre-existing Raynaud's phenomenon may occur. ( 5.4 ) 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including rash, angioedema, and anaphylaxis, have been reported with AIMOVIG in postmarketing experience. Most hypersensitivity reactions were not serious and occurred within hours of administration, although some occurred more than one week after administration. If a serious or severe hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy [see Contraindications (4) , and Patient Counseling Information (17) ] . 5.2 Constipation with Serious Complications Constipation with serious complications has been reported following the use of AIMOVIG in the postmarketing setting. There were cases that required hospitalization, including cases where surgery was necessary. In a majority of these cases, the onset of constipation was reported after the first dose of AIMOVIG; however, patients have also presented with constipation later on in treatment. AIMOVIG was discontinued in most reported cases of constipation with serious complications. Constipation was one of the most common (up to 3%) adverse reactions reported in clinical studies [see Adverse Reactions (6.1) ] . Monitor patients treated with AIMOVIG for severe constipation and manage as clinically appropriate [see Patient Counseling Information (17) ] . The concurrent use of medications associated with decreased gastrointestinal motility may increase the risk for more severe constipation and the potential for constipation-related complications. 5.3 Hypertension Development of hypertension and worsening of pre-existing hypertension have been reported following the use of AIMOVIG in the postmarketing setting. Many of the patients had pre-existing hypertension or risk factors for hypertension. There were cases requiring pharmacological treatment and, in some cases, hospitalization. Hypertension may occur at any time during treatment but was most frequently reported within seven days of dose administration. In the majority of the cases, the onset or worsening of hypertension was reported after the first dose. AIMOVIG was discontinued in many of the reported cases. Monitor patients treated with AIMOVIG for new-onset hypertension, or worsening of pre-existing hypertension, and consider whether discontinuation of AIMOVIG is warranted if evaluation fails to establish an alternative etiology. 5.4 Raynaud's Phenomenon Development of Raynaud's phenomenon and recurrence or worsening of pre-existing Raynaud's phenomenon have been reported in the postmarketing setting following the use of CGRP antagonists, including AIMOVIG. In reported cases with monoclonal antibody CGRP antagonists, symptom onset occurred a median of 71 days following dosing. Many of the cases reported serious outcomes, including hospitalizations and disability, generally related to debilitating pain. In most reported cases, discontinuation of the CGRP antagonist resulted in resolution of symptoms. AIMOVIG should be discontinued if signs or symptoms of Raynaud's phenomenon develop, and patients should be evaluated by a healthcare provider if symptoms do not resolve. Patients with a history of Raynaud's phenomenon should be monitored for, and informed about the possibility of, worsening or recurrence of signs and symptoms.

2 DOSAGE AND ADMINISTRATION For subcutaneous use only ( 2.1 , 2.2 ) Recommended dosage is 70 mg once monthly; some patients may benefit from a dosage of 140 mg once monthly ( 2.1 ) Administer in the abdomen, thigh, or upper arm subcutaneously ( 2.2 ) See Dosage and Administration for important administration instructions ( 2.2 ) 2.1 Recommended Dosing The recommended dosage of AIMOVIG is 70 mg injected subcutaneously once monthly. Some patients may benefit from a dosage of 140 mg injected subcutaneously once monthly. If a dose of AIMOVIG is missed, administer as soon as possible. Thereafter, AIMOVIG can be scheduled monthly from the date of the last dose. 2.2 Important Administration Instructions AIMOVIG is for subcutaneous use only. AIMOVIG is intended for patient self-administration. Prior to use, provide proper training to patients and/or caregivers on how to prepare and administer AIMOVIG using the single-dose prefilled autoinjector or single-dose prefilled syringe, including aseptic technique [see Instructions for Use] : Prior to subcutaneous administration, allow AIMOVIG to sit at room temperature for at least 30 minutes protected from direct sunlight [see How Supplied/Storage and Handling (16.2) ]. This is important for administering the entire dose and helps minimize discomfort. Do not warm by using a heat source such as hot water or a microwave. Do not shake the product. Inspect visually for particulate matter and discoloration prior to administration [see Dosage Forms and Strengths (3) ] . Do not use if the solution is cloudy or discolored or contains flakes or particles. Administer AIMOVIG in the abdomen, thigh, or upper arm subcutaneously. Do not inject into areas where the skin is tender, bruised, red, or hard. Both prefilled autoinjector and prefilled syringe are single-dose and deliver the entire contents.

3 DOSAGE FORMS AND STRENGTHS AIMOVIG is a sterile, clear to opalescent, colorless to light yellow solution available as follows: Injection: 70 mg/mL in a single-dose prefilled SureClick ® autoinjector Injection: 140 mg/mL in a single-dose prefilled SureClick ® autoinjector Injection: 70 mg/mL in a single-dose prefilled syringe Injection: 140 mg/mL in a single-dose prefilled syringe Injection: 70 mg/mL solution in a single-dose prefilled SureClick ® autoinjector ( 3 ) Injection: 140 mg/mL solution in a single-dose prefilled SureClick ® autoinjector ( 3 ) Injection: 70 mg/mL solution in a single-dose prefilled syringe ( 3 ) Injection: 140 mg/mL solution in a single-dose prefilled syringe ( 3 )

6 ADVERSE REACTIONS The following serious adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Constipation with Serious Complications [see Warnings and Precautions (5.2) ] Hypertension [see Warnings and Precautions (5.3) ] Raynaud's Phenomenon [see Warnings and Precautions (5.4) ] The most common adverse reactions in AIMOVIG clinical studies (occurring in at least 3% of treated patients and more often than placebo) are injection site reactions and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Medical Information at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience 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 clinical practice. The safety of AIMOVIG has been evaluated in 2537 patients with migraine who received at least one dose of AIMOVIG, representing 3040.2 patient-years of exposure. Of these, 2271 patients were exposed to 70 mg or 140 mg once monthly for at least 6 months, 1305 patients were exposed for at least 12 months, and 216 patients were exposed through 5 years. In placebo-controlled clinical studies (Studies 1, 2, and 3) of 2184 patients, 787 patients received at least one dose of AIMOVIG 70 mg once monthly, 507 patients received at least one dose of AIMOVIG 140 mg once monthly, and 890 patients received placebo during 3 months or 6 months of double-blind treatment [see Clinical Studies (14) ] . Approximately 84% were female, 91% were white, and the mean age was 42 years at study entry. The most common adverse reactions (incidence ≥ 3% and more often than placebo) in the migraine studies were injection site reactions and constipation. Table 1 summarizes the adverse reactions that occurred during the first 3 months in the migraine studies (Studies 1, 2, and 3). Table 1: Adverse Reactions Occurring with an Incidence of at Least 2% for Either Dose of AIMOVIG and at Least 2% Greater than Placebo During the First 3 Months in Studies 1, 2, and 3 Adverse Reaction AIMOVIG 70 mg Once Monthly N = 787 % AIMOVIG 140 mg Once Monthly N = 507 % Placebo N = 890 % Injection site reactions Injection site reactions include multiple adverse reactions related terms, such as injection site pain and injection site erythema. , The rate of injection site reactions reported in Table 1 is with the prefilled syringe. 6 5 3 Constipation 1 3 1 Cramps, muscle spasms < 1 2 < 1 In Studies 1, 2, and 3, 1.3% of patients treated with AIMOVIG 70 mg or 140 mg discontinued double-blind treatment because of adverse events. The most frequent injection site reactions were injection site pain, injection site erythema, and injection site pruritus. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of AIMOVIG. 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. Immune System Disorders: Hypersensitivity reactions, including rash, angioedema, and anaphylaxis [see Warnings and Precautions (5.1) ]. Gastrointestinal Disorders: Constipation with serious complications [see Warnings and Precautions (5.2) ] , oral mucosal ulceration . Skin and Subcutaneous Tissue Disorders: Rash, alopecia. Vascular Disorders: Hypertension [see Warnings and Precautions (5.3) ] , Raynaud's Phenomenon [see Warnings and Precautions (5.4) ].

8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AIMOVIG during pregnancy. Patients should be encouraged to enroll by calling 1-833-244-4083 or visiting https://www.genesispregnancyregistry.com/. Risk Summary There are no adequate data on the developmental risk associated with the use of AIMOVIG in pregnant women. No adverse effects on offspring were observed when pregnant monkeys were administered erenumab-aooe throughout gestation [see Data ]. Serum erenumab-aooe exposures in pregnant monkeys were greater than those in humans at clinical doses. 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. The estimated rate of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy. Data Animal Data In a study in which female monkeys were administered erenumab-aooe (0 or 50 mg/kg) twice weekly by subcutaneous injection throughout pregnancy (gestation day 20-22 to parturition), no adverse effects on offspring were observed. Serum erenumab-aooe exposures (AUC) in pregnant monkeys were approximately 20 times that in humans at a dose of 140 mg once monthly.

8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use Clinical studies of AIMOVIG did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AIMOVIG during pregnancy. Patients should be encouraged to enroll by calling 1-833-244-4083 or visiting https://www.genesispregnancyregistry.com/. Risk Summary There are no adequate data on the developmental risk associated with the use of AIMOVIG in pregnant women. No adverse effects on offspring were observed when pregnant monkeys were administered erenumab-aooe throughout gestation [see Data ]. Serum erenumab-aooe exposures in pregnant monkeys were greater than those in humans at clinical doses. 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. The estimated rate of major birth defects (2.2%-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy. Data Animal Data In a study in which female monkeys were administered erenumab-aooe (0 or 50 mg/kg) twice weekly by subcutaneous injection throughout pregnancy (gestation day 20-22 to parturition), no adverse effects on offspring were observed. Serum erenumab-aooe exposures (AUC) in pregnant monkeys were approximately 20 times that in humans at a dose of 140 mg once monthly. 8.2 Lactation Risk Summary There are no data on the presence of erenumab-aooe in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for AIMOVIG and any potential adverse effects on the breastfed infant from AIMOVIG or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use Clinical studies of AIMOVIG did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

12.1 Mechanism of Action Erenumab-aooe is a human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function.

12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Erenumab-aooe is a human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function. 12.2 Pharmacodynamics In a randomized, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab-aooe (140 mg intravenous, single-dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone. AIMOVIG is for subcutaneous use only. 12.3 Pharmacokinetics Erenumab-aooe exhibits non-linear kinetics as a result of binding to the CGRP receptor. The C max mean and AUC last mean following subcutaneous administration of a 70 mg once monthly and a 140 mg once monthly dose in healthy volunteers or migraine patients are included in Table 2. Less than 2-fold accumulation was observed in trough serum concentrations (C min ) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once monthly and 140 mg once monthly doses (see Table 2 ). Serum trough concentrations approached steady state by 3 months of dosing. The effective half-life of erenumab-aooe is 28 days. Table 2: Pharmacokinetic Parameters of AIMOVIG AIMOVIG 70 mg Subcutaneously Once Monthly AIMOVIG 140 mg Subcutaneously Once Monthly C max mean (SD) SD = standard deviation , from a single-dose study 6.1 (2.1) mcg/mL 15.8 (4.8) mcg/mL AUC last mean (SD) , 159 (58) day*mcg/mL 505 (139) day*mcg/mL C min (SD) Episodic migraine 5.7 (3.1) mcg/mL 12.8 (6.5) mcg/mL Chronic migraine 6.2 (2.9) mcg/mL 14.9 (6.5) mcg/mL Absorption Following a single subcutaneous dose of 70 mg or 140 mg erenumab-aooe administered to healthy adults, median peak serum concentrations were attained in approximately 6 days, and estimated absolute bioavailability was 82%. Distribution Following a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (V z ) was estimated to be 3.86 (0.77) L. Metabolism and Excretion Two elimination phases were observed for erenumab-aooe. At low concentrations, the elimination is predominantly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab-aooe is largely through a non-specific, non-saturable proteolytic pathway. Specific Populations The pharmacokinetics of erenumab-aooe were not affected by age, gender, race, or subtypes of migraine spectrum (episodic or chronic migraine) based on population pharmacokinetics analysis . Patients with Renal or Hepatic Impairment Population pharmacokinetic analysis of integrated data from the AIMOVIG clinical studies did not reveal a difference in the pharmacokinetics of erenumab-aooe in patients with mild or moderate renal impairment relative to those with normal renal function. Patients with severe renal impairment (eGFR < 30 mL/min/1.73 m 2 ) have not been studied. No dedicated clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the pharmacokinetics of erenumab-aooe. Renal or hepatic impairment is not expected to affect pharmacokinetics of erenumab-aooe. Drug Interaction Studies P450 Enzymes Erenumab-aooe is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely. Oral Contraceptives In an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous, single-dose) did not affect the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate. Sumatriptan In a study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effect on the pharmacokinetics of sumatriptan [see Clinical Pharmacology (12.2) ] . 12.6 Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those of erenumab-aooe. The immunogenicity of AIMOVIG has been evaluated using an immunoassay for the detection of binding anti-erenumab-aooe antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralizing antibodies. In controlled studies with AIMOVIG [see Clinical Studies (14) ] , the incidence of anti-erenumab-aooe antibody development was 6.2% (48/778) in patients receiving AIMOVIG 70 mg once monthly (2 of whom had in vitro neutralizing activity) and 2.6% (13/504) in patients receiving AIMOVIG 140 mg once monthly (none of whom had in vitro neutralizing activity). In a long-term study, including 12 weeks of double-blind treatment and up to 256 weeks of open-label treatment, the incidence of anti-erenumab-aooe antibody development was 11.1% (25/225) among patients whose AIMOVIG dose was 70 mg or 140 mg (2 of whom had in vitro neutralizing activity). The neutralizing anti-erenumab-aooe antibody positive rate may be underestimated because of limitations of the assay. Although these data do not demonstrate an impact of anti-erenumab-aooe antibody development on the efficacy or safety of AIMOVIG in these patients, the available data are too limited to make definitive conclusions.

12.2 Pharmacodynamics In a randomized, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab-aooe (140 mg intravenous, single-dose) with sumatriptan (12 mg subcutaneous, given as two 6 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone. AIMOVIG is for subcutaneous use only.

12.3 Pharmacokinetics Erenumab-aooe exhibits non-linear kinetics as a result of binding to the CGRP receptor. The C max mean and AUC last mean following subcutaneous administration of a 70 mg once monthly and a 140 mg once monthly dose in healthy volunteers or migraine patients are included in Table 2. Less than 2-fold accumulation was observed in trough serum concentrations (C min ) for episodic and chronic migraine patients following subcutaneous administration of 70 mg once monthly and 140 mg once monthly doses (see Table 2 ). Serum trough concentrations approached steady state by 3 months of dosing. The effective half-life of erenumab-aooe is 28 days. Table 2: Pharmacokinetic Parameters of AIMOVIG AIMOVIG 70 mg Subcutaneously Once Monthly AIMOVIG 140 mg Subcutaneously Once Monthly C max mean (SD) SD = standard deviation , from a single-dose study 6.1 (2.1) mcg/mL 15.8 (4.8) mcg/mL AUC last mean (SD) , 159 (58) day*mcg/mL 505 (139) day*mcg/mL C min (SD) Episodic migraine 5.7 (3.1) mcg/mL 12.8 (6.5) mcg/mL Chronic migraine 6.2 (2.9) mcg/mL 14.9 (6.5) mcg/mL Absorption Following a single subcutaneous dose of 70 mg or 140 mg erenumab-aooe administered to healthy adults, median peak serum concentrations were attained in approximately 6 days, and estimated absolute bioavailability was 82%. Distribution Following a single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (V z ) was estimated to be 3.86 (0.77) L. Metabolism and Excretion Two elimination phases were observed for erenumab-aooe. At low concentrations, the elimination is predominantly through saturable binding to target (CGRP receptor), while at higher concentrations the elimination of erenumab-aooe is largely through a non-specific, non-saturable proteolytic pathway. Specific Populations The pharmacokinetics of erenumab-aooe were not affected by age, gender, race, or subtypes of migraine spectrum (episodic or chronic migraine) based on population pharmacokinetics analysis . Patients with Renal or Hepatic Impairment Population pharmacokinetic analysis of integrated data from the AIMOVIG clinical studies did not reveal a difference in the pharmacokinetics of erenumab-aooe in patients with mild or moderate renal impairment relative to those with normal renal function. Patients with severe renal impairment (eGFR < 30 mL/min/1.73 m 2 ) have not been studied. No dedicated clinical studies were conducted to evaluate the effect of hepatic impairment or renal impairment on the pharmacokinetics of erenumab-aooe. Renal or hepatic impairment is not expected to affect pharmacokinetics of erenumab-aooe. Drug Interaction Studies P450 Enzymes Erenumab-aooe is not metabolized by cytochrome P450 enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely. Oral Contraceptives In an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous, single-dose) did not affect the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and norgestimate. Sumatriptan In a study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effect on the pharmacokinetics of sumatriptan [see Clinical Pharmacology (12.2) ] .

11 DESCRIPTION Erenumab-aooe is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to the calcitonin gene-related peptide receptor. Erenumab-aooe is produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. It is composed of 2 heavy chains, each containing 456 amino acids, and 2 light chains of the lambda subclass, each containing 216 amino acids, with an approximate molecular weight of 150 kDa. AIMOVIG (erenumab-aooe) injection is supplied as a sterile, preservative-free, clear to opalescent, colorless to light yellow solution for subcutaneous administration. Each 1 mL 70 mg single-dose prefilled autoinjector and 70 mg single-dose prefilled glass syringe contains 70 mg erenumab-aooe, acetate (1.5 mg), polysorbate 80 (0.10 mg), and sucrose (73 mg). Each 1 mL 140 mg single-dose prefilled autoinjector and 140 mg single-dose prefilled glass syringe contains 140 mg erenumab-aooe, acetate (2.0 mg), polysorbate 80 (0.10 mg), and sucrose (65 mg). Enclosed within the autoinjector is a single-dose, prefilled glass syringe. The solution of AIMOVIG has a pH of 5.2.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied AIMOVIG (erenumab-aooe) injection is a sterile, clear to opalescent, colorless to light yellow solution for subcutaneous administration. AIMOVIG prefilled autoinjectors and prefilled syringes are not made with natural rubber latex. Each single-dose prefilled SureClick ® autoinjector or single-dose prefilled syringe of AIMOVIG contains a Type 1 glass syringe and stainless steel needle and delivers 1 mL of 70 mg/mL or 140 mg/mL solution. AIMOVIG is supplied as follows: SureClick ® Autoinjector Pack of 1 autoinjector: 70 mg/mL single-dose prefilled autoinjector NDC 55513-841-01 Pack of 1 autoinjector: 140 mg/mL single-dose prefilled autoinjector NDC 55513-843-01 Syringe Pack of 1 syringe: 70 mg/mL single-dose prefilled syringe NDC 55513-840-01 Pack of 1 syringe: 140 mg/mL single-dose prefilled syringe NDC 55513-842-01 16.2 Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. If removed from the refrigerator, AIMOVIG should be kept at room temperature (up to 25°C [77°F]) in the original carton and must be used within 7 days. Throw away AIMOVIG that has been left at room temperature for more than 7 days. Do not freeze. Do not shake.

16.2 Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use. If removed from the refrigerator, AIMOVIG should be kept at room temperature (up to 25°C [77°F]) in the original carton and must be used within 7 days. Throw away AIMOVIG that has been left at room temperature for more than 7 days. Do not freeze. Do not shake.

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Information on Preparation and Administration Provide guidance to patients and caregivers on proper subcutaneous administration technique, including aseptic technique, and how to use the single-dose prefilled autoinjector or single-dose prefilled syringe [see Dosage and Administration (2.2) ] . Instruct patients and/or caregivers to read and follow the Instructions for Use each time they use AIMOVIG. Advise patients to let AIMOVIG sit at room temperature for at least 30 minutes prior to administration [see Dosage and Administration (2.2) ] . Hypersensitivity Reactions Advise patients to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reactions [see Warnings and Precautions (5.1) ] . Constipation with Serious Complications Advise patients that constipation with serious complications can occur with AIMOVIG and that they should contact their healthcare providers if they experience severe constipation [see Warnings and Precautions (5.2) ] . Hypertension Advise patients that development of hypertension and worsening of pre-existing hypertension can occur with AIMOVIG and that they should contact their healthcare providers if they experience elevation in their blood pressure [see Warnings and Precautions (5.3) ] . Pregnancy Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AIMOVIG during pregnancy [see Use in Specific Populations (8.1) ]. Raynaud's Phenomenon Inform patients that Raynaud's phenomenon can develop or worsen with AIMOVIG. Advise patients to discontinue AIMOVIG and contact their healthcare provider if they experience signs or symptoms of Raynaud's phenomenon [see Warnings and Precautions (5.4) ] .

INSTRUCTIONS FOR USE AIMOVIG ® [AIM-oh-vig] (erenumab-aooe) injection, for subcutaneous use 70 mg/mL single-dose prefilled SureClick ® autoinjector This Instructions for Use contains information on how to inject AIMOVIG with a SureClick autoinjector. If your healthcare provider decides that you or a caregiver may be able to give your injections of AIMOVIG at home, you should receive training on the right way to prepare and inject AIMOVIG. Do not try to inject yourself until you have been shown the right way to give the injections by your healthcare provider or nurse. The medicine in the AIMOVIG autoinjector is for injection under the skin (subcutaneous injection). See the AIMOVIG Patient Information for information about AIMOVIG. Getting to know your prefilled autoinjector Important Information You Need to Know Before Injecting AIMOVIG It is important that you do not try to give the injection until you have fully read and understood this Instructions for Use. Check the autoinjector label and prescription to make sure you have the correct medicine and dose. Do not use the autoinjector if the carton is damaged or the seal is broken. Do not use the autoinjector after the expiration date on the label. Do not shake the autoinjector. Do not remove the white cap from the autoinjector until you are ready to inject. Do not use the autoinjector if it has been frozen. Do not use the autoinjector if it has been dropped on a hard surface. Part of the autoinjector may be broken even if you cannot see the break. Use a new autoinjector, and call 1-800-77-AMGEN (1-800-772-6436). The autoinjector is not made with natural rubber latex. Frequently asked questions: For additional information and answers to frequently asked questions, visit www.aimovig.com . Where to get help: If you want more information or help using AIMOVIG: Contact your healthcare provider, Visit www.aimovig.com , or Call 1-800-77-AMGEN (1-800-772-6436) Storing and Preparing to Inject AIMOVIG 1 Refrigerate the autoinjector carton until you are ready to use it. Keep the autoinjector in the refrigerator between 36°F to 46°F (2°C to 8°C). Keep the autoinjector in the original carton to protect it from light or physical damage. Do not freeze the autoinjector. Do not store the autoinjector in extreme heat or cold. For example, avoid storing in your vehicle's glove box or trunk. Important: Keep the autoinjector and all medicines out of the sight and reach of children. WAIT 2 Wait 30 minutes for the autoinjector to reach room temperature. Let the autoinjector warm up naturally. Do not heat the autoinjector with hot water, a microwave, or direct sunlight. Do not shake the autoinjector at any time. Using the autoinjector at room temperature makes sure the full dose is delivered and allows for a more comfortable injection. 3 You may keep AIMOVIG at room temperature for up to 7 days, if needed. For example, when you are traveling, you may keep AIMOVIG at room temperature. Keep it at room temperature between 68°F to 77°F (20°C to 25°C). Do not put it back in the refrigerator. Record the date you removed it from the refrigerator and use it within 7 days. Important: Place the autoinjector in a sharps disposal container if it has reached room temperature and has not been used within 7 days. 4 Inspect the medicine. It should be clear and colorless to slightly yellow. It is okay to see air bubbles. Do not use the autoinjector if the medicine is cloudy, discolored, or contains flakes or particles. Important: If the medicine is cloudy, discolored, contains flakes or particles, or if the autoinjector is damaged or expired, call 1-800-77-AMGEN (1-800-772-6436). 5 Check the expiration date (Exp.) and inspect the autoinjector for damage. Do not use the autoinjector if the expiration date has passed. Do not use the autoinjector if: the white cap is missing or loose in carton. it has cracks or broken parts, or it has been dropped on a hard surface. Getting Ready to Inject AIMOVIG 6 Gather and place the following items for your injection on a clean, flat, and well-lit surface: AIMOVIG autoinjector (room temperature), Sharps disposal container [see Completing the Injection and Disposal ], Alcohol wipe, Adhesive bandage, and Cotton balls or gauze pads. 7 Select 1 of these injection sites. Select the thigh or stomach (except for 2 inches around the belly button). Someone else can inject in your thigh, stomach, or back of the upper arm. Important: Avoid areas with scars or stretch marks, or where the skin is tender, bruised, red, hard, raised, thick or scaly skin patch, or lesion. 8 Wash your hands thoroughly with soap and water. 9 Clean the injection site with an alcohol wipe. Let the skin dry on its own. Do not touch this area again before injecting. Injecting AIMOVIG Important: Only remove the white cap when you can inject right away (within 5 minutes) because the medicine can dry out. Do not recap. 10 Grasp the autoinjector so you can see the window. Pull the white cap straight off. You may need to pull hard. Do not twist, bend, or wiggle the white cap to pull it off. Never put the white cap back on. It may damage the needle. Do not put your finger inside the dark green safety guard. It is normal to see a drop of medicine come out of the needle or dark green safety guard. 11 Stretch or pinch the skin to create a firm surface at the injection site until the injection is finished. Place the dark green safety guard straight against the skin. Make sure you can see the window. Make sure the autoinjector is positioned straight on the injection site (at a 90-degree angle). PUSH and hold against skin 12 Firmly push the autoinjector down until the dark green safety guard stops moving. Hold the autoinjector down, do not lift. The dark green safety guard pushes in and unlocks the purple start button. PRESS purple start button 13 Keep pushing the autoinjector down and press the purple start button to start the injection. You may hear or feel a click. The window starts to turn yellow. It is okay to let go of the purple start button. WATCH window will turn fully yellow 14 Keep pushing the autoinjector down. Wait for the window to turn fully yellow. The injection may take up to 15 seconds to complete. You may hear or feel a click. After the window turns fully yellow, lift the autoinjector away from the skin. The dark green safety guard locks around the needle. Completing the Injection and Disposal CONFIRM 15 Confirm a full dose of medicine was injected. Do not touch the dark green safety guard. A small drop of liquid on the injection site is okay. Important: If the window has not turned fully yellow or if it looks like the medicine is still coming out, a full dose was not injected. Call your healthcare provider right away. 16 Check the injection site. Do not rub the injection site. If there is blood, press a cotton ball or gauze pad on your injection site. Apply an adhesive bandage if necessary. For more information or help call 1-800-77-AMGEN (1-800-772-6436). 17 Place the used autoinjector and white cap in an FDA-cleared sharps disposal. Important : Do not throw away the autoinjector in your household trash. Do not reuse the autoinjector. Do not touch the dark green safety guard. Additional information about your sharps disposal container If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. Disposing of sharps disposal containers: When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container . Keep the autoinjector and sharps disposal container out of the sight and reach of children. AIMOVIG ® (AIM - oh - vig) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 U.S. License Number 1080 © 2018 – 2025 Amgen Inc. All rights reserved. 1XXXXXX This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 6/2025 v12 Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image INSTRUCTIONS FOR USE AIMOVIG ® [AIM-oh-vig] (erenumab-aooe) injection, for subcutaneous use 140 mg/mL single-dose prefilled SureClick ® autoinjector This Instructions for Use contains information on how to inject AIMOVIG with a SureClick autoinjector. If your healthcare provider decides that you or a caregiver may be able to give your injections of AIMOVIG at home, you should receive training on the right way to prepare and inject AIMOVIG. Do not try to inject yourself until you have been shown the right way to give the injections by your healthcare provider or nurse. The medicine in the AIMOVIG autoinjector is for injection under the skin (subcutaneous injection). See the AIMOVIG Patient Information for information about AIMOVIG. Getting to know your prefilled autoinjector Important Information You Need to Know Before Injecting AIMOVIG It is important that you do not try to give the injection until you have fully read and understood this Instructions for Use. Check the autoinjector label and prescription to make sure you have the correct medicine and dose. Do not use the autoinjector if the carton is damaged or the seal is broken. Do not use the autoinjector after the expiration date on the label. Do not shake the autoinjector. Do not remove the orange cap from the autoinjector until you are ready to inject. Do not use the autoinjector if it has been frozen. Do not use the autoinjector if it has been dropped on a hard surface. Part of the autoinjector may be broken even if you cannot see the break. Use a new autoinjector, and call 1-800-77-AMGEN (1-800-772-6436). The autoinjector is not made with natural rubber latex. Frequently asked questions: For additional information and answers to frequently asked questions, visit www.aimovig.com . Where to get help: If you want more information or help using AIMOVIG: Contact your healthcare provider, Visit www.aimovig.com , or Call 1-800-77-AMGEN (1-800-772-6436) Storing and Preparing to Inject AIMOVIG 1 Refrigerate the autoinjector carton until you are ready to use it. Keep the autoinjector in the refrigerator between 36°F to 46°F (2°C to 8°C). Keep the autoinjector in the original carton to protect it from light or physical damage. Do not freeze the autoinjector. Do not store the autoinjector in extreme heat or cold. For example, avoid storing in your vehicle's glove box or trunk. Important: Keep the autoinjector and all medicines out of the sight and reach of children. WAIT 2 Wait 30 minutes for the autoinjector to reach room temperature. Let the autoinjector warm up naturally. Do not heat the autoinjector with hot water, a microwave, or direct sunlight. Do not shake the autoinjector at any time. Using the autoinjector at room temperature makes sure the full dose is delivered and allows for a more comfortable injection. 3 You may keep AIMOVIG at room temperature for up to 7 days, if needed. For example, when you are traveling, you may keep AIMOVIG at room temperature. Keep it at room temperature between 68°F to 77°F (20°C to 25°C). Do not put it back in the refrigerator. Record the date you removed it from the refrigerator and use it within 7 days. Important: Place the autoinjector in a sharps disposal container if it has reached room temperature and has not been used within 7 days. 4 Inspect the medicine. It should be clear and colorless to slightly yellow. It is okay to see air bubbles. Do not use the autoinjector if the medicine is cloudy, discolored, or contains flakes or particles. Important: If the medicine is cloudy, discolored, or contains flakes or particles, or if the autoinjector is damaged or expired, call 1-800-77-AMGEN (1-800-772-6436). 5 Check the expiration date (Exp.) and inspect the autoinjector for damage. Do not use the autoinjector if the expiration date has passed. Do not use the autoinjector if: the orange cap is missing or loose in carton. it has cracks or broken parts, or it has been dropped on a hard surface. Getting Ready to Inject AIMOVIG 6 Gather and place the following items for your injection on a clean, flat, and well-lit surface: AIMOVIG autoinjector (room temperature), Sharps disposal container [see Completing the Injection and Disposal ], Alcohol wipe, Adhesive bandage, and Cotton balls or gauze pads 7 Select 1 of these injection sites. Select the thigh or stomach (except for 2 inches around the belly button). Someone else can inject in your thigh, stomach, or back of the upper arm. Important: Avoid areas with scars or stretch marks, or where the skin is tender, bruised, red, hard, raised, thick or scaly skin patch, or lesion. 8 Wash your hands thoroughly with soap and water. 9 Clean the injection site with an alcohol wipe. Let the skin dry on its own. Do not touch this area again before injecting. Injecting AIMOVIG Important: Only remove the orange cap when you can inject right away (within 5 minutes) because the medicine can dry out. Do not recap. 10 Grasp the autoinjector so you can see the window. Pull the orange cap straight off. You may need to pull hard. Do not twist, bend, or wiggle the orange cap to pull it off. Never put the orange cap back on. It may damage the needle. Do not put your finger inside the yellow safety guard. It is normal to see a drop of medicine come out of the needle or yellow safety guard. 11 Stretch or pinch the skin to create a firm surface at the injection site until the injection is finished. Place the yellow safety guard straight against the skin. Make sure you can see the window. Make sure the autoinjector is positioned straight on the injection site (at a 90-degree angle). PUSH and hold against skin 12 Firmly push the autoinjector down until the yellow safety guard stops moving. Hold the autoinjector down, do not lift. The yellow safety guard pushes in and unlocks the gray start button. PRESS gray start button 13 Keep pushing the autoinjector down and press the gray start button to start the injection. You may hear or feel a click. The window starts to turn yellow. It is okay to let go of the gray start button. WATCH window will turn fully yellow 14 Keep pushing the autoinjector down. Wait for the window to turn fully yellow. The injection may take up to 15 seconds to complete. You may hear or feel a click. After the window turns fully yellow, lift the autoinjector away from the skin. The yellow safety guard locks around the needle. Completing the Injection and Disposal CONFIRM 15 Confirm a full dose of medicine was injected. Do not touch the yellow safety guard. A small drop of liquid on the injection site is okay. Important: If the window has not turned fully yellow or if it looks like the medicine is still coming out, a full dose was not injected. Call your healthcare provider right away. 16 Check the injection site. Do not rub the injection site. If there is blood, press a cotton ball or gauze pad on your injection site. Apply an adhesive bandage if necessary. For more information or help call 1-800-77-AMGEN (1-800-772-6436). 17 Place the used autoinjector and orange cap in an FDA-cleared sharps disposal. Important: Do not throw away the autoinjector in your household trash. Do not reuse the autoinjector. Do not touch the yellow safety guard. Additional information about your sharps disposal container If you do not have an FDA-cleared sharps disposal container, you may use a household container that is: made of a heavy-duty plastic, can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out, upright and stable during use, leak-resistant, and properly labeled to warn of hazardous waste inside the container. Disposing of sharps disposal containers: When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal Do not dispose of your used sharps disposal container in your household trash unless your community guidelines permit this. Do not recycle your used sharps disposal container. Keep the autoinjector and sharps disposal container out of the sight and reach of children. AIMOVIG ® (AIM-oh-vig) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 U.S. License Number 1080 © 2019 – 2025 Amgen Inc. All rights reserved. 1XXXXXX This Instructions for Use has been approved by the U.S. Food and Drug Administration. Revised: 6/2025 V11 Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image Instructions for Use AIMOVIG ® (AIM-oh-vig) (erenumab-aooe) Injection, For Subcutaneous Use Single-Dose Prefilled Syringe 70 mg/mL and 140 mg/mL Important: Needle is inside the gray needle cap. Important Before you use AIMOVIG prefilled syringe, read this important information: Storing your AIMOVIG prefilled syringe Keep the syringe out of the reach of children. Keep the syringe in the original carton to protect from light. The syringe should be kept in the refrigerator at 36°F to 46°F (2°C to 8°C). After removing AIMOVIG from the refrigerator, it can be stored at room temperature between 68°F to 77°F (20°C to 25°C) for up to 7 days. Throw away AIMOVIG that has been left at room temperature for more than 7 days. Do not freeze. Using your AIMOVIG prefilled syringe It is important that you do not try to give the injection unless you or your caregiver has received training from your healthcare provider. Do not use a syringe after the expiration date on the label. Do not shake the syringe. Do not remove the gray needle cap from the syringe until you are ready to inject. Do not use the syringe if it has been frozen. Do not use a syringe if it has been dropped on a hard surface. Part of the syringe may be broken even if you cannot see the break. Use a new syringe, and call 1-800-77-AMGEN (1-800-772-6436). The prefilled syringe is not made with natural rubber latex. Step 1: Prepare AIMOVIG comes as a single-dose (1 time) prefilled syringe. Your healthcare provider will prescribe the dose that is best for you. Before you inject, always check the label of your single-dose prefilled syringe to make sure you have the correct medicine and the correct dose of AIMOVIG. A Remove AIMOVIG prefilled syringe from the carton. Grab the syringe barrel to remove the syringe from the tray. Place finger or thumb on edge of tray to secure it while you remove the syringe. Grab Here For safety reasons: Do not grab the plunger rod. Do not grab the gray needle cap. Do not remove the gray needle cap until you are ready to inject. Do not remove the finger flange. This is part of the syringe. Leave the syringe at room temperature for at least 30 minutes before injecting. Do not put the syringe back in the refrigerator after it has reached room temperature. Do not try to warm the syringe by using a heat source such as hot water or microwave. Do not leave the syringe in direct sunlight. Do not shake the syringe. Important: Always hold the prefilled syringe by the syringe barrel. B Inspect the AIMOVIG prefilled syringe. Always hold the syringe by the syringe barrel. Make sure the medicine in the syringe is clear and colorless to slightly yellow. Do not use the syringe if the medicine is cloudy or discolored or contains flakes or particles. Do not use the syringe if any part appears cracked or broken. Do not use the syringe if the syringe has been dropped. Do not use the syringe if the gray needle cap is missing or not securely attached. Do not use the syringe if the expiration date printed on the label has passed. In all cases, use a new syringe, and call 1-800-77-AMGEN (1-800-772-6436). C Gather all materials needed for your injection. Wash your hands thoroughly with soap and water. On a clean, well-lit work surface, place the: New syringe Alcohol wipes Cotton balls or gauze pads Adhesive bandages Sharps disposal container D Prepare and clean your injection site. Only use these injection sites: Your thigh Stomach area (abdomen), except for a two inch area right around your navel Outer area of upper arm (only if someone else is giving you the injection) Clean your injection site with an alcohol wipe. Let your skin dry. Do not touch this area again before injecting. Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting directly into raised, thick, red, or scaly skin patch or lesion, or areas with scars or stretch marks. Step 2: Get ready E Pull gray needle cap straight out and away from your body, only when you are ready to inject. Do not leave the gray needle cap off for more than five minutes . This can dry out the medicine. It is normal to see a drop of liquid at the end of the needle. Do not twist or bend the gray needle cap. Do not put the gray needle cap back onto the syringe. Do not remove the gray needle cap from the syringe until you are ready to inject. Important: Throw the gray needle cap into the sharps disposal container. F Pinch your injection site to create a firm surface. Pinch skin firmly between your thumb and fingers, creating an area about two inches wide. Important: Keep skin pinched while injecting. Step 3: Inject G Hold the pinch. With the gray needle cap off, insert the syringe into your skin at 45 to 90 degrees. Do not place your finger on the plunger rod while inserting the needle. H Place your finger on the plunger rod. Using slow and constant pressure, push the plunger rod all the way down until the prefilled syringe stops moving. I When done, release your thumb, and gently lift the syringe off of your skin. Important: When you remove the syringe, if it looks like the medicine is still in the syringe barrel, this means you have not received a full dose. Call your healthcare provider immediately. Step 4: Finish J Discard the used syringe and the gray needle cap. Put the used AIMOVIG syringe and gray needle cap in a FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the syringe in your household trash. If you do not have a FDA-cleared sharps disposal container, you may use a household container that is: Made of a heavy-duty plastic Can be closed with a tight-fitting, puncture-resistant lid, without sharps being able to come out Upright and stable during use Leak-resistant Properly labeled to warn of hazardous waste inside the container When your sharps disposal container is almost full, you will need to follow your community guidelines for the right way to dispose of your sharps disposal container. There may be state or local laws about how you should throw away used needles and syringes. For more information about safe sharps disposal, and for specific information about sharps disposal in the state that you live in, go to the FDA's website at: http://www.fda.gov/safesharpsdisposal. Do not reuse the syringe. Do not recycle the syringe or sharps disposal container or throw them into household trash. Important: Always keep the sharps disposal container out of the reach of children. K Examine the injection site. If there is blood, press a cotton ball or gauze pad on your injection site. Do not rub the injection site. Apply an adhesive bandage if needed. For more information, go to www.aimovig.com or call 1-800-77-AMGEN (1-800-772-6436). AIMOVIG ® (erenumab-aooe) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, CA 91320-1799 USA U.S. License No. 1080 © 2018-2022, 2024 Amgen Inc. All rights reserved. Symbol table Do not reuse CAUTION, Prior to use, read the enclosed Instructions For Use for administration information and see package insert for full Prescribing Information Lot number This Instructions for Use has been approved by the U.S. Food and Drug Administration. Approved: 8/2024 [partnumber] v7 Image Image Image Image Image Image Image Image Image Image Image Image Image Image Image