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Fremanezumab-vfrm

Class: Calcitonin Gene-related Peptide (CGRP) Antagonists
- Anti-Calcitonin Gene-related Peptide Monoclonal Antibodies
- Anti-CGRP Monoclonal Antibodies
- Calcitonin Gene-related Peptide Antagonists
- CGRP Antagonists
Chemical Name: Immunoglobulin G2, anti-(human α-calcitonin gene-related peptide/β-calcitonin gene-related peptide) (human-Mus musculus monoclonal TEV-48125 heavy chain), disulfide with human-Mus musculus monoclonal TEV-48125 light chain, dimer
Molecular Formula: C6470H9952N1716O2016S46
CAS Number: 1655501-53-3
Brands: Ajovy

Medically reviewed by Drugs.com on May 10, 2021. Written by ASHP.

Introduction

Antimigraine agent; recombinant humanized IgG2a monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP) receptor function.

Uses for Fremanezumab-vfrm

Preventive Treatment of Migraine

Preventive treatment of migraine.

Substantially reduces the monthly average number of migraine or headache days and acute antimigraine agent- or headache medication-use days in patients with episodic or chronic migraine compared with placebo.

The American Headache Society (AHS) states that fremanezumab and other anti-CGRP monoclonal antibodies offer a number of advantages over some oral migraine preventive therapies, including no need for dosage escalation, rapid onset of therapeutic activity, demonstrated efficacy in patients in whom prior preventive treatments have failed as well as in those concurrently receiving oral preventive treatments, minimal risk of adverse drug interactions, and favorable overall tolerability profiles. However, because of the relatively high cost of anti-CGRP monoclonal antibodies, AHS recommends that anti-CGRP monoclonal antibodies be considered for use only in patients who are unable to tolerate oral preventive therapies and/or who have had an inadequate response to a 6-week trial of ≥2 oral preventive therapies (e.g., topiramate, valproate, β-adrenergic blocking agents, tricyclic antidepressants, SNRIs).

Fremanezumab-vfrm Dosage and Administration

Administration

Administer by sub-Q injection only.

Commercially available in single-use prefilled syringes and single-use prefilled auto-injectors (i.e., injection pens) containing 225 mg of the drug in 1.5 mL of solution. May be administered by a healthcare professional or caregiver or self-administered.

Sub-Q Administration

Administer by sub-Q injection into the abdomen, anterior thigh, or back of upper arm; avoid injections within 2 inches of the navel, knee, or groin.

May administer multiple injections of the drug (i.e., to achieve a 675-mg dose) at same body site but not at exact location of previous injection. Do not administer concomitantly with other parenteral drugs at the same injection site. Avoid injection into areas where the skin is tender, bruised, erythematous, or indurated.

Prior to use, provide patients and/or caregivers with proper training on how to prepare and administer fremanezumab-vfrm sub-Q using the prefilled syringes or auto-injectors, including aseptic technique. Consult manufacturer's labeling for detailed instructions.

Prior to sub-Q administration, remove prefilled syringe(s) or auto-injector(s) from the refrigerator and allow to sit at room temperature for 30 minutes; protect from exposure to direct sunlight. Do not warm syringes or auto-injectors using a heat source (e.g., microwave, hot water). Do not use if the solution is cloudy or discolored or contains particles.

Prefilled syringes and auto-injectors are intended for single use only; discard after use.

Dosage

Adults

Migraine
Preventive Treatment
Sub-Q

225 mg once monthly or 675 mg every 3 months (quarterly). Administer 675-mg doses as 3 consecutive injections of 225 mg each. (See Administration under Dosage and Administration.) Gradual dosage titration not necessary; may initiate therapy with either the 225-mg monthly dose or 675-mg quarterly dose.

When switching dosage regimens, administer the first dose of the new dosage regimen on the next scheduled date of administration.

If a dose is missed, administer the missed dose as soon as possible. May then schedule subsequent doses once monthly (225-mg doses) or every 3 months (675-mg doses) from the date of the last administered dose.

When initiating therapy with fremanezumab or another anti-CGRP monoclonal antibody in patients already receiving a preventive treatment for migraine, AHS recommends adding the anti-CGRP monoclonal antibody to the existing antimigraine regimen and avoiding making other changes until the clinical efficacy of the anti-CGRP monoclonal antibody is determined.

Some patients who do not experience a response to anti-CGRP monoclonal antibody therapy following the first dose may experience a response within 4 weeks after the second dose or within 4–8 weeks after the third dose. AHS recommends assessing clinical efficacy of fremanezumab 3 months after initiating treatment (if using the monthly dosage regimen) or 6 months after initiating treatment (if using the quarterly dosage regimen); continue therapy only if treatment benefits have been observed by that time.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Fremanezumab-vfrm

Contraindications

  • Serious hypersensitivity to fremanezumab or any excipients in the formulation. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity, and urticaria, reported during clinical trials. Most reactions were mild to moderate in severity; however, some resulted in drug discontinuance or required corticosteroid therapy. Most reactions occur within hours to 1 month after administration.

If a hypersensitivity reaction occurs, consider discontinuing the drug and initiate appropriate therapy. (See Contraindications under Cautions and see also Advice to Patients.)

Manufacturer states that fremanezumab-vfrm prefilled syringes and auto-injectors do not contain natural rubber latex.

Immunogenicity

Potential for immunogenicity. Antibodies to fremanezumab, including neutralizing antibodies to the drug, reported. Available data do not demonstrate an effect of anti-fremanezumab antibody development on efficacy or safety of the drug; however, data are too limited to make definitive conclusions.

Specific Populations

Pregnancy

No adequate data on the developmental risk associated with use of fremanezumab in pregnant women. Consider long half-life of the drug if used in pregnant women or those planning to become pregnant.

No adverse developmental effects observed when pregnant rats and rabbits received fremanezumab sub-Q at dosages resulting in systemic exposures up to approximately 2–3 times the exposure from the maximum recommended human dosage.

Estimated rates of major birth defects and miscarriage among deliveries to women with migraine (2.2–2.9 and 17%, respectively) are similar to rates reported in women without migraine. Possible increased risk of preeclampsia and gestational hypertension in women with migraine.

Lactation

Not known whether distributed into human milk. Effects on breast-fed infants and on milk production also unknown. Consider developmental and health benefits of breast-feeding, mother's clinical need for fremanezumab, and potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Manufacturer states that safety and efficacy not established in pediatric patients.

Pending further clinical experience with anti-CGRP monoclonal antibodies in pediatric patients, the Pediatric and Adolescent Headache special interest group of the AHS recommends limiting use of anti-CGRP monoclonal antibodies mainly to postpubertal adolescents with relatively frequent migraines (i.e., ≥8 headache days per month) who have moderate to severe disability associated with migraine (e.g., PedMIDAS score ≥30) and in whom ≥2 preventive therapies have failed. For younger pediatric patients with severe chronic migraine that is refractory to multiple preventive therapies, consider anti-CGRP monoclonal antibodies only in carefully selected patients with close monitoring (e.g., pubertal status, bone health, linear growth, weight, body mass index [BMI], infectious complications).

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Hepatic Impairment

Hepatic impairment not expected to substantially affect pharmacokinetics. (See Special Populations under Pharmacokinetics.)

Renal Impairment

Renal impairment not expected to substantially affect pharmacokinetics. (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Injection site reactions (e.g., pain, induration, erythema); usually mild to moderate in severity and self-limited.

Interactions for Fremanezumab-vfrm

Not metabolized by CYP isoenzymes. In addition, fremanezumab is unlikely to affect drug-metabolizing enzymes or drug transporters.

Risk of adverse drug interactions appears minimal.

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP isoenzymes: Pharmacokinetic interactions unlikely.

Substrates of CYP isoenzymes: Pharmacokinetic interactions unlikely.

Drugs Affected by Drug Transport Systems

Substrates of various drug transport systems: Pharmacokinetic interactions unlikely.

Specific Drugs

Drug

Interaction

Analgesics

Pharmacokinetic interactions unlikely

Ergot alkaloids

Pharmacokinetic interactions unlikely

Preventive antimigraine agents

Pharmacokinetic interactions unlikely

Selective serotonin type 1 receptor agonists (triptans)

Pharmacokinetic interactions unlikely

Fremanezumab-vfrm Pharmacokinetics

Absorption

Bioavailability

Median time to peak concentrations is 5–7 days following a single sub-Q dose.

Steady-state concentrations achieved in approximately 6 months following sub-Q administration of 225 mg monthly or 675 mg quarterly. Median systemic accumulation is approximately 2.3- or 1.2-fold following 225-mg once-monthly or 675-mg once-quarterly dosage regimens, respectively.

Exhibits dose-proportional pharmacokinetics over a sub-Q dose range of 225–900 mg.

Pharmacokinetics in patients with migraine are similar to those in healthy individuals.

Onset

Antimigraine effects of anti-CGRP monoclonal antibodies, including fremanezumab, usually evident following 1–3 monthly sub-Q injections or 1–2 quarterly sub-Q injections in responding patients.

Special Populations

Not formally studied in renal or hepatic impairment; renal or hepatic impairment not expected to substantially affect pharmacokinetics. Population pharmacokinetic analysis indicates that pharmacokinetics not affected by mild hepatic impairment.

Pharmacokinetics not affected by age, sex, race, body weight, or body mass index (BMI).

Distribution

Extent

Distributes minimally to extravascular tissues.

Due to large molecule size, unlikely to cross the blood-brain barrier.

Not known whether distributed into human milk.

Elimination

Elimination Route

Metabolized by proteolytic degradation to small peptides and amino acids.

Because of its large molecular size, renal excretion of intact fremanezumab is unlikely.

Half-life

Approximately 31 days.

Stability

Storage

Parenteral

Injection

2–8°C in original outer carton to protect from light; do not freeze. Avoid exposure to extreme heat or direct sunlight. Do not shake.

If necessary, may store at room temperature (≤30°C) in the original carton. Following removal from the refrigerator, use prefilled syringes and auto-injectors within 7 days or discard them. Do not return prefilled syringes and auto-injectors to the refrigerator after storage at room temperature.

Actions

  • A humanized IgG2a delta/kappa monoclonal antibody that inhibits CGRP function. Produced using recombinant DNA technology in Chinese hamster ovary cells.

  • CGRP is a potent vasodilator and pain-signaling neuropeptide associated with migraine pathophysiology. CGRP and its receptors are located at sites that are relevant to migraine development (e.g., trigeminal neurons); they also are widely distributed throughout the central and peripheral nervous systems as well as in nonneuronal tissues throughout the body.

  • Increased serum CGRP concentrations observed in individuals during acute migraine attacks (with or without aura); IV infusion of CGRP induces migraines in patients with a history of migraines.

  • Binds to the CGRP ligand and blocks its binding to the CGRP receptor.

  • Because of its large molecular size, unlikely to cross the blood-brain barrier; probably antagonizes CGRP function peripherally rather than centrally within the nervous system.

Advice to Patients

  • Importance of advising patients and/or caregivers to read the manufacturer's patient information and to read and follow the instructions for use each time they use fremanezumab.

  • Importance of providing guidance to patients and/or caregivers on proper sub-Q administration of fremanezumab-vfrm, including the use of aseptic technique, and how to use the single-dose prefilled syringes or auto-injectors.

  • Importance of informing patients receiving the 675-mg dose that the dose should be administered as 3 consecutive injections of 225 mg each.

  • If a dose is missed, administer the missed dose as soon as possible. Schedule subsequent doses monthly or quarterly from the date of the last administered dose.

  • Importance of informing patients of possible signs and symptoms of hypersensitivity reactions (e.g., rash, pruritus, urticaria), which can occur within hours and up to 1 month after administration. Patients should immediately contact their healthcare provider if signs or symptoms of a hypersensitivity reaction occur.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. (See Pregnancy under Cautions.)

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Fremanezumab-vfrm

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use only

225 mg/1.5 mL

Ajovy (available as single-dose prefilled auto-injectors [pens] and single-dose prefilled syringes)

Teva

AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 10, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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