Mirikizumab-Mrkz - Indication, Dosage, Precautions, and Pharmacological Aspects

Overview:

Mirikizumab-mrkz treats Crohn's disease and ulcerative colitis (UC). It was the first IL (interleukin) - 23p19 inhibitor licensed in Japan in March 2023. Patients with moderate to severe UC who have not reacted well to conventional or alternative medicines can use it for induction and maintenance therapy. In addition, the EU (European Union) approved using Mirikizumab in March 2023 for treating people with moderately to highly active ulcerative colitis, particularly those who did not respond well to conventional therapy or biological treatments or lost their responsiveness.

On October 26, 2023, the United States Food and Drug Administration (US FDA) approved Mirikizumab, a novel and highly efficacious medication for ulcerative colitis (UC), providing patients suffering from this severe and chronic inflammatory bowel disease with a new option for treatment.

Drug Group:

A treatment option for patients with intermediate to severe active ulcerative colitis is Mirikizumab, an anti-IL (interleukin) - 23 monoclonal antibody. It works similarly to a monoclonal antibody.

Available Doses and Dosage Forms:

• Doses:

  • For Mirikizumab-mrkz, the induction dosage is 300 milligrams (mg) intravenous (IV) infusion given at week zero, week four, and week eight for a minimum of 30 minutes.

  • The maintenance dose consists of a subcutaneous (SC) injection of 200 mg divided into two shots of 100 mg each, administered every four weeks beginning at week 12 and continuing every four weeks after that.

• Dosage Forms:

  • Mirikizumab-mrkz is offered in various formulations according to particular modes of administration.

  • IV Infusion - It is offered as an injection with 300 mg per 15 mL (milliliter) and as 20 mg/mL solution in a single-dose vial for intravenous infusion.

  • SC Use - It is offered as an injection with a 100 mg/mL solution in a single-dose prefilled pen for subcutaneous administration.

For Patients:

What Is Ulcerative Colitis?

Ulcerative colitis (UC) is a chronic illness that causes inflammation and ulcers in the colon. It belongs to a class of illnesses called inflammatory bowel diseases (IBD). Bloody diarrhea, abdominal cramps, and more frequent bowel motions are common signs of ulcerative colitis.

Symptoms of ulcerative colitis (UC) frequently follow a cyclical pattern in which patients experience flare-ups or episodes of severe symptoms interspersed with extended stretches of minimal to nonexistent symptoms (remission). When there is a flare-up, the symptoms worsen and can greatly affect day-to-day functioning; in contrast, remission periods are characterized by reduced symptoms; for individuals with UC, management techniques, including medication, lifestyle modifications, and occasionally surgery, are intended to manage symptoms and extend periods of remission.

How Does Mirikizumab-mrkz Work?

The interleukin-23p19 antagonist Mirikizumab-mrkz may be useful in treating adults with moderate to extremely severe ulcerative colitis. The IL-23 pathway's excessive stimulation of inflammation is a major factor in the pathophysiology of ulcerative colitis (UC). Mirikizumab-mrkz inhibits the IL-23 pathway by specifically targeting the p19 component of IL-23.

What Are the Things to Inform the Doctor Before Taking the Drug?

It is important to let the doctor or pharmacist know about all of the medical histories before starting Mirikizumab, especially if they have a history of persistent, recent, or recurrent infections like herpes (infection that is caused by herpes simplex virus resulting in blisters or ulcer) or tuberculosis (disease of the lungs). Mirikizumab can increase the chance of contracting infections or worsening pre-existing illnesses, so it is critical to discuss the medical history to choose the best course of action and analyze potential hazards. They must also inform the doctor about their drug history and the present medications. The doctor must also be informed if the patient is a lactating mother, pregnant, or planning to conceive.

How Is Mirikizumab-mrkz Administered?

• For IV Infusion:

  • Doctors usually screen patients for tuberculosis (TB) before starting treatment and watch for any symptoms throughout and after the drug course. Before starting Mirikizumab, any essential therapy for TB or other infections should be given.

  • A medical practitioner carefully administers the first three doses through an intravenous (IV) route for about half an hour. Subsequent doses consist of two consecutive injections beneath the skin, usually administered every four weeks as the physician prescribes. The dosage depends on the patient's health and response to therapy. For this reason, following the doctor's recommendation is essential.

  • Mirikizumab-mrkz is an intravenous solution that must be administered by a healthcare provider using aseptic techniques because it is a single-use product. Check the vial visually for discoloration or particle matter before administration to ensure the solution is clear to opalescent, colorless to slightly yellow to slightly brown, and free of visible particles. If the solution is hazy or has visible particles, do not use it. With an 18 to 21- gauge needle, remove 15 mL of the Mirikizumab-mrkz solution and transfer it, without mixing with any other medications or solutions, to an infusion bag (50 mL to 250 mL) filled with 0.9 percent sodium chloride injection or five percent dextrose injection. To mix, gently invert the bag; do not shake. Establish a connection with the IV administration set, prime the line, and give the infusion for at least half an hour.

  • Use the same rate for administering Mirikizumab-mrkz after the infusion to flush the line with either 0.9 percent sodium chloride or a five percent dextrose injection. Keep in mind that the flushing phase extends beyond the 30-minute infusion interval.

• For SC Use:

  • Mirikizumab-mrkz should only be used under a healthcare provider's direction and supervision. Patients who have received training in subcutaneous injection technique can self-inject Mirikizumab-mrkz. Give patients and caregivers instructions for administering Mirikizumab-mrkz subcutaneously per the product's instruction manual.

  • Clean hands by washing before taking this prescription. Allow Mirikizumab to come to room temperature thirty minutes before usage by removing it from the refrigerator. There is no other way to heat this medication. It should never be put in the microwave or submerged in hot water. Do not shake the medication. The drug should have a color that is either clear or somewhat yellow or brown. The product should not be used if particles, cloudiness, or discoloration are noticed.

  • It is crucial to prepare the area of injection with rubbing alcohol before administering each prefilled pen and to change up the injection location every time to reduce skin injury. The drug should be inserted into the back of the upper arms, the thighs, or the abdomen (at least two inches from the belly button). Steer clear from injecting into the hardened, bruised, painful, or sore skin.

  • Avoid skin that is hardened, red, bruised, or sensitive. Mirikizumab does not contain preservatives, so any leftovers should be thrown away immediately. Should a dose be overlooked, take it as soon as possible and restart the four-week dosing regimen.

• For this medicine to be completely effective, consistent use is essential. The patient may find it easier to follow the prescribed dose schedule if they set reminders on their calendar. If the condition worsens, they should also inform their doctor.

What Are the Side Effects of Mirikizumab-mrkz?

• Along with headaches or joint discomfort, common side effects like redness, soreness, or inflammation at the injection site may also happen. It is advised to notify the doctor immediately if these side effects worsen or persist.

• The immune system's efficacy may be lowered by Mirikizumab-mrkz, potentially increasing the risk of severe diseases. Call the doctor immediately if a patient develops infection-related symptoms, such as a persistent sore throat, fever, chills, or cough.

• Serious side effects that require immediate medical attention include prolonged vomiting or nausea, decreased appetite, skin or eye discoloration, and black urine.

• A serious adverse reaction to this medication is possible, although it is quite rare. If a patient experiences any symptoms, such as a rash, severe dizziness, breathing difficulties, swelling (especially of the neck, face, or tongue), and itching, get medical attention once.

Dietary Considerations: No dietary modifications unless advised by the doctor.

Missed Dose: It is important to take this medication as prescribed. It is advised to speak with a doctor or pharmacist immediately to get a revised dosing plan in case of a missed dose. It is crucial to avoid taking two doses to make up for a missed one.

Overdose: In cases of overdosing with noticeable symptoms like fainting or breathing problems, it is important to inform the doctor immediately and get medical attention urgently.

Storage: Preventing freezing temperatures is important while storing the drug in a refrigerator. Keep the product in its original carton to protect it from light until it is time to use it. All unused medication should be discarded after two weeks if the prefilled pen is left out of the refrigerator and kept at room temperature. Restoring a product to room temperature inside the refrigerator is not advised. All prescriptions must be kept out of their reach to protect children and pets.

For Doctors:

Indication:

Mirikizumab is used to treat patients with moderately to highly active ulcerative colitis.

Contraindication:

Those with a history of documented severe hypersensitivity responses to either Mirikizumab-mrkz or any of its constituents should not be given that medication. Before starting Mirikizumab-mrkz treatment, medical professionals must ensure no known hypersensitivity to the drug or any of its constituents by carefully reviewing the patient's medical history.

Dose:

The induction dosage for Mirikizumab-mrkz is an intravenous (IV) infusion of 300 mg administered over a minimum of 30 minutes at weeks zero, four, and eight. Subcutaneous (SC) injection of 200 mg divided into two injections of 100 mg each is the maintenance dose, which is given every four weeks starting at week 12 and continuing every four weeks after that.

What Are the Pharmacological Aspects of Mirikizumab-mrkz?

Description

• For Intravenous Infusion - Mirikizumab-mrkz injection is a sterile, non-preservative solution diluted and infused intravenously. It is colorless, slightly yellow, or slightly brown and can range in transparency to opalescence. The pH range of the Mirikizumab-mrkz solution falls between 5.0 and 6.0. This solution is contained within a single-dose vial and requires dilution before intravenous administration. Each milliliter's formulation consists of:

  • Mirikizumab-mrkz: 20 mg.

  • Anhydrous Citric Acid: 0.4 mg.

  • Polysorbate 80: 0.5 mg.

  • Sodium Chloride: 8.8 mg.

  • Sodium Citrate: 2.1 mg.

  • Water for injection.

• For Subcutaneous Use - Subcutaneous formulation of Mirikizumab-mrkz injection is offered as a sterile, preservative-free solution. It might be white, pale yellow, or somewhat brown, which seems transparent to opalescent. This subcutaneous formulation solution of Mirikizumab-mrkz has a pH range of 5.0 to 6.0. This formulation comes in a handy single-dose prefilled pen that makes administration simple. It is meant to be used subcutaneously. One milliliter single-dose prefilled pen contains the following:

  • Mirikizumab-mrkz: 100 mg.

  • Anhydrous Citric Acid: 0.4 mg.

  • Polysorbate 80: 0.3 mg.

  • Sodium Chloride: 8.8 mg.

  • Sodium Citrate: 2.1 mg.

  • Water for Injection.

• Mechanism of Action - The humanized IgG4 (immunoglobulin G4) monoclonal antibody Mirikizumab-mrkz is intended to specifically target the p19 subunit of human IL (interleukin)-23 cytokine, a particular immune system component. Mucosal inflammation is significantly influenced by IL-23, which also affects the growth, survival, and maturation of specific innate immune cells and T cell subtypes that generate pro-inflammatory cytokines. Mirikizumab-mrkz stops IL-23 from connecting with its receptor by specifically attaching to the p19 subunit of IL-23. Through this intervention, inflammation is prevented from being caused by the production of chemokines and pro-inflammatory cytokines. Inhibiting IL-23p19 has demonstrated potential in lowering intestinal inflammation in preclinical investigations utilizing animal models. This indicates that Mirikizumab-mrkz may have therapeutic potential in treating disorders related to excess inflammation, particularly in the gut.

• Pharmacokinetics - The body responds to Mirikizumab-mrkz consistently, with levels rising directly to the administered dose. The exposure of the drug in the body increases in proportion to the amount given, whether it is injected intravenously or subcutaneously. This dose-dependent trend was observed in experiments conducted on healthy adults with doses ranging from 60 to 2400 mg for intravenous injection and 200 to 400 mg for subcutaneous injection. Moreover, there was no discernible accumulation of Mirikizumab-mrkz in the blood over time when patients with ulcerative colitis had subcutaneous injections of the medication every four weeks. This implies that the medication does not substantially accumulate when given in this way over time.

• Pharmacodynamics - As per the studies conducted, frequencies of clinical remission and the clinical response showed a significant connection with the average concentration of Mirikizumab-mrkz. Increased levels of Mirikizumab-mrkz in patients' bodies were linked to significantly higher rates of eliciting a clinical response and reaching clinical remission.

Toxicity:

Studies on animals have not been conducted to determine whether Mirikizumab-mrkz can result in genetic alterations or cancer. On the other hand, no abnormal changes in organ weight or tissue structure were noticed when monkeys were administered a larger dose of seven times the approved human dose of Mirikizumab-mrkz subcutaneously once a week for 26 weeks. This treatment did not have any effect on the reproductive organs.

Clinical Studies

A trial was conducted from January 2016 to September 2017 to evaluate the safety and effectiveness of Mirikizumab in patients with moderate to highly active UC. Patients were recruited from 14 different countries. Mirikizumab showed promise in generating a clinical response in patients with ulcerative colitis (UC) over the first 12 weeks of treatment in a randomized trial. More investigation is necessary to determine the ideal dosage for causing remission. Additionally, the trial showed that Mirikizumab remained effective for the maintenance period, indicating a long-lasting and consistent effect on UC symptoms.

Adverse Reactions of Mirikizumab-mrkz

Upper respiratory tract infections and arthralgia are the most often reported side effects (occurring in two percent or more of people) following induction with Mirikizumab. During the maintenance phase, typical side effects include headaches, arthralgia, rash, herpes viral infection, injection site reactions, and upper respiratory tract infections.

Warnings and Precautions:

• Hypersensitivity Reactions - The administration of Mirikizumab-mrkz has been linked to severe hypersensitivity events, including anaphylaxis, especially when given intravenously. Furthermore, reports of infusion-related hypersensitivity responses, such as pruritus and mucocutaneous erythema, have been documented during the induction phase. If a serious hypersensitivity reaction occurs, it is advised to stop using Mirikizumab-mrkz and start treating the patient immediately.

• Infections - Using Mirikizumab-mrkz may increase the risk of infection. Patients with clinically significant current infections should only start Mirikizumab-mrkz medication once the infection has resolved or they receive appropriate treatment. When giving Mirikizumab-mrkz to patients with recurring or chronic infections, consider the risks and benefits carefully. Ask individuals who exhibit symptoms or indicate serious acute or chronic infection to consult a doctor immediately. Keep a close eye on the patient and stop giving Mirikizumab-mrkz until the infection clears up, if a serious infection develops, or if conventional treatment cannot treat it.

• Tuberculosis - It is important to screen patients for tuberculosis (TB) infection before starting Mirikizumab-mrkz medication. It is not appropriate to provide Mirikizumab-mrkz to people who have an active tuberculosis infection. It is best to start treating latent tuberculosis before administering Mirikizumab-mrkz. Suppose a patient has a history of latent or active TB, and an appropriate course of treatment cannot be determined. In that case, they should be considered for anti-TB therapy before starting Mirikizumab-mrkz.

• Hepatotoxicity - Before starting treatment with Mirikizumab-mrkz, monitor liver enzymes and bilirubin levels regularly. After that, monitor the results for at least 24 weeks. Continuous monitoring ought to be in line with standard procedures for patient care. When liver cirrhosis is evident, take alternative therapy choices into account. Investigate right away to rule out any possible causes of high liver enzymes, especially drug-induced liver injury. If drug-induced liver damage is suspected, stop the treatment for a short while until it is confirmed. Patients should be advised to get help if they experience any symptoms that point to liver impairment.

• Immunizations - Avoid giving live vaccinations to patients receiving Mirikizumab-mrkz therapy. Immune system-related medications may increase infection vulnerability after receiving live vaccinations. Patients must receive all age-appropriate vaccines according to current immunization standards before starting Mirikizumab-mrkz therapy. The available data on how Mirikizumab-mrkz treated patients respond to live and non-live vaccinations must be revised.

What Are the Drug Interactions of Mirikizumab-mrkz?

Studies on Mirikizumab-mrkz in populations with ulcerative colitis patients revealed that medications such as corticosteroids, aminosalicylates, and oral immunomodulators did not affect Mirikizumab’s clearance. Nevertheless, these patients were not subjected to particular drug interaction testing at the suggested Mirikizumab-mrkz dosage. Higher dosages of Mirikizumab-mrkz, however, did not affect the levels of different medicines metabolized by particular enzymes (CYP3A, CYP2C9, CYP2D6, CYP2C19, CYP1A2) in a different trial involving a different disease. This implies that the breakdown and efficacy of these other drugs were not hampered, even when Mirikizumab-mrkz was used at a dosage greater than usually advised.

Specific Considerations:

• Pregnancy - The effects of Mirikizumab on expectant mothers and their unborn children are not well enough understood. High-dose studies on monkeys did not reveal any harm to the young, but the treated groups saw a higher number of miscarried pregnancies, albeit within predicted limits. Pregnancy-related hazards for women with inflammatory bowel disease (IBD) could include smaller or premature newborns. If kids were exposed to Mirikizumab in the womb, it may be important to consider when to give them live vaccines after birth, as this could potentially damage the baby's immune system.

• Nursing Mother - There is currently no information about the presence of Mirikizumab-mrkz in human breast milk, its effects on breastfed infants, or how it affects milk production. Human milk can spread maternal IgG and monoclonal antibodies, such as Mirikizumab-mrkz. Nevertheless, little is known about the consequences of restricted systemic exposure and localized gastrointestinal exposure to Mirikizumab-mrkz in breastfed infants. The advantages of breastfeeding for the mother's development and health must be weighed against the clinical necessity of Mirikizumab-mrkz for the mother and the possible risks of Mirikizumab-mrkz and the underlying maternal condition for the breastfed child when deciding whether to use it.

• Pediatric Population - The safety and effectiveness of Mirikizumab-mrkz have not been confirmed in pediatric patients.

• Geriatric Population - Of the 795 participants treated with Mirikizumab-mrkz in two clinical studies, 64 (or eight percent) were 65 or older. In contrast, just ten (one percent) were 75 or older. These studies could not definitively establish if therapy response differs between older adults (65 and older) and younger adults (due to a small number of senior participants). Nevertheless, documented clinical experiences have not revealed appreciable differences in responsiveness between younger and older participants. Furthermore, when comparing patients 65 and older to younger adult subjects, no clinically significant variations in the pharmacokinetics, which is how the body processes Mirikizumab-mrkz, were seen.