AJOVY: Uses, Dosage & Side Effects

What Is AJOVY and What Is It Used For?

AJOVY contains the active substance fremanezumab, a humanized immunoglobulin G2a (IgG2a) monoclonal antibody produced using recombinant DNA technology in Chinese hamster ovary (CHO) cells. As a monoclonal antibody, AJOVY is a type of highly specialized protein engineered to recognize and bind to one specific molecular target in the body. In the case of AJOVY, that target is calcitonin gene-related peptide (CGRP), a 37-amino acid neuropeptide that has been identified as a central player in the pathophysiology of migraine.

CGRP is one of the most abundant neuropeptides in the human nervous system. It is found in both the peripheral and central nervous systems, with particularly high concentrations in the trigeminal ganglion and perivascular nerve fibers surrounding cerebral and meningeal blood vessels. During a migraine attack, CGRP is released in large quantities from trigeminal sensory neurons. This release triggers a cascade of events including vasodilation of intracranial blood vessels, neurogenic inflammation in the meninges, sensitization of pain-processing neurons in the trigeminal nucleus caudalis, and transmission of pain signals to higher brain centers. Elevated CGRP levels have been consistently measured in the jugular blood of patients during acute migraine attacks, and intravenous infusion of CGRP has been shown to provoke migraine-like headaches in susceptible individuals.

Fremanezumab works by selectively binding to both the alpha and beta isoforms of CGRP with high affinity. By binding to and neutralizing CGRP in the circulation before it can activate its receptor, fremanezumab effectively blocks the downstream signaling cascade that leads to migraine. This results in fewer migraine attacks, less severe headaches, and reduced reliance on acute migraine medications such as triptans and analgesics. Importantly, fremanezumab does not cross the blood-brain barrier in significant amounts; instead, it is thought to exert its preventive effects primarily in the peripheral trigeminovascular system, where CGRP-mediated signaling plays a crucial role in migraine initiation.

AJOVY is indicated for the preventive treatment of migraine in adults who experience at least 4 migraine days per month. This includes patients with both episodic migraine (fewer than 15 headache days per month) and chronic migraine (15 or more headache days per month, of which at least 8 are migraine days). AJOVY was evaluated in two pivotal phase III clinical trials:

• HALO Episodic Migraine (HALO-EM): This randomized, double-blind, placebo-controlled trial enrolled 875 adults with episodic migraine. Patients treated with fremanezumab (either monthly 225 mg or quarterly 675 mg) experienced a statistically significant reduction in the mean number of monthly migraine days compared with placebo over a 12-week treatment period. The monthly dosing group experienced an average reduction of 3.7 migraine days per month versus 2.2 for placebo, and the quarterly dosing group experienced a reduction of 3.4 days versus 2.2 for placebo.
• HALO Chronic Migraine (HALO-CM): This trial enrolled 1,130 adults with chronic migraine. Patients receiving fremanezumab showed significantly greater reductions in monthly headache days of at least moderate severity. The monthly dosing group experienced an average reduction of 4.6 headache days per month versus 2.5 for placebo, and the quarterly dosing group showed a reduction of 4.3 days versus 2.5 for placebo.

In both trials, the benefits of AJOVY were apparent as early as the first week after the initial injection, providing patients with rapid relief from their migraine burden. Long-term extension studies have demonstrated sustained efficacy over 12 months and beyond, with continued reductions in migraine frequency, headache days, and use of acute migraine medications. The proportion of patients achieving a 50% or greater reduction in monthly migraine days (a widely used clinical benchmark) was significantly higher in the AJOVY groups compared with placebo.

AJOVY was first approved by the U.S. Food and Drug Administration (FDA) in September 2018 and subsequently by the European Medicines Agency (EMA) in March 2019. It is now approved in more than 40 countries worldwide. AJOVY is part of a new class of preventive migraine therapies that target the CGRP pathway, representing a significant advancement over older preventive medications (such as beta-blockers, anticonvulsants, and antidepressants) that were originally developed for other conditions and repurposed for migraine prevention.

What Should You Know Before Taking AJOVY?

Contraindications

The primary contraindication to AJOVY use is hypersensitivity (allergy) to fremanezumab or to any of the other ingredients in the formulation. The excipients in AJOVY include L-histidine, L-histidine hydrochloride monohydrate, sucrose, disodium edetate dihydrate, polysorbate 80, and water for injections. If you have a known allergy to any of these substances, you must not use AJOVY.

Serious hypersensitivity reactions, including anaphylaxis, rash, urticaria (hives), and angioedema (swelling of the face, lips, tongue, or throat), have been reported in post-marketing experience. These reactions can occur within 24 hours of injection but have also been reported with a delayed onset of days or weeks. If you experience signs of a severe allergic reaction after using AJOVY, seek immediate medical attention and do not administer further doses until you have consulted your healthcare provider.

Warnings and Precautions

Before starting AJOVY, discuss the following with your healthcare provider:

• Cardiovascular disease: AJOVY has not been studied in patients with certain cardiovascular conditions, including uncontrolled hypertension, recent myocardial infarction (heart attack), unstable angina, heart failure (NYHA class III or IV), or a history of stroke or transient ischemic attack. CGRP plays a role in cardiovascular protection, including vasodilation and blood pressure regulation. While current evidence from clinical trials and post-marketing surveillance has not identified significant cardiovascular safety signals, patients with established cardiovascular disease should be monitored and should discuss the potential risks with their doctor.
• History of allergic reactions: If you have a history of significant allergic reactions to medications or biological products, inform your doctor before starting AJOVY. Hypersensitivity reactions have been reported, including rare cases of anaphylaxis.
• Latex sensitivity: The needle cap of the AJOVY pre-filled pen may contain dry natural rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex. Check the package labeling and inform your doctor if you have a latex allergy.

Children and Adolescents

AJOVY is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of fremanezumab have not been established in this age group, and there are currently no clinical data to support its use in pediatric patients. Migraine in children and adolescents may require different treatment approaches, and healthcare providers should consider age-appropriate alternatives.

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before using AJOVY. The effects of fremanezumab on human pregnancy have not been adequately studied. As a monoclonal antibody (IgG), fremanezumab is expected to cross the placenta, particularly during the second and third trimesters. Animal reproductive studies with fremanezumab have not demonstrated adverse developmental effects, but animal studies are not always predictive of human response. As a precaution, AJOVY should be avoided during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus. Women of childbearing potential should discuss contraception with their doctor.

It is not known whether fremanezumab is excreted in human breast milk. Human IgG antibodies are known to be present in breast milk, particularly during the first days after birth. A risk to the breastfed infant cannot be excluded. The decision to breastfeed during AJOVY treatment should be made in consultation with your doctor, weighing the benefits of breastfeeding for the infant against the benefits of AJOVY treatment for the mother.

Driving and Operating Machinery

AJOVY is not expected to affect your ability to drive or operate machinery. No studies on the effects of fremanezumab on the ability to drive and use machines have been performed, but based on its pharmacological properties and the known side effect profile, it is unlikely to impair these abilities. However, if you experience any adverse effects that could affect your ability to drive or operate machinery, refrain from these activities until you feel well again.

Important Information About Ingredients

AJOVY contains less than 1 mmol (23 mg) of sodium per dose, meaning it is essentially sodium-free. This is relevant for patients on a sodium-restricted diet. The solution also contains sucrose, L-histidine, L-histidine hydrochloride monohydrate, disodium edetate dihydrate, polysorbate 80, and water for injections. If you have any known intolerances or allergies to these components, inform your healthcare provider before starting treatment.

How Does AJOVY Interact with Other Drugs?

One of the significant practical advantages of AJOVY in the preventive treatment of migraine is its favorable drug interaction profile. Unlike many traditional oral preventive medications for migraine (such as topiramate, valproate, or propranolol), which are metabolized by hepatic enzymes and can interact with a wide range of other medications, fremanezumab is a monoclonal antibody that is degraded through general protein catabolic pathways rather than through cytochrome P450 (CYP) enzyme-mediated metabolism.

No formal drug interaction studies have been conducted with fremanezumab, and based on its mechanism of clearance, no clinically significant pharmacokinetic interactions are expected. Population pharmacokinetic analyses from the clinical trial program have not identified any meaningful effects of concomitant medications on fremanezumab pharmacokinetics. Similarly, fremanezumab is not expected to affect the metabolism or pharmacokinetics of other drugs.

In clinical trials, AJOVY was used concomitantly with a variety of medications commonly used by migraine patients, including:

Although no formal drug-drug interactions have been identified, it is important to inform your doctor or pharmacist about all medications, herbal supplements, and over-the-counter products you are currently using. This is a standard recommendation for any prescription medication and helps ensure comprehensive monitoring of your health and treatment outcomes.

It is worth noting that while AJOVY does not have pharmacokinetic drug interactions, there is a theoretical pharmacodynamic consideration when combining it with other CGRP pathway-targeting therapies (such as CGRP receptor antagonists like rimegepant or ubrogepant). Both approaches target the same signaling pathway, and while co-administration has been reported in clinical practice, the long-term safety of such combinations has not been fully characterized. Discuss with your headache specialist if you are considering or already using other CGRP-targeted treatments.

What Is the Correct Dosage of AJOVY?

AJOVY should always be used exactly as your doctor or pharmacist has instructed. The medication is administered as a subcutaneous injection (under the skin) and is available in pre-filled pens, each containing 225 mg of fremanezumab in 1.5 mL of solution. Your doctor will work with you to determine the most appropriate dosing schedule based on your migraine pattern, lifestyle, and personal preferences.

Adults

There are two recommended dosing regimens for AJOVY in adult patients:

Both dosing regimens have been shown to be effective in clinical trials. The monthly regimen offers the advantage of a lower volume per administration session (a single injection), while the quarterly regimen provides the convenience of less frequent dosing (only four administration sessions per year). When the quarterly dose (675 mg) is chosen, all three injections should be given consecutively at the same visit but at different injection sites.

AJOVY is injected subcutaneously into one of the following body areas:

• Abdomen (belly): Avoid the area approximately 5 cm (2 inches) around the navel.
• Front of the thighs: Choose the area approximately 5 cm above the knee and 5 cm below the groin.
• Back of the upper arms: Select the fatty tissue on the upper part of the back of the arm (this site may require assistance from a caregiver).

When administering multiple injections (quarterly dosing), the injections can be given in the same general area (e.g., abdomen) or in different areas, but should not be given at exactly the same spot. Rotate injection sites between administrations to reduce the risk of injection site reactions.

Children and Adolescents

AJOVY is not recommended for use in patients under 18 years of age. Safety and efficacy have not been established in this age group. Pediatric clinical trials are ongoing, and dosing recommendations for children may become available in the future.

Elderly Patients

No dose adjustment is required for elderly patients. Clinical trials included patients aged 65 and older, and no overall differences in safety or efficacy were observed between older and younger patients. However, as with any medication in elderly patients, careful monitoring is advisable.

Renal and Hepatic Impairment

No dose adjustment is necessary for patients with mild to moderate kidney (renal) or liver (hepatic) impairment. AJOVY has not been specifically studied in patients with severe renal or hepatic impairment. Since monoclonal antibodies are not cleared through renal or hepatic metabolism, clinically meaningful effects of organ impairment on fremanezumab clearance are not expected.

Missed Dose

If you miss a scheduled dose of AJOVY, administer the missed dose as soon as possible. Do not take a double dose to make up for a forgotten dose. After administering the missed dose, resume your regular dosing schedule from the date of that injection. If you are unsure about when to administer your next dose, contact your doctor, pharmacist, or nurse for guidance. Using a calendar, diary, or mobile phone reminder can help you remember your dosing schedule.

Overdose

If you have used more AJOVY than you should, inform your doctor immediately. In clinical trials, single doses of up to 2,000 mg (intravenous) and repeated subcutaneous doses of up to 900 mg were administered without dose-limiting toxicities. There is no specific antidote for fremanezumab overdose. Treatment of overdose should be supportive, with monitoring of vital signs and clinical status. Given the long half-life of approximately 31 days, monitoring may need to continue for an extended period.

How to Use the Pre-Filled Pen

Before using AJOVY, your doctor or nurse should train you or your caregiver on the proper injection technique. The following is a general overview of the injection process:

1. Preparation: Remove the pre-filled pen from the refrigerator and allow it to reach room temperature (below 30 °C) for approximately 30 minutes. Do not heat it in a microwave or any other heat source. Do not leave it in direct sunlight.
2. Inspection: Check the pen label to confirm it is AJOVY. Inspect the solution through the viewing window: it should be clear and colorless to slightly yellow. Small air bubbles are normal. Do not use the pen if the solution is cloudy, discolored, or contains particles, or if the pen appears damaged or the expiration date has passed.
3. Site preparation: Wash your hands thoroughly. Clean the chosen injection site with an alcohol swab and let it dry for 10 seconds. Do not inject into skin that is tender, red, bruised, hardened, tattooed, scarred, or has stretch marks.
4. Injection: Remove the safety cap by pulling it straight off (do not twist). Place the pen at a 90-degree angle to the skin and press down firmly. Hold for approximately 30 seconds until you hear a second click and the blue plunger has filled the viewing window.
5. Disposal: After injection, the needle guard will lock into place automatically. Place the used pen immediately into an approved sharps disposal container. Do not put it in household waste or attempt to reuse it.

After injection, gently press the injection site with a clean, dry cotton pad or gauze for a few seconds. Do not rub the injection site.

What Are the Side Effects of AJOVY?

Like all medicines, AJOVY can cause side effects, although not everyone who takes it will experience them. The side effects observed during clinical trials and post-marketing surveillance are categorized below by their frequency of occurrence. Overall, AJOVY has been shown to have a favorable tolerability profile, with the majority of reported side effects being mild to moderate injection site reactions.

Clinical trial data from the HALO studies and long-term extension trials, as well as post-marketing pharmacovigilance data, form the basis of the known safety profile of AJOVY. In the pivotal trials, the overall rate of adverse events was similar between AJOVY and placebo groups, with the exception of injection site reactions, which were more common with AJOVY.

Injection site reactions are the most frequently reported side effects with AJOVY. In clinical trials, injection site pain, induration, and erythema occurred in approximately 26–45% of patients receiving AJOVY, compared with 18–28% of patients receiving placebo. These reactions are generally mild to moderate in intensity and short-lived, typically resolving within a few days without specific treatment. Rotating injection sites between administrations can help minimize these reactions.

Hypersensitivity (allergic) reactions to AJOVY have been reported during clinical trials and in post-marketing experience. Most allergic reactions were mild to moderate, presenting as skin rash, hives, or localized swelling. In rare cases, severe allergic reactions (anaphylaxis) have occurred. If you notice symptoms such as difficulty breathing, facial or throat swelling, widespread rash, or a rapid drop in blood pressure after injecting AJOVY, seek emergency medical care immediately.

It is important to note that the overall discontinuation rate due to adverse events in clinical trials was low (approximately 2–3%) and comparable between AJOVY and placebo groups, indicating that AJOVY is generally well tolerated. There were no signals of hepatotoxicity (liver damage), cardiovascular events, suicidal ideation, or weight changes that differed significantly from placebo in clinical trials.

Long-term safety data from extension studies spanning up to 18 months of treatment have been consistent with the known safety profile. No new safety signals have emerged with prolonged use, and the incidence of adverse events has remained stable over time. The development of anti-drug antibodies (immunogenicity) was observed in a small proportion of patients (less than 2%), but these antibodies did not appear to affect the efficacy or safety of AJOVY.

How Should You Store AJOVY?

Proper storage of AJOVY is essential to maintain the quality, safety, and efficacy of the medication. As a biological product (monoclonal antibody), fremanezumab is sensitive to temperature extremes, light exposure, and physical agitation, all of which can compromise its structural integrity and therapeutic effectiveness.

Follow these storage guidelines carefully:

• Refrigerated storage: Store AJOVY in the refrigerator at 2–8 °C (36–46 °F). This is the primary storage condition for the pre-filled pens. Keep the pens in the outer carton to protect them from light.
• Do not freeze: Freezing can damage the protein structure of the monoclonal antibody and render the medication ineffective. If AJOVY has been accidentally frozen, do not use it.
• Temporary room temperature storage: AJOVY can be taken out of the refrigerator and stored at temperatures up to 30 °C (86 °F) for a single period of up to 7 days. After 7 days at room temperature, the medication must be discarded. Once removed from the refrigerator, do not put AJOVY back into the refrigerator.
• Keep out of reach of children: Store AJOVY in a safe location where children cannot access it.
• Check expiration date: Do not use AJOVY after the expiration date printed on the pen label and outer carton after “EXP.” The expiration date refers to the last day of that month.
• Inspect before use: Before each injection, visually inspect the solution through the viewing window. The solution should be clear and colorless to slightly yellow. Do not use AJOVY if the outer carton has been tampered with, the pen is damaged, or the solution is cloudy, discolored, or contains particles.
• Single use only: Each pre-filled pen is intended for single use only. Do not reuse or share pens between patients.
• Proper disposal: After use, place the pen immediately into an approved sharps disposal container. Do not dispose of pens in household waste. Do not recycle the sharps container. Ask your pharmacist how to properly dispose of used containers.

When traveling with AJOVY, use an insulated bag with a cold pack to maintain the appropriate temperature. Avoid exposing the medication to excessive heat, direct sunlight, or x-ray machines. Security screening at airports should not damage the medication, but carry it in your hand luggage rather than checked baggage to avoid extreme temperatures in the cargo hold.

What Does AJOVY Contain?

Understanding what your medication contains is important, particularly if you have known allergies or sensitivities to specific pharmaceutical ingredients. Below is a detailed breakdown of the composition of AJOVY.

Active Ingredient

The active substance is fremanezumab, a humanized IgG2a monoclonal antibody produced by recombinant DNA technology in Chinese hamster ovary (CHO) cells. Each pre-filled pen contains 225 mg of fremanezumab in 1.5 mL of solution (corresponding to a concentration of 150 mg/mL).

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

AJOVY is supplied as a clear and colorless to slightly yellow solution for injection in a single-use pre-filled pen. Each pen contains 1.5 mL of solution. AJOVY is available in packs of 1 pre-filled pen (suitable for the monthly dosing regimen) or 3 pre-filled pens (suitable for a single quarterly dose or three monthly doses). Not all pack sizes may be available in every country.

Marketing Authorization Holder and Manufacturer

AJOVY is manufactured by Merckle GmbH (Ulm, Germany) and marketed by Teva Pharmaceuticals. The marketing authorization holder for the European Union is TEVA GmbH (Ulm, Germany). In the United States, AJOVY is marketed by Teva Neuroscience, Inc. AJOVY is approved and available in more than 40 countries worldwide.