Ajovy (Solution) Instructions for Use

Marketing Authorization Holder

Teva Pharmaceutical Industries, Ltd. (Israel)

Manufactured By

Vetter Pharma-Fertigung, GmbH & Co. KG (Germany)

Labeled By

VETTER PHARMA-FERTIGUNG, GmbH & Co.KG (Germany)

Or

Merckle, GmbH (Germany)

Quality Control Release

Merckle, GmbH (Germany)

Contact Information

TEVA (Israel)

ATC Code

N02CD03 (Fremanezumab)

Active Substance

Fremanezumab (Rec.INN registered by WHO)

Dosage Form

Ajovy

Solution for subcutaneous administration 150 mg/1 ml: syringes 1.5 ml 1 or 3 pcs.

Dosage Form, Packaging, and Composition

Solution for subcutaneous administration clear or slightly opalescent, from colorless to light yellow.

Excipients: L-histidine – 0.543 mg, L-histidine hydrochloride monohydrate – 2.62 mg, sucrose – 66 mg, disodium edetate dihydrate – 0.136 mg, polysorbate 80 – 0.02% w/v, water for injections – up to 1 ml.

1.5 ml – disposable syringes (1) – blister packs (1) – cardboard packs with first opening control^×*.
1.5 ml – disposable syringes (3) – blister packs (1) – cardboard packs with first opening control^×*.
1.5 ml – disposable autoinjectors (pen-injectors) (1) – blister packs (1) – cardboard packs with first opening control^×*.
5 ml – disposable autoinjectors (pen-injectors) (3) – blister packs (1) – cardboard packs with first opening control^×*.

^× protective stickers may be additionally applied.
* some forms may not be currently available in the Russian Federation.

Clinical-Pharmacological Group

Monoclonal antibody for the preventive treatment of migraine

Pharmacotherapeutic Group

Calcitonin gene-related peptide receptor antagonists

Pharmacological Action

Fremanezumab is a fully humanized monoclonal antibody of the IgG2Δα/κ class that specifically binds to the calcitonin gene-related peptide (CGRP) ligand and blocks the binding of α- and β-isoforms of CGRP to the CGRP receptor.

The exact mechanism of action by which Fremanezumab prevents migraine attacks is unknown, but it is assumed that the beneficial effect is achieved through modulation of the trigeminal system. CGRP concentration increases significantly during a migraine attack and returns to normal after the headache subsides.

Fremanezumab is highly specific for CGRP and does not bind to other closely related members of this peptide family (e.g., amylin, calcitonin, intermedin, and adrenomedullin).

The efficacy of fremanezumab in preventing episodic or chronic migraine attacks was evaluated in two multicenter, randomized, double-blind, placebo-controlled studies of 12 weeks’ duration (Study 1 and Study 2, respectively). All study participant groups were balanced and comparable in terms of demographics and baseline disease characteristics.

Elderly individuals (over 70 years of age), patients using opioids or barbiturates for more than 4 days per month, and patients with a history of myocardial infarction, cerebrovascular, and thromboembolic events were excluded from the studies.

Episodic Migraine

Study 1 included adult patients with a history of episodic migraine (patients with < 15 headache days per month). All patients were randomized to receive subcutaneous injections of 675 mg fremanezumab once every 3 months (n=291), 225 mg fremanezumab once monthly (n=290), or placebo once monthly (n=294) over a 12-week treatment period.

A total of 875 patients (742 women and 133 men) aged 18 to 70 years were randomized in Study 1. The median age of patients was 42 years, 85% were female and 80% were White. The mean number of migraine days at baseline was approximately 9 days per month and was similar across treatment groups. A total of 791 patients completed the 12-week double-blind phase.

The primary endpoint was the mean change from baseline in the monthly number of migraine days over the 12-week treatment period. Secondary endpoints were: the proportion of patients who achieved at least a 50% reduction in the mean number of monthly migraine days (50% responder rate); the mean change from baseline in the subjective MIDAS score of monthly migraine days; and the mean change from baseline in the mean number of days of use of headache attack medications per month.

Monthly (once monthly) and quarterly (once every 3 months) fremanezumab treatment regimens demonstrated statistically significant improvements in efficacy endpoints compared to placebo from the first month and throughout the study period (see Table 1).

Table 1. Key Efficacy Indicators in Study 1 in Patients with Episodic Migraine

CI – confidence interval; MIDAS (Migraine Disability Assessment) – Migraine Disability Assessment Scale; SD – standard deviation.

^a For all endpoints, the mean and CI were calculated using a covariance model that included treatment, sex, region, and presence of baseline preventive therapy (yes/no) as fixed effects, and the corresponding baseline value and disease duration as covariates.

^b To assess the between-group difference, a mixed model for repeated measures was used, which included treatment, sex, region, presence of baseline preventive therapy (yes/no), month, and treatment month as fixed effects, and the corresponding baseline value and disease duration as covariates.

Chronic Migraine

Study 2 included adult patients with a history of chronic migraine (patients with > 15 headache days per month). The baseline headache frequency in patients averaged 21 days per month (with at least moderate severity on 13 days). All patients were randomized to receive subcutaneous injections of an initial dose of 675 mg fremanezumab followed by 225 mg fremanezumab once monthly (n=379), 675 mg fremanezumab once every 3 months (n=376), or placebo once monthly (n=375) over a 12-week treatment period.

A total of 1130 patients (991 women and 139 men) aged 18 to 70 years were randomized in Study 2. The median age of patients was 41 years, 88% were female and 79% were White. A total of 1034 patients completed the 12-week double-blind phase.

The primary endpoint was the mean change from baseline in the monthly number of days with headache of at least moderate severity over the 12-week treatment period. Secondary endpoints were: achieving at least a 50% reduction in the mean number of days with headache of at least moderate severity per month (50% responder rate); the mean change from baseline in the subjective HIT-6 score of monthly migraine days; and the mean change from baseline in the mean number of days of use of headache attack medications.

Both fremanezumab treatment regimens, once monthly and once every 3 months, demonstrated statistically significant improvements in key efficacy parameters compared to placebo from the first month and throughout the study period (see Table 2).

Table 2. Key Efficacy Indicators in Study 1 in Patients with Chronic Migraine

CI – confidence interval; HIT-6 – Headache Impact Test-6; SD – standard deviation.

^a For all endpoints, the mean and CI were calculated using a covariance model that included treatment, sex, region, and presence of baseline preventive therapy (yes/no) as fixed effects, and the corresponding baseline value and disease duration (in years) as covariates.

^b To assess the between-group difference, a mixed model for repeated measures was used, which included treatment, sex, region, presence of baseline preventive therapy (yes/no), month, and treatment month as fixed effects, and the corresponding baseline value and disease duration (in years) as covariates.

Long-term Study

In a long-term study (Study 3) in patients with episodic and chronic migraine receiving the drug at a dose of 225 mg once monthly or 675 mg once every 3 months, the efficacy of fremanezumab was maintained for up to 12 months. A total of 79% of patients completed Study 3.

After 15 months, the monthly frequency of migraine attacks with both dosing regimens collectively decreased from baseline in Studies 1 and 2 by 6.6 days. In the last month of the trial, a 50% response was achieved in 61% of patients who completed Study 3.

No drug safety signals were identified during the 15-month combined treatment period.

Internal and External Factors

The efficacy and safety of fremanezumab were independent of age, sex, race, presence of concomitant preventive drug therapy (beta-blockers, calcium channel blockers/benzocycloheptene derivatives, antidepressants, anticonvulsants), history of migraine treatment with topiramate or onabotulinumtoxin A, and overuse of acute headache medications. Data on the use of fremanezumab in individuals aged 65 years and older are limited (2% of patients).

Difficult-to-Treat Migraine

The efficacy and safety of fremanezumab in patients suffering from both episodic and chronic migraine with documented insufficient response to prior treatment with preventive migraine medications from 2 to 4 therapeutic classes were evaluated in a randomized study (Study 4).

The study consisted of a double-blind, placebo-controlled treatment period followed by an open-label period, both of 12 weeks’ duration.

A total of 838 patients were randomized in Study 4. All patients were randomized to receive subcutaneous injections of an initial dose of 675 mg fremanezumab followed by 225 mg fremanezumab once monthly (n=379), 675 mg fremanezumab once every 3 months (n=376), or placebo once monthly (n=375) over a 12-week treatment period.

The primary endpoint was the mean change from baseline in the monthly number of headache days over the 12-week treatment period.

Secondary endpoints were: achieving at least a 50% reduction in the mean number of days with headache of at least moderate severity per month; and the mean change from baseline in the mean number of days of use of headache attack medications.

Both fremanezumab dosing regimens (once monthly and once every 3 months) had a statistically and clinically significant advantage over placebo in terms of improvement from baseline according to key endpoints. Thus, the results of Study 4 are consistent with the main findings of previous efficacy studies and, furthermore, demonstrate efficacy in difficult-to-treat migraine, including a mean reduction in the monthly number of migraine days of -3.7 days (95% CI from -4.38 to -3.05) in patients taking Fremanezumab once every 3 months, and -4.1 days (95% CI from -4.73 to -3.41) in patients taking Fremanezumab once monthly, compared with -0.6 days (95% CI from -1.25 to 0.07) in patients receiving placebo. A reduction in the monthly number of migraine days of at least 50% was observed in 34% of patients receiving Fremanezumab once every 3 months and in 34% of patients receiving Fremanezumab once monthly compared with 9% of patients receiving placebo (p<0.0001) during the 12-week treatment period. The positive effect of the drug was observed from the first month of the study and persisted throughout the treatment period. No significant adverse events were identified during the 6-month treatment period.

Preclinical Safety Data

Preclinical studies revealed no special hazard for humans based on conventional studies of pharmacological safety, repeat dose toxicity, and reproductive toxicity.

Since Fremanezumab is a monoclonal antibody, studies on genotoxicity or carcinogenicity have not been conducted.

Pharmacokinetics

Absorption

After a single subcutaneous administration at doses of 225 mg and 675 mg, the median time to reach C_max (T_max) of fremanezumab ranges from 5 to 7 days, and the pharmacokinetic parameters are proportional. The absolute bioavailability in the dosage range from 225 mg to 900 mg is from 55% to 66%.

Distribution

When using the drug at a dose of 225 mg subcutaneously once a month and 675 mg subcutaneously once every 3 months, C_ss was observed after approximately 168 days (about 6 months) from the start of treatment. The median accumulation ratio for once-monthly and once-every-3-months dosing is about 2.4 and 1.2, respectively.

V_d after subcutaneous administration at doses of 225 mg, 675 mg, and 900 mg is 3.6 L.

Metabolism

Similar to other monoclonal antibodies, Fremanezumab is broken down by proteolytic enzymes into low molecular weight peptides and amino acids.

Elimination

The total clearance of fremanezumab is about 0.09 L/day, T_1/2 is 30 days. The low molecular weight peptides and amino acids formed during metabolism participate in de novo protein synthesis or are excreted by the kidneys.

Special Populations

As part of a population pharmacokinetic analysis based on data from 2546 patients, the influence of age, race, sex, and body weight on the drug’s efficacy was determined. According to the results obtained, dose adjustment for body weight ranging from 43.5 kg to 131.8 kg is not required.

Data on the exposure-efficacy relationship of fremanezumab in patients with body weight over 132 kg are not available.

Patients with impaired hepatic or renal function. Impaired hepatic or renal function is not expected to affect the pharmacokinetics of fremanezumab. A population pharmacokinetic analysis of pooled data from clinical trials of the drug did not reveal differences in the pharmacokinetics of fremanezumab in patients with mild or moderate hepatic impairment compared to patients with normal liver function (see the “Dosage Regimen” section). Patients with severe hepatic impairment did not participate in the clinical trials of fremanezumab.

Indications

• Preventive treatment of migraine in adults who have 4 or more migraine days per month.

ICD codes

Dosage Regimen

Therapy should be initiated under the guidance of a physician experienced in the diagnosis and treatment of migraine.

The drug is prescribed to patients who have 4 or more migraine days per month.

Two dosing regimens are available

1) Once a month: one pre-filled solution syringe or autoinjector (pen) (225 mg)

Or

2) Once every three months: three pre-filled solution syringes or autoinjectors (pens) (675 mg), administered via three consecutive injections.

The decision on the duration of the treatment course is made by the attending physician.

When switching from one regimen to another, the new dose of the drug should be administered on the next scheduled day, according to the previous therapy regimen.

After initiating therapy with fremanezumab, concomitant preventive migraine treatment may be continued if the physician deems it necessary.

The effectiveness of therapy should be assessed 3 months after its initiation. Any further decision to continue treatment should be made on an individual basis. Subsequently, the need for continued therapy should be regularly evaluated.

Missed Dose

If a dose of Ajovy is missed according to the schedule, it should be administered as soon as possible. Compensating for a missed dose by doubling it is not required.

Special Patient Groups

Elderly patients (over 65 years)

Data on the use of Ajovy in patients aged 65 years and older are limited. Based on the results of population pharmacokinetic analysis, dose adjustment is not required.

Renal and/or hepatic impairment

In patients with mild or moderate renal or hepatic impairment, dose adjustment is not required.

Children

The drug is not recommended for use in patients under 18 years of age, as the safety and efficacy of Ajovy in this patient group have not been established.

Method of Administration

The drug is administered subcutaneously.

Intravenous or intramuscular injections are not permissible.

Ajovy is administered subcutaneously in the abdomen, thigh, or upper arm. Injection sites should be rotated for repeated administration.

The injection of Ajovy can be performed by healthcare professionals, patients, and/or their caregivers. Before use, patients and/or their caregivers should receive appropriate training on the preparation and administration of Ajovy. Patients and/or their caregivers must be informed that they need to read the instructions for medical use and follow them each time they use Ajovy.

Instructions for Use of Ajovy

Instructions for use of Ajovy, solution for subcutaneous injection, 150 mg/ml, in a pre-filled syringe

Read these instructions carefully before using Ajovy.

Important Information

• Each syringe is for single use only.
• Each Ajovy syringe contains 225 mg of fremanezumab. Depending on the dosing regimen prescribed by your doctor, one or three syringes may be required.
• Ajovy is administered subcutaneously. Before use, you must receive appropriate training from your doctor or nurse on how to prepare and administer the Ajovy solution in the subcutaneous injection syringe.
• You should carefully read the instructions for medical use of Ajovy to learn more about the medicine.
• Do not pull the plunger back, as this may break the syringe.
• Do not shake the syringe, as this may affect the operation of the medical device.
• If there are unused syringes left in the carton, immediately put it back in the refrigerator.

Step 1. Preparation for Subcutaneous Injection

a) Make sure you have everything you need for the injection

• One (for a 225 mg dose) or three (for a 675 mg dose) disposable pre-filled Ajovy syringes,
• Alcohol wipe,
• Cotton ball,
• Container for used syringes or sharps waste.

b) Place the supplies on a clean, flat surface.

c) To reduce discomfort during the injection, allow Ajovy to reach room temperature for 30 minutes:

• avoid exposing the syringe to direct sunlight,
• do not heat the syringe using a microwave or any other heat source.

d) Wash your hands with soap and dry them thoroughly with a towel.

e) Inspect the Ajovy syringe, make sure that:

• The label says Ajovy,
• The syringe contains a clear or slightly opalescent solution from colorless to light yellow,
• The presence of small air bubbles in the pre-filled syringe is normal and acceptable.

DO NOT USE the syringe if

• The syringe is damaged,
• The expiration date on the syringe label (and the carton) has passed,
• The solution appears cloudy, has changed color, or contains visible foreign particles.

f) Choose an injection site

Possible areas for self-injectionthe abdominal area (avoid the area approximately 5 cm around the navel), the front of the thighs (the area that is at least 5 cm above the knee and 5 cm below the groin), the back of the upper arm. For injections in hard-to-reach areas (e.g., the back of the upper arm), assistance from another person may be required.

• If the same anatomical area is used for three separate injections (3 separate disposable pre-filled syringes) when administering a 675 mg dose, ensure that the second and third injections are not given in the same injection site used for previous injections.

DO NOT

• Inject into painful areas, reddened skin, areas with hardened skin, lumps, bruises, tattoos, scars, or stretch marks,
• Administer Ajovy into the same site where another medication was injected.

g) Prepare the injection site:

• Clean the injection area with an alcohol wipe. Let the injection area dry for 10 seconds.

Step 2. Technique for Performing the Subcutaneous Injection

a) Remove (pull straight off) the needle cap:

Do not twist the needle cap.

After removing the cap from the disposable syringe needle, do not touch the needle and do not recap the needle to avoid injury or infection.

b) Administer the medicine by performing the following 4 actions

1. Gently pinch at least 2.5 cm of skin in the cleaned injection area between your thumb and index finger to create a fold.

2. Holding the syringe needle at a 45-90 degree angle to the injection site, puncture the skin.

3. When the needle is fully inserted into the skin, press evenly with your thumb on the syringe plunger head.

4. Press slowly and evenly on the plunger head, injecting the entire contents of the syringe into the injection site.

c) Remove the needle by pulling the syringe straight out from the injection site.

d) Gently press a clean cotton ball against the injection site for a few seconds. Do not rub the injection site.

Step 3. Disposal

Place the syringe and associated materials into a container for used syringes or sharps waste. Do not throw away removed needles, the syringe, or the pre-filled syringe with household trash. Ask your doctor or pharmacist how to dispose of the medicine if it is no longer needed. These measures will help protect the environment. Keep syringes and associated materials out of the reach of children.

If you are prescribed a 675 mg dose (3 syringes), to fully administer it, repeat steps from Step 1 e) to Step 3 with the 2nd and 3rd pre-filled syringe.

Instructions for use of Ajovy, solution for subcutaneous injection, 150 mg/ml, in an autoinjector (pen)

Read these instructions carefully before using Ajovy.

Important Information

• Each autoinjector is for single use only.
• Each Ajovy autoinjector contains 225 mg of fremanezumab. Depending on the dosing regimen prescribed by your doctor, one or three autoinjectors may be required.
• Ajovy is administered subcutaneously. Before use, you must receive appropriate training from your doctor or nurse on how to prepare and administer the Ajovy solution in the autoinjector for subcutaneous injections.
• You should carefully read the instructions for medical use of Ajovy to learn more about the medicine.
• Do not shake the autoinjector, as this may affect the operation of the medical device.
• If there are unused autoinjectors left in the carton, immediately put it back in the refrigerator.

Autoinjector (pen) before use

Autoinjector (pen) after use

Step 1. Preparation for Injection

a) Make sure you have everything you need for the injection:

• One (for a 225 mg dose) or three (for a 675 mg dose) disposable pre-filled Ajovy autoinjectors (pens),
• Alcohol wipe,
• Cotton ball,
• Container for used syringes or sharps waste.

b) Place the supplies on a clean, flat surface.

c) To reduce discomfort during the injection, allow Ajovy to reach room temperature for 30 minutes:

• avoid exposing the autoinjector to direct sunlight,
• do not heat the autoinjector using a microwave or any other heat source.

d) Wash your hands with soap and dry them thoroughly with a towel.

e) Inspect the Ajovy autoinjector, make sure that

• The label says Ajovy,
• The medicine in the autoinjector viewing window appears as a clear or slightly opalescent solution from colorless to light yellow,
• The presence of small air bubbles is normal and acceptable.

DO NOT USE the autoinjector if

• The autoinjector is damaged,
• The expiration date on the autoinjector label (and the carton) has passed or the autoinjector has been out of the refrigerator for more than 24 hours;
• The solution appears cloudy, has changed color, or contains visible foreign particles.

f) Choose an injection site

Possible areas for self-injectionthe abdominal area (avoid the area approximately 5 cm around the navel), the front of the thighs (the area that is at least 5 cm above the knee and 5 cm below the groin), the back of the upper arm. For injections in hard-to-reach areas (e.g., the back of the upper arm), assistance from another person may be required.

• If the same anatomical area is used for three separate injections (3 separate autoinjectors) when administering a 675 mg dose, ensure that the second and third injections are not given in the same injection site used for previous injections.

DO NOT

• Inject into painful areas, reddened skin, areas with hardened skin, lumps, bruises, tattoos, scars, or stretch marks,
• Administer Ajovy into the same site where another medication was injected.

g) Prepare the injection site:

• Clean the injection area with an alcohol wipe. Let the injection area dry for 10 seconds.

Step 2. Injection Technique

a) Remove (pull straight off) the needle cap

• Do not twist the needle cap.
• After removing the cap from the autoinjector needle, do not touch the needle and do not recap the needle to avoid injury or infection.
• Do not touch the needle guard area.

b) Administer the medicine by performing the following actions

• Place the autoinjector at a 90° angle to the skin at the injection site

• Press the autoinjector and continue to hold it pressed against the skin for about 30 seconds. Do not stop pressing until the following 3 actions are completed

1. You hear the first “click” (this is the signal that the injection has started, and the blue plunger has begun to move).

2. You hear the second “click” (approximately 15 seconds after the first; the plunger will move to the bottom of the viewing window when the medicine has been administered).

3. Wait another 10 seconds (to ensure the medicine is fully administered).

c) Make sure the blue plunger has filled the viewing window and remove the autoinjector

• After the injection is complete (the blue plunger has filled the viewing window and the gray stopper is visible), remove the autoinjector by pulling it straight up and dispose of it in a sharps container (see Step 3).
• After removing the autoinjector, the needle guard returns to its original position and locks in place, covering the needle.
• Do not put the needle cap back on the autoinjector to avoid injury or infection.

d) Gently press a clean cotton ball against the injection site for a few seconds. Do not rub the injection site. Do not reuse the autoinjector.

Step 3. Disposal

Place the autoinjector and associated materials into a container for used syringes or sharps waste. Do not throw away removed needles, the autoinjector, or the pre-filled autoinjector with household trash. Ask your doctor or pharmacist how to dispose of the medicine if it is no longer needed. These measures will help protect the environment.

Keep autoinjectors and associated materials out of the reach of children.

If you are prescribed a 675 mg dose (3 autoinjectors (pens)), to fully administer it, repeat steps from Step 1 e) to Step 3 with the 2nd and 3rd autoinjector (pen).

Adverse Reactions

The safety of Ajovy was evaluated in more than 2500 migraine patients who received at least one dose of the drug. Thus, the exposure was more than 1900 patient-years. More than 1400 patients had therapy duration of at least 12 months.

Commonly occurring adverse reactions (AR) included injection site reactions [pain (24%), induration (17%), erythema (16%), and pruritus (2%)].

ARs described in clinical and post-marketing studies are listed according to the MedDRA system organ class. ARs are categorized according to the WHO classification: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000); frequency not known (cannot be estimated from the available data).

Description of selected adverse reactions

Injection site reactions The most frequently observed local injection site reactions were pain, induration, and erythema. All local injection site reactions were transient and mostly mild or moderate in severity. Pain, induration, and erythema generally occurred immediately after the injection, whereas pruritus and rash appeared on average after 24 and 48 hours, respectively. All injection site reactions typically resolved within several hours or days. In general, these adverse reactions did not require discontinuation of the medicinal product.

Serious hypersensitivity reactions In rare cases, anaphylactic reactions have been reported. Reactions usually occurred within 24 hours of drug administration, in some cases reactions developed later.

Immunogenicity In placebo-controlled studies, anti-drug antibodies (in low titer) were observed in 0.4% (6 out of 1701) of patients after initiation of treatment with fremanezumab. Neutralizing antibodies were detected in 1 out of 6 patients. After 12 months of treatment, anti-drug antibodies were detected in 2.3% (43 out of 1888) of patients, with 0.95% of patients having neutralizing antibodies. The presence of such antibodies did not affect the safety and efficacy of the medicinal product.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients of the drug;
• Age under 18 years.

Use with caution

Patients with serious cardiovascular diseases (see section “Special Precautions”).

Use in Pregnancy and Lactation

Pregnancy

It is recommended to avoid the use of the drug during pregnancy. Data on the use of Ajovy in pregnant women are limited. Results from preclinical safety pharmacology, repeat-dose toxicity, and reproductive and developmental toxicity studies indicate no direct or indirect adverse effects of the drug on human reproduction.

Since Fremanezumab is a monoclonal antibody, genotoxicity or carcinogenicity studies have not been conducted.

Breast-feeding period

There is no information on the passage of fremanezumab into breast milk, its effects on the breast-fed child, or on milk production. In the first days after birth, human IgG antibodies are excreted in breast milk, but their concentration therein decreases soon after. During this short period of time, a risk to the child cannot be excluded. Subsequently, the use of Ajovy during breast-feeding should be considered only if clinically necessary.

Fertility

There are no data on the effect of fremanezumab on human fertility. Based on results from preclinical studies, treatment with Ajovy is not expected to have a negative impact on fertility.

Use in Hepatic Impairment

No dose adjustment is required in patients with mild or moderate hepatic impairment.

Patients with severe hepatic impairment were not included in the clinical studies of fremanezumab.

Use in Renal Impairment

No dose adjustment is required in patients with mild or moderate renal impairment.

Pediatric Use

The drug is not recommended for use in patients under 18 years of age, as the safety and efficacy of Ajovy in this patient group have not been established.

Geriatric Use

Data on the use of Ajovy in patients aged 65 years and older are limited. Based on the results of a population pharmacokinetic analysis, no dose adjustment is required.

Special Precautions

Serious hypersensitivity reactions

In rare cases, anaphylactic reactions have been observed with the use of fremanezumab. Reactions occurred within 24 hours after drug administration, but in some cases, reactions were observed later.

Patients should be informed about symptoms associated with hypersensitivity reactions. In case of serious hypersensitivity reactions, appropriate therapy should be initiated and treatment with fremanezumab should be discontinued.

Patients with cardiovascular diseases

Patients with significant cardiovascular disease, vascular ischemia, or thrombotic events, such as acute cerebrovascular accident, transient ischemic attacks, deep vein thrombosis, or pulmonary embolism, were excluded from clinical studies. The safety and efficacy of Ajovy in such patients have not been established.

Excipients

One dose (1.5 ml) of Ajovy contains less than 1 mmol sodium (23 mg), that is to say, the drug is essentially sodium-free.

Storage

The drug should be stored in a refrigerator at a temperature between 2°C (35.6°F) and 8°C (46.4°F) in the original package to protect from light. If necessary, the drug may be stored at room temperature between 20°C (68°F) and 25°C (77°F) in the original package for no more than 7 days. After removal from the refrigerator, Ajovy must be used within 7 days or discarded. After storage at room temperature, the drug must not be placed back in the refrigerator.

Do not freeze or shake the drug. Furthermore, do not use the drug if it has been exposed to high temperatures or direct sunlight.

Effect on ability to drive and use machines

Ajovy does not affect the ability to drive and use machines. In case of adverse effects, caution should be exercised.

Overdose

The maximum dose of the drug in clinical studies was 2000 mg administered intravenously. No development of adverse reactions or dose-limiting toxicity was observed.

Treatment The patient should be placed under medical supervision to detect possible adverse reactions. Symptomatic treatment should be administered if necessary.

Drug Interactions

No formal clinical drug interaction studies with fremanezumab have been conducted.

Based on the properties of fremanezumab, pharmacological drug interactions are unlikely. Furthermore, concomitant use of medications taken for the treatment of a migraine attack (especially analgesics, ergot alkaloids, and triptans) and medications for the preventive treatment of migraine did not affect the pharmacokinetics of fremanezumab.

Storage Conditions

The drug should be stored at a temperature between 2°C (35.6°F) and 8°C (46.4°F) in the original package. Do not freeze.

Keep out of reach of children.

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.