Ajovy (Fremanezumab) is a drug from the same class as Emgality (Galcanezumab) and Aimovig (Erenumab). It belongs to the class of drugs called CGRPR Inhibitors.
CGRPR (calcitonin gene-related peptide receptor) Inhibitors are a novel class of drugs with a unique mechanism of action.
These drugs block the interaction between CGRP and CGRPR resulting in vasoconstriction of the cerebral vessels that cause a migraine headache.
Ajovy (Fremanezumab) Uses:
Ajovy (Fremanezumab) is a long-acting CGRPR inhibitor that is used to prevent recurrence and reduce the severity of migraine headaches.
Preventive medicines are indicated in the treatment of migraine headaches only if the episode of acute migraine headaches is intense, the duration of the attack lasts more than a day, or the headache is very frequent.
A person with a migraine headache should be treated with preventive migraine treatment if the headache occurs three times a month or more.
Preventive medicines may include any of the following groups of medicines:
- Beta-blockers such as propranolol
- Tricyclic antidepressants like amitriptyline and nortriptyline.
- Valproic acid
- Calcium channel blockers like Sibelium (Flunarizine) and Verapamil, and
- The novel agents, CGRPR inhibitors including Ajovy (Fremanezumab), Emgality (Galcanezumb), and Aimovig (Erenumab)
Ajovy (Fremanezumab) Dose and Dosage Forms:
Ajovy (Fremanezumab) is available in the market in 225 mg/1.5 ml single prefilled injection form.
It is administered in two different dosing schedules:
- 225 mg injection subcutaneously once a month, or
- 675 mg subcutaneously every three months.
If the 675 mg dosing schedule is followed, it is administered as three consecutive injections of 225 mg each.
For a person who wishes to switch from a once-monthly schedule to a once every three months schedule, three doses of the 225 mg/1.5 ml equivalent to 675 mg injection can be administered one month after the last dose (on the monthly scheduled dose).
For example, a person who is on a monthly schedule has had her/ his last dose on the first of April, can inject 675 mg on the 1st of May and then every three months thereafter.
However, a person who is on a three-monthly dose can switch to a monthly dose at least three months after the last dose.
Erenumab (Aimovig) Injectionfor Migraine
How to administer Ajovy?
Ajovy can be administered by your physician (especially the first dose or two), or caregiver, and can be self-administered as well after proper training.
Before administering the drug, the prefilled injection should be kept at room temperature for thirty minutes.
The solution of the injection should be inspected. It should be clean and clear or slightly opalescent. A cloudy solution or one that contains any particulate matter should not be injected.
The injection can be administered into the skin of the tummy 3 – 5 cm away from the navel, the skin of the buttocks or front of the thighs, and the skin of the back of the arms.
Each time the site of the injection should be changed. However, those injecting three consecutive injections (as in the once-three-monthly schedule) can inject all three injections on the same area of the skin slightly away from each other.
Patients may be monitored for hypersensitivity reactions manifesting as rash, itching, hives, or angioedema.
Ajovy (Fremanezumab) Use in Kidney and Liver impairment:
The drug has not been studied in patients with moderate or severe hepatic or renal impairment. It should be avoided in patients with severe kidney and liver impairment.
In those with mid to moderate disease, it can be safely given without the need to adjust the dose.
Ajovy (Fremanezumab) Use in Pregnancy and Breastfeeding:
Ajovy (Fremanezumab) has not been studied in human pregnant females. In animal models, when the drug was administered at the usual recommended doses, no adverse fetal outcomes were observed.
Even at supratherapeutic doses i.e. two to three times the maximum recommended doses, no adverse fetal effects were observed (when the drug was administered during the period of organogenesis).
The manufacturer has not made any recommendations regarding its safety in human pregnancies. However, since it has not been studied in human pregnant females, it should be ideally avoided during pregnancy.
Similarly, the drug has not been studied as to whether it gets excreted into breastmilk or not. The manufacturer recommends weighing the risks of drug exposure in the infant and the benefits of treating the nursing mother.
Ajovy (Fremanezumab) Contraindications and Warnings:
Ajovy (Fremanezumab) is contraindicated in all patients who are allergic to the drug or any of the constituents of the injection.
Hypersensitivity reactions can manifest soon after the injection or as late as weeks to a month after the administration of the injection.
The symptoms of hypersensitivity reactions can be in the form of itching, redness, hives, and rash at the site of the administration and then progressing to involve the whole body.
Severe reactions can manifest as angioedema and hypotension, although these reactions are very rare.
Immediate discontinuation of the drug and supportive treatment should be instituted in case an allergic reaction is observed.
Ajovy (Fremanezumab) Side effects:
Ajovy (Fremanezumab) is a very safe drug. Apart from injection site adverse drug reactions, no significant side effects of the drug have been observed.
Injection site reactions occurred in 43%, 48%, and 35% of patients in the Ajovy 225 mg, 675 mg, and placebo groups respectively.
These reactions included redness, swelling, pain, and itching at the site of the injection that resolve spontaneously.
Another side effect that is common with all monoclonal antibodies is the development of antibodies against the drug. Although the effect of these autoantibodies on the efficacy and safety of the drug has not been clearly identified, one should be cautious.
Less common side effects of Fremanezumab include flu-like symptoms, myalgias, arthralgias, and muscle spasms.
No specific drug-related monitoring parameters such as laboratory investigations have been advised by the manufacturer.
One should, however, monitor the response to treatment. It is not odd to change from one drug from the same class to another. Similarly, one can also switch from a once-monthly to once every three-monthly schedule.
Ajovy (Fremanezumab) Mechanism of Action (MOA) [Ref]:
Fremanezumab is a human monoclonal antibody that binds to the CGRP (calcitonin gene-related peptide) ligand and inhibits its interaction with its receptors (CGRPR).
When the interaction of the CGRP and CGRPR is inhibited, the process that takes place after its interaction is not executed.
Since CGRPR is involved in the vasodilation of blood vessels thought to cause a migraine headache, inhibiting these receptors cause vasoconstriction relieving migraine headaches.
- The time to reach the maximum plasma concentration after the administration of 225 mg, 675 mg, and 900 mg injection is 5 to 7 days.
- The steady-state concentration reaches after about 6 months (168 days) of repeated administration.
- It has a half-life elimination of approximately 31 days.
Metabolism and excretion:
- It is metabolized by enzymatic degradation resulting in smaller peptides and amino acids.
Ajovy single prefilled syringe containing 225 mg/1.5 ml of Fremanezumab.
Ajovy (Fremanezumab) Cost:
One single prefilled syringe of Ajovy costs USD $640.
This is equivalent to:
- USD $1920 for three months,
- USD $ 3840 for six months, and
- USD $ 7680 for one year.