Migraine, prevention (alternative agent):
Note: Avoid use in patients with recent cardiovascular or cerebrovascular ischemic events (Schwedt 2022). Limit use to patients with significant disability from frequent migraines who are unable to tolerate or do not respond to adequate trials of at least 2 other preventive therapies (AHS [Ailani 2021]; Loder 2018). An adequate trial for assessment of effect is considered to be at least 3 months at a therapeutic dose when administered monthly, or ≥6 months when administered quarterly (AHS [Ailani 2021]).
SUBQ: 225 mg monthly or 675 mg every 3 months (Dodick 2018). When switching dosage options, administer the first dose of the new regimen on the next scheduled date of administration.
There are no dosage adjustments provided in the manufacturer’s labeling. Renal impairment is not expected to affect the pharmacokinetics of fremanezumab.
There are no dosage adjustments provided in the manufacturer’s labeling. Hepatic impairment is not expected to affect the pharmacokinetics of fremanezumab.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Auto-injector, Subcutaneous:
Ajovy: Fremanezumab-vfrm 225 mg/1.5 mL (1.5 mL) [contains disodium edta, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Ajovy: Fremanezumab-vfrm 225 mg/1.5 mL (1.5 mL) [contains edetate (edta) disodium dihydrate, polysorbate 80]
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Auto-injector, Subcutaneous:
Ajovy: 225 mg/1.5 mL (1.5 mL) [contains disodium edta, polysorbate 80]
Solution Prefilled Syringe, Subcutaneous:
Ajovy: 225 mg/1.5 mL (1.5 mL) [contains disodium edta, polysorbate 80]
SUBQ: For SUBQ use only. Keep out of direct sunlight and allow prefilled syringe to come to room temperature for 30 minutes before administration. Do not warm by using a heat source (eg, hot water, microwave). Do not shake. Administer in the abdomen, thigh, or upper arm, avoiding areas that are tender, bruised, red, or indurated. The 675 mg dose should be administered as 3 consecutive 225 mg injections. For multiple injections, use the same body site, but not the exact location of the previous injection. Do not administer with other injectable drugs at the same injection site.
Migraine, prevention: Preventive treatment of migraine in adults.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%: Local: Injection site reaction (43% to 45%)
1% to 10%: Immunologic: Antibody development (≤2%; neutralizing <1%)
Frequency not defined: Hypersensitivity: Hypersensitivity reaction
Postmarketing: Hypersensitivity: Anaphylaxis, angioedema
Serious hypersensitivity (eg, anaphylaxis, angioedema) to fremanezumab or any component of the formulation.
Concerns related to adverse effects:
• Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, angioedema, rash, pruritus, drug hypersensitivity, and urticaria, have been reported. Most reactions were mild to moderate and were reported from within hours to 1 month after administration. If a hypersensitivity reaction occurs, consider discontinuing treatment and institute appropriate therapy.
Disease-related concerns:
• Cardiovascular disease: Patients with a history of significant cardiovascular disease, vascular ischemia, or thrombotic events, such as cerebrovascular accident, transient ischemic attacks, deep vein thrombosis, or pulmonary embolism were excluded from clinical trials; use with caution in these patients.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Other warnings/precautions:
• Immunogenicity: Anti-fremanezumab antibodies and neutralizing antibodies may develop.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
In general, preventive treatment for migraine in patients trying to become pregnant should be avoided; treatment should be individualized considering the available safety data and needs of the patient should pregnancy occur (AHS [Ailani 2021]). Consider the long half-life prior to use in patients who may become pregnant until information related to pregnancy is available (Tepper 2018).
Adverse events were not observed in animal reproduction studies.
Fremanezumab is a humanized monoclonal antibody (IgG2). Human IgG crosses the placenta. Exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
Outcome data following maternal use of fremanezumab during pregnancy are limited (Noseda 2021).
Fremanezumab is a calcitonin gene-related peptide (CGRP) receptor antagonist. Based on animal data, CGRP may help regulate placental blood flow, uterine relaxation, and maintain BP; CGRP antagonists could potentially increase the risk of gestational hypertension and preeclampsia. The risk of preeclampsia is also increased in pregnant patients with migraine (Dodick 2019; Parikh 2020).
In general, preventive treatment for migraine in pregnant patients should be avoided; treatment during pregnancy should be individualized considering the available safety data, the potential for adverse maternal and fetal events, and needs of the patient (AHS [Ailani 2021]). Based on available data, other agents may be preferred for the prevention of migraine in pregnant patients; use of CGRP receptor antagonists should be avoided until additional data are available (Burch 2019; Parikh 2020).
Data collection to monitor pregnancy and infant outcomes following exposure to fremanezumab is ongoing. Health care providers are encouraged to enroll patients exposed to fremanezumab during pregnancy in the Teva Migraine Pregnancy Registry (833-927-2605).
It is not known if fremanezumab is present in breast milk.
Fremanezumab is a humanized monoclonal antibody (IgG2). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. In general, preventive treatment for migraine in lactating patients should be avoided; treatment should be individualized considering the available safety data and needs of the patient (AHS [Ailani 2021]). Use of calcitonin gene-related peptide receptor antagonists should be avoided until additional data are available (Parikh 2020).
Fremanezumab is a humanized monoclonal antibody that binds to calcitonin gene-related peptide (CGRP) ligand and blocks its binding to the receptor.
Distribution: Vd: ~6 L
Metabolism: Degraded by enzymatic proteolysis into small peptides and amino acids.
Half-life elimination: ~31 days
Time to peak: 5 to 7 days
Excretion: Clearance: 0.141 L/day
Solution Auto-injector (Ajovy Subcutaneous)
225 mg/1.5 mL (per mL): $532.00
Solution Prefilled Syringe (Ajovy Subcutaneous)
225 mg/1.5 mL (per mL): $532.00
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