Brand name: Omvoh
Drug class: Immunomodulatory Agents

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

Introduction

Humanized immunoglobulin G4 (IgG₄) monoclonal antibody; interleukin-23 (IL-23) antagonist.¹

Uses for Mirikizumab-mrkz

Ulcerative Colitis

Treatment of moderately to severely active ulcerative colitis in adults.¹

American College of Gastroenterology (ACG) and American Gastroenterological Association (AGA) guidelines recommend specific treatments selected according to disease severity, disease location/extent, disease prognosis, and previous therapies used.^{4 5 6} For adult outpatients with moderate to severe ulcerative colitis, AGA recommends tumor necrosis factor (TNF) blocking therapies, vedolizumab, tofacitinib, or ustekinumab over no treatment.^{4 5} ACG recommends oral corticosteroids, TNF blocking agents, vedolizumab, or tofacitinib for induction of remission in patients with moderately to severely active ulcerative colitis.⁶ Early use of biologic agents with or without immunomodulator therapy is conditionally recommended over gradual step-up therapy after failure of 5-aminosalicylates.⁵ Consult guidelines for additional details.^{4 5 6} Mirikizumab-mrkz is not addressed in the current guidelines.^{4 5 6}

Mirikizumab-mrkz Dosage and Administration

General

Pretreatment Screening

• Evaluate for tuberculosis (TB) infection prior to initiating treatment.¹

• Obtain liver enzymes and bilirubin levels prior to initiation.¹

• Complete all age-appropriate vaccinations according to current immunization guidelines.¹

Patient Monitoring

• Evaluate liver enzymes and bilirubin levels for at least 24 weeks of treatment.¹ Monitor thereafter according to routine patient management.¹

Administration

Sterile and preservative free.¹ Discard any unused portion.¹

IV Administration

Do not mix with other drugs.¹ Do not dilute or infuse through same IV line with solutions other than 0.9% sodium chloride or 5% dextrose injection.¹

At end of infusion, flush line with 0.9% sodium chloride injection or 5% dextrose injection.¹ Administer flush at same infusion rate used for mirikizumab-mrkz administration.¹ Time required to flush solution from infusion line is in addition to minimum 30-minute infusion time.¹

Connect the IV administration set (infusion line) to prepared infusion bag and prime line.¹ Infusion should be started immediately after preparation.¹ If not used immediately, store diluted infusion solution in refrigerator at 2 to 8°C.¹ Use diluted infusion solution within 48 total hours, of which not more than 5 hours are permitted at non-refrigerated temperatures not to exceed 25°C starting from time of vial puncture.¹ Keep product away from direct heat or light.¹ Do not freeze diluted solution in prepared infusion bag.¹

Dilution

Using aseptic technique, withdraw 15 mL of solution from vial using 18- to 21-gauge needle and transfer to infusion bag ranging from 50 to 250 mL of 0.9% sodium chloride or 5% dextrose injection.¹ Gently invert infusion bag to mix contents.¹ Do not shake prepared infusion bag.¹

Prior to administration, inspect for particulate matter and discoloration; should be clear to opalescent, colorless to slightly yellow to slightly brown solution, and free of visible particles.¹ Do not use if cloudy or there are visible particles.¹

Rate of Administration

Administer over at least 30 minutes.¹

Sub-Q Administration

Maintenance dose requires 2 prefilled pens or syringes.¹

Patients may self-inject after training in sub-Q injection technique.¹ Provide proper training to patients and/or caregivers according to instructions provided with packaged product.¹

Before injection, remove prefilled pen or prefilled syringe from refrigerator and leave at room temperature for 30 minutes.¹ Inspect visually for particulate matter and discoloration prior to administration.¹ Solution should be clear to opalescent, colorless or slightly yellow to slightly brown solution, and free of visible particles.¹ Do not use if cloudy, discolored, or there are visible particles.¹ Do not shake prefilled pens or syringes.¹

Sites for injection include the abdomen, thigh, and back of upper arm.¹ Instruct patients to inject in a different location every time.¹ Administration in the back of upper arm may only be performed by another person.¹ Do not inject into areas where the skin is tender, bruised, erythematous, or indurated.¹

If a dose is missed, administer dose as soon as possible.¹ Thereafter, resume dosing every 4 weeks.¹

If needed, prefilled pen or prefilled syringe may be stored at room temperature up to 30°C for up to 2 weeks in original carton to protect from light.¹ Once stored at room temperature, do not return to refrigerator.¹ If these conditions are exceeded, must be discarded.¹

Dosage

Adults

Ulcerative Colitis

IV

Induction: 300 mg administered as an infusion over at least 30 minutes at week 0, week 4, and week 8.¹

Sub-Q

Maintenance: 200 mg, given as 2 consecutive injections of 100 mg each, at week 12 and every 4 weeks thereafter.¹

Special Populations

Hepatic Impairment

No specific population dosage recommendations at this time.¹

Renal Impairment

No specific population dosage recommendations at this time.¹

Geriatric Patients

No specific population dosage recommendations at this time.¹

Cautions for Mirikizumab-mrkz

Contraindications

• History of serious hypersensitivity reaction to mirikizumab-mrkz or any of the excipients.¹

Warnings/Precautions

Hypersensitivity

Serious hypersensitivity reactions, including anaphylaxis during IV infusion, reported.¹ Infusion-related hypersensitivity reactions, including mucocutaneous erythema and pruritis, reported.¹ If severe hypersensitivity reaction occurs, discontinue immediately and initiate appropriate treatment.¹

Infections

May increase risk of infection.¹

Do not initiate treatment in patients with clinically important active infection until infection resolves or is adequately treated.¹

In patients with chronic infection or history of recurrent infection, consider risks and benefits prior to prescribing.¹

Instruct patients to seek medical advice if signs or symptoms of clinically important acute or chronic infection occur.¹ If serious infection develops or an infection is not responding to standard therapy, monitor patient closely and do not administer until the infection resolves.¹

Tuberculosis

Evaluate patients for TB infection prior to initiating treatment.¹

Do not administer to patients with active TB infection.¹ Initiate treatment of latent TB prior to administration.¹ Consider anti-TB therapy prior to initiation in patients with past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.¹

Monitor patients for signs and symptoms of active TB during and after treatment.¹

Hepatoxicity

A case of drug-induced liver injury (ALT 18 times the upper limit of normal [ULN], AST 10 times the ULN, and total bilirubin 2.4 times the ULN) in conjunction with pruritis was reported in a clinical trial subject following a longer than recommended induction regimen.¹ Mirikizumab-mrkz was discontinued and liver test abnormalities eventually returned to baseline.¹

Evaluate liver enzymes and bilirubin at baseline and for at least 24 weeks of treatment.¹ Monitor thereafter according to routine patient management.¹

Consider other treatment options in patients with evidence of liver cirrhosis.¹ Prompt investigation of the cause of liver elevation is recommended to identify potential cases of drug-induced liver injury.¹ Interrupt treatment if drug-induced liver injury is suspected, until this diagnosis is excluded.¹ Instruct patients to seek immediate medical attention if they experience symptoms suggestive of hepatic dysfunction.¹

Immunizations

Avoid use of live vaccines.¹

Medications that interact with the immune system may increase risk of infection following administration of live vaccines.¹

Prior to initiating therapy, complete all age-appropriate vaccinations according to current immunization guidelines.¹ No data available on response to live or non-live vaccines in patients treated with mirikizumab-mrkz.¹

Immunogenicity

Observed incidence of anti-drug antibodies (ADAs) is highly dependent on the sensitivity and specificity of assay.¹ Differences in assay methods preclude meaningful comparisons of incidence of ADAs in the studies.¹

During the 52-week treatment period in clinical trials, 23% (88 out of 378 patients) of treated subjects at recommended dosage and evaluable for assessment, developed anti-mirikizumab-mrkz antibodies.¹ Of those who developed ADA, 38% (33 out of 88 patients) developed titers ≥1:160.¹ Of these, 10 had reduced serum trough concentrations compared to patients who did not develop anti-mirikizumab-mrkz antibodies, and 5 of these 10 subjects did not achieve clinical response at week 52.¹

There are insufficient data to assess whether observed ADA-associated pharmacokinetic changes reduced effectiveness.¹ There is no identified clinically significant effect of ADA on safety over the treatment duration of mirikizumab-mrkz of 52 weeks.¹

Specific Populations

Pregnancy

Insufficient evidence in pregnant females to evaluate drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.¹ There are risks of adverse pregnancy outcomes associated with increased disease activity in females with inflammatory bowel disease.¹ Adverse pregnancy outcomes associated with increased disease activity include preterm delivery (before 37 weeks' gestation), low birth weight (less than 2500 grams), and small for gestational age at birth.¹

Although there are no data on mirikizumab-mrkz, monoclonal antibodies can be actively transported across placenta, and mirikizumab-mrkz may cause immunosuppression in the in utero-exposed infant.¹ Transport of endogenous immunoglobulin G (IgG) antibodies across the placenta increases as pregnancy progresses, and peaks during third trimester.¹ Because mirikizumab-mrkz may interfere with immune response to infections, risks and benefits should be considered prior to administering live vaccines to infants exposed in utero.¹ No data regarding infant serum levels at birth and duration of persistence in infant serum after birth.¹ Although a specific timeframe to delay live virus immunizations in infants exposed in utero is unknown, a minimum of 2 months after birth should be considered because of the half-life of the product.¹

There is a pregnancy exposure registry that monitors pregnancy outcomes in females exposed to mirikizumab-mrkz during pregnancy.¹ Pregnant females exposed to mirikizumab-mrkz and clinicians are encouraged to contact manufacturer at 1-800-545-5979.¹

Lactation

There are no data on presence of mirikizumab-mrkz in human milk, effects on breast-fed infants, or effects on milk production.¹ Endogenous maternal IgG and monoclonal antibodies are transferred into human milk.¹ Effects of local GI exposure and limited systemic exposure in breast-fed infants are unknown.¹

Developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for mirikizumab-mrkz and any potential adverse effects on breast-fed child from mirikizumab-mrkz or from underlying maternal condition.¹

Pediatric Use

Safety and effectiveness not established.¹

Geriatric Use

Clinical studies did not include sufficient numbers of subjects aged ≥65 years to determine whether they respond differently than younger subjects.¹ Other reported clinical experience has not identified differences in responses between elderly and younger subjects.¹ No clinical meaningful differences in pharmacokinetics were observed in patients ≥65 years of age compared to younger adult patients.¹

Common Adverse Effects

Induction: Most common adverse effects (≥2% of patients): upper respiratory tract infections and arthralgia.¹

Maintenance: Most common adverse effects (≥2% of patients): upper respiratory tract infections, injection site reactions, arthralgia, rash, headache, herpes viral infection.¹

Drug Interactions

No drug-drug interaction studies conducted in ulcerative colitis at the recommended dosage.¹

Expected to be metabolized by proteolytic degradation to peptides and amino acids; not likely to have any direct effect on drug-metabolizing enzymes.⁷

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

May affect the pharmacokinetics of other drugs as result of improvement in inflammation.⁷ Inflammatory stimuli may lead to down-regulation of cytochrome (CYP) P450 enzymes, resulting in increased exposure of substrates of these enzymes relative to exposure in individuals without inflammatory conditions.⁷ As a result of reducing the inflammatory burden, CYP levels may be normalized, resulting in decreased exposure of CYP substrates.⁷

Results from trials in moderate-to-severe psoriasis (dosage of 250 mg sub-Q every 4 weeks) did not result in changes in the exposure of midazolam (CYP3A substrate), warfarin (CYP2C9 substrate), dextromethorphan (CYP2D6 substrate), omeprazole (CYP2C19 substrate), or caffeine (CYP1A2 substrate).⁷

Mirikizumab-mrkz Pharmacokinetics

Absorption

Bioavailability

Exhibits linear pharmacokinetics with dose-proportional increase in exposure over dose range of 60 to 2400 mg as IV injection and over dose range of 200 to 400 mg as sub-Q injection.¹

No apparent accumulation in serum over time when administered as sub-Q injection every 4 weeks.¹

Geometric mean bioavailability: 44%.¹

Injection site location (abdomen, upper arm, or thigh) does not significantly influence bioavailability following sub-Q injection.¹

Onset

Median time to maximum serum concentration: 5 days post-dose.¹

Special Populations

Following IV administration of 300 mg (recommended induction dose) in patients weighing ≥90 kg, estimated geometric mean average concentration (C_avg) was 20% lower compared with patients weighing <90 kg.¹

Following sub-Q administration of 200 mg (recommended maintenance dose) in patients weighing ≥90 kg, the estimated geometric mean C_avg was 38% lower compared with patients weighing <90 kg.¹

Rate of clinical remission and clinical response did not different significantly between patients weighing ≥90 kg and patients weighing <90 kg.¹

Distribution

Extent

Distributed into human milk.¹

Elimination

Metabolism

Expected to be degraded into small peptides and amino acids via catabolic pathways in same manner as endogenous IgG.¹

Half-life

9.3 days.¹

Special Populations1

No clinically significant differences in pharmacokinetics based on age (range: 18 to 79 years), sex, race, or mild and moderate renal impairment (estimated Cl_cr by Cockcroft-Gault equation 30—89 mL/minute).¹

Stability

Storage

IV

Store refrigerated at 2 to 8°C.¹ Do not freeze; do not use if has been frozen.¹ Keep in original carton to protect from light until ready to use.¹

Sub-Q

Store refrigerated at 2 to 8°C.¹ Do not freeze; do not use if has been frozen.¹ Keep in original carton to protect from light until ready to use.¹

If needed, may be stored at room temperature up to 30°C for up to 2 weeks in original carton to protect from light.¹ Once stored at room temperature, do not return to refrigerator.¹ If these conditions are exceeded, discard.¹

Actions

• Humanized IgG₄ variant monoclonal antibody; selectively binds to the p19 subunit of IL-23 cytokine and inhibits its interaction with IL-23 receptor; does not bind interleukin 12.¹

• IL-23 involved in mucosal inflammation and affects differentiation, expansion, and survival of T cell subsets, and innate immune cell subsets, which represent sources of pro-inflammatory cytokines.¹

• Inhibits release of pro-inflammatory cytokines and chemokines.¹

• Research in animal models has shown that pharmacologic inhibition of IL-23 p19 can ameliorate intestinal inflammation.¹

• Produced in Chinese hamster ovary cells by recombinant DNA technology and composed of two identical light chain polypeptides and two identical heavy chain polypeptides.¹

Advice to Patients

• Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).¹

• Advise the patient to discontinue mirikizumab-mrkz and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.¹

• Advise patients that mirikizumab-mrkz may lower the ability of the immune system to fight infections and to contact their clinician immediately if they develop any symptoms of infection.¹

• Advise patients to contact their clinician if they experience symptoms suggestive of tuberculosis (e.g., unexplained fever, cough, or difficulty breathing).¹

• Inform patients that mirikizumab-mrkz may cause liver injury.¹ Advise patients to seek immediate medical attention if they experience symptoms suggestive of liver dysfunction (e.g., unexplained rash, nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice and/or dark urine).¹

• Advise patients that vaccination with live vaccines is not recommended during, and immediately prior to or after, mirikizumab-mrkz treatment.¹ Medications that interact with the immune system may increase the risk of infection following administration of live vaccines.¹ Instruct patients to inform their clinician that they are taking mirikizumab-mrkz prior to receiving a vaccination.¹

• Advise females of reproductive potential to inform their clinician if they are or plan to become pregnant or plan to breast-feed.¹ Advise patients who are pregnant and taking mirikizumab-mrkz to contact the manufacturer at 1-800-545-5979.¹

• Instruct patients and/or caregivers in the preparation and administration of mirikizumab-mrkz, including choosing anatomical sites for sub-Q administration, and proper sub-Q injection technique.¹ Instruct patients and/or caregivers in the technique of pen or syringe disposal.¹ Inform patients and/or caregivers to administer two 100 mg prefilled pens or prefilled syringes to achieve the full 200 mg dose of mirikizumab-mrkz.¹

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.¹

• Inform patients of other important precautionary information.¹

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Mirikizumab-mrkz is obtained through designated specialty pharmacies and distributors. Contact manufacturer or consult the manufacturer’s website ([Web]) for specific availability information.

Biological Products Related to mirikizumab

Find detailed information on biosimilars for this medication.

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