Galcanezumab-gnlm (Monograph)

Brand name: Emgality
Drug 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 G4, anti-(human calcitonin gene-related peptide) (human-Mus musculus clone III heavy chain), disulfide with human-Mus musculus clone III kappa-chain, dimer
Molecular formula: C₆₃₉₂H₉₈₅₄N₁₆₈₆O₂₀₁₈S₄₆
CAS number: 1578199-75-3

Medically reviewed by Drugs.com on May 23, 2022. Written by ASHP.

Introduction

Antimigraine agent; recombinant humanized IgG₄ monoclonal antibody specific for calcitonin gene-related peptide (CGRP) ligand.

Uses for Galcanezumab-gnlm

Preventive Treatment of Migraine

Preventive treatment of migraine.

Substantially reduces monthly migraine days in patients with episodic or chronic migraine and reduces acute antimigraine agent-use days in patients with episodic migraine compared with placebo.

The American Headache Society (AHS) states that the potential benefit of using newer therapies such as the anti-CGRP monoclonal antibodies over established therapies should be considered on an individual basis.

AHS has established a criteria for initiating treatment with anti-CGRP monoclonal antibodies based on a balance of cost-effective considerations and access to care; according to this criteria, use of anti-CGRP monoclonal antibodies may be appropriate when patients with migraine are unable to tolerate and/or have an inadequate response to an 8-week trial of at least 2 oral preventive therapies (e.g., topiramate, valproate, β-adrenergic blocking agents, tricyclic antidepressants, selective serotonin- and norepinephrine-reuptake inhibitors).

Treatment of Episodic Cluster Headache

Treatment of episodic cluster headache.

In the principal efficacy study, substantially reduced weekly cluster headache attack frequency in patients with episodic cluster headache compared with placebo.

Related/similar drugs

Aimovig, Botox, acetaminophen, prednisone, ibuprofen, amitriptyline, naproxen

Galcanezumab-gnlm Dosage and Administration

General

Patient Monitoring

• Monitor for hypersensitivity reactions, including anaphylaxis.

Administration

Administer by sub-Q injection only.

Commercially available in single-dose prefilled auto-injectors (i.e., injection pens), which contain 120 mg of the drug, and single-dose prefilled syringes, which contain either 100 or 120 mg of the drug, and are intended for patient self-administration.

Sub-Q Administration

Administer by sub-Q injection into the abdomen, anterior thigh, back of upper arm, or buttocks; avoid injections within 2 inches of the navel, knee, or groin. May use back of the upper arm or buttocks if someone other than the patient is administering the injection (e.g., caregiver, healthcare professional).

May administer multiple injections of the drug (i.e., the initial loading dose for migraine consisting of 2 injections and the dose for treatment of episodic cluster headache consisting of 3 injections) at separate locations at the same body 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 galcanezumab-gnlm sub-Q using the prefilled auto-injectors or syringes, including aseptic technique. Consult manufacturer's labeling for detailed instructions.

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

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

Dosage

Adults

Migraine

Preventive Treatment

Sub-Q

Initiate therapy with a one-time loading dose of 240 mg (administered as 2 consecutive injections of 120 mg each) followed by monthly doses of 120 mg. In clinical studies, a higher dosage (240 mg once monthly) did not demonstrate additional clinical benefit.

If a dose is missed, administer the missed dose as soon as possible. May then schedule subsequent doses once monthly from the date of the last administered dose.

When initiating therapy with galcanezumab or another anti-CGRP monoclonal antibody in patients already receiving a preventive treatment for migraine, the AHS recommends adding the anti-CGRP monoclonal antibody to the existing antimigraine regimen. Consider onset and magnitude of effect with the anti-CGRP monoclonal antibody when deciding whether to discontinue other therapy.

Assess clinical efficacy after 3 months of treatment; continue therapy only if treatment benefits have been observed by that time.

Episodic Cluster Headache

Treatment

Sub-Q

300 mg (administered as 3 consecutive injections of 100 mg each) at the onset of the cluster period and then monthly until the end of the cluster period.

If a dose is missed, administer the missed dose as soon as possible. May then schedule subsequent doses once monthly from the date of the last administered dose until the end of the cluster period.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Cautions for Galcanezumab-gnlm

Contraindications

• Serious hypersensitivity to galcanezumab or any excipient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including anaphylaxis, angioedema, rash, urticaria, and dyspnea, reported. May occur days after drug administration and may be prolonged.

If a serious or severe hypersensitivity reaction occurs, discontinue the drug and initiate appropriate medical therapy.

Manufacturer states that prefilled auto-injectors and syringes of galcanezumab-gnlm are not made with natural rubber latex.

Immunogenicity

Potential for immunogenicity. Antibodies to galcanezumab, including neutralizing antibodies to the drug, reported. Available data do not demonstrate an effect of anti-galcanezumab antibody development on pharmacokinetics, 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 galcanezumab in pregnant females. No adverse effects on offspring observed when pregnant rats and rabbits received the drug sub-Q at dosages resulting in systemic exposures greater than those expected clinically.

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 in females with migraine.

Consider the long half-life of galcanezumab if used in pregnant females or those planning to become pregnant.

There is a pregnancy exposure registry that monitors fetal outcomes in females exposed to galcanezumab during pregnancy. Healthcare providers are encouraged to register patients by calling the pregnancy exposure registry at 833-464-4724 or by visiting [Web].

Lactation

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

Pediatric Use

Safety and efficacy not established in pediatric patients. A clinical study to evaluate the efficacy and safety of galcanezumab in the preventive treatment of episodic migraine in pediatric patients 6–17 years of age^{† [off-label]} is currently under way.

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 (e.g., erenumab, fremanezumab, galcanezumab) mainly to postpubertal adolescents^{† [off-label]} 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^{† [off-label]} 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 affect pharmacokinetics.

Renal Impairment

Renal impairment not expected to affect pharmacokinetics.

Common Adverse Effects

Preventive treatment of migraine (≥2% of patients receiving galcanezumab and ≥2% more frequently than with placebo): Injection site reactions (e.g., pain, erythema, pruritus, swelling), which are usually mild to moderate in severity and resolve within a few days to 2 weeks.

Treatment of episodic cluster headache: Tolerability profile is consistent with that observed in migraine patients.

Drug Interactions

Not metabolized by CYP isoenzymes. Unlikely to be affected by drug transport systems.

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.

Galcanezumab-gnlm Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved within approximately 5 days following sub-Q administration.

Steady-state concentrations achieved following a 240-mg sub-Q loading dose (i.e., the first dose). Steady-state concentrations achieved after the fourth dose with a 300-mg, once-monthly sub-Q dosage regimen.

Exhibits linear and dose-proportional pharmacokinetics with dosages of 1–600 mg.

Sub-Q injection site does not appear to substantially influence absorption.

Onset

Antimigraine effects usually evident following 1–3 monthly sub-Q injections in responding patients.

Special Populations

Not formally studied in renal or hepatic impairment; renal or hepatic impairment not expected to affect pharmacokinetics. Population pharmacokinetic analysis indicates that Cl_cr does not affect pharmacokinetics in patients with mild or moderate renal impairment and that serum bilirubin concentration (an indirect marker of hepatic function) does not substantially affect clearance. Not studied in patients with severe renal impairment (Cl_cr <30 mL/minute).

Population pharmacokinetic analysis indicates that pharmacokinetics not affected by age, sex, race, subtypes of migraine spectrum (e.g., episodic or chronic migraine), or headache diagnosis (e.g., migraine, episodic cluster headache). Body weight does not have a clinically important effect on pharmacokinetics.

Distribution

Extent

Possible limited distribution into the CNS and cerebrospinal fluid. Due to large molecular size, however, anti-CGRP monoclonal antibodies are unlikely to cross the blood-brain barrier in substantial amounts.

Not known whether distributed into human milk.

Elimination

Elimination Route

Expected to be degraded into small peptides and amino acids via catabolic pathways.

Half-life

Approximately 27 days.

Stability

Storage

Parenteral

Injection

2–8°C in original carton to protect from light until time of use; do not freeze. Do not shake.

If removed from the refrigerator, store at room temperatures (≤30°C) in the original carton; use within 7 days. Do not return to refrigerator if stored at room temperature for >1 hour.

Discard if stored at room temperature for >7 days, or if frozen or shaken vigorously (i.e., shaking beyond the normal vibration, shaking, or bumping that may occur during typical transport activities). If stored outside of recommended storage and handling conditions, may contact manufacturer for further information regarding stability and product quality assessment by calling 800-545-5979.

Actions

• A humanized IgG₄ 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 in substantial amounts; probably antagonizes CGRP activity peripherally rather than centrally within the nervous system.

Advice to Patients

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

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

• If a dose of galcanezumab for the preventive treatment of migraine is missed, administer the missed dose as soon as possible. Schedule subsequent doses monthly from the date of the last administered dose.

• If a dose of galcanezumab for the treatment of episodic cluster headache is missed, administer the missed dose as soon as possible. If the cluster headache period has not yet ended, schedule subsequent doses monthly from the date of the last administered dose until the end of the cluster period.

• Importance of informing patients of possible signs and symptoms of hypersensitivity reactions (e.g., rash, urticaria, dyspnea), which can occur days after administration and may be prolonged. Patients should seek immediate medical attention if symptoms of a serious or severe 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.

• Advise patients that there is a pregnancy exposure registry that monitors fetal outcomes in females exposed to galcanezumab during pregnancy.

• 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.

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