AJOVY

RECENT MAJOR CHANGES Indications and Usage ( 1 ) 8/2025 Dosage and Administration ( 2.1 , 2.2 ) 8/2025 Warnings and Precautions ( 5.2 ) 6/2026

1 INDICATIONS AND USAGE AJOVY is indicated for: the preventive treatment of migraine in adults, and the preventive treatment of episodic migraine in pediatric patients who are 6 to 17 years of age and who weigh 45 kg or more. AJOVY is a calcitonin gene-related peptide antagonist indicated for: the preventive treatment of migraine in adults, and the preventive treatment of episodic migraine in pediatric patients who are 6 to 17 years of age and who weigh 45 kg or more. ( 1 )

2 DOSAGE AND ADMINISTRATION For subcutaneous use only. Recommended dosage: Adults : Two subcutaneous dosing options of AJOVY are available to administer the recommended dosage; 225 mg monthly or 675 mg every 3 months (quarterly). The 675 mg quarterly dosage is administered as three consecutive injections of 225 mg each. ( 2.1 ) Pediatric patients 6 to 17 years of age and who weigh 45 kg or more : 225 mg monthly ( 2.1 ) Administer in the abdomen, thigh, or upper arm subcutaneously. ( 2.2 ) See Dosage and Administration for important administration instructions. ( 2.2 ) 2.1 Recommended Dosage Adults The recommended dosage in adults for the preventive treatment of migraine is administered by subcutaneous injection as one of the following options: 225 mg monthly, or 675 mg every 3 months (quarterly), which is administered as three consecutive subcutaneous injections of 225 mg each. When switching dosage options, administer the first dose of the new regimen on the next scheduled date of administration. Pediatric Patients who are 6 to 17 Years of Age and who Weigh 45 kg or More: The recommended dosage for the preventive treatment of episodic migraine in pediatric patients who are 6 to 17 years of age and who weigh 45 kg or more is administered by subcutaneous injection as follows: 225 mg monthly. AJOVY is not approved in pediatric patients weighing less than 45 kg because of the lack of an appropriate strength presentation [see Clinical Studies (14) and How Supplied/Storage and Handling (16.1)] . Missed Dose If a dose of AJOVY is missed, administer as soon as possible. Thereafter, AJOVY can be scheduled from the date of the last dose. 2.2 Important Administration Instructions AJOVY is for subcutaneous use only. AJOVY may be administered by healthcare providers, patients 13 years of age and older, and/or caregivers. In pediatric patients 6 to 12 years of age, AJOVY must be administered by a healthcare provider or adult caregiver. Prior to use, provide proper training to patients and/or caregivers on the preparation and administration of AJOVY prefilled syringe, including aseptic technique [see Instructions for Use ] : Remove AJOVY from the refrigerator. Prior to use, allow AJOVY to sit at room temperature for 30 minutes protected from direct sunlight. Do not warm by using a heat source such as hot water or a microwave. Do not use AJOVY if it has been at room temperature for 7 days or longer [see How Supplied/Storage and Handling ( 16.2 )]. Follow aseptic injection technique every time AJOVY is administered. Inspect AJOVY for particles or discoloration prior to administration [see Dosage Forms and Strengths ( 3 )] . Do not use if the solution is cloudy, discolored, or contains particles. Administer AJOVY by subcutaneous injection into areas of the abdomen, thigh, or upper arm that are not tender, bruised, red, or indurated. For multiple injections, you may use the same body site, but not the exact location of the previous injection. Do not co-administer AJOVY with other injectable drugs at the same injection site.

3 DOSAGE FORMS AND STRENGTHS AJOVY is a sterile, clear to opalescent, colorless to slightly yellow solution, available as follows: Injection: 225 mg/1.5 mL single-dose prefilled autoinjector Injection: 225 mg/1.5 mL single-dose prefilled syringe Injection: 225 mg/1.5 mL solution in a single-dose prefilled autoinjector. ( 3 ) Injection: 225 mg/1.5 mL solution in a single-dose prefilled syringe. ( 3 )

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

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hypersensitivity Reactions [see Warnings and Precautions ( 5.1 )] Constipation with Serious Complications [see Warnings and Precautions ( 5.2 )] Hypertension [see Warnings and Precautions ( 5.3 )] Raynaud’s Phenomenon [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥5% and greater than placebo) were injection site reactions. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug, and may not reflect the rates observed in clinical practice. Adults The safety of AJOVY was evaluated in 2512 patients with migraine who received at least 1 dose of AJOVY, representing 1279 patient-years of exposure. Of these, 1730 patients were exposed to AJOVY 225 mg monthly or AJOVY 675 mg quarterly for at least 6 months, 775 patients for at least 12 months, and 138 patients for at least 15 months. In placebo-controlled clinical trials (Studies 1 and 2), 662 patients received AJOVY 225 mg monthly for 12 weeks (with or without a loading dose of 675 mg), and 663 patients received AJOVY 675 mg quarterly for 12 weeks [see Clinical Studies ( 14 )] . In the controlled trials, 87% of patients were female, 80% were White, and the mean age was 41 years. The most common adverse reactions in the clinical trials for the preventive treatment of migraine (incidence at least 5% and greater than placebo) were injection site reactions. The adverse reactions that most commonly led to discontinuations were injection site reactions (1%). Table 1 summarizes adverse reactions reported in the 3-month placebo-controlled studies (Study 1 and Study 2), and the 1-month follow-up period after those studies. Table 1: Adverse Reactions Occurring with an Incidence of At Least 2% for Either Dosing Regimen of AJOVY and At Least 2% Greater Than Placebo in Studies 1 and 2 Adverse Reaction AJOVY 225 mg Monthly (n=290) % AJOVY 675 mg Quarterly (n=667) % Placebo Monthly (n=668) % Injection site reactions a 43 45 38 a Injection site reactions include multiple related adverse event terms, such as injection site pain, induration, and erythema. Pediatric Patients 6 to 17 Years of Age The safety of AJOVY was evaluated in 225 pediatric patients 6 to 17 years of age with episodic migraine who received at least one dose of AJOVY. Of these patients, 209 received AJOVY monthly for at least 6 months and 100 received AJOVY for at least 12 months. In the placebo-controlled trial (Study 3), 123 pediatric patients with episodic migraine were treated with AJOVY [see Clinical Studies (14)] . The most common adverse reactions of AJOVY observed in Study 3 were injection site reactions. Hypersensitivity reactions were also observed. Overall, the safety profile in pediatric patients is similar to the known safety profile in adults. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of AJOVY. 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. Gastrointestinal Disorders: Constipation [see Warnings and Precautions ( 5.2 )] Immune System Disorders : Anaphylactic reactions and angioedema [see Contraindications ( 4 ) and Warnings and Precautions ( 5.1 )] Vascular Disorders : Hypertension [see Warnings and Precautions ( 5.3 )] , Raynaud’s phenomenon [see Warnings and Precautions ( 5.4 )]

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to AJOVY during pregnancy. Healthcare providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-833-927-2605 or visiting www.tevamigrainepregnancyregistry.com. Risk Summary There are no adequate data on the developmental risk associated with the use of AJOVY in pregnant women. AJOVY has a long half-life [see Clinical Pharmacology ( 12.3 )] . This should be taken into consideration for women who are pregnant or plan to become pregnant while using AJOVY. Administration of fremanezumab-vfrm to rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation at doses resulting in plasma levels greater than those expected clinically did not result in adverse effects on development [see Animal Data] . In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The estimated rate of major birth defects (2.2-2.9%) and miscarriage (17%) among deliveries to women with migraine are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Published data have suggested that women with migraine may be at increased risk of preeclampsia and gestational hypertension during pregnancy. Data Animal Data When fremanezumab-vfrm (0, 50, 100, or 200 mg/kg) was administered to male and female rats by weekly subcutaneous injection prior to and during mating and continuing in females throughout organogenesis, no adverse embryofetal effects were observed. The highest dose tested was associated with plasma exposures (AUC) approximately 2 times that in humans at a dose of 675 mg. Administration of fremanezumab-vfrm (0, 10, 50, or 100 mg/kg) weekly by subcutaneous injection to pregnant rabbits throughout the period of organogenesis produced no adverse effects on embryofetal development. The highest dose tested was associated with plasma AUC approximately 3 times that in humans (675 mg). Administration of fremanezumab-vfrm (0, 50, 100, or 200 mg/kg) weekly by subcutaneous injection to female rats throughout pregnancy and lactation resulted in no adverse effects on pre- and postnatal development. The highest dose tested was associated with plasma AUC approximately 2 times that in humans (675 mg). 8.2 Lactation Risk Summary There are no data on the presence of fremanezumab-vfrm 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 AJOVY and any potential adverse effects on the breastfed infant from AJOVY or from the underlying maternal condition. 8.4 Pediatric Use Episodic Migraine The safety and effectiveness of AJOVY have been established in an adequate and well-controlled study for the preventive treatment of episodic migraine in pediatric patients who are 6 to 17 years of age and who weigh 45 kg or more (Study 3). The safety and efficacy profile of AJOVY in these patients was similar to the safety and efficacy profile seen in clinical trials in adults with migraine [see Adverse Reactions ( 6.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14 )]. AJOVY is not approved in pediatric patients weighing less than 45 kg because of the lack of an appropriate strength presentation. The safety and effectiveness of AJOVY for the preventive treatment of episodic migraine in pediatric patients younger than 6 years of age have not been established. Chronic Migraine The safety and effectiveness of AJOVY for the preventive treatment of chronic migraine in pediatric patients have not been established. Juvenile Animal Toxicity Data Subcutaneous administration of fremanezumab-v …

12.1 Mechanism of Action Fremanezumab-vfrm is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.

11 DESCRIPTION Fremanezumab-vfrm is a humanized IgG2Δa/kappa monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand. Fremanezumab-vfrm is produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. The antibody consists of 1324 amino acids and has a molecular weight of approximately 148 kDa. AJOVY (fremanezumab-vfrm) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution for subcutaneous injection, supplied in a single-dose 225 mg/1.5 mL prefilled autoinjector and a single-dose 225 mg/1.5 mL prefilled syringe. Each prefilled autoinjector or prefilled syringe delivers 1.5 mL of solution containing 225 mg fremanezumab-vfrm, disodium ethylenediaminetetraacetic acid dihydrate (EDTA) (0.204 mg), L-histidine (0.815 mg), L-histidine hydrochloride monohydrate (3.93 mg), polysorbate-80 (0.3 mg), sucrose (99 mg), and Water for Injection, and has a pH of 5.5.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied AJOVY (fremanezumab-vfrm) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution for subcutaneous administration. AJOVY is not made with natural rubber latex. AJOVY is supplied as follows: Prefilled Autoinjector Pack of 1 autoinjector: 225 mg/1.5 mL single-dose prefilled autoinjector NDC 51759-202-10 Pack of 3 autoinjectors: 3 x 225 mg/1.5mL single-dose prefilled autoinjectors NDC 51759-202-22 Prefilled Syringe Pack of 1 syringe: 225 mg/1.5 mL single-dose prefilled syringe NDC 51759-204-10 16.2 Storage and Handling Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original outer carton to protect from light. If necessary, AJOVY may be kept in the original carton at room temperature up to 30°C (86°F) for a maximum of 7 days. After removal from the refrigerator, AJOVY must be used within 7 days or discarded. Once stored at room temperature, do not place back in the refrigerator. Do not freeze. Do not expose to extreme heat or direct sunlight. Do not shake.