tivozanib (Rx)

Brand and Other Names:Fotivda
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 0.89mg
  • 1.34mg

Renal Cell Carcinoma

Indicated for relapsed or refractory advanced renal cell carcinoma in patients previously treated with ≥2 systemic therapies

1.34 mg PO qDay on Days 1-21 of repeated 28-day cycles

Continue until disease progression or unacceptable toxicity

Dosage Modifications

If dose modifications are required for adverse reactions, reduce to 0.89 mg qDay for 21 days followed by 7 days off treatment

Initiate medical management for diarrhea, nausea, or vomiting prior to dose interruption or reduction

Hypertension

  • Grade 3
    • Withhold for persistent Grade 3 despite optimal antihypertensive therapy
    • Resume at reduced dose when hypertension controlled at Grade ≤2
  • Grade 4
    • Permanently discontinue

Cardiac failure

  • Grade 3
    • Withhold until improves to Grade ≤1 or baseline
    • Resume at reduced dose or discontinue depending on severity and persistence
  • Grade 4
    • Permanently discontinue

Arterial thromboembolic events or reverse posterior leukoencephalopathy syndrome (RPLS)

  • Any grade: Permanently discontinue

Hemorrhagic events

  • Grade 3 or 4: Permanently discontinue

Proteinuria

  • 2 grams or greater proteinuria in 24 hr
    • Withhold until less than or equal to 2 grams of proteinuria per 24 hr
    • Resume at a reduced dose
    • Permanently discontinue for nephrotic syndrome

Other adverse reactions

  • Persistent or intolerable Grade 2 or 3 OR Grade 4 laboratory abnormality
    • Withhold until improves to Grade ≤1 or baseline; resume at reduced dose
  • Grade 4
    • Permanently discontinue

Renal impairment

  • Mild-to-severe (CrCl 15-89 mL/min): No dosage modifications
  • End-stage renal disease: Recommend dose not established

Hepatic impairment

  • Mild (total bilirubin [TB] ≤1.5x ULN with any AST): No dosage adjustment necessary
  • Moderate (TB >1.5 to 3x ULN with any AST): Reduce to 0.89 mg qDay
  • Severe (TB 3 to 10x ULN with any AST): Not established

Dosing Considerations

Verify pregnancy in females of reproductive potential before initiation

Safety and efficacy not established

Next:

Interactions

Interaction Checker

and tivozanib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (25)

              • amobarbital

                amobarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • apalutamide

                apalutamide will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • bosentan

                bosentan will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • butabarbital

                butabarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • butalbital

                butalbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • carbamazepine

                carbamazepine will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • dabrafenib

                dabrafenib will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • efavirenz

                efavirenz will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • enzalutamide

                enzalutamide will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • etravirine

                etravirine will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • ivosidenib

                ivosidenib will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • mitotane

                mitotane will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • nafcillin

                nafcillin will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • palifermin

                palifermin increases toxicity of tivozanib by Other (see comment). Avoid or Use Alternate Drug. Comment: Palifermin should not be administered within 24 hr before, during infusion of, or within 24 hr after administration of antineoplastic agents. Coadministration of palifermin within 24 hr of chemotherapy resulted in increased severity and duration of oral mucositis.

              • pentobarbital

                pentobarbital will decrease the level or effect of tivozanib by affecting hepatic enzyme CYP2E1 metabolism. Avoid or Use Alternate Drug.

              • phenobarbital

                phenobarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • phenytoin

                phenytoin will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • primidone

                primidone will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifabutin

                rifabutin will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifampin

                rifampin will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • rifapentine

                rifapentine will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • secobarbital

                secobarbital will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              • St John's Wort

                St John's Wort will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

              Monitor Closely (12)

              • armodafinil

                armodafinil will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • bexarotene

                bexarotene will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • brigatinib

                brigatinib will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • clobazam

                clobazam will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • elagolix

                elagolix will increase the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • encorafenib

                encorafenib will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • eslicarbazepine acetate

                eslicarbazepine acetate will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • lorlatinib

                lorlatinib will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • pexidartinib

                pexidartinib will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • ponesimod

                ponesimod and tivozanib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • siponimod

                siponimod and tivozanib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • telotristat ethyl

                telotristat ethyl will decrease the level or effect of tivozanib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              Minor (0)

                Previous
                Next:

                Adverse Effects

                >10%

                All grades

                • Fatigue (67%)
                • Creatinine increased (50%)
                • Glucose increased (50%)
                • Hypertension (44%)
                • Diarrhea (43%)
                • Decreased appetite (39%)
                • Phosphate decreased (38%)
                • Sodium decreased (36%)
                • Lipase increased (32%)
                • ALT increased (30%)
                • Alkaline phosphatase increased (30%)
                • Nausea (30%)
                • AST increased (28%)
                • Dysphonia (27%)
                • aPTT prolonged (26%)
                • Potassium increased (26%)
                • Magnesium decreased (26%)
                • Lymphocytes decreased (25%)
                • Hypothyroidism (24%)
                • Amylase increased (23%)
                • Cough (22%)
                • Stomatitis (21%)
                • Hemoglobin increased (19%)
                • Platelets decreased (19%)
                • Back pain (19%)
                • Rash (18%)
                • Vomiting (18%)
                • Bleeding (17%)
                • Weight decreased (17%)
                • Hemoglobin decreased (16%)
                • Palmoplantar erythrodysesthesia syndrome (16%)
                • Calcium increased (15%)
                • Dyspnea (15%)
                • Proteinuria (<15%)
                • Venous thromboembolism (<15%)
                • Arterial thromboembolism (<15%)
                • Hyperthyroidism (<15%)
                • Hepatobiliary disorders (<15%)
                • Osteonecrosis (<15%)
                • Cardiac failure (<15%)
                • Delirium (<15%)
                • Bilirubin increased (11%)

                Grade 3 or 4

                • Hypertension (24%)
                • Fatigue (13%)

                1-10%

                Grade 3 or 4

                • Sodium decreased (9%)
                • Lipase increased (9%)
                • Phosphate decreased (5%)
                • Lymphocytes decreased (5%)
                • Decreased appetite (5%)
                • ALT increased (4%)
                • Alkaline phosphatase increased (4%)
                • Glucose increased (3%)
                • Potassium increased (3%)
                • Bilirubin increased (3%)
                • Bleeding (3%)
                • Dyspnea (3%)
                • Decreased weight (3%)
                • Amylase increased (2%)
                • Calcium increased (2%)
                • Diarrhea (2%)
                • Stomatitis (2%)
                • Back pain (2%)
                • aPTT prolonged (1%)
                • AST increased (1%)
                • Hemoglobin decreased (1%)
                • Vomiting (1%)
                • Dysphonia (1%)
                • Hypothyroidism (1%)
                • Rash (1%)
                • Palmoplantar erythrodysesthesia syndrome (1%)
                Previous
                Next:

                Warnings

                Contraindications

                None

                Cautions

                May cause fetal harm

                Imprint ink on 0.89-mg capsule contains FD&C yellow No.5 (tartrazine), which may cause allergic-type reactions (including bronchial asthma) in certain susceptible patients; sensitivity is commonly seen in patients who also have aspirin hypersensitivity

                RPLS can occur; evaluate for RPLS in any patient presenting with seizures, headaches, visual disturbances, confusion, or altered mental function

                May cause thyroid dysfunction; monitor thyroid function before initiation of, and periodically throughout, treatment; treat hypothyroidism and hyperthyroidism to maintain euthyroid state before and during treatment

                Can cause serious, sometimes fatal, cardiac ischemia and arterial thromboembolic events; not studied in patients with significant bleeding or who have had an arterial thrombotic event, myocardial infarction, or unstable angina within the preceding 6 months before initiating

                Proteinuria reported; monitor for proteinuria before initiating, and periodically during treatment; discontinue if nephrotic syndrome develops

                Hypertension and hypertensive crisis

                • May cause severe hypertension and hypertensive crisis
                • Median time to onset of hypertension was 2 weeks
                • Not studied in patients with systolic blood pressure (BP) >150 mmHg or diastolic BP >100 mmHg
                • Control BP before treatment
                • Monitor BP after 2 weeks and at least monthly thereafter during treatment
                • Treat with antihypertensive therapy when hypertension occurs
                • If therapy interrupted, monitor patients receiving antihypertensive medications for hypotension

                Cardiac failure

                • Serious, sometimes fatal, cardiac failure may occur
                • Not studied in patients with symptomatic cardiac failure within the preceding 6 months before initiating
                • Periodically monitor for symptoms of cardiac failure throughout treatment

                Risk of impaired wound healing

                • Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway, such as tivozanib
                • May adversely affect wound healing
                • Withhold for at least 24 days prior to elective surgery
                • Do not administer for at least 2 weeks following major surgery and until adequate wound healing
                • Safety of resumption after resolution of wound healing complications has not been established

                Drug interaction overview

                • CYP3A4 substrate; inhibits BCRP
                • Strong CYP3A4 inducers
                  • Avoid coadministration
                  • Strong CYP3A4 inducers may decrease exposure and efficacy of tivozanib
                Previous
                Next:

                Pregnancy & Lactation

                Pregnancy

                No data are available on use

                Verify pregnancy status of females of reproductive potential before starting treatment

                Animal data

                • Oral administration of tivozanib to pregnant animals during organogenesis caused maternal toxicity, fetal malformations and embryofetal death at doses below the maximum recommended clinical dose on a mg/m2 basis

                Contraception

                • Females of reproductive potential: Use effective contraception during treatment and for 1 month after last dose
                • Males with female partners of reproductive potential: Use effective contraception during treatment and for 1 month after last dose

                Fertility

                • Females and males of reproductive potential: Can impair fertility

                Lactation

                There are no data on presence in human milk, effects on the breastfed children, or on milk production

                Advise not to breastfeed during treatment and for 1 month after last dose

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

                Previous
                Next:

                Pharmacology

                Mechanism of Action

                Tyrosine kinase inhibitor

                In vitro cellular kinase assays demonstrated that tivozanib inhibits phosphorylation of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2 and VEGFR-3 and inhibits other kinases including c-kit and PDGFR-beta at clinically relevant concentrations

                Absorption

                Peak plasma concentration: 86.9 ng/mL

                Peak plasma time: 10 hr

                AUC: 1510 ng⋅hr/mL

                Distribution

                Protein bound: ≥99%

                Vd: 123 L

                Mean blood-to-plasma concentration ratios: 0.495-0.615 (healthy subjects)

                Metabolism

                Metabolized predominately by CYP3A4

                Elimination

                Half-life: 111 hr

                Clearance: 0.75 L/hr

                Excretion (single 1.34-mg dose): Feces (79%; 26% unchanged); urine (12%; unchanged not detected)

                Previous
                Next:

                Administration

                Oral Administration

                Take with or without food

                Swallow capsule whole with a glass of water; do NOT open capsule

                Missed dose: Skip dose; take next dose at next scheduled time; do NOT take 2 doses at the same time

                Storage

                Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

                Keep out of reach of children

                Previous
                Next:

                Images

                No images available for this drug.
                Previous
                Next:

                Patient Handout

                A Patient Handout is not currently available for this monograph.
                Previous
                Next:

                Formulary

                FormularyPatient Discounts

                Adding plans allows you to compare formulary status to other drugs in the same class.

                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
                • Manage and view all your plans together – even plans in different states.
                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
                Additional Offers
                Email to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Email Forms to Patient

                From:

                To:

                The recipient will receive more details and instructions to access this offer.

                By clicking send, you acknowledge that you have permission to email the recipient with this information.

                Previous
                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.