Class: Calcitonin Gene-related Peptide (CGRP) Antagonists
- 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
Antimigraine agent; recombinant humanized IgG4 monoclonal antibody that inhibits calcitonin gene-related peptide (CGRP) function.
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 galcanezumab and other CGRP antagonists 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 after 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 CGRP antagonists, AHS recommends that CGRP antagonists 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).
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.
Galcanezumab-gnlm Dosage and 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.
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.
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 CGRP antagonist in patients already receiving a preventive treatment for migraine, AHS recommends adding the CGRP antagonist to the existing antimigraine regimen and avoiding making other changes until the clinical efficacy of the CGRP antagonist is determined.
Patients with migraine who respond to CGRP antagonist therapy usually respond following the first 3 doses. Therefore, AHS recommends assessing clinical efficacy of galcanezumab after 3 months of treatment; continue therapy only if treatment benefits have been observed by that time.
Episodic Cluster Headache
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.
No specific dosage recommendations.
No specific dosage recommendations.
No specific dosage recommendations.
Cautions for Galcanezumab-gnlm
Serious hypersensitivity to galcanezumab or any excipient in the formulation. (See Sensitivity Reactions under Cautions.)
Hypersensitivity reactions, including rash, urticaria, and dyspnea, reported during clinical trials. 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. (See Contraindications under Cautions and also see Advice to Patients.)
Manufacturer states that prefilled auto-injectors and syringes of galcanezumab-gnlm are not made with natural rubber latex.
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.
No adequate data on the developmental risk associated with use of galcanezumab in pregnant women. 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 women with migraine.
Consider the long half-life of galcanezumab if used in pregnant women or those planning to become pregnant.
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.
Manufacturer states that 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† is currently under way.
Pending further clinical experience with CGRP antagonists in pediatric patients, the Pediatric and Adolescent Headache special interest group of the AHS recommends limiting use of CGRP antagonists (e.g., erenumab, fremanezumab, galcanezumab) 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 CGRP antagonists only in carefully selected patients with close monitoring (e.g., pubertal status, bone health, linear growth, weight, body mass index [BMI], infectious complications).
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.
Hepatic impairment not expected to affect pharmacokinetics. (See Special Populations under Pharmacokinetics.)
Renal impairment not expected to affect pharmacokinetics. (See Special Populations under Pharmacokinetics.)
Common Adverse Effects
Preventive treatment of migraine: 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.
Interactions for Galcanezumab-gnlm
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.
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.
Antimigraine effects usually evident following 1–3 monthly sub-Q injections in responding patients.
Not formally studied in renal or hepatic impairment; renal or hepatic impairment not expected to affect pharmacokinetics. Population pharmacokinetic analysis indicates that Clcr 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 (Clcr <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.
Possible limited distribution into the CNS and cerebrospinal fluid. Due to large molecular size, however, CGRP antagonists are unlikely to cross the blood-brain barrier in substantial amounts.
Not known whether distributed into human milk.
Expected to be degraded into small peptides and amino acids via catabolic pathways.
Approximately 27 days.
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.
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. (See Pregnancy under Cautions.)
Importance of informing patients of other important precautionary information. (See Cautions.)
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.
Injection, for subcutaneous use only
100 mg/1 mL
Emgality (available as single-dose prefilled syringes)
120 mg/1 mL
Emgality (available as single-dose prefilled auto-injectors [pens] and single-dose prefilled syringes)
AHFS DI Essentials™. © Copyright 2021, Selected Revisions November 4, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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