Interactions between Melphalan flufenamide and Mirikizumab
1 drug interaction and 8 additional warnings found for the following 2 drugs:
- melphalan flufenamide
- mirikizumab
Drug interactions
Moderate drug interactions
Moderate:
melphalan flufenamide mirikizumab
Applies to: melphalan flufenamide and mirikizumab
Monitor
Coadministration of interleukin (IL) inhibitors with CYP450 substrates that are also immunosuppressants could result in an alteration of the plasma concentration of the CYP450 substrate and an increased risk of shared side effects, such as infection or myelosuppression. In general, inflammation is associated with an elevation of pro-inflammatory cytokines like IL-1 beta and IL-6, which can bind to receptors present on hepatocytes and affect the expression level of the CYP450 isoenzyme. Agents that target these cytokines may affect the levels of CYP450 isoenzymes and result in altered drug metabolism of their substrates. The therapeutic target and disease state being treated may play a role in the significance of this interaction. The most evidence is currently for agents targeting the actions of IL-6 and in disease states with high levels of inflammation, such as rheumatoid arthritis (RA), rather than in patients with psoriasis and atopic dermatitis. Clinical data are limited, variable, and not available for all agents that reduce cytokine production. Studies involving the IL-6 inhibitors tocilizumab and sarilumab in RA patients showed similar results on the CYP450 3A4 probe, simvastatin, with reductions in the systemic exposure (AUC) of simvastatin and its metabolite (simvastatin acid) of 45% to 57% and 36% to 39%, respectively. Smaller reductions in the AUC of other probe substrates, omeprazole (2C19) and dextromethorphan (2D6), were also observed following treatment with tocilizumab. However, the AUC of CYP450 substrates is not always reduced. A study with brodalumab showed an increase in the AUC of midazolam (3A4) by 24%. Alternatively, some IL inhibitors (e.g., risankizumab and tildrakizumab) have not been shown to affect any CYP450 substrates when evaluated with probe substrates.
Management
Caution may be advisable when IL inhibitors are prescribed to patients receiving concomitant drugs that are both CYP450 substrates and immunosuppressants. Clinical and/or laboratory monitoring may be appropriate following the initiation or withdrawal of such treatments, and the dosage(s) of the CYP450 substrate(s) adjusted accordingly. Clinicians should note that the effects of IL inhibitors on CYP450 activities may persist for several weeks after stopping therapy. Individual product labeling should be consulted for these products. Some manufacturers no longer recommend general precautions with CYP450 substrates due to updated study data indicating no clinically significant changes in the exposure of probe CYP450 substrates. However, CYP450 substrates that are also immunosuppressants may still require additional precautions given a similar adverse effect profile to the IL inhibitor.
References (15)
- (2003) "Product Information. Amevive (alefacept)." Biogen
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- (2008) "Product Information. Arcalyst (rilonacept)." Regeneron Pharmaceuticals Inc
- (2009) "Product Information. Stelara (ustekinumab)." Centocor Inc
- (2009) "Product Information. Ilaris (canakinumab)." Novartis Pharmaceuticals
- (2010) "Product Information. Actemra (tocilizumab)." Genentech
- (2014) "Product Information. Sylvant (siltuximab)." Janssen Biotech, Inc.
- (2015) "Product Information. Cosentyx (secukinumab)." Novartis Pharmaceuticals
- (2016) "Product Information. Taltz Autoinjector (ixekizumab)." Eli Lilly and Company
- (2023) "Product Information. Bimzelx (bimekizumab)." UCB Australia Pty Ltd T/A UCB Pharma Division of UCB Australia
- (2023) "Product Information. Bimzelx (bimekizumab)." UCB Pharma Ltd
- (2023) "Product Information. Bimzelx Prefilled Syringe (bimekizumab)." UCB Pharma Inc
- (2023) "Product Information. Bimzelx (bimekizumab)." UCB Canada Inc
- Bruin G, Hasselberg A, Koroleva I, et al. (2019) "Secukinumab treatment does not alter the pharmacokinetics of the cytochrome P450 3A4 substrate midazolam in patients with moderate to severe psoriasis." Clin Pharmacol Ther, 106, p. 1380-8
- de Jong LM, Klomp SD, Treijtel N, Rissmann R, Swen JJ, Manson ML (2022) "A systematic review on disease-drug-drug interactions with immunomodulating drugs: a critical appraisal of risk assessment and drug labelling." Br J Clin Pharmacol, 88, p. 4387-402
Food/lifestyle interactions
No alcohol/food interactions were found. However, this does not necessarily mean no interactions exist. Always consult your healthcare provider.
Disease interactions
8 potential interactions Applies to: 7 conditions, including Liver Disease, Cirrhosis, Infection, Tuberculosis, Active, and Tuberculosis, Latent.
Bone Marrow Depression/Low Blood Counts
Moderate:
melphalan flufenamide
Melphalan flufenamide has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.
Bone marrow suppression is the most significant toxicity associated with melphalan flufenamide in most patients. It is recommended to perform the following tests at the start of therapy and prior to each subsequent dose of melphalan flufenamide: platelet count, hemoglobin, white blood cell count, and differential. Thrombocytopenia and/or neutropenia are indications to withhold further therapy until the blood counts have sufficiently recovered. Monitor blood counts frequently to determine optimal dosage and to avoid toxicity. Consider prophylactic therapy such as leukocyte growth factor as clinically appropriate. Dose adjustment on the basis of blood counts at the nadir and day of treatment should be considered.
Cirrhosis
Moderate:
mirikizumab
Mirikizumab has a moderate potential interaction with Cirrhosis.
Mirikizumab can cause increased levels of liver enzymes and bilirubin. The effect of moderate to severe hepatic impairment on the pharmacokinetics of mirikizumab has not been evaluated. Other treatment options should be considered in patients with evidence of liver cirrhosis.
Infection
Major:
melphalan flufenamide
Melphalan flufenamide has a major potential interaction with Infection.
Because of their cytotoxic effects on rapidly proliferating tissues, antineoplastic agents frequently can, to varying extent, induce myelosuppression. The use of these drugs may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during antineoplastic therapy. Close clinical monitoring of hematopoietic function is recommended.
Moderate:
mirikizumab
Mirikizumab has a moderate potential interaction with Infection.
Mirikizumab may increase the risk of infection. Patients should be evaluated for active infection before and during treatment with mirikizumab, and administration should be avoided if infection is detected.
Liver Disease
Moderate:
mirikizumab
Mirikizumab has a moderate potential interaction with Liver Disease.
Mirikizumab can cause increased levels of liver enzymes and bilirubin. The effect of moderate to severe hepatic impairment on the pharmacokinetics of mirikizumab has not been evaluated. Other treatment options should be considered in patients with evidence of liver cirrhosis.
Renal Dysfunction
Moderate:
melphalan flufenamide
Melphalan flufenamide has a moderate potential interaction with Renal Dysfunction.
No dose adjustment of melphalan flufenamide is recommended in patients with creatinine clearance (CrCl) 45 to 89 mL/min. Care should be exercised when using this agent in patients with CrCl 15 to 44 mL/min as the safety and efficacy has not been studied in these patients.
Tuberculosis, Active
Moderate:
mirikizumab
Mirikizumab has a moderate potential interaction with Tuberculosis, Active.
Patients treated with mirikizumab may be at increased risk for tuberculosis. Patients should be evaluated for TB before treatment with mirikizumab and therapy should be avoided in patients with active TB. Anti-TB therapy should be considered for patients with a history of latent or active TB.
Tuberculosis, Latent
Moderate:
mirikizumab
Mirikizumab has a moderate potential interaction with Tuberculosis, Latent.
Patients treated with mirikizumab may be at increased risk for tuberculosis. Patients should be evaluated for TB before treatment with mirikizumab and therapy should be avoided in patients with active TB. Anti-TB therapy should be considered for patients with a history of latent or active TB.
Report options
More resources
melphalan flufenamide
A total of 275 drugs are known to interact with melphalan flufenamide.
- Melphalan flufenamide is in the drug class alkylating agents.
- Melphalan flufenamide is used to treat Multiple Myeloma.
mirikizumab
A total of 361 drugs are known to interact with mirikizumab.
- Mirikizumab is in the drug class interleukin inhibitors.
- Mirikizumab is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.