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.

ic 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.

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) ].

hich 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.

istered 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.

ients 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.

cg/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) ] .

6 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 4 to 6. secondary endpoints included the achievement of a ≥ 50% reduction from baseline in mean monthly migraine days over months 4 to 6 ("≥ 50% mmd responders"), the change from baseline in mean monthly acute migraine-specific medication days over months 4 to 6, and the change from baseline in mean migraine physical function impact diary (mpfid) over months 4 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 0 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 a 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 8 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 4 to 6 in study 1 aimovig 70 mg once monthly aimovig 140 mg once monthly placebo n = 312 n = 318 n = 316 monthly 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 % responders 43.3% 50.0% 26.6% difference from placebo 16.7% 23.4% odds ratio relative to placebo 2.1 2.8 p- value < 0.001 < 0.001 monthly 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 < 0.001 figure 1: change from baseline in monthly migraine days in study 1 least-square means and 95% confidence intervals are presented. figure 2 shows the distribution of change from baseline in mean monthly migraine days over months 4 to 6 in bins of 2 days by treatment group. a treatment benefit over placebo for both doses of aimovig is seen across a range of changes from baseline in monthly migraine days. figure 2: distribution of change from baseline in mean monthly migraine days over months 4 to 6 by treatment group in study 1 figure 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 4 to 6 [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 4 to 6 [difference from placebo: −1.9 for aimovig 70 mg and −2.4 for aimovig 140 mg; p- value < 0.001 for both]. study 2 (nct 02483585) was a randomized, multi-center, 3-month, placebo-controlled, double-blind study evaluating aimovig for the preventive treatment of episodic migraine. a total of 577 patients with a history of episodic migraine were randomized to receive either aimovig 70 mg (n = 286) or placebo (n = 291) by subcutaneous injection once monthly for 3 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 a ≥ 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 a 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 a 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 8 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 3 for study 2 aimovig 70 mg once monthly placebo n = 282 n = 288 monthly migraine days (mmd) change from baseline −2.9 −1.8 difference from placebo −1.0 p- value < 0.001 ≥ 50% mmd responders % responders 39.7% 29.5% difference from placebo 10.2% odds ratio relative to placebo 1.6 p- value 0.010 monthly acute migraine-specific medication days change from baseline −1.2 −0.6 difference from placebo −0.6 p- value 0.002 figure 3: change from baseline in monthly migraine days in study 2 least-square means and 95% confidence intervals are presented. figure 4 shows the distribution of change from baseline in monthly migraine days at month 3 in bins of 2 days by treatment group. a treatment benefit over placebo for aimovig is seen across a range of changes from baseline in monthly migraine days. figure 4: distribution of change from baseline in monthly migraine days at month 3 by treatment group in study 2 figure excludes patients with missing data. the pre-specified analysis for the mpfid was based on at least a 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 migraine study 3 (nct 02066415) was a randomized, multi-center, 3-month, placebo-controlled, double-blind study evaluating aimovig as a preventive treatment of chronic migraine. a total of 667 patients with a 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 3 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 a ≥ 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 a 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 3 in study 3 aimovig 70 mg once monthly aimovig 140 mg once monthly placebo n = 188 n = 187 n = 281 monthly 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 % responders 39.9% 41.2% 23.5% difference from placebo 16.4% 17.7% odds ratio relative to placebo 2.2 2.3 p- value < 0.001 < 0.001 monthly 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 < 0.001 figure 5: change from baseline in monthly migraine days in study 3 least-square means and 95% confidence intervals are presented. figure 6 shows the distribution of change from baseline in monthly migraine days at month 3 in bins of 3 days by treatment group. a treatment benefit over placebo for both doses of aimovig is seen across a range of changes from baseline in migraine days. figure 6: distribution of change from baseline in monthly migraine days at month 3 by treatment group in study 3 figure excludes patients with missing data. figure 5 figure 6

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.

cur 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) ] .

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 i take 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) 1 time each month. aimovig comes in 2 different types of devices: a single-dose (1 time) prefilled autoinjector or a 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 1 time each month from the date of your last dose. what are possible side effects of aimovig? aimovig 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 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 or constipation associated with symptoms such as severe or constant belly pain, vomiting, swelling of belly or bloating. 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 i store aimovig? store aimovig in the refrigerator between 36°f to 46°f (2°c to 8°c). 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 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. 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 a patient information leaflet. do not use aimovig for a 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 aimovig? active ingredient: erenumab-aooe inactive ingredients: acetate, polysorbate 80, and sucrose aimovig prefilled autoinjectors and prefilled syringes are not made with natural rubber latex. aimovig ® (erenumab-aooe) manufactured by: amgen inc. one amgen center drive thousand oaks, ca 91320-1799 u.s.a. u.s. license no. 1080 patent: http://pat.amgen.com/aimovig/ © 2018-2022 amgen inc. all rights reserved. for more information, go to www.aimovig.com or call 1-800-77-amgen (1-800-772-6436).