PREGNANCY SECTION.

8.1 Pregnancy. Risk SummaryThere 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 RiskPublished data have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy.. Data. Animal DataIn 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 dose of 140 mg once monthly.

ADVERSE REACTIONS SECTION.

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)] 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)] 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.. 6.1Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 2310 patient-years of exposure. Of these, 2057 patients were exposed to 70 mg or 140 mg once monthly for at least months, 1198 patients were exposed for at least 12 months, and 287 patients were exposed for at least 18 months.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 months or 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 summarizes the adverse reactions that occurred during the first 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 Months in Studies 1, 2, and 3Adverse ReactionAIMOVIG70 mg Once MonthlyN 787%AIMOVIG 140 mg Once MonthlyN 507%Placebo = 890%Injection site reactionsInjection 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 is with the prefilled syringe. 653Constipation131Cramps, muscle spasms< 12< 1In Studies 1, 2, and 3, 1.3% of patients treated with AIMOVIG 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 Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation, including neutralizing antibodies, is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to erenumab-aooe in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.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, 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). 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.. 6.3 Postmarketing Experience. The following adverse reactions have been identified during postapproval use of AIMOVIG. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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)].

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisThe carcinogenic potential of erenumab-aooe has not been assessed.. MutagenesisGenetic toxicology studies of erenumab-aooe have not been conducted.. Impairment of FertilityMating studies have not been conducted on erenumab-aooe. No histopathological changes in male or female reproductive organs were observed in monkeys administered erenumab-aooe (0, 25, or 150 mg/kg) by subcutaneous injection twice weekly for up to months. Serum erenumab-aooe exposures (AUC) at the higher dose tested were more than 100 times that in humans at dose of 140 mg once monthly.

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Erenumab-aooe is human monoclonal antibody that binds to the calcitonin gene-related peptide (CGRP) receptor and antagonizes CGRP receptor function.. 12.2 Pharmacodynamics. In 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 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 result of binding to the CGRP receptor. The Cmax mean and AUClast mean following subcutaneous administration of 70 mg once monthly and 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 (Cmin) 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 months of dosing. The effective half-life of erenumab-aooe is 28 days.Table 2: Pharmacokinetic Parameters of AIMOVIGAIMOVIG 70 mgSubcutaneously Once MonthlyAIMOVIG 140 mgSubcutaneously Once MonthlyCmax mean (SD)SD standard deviation from single-dose study 6.1 (2.1) mcg/mL15.8 (4.8) mcg/mLAUClast mean (SD) 159 (58) daymcg/mL505 (139) daymcg/mLCmin (SD) Episodic migraine5.7 (3.1) mcg/mL12.8 (6.5) mcg/mL Chronic migraine6.2 (2.9) mcg/mL14.9 (6.5) mcg/mL. AbsorptionFollowing single subcutaneous dose of 70 mg or 140 mg erenumab-aooe administered to healthy adults, median peak serum concentrations were attained in approximately days, and estimated absolute bioavailability was 82%.. DistributionFollowing single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be 3.86 (0.77) L.. Metabolism and ExcretionTwo 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 non-specific, non-saturable proteolytic pathway.. Specific PopulationsThe 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 ImpairmentPopulation pharmacokinetic analysis of integrated data from the AIMOVIG clinical studies did not reveal 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 m2) 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 EnzymesErenumab-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 ContraceptivesIn an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous, single-dose) did not affect the pharmacokinetics of combined oral contraceptive containing ethinyl estradiol and norgestimate.. SumatriptanIn study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effect on the pharmacokinetics of sumatriptan [see Clinical Pharmacology (12.2)].

CLINICAL STUDIES SECTION.

14 CLINICAL STUDIES. The efficacy of AIMOVIG was evaluated as preventive treatment of episodic or chronic migraine in three randomized, double-blind, placebo-controlled studies: two studies in patients with episodic migraine (4 to 14 migraine days per month) (Study and Study 2) and one study in patients with chronic migraine (>= 15 headache days per month with >= migraine days per month) (Study 3). The studies enrolled patients with history of migraine, with or without aura, according to the International Classification of Headache Disorders (ICHD-III) diagnostic criteria.. Episodic MigraineStudy (NCT 02456740) was randomized, multi-center, 6-month, placebo-controlled, double-blind study evaluating AIMOVIG for the preventive treatment of episodic migraine. total of 955 patients with history of episodic migraine were randomized to receive either AIMOVIG 70 mg (N 317), AIMOVIG 140 mg (N 319), or placebo (N 319) by subcutaneous injection once monthly (QM) for months. Patients were allowed to use acute headache treatments including migraine-specific medications (i.e., triptans, ergotamine derivatives) and NSAIDs during the study.The study excluded patients with medication overuse headache as well as patients with myocardial infarction, stroke, transient ischemic attacks, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.The primary efficacy endpoint was the change from baseline in mean monthly migraine days over months to 6. Secondary endpoints included the achievement of >= 50% reduction from baseline in mean monthly migraine days over months to (>= 50% MMD responders), the change from baseline in mean monthly acute migraine-specific medication days over months to 6, and the change from baseline in mean Migraine Physical Function Impact Diary (MPFID) over months to 6. The MPFID measures the impact of migraine on everyday activities (EA) and physical impairment (PI) using an electronic diary administered daily. Monthly MPFID scores are averaged over 28 days, including days with and without migraine; scores are scaled from to 100. Higher scores indicate worse impact on EA and PI. Reductions from baseline in MPFID scores indicate improvement.A total of 858 (90%) patients completed the 6-month double-blind study. Patients had median age of 42 years (range: 18 to 65 years), 85% were female, and 89% were white. Three percent of patients were taking concomitant preventive treatments for migraine. The mean migraine frequency at baseline was approximately migraine days per month and was similar across treatment groups.AIMOVIG treatment demonstrated statistically significant improvements for key efficacy endpoints compared to placebo, as summarized in Table 3.Table 3: Efficacy Endpoints Over Months to in Study 1AIMOVIG70 mg Once MonthlyAIMOVIG140 mg Once MonthlyPlaceboN 312N 318N 316Monthly Migraine Days (MMD) Change from baseline-3.2-3.7-1.8 Difference from placebo-1.4-1.9 p-value< 0.001< 0.001>= 50% MMD responders Responders43.3%50.0%26.6% Difference from placebo16.7%23.4% Odds ratio relative to placebo2.12.8 p-value< 0.001< 0.001Monthly acute migraine-specific medication days Change from baseline-1.1-1.6-0.2 Difference from placebo-0.9-1.4 p-value< 0.001< 0.001Figure 1: Change from Baseline in Monthly Migraine Days in Study 1Least-square means and 95% confidence intervals are presented. Figure shows the distribution of change from baseline in mean monthly migraine days over months to in bins of days by treatment group. treatment benefit over placebo for both doses of AIMOVIG is seen across range of changes from baseline in monthly migraine days.Figure 2: Distribution of Change from Baseline in Mean Monthly Migraine Days Over Months to by Treatment Group in Study 1Figure excludes patients with missing data.Compared to placebo, patients treated with AIMOVIG 70 mg once monthly and 140 mg once monthly showed greater reductions from baseline in mean monthly MPFID everyday activity scores averaged over months to [difference from placebo: -2.2 for AIMOVIG 70 mg and -2.6 for AIMOVIG 140 mg; p-value 0.001 for both], and in mean monthly MPFID physical impairment scores averaged over months to [difference from placebo: -1.9 for AIMOVIG 70 mg and -2.4 for AIMOVIG 140 mg; p-value 0.001 for both].Study (NCT 02483585) was randomized, multi-center, 3-month, placebo-controlled, double-blind study evaluating AIMOVIG for the preventive treatment of episodic migraine. total of 577 patients with history of episodic migraine were randomized to receive either AIMOVIG 70 mg (N 286) or placebo (N 291) by subcutaneous injection once monthly for months. Patients were allowed to use acute headache treatments including migraine-specific medications (i.e., triptans, ergotamine derivatives) and NSAIDs during the study.The study excluded patients with medication overuse headache as well as patients with myocardial infarction, stroke, transient ischemic attacks, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening.The primary efficacy endpoint was the change from baseline in monthly migraine days at month 3. Secondary endpoints included the achievement of >= 50% reduction from baseline in monthly migraine days (>= 50% MMD responders), the change from baseline in monthly acute migraine-specific medication days at month 3, and the proportion of patients with at least 5-point score reduction from baseline in MPFID at month 3.A total of 546 (95%) patients completed the 3-month double-blind study. Patients had median age of 43 years (range: 18 to 65 years), 85% were female, and 90% were white. Six to seven percent of patients were taking concomitant preventive migraine treatment. The mean migraine frequency at baseline was approximately migraine days per month and was similar between treatment groups.AIMOVIG treatment demonstrated statistically significant improvements for key efficacy endpoints compared to placebo, as summarized in Table 4.Table 4: Efficacy Endpoints at Month for Study 2AIMOVIG70 mg Once MonthlyPlaceboN 282N 288Monthly Migraine Days (MMD) Change from baseline-2.9-1.8 Difference from placebo-1.0 p-value< 0.001>= 50% MMD responders Responders39.7%29.5% Difference from placebo10.2% Odds ratio relative to placebo1.6 p-value0.010Monthly acute migraine-specific medication days Change from baseline-1.2-0.6 Difference from placebo-0.6 p-value0.002Figure 3: Change from Baseline in Monthly Migraine Days in Study 2Least-square means and 95% confidence intervals are presented. Figure shows the distribution of change from baseline in monthly migraine days at month in bins of days by treatment group. treatment benefit over placebo for AIMOVIG is seen across range of changes from baseline in monthly migraine days.Figure 4: Distribution of Change from Baseline in Monthly Migraine Days at Month by Treatment Group in Study 2Figure excludes patients with missing data.The pre-specified analysis for the MPFID was based on at least 5-point reduction within-patient responder definition. AIMOVIG 70 mg once monthly was not significantly better than placebo for the proportion of responders for everyday activity [difference from placebo: 4.7%; odds ratio 1.2; p-value 0.26] and physical impairment [difference from placebo: 5.9%; odds ratio 1.3; p-value 0.13]. In an exploratory analysis of the change from baseline in the mean MPFID scores at month 3, patients treated with AIMOVIG 70 mg, as compared to placebo, showed nominally greater reductions of physical impairment scores [difference from placebo: -1.3; p-value 0.021], but not of everyday activities scores [difference from placebo: -1.1; p-value 0.061].. Figure 1. Figure 2. Figure 3. Figure 4. Chronic MigraineStudy (NCT 02066415) was randomized, multi-center, 3-month, placebo-controlled, double-blind study evaluating AIMOVIG as preventive treatment of chronic migraine. total of 667 patients with history of chronic migraine with or without aura were randomized to receive AIMOVIG 70 mg (N 191), AIMOVIG 140 mg (N 190), or placebo (N 286) by subcutaneous injections once monthly for months. Patients were allowed to use acute headache treatments including migraine-specific medications (i.e., triptans, ergotamine derivatives) and NSAIDs during the study.The study excluded patients with medication overuse headache caused by opiate overuse and patients with concurrent use of migraine preventive treatments. Patients with myocardial infarction, stroke, transient ischemic attacks, unstable angina, coronary artery bypass surgery, or other revascularization procedures within 12 months prior to screening were also excluded.The primary efficacy endpoint was the change from baseline in monthly migraine days at month 3. Secondary endpoints included the achievement of >= 50% reduction from baseline in monthly migraine days (>= 50% MMD responders) and change from baseline in monthly acute migraine-specific medication days at month 3.A total of 631 (95%) patients completed the 3-month double-blind study. Patients had median age of 43 years (range: 18 to 66 years), 83% were female, and 94% were white. The mean migraine frequency at baseline was approximately 18 migraine days per month and was similar across treatment groups.AIMOVIG treatment demonstrated statistically significant improvements for key efficacy outcomes compared to placebo, as summarized in Table 5.Table 5: Efficacy Endpoints at Month in Study 3AIMOVIG70 mg Once MonthlyAIMOVIG140 mg Once MonthlyPlaceboN 188N 187N 281Monthly Migraine Days (MMD) Change from baseline-6.6-6.6-4.2 Difference from placebo-2.5-2.5 p-value< 0.001< 0.001>= 50% MMD responders Responders39.9%41.2%23.5% Difference from placebo16.4%17.7% Odds ratio relative to placebo2.22.3 p-value< 0.001< 0.001Monthly acute migraine-specific medication days Change from baseline-3.5-4.1-1.6 Difference from placebo-1.9-2.6 p-value< 0.001< 0.001Figure 5: Change from Baseline in Monthly Migraine Days in Study 3Least-square means and 95% confidence intervals are presented. Figure shows the distribution of change from baseline in monthly migraine days at month in bins of days by treatment group. treatment benefit over placebo for both doses of AIMOVIG is seen across range of changes from baseline in migraine days.Figure 6: Distribution of Change from Baseline in Monthly Migraine Days at Month by Treatment Group in Study 3Figure excludes patients with missing data.. Figure 5. Figure 6.

CLINICAL TRIALS EXPERIENCE SECTION.

6.1Clinical Trials Experience. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of 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 2310 patient-years of exposure. Of these, 2057 patients were exposed to 70 mg or 140 mg once monthly for at least months, 1198 patients were exposed for at least 12 months, and 287 patients were exposed for at least 18 months.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 months or 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 summarizes the adverse reactions that occurred during the first 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 Months in Studies 1, 2, and 3Adverse ReactionAIMOVIG70 mg Once MonthlyN 787%AIMOVIG 140 mg Once MonthlyN 507%Placebo = 890%Injection site reactionsInjection 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 is with the prefilled syringe. 653Constipation131Cramps, muscle spasms< 12< 1In Studies 1, 2, and 3, 1.3% of patients treated with AIMOVIG 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.

CONTRAINDICATIONS SECTION.

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).

DESCRIPTION SECTION.

11 DESCRIPTION. Erenumab-aooe is 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 heavy chains, each containing 456 amino acids, and 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 sterile, preservative-free, clear to opalescent, colorless to light yellow solution for subcutaneous administration. Each 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 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 single-dose, prefilled glass syringe. The solution of AIMOVIG has pH of 5.2.

RECENT MAJOR CHANGES SECTION.

Dosage and Administration (2.2)02/2021.

SPL PATIENT PACKAGE INSERT SECTION.

Patient Information AIMOVIG(R) (AIM-oh-vig) (erenumab-aooe) injection, for subcutaneous useThis Patient Information has been approved by the U.S. Food and Drug Administration.[part number] v6Revised: 11/2021 What is AIMOVIGAIMOVIG is prescription medicine used for the preventive treatment of migraine in adults. It is not known if AIMOVIG is safe and effective in children under 18 years of age.Who should not use AIMOVIGDo not use AIMOVIG if you are allergic to erenumab-aooe or any of the ingredients in AIMOVIG. See the end of this Patient Information for complete list of ingredients in AIMOVIG.Before you start using AIMOVIG, tell your healthcare provider about all your medical conditions, including if you are:Allergic to rubber or latex. The needle shield within the white or orange cap of the single-dose prefilled SureClick(R) autoinjectors and the gray needle cap of the single-dose prefilled syringes contain dry natural rubber. Pregnant or plan to become pregnant. It is not known if AIMOVIG will harm your unborn baby.Breastfeeding or plan to breastfeed. It is not known if AIMOVIG passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while using AIMOVIG. Tell your pharmacist or healthcare provider about all the medicines you take, including any prescription and over-the-counter medicines, vitamins, or herbal supplements.How should take AIMOVIGSee the detailed Instructions for Use on complete information on how to take AIMOVIG.Take AIMOVIG exactly as your healthcare provider tells you to take it. Before you inject, always check the label of your single-dose prefilled autoinjector or single-dose prefilled syringe to make sure you have the correct medicine and the correct dose of AIMOVIG.Also, before you inject, leave AIMOVIG at room temperature for at least 30 minutes protected from direct sunlight.AIMOVIG is injected under your skin (subcutaneously) time each month.AIMOVIG comes in different types of devices: single-dose (1 time) prefilled autoinjector or single-dose (1 time) prefilled syringe. Your healthcare provider will prescribe the type and dose that is best for you.If you forget to take AIMOVIG or are not able to take the dose at the regular time, take your missed dose as soon as you remember. After that, you can continue to take AIMOVIG time each month from the date of your last dose.What are possible side effects of AIMOVIGAIMOVIG may cause serious side effects, including:Allergic reactions. Allergic reactions, including rash or swelling can happen after receiving AIMOVIG. This can happen within hours to days after using AIMOVIG. Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms of an allergic reaction: swelling of the face, mouth, tongue, or throattrouble breathing Constipation with serious complications. Severe constipation can happen after receiving AIMOVIG. In some cases, people have been hospitalized or needed surgery. Contact your healthcare provider if you have severe constipation.High blood pressure. High blood pressure or worsening of high blood pressure can happen after receiving AIMOVIG. Contact your healthcare provider if you have an increase in blood pressure.The most common side effects of AIMOVIG include: pain, redness, or swelling at the injection site and constipation.Tell your healthcare provider if you have any side effect that bothers you or that does not go away.These are not all of the possible side effects of AIMOVIG. Ask your pharmacist or healthcare provider for more information.Call your healthcare provider for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects to Amgen at 1-800-77-AMGEN (1-800-772-6436).How should store AIMOVIGStore AIMOVIG in the refrigerator between 36F to 46F (2C to 8C). Keep AIMOVIG in the original carton. This will protect the medicine from light. After removing AIMOVIG from the refrigerator, it can be stored at room temperature between 68F to 77F (20C to 25C) for up to days.Throw away AIMOVIG that has been left at room temperature for more than days. Do not freeze. Do not shake. Keep AIMOVIG and all medicines out of the reach of children.General information about the safe and effective use of AIMOVIG.Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflet. Do not use AIMOVIG for condition for which it is not prescribed. Do not give AIMOVIG to other people, even if they have the same symptoms that you have. It can harm them. You can ask your pharmacist or healthcare provider for information about AIMOVIG that is written for healthcare professionals. What are the ingredients in AIMOVIGActive Ingredient: erenumab-aooeInactive Ingredients: acetate, polysorbate 80, and sucroseAIMOVIG(R) (erenumab-aooe) Manufactured by: Amgen Inc.One Amgen Center DriveThousand Oaks, CA 91320-1799 U.S.A.U.S. License No. 1080 Patent: http://pat.amgen.com/aimovig/(C) 2018-2021 Amgen Inc. All rights reserved.For more information, go to www.aimovig.com or call 1-800-77-AMGEN (1-800-772-6436).. Allergic to rubber or latex. The needle shield within the white or orange cap of the single-dose prefilled SureClick(R) autoinjectors and the gray needle cap of the single-dose prefilled syringes contain dry natural rubber. Pregnant or plan to become pregnant. It is not known if AIMOVIG will harm your unborn baby.. Breastfeeding or plan to breastfeed. It is not known if AIMOVIG passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby while using AIMOVIG. See the detailed Instructions for Use on complete information on how to take AIMOVIG.. Take AIMOVIG exactly as your healthcare provider tells you to take it. Before you inject, always check the label of your single-dose prefilled autoinjector or single-dose prefilled syringe to make sure you have the correct medicine and the correct dose of AIMOVIG.. Also, before you inject, leave AIMOVIG at room temperature for at least 30 minutes protected from direct sunlight.. AIMOVIG is injected under your skin (subcutaneously) time each month.. AIMOVIG comes in different types of devices: single-dose (1 time) prefilled autoinjector or single-dose (1 time) prefilled syringe. Your healthcare provider will prescribe the type and dose that is best for you.. If you forget to take AIMOVIG or are not able to take the dose at the regular time, take your missed dose as soon as you remember. After that, you can continue to take AIMOVIG time each month from the date of your last dose.. Allergic reactions. Allergic reactions, including rash or swelling can happen after receiving AIMOVIG. This can happen within hours to days after using AIMOVIG. Call your healthcare provider or get emergency medical help right away if you have any of the following symptoms of an allergic reaction: swelling of the face, mouth, tongue, or throattrouble breathing swelling of the face, mouth, tongue, or throat. trouble breathing. Constipation with serious complications. Severe constipation can happen after receiving AIMOVIG. In some cases, people have been hospitalized or needed surgery. Contact your healthcare provider if you have severe constipation.. High blood pressure. High blood pressure or worsening of high blood pressure can happen after receiving AIMOVIG. Contact your healthcare provider if you have an increase in blood pressure.. Store AIMOVIG in the refrigerator between 36F to 46F (2C to 8C). Keep AIMOVIG in the original carton. This will protect the medicine from light. After removing AIMOVIG from the refrigerator, it can be stored at room temperature between 68F to 77F (20C to 25C) for up to days.. Throw away AIMOVIG that has been left at room temperature for more than days. Do not freeze. Do not shake. Active Ingredient: erenumab-aooe. Inactive Ingredients: acetate, polysorbate 80, and sucrose.

SPL UNCLASSIFIED SECTION.

2.1Recommended Dosing. The recommended dosage of AIMOVIG is 70 mg injected subcutaneously once monthly. Some patients may benefit from dosage of 140 mg injected subcutaneously once monthly.If dose of AIMOVIG is missed, administer as soon as possible. Thereafter, AIMOVIG can be scheduled monthly from the date of the last dose.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. For subcutaneous use only (2.1, 2.2)Recommended dosage is 70 mg once monthly; some patients may benefit from dosage of 140 mg once monthly (2.1)The needle shield within the white or orange cap of the prefilled autoinjector and the gray needle cap of the prefilled syringe contain dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex (2.2)Administer in the abdomen, thigh, or upper arm subcutaneously (2.2)See Dosage and Administration for important administration instructions (2.2). For subcutaneous use only (2.1, 2.2). Recommended dosage is 70 mg once monthly; some patients may benefit from dosage of 140 mg once monthly (2.1). The needle shield within the white or orange cap of the prefilled autoinjector and the gray needle cap of the prefilled syringe contain dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex (2.2). Administer in the abdomen, thigh, or upper arm subcutaneously (2.2). See Dosage and Administration for important administration instructions (2.2). 2.1Recommended Dosing. The recommended dosage of AIMOVIG is 70 mg injected subcutaneously once monthly. Some patients may benefit from dosage of 140 mg injected subcutaneously once monthly.If dose of AIMOVIG is missed, administer as soon as possible. Thereafter, AIMOVIG can be scheduled monthly from the date of the last dose.. 2.2Important Administration Instructions. AIMOVIG is for subcutaneous use only.The needle shield within the white or orange cap of the AIMOVIG prefilled autoinjector and gray needle cap of the AIMOVIG prefilled syringe contain dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex.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 heat source such as hot water or 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.. 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 heat source such as hot water or 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.

DOSAGE FORMS & STRENGTHS SECTION.

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

GERIATRIC USE SECTION.

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.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. 16.1How Supplied. AIMOVIG (erenumab-aooe) injection is sterile, clear to opalescent, colorless to light yellow solution for subcutaneous administration.The needle shield within the white or orange cap of the AIMOVIG prefilled autoinjector and gray needle cap of the AIMOVIG prefilled syringe contain dry natural rubber (a derivative of latex). Each single-dose prefilled SureClick(R) autoinjector or single-dose prefilled syringe of AIMOVIG contains Type glass syringe and stainless steel needle and delivers mL of 70 mg/mL or 140 mg/mL solution.AIMOVIG is supplied as follows:SureClick(R) AutoinjectorPack of autoinjector: 70 mg/mL single-dose prefilled autoinjector NDC 55513-841-01Pack of autoinjector: 140 mg/mL single-dose prefilled autoinjector NDC 55513-843-01SyringePack of syringe: 70 mg/mL single-dose prefilled syringe NDC 55513-840-01Pack of syringe: 140 mg/mL single-dose prefilled syringe NDC 55513-842-01. Pack of autoinjector: 70 mg/mL single-dose prefilled autoinjector NDC 55513-841-01. Pack of autoinjector: 140 mg/mL single-dose prefilled autoinjector NDC 55513-843-01. Pack of syringe: 70 mg/mL single-dose prefilled syringe NDC 55513-840-01. Pack of syringe: 140 mg/mL single-dose prefilled syringe NDC 55513-842-01. 16.2Storage and Handling. Store refrigerated at 2C to 8C (36F to 46F) 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 25C [77F]) in the original carton and must be used within days. Throw away AIMOVIG that has been left at room temperature for more than days. Do not freeze. Do not shake.. Store refrigerated at 2C to 8C (36F to 46F) 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 25C [77F]) in the original carton and must be used within days. Throw away AIMOVIG that has been left at room temperature for more than days.. Do not freeze.. Do not shake.

IMMUNOGENICITY.

6.2 Immunogenicity. As with all therapeutic proteins, there is potential for immunogenicity. The detection of antibody formation, including neutralizing antibodies, is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to erenumab-aooe in the studies described below with the incidence of antibodies in other studies or to other products may be misleading.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, 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). 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.

INDICATIONS & USAGE SECTION.

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

STORAGE AND HANDLING SECTION.

16.2Storage and Handling. Store refrigerated at 2C to 8C (36F to 46F) 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 25C [77F]) in the original carton and must be used within days. Throw away AIMOVIG that has been left at room temperature for more than days. Do not freeze. Do not shake.. Store refrigerated at 2C to 8C (36F to 46F) 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 25C [77F]) in the original carton and must be used within days. Throw away AIMOVIG that has been left at room temperature for more than days.. Do not freeze.. Do not shake.

INFORMATION FOR PATIENTS SECTION.

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 latex-sensitive patients that the needle shield within the white or orange cap of the AIMOVIG prefilled autoinjector and gray needle cap of the AIMOVIG prefilled syringe contain dry natural rubber (a derivative of latex) that may cause allergic reactions in individuals sensitive to latex [see Dosage and Administration (2.2)].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)].

INSTRUCTIONS FOR USE SECTION.

Instructions for Use AIMOVIG(R) (AIM-oh-vig) (erenumab-aooe) Injection, For Subcutaneous Use Single-Dose Prefilled SureClick(R) Autoinjector 70 mg/mL. Important: Needle is inside the green safety guard.ImportantBefore you use AIMOVIG SureClick autoinjector, read this important information:Storing your AIMOVIG SureClick autoinjectorKeep the autoinjector out of the reach of children.Keep the autoinjector in the original carton to protect from light.The autoinjector should be kept in the refrigerator at 36F to 46F (2C to 8C). After removing AIMOVIG from the refrigerator, it can be stored at room temperature between 68F to 77F (20C to 25C) for up to days.Throw away AIMOVIG that has been left at room temperature for more than days. Do not freeze.Using your AIMOVIG SureClick autoinjectorThe needle shield within the white cap of the AIMOVIG autoinjector contains dry natural rubber, which is made from latex. Tell your healthcare provider if you are allergic to latex. 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 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 freeze or use the autoinjector if it has been frozen.Do not use the autoinjector if it has been dropped on hard surface. Part of the autoinjector may be broken even if you cannot see the break. Use new autoinjector, and call 1-800-77-AMGEN (1-800-772-6436). Step 1: PrepareAIMOVIG comes as single-dose (1 time) prefilled autoinjector. Your healthcare provider will prescribe the dose that is best for you.Before you inject, always check the label of your single-dose prefilled autoinjector to make sure you have the correct medicine and the correct dose of AIMOVIG.A Remove autoinjector from the carton.Carefully lift the autoinjector straight up out of the carton.Leave the autoinjector at room temperature for at least 30 minutes before injecting.Do not put the autoinjector back in the refrigerator after it has reached room temperature.Do not try to warm the autoinjector by using heat source such as hot water or microwave.Do not leave the autoinjector in direct sunlight.Do not shake the autoinjector.Do not remove the white cap from the autoinjector yet.B Inspect the autoinjector.Green safety guard (needle inside)Make sure the medicine in the window is clear and colorless to slightly yellow.Do not use the autoinjector if the medicine is cloudy or discolored or contains flakes or particles.Do not use the autoinjector if any part appears cracked or broken.Do not use the autoinjector if the autoinjector has been dropped.Do not use the autoinjector if the white cap is missing or not securely attached.Do not use the autoinjector if the expiration date printed on the label has passed.In all cases, use new autoinjector, 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 clean, well-lit work surface, place the:New autoinjector Alcohol wipesCotton balls or gauze padsAdhesive bandagesSharps disposal container (See Step 4: Finish)D Prepare and clean your injection site.Only use these injection sites:Your thighStomach area (abdomen), except for two inch area right around your navelOuter 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 readyE Pull the white cap straight off, only when you are ready to inject. Do not leave the white cap off for more than five minutes. This can dry out the medicine. White capIt is normal to see drop of liquid at the end of the needle or green safety guard.Do not twist or bend the white cap.Do not put the white cap back onto the autoinjector. Do not put fingers into the green safety guard. Do not remove the white cap from the autoinjector until you are ready to inject.F Create firm surface at the selected injection site (thigh, stomach, or outer areas of the upper arm), by using either the Stretch method or the Pinch method.Stretch the skin firmly by moving your thumb and fingers in opposite directions, creating an area about two inches wide.Pinch the skin firmly between your thumb and fingers, creating an area about two inches wide.Important: it is important to keep skin stretched or pinched while injecting.Step 3: InjectG Keep holding the stretched or pinched skin. With the white cap off, put the green safety guard on your skin at 90 degrees. The needle is inside the green safety guard. Do not touch the purple start button yet.Green safety guard (needle inside)H Firmly push the autoinjector down onto skin until the autoinjector stops moving.Important: You must push all the way down but do not touch the purple start button until you are ready to inject.I When you are ready to inject, press the purple start button. You will hear click. Keep pushing down on your skin. Then lift your thumb while still holding the autoinjector on your skin. Your injection could take about 15 seconds. Window turns from clear to yellow when injection is done. You may hear second click.Note: After you remove the autoinjector from your skin, the needle will be automatically covered.Important: When you remove the autoinjector, if the window has not turned yellow, or if it looks like the medicine is still injecting, this means you have not received full dose. Call your healthcare provider immediately.Step 4: FinishK Discard the used autoinjector and the white cap.Put the used AIMOVIG autoinjector and white cap in FDA-cleared sharps disposal container right away after use. Do not throw away (dispose of) the SureClick autoinjector in your household trash.If you do not have FDA-cleared sharps disposal container, you may use household container that is:Made of heavy-duty plasticCan be closed with tight-fitting, puncture-resistant lid, without sharps being able to come outUpright and stable during useLeak-resistantProperly 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 FDAs website at: http://www.fda.gov/safesharpsdisposalDo not reuse the autoinjector.Do not recycle the autoinjector or sharps disposal container or throw them into household trash.Important: Always keep the sharps disposal container out of the reach of children.L Examine the injection site. If there is blood, press cotton ball or gauze pad on your injection site. Do not rub the injection site. Apply an adhesive bandage if needed.Commonly asked questionsWhat will happen if press the purple start button before am ready to do the injection on my skinEven when you press the purple start button, the injection will only happen when the green safety guard is also pushed into the autoinjector. Can move the autoinjector around on my skin while am choosing an injection siteIt is okay to move the autoinjector around on the injection site as long as you do not press the purple start button. However, if you press the purple start button and the green safety guard is pushed into the autoinjector, the injection will begin.Can release the purple start button after start my injectionYou can release the purple start button, but continue to hold the autoinjector firmly against your skin during the injection.Will the purple start button pop up after release my thumbThe purple start button may not pop up after you release your thumb if you held your thumb down during the injection. This is okay.What do do if did not hear click after pushing the device down on my skin for 15 secondsIf you did not hear click, you can confirm complete injection by checking that the window has turned yellow. Whom do contact if need help with the autoinjector or my injectionIf you need more information or help, visit www.aimovig.com or call 1-800-77-AMGEN (1-800-772-6436). This Instructions for Use has been approved by the U.S. Food and Drug Administration. AIMOVIG(R) (erenumab-aooe)Manufactured by:Amgen Inc.One Amgen Center DriveThousand Oaks, CA 91320-1799 USAU.S. License No. 1080(C) 2018-2021 Amgen Inc. All rights reserved.<partnumber> Revised: 11/2021 v5Symbol tableThis product contains dry natural rubberDo not reuseCAUTION, Prior to use, read the enclosed Instructions For Use for administration information and see package insert for full Prescribing InformationLot number. Keep the autoinjector out of the reach of children.. Keep the autoinjector in the original carton to protect from light.. The autoinjector should be kept in the refrigerator at 36F to 46F (2C to 8C). After removing AIMOVIG from the refrigerator, it can be stored at room temperature between 68F to 77F (20C to 25C) for up to days.. Throw away AIMOVIG that has been left at room temperature for more than days. Do not freeze.. The needle shield within the white cap of the AIMOVIG autoinjector contains dry natural rubber, which is made from latex. Tell your healthcare provider if you are allergic to latex. 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 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 freeze or use the autoinjector if it has been frozen.. Do not use the autoinjector if it has been dropped on hard surface. Part of the autoinjector may be broken even if you cannot see the break. Use new autoinjector, and call 1-800-77-AMGEN (1-800-772-6436). Do not put the autoinjector back in the refrigerator after it has reached room temperature.. Do not try to warm the autoinjector by using heat source such as hot water or microwave.. Do not leave the autoinjector in direct sunlight.. Do not shake the autoinjector.. Do not remove the white cap from the autoinjector yet.. Do not use the autoinjector if the medicine is cloudy or discolored or contains flakes or particles.. Do not use the autoinjector if any part appears cracked or broken.. Do not use the autoinjector if the autoinjector has been dropped.. Do not use the autoinjector if the white cap is missing or not securely attached.. Do not use the autoinjector if the expiration date printed on the label has passed.. New autoinjector Alcohol wipes. Cotton balls or gauze pads. Adhesive bandages. Sharps disposal container (See Step 4: Finish). Your thigh. Stomach area (abdomen), except for two inch area right around your navel. Outer area of upper arm (only if someone else is giving you the injection). 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. Do not twist or bend the white cap.. Do not put the white cap back onto the autoinjector. Do not put fingers into the green safety guard. Do not remove the white cap from the autoinjector until you are ready to inject.. Made of heavy-duty plastic. Can be closed with 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 Do not reuse the autoinjector.. Do not recycle the autoinjector or sharps disposal container or throw them into household trash.. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image. Image.

LACTATION SECTION.

8.2 Lactation. Risk SummaryThere 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 mothers clinical need for AIMOVIG and any potential adverse effects on the breastfed infant from AIMOVIG or from the underlying maternal condition.

MECHANISM OF ACTION SECTION.

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

NONCLINICAL TOXICOLOGY SECTION.

13 NONCLINICAL TOXICOLOGY. 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility. CarcinogenesisThe carcinogenic potential of erenumab-aooe has not been assessed.. MutagenesisGenetic toxicology studies of erenumab-aooe have not been conducted.. Impairment of FertilityMating studies have not been conducted on erenumab-aooe. No histopathological changes in male or female reproductive organs were observed in monkeys administered erenumab-aooe (0, 25, or 150 mg/kg) by subcutaneous injection twice weekly for up to months. Serum erenumab-aooe exposures (AUC) at the higher dose tested were more than 100 times that in humans at dose of 140 mg once monthly.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PRINCIPAL DISPLAY PANEL 70 mg/mL Syringe Carton. AMGEN(R) x 70 mg/mL Prefilled SyringeNDC 55513-840-01Rx Onlyaimovig(R) (erenumab-aooe)Injection70mg/mL70 mg/mLSingle-dose Prefilled SyringeFor Subcutaneous Use OnlyStore refrigerated at 2C to 8C (36F to 46F) in original carton to protect from light. Do Not Freeze. Do Not Shake.Before injecting, allow AIMOVIG to sitat room temperature for at least 30 minuteswith cap on, protected from direct sunlight.Keep out of the sight and reach of children.For more information, go to Aimovig.com orcall 1-800-77-AMGEN (1-800-772-6436).CAUTION, Prior to use,read the enclosedInstructions for Use for administration informationand see package insert for full PrescribingInformationDo Not ReuseThis Product ContainsDry Natural Rubber.. PRINCIPAL DISPLAY PANEL 70 mg/mL Syringe Carton.

PEDIATRIC USE SECTION.

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

PHARMACODYNAMICS SECTION.

12.2 Pharmacodynamics. In 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 mg doses separated by one hour) had no effect on resting blood pressure compared with sumatriptan alone. AIMOVIG is for subcutaneous use only.

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. Erenumab-aooe exhibits non-linear kinetics as result of binding to the CGRP receptor. The Cmax mean and AUClast mean following subcutaneous administration of 70 mg once monthly and 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 (Cmin) 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 months of dosing. The effective half-life of erenumab-aooe is 28 days.Table 2: Pharmacokinetic Parameters of AIMOVIGAIMOVIG 70 mgSubcutaneously Once MonthlyAIMOVIG 140 mgSubcutaneously Once MonthlyCmax mean (SD)SD standard deviation from single-dose study 6.1 (2.1) mcg/mL15.8 (4.8) mcg/mLAUClast mean (SD) 159 (58) daymcg/mL505 (139) daymcg/mLCmin (SD) Episodic migraine5.7 (3.1) mcg/mL12.8 (6.5) mcg/mL Chronic migraine6.2 (2.9) mcg/mL14.9 (6.5) mcg/mL. AbsorptionFollowing single subcutaneous dose of 70 mg or 140 mg erenumab-aooe administered to healthy adults, median peak serum concentrations were attained in approximately days, and estimated absolute bioavailability was 82%.. DistributionFollowing single 140 mg intravenous dose, the mean (SD) volume of distribution during the terminal phase (Vz) was estimated to be 3.86 (0.77) L.. Metabolism and ExcretionTwo 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 non-specific, non-saturable proteolytic pathway.. Specific PopulationsThe 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 ImpairmentPopulation pharmacokinetic analysis of integrated data from the AIMOVIG clinical studies did not reveal 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 m2) 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 EnzymesErenumab-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 ContraceptivesIn an open-label drug interaction study in healthy female volunteers, erenumab-aooe (140 mg subcutaneous, single-dose) did not affect the pharmacokinetics of combined oral contraceptive containing ethinyl estradiol and norgestimate.. SumatriptanIn study in healthy volunteers, concomitant administration of erenumab-aooe with sumatriptan had no effect on the pharmacokinetics of sumatriptan [see Clinical Pharmacology (12.2)].

POSTMARKETING EXPERIENCE SECTION.

6.3 Postmarketing Experience. The following adverse reactions have been identified during postapproval use of AIMOVIG. Because these reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish 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)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. 8.1 Pregnancy. Risk SummaryThere 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 RiskPublished data have suggested that women with migraine may be at increased risk of preeclampsia during pregnancy.. Data. Animal DataIn 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 dose of 140 mg once monthly.. 8.2 Lactation. Risk SummaryThere 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 mothers 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. Hypersensitivity Reactions: If 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) Hypersensitivity Reactions: If 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) 5.1Hypersensitivity 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 serious or severe hypersensitivity reaction occurs, discontinue administration of AIMOVIG and initiate appropriate therapy [see Contraindications (4), and Patient Counseling Information (17)].. 5.2Constipation 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 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.. 5.3Hypertension. 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.