CLASSES
Calcitonin Gene-Related Peptide (CGRP) Antagonists
DESCRIPTION
Injectable, selective calcitonin gene-related peptide (CGRP) receptor antagonist
Used for migraine prophylaxis in adults
Significantly reduces monthly migraine days
HOW SUPPLIED
AJOVY Subcutaneous Inj Sol: 1.5mL, 225mg
DOSAGE & INDICATIONS
For migraine prophylaxis.
Subcutaneous dosage
Adults
225 mg subcutaneously once monthly or 675 mg subcutaneously every 3 months.
MAXIMUM DOSAGE
Adults
225 mg/month or 675 mg every 3 months subcutaneously.
Geriatric
225 mg/month or 675 mg every 3 months subcutaneously.
Adolescents
Safety and efficacy have not been established.
Children
Safety and efficacy have not been established.
Infants
Safety and efficacy have not been established.
Neonates
Safety and efficacy have not been established.
DOSING CONSIDERATIONS
Hepatic Impairment
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Renal Impairment
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
ADMINISTRATION
Injectable Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if the fremanezumab solution is cloudy, discolored, or contains particles. Fremanezumab is a clear to opalescent, colorless to slightly yellow solution.
Subcutaneous Administration
Fremanezumab is intended for patient self-administration. Provide proper training to patients and/or caregivers on how to prepare and administer fremanezumab, including aseptic technique.
Before administration, allow fremanezumab to sit at room temperature for at least 30 minutes protected from direct sunlight. Do not warm using a heat source such as hot water or microwave. Do not use if the product has been at room temperature for 7 days or more.
Do not shake.
Clean injection site on the abdomen, thigh, or upper arm with an alcohol wipe and allow skin to dry.
Do not inject into areas where the skin is tender, bruised, red, or hard. Avoid injecting directly into raised, thick, red, or scaly skin patch or lesion, or areas with scars or stretch marks.
If using the same body area for the 3 separate injections needed for the 675 mg dose, ensure the injections are not at same location used for the previous injection.
Do not coadminister fremanezumab with other injectable drugs at the same injection site.
When switching between monthly and quarterly dosage options, administer the first dose of the new regimen on the next scheduled date of administration.
If a dose is missed, give the next dose as soon as possible. Subsequently, schedule from the date of the last dose.
Storage: After removing fremanezumab from the refrigerator, it can be stored at room temperature up to 86 degrees F (30 degrees C) for up to 7 days. Discard if not used within 7 days after removal from refrigerator. Do not place back in refrigerator once stored at room temperature.[63551]
Single-dose, Prefilled Syringe
Always hold syringe by the barrel.
Pull needle cap straight out and away from body.
Pinch injection site skin firmly between thumb and fingers.
Hold the pinch, and insert the syringe into skin at 45 to 90 degrees.
Using slow and constant pressure, push the plunger rod all the way down with thumb until the prefilled syringe stops moving.
When done, release thumb, and gently lift syringe off the skin.
Discard the prefilled syringe in a FDA-cleared sharps disposal container. Do not discard in household trash.[63551]
Single-dose, Prefilled Autoinjector
Pull the protective cap straight off the autoinjector.
Place the autoinjector at a 90-degree angle against the skin.
Press the autoinjector down onto the skin for approximately 30 seconds to deliver the dose.
A click will be heard when the injection starts and approximately 15 seconds into the injection. Wait 10 seconds after the second click before removing the autoinjector from the skin to ensure all of the dose is injected. The blue plunger will fill the viewing window when the dose is delivered.
Discard the prefilled autoinjector in a FDA-cleared sharps disposal container. Do not discard in household trash.[63551]
STORAGE
AJOVY:
- Discard product if it contains particulate matter, is cloudy, or discolored
- Discard product if stored above 77 degrees F for more than 24 hours
- Do not freeze
- Protect from direct sunlight
- Protect from extreme heat
- Protect from light
- Store in original carton in refrigerator (35 to 46 degrees F) until time of use
CONTRAINDICATIONS / PRECAUTIONS
General Information
Fremanezumab is contraindicated in patients with serious hypersensitivity to fremanezumab or any of the excipients. Anaphylaxis and angioedema have been reported with fremanezumab.
Pregnancy
There are no adequate data on the developmental risk associated with fremanezumab use during human pregnancy. Fremanezumab has a half-life of approximately 31 days, which should be taken into consideration for women who are pregnant or who intend to become pregnant while using the drug. No adverse developmental effects were observed when rabbits were given fremanezumab throughout organogenesis or when rats were given fremanezumab prior to and during mating and throughout pregnancy and lactation at doses associated with exposures approximately 2 to 3 times that in humans at a dose of 675 mg. Women with migraine may be at increased risk of preeclampsia during pregnancy. There is a pregnancy exposure registry that monitors outcomes in women exposed to fremanezumab during pregnancy. Health care providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-833-927-2605 or visiting www.tevamigrainepregnancyregistry.com.
Breast-feeding
There are no data on the presence of fremanezumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for fremanezumab and any potential adverse effects on the breast-fed infant from fremanezumab or the underlying maternal condition.
ADVERSE REACTIONS
Severe
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
Moderate
antibody formation / Delayed / 0.4-1.6
erythema / Early / Incidence not known
constipation / Delayed / Incidence not known
Mild
injection site reaction / Rapid / 43.0-45.0
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
DRUG INTERACTIONS
There are no drug interactions associated with Fremanezumab products.
PREGNANCY AND LACTATION
Pregnancy
There are no adequate data on the developmental risk associated with fremanezumab use during human pregnancy. Fremanezumab has a half-life of approximately 31 days, which should be taken into consideration for women who are pregnant or who intend to become pregnant while using the drug. No adverse developmental effects were observed when rabbits were given fremanezumab throughout organogenesis or when rats were given fremanezumab prior to and during mating and throughout pregnancy and lactation at doses associated with exposures approximately 2 to 3 times that in humans at a dose of 675 mg. Women with migraine may be at increased risk of preeclampsia during pregnancy. There is a pregnancy exposure registry that monitors outcomes in women exposed to fremanezumab during pregnancy. Health care providers are encouraged to register pregnant patients, or pregnant women may enroll themselves in the registry by calling 1-833-927-2605 or visiting www.tevamigrainepregnancyregistry.com.
There are no data on the presence of fremanezumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for fremanezumab and any potential adverse effects on the breast-fed infant from fremanezumab or the underlying maternal condition.
MECHANISM OF ACTION
Fremanezumab is a human immunoglobulin G2 (IgG2) monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor. CGRP is distributed throughout the nervous system, and it is concentrated at anatomical sites, such as the trigeminovascular system, which are involved in migraine pathophysiology. Centrally, CGRP is involved in nociceptive transmission through second and third order neurons and pain modulation in the brainstem. Peripherally, CGRP mediates vasodilation through smooth muscle receptors. CGRP concentrations are elevated during acute migraine attacks and may be chronically elevated in chronic migraineurs.[63169] [63551]
PHARMACOKINETICS
Fremanezumab is administered subcutaneously. Steady-state is achieved by 6 months after both monthly and quarterly dosing regimens. Fremanezumab has an apparent volume of distribution of 6 L, suggesting minimal distribution to extravascular tissues. Fremanezumab is degraded by enzymatic proteolysis into small peptides and amino acids. Fremanezumab apparent clearance is approximately 0.141 L/day. The half-life of fremanezumab is 31 days.[63551] Affected cytochrome P450 isoenzymes and drug transporters: none
Subcutaneous Route
After single fremanezumab doses of 225, 675, or 900 mg, the median Tmax was 5 to 7 days. Dose-proportionality was observed between 225 to 900 mg. The median accumulation ratio based on once-monthly and once-quarterly dosing regimens is approximately 2.3 and 1.2, respectively.