VinBLAStine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous, as sulfate:

Generic: 1 mg/mL (10 mL)

Pharmacology

Mechanism of Action

Vinblastine binds to tubulin and inhibits microtubule formation, therefore, arresting the cell at metaphase by disrupting the formation of the mitotic spindle; it is specific for the M and S phases. Vinblastine may also interfere with nucleic acid and protein synthesis by blocking glutamic acid utilization.

Pharmacokinetics/Pharmacodynamics

Metabolism

Hepatic (via CYP3A) to active metabolite

Excretion

Feces (10%); urine (14%)

Half-Life Elimination

Terminal: ~25 hours

Use: Labeled Indications

Hodgkin Lymphoma: Treatment of Hodgkin lymphoma

Kaposi sarcoma: Treatment of Kaposi sarcoma

Langerhans cell histiocytosis: Treatment of histiocytosis X (Letterer-Siwe disease)

Non-Hodgkin lymphomas: Treatment of lymphocytic lymphoma, histiocytic lymphoma, and advanced mycosis fungoides

Testicular cancer: Treatment of testicular cancer

Has also been used in the treatment of resistant choriocarcinoma

Use: Off Label

Bladder cancera

Data from multiple phase III studies support the use of vinblastine (in combination with methotrexate, doxorubicin, and cisplatin) in the treatment of metastatic bladder cancer Bamias 2004, Sternberg 2001, Sternberg 2006, von der Maase 2000.

Data from 2 randomized phase III studies support the use of vinblastine (in combination with methotrexate, doxorubicin and cisplatin or in combination with methotrexate, cisplatin and leucovorin) for the neoadjuvant treatment of locally advanced or invasive bladder cancer Griffiths 2011, Grossman 2003.

Kaposi sarcoma, oral lesions (intralesional)c

Clinical experience suggests that intralesional vinblastine may be of palliative benefit in reducing oral Kaposi sarcoma lesions Epstein 1993.

Non-small cell lung cancer (NSCLC)a

Data from a large randomized study support the use of vinblastine (in combination with cisplatin) in the adjuvant treatment of completely resected non-small cell lung cancer Arriagada 2004.

Data from a large randomized phase III study support the use of vinblastine (in combination with cisplatin and concurrent radiation therapy) in the treatment of stage III non-small cell lung cancer Curran 2011.

Soft tissue sarcoma (desmoid tumors, aggressive fibromatosis), advancedb

Data from a phase II study support the use of vinblastine (in combination with methotrexate) in the treatment of advanced (inoperable) desmoid tumors/aggressive fibromatosis Azzarelli 2001.

Contraindications

Significant granulocytopenia (unless as a result of condition being treated); presence of bacterial infection

Canadian labeling: Additional contraindications not in the US labeling: Pregnancy

Documentation of allergenic cross-reactivity for drugs in this class is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

Note: For IV use only; fatal if administered by other routes. The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a minibag (NOT a syringe).

Bladder cancer (off-label use): IV:

Metastatic disease:

Dose-dense MVAC regimen: 3 mg/m² on day 2 every 14 days (in combination with methotrexate, doxorubicin, cisplatin, and filgrastim) until disease progression or unacceptable toxicity (Sternberg 2001; Sternberg 2006).

MVAC regimen: 3 mg/m² on days 2, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, and cisplatin) for up to 6 cycles (von der Maase 2000) or 3 mg/m² on days 2, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, and cisplatin) until disease progression or unacceptable toxicity (Sternberg 2001; Sternberg 2006) or 3 mg/m² on days 1, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, cisplatin, and filgrastim) for up to 6 cycles (Bamias 2004).

Neoadjuvant treatment:

MVAC regimen: 3 mg/m² on days 2, 15, and 22 every 28 days (in combination with methotrexate, doxorubicin, and cisplatin) for 3 cycles (Grossman 2003).

CMV regimen: 4 mg/m² on days 1 and 8 every 21 days (in combination with methotrexate, cisplatin, and leucovorin) for 3 cycles (Griffiths 2011).

Hodgkin lymphoma (off-label dosing): IV:

ABVD regimen:

Favorable/early stage disease: 6 mg/m² on days 1 and 15 of a 28-day cycle (in combination with doxorubicin, bleomycin, dacarbazine, and radiation therapy) for 2 cycles (Engert 2007).

Unfavorable/early stage disease: 6 mg/m² on days 1 and 15 of a 28-day cycle (in combination with doxorubicin, bleomycin, dacarbazine, and radiation therapy) for 4 cycles (Eich 2010).

Unfavorable/advanced stage disease: 6 mg/m² on days 1 and 15 of a 28-day cycle (in combination with doxorubicin, bleomycin, dacarbazine, and radiation therapy) for 6 to 8 cycles (Canellos 1992; Gordon 2013).

Stanford V regimen:

Favorable/early stage disease: 6 mg/m² in weeks 1, 3, 5, and 7 (in combination with doxorubicin, mechlorethamine, vincristine, bleomycin, etoposide, prednisone, and radiation therapy) (Advani 2013).

Unfavorable/advanced stage disease: 6 mg/m² in weeks 1, 3, 5, 7, 9, and 11 (in combination with doxorubicin, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone) (Bartlett 1995; Gordon 2013; Horning 2002).

VEPEMB regimen: Adults ≥60 years of age: 6 mg/m² on day 1 of each 28-day cycle (in combination with cyclophosphamide, prednisone/prednisolone, procarbazine, etoposide, mitoxantrone, and bleomycin, ± radiation therapy) for 3 cycles (stage 1A or IIA disease) or for 6 cycles (stage IIB, III, or IV disease) (Levis 2004; Proctor 2012).

Kaposi sarcoma, oral lesions (off-label route; based on limited data): Intralesional: 0.1 mL per 0.5 cm² lesion injected directly into the lesion (a 0.2 mg/mL vinblastine solution was used). Larger lesions may require multiple injections; reported range of volume injected: 0.8 to 4 mL (Epstein 1993).

Non-small cell lung cancer (off-label use): IV:

Adjuvant treatment after complete resection: 4 mg/m² on days 1, 8, 15, 22, and 29, then every 2 weeks (in combination with cisplatin) until last cisplatin dose (Arriagada 2004).

Concurrent radiation: 5 mg/m² on days 1, 8, 15, 22, and 29 (in combination with cisplatin and concurrent radiation therapy) (Curran 2011).

Soft tissue sarcoma (desmoid tumors, aggressive fibromatosis), advanced (off-label use): IV: 6 mg/m² every 7 to 10 days (dose usually rounded to 10 mg) in combination with methotrexate for 1 year (Azzarelli 2001).

Testicular cancer (off-label dosing): VeIP regimen: IV: 0.11 mg/kg daily for 2 days every 21 days (in combination with ifosfamide, cisplatin, and mesna) for 4 cycles (Loehrer 1988; Loehrer 1988 [correction]; Loehrer 1998).

Manufacturer's labeling:Hodgkin lymphoma, non-Hodgkin lymphomas (lymphocytic lymphoma, histiocytic lymphoma, advanced mycosis fungoides), testicular cancer, Kaposi sarcoma, Langerhans cell histiocytosis (histiocytosis X, Letterer-Siwe disease): Dosing in the prescribing information may not reflect current clinical practice. IV: 3.7 mg/m²; adjust dose every 7 days (based on white blood cell response) up to 5.5 mg/m² (second dose); 7.4 mg/m² (third dose); 9.25 mg/m² (fourth dose); and 11.1 mg/m² (fifth dose); do not administer more frequently than every 7 days. Usual dosage range: 5.5 to 7.4 mg/m² every 7 days; Maximum dose: 18.5 mg/m²; dosage adjustment goal is to reduce white blood cell count to ~3,000/mm³. Frequency and duration of therapy may vary by indication, concomitant combination chemotherapy and hematologic response.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Dosing and frequency may vary by indication, protocol, and/or treatment phase and hematologic response; refer to specific protocol. For IV use only. In order to prevent inadvertent intrathecal administration, the Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a minibag (NOT a syringe).

Hodgkin lymphoma: Infants, Children, and Adolescents: IV:

Manufacturer's labeling: Initial dose: 6 mg/m²/dose; do not administer more frequently than every 7 days

ABVD regimen: 6 mg/m²/dose administered on days 1 and 15 of a 28 day cycle in combination with doxorubicin, bleomycin, and darcarbazine (Hutchinson, 1989)

ChlVPP regimen: 6 mg/m²/dose administered on days 1 and 8 of a 28 day cycle in combination with chlorambucil, procarbazine, and prednisolone; minimum reported age: 7 months (Atra, 2002; Capra, 2007; Hall, 2007; Stoneham, 2007)

Langerhans cell histiocytosis; multisystem (Letterer-Siwe disease; Histiocytosis X): Infants, Children, and Adolescents: IV:

Manufacturer's labeling: Initial dose: 6.5 mg/m²/dose; do not administer more frequently than every 7 days

Alternate dosing: Limited data available: Induction: 6 mg/m²/dose every 7 days in combination with prednisone for 6 to 12 weeks depending upon clinical response; then begin maintenance therapy of 6 mg/m²/dose every 3 weeks in combination with prednisone, continue for a total duration of vinblastine therapy of 12 months (Gadner, 2013; Haupt, 2013)

Germ cell tumors; extracranial (eg, testicular, ovarian, mediastinal): Infants, Children, and Adolescents: IV: Initial dose: 3 mg/m²/dose; per the manufacturer, do not administer more frequently than every 7 days; however, in some trials, a single dose was used (Lopes, 2009) and others used a daily dose of vinblastine administered over 1 hour for 2 days (Göbel, 2001; Schneider, 2000)

Dosing: Obesity

ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient's actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs 2012).

Reconstitution

Note: The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a minibag (NOT in a syringe).

For infusion, dilute in 25 to 50 mL NS, D5W, or LR; dilution in larger volumes (≥100 mL) of IV fluids is not recommended.

Administration

IV: The Institute for Safe Medication Practices (ISMP) strongly recommends dispensing vinblastine in a minibag (NOT in a syringe). For IV administration only. Fatal if administered by other routes. The preferred administration is as a short infusion in a 25 to 50 mL minibag. Prolonged administration times (≥30 to 60 minutes) and/or increased administration volumes may increase the risk of vein irritation and extravasation.

Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); initiate hyaluronidase antidote; remove needle/cannula; apply dry warm compresses for 20 minutes 4 times a day for 1 to 2 days; elevate extremity (Perez Fidalgo 2012). Remaining portion of the vinblastine dose should be infused through a separate vein.

Hyaluronidase: If needle/cannula still in place, administer 1 to 6 mL hyaluronidase (150 units/mL) into the existing IV line; the usual dose is 1 mL hyaluronidase for each 1 mL of extravasated drug (Perez Fidalgo 2012; Schulmeister 2011). If needle/cannula was removed, inject 1 to 6 mL (150 units/mL) subcutaneously in a clockwise manner using 1 mL for each 1 mL of drug extravasated (Schulmeister 2011) or administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) subcutaneously into the extravasation site (Polovich 2009).

Intralesional (off-label route): Administer local anesthesia prior to vinblastine intralesional injections; analgesia may be required for 1 to 2 days following vinblastine administration (Epstein 1993).

Storage

Note: Vinblastine should be dispensed in a minibag (ISMP 2018).

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. Solutions diluted for infusion in NS, D5W, or LR (20 mcg/mL concentration) are stable for up to 21 days if protected from light (Beijnen 1989). The formulation of vinblastine may have changed since this stability study was conducted; consult the manufacturer's prescribing information for further information. Follow USP 797 recommendations for beyond use dates based on the level of risk for preparation.

Drug Interactions

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Baricitinib: Immunosuppressants may enhance the immunosuppressive effect of Baricitinib. Management: Use of baricitinib in combination with potent immunosuppressants such as azathioprine or cyclosporine is not recommended. Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted. Consider therapy modification

BCG (Intravesical): Immunosuppressants may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the immunosuppressive effect of Immunosuppressants. Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants may diminish the diagnostic effect of Coccidioides immitis Skin Test. Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates (High risk with Inducers). Management: Consider an alternative for one of the interacting drugs. Some combinations may be specifically contraindicated. Consult appropriate manufacturer labeling. Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Consider therapy modification

Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Monitor therapy

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Echinacea: May diminish the therapeutic effect of Immunosuppressants. Consider therapy modification

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Fingolimod: Immunosuppressants may enhance the immunosuppressive effect of Fingolimod. Management: Avoid the concomitant use of fingolimod and other immunosuppressants when possible. If combined, monitor patients closely for additive immunosuppressant effects (eg, infections). Consider therapy modification

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Avoid combination

Itraconazole: May increase the serum concentration of VinBLAStine. Monitor therapy

Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Consider therapy modification

Lenograstim: Antineoplastic Agents may diminish the therapeutic effect of Lenograstim. Management: Avoid the use of lenograstim 24 hours before until 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lipegfilgrastim: Antineoplastic Agents may diminish the therapeutic effect of Lipegfilgrastim. Management: Avoid concomitant use of lipegfilgrastim and myelosuppressive cytotoxic chemotherapy. Lipegfilgrastim should be administered at least 24 hours after the completion of myelosuppressive cytotoxic chemotherapy. Consider therapy modification

Lopinavir: May increase the serum concentration of VinBLAStine. Management: Monitor closely for signs and symptoms of vinblastine toxicity; consider temporary interruption of lopinavir/ritonavir antiviral therapy if patients develop significant toxicity with concurrent use. Consider therapy modification

Lorlatinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Avoid concurrent use of lorlatinib with any CYP3A4 substrates for which a minimal decrease in serum concentrations of the CYP3A4 substrate could lead to therapeutic failure and serious clinical consequences. Consider therapy modification

Macrolide Antibiotics: May increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Macrolides may also increase the distribution of Vinca Alkaloids into certain cells and/or tissues. Management: Consider an alternative to using a macrolide antibiotic when possible in order to avoid the potential for increased vinca alkaloid toxicity. Exceptions: Azithromycin (Systemic); Fidaxomicin; Roxithromycin; Spiramycin. Consider therapy modification

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Consider therapy modification

MitoMYcin (Systemic): Antineoplastic Agents (Vinca Alkaloids) may enhance the adverse/toxic effect of MitoMYcin (Systemic). Specifically, the risk of pulmonary toxicity may be increased. Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Consider therapy modification

Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Avoid combination

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Nivolumab: Immunosuppressants may diminish the therapeutic effect of Nivolumab. Consider therapy modification

Ocrelizumab: May enhance the immunosuppressive effect of Immunosuppressants. Monitor therapy

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Palifermin: May enhance the adverse/toxic effect of Antineoplastic Agents. Specifically, the duration and severity of oral mucositis may be increased. Management: Do not administer palifermin within 24 hours before, during infusion of, or within 24 hours after administration of myelotoxic chemotherapy. Consider therapy modification

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Pidotimod: Immunosuppressants may diminish the therapeutic effect of Pidotimod. Monitor therapy

Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Posaconazole: May enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Posaconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Management: Avoid the concomitant use of posaconazole and vinca alkaloids when possible. If combined, monitor for increased vinca alkaloid toxicities (eg, neurotoxicity, gastrointestinal toxicity). Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Ritonavir: May increase the serum concentration of VinBLAStine. Management: Monitor closely for signs and symptoms of vinblastine toxicity; consider temporary interruption of ritonavir antiviral therapy if patients develop significant toxicity with concurrent use. Consider therapy modification

Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Consider therapy modification

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Monitor therapy

Siponimod: Immunosuppressants may enhance the immunosuppressive effect of Siponimod. Monitor therapy

Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Management: Evaluate patients to see if it is medically appropriate to reduce or discontinue therapy with immunosuppressants prior to initiating sipuleucel-T therapy. Consider therapy modification

Smallpox and Monkeypox Vaccine (Live): Immunosuppressants may diminish the therapeutic effect of Smallpox and Monkeypox Vaccine (Live). Monitor therapy

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Consider therapy modification

Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Avoid combination

Tertomotide: Immunosuppressants may diminish the therapeutic effect of Tertomotide. Monitor therapy

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Monitor therapy

Tofacitinib: Immunosuppressants may enhance the immunosuppressive effect of Tofacitinib. Management: Concurrent use with antirheumatic doses of methotrexate or nonbiologic disease modifying antirheumatic drugs (DMARDs) is permitted, and this warning seems particularly focused on more potent immunosuppressants. Consider therapy modification

Tolterodine: VinBLAStine may increase the serum concentration of Tolterodine. Management: Reduce tolterodine dose to 1 mg twice daily (regular release formulation) or 2 mg daily (extended release formulation) (adult doses) and monitor for increased levels/effects of tolterodine with initiation of vinblastine therapy. Consider therapy modification

Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Monitor therapy

Upadacitinib: Immunosuppressants may enhance the immunosuppressive effect of Upadacitinib. Avoid combination

Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Consider therapy modification

Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: Smallpox and Monkeypox Vaccine (Live). Avoid combination

Voriconazole: May enhance the adverse/toxic effect of Antineoplastic Agents (Vinca Alkaloids). Voriconazole may increase the serum concentration of Antineoplastic Agents (Vinca Alkaloids). Consider therapy modification

Adverse Reactions

Frequency not defined.

Cardiovascular: Angina pectoris, cerebrovascular accident, ECG abnormality, hypertension (common), ischemic heart disease, limb ischemia, myocardial infarction, Raynaud's phenomenon

Central nervous system: Decreased deep tendon reflex, depression, dizziness, headache, malaise (common), metallic taste, neurotoxicity (duration: >24 hours), paresthesia, peripheral neuritis, seizure, tumor pain (common), vertigo

Dermatologic: Alopecia (common), dermatitis, skin blister, skin photosensitivity (rare), skin rash

Endocrine & metabolic: Hyperuricemia, SIADH (syndrome of inappropriate antidiuretic hormone secretion)

Gastrointestinal: Abdominal pain, anorexia, constipation (common), diarrhea, enterocolitis (hemorrhagic), gastrointestinal hemorrhage, intestinal obstruction, nausea (mild), paralytic ileus, stomatitis, toxic megacolon, vomiting (mild)

Genitourinary: Azoospermia, urinary retention

Hematologic & oncologic: Anemia, bone marrow depression (common), granulocytopenia (common; nadir: 5 to 10 days; recovery: 7 to 14 days; dose-limiting toxicity), hemolytic uremic syndrome, leukopenia (common; nadir: 5 to 10 days; recovery: 7 to 14 days; dose-limiting toxicity), rectal hemorrhage, thrombocytopenia (recovery within a few days), thrombotic thrombocytopenic purpura

Local: Local irritation

Neuromuscular & skeletal: Jaw pain (common), myalgia, ostealgia (common), weakness

Ophthalmic: Nystagmus

Otic: Auditory disturbance, deafness, vestibular disturbance

Respiratory: Bronchospasm, dyspnea, pharyngitis

Miscellaneous: Radiation recall phenomenon

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Leukopenia commonly occurs; granulocytopenia may be severe with higher doses. The leukocyte nadir generally occurs 5 to 10 days after administration; recovery typically occurs 7 to 14 days later. Monitor for infections if WBC <2,000/mm³. Leukopenia may be more pronounced in cachectic patients and patients with skin ulceration and may be less pronounced with lower doses used for maintenance therapy. Leukocytes and platelets may fall considerably with moderate doses when marrow is infiltrated with malignant cells (further use in this situation is not recommended). Thrombocytopenia and anemia may occur rarely.
• Extravasation: [US Boxed Warning]: Vinblastine is a vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation. Extravasation may cause significant irritation. Individuals administering should be experienced in vinblastine administration. If extravasation occurs, discontinue immediately and initiate appropriate extravasation management, including local injection of hyaluronidase and moderate heat application to the affected area. Use a separate vein to complete administration.
• Gastrointestinal toxicity: Stomatitis may occur (rare); may be disabling, but is usually reversible.
• Neurotoxicity: May rarely cause disabling neurotoxicity; usually reversible. Seizures and severe and permanent CNS damage have occurred with higher than recommended doses and/or when administered more frequently than recommended.
• Pulmonary toxicity: Acute shortness of breath and severe bronchospasm have been reported, most often in association with concurrent administration of mitomycin; may occur within minutes to several hours following vinblastine administration or up to 14 days following mitomycin administration; use caution in patients with preexisting pulmonary disease.

Disease-related concerns:

• Hepatic impairment: Use with caution in patients with hepatic impairment; toxicity may be increased; may require dosage modification.
• Ischemic heart disease: Use with caution in patients with ischemic heart disease.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.

Special handling:

• Ocular exposure: Avoid eye contamination (exposure may cause severe irritation).

Other warnings/precautions:

• Experienced physician: [US Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.
• NOT for intrathecal use: [US Boxed Warning]: For IV use only. Administration by other routes may result in death. To prevent administration errors, the Institute for Safe Medication Practices (ISMP) Targeted Medication Safety Best Practices for Hospitals initiative strongly recommends dispensing vinblastine diluted in a minibag (ISMP 2018). Vinblastine should NOT be prepared during the preparation of any medications intended for CNS administration. After preparation, keep vinblastine in a location away from the separate storage location recommended for medications intended for CNS administration. Vinblastine should NOT be delivered to the patient at the same time with any medications intended for CNS administration. Refer to vinblastine manufacturer labeling for information regarding management of inadvertent intrathecal vinblastine exposure.

Monitoring Parameters

CBC with differential and platelet count, serum uric acid, hepatic function tests

Pregnancy

Pregnancy Considerations

Based on placental perfusion studies, vinblastine is expected to cross the placenta (Sudhakaran 2008). Outcome information following maternal use of vinblastine as a single agent or as part of combination therapy during pregnancy is available (Avilés 2018; Eyre 2015).

The European Society for Medical Oncology (ESMO) has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The ESMO guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team). In general, if chemotherapy is indicated, it should be avoided during in the first trimester, there should be a 3-week time period between the last chemotherapy dose and anticipated delivery, and chemotherapy should not be administered beyond week 33 of gestation (Peccatori 2013). An international consensus panel has published guidelines for hematologic malignancies during pregnancy. Vinblastine is a component of the ABVD regimen, which is used for the treatment of Hodgkin lymphoma. If treatment cannot be deferred until after delivery in patients with early stage Hodgkin lymphoma, ABVD may be administered safely and effectively in the latter phase of pregnancy (based on limited data); for patients with advanced-stage disease, ABVD can be administered in the second and third trimesters (Lishner 2016).

Females of reproductive potential should avoid becoming pregnant during vinblastine treatment. Reversible amenorrhea may occur when vinblastine is used in some combination regimens (dose related). Aspermia has been reported in males who have received treatment with vinblastine.

A pregnancy registry is available for all cancers diagnosed during pregnancy at Cooper Health (877-635-4499).

Patient Education

What is this drug used for?

• It is used to treat cancer.

Frequently reported side effects of this drug

• Hair loss
• Jaw pain
• Bone pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infection
• Severe injection site pain, swelling, blisters, or irritation
• Chest pain
• Fast heartbeat
• Passing out
• Abnormal heartbeat
• Burning or numbness feeling
• Severe constipation
• Severe abdominal pain
• Severe loss of strength and energy
• Bruising
• Bleeding
• Shortness of breath
• Seizures
• Severe headache
• Dizziness
• Vision changes
• Depression
• Trouble hearing
• Noise or ringing in the ears
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.