Galcanezumab - Uses, Dosage, Side Effects, and More

Overview

Galcanezumab is a drug that is used for the treatment and preventive management of migraine in adult patients. The recommended dose of Galcanezumab includes two injections of 120 mg each, which is to be administered subcutaneously in a consecutive pattern. Thus the total dose is 240 mg. The first dose is called a loading dose, and the next dose is called the monthly dose. In case a dose of Galcanezumab is missed, one must soon administer the same on remembrance. Therefore, Galcanezumab must be administered on the same day of every month. About the dosage of Galcanezumab for cluster headaches, the dose that has been recommended is 300 mg which three injections must administer in a consecutive pattern, each of which is 100 mg. This will continue until the deprivation of cluster headaches.

Galcanezumab is an antagonist to calcitonin-gene, which is related to a peptide group. Galcanezumab received approval from the Food and Drug Administration (FDA) on the 4th of June 2019, specifically for treating cluster headaches. Prior to this, Galcanezumab had already conferred the Food and Drug Administration approval for preventive treatment of migraine in adult patients on the 27th of September 2018. 

Galcanezumab must strictly be administered through the subcutaneous route. Generally, Galcanezumab is administered by the patient themselves or their family members. The patient, the family member, or the patient’s caregiver must be thoroughly instructed and trained regarding the subcutaneous administration of Galcanezumab. The working of aseptic procedures of the single-dose prefilled syringe or single-dose prefilled pen is additionally explained to the patient or related individuals. Both kinds of administrative devices can deliver the entire single dose of Galcanezumab in one go. Galcanezumab must be protected from a direct source of sunlight. Suppose the administration device of Galcanezumab is kept inside the refrigerator. In that case, it should be seen that the device remains at room temperature for a minimum of thirty minutes before administration of the drug. Galcanezumab must never be heated in a microwave oven or boiled in hot water. The device must not be roughly handled before administration and thus should not be shaken. Prior to administration, the drug must be examined for a change in color and texture. If Galcanezumab has changed into a cloudy substance with clearly visible particulate matter, it is not fit to be used anymore. Subcutaneous administration of Galcanezumab can be done in the upper arm, thigh, abdomen, buttocks, or posterior region. If the skin or the tissues around the injection site has changed color, are inflamed or irritated, show reddish-blue discoloration, or are hard and tender, the administration location must be altered.

Galcanezumab has been contraindicated in patients who have a known hypersensitivity to Galcanezumab or a history of a severe anaphylactic episode to Galcanezumab. The drug must be immediately halted if a hypersensitivity reaction begins after administration, and necessary treatment must be provided for the same. It should be noted that an episode of hypersensitive response to Galcanezumab can occur immediately, after a week, or even after several days. One of the most commonly recorded hypersensitivity reactions to Galcanezumab is irritation and abnormalities at the injection site.

What Is Galcanezumab?

Galcanezumab is a drug that is used in the prevention and management of migraine as well as cluster headaches. The drug is supposed to be injected at specific sites of the body through a subcutaneous route. Migraine refers to episodes of throbbing headache that may get severe over time and may also be accompanied by sensitivity to light, sound, and vomiting tendencies. Caffeine and chocolate are two of the most common trigger factors of migraine-type headaches. Cluster headaches refer to on and off episodes of headaches on any side of the head or only around any one of the eyes. Being from amongst the categories of monoclonal antibody drugs, Galcanezumab releases the mechanism of action because of blocking the normal functioning of certain chemicals and hormones of the body that are known to result in migraine headaches and cluster headaches.

What Are the Dosage Strengths, Administration Details, and Forms of Galcanezumab?

For migraine, two consecutive injections administered through the subcutaneous route with a strength of 120 mg is the recommended dose of Galcanezumab. Therefore, the total equivalent dose comes to 240 mg. The first dose is called the loading dose and the second dose is a monthly dose, both of which are injected via the subcutaneous route. In case any of the doses are missed, the administration must be done as soon as the patient recollects the same. Therefore, the administration of the drug must be scheduled on the same day every month.

For episodes of cluster headache, 300 mg is the recommended dose of Galcanezumab injection, which should be administered through the subcutaneous route in three consecutive patterns. The first dose is administered at the onset of the episode of cluster headache, the second dose is referred to as the monthly dose, and the last dose is to be given at the end of the episodic cluster headache dose. In case a dosage of Galcanezumab injection is missed, it must be subcutaneously administered as soon as remembered. For episodes of cluster headache, Galcanezumab must be scheduled on the same date every month until the treatment is over.

Being only a subcutaneous injection, Galcanezumab is to be administered by self or the caregiver. The patient is provided with all the necessary details and proper training for the subcutaneous administration of Galcanezumab. The drug's preparation and dosage, and storage instructions are also provided. Galcanezumab is present in a single-use pen or a syringe that is prefilled with an aseptic technique. Galcanezumab should be kept away from sunlight. Before subcutaneous administration of the drug, it should be kept at room temperature for thirty minutes in case it is stored in the refrigerator. The drug must not be heated through an external source of heating such as a microwave or boiling water. The drug must also not be shaken vigorously before administration. Galcanezumab must be free of any discoloration or presence of any particulate substances. A cloudy appearance of the drug with clear visibility of substances are signs of contamination, and thus, the drug does not become suitable for administration.

What Are the Sites of Injection for Galcanezumab?

Galcanezumab must be administered through the subcutaneous route and no other route. The drug administration should be explained in great detail to the patient and the caregiver since the drug is self-administered. Prefilled pens and syringes that provide single doses of Galcanezumab are available. In case there is any kind of redness, irritation, wound, bruise, tenderness, or hardness present in the selected site of drug administration, the injection must not be given on that particular spot.

Mentioned below are the several sites of administration that are suggested for Galcanezumab.

• Abdomen.

• Thighs.

• Upper arm.

• Buttocks.

What Are the Strengths and Dosage of Galcanezumab?

Galcanezumab has been established to be a sterile and transparent liquid that is colorless and opalescent with a slight tinge of yellow or brown.

Mentioned below are the strengths and dosage forms of Galcanezumab. All the available forms are only for subcutaneous injection.

• 120 mg per mL as a prefilled single-dose pen.

• 120 mg per mL as a prefilled single-dose syringe

• 100 mg per mL as a prefilled single-dose syringe.

What Are the Indications of Galcanezumab?

Galcanezumab is indicated for the preventive management of Migraine. Galcanezumab is additionally indicated in patients suffering from episodes of cluster headaches. Subcutaneous injection of Galcanezumab works as an antagonist to calcitonin-gene and peptides that are related to calcitonin-gene.

What Are the Contraindications of Galcanezumab?

The subcutaneous administration of Galcanezumab injection is contraindicated in patients who are known to be hypersensitive to drugs or have a known hypersensitive reaction with Galcanezumab-glnm in particular.

What Are the Precautions That Must Be Taken Into Consideration Regarding Galcanezumab?

It should be noted that there are quite a few precautions that are supposed to be taken by the patient who is undergoing therapy with Galcanezumab. Hypersensitivity reaction is one of the most common conditions, generally seen immediately, after a week, or even after several days of administration of Galcanezumab. A hypersensitivity reaction can be understood as the presence of rash, difficulty in breathing, and urticaria. The patient is advised to immediately discontinue the administration of Galcanezumab in case any of the hypersensitivity reactions manifest.

What Are the Adverse Reactions of Galcanezumab?

Hypersensitivity reaction that results in clinical manifestations such as skin irritation, urticaria, redness, and swelling of the skin, is one of the most common adverse reactions of Galcanezumab.

What Are the Clinical Study and Trial Experiences With Galcanezumab?

All clinical studies and clinical trials take place in certain conditions that vary from each other. Because of the variation in the adverse reactions and discrepancy between the trial conditions, the observation in a clinical setup may not be completely parallel with the trial results and establishment.

Approximately 2586 patients who have been suffering from migraine were evaluated for the safety and efficiency of Galcanezumab. Out of these patients, 1920 were directly exposed to Galcanezumab for a span of six months with the administration of a single dose per month. The remaining patients were under therapy with Galcanezumab for twelve months with a single dose administration of the drug every month. Throughout the study, the strength of the medicine was 120 mg of Galcanezumab every month. The study was a double-blind trial treatment. 85 % of the candidates were female, and 77 % of them were Caucasian with an average age of 41 years. Hypersensitivity reaction was observed to be one of the most common adverse reactions of Galcanezumab in patients suffering from migraine. In addition, pain and discomfort at the site of injection, itch, rash, erythema, and swelling were some signs and symptoms of the adverse reactions to Galcanezumab.

Around 106 patients had been evaluated for the safety and efficiency of Galcanezumab in patients suffering from cluster headache episodes. Forty-nine of these patients were exposed to Galcanezumab, and the rest were on a placebo. The ones who were treated with Galcanezumab consisted of 88 % caucasian patients with an average age of 47 years. The study was documented in a double-blind treatment manner. The strength of Galcanezumab in the trials done in patients suffering from cluster headache episodes was 300 mg administered monthly.

What Are the Immunogenicity Factors of Galcanezumab?

Galcanezumab has potential for the development of immunogenicity, which is parallel to almost all available drugs. Depending on the type of assay and the sensitivity of the assay, the antibodies are detected. There are additional factors and changes that will have an effect on the presence of antibodies as well as neutralizing antibodies. Some of the elements are the method of the assay, the way the sample is handled, the time at which the collection occurs, medications that are concomitant, and any presence of underlying medical diseases. In vitro immunoassay is the kind of assay that was used for the detection and presence of antibodies that do not bind themselves to the Galcanezumab-gnlm antibodies. Patients with positive sera in the immunoassay screening test had to undergo an additional in vitro ligand binding immunoassay in order to confirm the presence of neutralizing antibodies. The clinical studies and trials of Galcanezumab were done for around six months, and it was observed that 4.8 % is the incidence rate of anti-Galcanezumab-gnlm antibodies. In studies that were conducted for approximately twelve months, 12.5 % was the rate of incidence of antibodies due to Galcanezumab.

Is There a Risk to Pregnant Patients With Galcanezumab?

There have not been a sufficient amount of studies on pregnant patients who are supposed to undergo therapy with Galcanezumab. Thus the amount of established results and shreds of evidence about a pregnant patient undergoing Galcanezumab treatment is not sufficient to deliver a strong safety and efficiency summary. However, it should be noted that a good amount of established results prove an increased risk in pregnant patients for developing preeclampsia. There had been no adverse effects on the embryonic and fetal development of lab rats who were put under Galcanezumab therapy. There had not been any prenatal or postnatal alterations in lab rats.

Is There a Risk to Lactating Patients With Galcanezumab?

There has not been enough research done on patients who are lactating. Animal tests and trials that were done on lactating lab rats did not find any specific presence of Galcanezumab in the milk. It should be noted that the high potency of drugs to excrete in human milk, as well as no clinical trial done and no human milk tested for the presence of Galcanezumab, should lead to solid questioning and need for the drug in patients who are lactating.

Can Galcanezumab Be Used in Pediatric and Geriatric Age Groups?

The safety and efficacy of Galcanezumab have not been established in the pediatric group of patients and patients above the age of 65 because the age group comprising pediatric and geriatric individuals was not part of any single clinical study or trial.

Galcanezumab for Doctors:

Galcanezumab-gnlm is an igG4 monoclonal humanized antibody that is specific for CGRP or calcitonin-gene-related peptides ligand. Galcanezumab is produced and developed in CHO cells, known as Chinese Hamster Ovary, with the help of recombinant DNA technology. Galcanezumab comprises two immunoglobulin kappa light chains that are identical to each other. In addition to this, there are two immunoglobulin gamma heavy chains that are identical to each other. The overall molecular weight is around 147 kilodaltons.

What Is Galcanezumab?

Galcanezumab is a sterile injection that is free of preservatives and looks clear or opalescent. It has no color, but there may be some tinge of yellow to brown. Galcanezumab is only for subcutaneous administration and should not be used through any other route. Galcanezumab is supplied and stored in a single-dose 1 mL pen that is prefilled with 120 mg of Galcanezumab. The 1 mL pen can also be in the form of a syringe with 100 mg to 200 mg of Galcanezumab. A 1mL dose of Galcanezumab contains 0.5 mg of L-histidine, 1.5 mg of L-histidine hydrochloride monohydrate, 0.5 mg of Polysorbate 80, 8.8 mg of sodium chloride, and water with a broad pH range between 5.3 to 6.3.

What Is the Mechanism of Action of Galcanezumab?

Galcanezumab is a monoclonal antibody that is humanized, and it binds to the CGRP ligand, also known as the calcitonin-gene-related peptide ligand. Galcanezumab also blocks the calcitonin-gene-related peptide ligand binding to its receptor site.

What Is the Pharmacodynamic Action of Galcanezumab?

There has not been any deeper investigation into the pharmacodynamics of Galcanezumab, and thus there is no relevant data about the pharmacodynamic alterations done by Galcanezumab.

What Is the Pharmacokinetics of Galcanezumab?

Galcanezumab displays a linear pattern of pharmacokinetics, and the exposure to the drug is directly proportional to the dose that had been administered. The loading dose after the first dose of Galcanezumab is 240 mg, which is achieved along with the steady-state of serum Galcanezumab. It should be noted that, in the several studies and trials done with Galcanezumab, there had not been any discrepancy or dissimilarity in the pharmacokinetics of Galcanezumab between healthy subjects and subjects that were ill or had been suffering from chronic migraine and cluster headaches.

• Absorption:

The time it takes for Galcanezumab to attain the maximum amount of concentration is approximately five days. The subcutaneous injection of Galcanezumab at any chosen administration site did not alter the rate of absorption.

• Distribution:

The V/F, known as the apparent volume of distribution of the Galcanezumab, is 34 % IIV, or 34, and inter-individual variability equals 7.3 L.

• Elimination and Metabolism:

It is expected for Galcanezumab to be degraded into minute peptides as well as small amino acids through a catabolic route, which is similar to the pathway followed by endogenous IgG. The CL/F or the apparent clearance of Galcanezumab is 0.008 L/h. The half-life for the elimination of Galcanezumab is around 27 days.

• Specific Population:

Age, race, sex, diagnosis of the headache, and the kind of spectrum that the migraine falls in do not lead to any drastic change in the pharmacokinetics of Galcanezumab, which applies for both conditions- migraine and cluster headaches. In addition, the patient's body mass index does not pose any changes in the drug's pharmacokinetics.

• Hepatic Impairment and Renal Impairment:

Patients who are known to be suffering from impairment of the renal system or the hepatic system of the body will not show any alterations in the pharmacokinetics of Galcanezumab. Therefore, the creatinine clearance of patients suffering from renal and hepatic abnormalities may not lead to any kind of pharmacokinetic changes due to Galcanezumab. It should be noted that there has not been a deep study into the pharmacokinetic changes in patients suffering from hepatic and renal impairments.

• Drug Interactions:

P450 enzyme is one of the cytochrome enzymes that does not metabolize Galcanezumab. Therefore, the interaction between Galcanezumab and P450 enzyme and concomitant drugs that may be inducers, substrates, or even cytochrome P450 enzyme inhibitors does not occur.

What Are the Nonclinical Toxicology Factors of Galcanezumab?

There has not been any kind of carcinogenic and mutagenic study to understand the potential of Galcanezumab under the same aspects. The fertility of lab rats was not hampered due to the injection of Galcanezumab. The strength of Galcanezumab that was administered to the lab rats was approximately eight times more than the suggested dosage for human beings. Even before mating, subcutaneous administration of Galcanezumab in males and female lab rats did not lead to any abnormality in the pharmacokinetics of Galcanezumab.

Galcanezumab for Patients:

Galcanezumab is a drug used for the preventive management of cluster headaches and migraine attacks. Galcanezumab is an antagonist to calcitonin-gene, which is related to a peptide group. Galcanezumab received approval from the Food and Drug Administration (FDA) on the 4th of June 2019, specifically for treating cluster headaches. Prior to this, Galcanezumab had already conferred the Food and Drug Administration approval for preventive treatment of migraine in adult patients on the 27th of September 2018.

What Is Galcanezumab?

Galcanezumab is a drug that is used for the treatment and preventive management of migraine in adult patients. The recommended dose of Galcanezumab includes two injections of 120 mg each that is to be administered subcutaneously in a consecutive pattern. Thus the total dose is 240 mg. The first dose is called a loading dose, and the next dose is called the monthly dose. In case a dose of Galcanezumab is missed, one must soon administer the same on recollection. Therefore, Galcanezumab must be administered on the same day of every month. About the dosage of Galcanezumab for cluster headaches, the dose that has been recommended is 300 mg which three injections must administer in a consecutive pattern, each of which is 100 mg. This will continue until the deprivation of cluster headaches.

What Are the Ingredients of Galcanezumab?

Galcanezumab is supplied and stored in a single-dose 1 mL pen that is prefilled with 120 mg of Galcanezumab. The 1 mL pen can also be in the form of a syringe with 100 mg to 200 mg of Galcanezumab. A 1mL dose of Galcanezumab contains 0.5 mg of L-histidine, 1.5 mg of L-histidine hydrochloride monohydrate, 0.5 mg of Polysorbate 80, 8.8 mg of sodium chloride, and water with an overall pH range between 5.3 to 6.3.

Who Should Not Use Galcanezumab?

Patients who are known to be allergic to Galcanezumbad or similar drugs, or even the different components of the drug, are not allowed to go ahead with therapy from Galcanezumab. Instead, the patients are advised to discuss with their respective health care providers in case they are pregnant or are planning to get pregnant, whether they are lactating, are suffering from any underlying medical condition, have a known hypersensitivity condition to any particular drug, and if they are allergic for specific groups of medicines.

What Are the Side Effects of Galcanezumab?

Hypersensitivity and allergic reactions are two of the most common side effects of Galcanezumab.

Mentioned below are the several side effects of the subcutaneous administration of Galcanezumab.

• Skin redness.

• Hives.

• Rashes.

• Irritations at the site of injection.

• Swelling.

• Difficulty in breathing.

• Sore throat.

• Inflammation of the tongue and the face.

• Bumps in the oral mucosa.

• Pain at the injection site.

• Blisters.

• Heat boils.

How Is Galcanezumab Administered?

Galcanezumab is a subcutaneous injection self-administered by the patient or the caregiver. The accurate and exact manner of administration of the injection will be explained in great detail by the respective health care provider. The drug is available in single shots of pens or syringes. Particular drug administration sites are available such as the buttocks, thigh, and abdomen, and their health care providers, usually the upper arm, but the preferred locations of drug administration after performing a test dose for any hypersensitivity reactions.

How Is Galcanezumab Supplied?

Being only a subcutaneous injection, Galcanezumab is to be administered by self or the caregiver. The patient is provided with all the necessary details and proper training for the subcutaneous administration of Galcanezumab. The drug's preparation and dosage, and storage instructions are also provided. Galcanezumab is present in a single-use pen or a syringe that is prefilled with an aseptic technique. Galcanezumab injection is a subcutaneous injection that is free of preservatives, sterile, opalescent, or transparent, and does not have any color but may show a slight tinge of yellow or brown. It should be noted that Galcanezumab is not prepared with any kind of natural rubber latex.

Mentioned below are the different sources of supply of Galcanezumab.

• A single-dose prefilled pen of 120 mg/mL.

• A single-dose prefilled syringe of 100 mg/mL.

• A single-dose prefilled syringe of 120 mg/mL.

How Is Galcanezumab Stored?

Galcanezumab must be refrigerated and stored within a temperature range of 36 degrees Fahrenheit to 46 degrees Fahrenheit or two degrees Celsius to eight degrees Celcius. Galcanezumab must not be stored under direct sunlight and should be strictly kept from sunlight and other heat sources. The drug should not be frozen, nor should the drug be shaken before administration. Galcanezumab must be kept at room temperature for approximately thirty minutes before the subcutaneous injection. The drug must not be stored outside the suggested temperature ranges for more than seven days. Once the pill is unsealed, it must not be held again and thus must be used all at once. The puncture-resistant container must be discarded even if a single dose is contaminated, as mentioned in earlier instructions. In case the color of the drug is changed to gray or any other color other than those noted above, the drug is no longer fit to be subcutaneously administered and thus must be immediately discarded.