vinblastine

Vinca Alkaloids and Analogs

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 1
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Minimal
Extravasation Risk
Vesicant
Administer drug through a central venous line.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Vinblastine is for intravenous (IV) use only; fatalities have been associated with intrathecal administration of vinca alkaloids.[64308]
The Institute for Safe Medication Practices (ISMP) recommend dispensing vinca alkaloids in a minibag of a compatible solution to prevent accidental intrathecal administration; this best practice is supported by other accrediting and professional organizations.[64256] [64348] [64349] [64350] [64351]
Ensure the IV needle or catheter is properly positioned before administration; monitor the infusion site and immediately discontinue and administer appropriate treatment (e.g., hyaluronidase, application of heat) if extravasation occurs. [64308]
Intermittent IV Infusion (off-label administration)
In a flexible plastic container (i.e., minibag), dilute the calculated dose/volume of vinblastine in a small volume of compatible IV fluid (e.g., 0.9% Sodium Chloride injection or 5% Dextrose injection).[64308]
ISMP recommends a diluent volume of 25 mL for pediatric patients and 50 mL for adults.[64256]
Label the admixture: For Intravenous Use Only.
Administer as a short IV infusion (less than 30 minutes) via an intact, free-flowing IV needle or catheter.[64308]
IV Injection
NOTE: Several accrediting and professional organizations advise against the administration of vinca alkaloids in a syringe due to the risk of accidental intrathecal administration.[64256] [64348] [64349] [64350] [64351]
According to the manufacturer, withdraw the calculated volume of vinblastine into a syringe.
Label the syringe: FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.
Place the syringe in an overwrap with label: DO NOT REMOVE COVERING UNTIL MOMENT OF INJECTION. FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.
To minimize further the possibility of extravascular spillage, it is suggested that the syringe and needle be rinsed with venous blood before withdrawal of the needle.
Administer as an IV bolus over 1 minute or less directly into a vein or into the tubing of a running IV infusion.[64308]

enterocolitis / Delayed / Incidence not known
peptic ulcer / Delayed / Incidence not known
ileus / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known
muscle paralysis / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
stroke / Early / Incidence not known
bronchospasm / Rapid / Incidence not known
SIADH / Delayed / Incidence not known
hearing loss / Delayed / Incidence not known
seizures / Delayed / Incidence not known

leukopenia / Delayed / 10.0
constipation / Delayed / 10.0
anemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
infertility / Delayed / Incidence not known
angina / Early / Incidence not known
hypertension / Early / Incidence not known
dyspnea / Early / Incidence not known
neuritis / Delayed / Incidence not known
depression / Delayed / Incidence not known
nystagmus / Delayed / Incidence not known
bone pain / Delayed / Incidence not known

photosensitivity / Delayed / 0-1.0
alopecia / Delayed / 10.0
infection / Delayed / Incidence not known
anorexia / Delayed / Incidence not known
nausea / Early / Incidence not known
pharyngitis / Delayed / Incidence not known
vomiting / Early / Incidence not known
abdominal pain / Early / Incidence not known
diarrhea / Early / Incidence not known
skin irritation / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
weakness / Early / Incidence not known
dizziness / Early / Incidence not known
headache / Early / Incidence not known
vertigo / Early / Incidence not known
paresthesias / Delayed / Incidence not known
malaise / Early / Incidence not known

Vinblastine is considered a vesicant. Intramuscular administration and subcutaneous administration of vinblastine should be avoided due to severe skin and tissue necrosis that may occur following administration via these routes. Extravasation of vinblastine infusions should be avoided. Patients should be closely monitored for signs and symptoms of extravasation including pain, swelling, and poor blood return. In case of extravasation, local injection of hyaluronidase (see hyaluronidase monograph, Dosage section) and the application of moderate heat to the area of extravasation help disperse the drug and are thought to minimize discomfort and the possibility of cellulitis.

Fatal neurological effects (e.g., destruction of the central nervous system) have occurred following intrathecal administration of vinca alkaloids; therefore, this route must not be used for vinblastine. The Institute for Safe Medication Practices (ISMP) recommend dispensing vinca alkaloids in a minibag of a compatible solution to prevent accidental intrathecal administration; this best practice is supported by other accrediting and professional organizations.[64256] [64348] [64349] [64350] [64351]

Vinblastine is an extremely toxic drug with a low therapeutic index, and therapeutic doses are likely to cause toxicity. Therefore, this drug requires an experienced clinician knowledgeable in administering chemotherapy.

Rx

Vinblastine is a member of the Vinca alkaloid antineoplastic agents; extracted from the periwinkle plant; similar to vincristine in action and structure, but the alkaloids significantly differ in toxicities and spectrum of activity; the dose-limiting toxicity of vinblastine is bone-marrow suppression.

4.5 mg/m2 IV on day 1 of every 21 days in combination with doxorubicin and thiotepa.

0.1 mg/kg/dose IV weekly with corticosteroids until radiographic resolution of lesions. Alternatively, a regimen of 0.4 mg/kg/dose IV once every 7—10 days has been used.

6 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11, in combination with mechlorethamine (6 mg/m2 IV on weeks 1, 5, and 9), doxorubicin (25 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11), vincristine (1.4 mg/m2 (max: 2 mg) IV on weeks 2, 4, 6, 8, 10, and 12), bleomycin (5 units/m2 IV on weeks 2, 4, 6, 8, 10, and 12), etoposide (60 mg/m2/day IV on 2 consecutive days in weeks 3, 7, and 11), and prednisone (40 mg/m2 PO every other day for 10 weeks then tapered by 10 mg PO every other day between weeks 10 and 12). Total duration of Stanford V regimen is 12 weeks (three 4-week cycles). Doses of mechlorethamine, doxorubicin, vinblastine, and etoposide have been reduced to 65% if ANC less than 1,000 cells/mm3 (treatment delayed if ANC less than 500 cells/mm3). Prophylactic sulfamethoxazole-trimethoprim, acyclovir, and a H2-blocker were given throughout the treatment period. G-CSF has also been used to maintain dose intensity as needed after the first dose reduction. Alternative prophylactic medications have also been used.

6 mg/m2 IV on days 1 and 15 repeated every 28 days in combination with vinblastine, bleomycin, and dacarbazine (ABVD regimen).

6 mg/m2 IV in combination with brentuximab vedotin 1.2 mg/kg IV (not to exceed 120 mg/dose), doxorubicin 25 mg/m2 IV, and dacarbazine 375 mg/m2 IV each given on days 1 and 15 repeated every 28 days for up to 6 cycles was evaluated in a randomized, phase III trial. Patients should receive primary prophylaxis with a granulocyte colony-stimulating factor due to the high incidence of febrile neutropenia.

4 mg/m2/day IV on days 1 and 2 of a 28 day cycle in combination with cisplatin and bleomycin.

6 mg/m2 IV on days 1 and 2 every 21—28 days along with cisplatin and bleomycin (PVB regimen) or 0.11 mg/kg IV on days 1 and 2 every 21 days with cisplatin and ifosfamide. Alternatively, in children, a dose of 0.2 mg/kg IV on days 1 and 2 every 3 weeks for 4 cycles has been used.

10 mg IV once every other week in combination with bleomycin and prednisone.

3 mg/m2 IV weekly for 3 weeks, then 6 mg/m2 IV every 3 weeks.

Inject each lesion with vinblastine solution 0.3 mg/ml until blanching occurs. Most lesions require 2 ml total. Repeat every 3 weeks as needed.

4 mg/m2 IV bolus and methotrexate 30 mg/m2 IV bolus on days 1 and 8 plus cisplatin 100 mg/m2 IV infusion on day 2 repeated every 21 days (MCV regimen) for 3 cycles prior to local radical treatment (LRT) with cystectomy, full-dose external-beam radiotherapy, or preoperative radiotherapy and cystectomy resulted in a nonsignificantly higher 3-year overall survival (OS) rate compared with LRT alone (55.5% vs. 50% (hazard ratio (HR) = 0.85; 95% CI, 0.71 to 1.02; p = 0.075) in a randomized phase III trial in 976 patients with muscle-invasive bladder cancer; however, the 10-year OS rate was significantly improved in the MCV arm in a long-term analysis (36% vs. 30%; HR = 0.84; 0.72 to 0.99; p = 0.037). Folinic acid 15 mg orally or IV every 6 hours for 4 doses was given 24 hours after each methotrexate dose. Five treatment-related deaths occurred in the MCV arm. In another randomized, phase III trial in 317 patients, vinblastine 3 mg/m2 IV on days 2, 15, and 22 in combination with methotrexate 30 mg/m2 on days 1, 15, and 22, doxorubicin 30 mg/m2 on day 2, and cisplatin 70 mg/m2 on day 2 repeated every 28 days (MVAC regimen) for 3 cycles followed by radical cystectomy led to a nonsignificantly improved median OS time (primary endpoint) compared with radical cystectomy alone; although significantly more patients were pathologically free from disease at cystectomy in the MVAC arm (48% vs. 15%; p < 0.001). No treatment-related deaths were reported in this study.

3 mg/m2 IV on days 2, 15, and 22 in combination with methotrexate (30 mg/m2 IV on days 1, 15, and 22), doxorubicin (30 mg/m2 IV on day 2), and cisplatin (70 mg/m2 IV on day 2) repeated every 28 days (MVAC regimen) for up to 6 cycles has been evaluated in patients with advanced or metastatic transitional cell carcinoma of the bladder in a long-term analysis of a multicenter, randomized, phase III trial. Vinblastine 3 mg/m2 IV on days 1, 15, and 22 plus methotrexate (30 mg/m2 IV on days 1, 15, and 22), doxorubicin (30 mg/m2 IV on day 1), and cisplatin (70 mg/m2 IV on day 1) repeated every 4 weeks was studied in another randomized, phase III trial. All patients in this study received granulocyte colony-stimulating factor (G-CSF) following chemotherapy.

Various regimens have been studied. In a randomized, phase III trial in 395 patients, vinblastine 1.2 mg/m2/day IV on days 1 to 4 in combination with dacarbazine 800 mg/m2 IV over 1 hour on day 1 and cisplatin 20 mg/m2/day IV over 30 minutes on days 1 to 4 repeated every 21 days (CVD regimen) for up to 4 cycles resulted in a median overall survival (OS) time of 8.7 months compared with 9 months in patients who received CVD plus interleukin-2 and interferon alfa-2b (biochemotherapy (BCT) arm) (hazard ratio (HR) = 0.95; 95% CI, 0.78 to 1.17; p = 0.639). All patients in the BCT arm received granulocyte colony-stimulating factor. In another randomized, phase III trial in 190 patients, vinblastine 2 mg/m2/day IV on days 1 to 4 and days 22 to 25 in combination with dacarbazine 800 mg/m2 IV on day 1 and 22 and cisplatin 20 mg/m2/day IV on days 1 to 4 and days 22 to 25) followed by interleukin-2 and interferon alfa-2b resulted in a significantly higher overall response rate (primary endpoint) (48% vs 25%; p = 0.001) and median OS time (11 vs 9.2 months; p = 0.03) compared with 2 cycles of CVD alone; however, the addition of BCT was not associated with significantly improved survival in an analysis that adjusted for baseline prognostic factors (adjusted HR = 1.3; 95% CI, 1 to 1.8; p = 0.07). In both studies, the incidence of grade 3 or higher adverse effects was higher with BCT compared with CVD alone.

5 mg/m2 IV weekly on days 1, 8, 15, 22, and 29 plus cisplatin 100 mg/m2 IV on days 1 and 29 with sequential or concurrent radiotherapy (RT) has been studied in patients with inoperable, stage II or III non-small cell lung cancer (NSCLC) in randomized clinical studies. Median overall survival (OS) times were significantly improved with vinblastine plus cisplatin followed by standard RT (total dose of 60 Gy over 6 weeks) compared with standard RT or hyperfractionated twice daily RT alone in a randomized, phase III trial in 458 patients (13.2 months vs 11.4 and 12 months, respectively; p = 0.04). Additionally, the median OS time was significantly improved with vinblastine plus cisplatin followed by standard RT compared with standard RT alone (13.7 vs 9.6 months; p = 0.012) in 155 patients with inoperable, stage III NSCLC in a long-term update of a randomized controlled trial which was stopped early after an interim analysis. The median OS time was significantly improved when vinblastine plus cisplatin was given concurrently with once daily RT (17 months; p = 0.046) compared with vinblastine plus cisplatin followed by standard RT (sequential RT arm) (14.6 months) in a randomized, phase III trial in 595 patients presented in abstract form. There was no difference in the median OS time with induction chemotherapy with vinblastine plus cisplatin followed by cisplatin (75 mg/m2 IV on days 50, 71, and 92) and concurrent RT compared with cisplatin (50 mg/m2 IV on days 1 and 8) plus oral etoposide (50 mg twice daily) with concurrent twice daily RT (16.4 vs 15.5 months) in a long-term follow-up analysis of a randomized, phase II study in 168 patients.

Multiple dosage regimens have been studied. In one study, vinblastine 4 mg/m2/dose IV was given weekly during days 1 through 29, then every 2 weeks after day 43 with cisplatin. Vinblastine was given until the last cisplatin dose. In this study of 1867 patients, a 4.1% absolute difference in 5-year overall survival (OS) was reported in patients who received cisplatin-based adjuvant chemotherapy (CT) following surgery +/- radiotherapy (RT) compared with surgery +/- RT alone (HR = 0.86; 95% CI, 0.76 to 0.98; p < 0.03). In subgroup analyses in patients who received cisplatin in combination with a vinca alkaloid, including vinblastine, OS was not significantly different with adjuvant CT compared with surgery +/- RT alone. In a long-term analysis of this study (median follow-up of 7.5 years), OS was no longer significant (HR = 0.91; 95% CI, 0.81 to 1.02). Additionally, OS was found to be significantly worse after 5 years in patients who received adjuvant CT (HR: 1.45; 95% CI, 1.02 to 2.07). In another trial that was stopped after 381 patients were randomized (target accrual, 500 patients), vinblastine 6 mg/m2 IV on day 1 repeated every 3 weeks was given with mitomycin and cisplatin (MVP regimen). The median OS (33.9 vs 32.6 months; HR = 1.02; 95% CI, 0.77 to 1.35) and median progression-free survival (27 vs 24.7 months; HR = 0.97; 95% CI, 0.74 to 1.26) were not significantly improved with cisplatin-based adjuvant therapy following surgery +/- RT compared with surgery +/- RT alone.

6 mg/m2 IV on day 1 with cisplatin 50 mg/m2 IV and mitomycin 6 or 8 mg/m2 IV repeated every 3 weeks (MVP regimen) for 4 cycles has been studied in patients with inoperable stage III or IV non-small cell lung cancer (NSCLC) in randomized clinical studies. There was no significant difference in the median overall survival (OS) time (8.7 vs 9.5 months), 1-year OS rate (35% vs 39%), or 2-year OS rate (13% vs 13%) in patients who received MVP or mitomycin, ifosfamide, and cisplatin (MIC regimen) compared with docetaxel plus carboplatin (DC regimen) in a multicenter, randomized, phase III trial in 433 patients. Serious toxicity, including grade 3 and 4 neutropenia and leucopenia, was reported significantly less often in the MVP/MIC arm compared with the DC arm (22% vs 41%; p < 0.005); additionally, patients in the MVP/MIC arm had significantly less overnight hospital stays due to toxicity and antibiotic use. In another randomized, phase III trial in 372 patients, there was no significant difference in the median OS time (248 vs 236 days), 1-year OS rate (32.5% vs 33.2%), or 2-year OS rate (11.8% vs 6.9%) in patients who received MVP or MIC compared with gemcitabine plus carboplatin (GC regimen). Significantly less grade 3 and 4 neutropenia and thrombocytopenia and antibiotic use were reported with MVP/MIC compared with GC; however, emergent overnight hospital stays occurred significantly more often in the MVP/MIC arm.

The use of vinblastine in combination with estramustine has not been established in men with hormone-refractory prostate cancer (HRPC). First-line chemotherapy with vinblastine plus estramustine led to a median overall survival (OS) time (primary endpoint) of 11.9 months compared with 9.2 months in patients who received vinblastine alone in a randomized, phase III trial in men with metastatic HRPC (p = 0.08); however, the median time to progression (3.7 vs 2.2 months; p < 0.0004) and prostate-specific antigen (PSA) response (defined as a PSA level decline of 50% or greater from baseline) rate (25.3% vs 3.2%; p < 0.001) were significantly improved with combination therapy. Grade 2 or higher nausea and leg edema were reported significantly more often in the vinblastine plus estramustine arm compared with the vinblastine alone arm; additionally, 3 patients experienced lower extremity deep venous thrombosis and 3 patients had grade 3 or 4 congestive heart failure with combination therapy. In a randomized, phase II study in 92 men with metastatic HRPC, first-line chemotherapy with vinblastine plus estramustine and estramustine alone led to low PSA response rates (24.6% and 28.9%, respectively) and approximately 30% of patients in this study discontinued therapy due to toxicity; additionally 2 deaths (due to myocardial infarction and cerebrovascular accident) possibly related to treatment occurred in the combination arm. In another randomized, phase II study in 71 men with metastatic HRPC, treatment with ketoconazole and doxorubicin alternating with vinblastine and estramustine (KA/VE regimen) resulted in a nonsignificantly higher PSA response rate (56% vs 41%) and median OS time (23.4 vs 16.9 months) compared with paclitaxel, estramustine, and etoposide (TEE regimen); however, 24% of patients in this study did not complete 6 weeks of treatment and there were 5 treatment-related deaths (KA/VE arm, n=2; TEE arm, n=3).

6 mg/m2/dose IV in combination with methotrexate 30 mg/m2/dose IV every 7 to 10 days for 1 year resulted in a partial response (PR) rate of 40% and a minor response or stable disease in 60% in a phase II study in 30 patients (age range, 4 to 68 years) with recurrent or primary inoperable aggressive fibromatosis. At a median follow-up of 75 months (range, 14 to 125 months), 29 patients were alive and the overall actuarial progression-free interval at 5 and 10 years was 67%.

6 mg/m2/dose IV in combination with methotrexate 30 mg/m2/dose IV every 7 to 10 days for 1 year resulted in a partial response (PR) rate of 40% and a minor response or stable disease in 60% in a phase II study in 30 patients (age range, 4 to 68 years). At a median follow-up of 75 months (range, 14 to 125 months), 29 patients were alive and the overall actuarial progression-free interval at 5 and 10 years was 67%. In another phase II trial of 26 children, vinblastine 5 mg/m2/dose and methotrexate 30 mg/m2/dose IV weekly for 26 weeks then every other week for an additional 26 weeks led to an ORR of 19.2% and a 3-year progression-free survival rate of 32.5%. Serious adverse effects in this study included grade 4 neutropenia (n=5), mood alteration (n=1), and uncomplicated generalized seizure (n=1).

†Indicates off-label use

Bilirubin concentrations 1.5 to 3 mg/dL: Consider reducing the dose by 50%.
Bilirubin concentration greater than 3 mg/dL: Consider avoiding administration.
 
Aminotransferase concentrations greater than 3 times the ULN: Consider avoiding administration.
 
AST concentrations 60 to 180 International Units/L: Consider reducing the dose by 50%.
AST concentrations greater than 180 International Units/L: Consider avoiding administration.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Adagrasib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with adagrasib is necessary. Vinblastine is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor.
Amiodarone: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with amiodarone is necessary. Vinblastine is a CYP3A4 substrate and amiodarone is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with clarithromycin is necessary. Vinblastine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Aprepitant, Fosaprepitant: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with a multi-day regimen of aprepitant is necessary. Vinblastine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Atazanavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with atazanavir is necessary. Vinblastine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor.
Atazanavir; Cobicistat: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with atazanavir is necessary. Vinblastine is a CYP3A4 substrate and atazanavir is a strong CYP3A4 inhibitor. (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinblastine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Berotralstat: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with berotralstat is necessary. Vinblastine is a CYP3A4 substrate and berotralstat is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Ceritinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ceritinib is necessary. Vinblastine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chloramphenicol: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with chloramphenicol is necessary. Vinblastine is a CYP3A4 substrate and chloramphenicol is a strong CYP3A4 inhibitor.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciprofloxacin: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ciprofloxacin is necessary. Vinblastine is a CYP3A4 substrate and ciprofloxacin is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Clarithromycin: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with clarithromycin is necessary. Vinblastine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Cobicistat: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinblastine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Conivaptan: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with conivaptan is necessary. Vinblastine is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with crizotinib is necessary. Vinblastine is a CYP3A4 substrate and crizotinib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Cyclosporine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cyclosporine is necessary. Vinblastine is a CYP3A4 substrate and cyclosporine is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Danazol: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with danazol is necessary. Vinblastine is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Darunavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with darunavir is necessary. Vinblastine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinblastine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with darunavir is necessary. Vinblastine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinblastine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with darunavir is necessary. Vinblastine is a CYP3A4 substrate and darunavir is a strong CYP3A4 inhibitor.
Delavirdine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with delavirdine is necessary. Vinblastine is a CYP3A4 substrate and delavirdine is a strong CYP3A4 inhibitor.
Diltiazem: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with diltiazem is necessary. Vinblastine is a CYP3A4 substrate and diltiazem is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Dronedarone: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with dronedarone is necessary. Vinblastine is a CYP3A4 substrate and dronedarone is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Duvelisib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with duvelisib is necessary. Vinblastine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinblastine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with cobicistat is necessary. Vinblastine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Erythromycin: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with erythromycin is necessary. Vinblastine is a CYP3A4 substrate and erythromycin is a CYP3A4 inhibitor. Enhanced toxicity has been reported in patients receiving concomitant erythromycin.
Febuxostat: (Major) Coadministration of febuxostat and cytotoxic antineoplastic agents has not been studied. After antineoplastic therapy, tumor cell breakdown may greatly increase the rate of purine metabolism to uric acid. Febuxostat inhibits uric acid formation, but does not affect xanthine and hypoxanthine formation. An increased renal load of these two uric acid precursors can occur and result in xanthine nephropathy and calculi.
Fedratinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with fedratinib is necessary. Vinblastine is a CYP3A4 substrate and fedratinib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Filgrastim, G-CSF: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Fluconazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with fluconazole is necessary. Vinblastine is a CYP3A4 substrate and fluconazole is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Fluoxetine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with fluoxetine is necessary. Vinblastine is a CYP3A4 substrate and norfluoxetine, the active metabolite of fluoxetine, is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Fluvoxamine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with fluvoxamine is necessary. Vinblastine is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Fosamprenavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with fosamprenavir is necessary. Vinblastine is a CYP3A substrate and fosamprenavir is a moderate CYP3A inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A inhibitor.
Gadobenate Dimeglumine: (Moderate) Gadobenate dimeglumine is a substrate for the canalicular multi-specific organic anion transporter (MOAT). Use with other MOAT substrates, such as vinca alkaloids, may result in prolonged systemic exposure of the coadministered drug. Caution is advised if these drugs are used together.
Ganciclovir: (Moderate) Use ganciclovir and vinca alkaloids together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of pibrentasvir and vinblastine as coadministration may increase serum concentrations of vinblastine and increase the risk of adverse effects. Vinblastine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
Grapefruit juice: (Major) Advise patients to avoid grapefruit or grapefruit juice during vinblastine treatment due to the increased risk of avapritinib-related adverse reactions. Vinblastine is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
Idelalisib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with idelalisib is necessary. Vinblastine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Imatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with imatinib is necessary. Vinblastine is a CYP3A4 substrate and imatinib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Indinavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with indinavir is necessary. Vinblastine is a CYP3A4 substrate and indinavir is a strong CYP3A4 inhibitor.
Isavuconazonium: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with isavuconazonium is necessary. Vinblastine is a CYP3A4 substrate and isavuconazonium is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Itraconazole: (Major) Avoid the use of vinblastine during and for 2 weeks after discontinuation of itraconazole due to the risk of an earlier onset and/or increased severity of vinblastine-related adverse reactions including severe myelosuppression. Vinblastine is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Concomitant administration of another vinca alkaloid with itraconazole has resulted in an increased incidence of neurotoxicity.
Ketoconazole: (Moderate) Avoid coadministration of vinblastine with ketoconazole due to increased plasma concentrations of vinblastine, resulting in an earlier onset and/or increased severity of neuromuscular, myelosuppressive, or other side effects. Vinblastine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Enhanced toxicity has been reported in patients receiving a concomitant moderate CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with clarithromycin is necessary. Vinblastine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Lefamulin: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with oral lefamulin is necessary. Vinblastine is a CYP3A4 substrate and oral lefamulin is a moderate CYP3A4 inhibitor; an interaction is not expected with intravenous lefamulin. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Lenacapavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with lenacapavir is necessary. Vinblastine is a CYP3A substrate and lenacapavir is a moderate CYP3A inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A inhibitor.
Letermovir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with letermovir is necessary; the magnitude of this interaction may be amplified in patients who are also receiving treatment with cyclosporine. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Levoketoconazole: (Moderate) Avoid coadministration of vinblastine with ketoconazole due to increased plasma concentrations of vinblastine, resulting in an earlier onset and/or increased severity of neuromuscular, myelosuppressive, or other side effects. Vinblastine is a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor. Enhanced toxicity has been reported in patients receiving a concomitant moderate CYP3A4 inhibitor.
Lonafarnib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with lonafarnib is necessary. Vinblastine is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Major) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ritonavir is necessary. Vinblastine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Mifepristone: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with mifepristone is necessary. Vinblastine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Mitomycin: (Moderate) Monitor for pulmonary toxicity if coadministration of mitomycin and vinca alkaloids is necessary. Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids in patients who had previously or simultaneously received mitomycin. The onset of acute respiratory distress occurred within minutes to hours after vinca alkaloid administration. Treatment with bronchodilators, steroids, and/or oxygen may provide symptomatic relief.
Nefazodone: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with nefazodone is necessary. Vinblastine is a CYP3A4 substrate and nefazodone is a strong CYP3A4 inhibitor.
Nelfinavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with nelfinavir is necessary. Vinblastine is a CYP3A4 substrate and nelfinavir is a strong CYP3A4 inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with netupitant is necessary. Vinblastine is a CYP3A4 substrate and netupitant is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Nilotinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with nilotinib is necessary. Vinblastine is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Major) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ritonavir is necessary. Vinblastine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Olanzapine; Fluoxetine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with fluoxetine is necessary. Vinblastine is a CYP3A4 substrate and norfluoxetine, the active metabolite of fluoxetine, is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Pegfilgrastim: (Major) Pegfilgrastim induces the proliferation of neutrophil-progenitor cells, and because antineoplastic agents exert toxic effects against rapidly growing cells, pegfilgrastim should not be given 14 days before or for 24 hours after cytotoxic chemotherapy.
Posaconazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with posaconazole is necessary. Vinblastine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor.
Ribociclib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ribociclib is necessary. Vinblastine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ribociclib is necessary. Vinblastine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ritlecitinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ritlecitinib is necessary. Vinblastine is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A inhibitor.
Ritonavir: (Major) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with ritonavir is necessary. Vinblastine is a CYP3A4 substrate and ritonavir is a strong CYP3A4 inhibitor.
Saquinavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with saquinavir is necessary. Vinblastine is a CYP3A4 substrate and saquinavir is a strong CYP3A4 inhibitor.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Tbo-Filgrastim: (Major) Filgrastim induces the proliferation of neutrophil-progenitor cells, and, because antineoplastic agents exert toxic effects against rapidly growing cells, filgrastim is contraindicated for use during the 24 hours before or after cytotoxic chemotherapy.
Tipranavir: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with tipranavir is necessary. Vinblastine is a CYP3A4 substrate and tipranavir is a strong CYP3A4 inhibitor.
Trandolapril; Verapamil: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with verapamil is necessary. Vinblastine is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Tucatinib: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with tucatinib is necessary. Vinblastine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valganciclovir: (Moderate) Use valganciclovir and vinca alkaloids together only if the potential benefits outweigh the risks; bone marrow suppression, spermatogenesis inhibition, skin toxicity, and gastrointestinal toxicity may be additive as both drugs inhibit rapidly dividing cells.
Verapamil: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with verapamil is necessary. Vinblastine is a CYP3A4 substrate and verapamil is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with clarithromycin is necessary. Vinblastine is a CYP3A4 substrate and clarithromycin is a strong CYP3A4 inhibitor.
Voriconazole: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with voriconazole is necessary. Vinblastine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor.
Voxelotor: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with voxelotor is necessary. Vinblastine is a CYP3A substrate and voxelotor is a moderate CYP3A inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A inhibitor.

Vinblastine/Vinblastine Sulfate Intravenous Inj Sol: 1mg, 1mL

18.5 mg/m2 IV administered in weekly intervals.

18.5 mg/m2 IV administered in weekly intervals.

12.5 mg/m2/day IV administered weekly.

12.5 mg/m2/day IV administered weekly.

Mechanism of Action: Vinblastine, as with all vinca alkaloids, primarily exerts its cytotoxic effects on the cell by interfering with microtubules, which compose mitotic spindle fibers leading to cell cycle arrest in the metaphase. Vinca alkaloids bind to a common pair of sites on each subunit of tubulin (alpha, beta) during the M-phase of the cell cycle. The binding sites for vinca alkaloids are different from the binding sites of the taxanes and colchicine. There are at least 2 types of tubulin binding sites for vinca alkaloids. The high-affinity sites, which are found in small numbers, are responsible for the disruption of microtubule assembly. Vinca alkaloid binding to the low-affinity binding sites results in the splitting of the microtubules into spiral aggregates or spiral protofilaments, which leads to the disintegration of the microtubule. Binding to the low-affinity sites occurs at high drug concentrations. The concentration of vinca alkaloids that induces metaphase arrest in 50% of cells results in inhibition of cell proliferation. At their lowest effective concentration, vinca alkaloids cause metaphase arrest by inhibition of mitotic spindle function. At higher concentrations, the organization of the microtubules and chromosomes deteriorates. After exposure to vinca alkaloids, some cells undergo a cell cycle block, or stathmokinesis, which is only temporary. If the drug concentration falls beneath a certain level, these cells may avoid the cytotoxic effects and divide normally. Vinca alkaloids also affect microtubules involved in chemotaxis, migration, intracellular transport, movement of organelles such as mitochondria, secretory processes, membrane trafficking, transmission of receptor signals and cell structural integrity. Vinca alkaloids have other effects that may or may not be related to their effects on tubulin. These activities include competition for transport of amino acids into cells, inhibition of purine synthesis, inhibition of RNA, DNA and protein synthesis, disruption of lipid metabolism, inhibition of glycolysis, changes in antidiuretic hormone release and disruption of cell membrane integrity and membrane function. Differences in the cytotoxic effects of different vinca alkaloids may be due to differences in cellular retention, intracellular concentrations of guanosine triphosphate (GTP), and pharmacokinetics.Resistance to vinca alkaloids is thought to occur through a couple of mechanisms. Multidrug resistance (MDR) results in decreased intracellular drug accumulation and retention. MDR is due to overexpression of the mdr-1 gene, which codes for a membrane P-glycoprotein (P-gp) that acts as a drug efflux pump. The degree of resistance is proportional to the amount of P-gp. P-gp is expressed in many malignancies including renal and large bowel cancers, and in post-treatment lymphomas, leukemias and multiple myeloma. The second mechanism of resistance to vinca alkaloids is due to alterations in the alpha- and beta-tubulin subunits. These changes result in either decreased drug binding or increased resistance to microtubule disassembly. This type of resistance to vinca alkaloids may confer sensitivity to taxanes, which inhibit microtubule disassembly.

Vinblastine is administered parenterally and is not available as an oral formulation. It is widely distributed throughout many tissues in the body and binds readily to leukocytes and platelets. Approximately 50% of the dose is bound to platelets, red blood cells, and white blood cells within 20 minutes of administration. High platelet and leukocyte binding is due to the increased concentration of tubulin within these cells. Vinblastine is more highly bound to tissues and has a larger volume of distribution than vincristine. Vinblastine does not cross the blood-brain barrier. It is not cleared readily from the CSF after accidental intrathecal administration, and this route of administration universally leads to death. Elimination of vinblastine is best described using a three-compartment model. The alpha half-life is <5 minutes, beta half-life is 50—155 minutes and the final elimination half-life of vinblastine is 23—85 hours. Vinblastine undergoes hepatic metabolism via the CYP 3A4 isoenzyme and then is eliminated through the bile and feces. At least one active metabolite has been described, desacetyl-vinblastine (VDS), which may be as active as the parent compound.

Vinblastine is classified as FDA pregnancy risk category D. There are no data concerning the effects in pregnant women. In animal studies, vinblastine is teratogenic. Females of childbearing potential should be instructed to avoid becoming pregnant during therapy. If a women becomes pregnant while receiving this drug, she should be counseled of the potential harm to the fetus and the possibility of loss of pregnancy.

It is unknown whether vinblastine is excreted in breast milk. Breast-feeding should be discontinued during vinblastine therapy because of the possibility of severe adverse reactions to the infant.