Consumer medicine information

Aimovig

Erenumab

BRAND INFORMATION

Brand name

Aimovig

Active ingredient

Erenumab

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Aimovig.

What is in this leaflet

This leaflet answers some common questions about AIMOVIG. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking AIMOVIG against the benefits they expect it will have for you.

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

You can also download the most up to date leaflet from www.novartis.com.au. Those updates may contain important information about the medicine and its use of which you should be aware.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What AIMOVIG is used for

AIMOVIG contains the active substance erenumab. It belongs to a group of medicines called anti CGRP antibodies (CGRP stands for calcitonin gene related peptide).

AIMOVIG works by blocking the activity of the CGRP molecule, which has been linked to migraine.

AIMOVIG is used to treat migraine. It is intended to reduce the number of days each month you have a migraine.

Ask your doctor if you have any questions about why this medicine has been prescribed for you. Your doctor may have prescribed it for another reason.

This medicine is not addictive.

This medicine is available only with a doctor's prescription.

This medicine is not expected to affect your ability to drive a car or operate machinery.

Before you take AIMOVIG

When you must not take it

Do not take AIMOVIG if you have an allergy to:

  • erenumab
  • any of the ingredients listed at the end of this leaflet.

Allergic reactions can happen within minutes, but some may happen more than one week after using AIMOVIG.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin

Do not give this medicine to a child or adolescent under the age of 18 years. Safety and effectiveness in children younger than 18 years have not been studied in this age group.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • problems with your kidneys
  • problems with your liver
  • high blood pressure.

Tell your doctor if you have or ever have had an allergic reaction to latex. The pen used to inject AIMOVIG contains natural rubber latex within the cap.

Tell your doctor if you are pregnant or plan to become pregnant or are breast-feeding. Your doctor can discuss with you the risks and benefits involved.

AIMOVIG has not been studied in pregnant women. It is not known whether AIMOVIG could harm your unborn baby.

It is not known whether AIMOVIG passes into breast milk. Your doctor will help you decide whether you should stop breast feeding or stop taking AIMOVIG.

AIMOVIG contains sodium

AIMOVIG contains less than 1 mmol sodium (23 mg) per dose, this means it is essentially "sodium free" and should not affect a sodium controlled diet.

If you have not told your doctor about any of the above, tell him/her before you start taking AIMOVIG.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including any that you get without a prescription from your pharmacy, supermarket or health food shop.

Tell your doctor if you are taking any medication to prevent migraines.

How to take AIMOVIG

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet. If your doctor has prescribed AIMOVIG with another migraine medicine, follow your doctor's instructions on how to use these medicines together.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

How much to take

Each pen contains 70 mg or 140 mg AIMOVIG. The usual dose of Aimovig is 70 mg once every 4 weeks. Your doctor might also decide you need 140 mg once every 4 weeks. Take Aimovig exactly as instructed by your doctor.

70 mg/mL solution for injection
If your doctor prescribed the 70 mg dose you should have one injection once every 4 weeks in your abdomen, thigh or upper arm. If your doctor prescribed the 140 mg dose you should have two 70 mg injections once every 4 weeks. The second injection must be given immediately after the first.

140 mg/mL solution for injection
If your doctor prescribed the 140 mg dose, you will have one injection (subcutaneous) in your abdomen, thigh, or upper arm.

Make sure that you inject the entire contents of each pen.

How to take it

AIMOVIG is supplied in a pre-filled pen for single use. It is given as an injection under your skin (known as a subcutaneous injection). You or your caregiver can administer the injection into your abdomen, thigh or into the outer area of the upper arm (only if someone else is giving you the injection). Injection sites should be rotated and injections should not be given into areas where the skin is tender, bruised, red or hard.

Your doctor or nurse will give you or your caregiver training in the right way to prepare and inject AIMOVIG. Do not try to inject AIMOVIG until this training has been given.

Instructions for use of Aimovig pre-filled pen

Important: Needle is inside the pen

Single-Use Autoinjector/Pen 70 mg/mL

Single-Use Autoinjector/Pen 140 mg/mL

Step 1: Prepare

Your healthcare provider has prescribed a 70 mg or a 140 mg dose.

For a 70 mg dose, inject one autoinjector of 70 mg/mL.

For a 140 mg dose, inject either two autoinjectors of 70 mg/mL one after the other, or one autoinjector of 140 mg/mL if you were prescribed the 140 mg/mL formulation.

A) Carefully lift the pen(s) out of the carton

To avoid discomfort at the site of injection, leave the pen(s) at room temperature for at least 30 minutes before injecting.

Important:

  • Do not put the pen(s) back in the refrigerator once they have reached room temperature.
  • Do not try to warm the pen(s) by using a heat source such as hot water or microwave.
  • Do not leave the pen(s) in direct sunlight.
  • Do not shake the pen(s).
  • Do not remove the white cap from the pen(s) at this stage.

B) Inspect each pen

Make sure the solution you see in the window is clear and colourless to light yellow.

Important:

  • Do not use the pen if you notice that the solution contains easily visible particles, is cloudy or is distinctly yellow.
  • Do not use the pen if any part of it appears cracked or broken.
  • Do not use the pen if it has been dropped.
  • Do not use the pen if white or orange cap is missing or is not securely attached.
  • Do not use the pen after the expiry date stated on the label.

In all cases described above, use a new pen, and if you are unsure contact your doctor or pharmacist.

C) Gather all materials needed for the injection(s):

Wash your hands thoroughly with soap and water.

On a clean, well-lit work surface, place the:

  • One or two new pen(s)
  • Alcohol wipes
  • Cotton balls or gauze pads
  • Adhesive plasters
  • Sharps disposal container

D) Prepare and clean the injection site(s).

You can use any of the following injection sites:

  • Thigh
  • Stomach area (abdomen) (except for a 5 cm area around the navel)
  • Outer area of upper arm (only if someone else is giving you the injection)

Clean the injection site with an alcohol wipe and let the skin dry.

Choose a different site each time you give yourself an injection. If you need to use the same injection site, just make sure it is not the same spot on that site you used last time.

Important:

  • After you have cleaned the area, do not touch it again before injecting.
  • Do not choose an area where the skin is tender, bruised, red, or hard. Avoid injecting into a raised, thick, red or scaly skin patch or lesion, or areas with scars or stretch marks.

Step 2: Get ready

E) Pull the white or orange cap straight off, only when you are ready to inject. The injection must be administered within 5 minutes. It is normal to see a drop of liquid at the end of the needle or green or yellow safety guard.

Important:

  • Do not remove the white or orange cap from the pen until you are ready to inject.

  • Do not leave the white or orange cap off for more than 5 minutes. This can dry out the medicine.
  • Do not twist or bend the white orange cap.
  • Do not put the white or orange cap back onto the pen once it has been removed.

F) Stretch or pinch the injection site to create a firm surface.

Stretch method

Stretch skin firmly by moving your thumb and fingers in opposite directions, creating an area about five cm wide.

Or

Pinch method

Pinch skin firmly between your thumb and fingers, creating an area about five cm wide.

Important:

Keep skin stretched or pinched while injecting.

Step 3: Inject

G) Keep holding the stretch or pinch. With the white or orange cap off, place the pen on the skin at an angle of 90 degrees.

Important:

Do not touch the purple or grey start button yet.

H) Firmly push the pen down onto the skin until it stops moving.

Important: You must push all the way down but do not touch the purple or grey start button until you are ready to inject.

I) When you are ready to inject, press the purple or grey start button.

You will hear a click.

J) Keep pushing down on the skin. The injection could take about 15 seconds.

Important: Window turns yellow when injection is completed.

Note: After you remove the pen from the skin, the needle will automatically be covered by the green or yellow safety guard.

Important: When you remove the pen, if the window has not turned yellow, or if it looks like the medicine is still injecting, this means you have not received a full dose.

Contact your doctor immediately.

Step 4: Finish

K) Discard the used pen and the white or orange cap.

Put the used pen in a sharps disposal container immediately after use. Talk to your doctor or pharmacist about proper disposal. There may be local regulations for disposal.

Important:

  • Do not reuse the pen.
  • Do not recycle the pen or sharps disposal container, or throw them into household waste.

Always keep the sharps disposal container out of the sight and reach of children.

L) Examine the injection site.

If there is a small sign of blood, press a cotton ball or gauze pad onto the injection site. Do not rub the injection site. Apply an adhesive plaster if needed.

If you have been prescribed a 140 mg dose using two 70 mg/mL pens, a second injection is required. Repeat all steps with the second pen to inject the full 140 mg dose.

When to take it

The usual dose of Aimovig is 70 mg once every 4 weeks. Your doctor might also decide you need 140 mg once every 4 weeks. Take Aimovig exactly as instructed by your doctor. Each pen contains 70 mg or 140 mg AIMOVIG.

How long to take it

Continue taking your medicine for as long as your doctor tells you.

You should see your doctor after you have been using AIMOVIG for 8 to 12 weeks to discuss whether you should keep using AIMOVIG or whether your dose should be changed. You should continue to see your doctor every 3 to 6 months while taking AIMOVIG.

If you forget to take it

Take it as soon as you remember, and then contact your doctor, who will tell you when you should schedule your next dose. Follow the new schedule exactly as your doctor has told you.

Do not take a double dose to make up for the dose that you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice if you think that you or anyone else may have taken too much AIMOVIG. Do this even if there are no signs of discomfort or poisoning.

While you are using AIMOVIG

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking AIMOVIG.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking this medicine.

If you become pregnant while taking this medicine, tell your doctor immediately.

Things you must not do

Do not take AIMOVIG to treat any other complaints unless your doctor tells you to.

Do not give your medicine to anyone else, even if they have the same condition as you.

Do not stop taking your medicine or lower the dosage without checking with your doctor.

Do not stop using Aimovig without talking to your doctor first. Your symptoms may return if you stop the treatment.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking AIMOVIG.

This medicine helps most people with migraine, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical attention if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • constipation
  • itching
  • muscle spasms
  • injection site reactions, such as pain, redness and/or swelling where the injection is given
  • hair loss
  • mouth or lip sores.

Tell your doctor as soon as possible if you notice:

  • allergic reactions such as rash or swelling, or sometimes difficulty breathing.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also occur in some people. Some side effects may not give you any symptoms and can only be found when tests are done. For example, the development or worsening of high blood pressure.

After using AIMOVIG

Storage

Keep the pen in the outer carton until it is time to take it. If you take the pen out of the carton it may not keep well.

Keep pens in a refrigerator (2°C - 8°C). Do not freeze. Do not shake. After AIMOVIG has been taken out of the refrigerator, it must be kept at room temperature (up to 30°C) in the outer carton box and must be used within 14 days. Do not put AIMOVIG back in the refrigerator after it has reached room temperature.

Do not store AIMOVIG or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Do not use this medicine after the expiry date which is stated on the label and carton after EXP. The expiry date refers to the last day of that month.

Do not use this medicine if you notice that the solution contains easily visible particles, is cloudy or is distinctly yellow.

Disposal

AIMOVIG pen is for single use only.

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Do not throw away any medicines via wastewater or household waste.

Product description

What it looks like

AIMOVIG is a solution which is clear to opalescent, colourless to light yellow, and practically free from particles. Do not use the solution if you notice that it contains easily visible particles, is cloudy or is distinctly yellow.

Ingredients

AIMOVIG contains 70 mg or 140 mg of erenumab as the active ingredient.

It also contains the following inactive ingredients:

  • Sucrose
  • polysorbate 80
  • sodium hydroxide
  • glacial acetic acid
  • water for injections.

This medicine does not contain lactose, gluten, tartrazine or any other azo dyes.

This product contains natural rubber latex within the needle cap.

Sponsor

AIMOVIG is supplied in Australia by:

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone 1 800 671 203
Web site: www.novartis.com.au

® = Registered Trademark

© Copyright

This leaflet was prepared in May 2021.

AIMOVIG 70 mg solution of injection in pre-filled pen AUST R 289959

AIMOVIG 140 mg solution for injection in pre-filled pen AUST R 309205

*Not all presentations marketed.

(aimpen250521c.doc based on PI aim250521i.doc)

Published by MIMS July 2021

BRAND INFORMATION

Brand name

Aimovig

Active ingredient

Erenumab

Schedule

S4

 

1 Name of Medicine

The active ingredient of Aimovig is erenumab.

2 Qualitative and Quantitative Composition

Aimovig 70 mg/mL contains 70 mg of erenumab in 1.0 mL.
Aimovig 140 mg/mL contains 140 mg of erenumab in 1.0 mL.
Aimovig is a human immunoglobulin G2 (IgG2) monoclonal antibody that has high affinity binding to the CGRP receptor. Aimovig is composed of 2 heavy chains, each containing 456 amino acids and 2 light chains of the lambda subclass, each containing 216 amino acids.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Solution for injection, for subcutaneous use.
Aimovig is a sterile, preservative-free solution, clear to opalescent; colourless to yellowish solution, practically free from particles.

4 Clinical Particulars

4.1 Therapeutic Indications

Aimovig is indicated for prophylaxis of migraine in adults.

4.2 Dose and Method of Administration

Dosage.

Aimovig should be initiated under the guidance of a neurologist or specialist in the management of migraine.
The recommended dose of Aimovig is 70 mg injected subcutaneously once every 4 weeks. Some patients may benefit from a dosage of 140 mg injected subcutaneously once every 4 weeks.
Treatment response should be evaluated by the prescriber after 8-12 weeks as recommended by the current Australian treatment guideline.
If Aimovig dose is missed, administer as soon as possible. Thereafter, Aimovig can be scheduled monthly from the date of the last dose.
The need for treatment continuation should be re-evaluated within regular intervals of 3-6 months as recommended by the current treatment guideline.
Efficacy and safety of erenumab in patients has not been assessed in patients with fewer than 4 migraine days per month.
Efficacy and safety of concomitant administration of Aimovig with other prophylactic treatments for migraine was not formally evaluated, although concomitant use of prophylactic medication was allowed in a subset of patients in the pivotal study for episodic migraine.

Method of administration.

Aimovig is administered subcutaneously as a single injection of the 70 mg or 140 mg dose.
Aimovig is intended for patient self-administration.
Administration should be performed by an individual who has been trained to administer the product.
For detailed instructions on storage, handling and administration, follow the directions provided in the "Instructions for Use" available in the package leaflet.

Important administration instructions.

Visually inspect Aimovig for particles and discoloration. Aimovig is a clear to opalescent, colourless to light yellow solution. Do not use if the solution is cloudy or discoloured or contains flakes or particles.
Administer Aimovig in the abdomen, thigh, or upper arm subcutaneously. If you want to use the same injection site, make sure it is not the same spot you used for a previous injection. Do not inject into areas where the skin is tender, bruised, red, or hard.
Both prefilled syringe and prefilled pen are for single use in one patient only and designed to deliver the entire contents with no residual content remaining. Discard any residue.
The needle cover of the Aimovig prefilled syringe and pen contain dry natural rubber, which may cause allergic reactions in individuals sensitive to latex.
Prior to subcutaneous administration, allow Aimovig to sit at room temperature for at least 30 minutes and protect from direct sunlight. Do not warm by using a heat source such as hot water or microwave.

4.3 Contraindications

Aimovig is contraindicated in patients with hypersensitivity to erenumab or to any of the excipients (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

4.4 Special Warnings and Precautions for Use

Hypersensitivity reactions.

Hypersensitivity reactions (some of which were serious), including rash, angioedema, and anaphylactoid reactions, have been reported with Aimovig in post-marketing experience. These reactions may occur within minutes, although some may occur more than one week after treatment. If a serious or severe hypersensitivity reaction occurs, discontinue administration of Aimovig and initiate appropriate therapy (see Section 4.3 Contraindications).

Constipation with serious complications.

Constipation with serious complications has been reported following the use of Aimovig in the post-marketing 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. Many of the cases of constipation with serious complications were reported for patients who have a history of constipation or concurrently use medications associated with decreased gastrointestinal motility. Constipation was one of the most common (up to 3%) adverse reactions reported in clinical studies (see Section 4.8 Adverse Effects (Undesirable Effects)).
Monitor patients treated with Aimovig for severe constipation and manage as clinically appropriate. 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.

Hypertension.

Development of hypertension and worsening of pre-existing hypertension have been reported following the use of Aimovig in the post-marketing setting. Many of the patients had pre-existing hypertension or risk factors for hypertension. There were cases requiring pharmacological treatment and, in some cases, hospitalisation. 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.

Traceability.

In order to improve the traceability of biological medicinal products, the name and batch number of the administered medicinal product should be clearly recorded.

Use in hepatic impairment.

No clinical studies have been performed in patients with hepatic impairment. Erenumab, as a human monoclonal antibody, is not metabolised by cytochrome P450 enzymes and hepatic clearance is not a major clearance pathway for erenumab.

Use in renal impairment.

No dose adjustment is necessary in patients with mild to moderate renal impairment. 57 patients with moderate renal impairment have been studied. Population pharmacokinetic analysis of integrated data from the Aimovig clinical trials did not reveal a difference in the pharmacokinetics of erenumab in patients with mild or moderate renal impairment relative to those with normal renal function. Patients with severe renal impairment (eGFR < 30 mL/min/1.73 m2) have not been studied.

Use in the elderly.

Clinical studies of Aimovig did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. No dose adjustment is required as the pharmacokinetics of erenumab are not affected by age.

Paediatric use.

The safety and effectiveness of Aimovig has not been studied in paediatric patients.

Effects on laboratory tests.

Interference of Aimovig with laboratory and/or diagnostic tests has not been studied.

4.5 Interactions with Other Medicines and Other Forms of Interactions

In an open-label, pharmacokinetic drug interaction study of Aimovig and a combined oral contraceptive in healthy female subjects, erenumab (140 mg subcutaneous [SC], single-dose) did not affect the pharmacokinetics of a combined oral contraceptive containing ethinylestradiol and norgestimate.
In a randomised, double-blind, placebo-controlled study in healthy volunteers, concomitant administration of erenumab (140 mg intravenous [IV], single-dose) with sumatriptan had no effect on resting blood pressure compared with sumatriptan alone. Aimovig had no effect on the pharmacokinetics of sumatriptan.
Erenumab is not metabolised by cytochrome P450 enzymes and is unlikely to cause marked changes in pro-inflammatory cytokines that may impact cytochrome P450 enzyme expression or activity. As a result, interactions with concomitant medications that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data are available on the effect of Aimovig on human fertility. However, there were no adverse effects on surrogate markers of fertility (anatomic pathology or histopathology changes in reproductive organs) in the chronic toxicology study in sexually mature monkeys subcutaneously administered Aimovig at dose levels up to 150 mg/kg twice weekly for 6 months, at systemic exposures up to 283 or 123-fold higher than the clinical dose of 70 mg or 140 mg once monthly, respectively, based on serum AUC.
(Category B1)
There are no adequate and well controlled studies on the use of Aimovig in pregnant women. In a cynomolgus monkey reproduction study, there were no effects on pregnancy, embryo-fetal or post-natal development (up to 6 months age) when erenumab was dosed throughout pregnancy at exposure levels 40 or 17-fold higher than those achieved in patients receiving erenumab at the 70 or 140 mg once monthly dosing regimen, respectively based on area under the concentration curve (AUC). Measurable erenumab serum concentrations were observed in the infant monkeys at birth, confirming that erenumab, like other IgG antibodies, crosses the placental barrier.
Animal studies are not always predictive of human response and therefore, it is not known whether Aimovig can cause fetal harm when administered to a pregnant woman. Aimovig should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
 It is not known whether Aimovig is present in human milk. There are no data on the effects of Aimovig on the breastfed child or the effects of Aimovig on milk production. Because drugs are excreted in human milk and because of the potential for adverse effects in nursing infants from Aimovig, a decision should be made whether to discontinue nursing or discontinue Aimovig, taking into account the potential benefit of Aimovig to the mother and the potential benefit of breast feeding to the infant.

4.7 Effects on Ability to Drive and Use Machines

Aimovig is expected to have no influence on the ability to drive and use machines.

4.8 Adverse Effects (Undesirable Effects)

Summary of the safety profile.

Data from two phase 3 and two phase 2 clinical studies in migraine were pooled to evaluate the safety of Aimovig in comparison to placebo up to 12 weeks after treatment initiation.
There were a total of 2656 patients (1613 Aimovig and 1043 placebo) in these studies. Of these, 893 subjects received 70 mg dose of Aimovig and 507 subjects received 140 mg dose of Aimovig.
The overall safety population for including ongoing open label extension phase with Aimovig includes 2537 patients (3040.2 patient years) who received at least one dose of Aimovig: 2280 patients were exposed for at least 6 months and 1320 patients were exposed for at least 12 months, and 217 patients were exposed through 5 years. The overall safety profile of Aimovig remained consistent through 5 years of long-term open-label treatment.

Tabulated summary of adverse reactions.

Table 1 summarises all treatment-emergent adverse events which were reported by ≥ 1% and Table 2 summarises all adverse reactions that occurred in Aimovig-treated patients during the 12-week placebo-controlled period of the pooled trials. Most Adverse Drug Reactions were mild or moderate in severity.
The incidence of severe adverse events was 1.0% for Aimovig 140 mg and 1.5% for placebo. The incidence of discontinuation due to adverse events was 2.0% for Aimovig 140 mg and 1.0% for placebo.
In the integrated 12-week placebo controlled period of studies, majority of all AEs, 93.1% in the Aimovig 140 mg group and 93.5% in the placebo group, respectively were grade 1 (mild) or 2 (moderate) in severity and were balanced across the groups. A limited number of grade ≥ 3 (severe) adverse events were reported. None of common adverse events were grade 4 (life-threatening) or grade 5 (fatal). Subject incidence rates of adverse events in the Cardiac disorders SOC was 1.2% in the placebo group and 1.4% in the Aimovig 140 mg group. There was no evidence of Aimovig related adverse effects on cardiovascular system.
While the data are limited for a comprehensive assessment of withdrawal and rebound effects, there is no evidence of such an effect based on review of migraine adverse events.
Review of adverse events open-label extension/active treatment period combined over a minimum period of 1 year did not reveal any signals or trends that would suggest a potential safety concern with long-term exposure to Aimovig.

Description of selected adverse reactions.

Injection site reactions.

In the integrated 12-week placebo controlled period of studies, in subjects treated with Aimovig the most frequent injection site reactions were injection site pain, injection site erythema, and injection site pruritus. A majority of injection site reactions were grade 1 (mild) in severity. In the healthy volunteer study, injection site pain was transient and typically subsided within 1 hour after administration. One subject treated with Aimovig 70 mg SC discontinued due to injection site rash and no subject treated with Aimovig 140 mg SC discontinued due to injection site reactions in the 12-week placebo-controlled period of studies.

Constipation.

In the integrated 12-week placebo-controlled period of studies, 28 cases of constipation were reported out of 1400 Aimovig-treated patients. All were mild or moderate severity. A majority of the cases (23) had onset within one month after the first dose; however, some patients also presented with constipation later on in treatment. In most cases (18), constipation resolved within 3 months. All but one case continued treatment.

Post-marketing experience.

Immune system disorders.

Hypersensitivity reactions including rash, angioedema and anaphylactoid reactions (see Section 4.4 Special Warnings and Precautions for Use).

Gastrointestinal disorders.

Constipation with serious complications (see Section 4.4 Special Warnings and Precautions for Use).
Oral sores, e.g. stomatitis, mouth ulceration, oral mucosal blistering.

Skin and subcutaneous tissue disorders.

Alopecia.
Rash, e.g. rash papular, exfoliative rash, rash erythematous, urticaria, blister.

Vascular disorders.

Hypertension (see Section 4.4 Special Warnings and Precautions for Use).

Immunogenicity.

As with all therapeutic proteins, there is potential for immunogenicity. The immunogenicity of Aimovig has been evaluated using an immunoassay for the detection of binding anti-erenumab antibodies. For patients whose sera tested positive in the screening immunoassay, an in vitro biological assay was performed to detect neutralising antibodies.
During the double-blind treatment phase of the four migraine prophylaxis efficacy studies, [20120178, 20120295, 20120296 and 20120297], the incidence of anti-erenumab antibody development during the double-blind treatment phase was 6.3% (56/884) among subjects receiving the 70 mg dose of Aimovig (3 of whom had in vitro neutralising activity) and 2.6% (13/504) among subjects receiving the 140 mg dose of Aimovig (none of whom had in vitro neutralising activity). The mean trough levels of erenumab at week 12 were 40% lower among anti-erenumab antibody-positive subjects than among antibody-negative subjects. Including overall data from the 4 studies through the open-label extension, the incidence of anti-erenumab antibody development was 8.0% (185/2303) among patients who only received 70 mg or 140 mg of Aimovig throughout the entire study (8 of whom had in vitro neutralizing activity). There was no impact of anti-erenumab antibody development on efficacy or safety of erenumab.
The incidence of anti-drug antibodies (ADAs) is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody (including neutralising antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to erenumab with the incidence of antibodies to other products may be misleading.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

There is no experience with overdose in clinical trials with Aimovig. Doses up to 280 mg SC have been administered in clinical trials with no evidence of dose limiting toxicity.
In the event of an overdose, the patient should be treated symptomatically and supportive measures instituted as required.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Pharmacokinetic group.

Nervous system, antimigraine preparations: calcitonin gene-related (CGRP) antagonists, ATC code NO2CD01.

5.1 Pharmacodynamic Properties

Mechanism of action.

Erenumab is a human monoclonal antagonist antibody against the CGRP receptor with no significant pharmacological activity at adrenomedullin, calcitonin, and amylin receptors and lacks agonist activity at the CGRP receptor.
CGRP is a neuropeptide that modulates nociceptive signalling and a vasodilator that has been associated with migraine pathophysiology. In contrast with other neuropeptides, CGRP levels have been shown to increase significantly during migraine and return to normal with headache relief. Intravenous infusion of CGRP induces migraine-like headache in patients suggesting that CGRP may play a causal role in migraine.
CGRP receptor is located at sites that are relevant to migraine pathophysiology. Erenumab potently and specifically competes with the binding of CGRP and inhibits its function at the CGRP receptor.

Pharmacodynamics.

In a randomised, double-blind, placebo-controlled study (20140254) to evaluate the effect of Aimovig (140 mg IV, single dose) in patients with stable angina, Aimovig did not decrease exercise duration during a treadmill test compared to placebo.
A benefit of treatment with erenumab was seen within 4 weeks of commencing treatment.

Clinical trials.

Aimovig was evaluated for prophylaxis of migraine in two pivotal studies across the spectrum of episodic and chronic migraine. Both studies enrolled patients with a history of migraine, with or without aura according to the International Classification of Headache Disorders (ICHD-III) diagnostic criteria.
Excluded from the study were migraine patients with myocardial infarction, stroke, transient ischaemic attacks, unstable angina, coronary artery bypass surgery or other revascularisation procedures within 12 months prior to screening.
Aimovig treatment demonstrated statistically significant and clinically meaningful improvements from baseline compared to placebo for key efficacy outcomes.
Chronic migraine.

Study 20120295.

Aimovig was evaluated for prophylaxis of chronic migraine in a randomised, multi centre, 12 week, placebo controlled, double blind study. A total of 667 patients with a history of migraine with or without aura (≥ 15 headache days per month with ≥ 8 migraine days per month) were randomised to receive placebo (n = 286), Aimovig 70 mg (n = 191) or Aimovig 140 mg (n = 190) subcutaneous injections every 4 weeks for 12 weeks. Randomisation was stratified by region (North America vs. other) and the presence of acute medication overuse (present in 41% of overall patients) excluding patients with opioid overuse. The mean migraine frequency at baseline was approximately 18 migraine days per month and was similar across treatment groups. Patients were allowed to use acute headache treatments including triptans, ergotamine derivatives and NSAIDs during the study.
Patients had a median age of 43 years (range: 18 - 66 years), 83% were female and 94% were White. Patients could have failed (i.e. no therapeutic response) up to three previous prophylactic treatment categories due to lack of efficacy, while there was no limit to the number of previous failures for poor tolerability. Overall, in this study population, 68% had failed one or more previous prophylactic treatments due to lack of efficacy or poor tolerability, and 49% had failed two or more previous prophylactic treatments due to lack of efficacy or poor tolerability. In addition to excluding patients with opioid overuse, the study excluded patients with concurrent use of migraine prophylactic treatments. A total of 182 (96%) patients in the Aimovig 140 mg group, 184 (96%) patients in the Aimovig 70 mg group and 265 (93%) patients in the placebo arm completed the study (completed week 12 assessment). Of the 23 (3.4%) patients who discontinued treatment, 2 patients in the Aimovig 140 mg group, none of the patients in the Aimovig 70 mg group and 2 patients in the placebo group discontinued due to adverse events.
The primary outcome measure was the change from baseline at month 3 in monthly migraine days. Secondary outcome measures included the achievement of at least 50% reduction in monthly migraine days from baseline (≥ 50% responders), change from baseline in monthly acute migraine-specific medication days, and change from baseline in cumulative monthly headache hours. Other than for cumulative monthly headache hours, Aimovig treatment demonstrated statistically significant and clinically meaningful improvements from baseline at month 3 compared to placebo for efficacy outcomes as summarised in Figure 1 and Table 3. Reduction in mean monthly migraine days from placebo was observed in a monthly analysis from month 1 and in a follow-up weekly analysis an onset of Aimovig effect was seen from the first week of administration.
The mean difference from placebo in the number of migraine days per month for Aimovig 140 mg after 12 weeks of treatment was 2.45 days on a background of 18 migraine days per month. No comparisons between the 70 mg and 140 mg Aimovig dose regimens were performed.
Based on a pre-specified analysis, Aimovig was efficacious in patients who had previously failed migraine prophylactic treatments due to lack of efficacy or intolerance and in patients with a history of medication overuse.
In general, the efficacy of Aimovig across subgroups in this study were robust and comparable to the general population.
In the open label extension of Study 1 patients received 70 mg and/or 140 mg Aimovig. 74.1% of patients completed the 52 week extension. Pooled across the two doses, a reduction of 9.3 MMD was observed after 52 weeks relative to core study baseline. 59% of patients completing the study achieved a 50% response in the last month of the study.
Episodic migraine.

Study 20120296.

Study 2 was a randomised, multi centre, 24 week, placebo controlled, double blind study evaluating Aimovig for prophylaxis of episodic migraine. A total of 955 patients with history of migraine with or without aura for a duration of ≥ 12 months and 4-14 migraine days per month were randomised to receive either Aimovig 140 mg (n = 319), Aimovig 70 mg (n = 317) or placebo (n = 319) by subcutaneous injection every 4 weeks for 6 months. Randomisation was stratified by use of prophylactic medications (concomitant, prior use or no prior use) and region (North America vs. other). The mean migraine frequency at baseline was approximately 8 migraine days per month and was similar across treatment groups. Patients were allowed to use acute headache treatments including triptans, ergotamine derivatives and NSAIDs during the study. Concomitant use of prophylactic medication was allowed in a subset of patients. 10 patients (3.1%) in the placebo group and 8 patients (2.5%) in the 140 mg group received concomitant prophylactic medication.
Patients had a median age of 42 years (range: 18-65 years), 85% were female and 89% were White. Patients could have failed to respond up to two previous prophylactic treatments. The study excluded patients with medication overuse. Overall, 865 (90.6%) patients completed the double-blind phase, including 294 (92.2%) patients in the Aimovig 140 mg group, 287 (90.5%) patients in the Aimovig 70 mg group and 284 (89.0%) patients in the placebo arm completed the double-blind phase. Of the 87 (9.1%) patients who discontinued treatment, 7 patients in the 70 mg Aimovig group, 6 patients in the 140 mg Aimovig group and 7 patients in the placebo group discontinued due to adverse events.
The primary outcome measure was the change from baseline during months 4-6 in monthly migraine days. Secondary outcome measures included the achievement of a at least 50% reduction in mean monthly migraine days from baseline (≥ 50% responders), change from baseline in mean monthly acute migraine specific medication days and change from baseline in the 2 Migraine Physical Function Impact Diary (MPFID) domains scores: physical impairment (PI) and impact on everyday activities (EA). 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.
Aimovig treatment demonstrated statistically significant and clinically meaningful improvements from baseline during months 4-6 compared to placebo for efficacy outcomes as summarised in Figure 2 and Table 4. Differences from placebo were observed as early as month 1.
The mean difference from placebo in the number of migraine days per month for Aimovig 140 mg after 4-6 months of treatment was 1.84 days per month on a background of 8 migraine days per month. No comparisons between the 70 mg and 140 mg Aimovig dose regimens were performed.
Based on a pre-specified analysis, Aimovig 140 mg and 70 mg was efficacious in patients who had previously failed migraine prophylactic treatments due to lack of efficacy or intolerance.
In patients failing one or more prophylactic pharmacotherapies the treatment difference for the reduction of MMD observed between erenumab 140 mg and placebo was 2.5 (95% CI: 3.4, 1.7) and between erenumab 70 mg and placebo 2.0 (95% CI: 2.8, 1.2). There was also a higher proportion of subjects treated with erenumab who achieved at least 50% reduction of MMD compared to placebo (39.7% for 140 mg and 38.6% for 70 mg, with an odds ratio of 3.1 [95% CI: 1.7, 5.5] and 2.9 [95% CI: 1.6, 5.3], respectively).
In general, the efficacy of Aimovig across subgroups in this study were robust and comparable to the general population.
Open label extension studies suggest that patients remaining on treatment continue to benefit. Withdrawal effects were not seen.

Study 20120178.

Study 20120178 was a phase 2, randomised, multi-centre, 12-week, double-blind, placebo-controlled, study followed by a 256-week, open-label treatment phase evaluating Aimovig for prophylaxis of episodic migraine. In the double-blind treatment phase, a total of 483 patients were randomized to receive placebo, Aimovig 7 mg, 21 mg or 70 mg monthly, and 383 patients continued into the open-label treatment phase initially receiving Aimovig 70 mg (median exposure: 2.0 years), of which 250 patients increased their dose to 140 mg (median exposure: 2.7 years). Among those 250 patients, 214 (85.6%) patients completed the open-label treatment phase. Out of the 383 patients who entered the 256-week, open-label treatment phase, the most common reasons for discontinuing Aimovig were patient request (84 patients, 21.9%), adverse events (19 patients, 5.0%), and lost to follow-up (14 patients, 3.7%).
Patients who entered the open-label treatment phase had a median age of 43 years (range: 18 - 60 years) at study baseline, 79% were female, and 92% were white. Baseline disease characteristics were consistent across the prior placebo and Aimovig treatment groups.
The long-term efficacy results are summarized for patients who increased their dose to 140 mg (Table 5).

5.2 Pharmacokinetic Properties

Erenumab exhibits non-linear kinetics as a result of binding to CGRP receptor. Subcutaneous administration of a 70 mg and 140 mg (2 x 70 mg) dose in healthy volunteers resulted in a Cmax mean (standard deviation [SD]) of 6.1 (2.1) microgram/mL and 15.8 (4.8) microgram/mL respectively and AUClast mean (SD) of 159 (58) day*microgram/mL and 505 (139) day*microgram/mL.
Less than 2-fold accumulation was observed in trough serum concentrations (Cmin [SD] 5.7 [3.1] and 6.2 [2.9] microgram/mL for episodic and chronic migraine subjects, respectively following 70 mg doses; Cmin [SD] 12.8 [6.53] and 14.9 [6.45] microgram/mL for episodic and chronic migraine subjects, respectively following 140 mg doses).
Serum trough concentrations approached steady state by 12 weeks of dosing. The effective half-life of Aimovig is 28 days.

Absorption.

Following a single subcutaneous dose of 70 mg and 140 mg Aimovig administered to healthy adults, median peak serum concentrations were attained in approximately 6 days, and estimated absolute bioavailability was 82%.

Distribution.

Volume distribution at steady state (7600 mL) suggested limited tissue distribution outside of plasma.

Metabolism and excretion.

Two elimination phases were observed for Aimovig. At low concentrations, the elimination is predominantly through saturable binding to target (CGRP-R), while at higher concentrations the elimination of Aimovig is largely through a non-specific, non-saturable proteolytic pathway.

Specific populations.

The pharmacokinetics of erenumab were not affected by age, gender, race, migraine subtype (episodic or chronic migraine), or creatinine clearance, across all approved populations based on population pharmacokinetics (PK) analysis.

5.3 Preclinical Safety Data

Genotoxicity.

The mutagenic potential of Aimovig has not been evaluated; however, monoclonal antibodies are not expected to alter DNA or chromosomes.

Carcinogenicity.

Carcinogenicity studies have not been conducted with Aimovig. A comprehensive carcinogenicity assessment based on non-clinical and clinical data and literature did not identify any carcinogenic risk associated with the mechanism of action of Aimovig blocking the receptor for CGRP.

6 Pharmaceutical Particulars

6.1 List of Excipients

70 mg per mL prefilled syringe, prefilled autoinjector/pen: Sucrose: 73 mg/7.3% (w/v); NF, PhEur, JP; Glacial acetic acid: 1.5 mg/25 mM; USP, PhEur, JP; Polysorbate 80: 0.10 mg/0.010% (w/v); NF, PhEur, JP; Water for injection; Sodium hydroxide to pH of 5.2; NF, PhEur, JP.
140 mg per mL prefilled syringe, prefilled autoinjector: Sucrose: 65 mg/6.5% (w/v); NF, PhEur, JP; Glacial acetic acid: 2.0 mg/34 mM; USP, PhEur, JP; Polysorbate 80: 0.10 mg/0.010% (w/v); NF, PhEur, JP; Water for injection; Sodium hydroxide to pH of 5.2; NF, PhEur, JP.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

36 months at 2°C to 8°C.

6.4 Special Precautions for Storage

Store refrigerated at 2°C to 8°C in the original carton to protect from light until time of use.
If removed from the refrigerator, Aimovig should be kept at controlled room temperature (up to 30°C) 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.

6.5 Nature and Contents of Container

Aimovig is provided as:
Carton of two 70 mg/mL (140 mg dose) (injection) prefilled syringe with Type 1 glass syringe and stainless-steel needle.
Carton of one (70 mg dose), two or six (multipack of 3x2) 70 mg/mL (140 mg dose) (injection) prefilled pen SureClick autoinjector with Type 1 glass syringe and stainless-steel needle.
Carton of one 140 mg/mL (injection) prefilled syringe with Type 1 glass syringe and stainless-steel needle.
Carton of one 140 mg/mL (injection) prefilled SureClick autoinjector with Type 1 glass syringe and stainless-steel needle.
Not all pack sizes or presentations may be marketed.
The needle shield within the white or orange cap of the prefilled autoinjector and the gray needle cap of the prefilled syringe contain dry natural rubber (a derivative of latex).

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical name.

Immunoglobulin G2-lambda, anti-(human calcitonin gene-related peptide type 1 receptor (CGRP type 1 receptor; calcitonin receptor-like receptor); human monoclonal antibody.

CAS number.

1582205-90-0.

Molecular formula.

C6472H9964N1728O2018S50 (peptide).

Molecular weight.

Aimovig has an approximate molecular weight (MW) of 150 kDa.

7 Medicine Schedule (Poisons Standard)

Schedule 4 - Prescription medicine.

Summary Table of Changes