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Drug overview for AVASTIN (bevacizumab):
Generic name: BEVACIZUMAB (BE-va-SIZ-oo-mab)
Drug class: Vascular Endothelial Growth Factor(VEGF) Monoclonal Antibody
Therapeutic class: Antineoplastics
Bevacizumab, bevacizumab-adcd, bevacizumab-awwb, bevacizumab-bvzr, and bevacizumab-maly, recombinant humanized monoclonal antibodies, are antineoplastic agents. Bevacizumab-adcd (Vegzelma(R)), bevacizumab-awwb (Mvasi(R)), bevacizumab-bvzr (Zirabev(R)), and bevacizumab-maly (Alymsys(R)) are biosimilar to bevacizumab (Avastin(R)). FDA defines a biosimilar as a biological product that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency.
The claim of biosimilarity is based on a totality-of-evidence approach, which includes consideration of data from analytical, animal, and clinical studies (e.g., human pharmacokinetic and pharmacodynamic studies, clinical immunogenicity assessment, additional comparative clinical studies). Therefore, biosimilarity may be established even when there are formulation or minor structural differences as long as these differences are not clinically meaningful. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between the proposed biological and the reference biological but does not independently establish safety and effectiveness of the proposed biological.
In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product; these requirements include demonstrating that the biological product can be expected to produce the same clinical results as the reference product in any given patient and, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is no greater than the risk of using the reference product without such alteration or switch. Biosimilar products that are interchangeable can be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. None of the currently available bevacizumab biosimilars have interchangeable data at this time. In this monograph, unless otherwise stated, the term ''bevacizumab products'' refers to bevacizumab (the reference drug) and its biosimilars (bevacizumab-adcd, bevacizumab-awwb, bevacizumab-bvzr, and bevacizumab-maly).
Several bevacizumab biosimilars are available. Biosimilarity of these products has been demonstrated for the indications described in Table 1. Biosimilarity to originator bevacizumab is additionally supported by comparative clinical studies in patients with non-small cell lung cancer.
Table 1. Bevacizumab Biosimilar Products and FDA-licensed Indications. FDA Metastat NSCLC GBM Metastat Cervical Ovarian HCC labeled ic CRC ic RCC cancer cancer indicati on Bevacizu X X X X X X mab-adcd (Vegzelm a(R)) Bevacizu X X X X X X mab-awwb (Mvasi(R )) Bevacizu X X X X X X mab-bvzr (Zirabev (R)) Bevacizu X X X X X X mab-maly (Alymsys (R)) Bevacizumab-maly (Alymsys(R)) is only labeled for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for the treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have received no more than 2 prior chemotherapy regimens.
Other biosimilars have additional ovarian cancer indications (same ovarian cancer indications as originator bevacizumab). CRC, colorectal cancer; GBM, glioblastoma; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma.
Generic name: BEVACIZUMAB (BE-va-SIZ-oo-mab)
Drug class: Vascular Endothelial Growth Factor(VEGF) Monoclonal Antibody
Therapeutic class: Antineoplastics
Bevacizumab, bevacizumab-adcd, bevacizumab-awwb, bevacizumab-bvzr, and bevacizumab-maly, recombinant humanized monoclonal antibodies, are antineoplastic agents. Bevacizumab-adcd (Vegzelma(R)), bevacizumab-awwb (Mvasi(R)), bevacizumab-bvzr (Zirabev(R)), and bevacizumab-maly (Alymsys(R)) are biosimilar to bevacizumab (Avastin(R)). FDA defines a biosimilar as a biological product that is highly similar to an FDA-licensed reference biological with the exception of minor differences in clinically inactive components and for which there are no clinically meaningful differences in safety, purity, or potency.
The claim of biosimilarity is based on a totality-of-evidence approach, which includes consideration of data from analytical, animal, and clinical studies (e.g., human pharmacokinetic and pharmacodynamic studies, clinical immunogenicity assessment, additional comparative clinical studies). Therefore, biosimilarity may be established even when there are formulation or minor structural differences as long as these differences are not clinically meaningful. Biosimilars are approved through an abbreviated licensure pathway that establishes biosimilarity between the proposed biological and the reference biological but does not independently establish safety and effectiveness of the proposed biological.
In order to be considered an interchangeable biosimilar, a biological product must meet additional requirements beyond demonstrating biosimilarity to its reference product; these requirements include demonstrating that the biological product can be expected to produce the same clinical results as the reference product in any given patient and, for a biological product that is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is no greater than the risk of using the reference product without such alteration or switch. Biosimilar products that are interchangeable can be substituted for the reference product without the intervention of the healthcare provider who prescribed the reference product. None of the currently available bevacizumab biosimilars have interchangeable data at this time. In this monograph, unless otherwise stated, the term ''bevacizumab products'' refers to bevacizumab (the reference drug) and its biosimilars (bevacizumab-adcd, bevacizumab-awwb, bevacizumab-bvzr, and bevacizumab-maly).
Several bevacizumab biosimilars are available. Biosimilarity of these products has been demonstrated for the indications described in Table 1. Biosimilarity to originator bevacizumab is additionally supported by comparative clinical studies in patients with non-small cell lung cancer.
Table 1. Bevacizumab Biosimilar Products and FDA-licensed Indications. FDA Metastat NSCLC GBM Metastat Cervical Ovarian HCC labeled ic CRC ic RCC cancer cancer indicati on Bevacizu X X X X X X mab-adcd (Vegzelm a(R)) Bevacizu X X X X X X mab-awwb (Mvasi(R )) Bevacizu X X X X X X mab-bvzr (Zirabev (R)) Bevacizu X X X X X X mab-maly (Alymsys (R)) Bevacizumab-maly (Alymsys(R)) is only labeled for use in combination with paclitaxel, pegylated liposomal doxorubicin, or topotecan for the treatment of platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who have received no more than 2 prior chemotherapy regimens.
Other biosimilars have additional ovarian cancer indications (same ovarian cancer indications as originator bevacizumab). CRC, colorectal cancer; GBM, glioblastoma; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; RCC, renal cell carcinoma.
DRUG IMAGES
AVASTIN 100 MG/4 ML VIAL
AVASTIN 400 MG/16 ML VIAL
The following indications for AVASTIN (bevacizumab) have been approved by the FDA:
Indications:
Carcinoma of cervix
Epithelial ovarian cancer
Glioblastoma multiforme
Liver cell carcinoma
Metastatic colorectal cancer
Metastatic renal cell carcinoma
Nonsquamous non-small cell lung cancer
Professional Synonyms:
Carcinoma of ovary
Cervical carcinoma cancer
Cervical carcinoma
Epithelial carcinoma of ovary
Epithelial ovarian carcinoma
Grade IV astrocytoma
Hepatocarcinoma
Hepatocellular carcinoma
Malignant epithelial neoplasm of ovary
Metastatic carcinoma of kidney
Metastatic Grawitz tumor
Metastatic hypernephroid carcinoma
Metastatic hypernephroma
Metastatic kidney adenocarcinoma
Metastatic nephroid carcinoma
Metastatic renal adenocarcinoma
Metastatic renal carcinoma
Metastatic renal cell adenocarcinoma
Metastatic renal cell cancer
Nonsquamous NSCLC
Ovarian carcinoma
Indications:
Carcinoma of cervix
Epithelial ovarian cancer
Glioblastoma multiforme
Liver cell carcinoma
Metastatic colorectal cancer
Metastatic renal cell carcinoma
Nonsquamous non-small cell lung cancer
Professional Synonyms:
Carcinoma of ovary
Cervical carcinoma cancer
Cervical carcinoma
Epithelial carcinoma of ovary
Epithelial ovarian carcinoma
Grade IV astrocytoma
Hepatocarcinoma
Hepatocellular carcinoma
Malignant epithelial neoplasm of ovary
Metastatic carcinoma of kidney
Metastatic Grawitz tumor
Metastatic hypernephroid carcinoma
Metastatic hypernephroma
Metastatic kidney adenocarcinoma
Metastatic nephroid carcinoma
Metastatic renal adenocarcinoma
Metastatic renal carcinoma
Metastatic renal cell adenocarcinoma
Metastatic renal cell cancer
Nonsquamous NSCLC
Ovarian carcinoma
The following dosing information is available for AVASTIN (bevacizumab):
Bevacizumab product dosage reductions are not recommended in any patient; instead, the drug generally should either be temporarily suspended or permanently discontinued, according to causality (see Table 2).
Table 2. Recommended Dosage Modification for Bevacizumab Product Adverse Reactions.
Adverse Reaction Dosage Modification based on Severity Arterial thromboembolism Discontinue bevacizumab product if severe Congestive heart failure Discontinue bevacizumab product Fistula Grade 4 or involving any internal organ: discontinue bevacizumab product GI perforation Any grade: discontinue bevacizumab product Hemorrhage Grade 3 or 4 hemorrhage: discontinue bevacizumab product Recent history of hemoptysis of 0.5 teaspoon or more: withhold bevacizumab product Hypertension Severe hypertension: withhold bevacizumab product if not controlled with medical management; resume bevacizumab product once controlled Hypertensive crisis or hypertensive encephalopathy: discontinue bevacizumab product Infusion-related reactions Mild, clinically insignificant: decrease infusion rate Clinically significant: interrupt infusion; resume at a decreased rate of infusion after symptoms resolve Severe: discontinue bevacizumab product Necrotizing fasciitis Discontinue bevacizumab product Posterior reversible encephalopathy Discontinue bevacizumab product syndrome (PRES) Renal injury and proteinuria Proteinuria >=2 g per 24 hours in the absence of nephrotic syndrome: withhold bevacizumab product until proteinuria decreases to <2 g per 24 hours Nephrotic syndrome: discontinue bevacizumab product Tracheoesophageal fistula Any grade: discontinue bevacizumab product Venous thromboembolism Grade 4: discontinue bevacizumab product Wound healing complications Withhold bevacizumab product until adequate wound healing has occurred; the safety of resuming bevacizumab products after resolution of wound healing complications has not been established
Table 2. Recommended Dosage Modification for Bevacizumab Product Adverse Reactions.
Adverse Reaction Dosage Modification based on Severity Arterial thromboembolism Discontinue bevacizumab product if severe Congestive heart failure Discontinue bevacizumab product Fistula Grade 4 or involving any internal organ: discontinue bevacizumab product GI perforation Any grade: discontinue bevacizumab product Hemorrhage Grade 3 or 4 hemorrhage: discontinue bevacizumab product Recent history of hemoptysis of 0.5 teaspoon or more: withhold bevacizumab product Hypertension Severe hypertension: withhold bevacizumab product if not controlled with medical management; resume bevacizumab product once controlled Hypertensive crisis or hypertensive encephalopathy: discontinue bevacizumab product Infusion-related reactions Mild, clinically insignificant: decrease infusion rate Clinically significant: interrupt infusion; resume at a decreased rate of infusion after symptoms resolve Severe: discontinue bevacizumab product Necrotizing fasciitis Discontinue bevacizumab product Posterior reversible encephalopathy Discontinue bevacizumab product syndrome (PRES) Renal injury and proteinuria Proteinuria >=2 g per 24 hours in the absence of nephrotic syndrome: withhold bevacizumab product until proteinuria decreases to <2 g per 24 hours Nephrotic syndrome: discontinue bevacizumab product Tracheoesophageal fistula Any grade: discontinue bevacizumab product Venous thromboembolism Grade 4: discontinue bevacizumab product Wound healing complications Withhold bevacizumab product until adequate wound healing has occurred; the safety of resuming bevacizumab products after resolution of wound healing complications has not been established
Bevacizumab products are administered by IV infusion. Bevacizumab products are commercially available in single-dose vials at a concentration of 25 mg/mL. For IV infusion, the appropriate dose of the bevacizumab product should be withdrawn into a syringe and diluted in a total volume of 100 mL of 0.9%
sodium chloride using aseptic technique. Bevacizumab product infusions should not be administered or mixed with dextrose solutions. Any unused portion left in the vial should be discarded since the injection contains no preservative.
The initial dose of bevacizumab products should be infused over 90 minutes; if the first infusion is tolerated, the second dose may be infused over 60 minutes. If this second infusion also is tolerated, all subsequent doses may be infused over 30 minutes. One institution has reported use of shorter infusion times for bevacizumab at an infusion rate of 0.5
mg/kg per minute. The manufacturers state that no incompatibilities have been observed between originator bevacizumab, bevacizumab-awwb (Mvasi(R)), bevacizumab-bvzr (Zirabev(R)), or bevacizumab-maly (Alymsys(R)) and polyvinylchloride or polyolefin bags. No incompatibilities have been observed between bevacizumab-adcd (Vegzelma(R)) and polyolefin (polypropylene and polyethylene) bags.
Bevacizumab product vials should be protected from light and stored in the original carton at 2-8degreesC until use; freezing should be avoided. The injection should not be shaken prior to use. Once diluted, originator bevacizumab and bevacizumab-awwb (Mvasi(R)) may be stored at 2-8degreesC for up to 8 hours, bevacizumab-maly (Alymsys(R)) may be stored at 2-8degreesC for up to 12 hours, and bevacizumab-bvzr (Zirabev(R)) may be stored at 2-8degreesC for up to 16 days. Diluted bevacizumab-adcd (Vegzelma(R)) may be stored at 2-8degreesC for up to 24 hours or at room temperature (up to 30degreesC) for up to 4 hours.
sodium chloride using aseptic technique. Bevacizumab product infusions should not be administered or mixed with dextrose solutions. Any unused portion left in the vial should be discarded since the injection contains no preservative.
The initial dose of bevacizumab products should be infused over 90 minutes; if the first infusion is tolerated, the second dose may be infused over 60 minutes. If this second infusion also is tolerated, all subsequent doses may be infused over 30 minutes. One institution has reported use of shorter infusion times for bevacizumab at an infusion rate of 0.5
mg/kg per minute. The manufacturers state that no incompatibilities have been observed between originator bevacizumab, bevacizumab-awwb (Mvasi(R)), bevacizumab-bvzr (Zirabev(R)), or bevacizumab-maly (Alymsys(R)) and polyvinylchloride or polyolefin bags. No incompatibilities have been observed between bevacizumab-adcd (Vegzelma(R)) and polyolefin (polypropylene and polyethylene) bags.
Bevacizumab product vials should be protected from light and stored in the original carton at 2-8degreesC until use; freezing should be avoided. The injection should not be shaken prior to use. Once diluted, originator bevacizumab and bevacizumab-awwb (Mvasi(R)) may be stored at 2-8degreesC for up to 8 hours, bevacizumab-maly (Alymsys(R)) may be stored at 2-8degreesC for up to 12 hours, and bevacizumab-bvzr (Zirabev(R)) may be stored at 2-8degreesC for up to 16 days. Diluted bevacizumab-adcd (Vegzelma(R)) may be stored at 2-8degreesC for up to 24 hours or at room temperature (up to 30degreesC) for up to 4 hours.
No dosing information available.
No generic dosing information available.
The following drug interaction information is available for AVASTIN (bevacizumab):
There are 4 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Efalizumab; Natalizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Natalizumab,(1-3) efalizumab,(4) immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of natalizumab(1-3) or efalizumab(4) with immunosuppressives or immunomodulators may result in an increased risk of infections, including progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV). PREDISPOSING FACTORS: Previous JCV infection, longer duration of natalizumab treatment - especially if greater than 2 years, and prior or concomitant treatment with immunosuppressant medication are all independent risk factors which increase the risk for PML.(1,5) The FDA has estimated PML incidence stratified by risk factors: If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment less than 25 months, incidence <1/1,000. If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment less than 25 months, incidence 2/1,000 If anti-JCV antibody positive, no prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 4/1,000 If anti-JCV antibody positive, history of prior immunosuppressant use and natalizumab treatment 25-48 months, incidence 11/1,000. PATIENT MANAGEMENT: The US manufacturer of natalizumab states patients with Crohn's disease should not receive concurrent immunosuppressants, with the exception of limited overlap of corticosteroids, due to the increased risk for PML. For new natalizumab patients currently receiving chronic oral corticosteroids for Crohn's Disease, begin corticosteroid taper when therapeutic response to natalizumab has occurred. If corticosteroids cannot be discontinued within six months of starting natalizumab, discontinue natalizumab.(3) The US manufacturer of natalizumab states that natalizumab should not ordinarily be used in multiple sclerosis patients receiving immunosuppressants or immunomodulators due to the increased risk for PML. Immunosuppressives include, but are not limited to azathioprine, cyclophosphamide, cyclosporine, mercaptopurine, methotrexate, mitoxantrone, mycophenolate, and corticosteroids.(3,6) The UK manufacturer of natalizumab states that concurrent use with immunosuppressives or antineoplastic agents is contraindicated.(1) The Canadian manufacturer of natalizumab states that natalizumab should not be used with immunosuppressive or immunomodulatory agents.(2) The US manufacturer of certolizumab states that concurrent therapy with natalizumab is not recommended.(7) DISCUSSION: Progressive multifocal leukoencephalopathy has been reported in patients receiving concurrent natalizumab were recently or concomitantly taking immunomodulators or immunosuppressants.(1-5,8,9) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(10) |
TYSABRI |
| Live Vaccines/Bevacizumab SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Systemic bevacizumab suppresses the immune system. Immunocompromised patients may be at increased risk for uninhibited replication after administration of live, attenuated vaccines. Immune response to vaccines may be decreased during periods of immunocompromise.(1) CLINICAL EFFECTS: The expected serum antibody response may not be obtained and/or the vaccine may result in illness.(1) PREDISPOSING FACTORS: Immunosuppressive diseases (e.g. hematologic malignancies, HIV disease), treatments (e.g. radiation) and drugs may all increase the magnitude of immunodeficiency. Intravitreal injections of small doses of bevacizumab for macular degeneration or macular edema are not expected to suppress immune function. PATIENT MANAGEMENT: The Centers for Disease Control(CDC) Advisory Committee on Immunization Practices (ACIP) states that live-virus and live, attenuated vaccines should not be administered to patients who are immunocompromised. The magnitude of immunocompromise and associated risks should be determined by a physician.(1) Intravitreal injections of small doses of bevacizumab for macular degeneration or macular edema are not expected to suppress immune function. For patients scheduled to receive chemotherapy, vaccination should ideally precede the initiation of chemotherapy by 14 days. Patients vaccinated while on immunosuppressive therapy or in the 2 weeks prior to starting therapy should be considered unimmunized and should be revaccinated at least 3 months after discontinuation of therapy.(1) DISCUSSION: Killed or inactivated vaccines do not pose a danger to immunocompromised patients.(1) Patients with a history of leukemia who are in remission and have not received chemotherapy for at least 3 months are not considered to be immunocompromised.(1) |
ACAM2000 (NATIONAL STOCKPILE), ADENOVIRUS TYPE 4, ADENOVIRUS TYPE 4 AND TYPE 7, ADENOVIRUS TYPE 7, BCG VACCINE (TICE STRAIN), DENGVAXIA, ERVEBO (NATIONAL STOCKPILE), FLUMIST 2025-2026, FLUMIST HOME 2025-2026, M-M-R II VACCINE, PRIORIX, PROQUAD, ROTARIX, ROTATEQ, STAMARIL, VARIVAX VACCINE, VAXCHORA ACTIVE COMPONENT, VAXCHORA VACCINE, VIVOTIF, YF-VAX |
| Talimogene laherparepvec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Talimogene laherparepvec is a live, attenuated herpes simplex virus.(1) CLINICAL EFFECTS: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Talimogene laherparepvec is contraindicated in immunosuppressed patients.(1) The magnitude of immunocompromise and associated risks due to immunosuppressant drugs should be determined by a physician. DISCUSSION: Concurrent use of talimogene laherparepvec in patients receiving immunosuppressive therapy may cause a life-threatening disseminated herpetic infection.(1) |
IMLYGIC |
| Nadofaragene Firadenovec/Selected Immunosuppressants SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Nadofaragene firadenovec may contain low levels of replication-competent adenovirus.(1) CLINICAL EFFECTS: Concurrent use of nadofaragene firadenovec in patients receiving immunosuppressive therapy may cause disseminated adenovirus infection.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Individuals who are immunosuppressed or immune-deficient should not receive nadofaragene firadenovec.(1) DISCUSSION: Nadofaragene firadenovec is a non-replicating adenoviral vector-based gene therapy but may contain low levels of replication-competent adenovirus. Immunocompromised persons, including those receiving immunosuppressant therapy, may be at risk for disseminated adenovirus infection.(1) |
ADSTILADRIN |
There are 22 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Bevacizumab/Sunitinib SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The mechanism of this interaction is not known at this time. CLINICAL EFFECTS: Concurrent use of sunitinib and bevacizumab may result in the development microangiopathic hemolytic anemia.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Use sunitinib with bevacizumab may result in microangiopathic hemolytic anemia. Bevacizumab is not approved for use in combination with sunitinib malate and this combination is not recommended.(1) DISCUSSION: Twenty-five patients were enrolled in a Phase I dose-escalation study combining Avastin and sunitinib malate. The study consisted of 3 cohorts using a fixed dose of Avastin at 10mg/kg/IV every 2 weeks and escalating doses of sunitinib that included 25, 37.5, and 50 mg orally daily given in a 4 weeks on/ 2 weeks off schedule. Two of these cases were considered severe with evidence of thrombocytopenia, anemia, reticulocytosis, reductions in serum haptoglobin, schistocytes on peripheral smear, modest increases in serum creatinine levels, and severe hypertension, reversible posterior leukoencephalopathy syndrome, and proteinuria. The findings in these two cases were reversible within three weeks upon discontinuation of both drugs without additional interventions. These drugs are not recommended to be administered together.(1) |
SUNITINIB MALATE, SUTENT |
| Deferiprone/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of deferiprone with other drugs known to be associated with neutropenia or agranulocytosis may increase the frequency or risk for severe toxicity.(1) CLINICAL EFFECTS: Concurrent use of deferiprone and myelosuppressive agents may result in severe neutropenia or agranulocytosis, which may be fatal. PREDISPOSING FACTORS: Agranulocytosis may be less common in patients receiving deferiprone for thalassemia, and more common in patients treated for other systemic iron overload conditions (e.g. myelodysplastic syndromes, sickle cell disease).(2,3) Inadequate monitoring appears to increase the risk for severe outcomes. Manufacturer post market surveillance found that in all fatal cases of agranulocytosis reported between 1999 and 2005, data on weekly white blood count (WBC) monitoring was missing. In three fatal cases, deferiprone was continued for two to seven days after the detection of neutropenia or agranulocytosis.(2) PATIENT MANAGEMENT: If possible, discontinue one of the drugs associated with risk for neutropenia or agranulocytosis. If alternative therapy is not available, documentation and adherence to the deferiprone monitoring protocol is essential. Baseline absolute neutrophil count (ANC) must be at least 1,500/uL prior to starting deferiprone. Monitor ANC weekly during therapy. If infection develops, interrupt deferiprone therapy and monitor ANC more frequently. If ANC is less than 1,500/uL but greater than 500/uL, discontinue deferiprone and any other drugs possibly associated with neutropenia. Initiate ANC and platelet counts daily until recovery (i.e. ANC at least 1,500/uL). If ANC is less than 500/uL, discontinue deferiprone, evaluate patient and hospitalize if appropriate. Do not resume deferiprone unless potential benefits outweigh potential risks.(1) DISCUSSION: Drugs linked to this monograph have an FDA Boxed Warning for risk of neutropenia, agranulocytosis, or pancytopenia, or have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(1-25) In pooled clinical studies submitted to the FDA, 6.1% of deferiprone patients met criteria for neutropenia and 1.7% of patients developed agranulocytosis.(1) The time to onset of agranulocytosis was highly variable with a range of 65 days to 9.2 years (median, 161 days).(3) |
DEFERIPRONE, DEFERIPRONE (3 TIMES A DAY), FERRIPROX, FERRIPROX (2 TIMES A DAY), FERRIPROX (3 TIMES A DAY) |
| Tofacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of tofacitinib and azathioprine, other biologic disease-modifying antirheumatic drugs (DMARDs), or potent immunosuppressants may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants use may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Tofacitinib should not be used concurrently with azathioprine, other biologic DMARDs, or cyclosporine.(1) Patient should be monitored for decreases in lymphocytes and neutrophils. Therapy should be adjusted based on the indication. - For all indications: If absolute neutrophil count (ANC) or lymphocyte count is less than 500 cells/mm3, discontinue tofacitinib. - For rheumatoid arthritis or psoriatic arthritis and absolute neutrophil count (ANC) 500 to 1000 cells/mm3: interrupt dosing. When ANC is greater than 1000 cells/mm3, resume Xeljanz 5 mg twice daily or Xeljanz XR 11 mg once daily. - For ulcerative colitis and ANC 500 to 1000 cells/mm3: -If taking Xeljanz 10 mg twice daily, decrease to 5 mg twice daily. When ANC is greater than 1000 cells/mm3, increase to 10 mg twice daily based on clinical response. -If taking Xeljanz 5 mg twice daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 5 mg twice daily. -If taking Xeljanz XR 22 mg once daily, decrease to 11 mg once daily. When ANC is greater than 1000 cells/mm3, increase to 22 mg once daily based on clinical response. -If taking Xeljanz XR 11 mg once daily, interrupt dosing. When ANC is greater than 1000 cells/mm3, resume 11 mg once daily. - For polyarticular course juvenile idiopathic arthritis (pcJIA) and ANC 500 to 1000 cells/mm3: interrupt dosing until ANC is greater than 1000 cells/mm3.(1) DISCUSSION: Concurrent use of tofacitinib and azathioprine, other biologic DMARDs, or potent immunosuppressants may increase the risk of infection.(1) |
TOFACITINIB CITRATE, XELJANZ, XELJANZ XR |
| Clozapine/Selected Myelosuppressive Agents SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clozapine and other myelosuppressive agents may be associated with neutropenia or agranulocytosis.(2) CLINICAL EFFECTS: Moderate neutropenia, even if due to combination therapy, may require abrupt discontinuation of clozapine resulting in decompensation of the patient's psychiatric disorder (e.g. schizophrenia). The disease treated by the myelosuppressive agent may be compromised if myelosuppression requires dose reduction, delay, or discontinuation of the myelosuppressive agent. Undetected severe neutropenia or agranulocytosis may be fatal. PREDISPOSING FACTORS: Low white blood counts prior to initiation of the myelosuppressive agent may increase risk for clinically significant neutropenia. PATIENT MANAGEMENT: If a patient stabilized on clozapine therapy requires treatment with a myelosuppressive agent, the clozapine prescriber should consult with prescriber of the myelosuppressive agent (e.g. oncologist) to discuss treatment and monitoring options.(2) More frequent ANC monitoring or treatment alternatives secondary to neutropenic episodes may need to be considered. Clozapine is only available through a restricted distribution system which requires documentation of the absolute neutrophil count (ANC) prior to dispensing.(1-2) For most clozapine patients, clozapine treatment must be interrupted for a suspected clozapine-induced ANC < 1000 cells/microliter. For patients with benign ethnic neutropenia (BEN), treatment must be interrupted for suspected clozapine-induced neutropenia < 500 cells/microliter.(2) DISCUSSION: Clozapine is only available through a restricted distribution system which requires documentation of the ANC prior to dispensing.(1) Agents linked to this interaction generally have > 5% risk for neutropenia and/or warnings describing risk for myelosuppression in manufacturer prescribing information.(3-26) |
CLOZAPINE, CLOZAPINE ODT, CLOZARIL, VERSACLOZ |
| Selected Multiple Sclerosis Agents/Immunosuppressants; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ocrelizumab or ofatumumab in combination with immunosuppressives and immune-modulators all suppress the immune system.(1,2) CLINICAL EFFECTS: Concurrent use of ocrelizumab or ofatumumab with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1,2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ocrelizumab US prescribing information states: - Ocrelizumab and other immune-modulating or immunosuppressive therapies, (including immunosuppressant doses of corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with ocrelizumab. When switching from drugs with prolonged immune effects, such as daclizumab, fingolimod, natalizumab, teriflunomide, or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating ocrelizumab.(1) The ofatumumab US prescribing information states: - Ofatumumab and other immunosuppressive therapies (including systemic corticosteroids) may have the potential for increased immunosuppressive effects and increase the risk of infection. When switching between therapies, the duration and mechanism of action of each therapy should be considered due to the potential for additive immunosuppressive effects. Ofatumumab for MS therapy has not been studied in combination with other MS agents that suppress the immune system.(2) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1,2) In a retrospective cohort study of multiple sclerosis patients newly initiated on a disease-modifying therapy, use of high-efficacy agents (alemtuzumab, natalizumab, or ocrelizumab) resulted in the same risk of overall infections as moderate-efficacy agents, but there was an elevated risk of serious infections (adjusted hazard ratio [aHR] = 1.24, 95% confidence interval (CI) = 1.06-1.44) and UTIs (aHR = 1.21, 95% CI = 1.14-1.30).(3) |
KESIMPTA PEN, OCREVUS, OCREVUS ZUNOVO |
| Upadacitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Upadacitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of upadacitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of upadacitinib states that concurrent use of upadacitinib with immunosuppressives or immunomodulators is not recommended. DISCUSSION: Serious infections have been reported in patients receiving upadacitinib. Reported infections included pneumonia, cellulitis, tuberculosis, multidermatomal herpes zoster, oral/esophageal candidiasis, cryptococcosis. Reports of viral reactivation, including herpes virus reactivation and hepatitis B reactivation, were reported in clinical studies with upadacitinib.(1) |
RINVOQ, RINVOQ LQ |
| Inebilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inebilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of inebilizumab with immunosuppressive or immunomodulating agents may result in myelosuppression including neutropenia resulting in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of inebilizumab states that the concurrent use of inebilizumab with immunosuppressive agents, including systemic corticosteroids, may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Inebilizumab has not been studied in combination with other immunosuppressants. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents. The most common infections reported by inebilizumab treated patients in the randomized and open-label clinical trial periods included urinary tract infections (20%), nasopharyngitis (13%), upper respiratory tract infections (8%), and influenza (7%). Although there been no cases of Hepatitis B virus reactivation or progressive multifocal leukoencephalopathy reported in patients taking inebilizumab, these infections have been observed in patients taking other B-cell-depleting antibodies.(1) |
UPLIZNA |
| Baricitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of baricitinib with other biologic disease-modifying antirheumatic drugs (DMARDs) or potent immunosuppressants such as azathioprine or cyclosporine may result in additive or synergistic effects on the immune system. CLINICAL EFFECTS: Concurrent use of baricitinib with other biologic DMARDs or potent immunosuppressants such as azathioprine or cyclosporine may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of baricitinib states that concurrent use of baricitinib with biologic DMARDs or potent immunosuppressants is not recommended.(1) DISCUSSION: Most patients who developed serious infections while being treated with baricitinib were on concomitant immunosuppressants like methotrexate and corticosteroids. The combination of baricitinib with other biologic DMARDs has not been studied.(1) |
OLUMIANT |
| Leflunomide; Teriflunomide/Selected Immunosuppressants SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of leflunomide or teriflunomide and potent immunosuppressants may result in additive or synergistic effects on the immune system.(1,2) Leflunomide is a prodrug and is converted to its active metabolite teriflunomide.(1) CLINICAL EFFECTS: Concurrent use of leflunomide or teriflunomide with immunosuppressants may result in an increased risk of serious infections, including opportunistic infections, especially Pneumocystis jiroveci pneumonia, tuberculosis (including extra-pulmonary tuberculosis), and aspergillosis. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If leflunomide or teriflunomide is used concurrently with immunosuppressive agents, chronic CBC monitoring should be performed more frequently, every month instead of every 6 to 8 weeks. If bone marrow suppression or a serious infection occurs, leflunomide or teriflunomide should be stopped and rapid drug elimination procedure should be performed.(1,2) DISCUSSION: Pancytopenia, agranulocytosis and thrombocytopenia have been reported in patients receiving leflunomide or teriflunomide alone, but most frequently in patients taking concurrent immunosuppressants.(1,2) Severe and potentially fatal infections, including sepsis, have been reported in patients receiving leflunomide or teriflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. Tuberculosis has also been reported.(1,2) |
ARAVA, AUBAGIO, LEFLUNICLO, LEFLUNOMIDE, TERIFLUNOMIDE |
| Ponesimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ponesimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ponesimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ponesimod US prescribing information states ponesimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ponesimod after alemtuzumab is not recommended. However, ponesimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
PONVORY |
| Sodium Iodide I 131/Myelosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1) DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1) |
HICON, SODIUM IODIDE I-131 |
| Fingolimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fingolimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-3) CLINICAL EFFECTS: Concurrent use of fingolimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-3) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for fingolimod regarding this interaction differ between regulatory approving agencies. The fingolimod US prescribing information states: - Antineoplastic, immune-modulating, or immunosuppressive therapies, (including corticosteroids) are expected to increase the risk of immunosuppression, and the risk of additive immune system effects must be considered if these therapies are coadministered with fingolimod. When switching from drugs with prolonged immune effects, such as natalizumab, teriflunomide or mitoxantrone, the duration and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects when initiating fingolimod.(1) The fingolimod Canadian prescribing information states: - Concurrent use with immunosuppressive or immunomodulatory agents is contraindicated due to the risk of additive immune system effects. However, co-administration of a short course of corticosteroids (up to 5 days) did not increase the overall rate of infection in patients participating Phase III clinical trials.(2) The fingolimod UK specific product characteristics states: - Fingolimod is contraindicated in patients currently receiving immunosuppressive therapies or those immunocompromised by prior therapies. When switching patients from another disease modifying therapy to Gilenya, the half-life and mode of action of the other therapy must be considered in order to avoid an additive immune effect whilst at the same time minimizing the risk of disease activation.(3) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-3) |
FINGOLIMOD, GILENYA, TASCENSO ODT |
| Ozanimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ozanimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ozanimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The ozanimod US prescribing information state this information regarding this interaction: -Ozanimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with ozanimod after alemtuzumab is not recommended. However, ozanimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
ZEPOSIA |
| Siponimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Siponimod in combination with immunosuppressives and immune-modulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of siponimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The siponimod US prescribing information state this information regarding this interaction: -Siponimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Caution should be used during concomitant administration because of the risk of additive immune effects during therapy and in the week following administration. When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects. Initiating treatment with siponimod after alemtuzumab is not recommended. However, siponimod can generally be started immediately after discontinuation of beta interferon or glatiramer acetate.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1) |
MAYZENT |
| Cladribine/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cladribine in combination with immunosuppressives and immune-modulators all suppress the immune system.(1-2) CLINICAL EFFECTS: Concurrent use of cladribine with immunosuppressive or immune-modulating agents may result in an increased risk of serious infections, such as disseminated herpetic infection or progressive multifocal leukoencephalopathy (PML), an opportunistic infection caused by the JC virus (JCV).(1-2) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: Recommendations for cladribine regarding this interaction differ between regulatory approving agencies. The cladribine US prescribing information states: -Concomitant use with myelosuppressive or other immunosuppressive drugs is not recommended. Acute short-term therapy with corticosteroids can be administered. In patients who have previously been treated with immunomodulatory or immunosuppressive drugs, consider potential additive effect, the mode of action, and duration of effect of the other drugs prior to initiation of cladribine.(1) The cladribine Canadian prescribing information states: -Use of cladribine in immunocompromised patients is contraindicated because of a risk of additive effects on the immune system. Acute short-term therapy with corticosteroids can be administered during cladribine treatment.(2) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients who previously received immunomodulators or immunosuppressants.(1-2) |
CLADRIBINE, MAVENCLAD |
| IgG Antibodies and Derivatives/Efgartigimod-alfa SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3) |
VYVGART, VYVGART HYTRULO |
| Anifrolumab/Biologic Therapies SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of anifrolumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of anifrolumab with other biologic therapies may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of anifrolumab with other biologic therapies is not recommended.(1) DISCUSSION: The combination of anifrolumab with other biologic therapies has not been studied and is not recommended.(1) |
SAPHNELO |
| Ritlecitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ritlecitinib, immunosuppressives, and immunomodulators all suppress the immune system. CLINICAL EFFECTS: Concurrent use of ritlecitinib with immunosuppressives or immunomodulators may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ritlecitinib states that concurrent use of ritlecitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) DISCUSSION: Serious infections have been reported in patients receiving ritlecitinib. Reported infections included appendicitis, COVID-19 infection (including pneumonia), and sepsis. Reports of viral reactivation, including herpes virus reactivation was reported in clinical studies with ritlecitinib.(1) |
LITFULO |
| Etrasimod/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etrasimod causes reversible sequestration of lymphocytes in lymphoid tissues, resulting in a mean 55% decrease in peripheral blood lymphocyte count at 52 weeks.(1) Other immunosuppressives and immune-modulators also suppress the immune system. CLINICAL EFFECTS: Concurrent use of etrasimod with immunosuppressive or immune-modulating agents may result in an increased risk of serious and fatal infections, such as disseminated herpetic infection, cryptococcal infection, or progressive multifocal leukoencephalopathy (PML).(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications increases the risk of adverse effects. PATIENT MANAGEMENT: The etrasimod US prescribing information states etrasimod has not been studied in combination with anti-neoplastic, immune-modulating, or immunosuppressive therapies. Concomitant administration of these therapies with etrasimod should be avoided because of the risk of additive immune effects during therapy and in the weeks following administration. Etrasimod's effect on peripheral lymphocytes may persist for up to 5 weeks after discontinuation.(1) When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered in order to avoid unintended additive immunosuppressive effects.(1) DISCUSSION: Fatal disseminated herpes zoster and herpes simplex infections, cryptococcal meningitis, disseminated cryptococcal infections, and cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients treated with other sphingosine-1 phosphate receptor modulators.(1) |
VELSIPITY |
| Ropeginterferon alfa-2b/Slt Immunosuppress; Immunomodulator SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ropeginterferon alfa-2b and immunosuppressives both suppress the immune system. CLINICAL EFFECTS: Concurrent use of ropeginterferon alfa-2b with immunosuppressives may result in an increased risk of serious infections. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid concurrent use of myelosuppressive agents.(1-2) If concurrent use cannot be avoided, monitor for effects of excessive immunosuppression. DISCUSSION: In clinical trials, 20% of patients experienced leukopenia. Interferon alfa products may cause fatal or life-threatening infections.(1-2) |
BESREMI |
| Deuruxolitinib/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Deuruxolitinib, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of deuruxolitinib and potent immunosuppressants may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of deuruxolitinib states that concurrent use of deuruxolitinib with other JAK inhibitors, biologic immunomodulators, cyclosporine or other potent immunosuppressants is not recommended.(1) If concurrent use cannot be avoided, patients should be monitored for signs and symptoms of infection. If a patient develops a serious or opportunistic infection, interrupt deuruxolitinib treatment until the infection is controlled. DISCUSSION: Serious infections have been reported in patients receiving treatment with deuruxolitinib.(1) |
LEQSELVI |
| IgG Antibodies and Derivatives/Nipocalimab-aahu SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3) DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3) |
IMAAVY |
There are 9 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Erlotinib/Anti-Angiogenic Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. CLINICAL EFFECTS: Concurrent use of anti-angiogenic agents may increase the risk of gastrointestinal perforation in patients receiving erlotinib. Fatalities have been reported.(1) PREDISPOSING FACTORS: Patients with a history of peptic ulceration or diverticular disease or who are receiving concomitant corticosteroids, NSAIDs, and/or taxane-based chemotherapy may be an increased risk of gastrointestinal perforation.(1) PATIENT MANAGEMENT: Monitor patients receiving concurrent therapy for signs of gastrointestinal perforation. Discontinue erlotinib in patients who develop gastrointestinal perforation.(1) DISCUSSION: In a phase II trial of concurrent bevacizumab plus erlotinib, 2 of 13 patients suffered fatal gastrointestinal perforations.(2) In another phase II trial of concurrent bevacizumab with erlotinib, 1 of 104 patients died of gastrointestinal perforation.(3) |
ERLOTINIB HCL |
| Naloxegol/Bevacizumab SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The exact mechanism is unknown. Both naloxegol and bevacizumab have been reported to cause gastrointestinal perforation. CLINICAL EFFECTS: Concurrent use of bevacizumab may increase the risk of gastrointestinal perforation in patients receiving naloxegol.(1) PREDISPOSING FACTORS: Patients with infiltrative gastrointestinal tract malignancy, recent gastrointestinal tract surgery, diverticular disease including diverticulitis, and/or ischemic colitis may be at increased risk of gastrointestinal perforation.(1) PATIENT MANAGEMENT: Consider the risk-benefit profile when using naloxegol in patients on concurrent bevacizumab, especially if they have conditions which might result in impaired integrity of the gastrointestinal tract wall (e.g., Crohn's disease). Monitor for the development of severe, persistent or worsening abdominal pain. Discontinue naloxegol in patients who develop gastrointestinal perforation.(1) DISCUSSION: There are no published reports of gastrointestinal perforation with the combination of naloxegol and bevacizumab. The FDA Adverse Events Reporting System (FAERS) database contains one report of a 45 year old man with metastatic rectal cancer who developed small intestinal perforation while on naloxegol and bevacizumab. |
MOVANTIK |
| Ustekinumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ustekinumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ustekinumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of ustekinumab recommends caution because the concurrent use of ustekinumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Ustekinumab has not been studied in combination with other immunosuppressants in psoriasis studies. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab. In Crohn's disease and ulcerative colitis studies, concomitant use of immunosuppressants or corticosteroids did not appear to influence the safety or efficacy of ustekinumab. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by ustekinumab treated patients in the clinical trial periods included nasopharyngitis(8%) and upper respiratory tract infection(5%). Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab. Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia resulting in respiratory failure or prolonged hospitalization have been reported in patients receiving ustekinumab.(1) |
IMULDOSA, OTULFI, PYZCHIVA, PYZCHIVA AUTOINJECTOR, SELARSDI, STELARA, STEQEYMA, USTEKINUMAB, USTEKINUMAB-AEKN, USTEKINUMAB-TTWE, WEZLANA, YESINTEK |
| COVID-19 Vaccines/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Immunosuppressants and immunomodulators may prevent the immune system from properly responding to the COVID-19 vaccine.(1,2) CLINICAL EFFECTS: Administration of a COVID-19 vaccine with immunosuppressants or immunomodulators may interfere with vaccine-induced immune response and impair the efficacy of the vaccine. However, patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: In an effort to optimize COVID-19 vaccine response, the American College of Rheumatology (ACR) published conditional recommendations for administration of COVID-19 vaccines with immunosuppressants and immunomodulators.(1) The CDC also provides clinical considerations for COVID-19 vaccination in patients on immunosuppressants.(2) The CDC states that all immunocompromised patients over 6 months of age should receive at least 1 dose of COVID-19 vaccine if eligible. See the CDC's Interim Clinical Considerations for Use of COVID-19 Vaccines for specific recommendations based on age, vaccination history, and vaccine manufacturer.(2) The ACR states that in general, immunosuppressants and immunomodulators should be held for 1-2 weeks after each vaccine dose. See below for specific recommendations for certain agents.(1) The CDC advises planning for vaccination at least 2 weeks before starting or resuming immunosuppressive therapy.(2) Patients should be offered and given a COVID-19 vaccine even if the use and timing of immunosuppressive agents cannot be adjusted.(1,2) B-cell depleting agents, including rituximab: The ACR recommends consulting with the rheumatologist to determine optimal timing of COVID-19 vaccination. Measuring CD19 B cells may be considered to determine need for a booster vaccine dose. If B cell levels are not measured, a supplemental vaccine dose 2-4 weeks before the next scheduled dose of rituximab is recommended.(1) The CDC states that the utility of B-cell quantification to guide clinical care is not known and is not recommended. Patients who receive B-cell depleting therapy should receive COVID-19 vaccines about 4 weeks before the next scheduled dose. For patients who received 1 or more doses of COVID-19 vaccine during treatment with B-cell-depleting therapies that were administered over a limited period (e.g., as part of a treatment regimen for certain malignancies), revaccination may be considered. The suggested interval to start revaccination is about 6 months after completion of the B-cell-depleting therapy.(2) Abatacept: - Subcutaneous abatacept should be withheld for 1-2 weeks after each vaccine dose, as disease activity allows. - For intravenous abatacept, time administration so that vaccination will occur 1 week before the next abatacept infusion.(1) Cyclophosphamide: When feasible, administer cyclophosphamide one week after each COVID-19 vaccine dose.(1) Recipients of hematopoietic cell transplant or CAR-T-cell therapy who received one or more doses of COVID-19 vaccine prior to or during treatment should undergo revaccination following the current CDC recommendations for unvaccinated patients. Revaccination should start at least 3 months (12 weeks) after transplant or CAR-T-cell therapy.(2) TNF-alpha inhibitors and cytokine inhibitors: The ACR was not able to reach consensus on whether to modify dosing or timing of these agents with COVID-19 vaccination.(1) The CDC includes these agents in their general recommendation to hold therapy for at least 2 weeks following vaccination.(2) DISCUSSION: The ACR convened a COVID-19 Vaccine Guidance Task Force to provide guidance on optimal use of COVID-19 vaccines in rheumatology patients. These recommendations are based on limited clinical evidence of COVID-19 vaccines in patients without rheumatic and musculoskeletal disorders and evidence of other vaccines in this patient population.(1) The ACR recommendation for rituximab is based on studies of humoral immunity following receipt of other vaccines. These studies have uncertain generalizability to vaccination against COVID-19, as it is unknown if efficacy is attributable to induction of host T cells versus B cell (antibody-based) immunity.(1) The ACR recommendation for mycophenolate is based on preexisting data of mycophenolate on non-COVID-19 vaccine immunogenicity. Emerging data suggests that mycophenolate may impair SARS-CoV-2 vaccine response in rheumatic and musculoskeletal disease and transplant patients.(1) The ACR recommendation for methotrexate is based on data from influenza vaccines and pneumococcal vaccines with methotrexate.(1) The ACR recommendation for JAK inhibitors is based on concerns related to the effects of JAK inhibitors on interferon signaling that may result in a diminished vaccine response.(1) The ACR recommendation for subcutaneous abatacept is based on several studies suggesting a negative effect of abatacept on vaccine immunogenicity. The first vaccine dose primes naive T cells, naive T cell priming is inhibited by CTLA-4, and abatacept is a CTLA-4Ig construct. CTLA-4 should not inhibit boosts of already primed T cells at the time of the second vaccine dose.(1) |
COMIRNATY 2025-2026 (12Y UP), COMIRNATY 2025-2026(5-11Y), MNEXSPIKE 2025-2026 (12Y UP), MODERNA COVID 24-25(6M-11Y)EUA, NOVAVAX COVID 2024-2025 (EUA), NUVAXOVID 2025-2026, SPIKEVAX 2024-2025, SPIKEVAX 2025-2026 (12Y UP), SPIKEVAX 2025-2026 (6M-11Y) |
| Sarilumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sarilumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of sarilumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of sarilumab recommends caution because the concurrent use of sarilumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Sarilumab was studied as monotherapy and in combination with methotrexate or conventional disease modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis studies. Sarilumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by sarilumab treated patients in the clinical trial periods included pneumonia and cellulitis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving sarilumab. Cases of tuberculosis, candidiasis, and pneumocystis with sarilumab have been reported.(1) |
KEVZARA |
| Ublituximab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Ublituximab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of ublituximab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: Incomplete washout of previously prescribed immunosuppressive or immune-modulating medications. PATIENT MANAGEMENT: The US manufacturer of ublituximab recommends caution because the concurrent use of ublituximab with immunomodulating or immunosuppressive agents, including immunosuppressant doses of corticosteroids, may increase the risk of infection.(1) If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents. When switching from agents with immune effects, the half-life and mechanism of action of these drugs must be taken into consideration in order to prevent additive immunosuppressive effects.(1) DISCUSSION: The most common infections reported by ublituximab-treated patients in the clinical trial periods included upper respiratory tract infections and urinary tract infections. Serious, including life-threatening or fatal, bacterial and viral infections were observed in patients receiving ublituximab.(1) Serious and/or fatal bacterial, fungal, and new or reactivated viral infections have been associated with other anti-CD20 B-cell depleting therapies. There were no cases of progressive multifocal leukoencephalopathy (PML) reported during the clinical trials; however, there have been reports of PML during or following completion of other anti-CD20 B-cell depleting therapies.(1) |
BRIUMVI |
| Belimumab/Biologic Therapies SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Concurrent use of belimumab with other biologic therapies may result in additive or synergistic effects on the immune system.(1) CLINICAL EFFECTS: Concurrent use of belimumab with other biologic therapies may increase the risk of serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of belimumab with other biologic therapies should be approached with caution.(1) DISCUSSION: In a randomized, double-blind, placebo-controlled trial, more patients who received belimumab and rituximab experienced serious adverse events, serious infections, and post-injection systemic reactions (22.2%, 9%, and 13.2%, respectively) than patients who received belimumab with placebo (13.9%, 2.8%, 9.7%) or standard therapy (19.7%, 5.3%, 5.3%).(1) The combination of belimumab with other biologic therapies has not been studied and should be used cautiously.(1) |
BENLYSTA |
| IgG Antibodies and Derivatives/Rozanolixizumab-noli SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3) CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3) DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3) |
RYSTIGGO |
| Tocilizumab/Immunosuppressives; Immunomodulators SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Tocilizumab, immunosuppressives, and immunomodulators all suppress the immune system.(1) CLINICAL EFFECTS: Concurrent use of tocilizumab with immunosuppressive or immunomodulating agents may result in an increased risk for serious infections.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of tocilizumab recommends caution because the concurrent use of tocilizumab with immunosuppressive agents may increase the risk of infection. If concurrent therapy is warranted, consider the risk of additive immune suppression and monitor based on prescribing information for both agents.(1) DISCUSSION: Tocilizumab was studied as monotherapy and in combination with methotrexate, non-biologic DMARDs or corticosteroids, depending on the indication. Tocilizumab has not been studied with biological DMARDs and concurrent use should be avoided. If concurrent therapy is warranted, consider the potential for increased immunosuppressive risks from both agents.(1) The most common infections reported by tocilizumab treated patients in the clinical trial periods included pneumonia, urinary tract infection, cellulitis, herpes zoster, gastroenteritis, diverticulitis, sepsis and bacterial arthritis. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving tocilizumab. Cases of tuberculosis, cryptococcus, aspergillosis, candidiasis, and pneumocystosis have been reported.(1) |
ACTEMRA, ACTEMRA ACTPEN, TOFIDENCE, TYENNE, TYENNE AUTOINJECTOR |
The following contraindication information is available for AVASTIN (bevacizumab):
Drug contraindication overview.
*None.
*None.
There are 12 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Abnormal vaginal bleeding |
| Alveolar hemorrhage |
| Gastrointestinal fistula |
| Gastrointestinal hemorrhage |
| Gastrointestinal perforation |
| Intracerebral hemorrhage |
| Lactation |
| Necrotizing fasciitis |
| Nephrotic syndrome |
| New fistula formation involving an internal organ |
| Posterior reversible encephalopathy syndrome |
| Tracheoesophageal fistula |
There are 15 severe contraindications.
Adequate patient monitoring is recommended for safer drug use.
| Severe List |
|---|
| Acute myocardial infarction |
| Angina |
| Chemotherapy-induced neutropenia |
| Chronic heart failure |
| Erosive esophagitis |
| Female hypogonadism |
| Hypertension |
| Impaired wound healing |
| Invasive surgical procedure |
| Neutropenic disorder |
| Pregnancy |
| Proteinuria |
| Surgical wound dehiscence |
| Thromboembolic disorder |
| Transient cerebral ischemia |
There are 1 moderate contraindications.
Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.
| Moderate List |
|---|
| Secondary ovarian failure |
The following adverse reaction information is available for AVASTIN (bevacizumab):
Adverse reaction overview.
Adverse effects reported in more than 10% of patients receiving bevacizumab (alone or with chemotherapy) include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
Adverse effects reported in more than 10% of patients receiving bevacizumab (alone or with chemotherapy) include epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, hemorrhage, lacrimation disorder, back pain, and exfoliative dermatitis.
There are 72 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Dyspnea Exfoliative dermatitis Gastrointestinal hemorrhage Hyperbilirubinemia Hypertension Increased alanine transaminase Increased aspartate transaminase Leukopenia Neutropenic disorder Proteinuria Rectal bleeding Secondary ovarian failure Stomatitis Venous thrombosis |
Chest pain Colitis Deep venous thrombosis Dehydration Gastrointestinal ulcer Hypersensitivity drug reaction Hypomagnesemia Hyponatremia Hypotension Ileus Infection Kidney disease with reduction in glomerular filtration rate (GFr) Left ventricular failure Skin ulcer Syncope Thrombocytopenic disorder Thrombotic disorder |
| Rare/Very Rare |
|---|
|
Abnormal vaginal bleeding Acute arterial thromboembolism Acute myocardial infarction Acute occlusion of mesenteric vein Anaphylaxis Arterial aneurysm Arterial dissection Aseptic necrosis of jaw bone Bleeding esophageal varices Bloody vomit Cerebral ischemia Cerebrovascular accident Chronic heart failure Conjunctival hemorrhage Dissection of aorta Endophthalmitis Gastrointestinal fistula Gastrointestinal perforation Gastrojejunal ulcer Hemoptysis Hemorrhage Hypertensive crisis Hypokalemia Impaired wound healing Intestinal ischemic necrosis Intracerebral hemorrhage Nasal septal perforation Necrotizing fasciitis Nephrotic syndrome New fistula formation involving an internal organ Pancytopenia Perforation of gallbladder Polyserositis Posterior reversible encephalopathy syndrome Pulmonary hemorrhage Pulmonary hypertension Retinal detachment Surgical wound dehiscence Thrombotic thrombocytopenic purpura Tracheoesophageal fistula Transient cerebral ischemia |
There are 46 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Acute abdominal pain Anorexia Arthralgia Back pain Diarrhea Dizziness Dry skin Dysgeusia Epistaxis Eye tearing Fatigue General weakness Headache disorder Myalgia Nausea Peripheral sensory neuropathy Rhinitis Upper respiratory infection Vomiting |
Alopecia Anal fistula Angina Constipation Dysarthria Dyspepsia Hemorrhoids Hyperglycemia Hyperhidrosis Hypoalbuminemia Lymphopenia Muscle weakness Nasal passage irritation Pain Pelvic pain Peripheral edema Rectal pain Rhinorrhea Symptoms of anxiety Urinary tract infection Voice change Weight loss Xerostomia |
| Rare/Very Rare |
|---|
|
Blurred vision Ocular inflammation Vitreous floater Wheezing |
The following precautions are available for AVASTIN (bevacizumab):
Safety and efficacy of bevacizumab have not been established in pediatric patients younger than 18 years of age. Addition of bevacizumab to standard of care did not improve event-free survival in pediatric patients with high-grade glioma, metastatic rhabdomyosarcoma, or non-rhabdomyosarcoma soft tissue sarcoma in 2 clinical studies. Antitumor activity was also not observed in 8 pediatric patients who received bevacizumab plus irinotecan for relapsed glioblastoma.
Non-mandibular osteonecrosis has been reported in pediatric patients younger than 18 years of age who have received bevacizumab. Based on a population pharmacokinetic analysis of data from 152 pediatric and young adult patients with cancer (age range: 7 months to 21 years of age), the clearance of bevacizumab normalized by body weight in the pediatric patients was comparable to that in adults.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Non-mandibular osteonecrosis has been reported in pediatric patients younger than 18 years of age who have received bevacizumab. Based on a population pharmacokinetic analysis of data from 152 pediatric and young adult patients with cancer (age range: 7 months to 21 years of age), the clearance of bevacizumab normalized by body weight in the pediatric patients was comparable to that in adults.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
Based on its mechanism of action and findings from animal studies, bevacizumab may cause fetal harm when administered to pregnant women. Limited postmarketing reports describe cases of fetal malformations with use of bevacizumab in pregnancy; however, these reports are insufficient to determine drug-associated risks. When bevacizumab was administered IV to pregnant rabbits every 3 days during the period of organogenesis at dosages approximately 1-10 times the clinical dosage of 10 mg/kg, fetal resorptions, decreased maternal and fetal weight gain, and multiple congenital malformations, including corneal opacities and abnormal ossification of the skull and skeleton (including limb and phalangeal defects), were observed.
Animal models also link angiogenesis, VEGF, and VEGFR2 to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus.
Animal models also link angiogenesis, VEGF, and VEGFR2 to critical aspects of female reproduction, embryofetal development, and postnatal development. Advise pregnant women of the potential risk to a fetus.
It is not known whether bevacizumab is distributed into milk. Human immunoglobulin G1 (IgG1) is distributed into milk; however, published data suggest that antibodies in breast milk do not enter the neonatal and infant circulation in substantial amounts. The effects of bevacizumab on the breast-fed infant and on milk production also are unknown. Because of the potential for serious adverse reactions in nursing infants, advise women not to breast-feed during treatment with bevacizumab and for 6 months after the last dose.
Analysis of pooled data from 5 randomized controlled trials involving 1745 patients (35% were 65 years of age or older) showed that arterial thromboembolic events occurred more frequently in all patients receiving bevacizumab with chemotherapy compared with those receiving chemotherapy alone, regardless of age. However, the increase in the incidence of arterial thromboembolic events associated with concomitant bevacizumab therapy was greater in patients 65 years of age or older (8 versus 3%) compared with those younger than 65 years of age (2 versus 1%).
The following prioritized warning is available for AVASTIN (bevacizumab):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for AVASTIN (bevacizumab)'s list of indications:
| Carcinoma of cervix | |
| C53 | Malignant neoplasm of cervix uteri |
| C53.0 | Malignant neoplasm of endocervix |
| C53.1 | Malignant neoplasm of exocervix |
| C53.8 | Malignant neoplasm of overlapping sites of cervix uteri |
| C53.9 | Malignant neoplasm of cervix uteri, unspecified |
| Epithelial ovarian cancer | |
| C48.1 | Malignant neoplasm of specified parts of peritoneum |
| C48.2 | Malignant neoplasm of peritoneum, unspecified |
| C48.8 | Malignant neoplasm of overlapping sites of retroperitoneum and peritoneum |
| C56 | Malignant neoplasm of ovary |
| C56.1 | Malignant neoplasm of right ovary |
| C56.2 | Malignant neoplasm of left ovary |
| C56.3 | Malignant neoplasm of bilateral ovaries |
| C56.9 | Malignant neoplasm of unspecified ovary |
| C57.01 | Malignant neoplasm of right fallopian tube |
| C57.02 | Malignant neoplasm of left fallopian tube |
| Glioblastoma multiforme | |
| C71 | Malignant neoplasm of brain |
| C71.0 | Malignant neoplasm of cerebrum, except lobes and ventricles |
| C71.1 | Malignant neoplasm of frontal lobe |
| C71.2 | Malignant neoplasm of temporal lobe |
| C71.3 | Malignant neoplasm of parietal lobe |
| C71.4 | Malignant neoplasm of occipital lobe |
| C71.5 | Malignant neoplasm of cerebral ventricle |
| C71.6 | Malignant neoplasm of cerebellum |
| C71.7 | Malignant neoplasm of brain stem |
| C71.8 | Malignant neoplasm of overlapping sites of brain |
| C71.9 | Malignant neoplasm of brain, unspecified |
| Liver cell carcinoma | |
| C22.0 | Liver cell carcinoma |
| Metastatic colorectal cancer | |
| C18 | Malignant neoplasm of colon |
| C18.0 | Malignant neoplasm of cecum |
| C18.1 | Malignant neoplasm of appendix |
| C18.2 | Malignant neoplasm of ascending colon |
| C18.3 | Malignant neoplasm of hepatic flexure |
| C18.4 | Malignant neoplasm of transverse colon |
| C18.5 | Malignant neoplasm of splenic flexure |
| C18.6 | Malignant neoplasm of descending colon |
| C18.7 | Malignant neoplasm of sigmoid colon |
| C18.8 | Malignant neoplasm of overlapping sites of colon |
| C18.9 | Malignant neoplasm of colon, unspecified |
| C19 | Malignant neoplasm of rectosigmoid junction |
| C20 | Malignant neoplasm of rectum |
| C21.8 | Malignant neoplasm of overlapping sites of rectum, anus and anal canal |
| Metastatic renal cell carcinoma | |
| C64 | Malignant neoplasm of kidney, except renal pelvis |
| C64.1 | Malignant neoplasm of right kidney, except renal pelvis |
| C64.2 | Malignant neoplasm of left kidney, except renal pelvis |
| C64.9 | Malignant neoplasm of unspecified kidney, except renal pelvis |
| Nonsquamous non-small cell lung cancer | |
| C34 | Malignant neoplasm of bronchus and lung |
| C34.0 | Malignant neoplasm of main bronchus |
| C34.00 | Malignant neoplasm of unspecified main bronchus |
| C34.01 | Malignant neoplasm of right main bronchus |
| C34.02 | Malignant neoplasm of left main bronchus |
| C34.1 | Malignant neoplasm of upper lobe, bronchus or lung |
| C34.10 | Malignant neoplasm of upper lobe, unspecified bronchus or lung |
| C34.11 | Malignant neoplasm of upper lobe, right bronchus or lung |
| C34.12 | Malignant neoplasm of upper lobe, left bronchus or lung |
| C34.2 | Malignant neoplasm of middle lobe, bronchus or lung |
| C34.3 | Malignant neoplasm of lower lobe, bronchus or lung |
| C34.30 | Malignant neoplasm of lower lobe, unspecified bronchus or lung |
| C34.31 | Malignant neoplasm of lower lobe, right bronchus or lung |
| C34.32 | Malignant neoplasm of lower lobe, left bronchus or lung |
| C34.8 | Malignant neoplasm of overlapping sites of bronchus and lung |
| C34.80 | Malignant neoplasm of overlapping sites of unspecified bronchus and lung |
| C34.81 | Malignant neoplasm of overlapping sites of right bronchus and lung |
| C34.82 | Malignant neoplasm of overlapping sites of left bronchus and lung |
| C34.9 | Malignant neoplasm of unspecified part of bronchus or lung |
| C34.90 | Malignant neoplasm of unspecified part of unspecified bronchus or lung |
| C34.91 | Malignant neoplasm of unspecified part of right bronchus or lung |
| C34.92 | Malignant neoplasm of unspecified part of left bronchus or lung |
| C39.9 | Malignant neoplasm of lower respiratory tract, part unspecified |
Formulary Reference Tool