Does Ajovy Help Migraine?

Does Ajovy Help Migraine?

Ajovy (fremanezumab) is a new Calcitonin Gene-Related Peptide (CBRP) for treating migraine.  The migraine process generates three neurochemicals, Neurokinan A, Substance P, and CGRP.  These neurochemicals are released by the ganglia of the trigeminal nerve and cerebral arteries.  They inflame the trigeminal nerve, the cerebral arteries, and the thalamus.  They also cause the cerebral arteries to dilate.  The thalamus is the “pain center” of the brain and only migraine patients have inflammation of the thalamus like migraine does.  Triptans, if taken early in the migraine process, 20-40 minutes after headache onset, block the release of these inflammatory neurochemicals and are the best drugs currently for acute therapy for migraine.

Research involving cannulating the jugular vein and sampling chemicals in the blood as it leaves the brain has revealed that these neurochemicals are released by the migraine process.  After migraine starts there is an increase in the 3 inflammatory neuropeptides, and they go to the liver and then out of the body to the toilet.  Ajovy blocks the activation of CGRP and is a new drug for migraine prevention.  None of the older preventive drugs for migraine enter into the migraine process and work like this.

The Migraine Timing Cycle

The Migraine Timing Cycle

The picture above is the Migraine Timing Cycle and stage 2 shows the release of CGRP.

Does Ajovy Help Migraine?  Yes, the FDA released Ajovy for use in the United States in August 2018 and it has had grand success for migraine patients.  But perhaps more interestingly, it is one of the first drugs recently developed specifically for migraine prevention. Three of these drugs have now been released.  Ajovy is given as a subcutaneous needle injection either in the top of the thigh or near the umbilicus in the abdomen.

Related questions.

How is Ajovy administered?  It is given as a 225 mg subcutaneous injection in the anterior leg or 2 inches from the umbilicus once a month, or as three times the dose-675 mg every 3 months.

Give the shot here

Give the shot here

What kind of injector is used for Ajovy?  Ajovy comes in a prefilled syringe and should be disposed in a safe sharps container after injection.

Ajovy syringe

Ajovy syringe


Are there any special precautions with using Ajovy?  Ajovy should be stored in a refrigerator in its original carton to protect from light.  The syringe should be left at room temperature 30 minutes before injection.  The thigh or abdomen should be cleaned with an alcohol sponge before injection.

Does Ajovy interact with other drugs?  Most modern drugs are made from the dirt or plants in the world and then are processed by drug companies and used to treat a specific illness.  For instance, penicillin is a mold that accidentally dropped on an agar plate Fleming had put on his window ledge. It was found to kill bacteria and later manufactured and sold to treat bacterial illnesses.  Penicillin has 10 different drug contraindications.  This means that penicillin should not be used with those listed drugs.  However, Ajovy can be used with any drug and has no drug to drug contraindication.

Ajovy is made by DNA polymerization and then injected in the body.  CGRP drugs are made by DNA polymerization, a lab process of spinning out strands of DNA.  This is a completely novel method of drug production and safe regarding use with other existing drugs.

Plays well with others.

Plays well with others.


What are the side effects from taking Ajovy?  Serious side effects are hypersensitivity reaction; common side effects are injection site reaction and muscle cramps or spasms.  Usual side effects are not very significant.

Select Safety Information.  Ajovy may cause allergic reactions, such as itching, rash, hives, and trouble breathing. Allergic reactions can happen a month after using Ajovy.  Users are instructed to contact their healthcare provider or get emergency medical help right away if they experience any of the following symptoms, which may be part of an allergic reaction:  swelling of face, mouth, tongue, or throat, trouble breathing

Serious side effects are very rare and the common side effects are not very bad.  The injection site reaction is like the small bruise one gets following getting blood drawn in your arm for lab studies.

Instructions for using Ajovy are online at

What are the benefits from using Ajovy?  Ajovy has a half-life of 31 days.  Patients with a mean baseline of 12.8 headache days of at least moderate severity per month experienced 4.6 fewer headache days per month, on average, with monthly dosing (vs 2.5 days with placebo).

Patients with a mean baseline of 13.2 headache days of at least moderate severity per month experienced fewer headache days per month, on average, with quarterly dosing (vs 2.5 days with placebo

Patients with a mean baseline of 8.9 migraine days per month experienced 3.7 fewer migraine days per month, on average, with monthly dosing (vs 2.2 days with placebo).

Patients with a mean baseline of 9.2 migraine days per month experienced 3.4 fewer migraine days per month, on average, with quarterly dosing (vs 2.2 days with placebo).

Ajovy was specifically developed for migraine.  Historically, many migraine preventive medicines were designed for other conditions.  Ajovy was specifically developed to bind to CGRP, a substance in the brain that may play a key role in migraine and block its binding to the receptor.

“The most exciting thing about these drugs is not the FDA-required endpoints,” says Alan Rapoport, MD, a clinical professor of neurology at UCLA’s David Geffen Medical School who has been a leader in headache research and treatment. The value of the CGRP class is its potential to significantly reduce migraines for a reasonable number of patients. He says about 30% of patients may see 75% reduction, and between 15% and 20% may see a 100% reduction.

These are astounding results for migraine therapy and much better than the results of any previously used migraine preventive drug.




What are the results of previous migraine preventive drugs?  The standard migraine preventive drugs are amitriptyline, topiramate, valproic acid, and the beta blockers-propanalol and atenolol. 

All of these drugs work indirectly on the migraine process, while Ajovy, blocking CGRP, acts directly in the migraine process.  These older preventive drugs could reduce migraines bout 30 % in a month and had a lot of side effects that resulted in poor compliance so that many patients just quit taking them.

Amitriptyline is an older antidepressant active at a dose of 100-125 mg and with possible side effects of weight gain, dryness of mouth, or constipation.  Neurologists use dose of 10-20 mg with reduced, but still active side effects.  However, it is the only migraine preventive drug, including the CGRP blockers, that helps with sleep and many migraine patients don’t sleep that well.

Topiramate is used at doses of 100-200 mg and also has predictable side effects of tingling lips and fingers, “cola tastes flat,” and trouble with cognition and word finding.  Despairingly patients called it “dopamax.”  Originally dosed every 12 hours, long acting, once a day topiramate is available as Trokendi XR and Quedexy XR. It was originally used to treat epilepsy and then found to help with migraine.

Depakote ER or Valproic acid is another anticonvulsant drug later found to help migraine that has a complete contraindication for fertile women.  It may cause malformed or “teratogenic” defects in babies which is unfortunate because migraine prevalence peaks at age 42 where 25 % of women get migraine and they are still having menstrual cycles and can’t take Depakote.

The betablockers propanalol and atenolol prevent the vasodilation that occurs during migraine, but they can also slow the pulse.  They may cause a “tired syndrome” which makes them difficult to use although propanalol had the first FDA indication for a preventive migraine drug in 1974.

H mmm.



Special cardiovascular and cerebrovascular lack of risk.  Migraine, especially migraine with aura, has an increased risk of cardiovascular and cerebrovascular risk.  The main acute therapy drugs, the triptans, are contraindicated with cardiovascular and cerebrovascular disease because of a suspected increase of vasoconstriction with resultant heart attack or stroke.

However, an increasing number of studies show that vasodilation is not significant in migraine and that the new CGRP drugs are safe.  The CGRP drugs are new and there are cries from some headache experts that more research should be done to further certify that CGRP drugs don’t relate to cardiovascular or cerebrovascular disease.  Currently the FDA says that Ajovy can be used in patients with cardiovascular and cerebrovascular disease risk.


What about use of the new CGRP antibody drugs for pregnancy or lactation?  There is no current indication for the use of CGRP antibody drugs during pregnancy or while breastfeeding.  The FDA statement regarding CGRP antibody drugs is: 

Can’t use for pregnancy and breastfeeding.

Can’t use for pregnancy and breastfeeding.


Pregnancy-caution is advised during pregnancy.  No human data is available, no known risk of fetal harm based on animal data at 20 times recommended human dose.

Lactation–caution is advised for breast-feeding.  No human data available to assess risk of infant harm or effects on milk production.

Good luck with this.

Britt Talley Daniel MD

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