Oncovin

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
Pediatrics: Doses 1.5 mg/m2/dose or lower: Minimal
Adults: Low
Administer routine antiemetic prophylaxis prior to treatment.
Extravasation Risk
Vesicant
Administer drug through a central venous line.

Injectable Administration

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

Intravenous Administration

Vincristine is for intravenous (IV) use only; fatalities have been associated with intrathecal administration of vinca alkaloids.
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] [64350] [64351]
The administration of vincristine in a syringe is not supported in the product label and should be avoided.
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.
Intermittent IV Infusion
In a flexible plastic container (i.e., minibag), dilute the calculated dose/volume of vincristine in a compatible IV fluid (e.g., 0.9% Sodium Chloride injection or 5% Dextrose injection); ISMP recommends a diluent volume of 25 mL for pediatric patients and 50 mL for adults. [64256]
Label the admixture: FOR INTRAVENOUS USE ONLY - FATAL IF GIVEN BY OTHER ROUTES.
Storage of admixture (for final admixture concentration between 0.0015 to 0.08 mg/mL and diluted in 0.9% Sodium Chloride injection): Store for up to 24 hours when diluted in 0.9% Sodium Chloride injection and protected from light or for 8 hours under normal light at 25 degrees C.
Administer via an intact, free-flowing IV needle or catheter.

Severe

seizures / Delayed / Incidence not known
coma / Early / Incidence not known
hearing loss / Delayed / Incidence not known
ileus / Delayed / Incidence not known
bowel necrosis / Delayed / Incidence not known
GI perforation / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
SIADH / Delayed / Incidence not known
muscle paralysis / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
acute respiratory distress syndrome (ARDS) / Early / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
sinusoidal obstruction syndrome (SOS) / Delayed / Incidence not known
veno-occlusive disease (VOD) / Delayed / Incidence not known
optic atrophy / Delayed / Incidence not known

Moderate

nystagmus / Delayed / Incidence not known
peripheral neuropathy / Delayed / Incidence not known
neuropathic pain / Delayed / Incidence not known
ataxia / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
constipation / Delayed / Incidence not known
hypertension / Early / Incidence not known
hypotension / Rapid / Incidence not known
urinary retention / Early / Incidence not known
dysuria / Early / Incidence not known
hyponatremia / Delayed / Incidence not known
nephrolithiasis / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
anemia / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
dyspnea / Early / Incidence not known
edema / Delayed / Incidence not known
dehydration / Delayed / Incidence not known

Mild

dizziness / Early / Incidence not known
headache / Early / Incidence not known
hyporeflexia / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
vertigo / Early / Incidence not known
anorexia / Delayed / Incidence not known
diarrhea / Early / Incidence not known
nausea / Early / Incidence not known
abdominal pain / Early / Incidence not known
weight loss / Delayed / Incidence not known
vomiting / Early / Incidence not known
alopecia / Delayed / Incidence not known
rash / Early / Incidence not known
polyuria / Early / Incidence not known
skin irritation / Early / Incidence not known
injection site reaction / Rapid / Incidence not known
myalgia / Early / Incidence not known
back pain / Delayed / Incidence not known
fever / Early / Incidence not known
azoospermia / Delayed / Incidence not known
amenorrhea / Delayed / Incidence not known

Extravasation

Vincristine is considered a vesicant; avoid extravasation. Ensure proper needle or catheter placement prior to IV infusion. If extravasation occurs, discontinue the infusion and administer the remainder of the dose in another vein. Additionally, a local injection of hyaluronidase and the application of moderate heat to the area may help to disperse the drug and minimize discomfort and the risk of cellulitis.

Intrathecal administration, requires an experienced clinician

Fatal neurological effects (e.g., destruction of the central nervous system) have occurred following intrathecal administration of vinca alkaloids, including vincristine; this route must not be used. 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] Vincristine administration requires an experienced clinician who has experience with chemotherapy drugs.

Oncovin, Vincasar PFS

Rx

A vinca alkaloid agent
Used for acute leukemias in pediatric and adult patients; used as part of combination therapy for Hodgkin lymphoma, non-Hodgkin lymphoma, rhabdomyosarcoma, neuroblastoma, and Wilms tumor
For IV use only; may be fatal if given as an intrathecal injection

For the treatment of acute lymphocytic leukemia (ALL). Intravenous dosage Adults

1.4 mg/m2 IV once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents

1.5 to 2 mg/m2 IV once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg or 2.5 mg in some pediatric studies.

Infants

0.05 mg/kg IV once weekly in infants weighing 10 kg or less OR 1.5 to 2 mg/m2 IV once weekly in infants weighing more than 10 kg. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of neuroblastoma, in combination with other oncolytic agents. Intravenous dosage Adults

1.4 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents

1.5 to 2 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg or 2.5 mg in some pediatric studies.

Infants

0.05 mg/kg IV in infants weighing 10 kg or less OR 1.5 to 2 mg/m2 IV in infants weighing more than 10 kg in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of Hodgkin lymphoma. For the treatment of Hodgkin lymphoma as part of the Stanford V regimen. Intravenous dosage Adolescents 15 years and older and adults

1.4 mg/m2 (maximum dose of 2 mg) IV on weeks 2, 4, 6, 8, 10, and 12 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), vinblastine (6 mg/m2 IV on weeks 1, 3, 5, 7, 9, and 11), bleomycin (5 units/m2 IV on weeks 2, 4, 6, 8, 10, and 12), etoposide (60 mg/m2 per 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 an 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.

For the treatment of Hodgkin lymphoma as part of the BEACOPP regimen. Intravenous dosage Adolescents 15 years and older and adults

1.4 mg/m2 (maximum dose of 2 mg) IV on day 8 in combination with bleomycin (10 units/m2 IV on day 8), etoposide (100 mg/m2 IV daily on days 1, 2, and 3), doxorubicin (25 mg/m2 IV on day 1), cyclophosphamide (650 mg/m2 IV on day 1), procarbazine (100 mg/m2 PO daily on days 1 to 7), and prednisone (40 mg/m2 PO daily on days 1 to 14). Cycles are repeated every 21 days for up to 8 cycles. Filgrastim was administered beginning on day 8 of each cycle and continued until the leukocyte count returned to normal in some clinical trials. The escalated dose BEACOPP regimen includes vincristine 1.4 mg/m2 (maximum dose of 2 mg) IV on day 8 in combination with bleomycin (10 units/m2 IV on day 8), etoposide (200 mg/m2 IV daily on days 1, 2 and 3), doxorubicin (35 mg/m2 IV on day 1), cyclophosphamide (1,200 mg/m2 IV on day 1), procarbazine (100 mg/m2 PO daily on days 1 to 7), and prednisone (40 mg/m2 PO daily on days 1 to 14). Cycles are repeated every 21 days for up to 8 cycles. Filgrastim was administered beginning on day 8 of each cycle and continued until the leukocyte count returned to normal in some clinical trials. The standard dose BEACOPP and escalated dose BEACOPP regimens have shown benefit for the treatment of advanced Hodgkin lymphoma in clinical trials. Escalated dose BEACOPP has shown a significantly better freedom from treatment failure at 10 years (82% vs. 70%, p less than 0.0001) and overall survival at 10 years (86% vs. 80%, p = 0.0053) compared to standard dose BEACOPP. A regimen of four cycles of escalated dose BEACOPP followed by 4 cycles of standard dose BEACOPP has also been used in patients who achieve a complete response after the initial 4 cycles of escalated dose BEACOPP.

For the treatment of Hodgkin lymphoma, in combination with other oncolytic agents. Intravenous dosage Adults

1.4 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents

1.5 to 2 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg or 2.5 mg in some pediatric studies.

Infants

0.05 mg/kg IV in infants weighing 10 kg or less OR 1.5 to 2 mg/m2 IV in infants weighing more than 10 kg in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of previously untreated, high-risk classical Hodgkin lymphoma, in combination with brentuximab vedotin, doxorubicin, etoposide, prednisone, and cyclophosphamide.
NOTE: Brentuximab vedotin is FDA approved for this indication.
Intravenous dosage Children 2 years and older and Adolescents

1.4 mg/m2 IV on day 8 in combination with brentuximab vedotin 1.8 mg/kg (not to exceed 180 mg/dose) IV on day 1; doxorubicin 25 mg/m2 IV on days 1 and 2; etoposide 125 mg/m2 IV on days 1, 2, and 3; prednisone 20 mg/m2 PO twice daily on days 1 to 7; and cyclophosphamide 600 mg/m2 IV on days 1 and 2 repeated every 3 weeks for up to 5 cycles. Administer primary prophylaxis with a granulocyte colony-stimulating factor starting in cycle 1 due to the high incidence of febrile neutropenia. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. At a median follow-up time of 42.1 (range, 0.1 to 80.9) months, the 3-year event-free survival rate was significantly improved in patients (median age, 15.6 years; range, 3.4 to 21.99 years) with newly diagnosed, stage IIB with bulk tumor or stage IIIB, IVA, or IVB classic Hodgkin lymphoma who received brentuximab vedotin plus AVEPC compared with doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) (92.1% vs. 82.5%; hazard ratio = 0.41; 95% CI, 0.25 to 0.67) in a multicenter, randomized, phase 3 trial (n = 587). The 3-year overall survival rates were 99.3% and 98.5% in the brentuximab vedotin plus AVEPC and ABVE-PC arms, respectively.

For the treatment of non-Hodgkin's lymphoma (NHL), in combination with other oncolytic agents. Intravenous dosage Adults

1.4 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Vincristine 1.4 mg/m2 (maximum dose of 2 mg) IV on day 1 repeated every 21 days has been administered as part of the CHOP, rituximab-CHOP, CVP, and rituximab-CVP regimens.

Children and Adolescents

1.5 to 2 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg or 2.5 mg in some pediatric studies.

Infants

0.05 mg/kg IV in infants weighing 10 kg or less OR 1.5 to 2 mg/m2 IV in infants weighing more than 10 kg in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of rhabdomyosarcoma. For the treatment of metastatic rhabdomyosarcoma in combination with cyclophosphamide and topotecan alternating with VAC†. Intravenous dosage Adults, Adolescents, Children, and Infants

Dosage not established. Vincristine (age greater than 3 years: 1.5 mg/m2 ; age 1 to 3 years: 0.05 mg/kg; age less than 1 year: 0.025 mg/kg) IV day 1 in combination with topotecan 0.75 mg/m2 IV daily on days 1, 2, 3, 4, and 5 immediately following cyclophosphamide 250 mg/m2 IV daily on days 1, 2, 3, 4, and 5 (VTC) in weeks 3, 9, 21, 27, 33, and 39 alternating with vincristine day 1, dactinomycin (age 1 years or more: 0.045 mg/kg; age less than 1 year: 0.025 mg/kg; max 2.5 mg) IV day 1, and cyclophosphamide (age greater than 3 years: 2,200 mg/m2 ; age 1 to 3 years: 73 mg/kg; age less than 1 years: 36 mg/kg) IV day 1 (VAC) in weeks 0, 6, 12, 24, 30, 36; vincristine was given alone in weeks 1, 2, 4, 5, 7, 8, 10, 11, 19, 20, 22, 23, 34, and 35. To prevent hemorrhagic cystitis, mesna 250 mg/m2 IV daily on days 1, 2, 3, 4, and 5 was given immediately prior to cyclophosphamide administration. During the VAC segment, mesna 450 mg/m2 IV was given immediately before cyclophosphamide and every 3 hours for 3 additional doses after cyclophosphamide. In a phase 3 trial, VAC/VTC was compared to VAC in 617 patients with previously untreated intermediate-risk rhabdomyosarcoma. The primary endpoint, failure-free survival, was not significantly different between the 2 treatment arms (68% VAC/VTC vs. 73% VAC, p = 0.3) when measured at 4 years. In addition, the estimated overall survival (OS) at 4 years was 79% for both treatment groups. Neutropenia occurred significantly more often in patients who received VAC only (78% vs. 85%, p = 0.04). In a phase 2 trial of newly diagnosed metastatic rhabdomyosarcoma, 61 patients under the age of 21 received VTC alternating with VAC. After 41 weeks of therapy, 34% achieved a CR. Disease-free survival at 3 years was 10% while the 3-year OS rate was 20%. No unexpected toxicities occurred during treatment.

For the first-line treatment of rhabdomyosarcoma in children and adolescents in combination with ifosfamide, dactinomycin, and doxorubicin†. Intravenous dosage Children and Adolescents

Ifosfamide 6,000 mg/m2 continuous IV (CIV) over 48 hours on days 1, 29, and 50 in combination with mesna 6,000 mg/m2 CIV over 48 hours on days 1, 29, and 50; doxorubicin 40 mg/m2 IV daily on days 29 and 30; dactinomycin 0.5 mg/m2 IV daily on days 1, 2, and 3 and 50, 51, and 52; and vincristine 1.5 mg/m2 IV on days 1, 8, 15, and 22. The duration of therapy was dependent on stage at diagnosis (stage I: 16 weeks; II: 26 weeks; III: 40 weeks; IV: 48 weeks).

For the treatment of rhabdomyosarcoma, in combination with other oncolytic agents. Intravenous dosage Adults

1.4 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents

1.5 to 2 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg or 2.5 mg in some pediatric studies.

Infants

0.05 mg/kg IV in infants weighing 10 kg or less OR 1.5 to 2 mg/m2 IV in infants weighing more than 10 kg in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of Wilms' tumor, in combination with other oncolytic agents. Intravenous dosage Adults

1.4 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Children and Adolescents

1.5 to 2 mg/m2 IV in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg or 2.5 mg in some pediatric studies.

Infants

0.05 mg/kg IV in infants weighing 10 kg or less OR 1.5 to 2 mg/m2 IV in infants weighing more than 10 kg in combination with other oncolytic agents; vincristine is typically repeated no sooner than once weekly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

For the treatment of previously untreated, low-grade malignant glioma† in combination with carboplatin. Intravenous dosage Adolescents <= 16 years, Children, and Infants > 3 months

1.5 mg/m2 IV (maximum dose, 2 mg) once weekly on weeks 1—10 in combination with carboplatin 175 mg/m2 IV once weekly on weeks 1—4 and 7—10 as induction therapy. Begin maintenance therapy on week 12 with vincristine 1.5 mg/m2 (maximum dose, 2 mg) IV once weekly for 3 weeks and carboplatin 175 mg/m2 IV once weekly for 4 weeks repeated every 6 weeks for 8 cycles. Do not start maintenance therapy or the next cycle of maintenance therapy until the ANC is > 1000 cells/mm3 and the platelet count is > 100,000 cells/mm3.

For the treatment of high-risk gestational trophoblastic disease†. Intravenous dosage Adults

0.8—1 mg/m2 (max dose: 2 mg) IV on day 8 in combination with etoposide, methotrexate, leucovorin, actinomycin D, and cyclophosphamide (EMA-CO regimen), repeated every 2—3 weeks depending on toxicity. Multiple studies have been reported with cure rates ranging from 70—90% in women with high-risk gestational trophoblastic disease. Results are typically better in women who receive EMA-CO as primary therapy and in women without metastatic disease. Growth-factor support should be considered to maintain dose-intensity and prevent hematological toxicity. Complete response is typically defined as three consecutive weekly human chorionic gonadotropin (hCG) levels that are undetectable or less than the upper limit of normal. In studies, treatment was continued for 2—3 additional courses after complete hCG response.

For the treatment of immune thrombocytopenic purpura (ITP)†. Intravenous dosage Adults and Children

2 mg IV monthly as needed.

For the treatment of newly-diagnosed small cell lung cancer (SCLC)† in combination with cyclophosphamide and doxorubicin. Intravenous dosage Adults

Multiple dosage regimens have been studied. Vincristine 1.2 mg/m2 (max = 2 mg) IV on day 1 in combination with cyclophosphamide 750 mg/m2 IV on day 1 and doxorubicin 40 mg/m2 IV on day 1, every 4 weeks for 4 cycles. Vincristine 1.4 mg/m2 (max = 2 mg) IV on day 1 in combination with cyclophosphamide 800 mg/m2 IV on day 1 and doxorubicin 50 mg/m2 IV on day 1, every 3—4 weeks for 4 cycles. Vincristine 1 mg/m2 (max = 2mg) IV on day 1 in combination with cyclophosphamide 1000 mg/m2 IV on day 1 and doxorubicin 40 mg/m2 IV on day 1, every 3 weeks for 6 cycles.

For induction therapy prior to autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma†, in combination with doxorubicin and dexamethasone. Intravenous dosage Adults 18 to 65 years

0.4 mg/day IV and doxorubicin 9 mg/m2/day IV on days 1—4 plus dexamethasone (VAD regimen) repeated every 4 weeks for 3—4 cycles as induction therapy prior to autologous stem-cell transplantation has been studied in previously untreated multiple myeloma patients. Doxorubicin and vincristine were administered as a continuous IV infusion over 24 hours/day or as a daily IV infusion. Dexamethasone was given as 40 mg PO daily on days 1—4, 9—12, and 17—20 or as 40 mg PO daily days 1—4 on all cycles and days 9—12 and 17—20 on cycles 1 and 2 only.]

For the treatment of head and neck cancer†. Intravenous dosage Adults

2 mg IV on days 1, 8 and 15 in combination with methotrexate 40 mg/m2 IV on days 1 and 15, bleomycin 10 mg IV on days 1, 8, and 15, and cisplatin 50 mg/m2 IV on day 4, every 21 days for 3 cycles.

For the treatment of unresectable, advanced thymoma†, in combination with cisplatin, doxorubicin, and cyclophosphamide. Intravenous dosage Adults

0.6 mg/m2 IV on day 3 plus cisplatin 50 mg/m2 IV on day 1, doxorubicin 40 mg/m2 IV on day 1, and cyclophosphamide 700 mg/m2 IV on day 4 repeated every 3 weeks (median of 5 cycles, range, 3—7 cycles) resulted in a favorable overall response rate in a nonrandomized study of 37 patients.

For the treatment of AIDS-related Kaposi's sarcoma in combination with bleomycin and doxorubicin†. Intravenous dosage Adults

1 mg IV on day 1 in combination with bleomycin (15 units IV on day 1) and doxorubicin (10 mg/m2 IV on day 1), repeated every 2 weeks. Alternately, vincristine 1 mg IV on day 1 has been given in combination with bleomycin (10 mg/m2 IV on day 1) and doxorubicin (20 mg/m2 IV on day 1), repeated every 2 weeks for 6 cycles.

†Indicates off-label use

Hepatic Impairment

There are differing recommendations for vincristine dosage adjustments.
 
Direct bilirubin concentration greater than 3 mg/dL: The manufacturer recommends reducing the dose by 50%. Other sources recommend avoiding administration.
Direct bilirubin concentrations 1.5 to 3 mg/dL: The manufacturer does not address dosage adjustments for these concentrations; other sources recommend reducing the dose by 50%.
 
Aminotransferase concentrations greater than 3 times the ULN: Consider reducing the dose by 50%.
 
AST concentrations greater than 180 International Units/L: Consider avoiding administration.
AST concentrations 60 to 180 International Units/L: Consider reducing the dose by 50%.

Renal Impairment

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

Abrocitinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of abrocitinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and abrocitinib is a P-gp inhibitor.
Adagrasib: (Major) Avoid coadministration of vincristine with adagrasib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A and P-gp substrate and adagrasib is a strong CYP3A and P-gp inhibitor.
Amiodarone: (Major) Amiodarone inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Amobarbital: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Postmarketing reports of interactions, including serious toxicity, between clarithromycin or similar macrolides and vinca alkaloids have been noted.
Apalutamide: (Major) Avoid coadministration of vincristine with apalutamide due to decreased plasma concentrations of vincristine. Vincristine is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer.
Aprepitant, Fosaprepitant: (Moderate) Aprepitant, fosaprepitant is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting and may be used in combination with vincristine. However, use caution and monitor for a possible increase in non-emetogenic vincristine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Vincristine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and theoretically could increase plasma concentrations of vincristine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Armodafinil: (Minor) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including armodafinil (in vitro). Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Asparaginase Erwinia chrysanthemi: (Moderate) Use L-asparaginase and vincristine together with caution; increased vincristine-related toxicity may occur. L-asparaginase administered before or concurrently with vincristine may reduce the hepatic clearance of vincristine. If these drugs are used together, administer vincristine 12 to 24 hours before L-asparaginase to minimize toxicity.
Aspirin, ASA; Butalbital; Caffeine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Atazanavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Atazanavir; Cobicistat: (Major) Avoid coadministration of vincristine with cobicistat due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Barbiturates: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Berotralstat: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of berotralstat is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and berotralstat is a P-gp inhibitor.
Bexarotene: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including bexarotene. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like vincristine; the risk of peripheral neuropathy may be additive.
Brigatinib: (Moderate) Monitor for an increased incidence or earlier onset of vincristine-related adverse reactions if coadministration with brigatinib is necessary. Vincristine is a substrate of P-glycoprotein (P-gp). Brigatinib inhibits P-gp in vitro and may have the potential to increase concentrations of P-gp substrates.
Butabarbital: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Butalbital; Acetaminophen: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Butalbital; Acetaminophen; Caffeine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Cabozantinib: (Moderate) Monitor for an increase in vincristine-related adverse reactions, including neurotoxicity and severe constipation, if coadministration of with cabozantinib is necessary. Cabozantinib is a P-glycoprotein (P-gp) inhibitor and has the potential to increase plasma concentrations of P-gp substrates such as vincristine; however, the clinical relevance of this finding is unknown. The effect of concomitant use of P-gp inhibitors with vincristine has not been investigated, but it is likely that these agents will alter the pharmacokinetics or pharmacodynamics of vincristine.
Cannabidiol: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of cannabidiol is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and cannabidiol is a P-gp inhibitor.
Capmatinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of capmatinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-glycoprotein (P-gp) substrate and capmatinib is a P-gp inhibitor.
Carbamazepine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 such as carbamazepine may increase the metabolism of vincristine and decrease the efficacy of drug. In addition, myelosuppressive antineoplastic agents possess hematologic toxicities similar to carbamazepine, and should be used concomitantly with caution.
Carvedilol: (Moderate) Increased concentrations of vincristine may occur if it is coadministered with carvedilol; exercise caution. Carvedilol is a P-glycoprotein (P-gp) inhibitor and vincristine is a P-gp substrate.
Ceritinib: (Major) Avoid coadministration of vincristine with ceritinib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor.
Chloramphenicol: (Major) Chloramphenicol inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
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.
Cimetidine: (Moderate) Cimetidine is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Clarithromycin: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Postmarketing reports of interactions, including serious toxicity, between clarithromycin or similar macrolides and vinca alkaloids have been noted.
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: (Major) Avoid coadministration of vincristine with cobicistat due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Conivaptan: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of conivaptan is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and conivaptan is a P-gp inhibitor.
Cyclosporine: (Moderate) Use cyclosporine and vincristine together with caution; concomitant use may result in increased vincristine plasma concentrations and increased vincristine toxicity. Cyclosporine is a CYP3A4 and P-glycoprotein (P-gp) inhibitor and vincristine is a CYP3A4 and P-gp substrate. Early onset and/or increased severity of neuromuscular adverse events have been reported when vincristine was administered with a strong CYP3A4 and P-gp inhibitor.
Dabrafenib: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including dabrafenib. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Darunavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Darunavir; Cobicistat: (Major) Avoid coadministration of vincristine with cobicistat due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid coadministration of vincristine with cobicistat due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor. (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Delavirdine: (Major) Delavirdine is a potent inhibitor of CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Desmopressin: (Major) Additive hyponatremic effects may be seen in patients treated with desmopressin and drugs associated with SIADH including vincristine. Use combination with caution, and monitor patients for signs and symptoms of hyponatremia.
Desogestrel; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Dextromethorphan; Quinidine: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Dronedarone: (Moderate) Dronedarone is metabolized by and is an inhibitor of CYP3A; dronedarone also inhibits P-gp. Vincristine is a substrate for CYP3A4 and P-gp. The concomitant administration of dronedarone with CYP3A4 and P-gp substrates may result in increased exposure of the substrate and should, therefore, be undertaken with caution.
Drospirenone; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Elacestrant: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of elacestrant is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and elacestrant is a P-gp inhibitor.
Elbasvir; Grazoprevir: (Moderate) Administering vincristine with elbasvir; grazoprevir may result in elevated vincristine plasma concentrations. Vincristine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Major) Eliglustat inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid coadministration of vincristine with cobicistat due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid coadministration of vincristine with cobicistat due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and cobicistat is a strong CYP3A4 inhibitor.
Enasidenib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of enasidenib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and enasidenib is a P-gp inhibitor.
Enzalutamide: (Major) Avoid coadministration of vincristine with enzalutamide due to decreased plasma concentrations of vincristine. Vincristine is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer.
Erythromycin: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Erythromycin is an inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Reports of interactions between erythromycin and vinca alkaloids have been noted.
Eslicarbazepine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including eslicarbazepines. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Ethinyl Estradiol; Norelgestromin: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Ethinyl Estradiol; Norgestrel: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Etonogestrel; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Etravirine: (Moderate) Etravirine is a CYP3A4 inducer/substrate and a P-glycoprotein (PGP) inhibitor and vincristine is a CYP3A4 and PGP substrate. Caution is warranted if these drugs are coadministered.
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.
Felbamate: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including felbamate. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
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: (Minor) Concomitant use of vincristine and fluconazole may increase the risk for vincristine-related adverse effects such as neurotoxicity. The data supporting the risk of adverse effects associated with this combination is limited to retrospective observational studies and results have been inconsistent. Some data suggest that short courses of low-dose, prophylactic fluconazole may be used safely. Vincristine is a CYP3A substrate and fluconazole is a moderate CYP3A inhibitor.
Flutamide: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including flutamide (in vitro). Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Fosamprenavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Fosphenytoin: (Major) Fosphenytoin is a prodrug of phenytoin, and the concomitant use of phenytoin and vincristine is to be avoided. Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 such as phenytoin may increase the metabolism of vincristine and decrease the efficacy of drug. Also, simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included non-liposomal vincristine sulfate have been reported to reduce blood levels of phenytoin and to increase seizure activity. Concurrent treatment with vinca alkaloids and phenytoin has resulted in 50% decreases in phenytoin concentrations and seizures. Reduced phenytoin concentrations may be noted within 24 hours and continue for up to 10 days.
Futibatinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of futibatinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and futibatinib is a P-gp 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.
Gilteritinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of gilteritinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and gilteritinib is a P-gp inhibitor.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of pibrentasvir and vincristine as coadministration may increase serum concentrations of vincristine and increase the risk of adverse effects. Vincristine is a substrate of P-glycoprotein (P-gp); pibrentasvir is an inhibitor of P-gp.
Grapefruit juice: (Major) Grapefruit juice inhibits CYP3A4 and P-glycoprotein (P-gp); vincristine is both a CYP3A and P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vincristine, a CYP3A substrate, as vincristine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Imatinib: (Moderate) Imatinib, STI-571, inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Indinavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with vincristine may result in increased serum concentrations of vincristine. Vincristine is a substrate of the hepatic isoenzyme CYP3A4 and drug transporter P-glycoprotein (P-gp); isavuconazole, the active moiety of isavuconazonium, is an inhibitor of CYP3A4 and P-gp. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifampin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Isoniazid, INH; Rifampin: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifampin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Istradefylline: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of istradefylline is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and istradefylline is a P-gp inhibitor.
Itraconazole: (Major) Avoid the use of vincristine during and for 2 weeks after discontinuation of itraconazole due to the risk of an earlier onset and/or increased severity of vincristine-related adverse reactions, including constipation and peripheral neuropathy. Vincristine is a CYP3A4 substrate and itraconazole is a strong CYP3A4 inhibitor. Concomitant administration of vincristine and itraconazole has resulted in an increased incidence of neurotoxicity.
Ketoconazole: (Major) Avoid coadministration of vincristinewith ketoconazole if possible due to increased plasma concentrations of vincristine. Monitor for an earlier onset and/or increased severity of neuromuscular, myelosuppressive, or other side effects. Vincristine is a substrate of P-glycoprotein (P-gp) in vitro and ketoconazole is a P-gp inhibitor. Vincristine is also a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Postmarketing reports of interactions, including serious toxicity, between clarithromycin or similar macrolides and vinca alkaloids have been noted.
Lapatinib: (Moderate) Monitor for an increase in vincristine-related adverse reactions if coadministration with lapatinib is necessary. Vincristine is a P-glycoprotein (P-gp) substrate and lapatinib is a P-gp inhibitor.
Lasmiditan: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of lasmiditan is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and lasmiditan is a P-gp inhibitor.
L-Asparaginase Escherichia coli: (Moderate) Use L-asparaginase and vincristine together with caution; increased vincristine-related toxicity may occur. L-asparaginase administered before or concurrently with vincristine may reduce the hepatic clearance of vincristine. If these drugs are used together, administer vincristine 12 to 24 hours before L-asparaginase to minimize toxicity.
Ledipasvir; Sofosbuvir: (Moderate) Caution and close monitoring of vincristine-associated adverse reactions is advised with concomitant administration of ledipasvir. Vincristine is a substrate of the drug transporter P-glycoprotein (P-gp); ledipasvir is a P-gp inhibitor. Taking these drugs together may increase vincristine plasma concentrations.
Lenacapavir: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of lenacapavir is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and lenacapavir is a P-gp inhibitor.
Letermovir: (Major) Avoid coadministration of letermovir and vincristine in patients additionally receiving cyclosporine due to increased plasma concentrations of vincristine. Vinorelbine is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor that may be administered with vincristine; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. An increase in plasma concentrations of vincristine may occur during concurrent administration with letermovir; in patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified.
Levoketoconazole: (Major) Avoid coadministration of vincristinewith ketoconazole if possible due to increased plasma concentrations of vincristine. Monitor for an earlier onset and/or increased severity of neuromuscular, myelosuppressive, or other side effects. Vincristine is a substrate of P-glycoprotein (P-gp) in vitro and ketoconazole is a P-gp inhibitor. Vincristine is also a CYP3A4 substrate and ketoconazole is a strong CYP3A4 inhibitor.
Levonorgestrel; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Live Vaccines: (Contraindicated) Do not administer live vaccines to vincristine recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving vincristine. At least 2 weeks before initiation of vincristine therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Vincristine recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased.
Lonafarnib: (Major) Avoid coadministration of vincristine with lonafarnib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 and P-gp substrate and lonafarnib is a P-gp and strong CYP3A4 inhibitor.
Lopinavir; Ritonavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Lorlatinib: (Major) Avoid coadministration of vincristine and lorlatinib due to the risk of decreased vincristine exposure which may reduce its efficacy. Vincristine is a P-glycoprotein (P-gp) substrate and lorlatinib is a P-gp inducer.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may alter the exposure of vincristine. If coadministration is necessary, use caution and monitor closely. Vincristine is a substrate of CYP3A and the P-glycoprotein (P-gp) drug transporter. Lumacaftor is a strong CYP3A inducer; in vitro data suggest lumacaftor; ivacaftor may also induce and/or inhibit P-gp. Although induction of vincristine metabolism through the CYP3A pathway may lead to decreased drug efficacy, the net effect of lumacaftor; ivacaftor on P-gp transport is not clear. Monitor the patient for decreased chemotherapeutic efficacy and vincristine-related toxicity.
Maribavir: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of maribavir is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and maribavir is a P-gp inhibitor.
Mefloquine: (Major) Mefloquine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Methohexital: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Methotrexate: (Major) Monitor for increased serum concentrations and toxicities of methotrexate when administered concurrently with vincristine. When given 0 to 1 hour prior to methotrexate, vincristine increases the cellular retention of methotrexate by inhibiting methotrexate efflux from the cell. Since the window of opportunity for a synergistic interaction is short, the effects in vivo are clinically not seen. Therapeutic synergism is noted when methotrexate is given 8 to 48 hours before vincristine. The mechanism for this interaction has not been clearly defined.
Mifepristone: (Moderate) Increased concentrations of vincristine are likely if chronic mifepristone therapy is given concurrently; exercise caution and monitor for vincristine-related side effects, including neurotoxicity. Mifepristone is an inhibitor of CYP3A4 and possibly an inhibitor of P-gp. Vincristine is a CYP3A4 and P-gp substrate. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Use the lowest dose of vincristine necessary, with appropriate monitoring and follow-up.
Mitapivat: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of mitapivat is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and mitapivat is a P-gp inhibitor.
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.
Mitotane: (Major) Concomitant use of mitotane with vincristine should be undertaken with caution as it could result in decreased plasma concentrations of vincristine, leading to reduced efficacy. Mitotane is a strong CYP3A4 inducer and vincristine is a CYP3A4 substrate.
Modafinil: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including modafinil. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Nafcillin: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including nafcillin (in vitro). Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Nelfinavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Neratinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of neratinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-glycoprotein (P-gp) substrate and neratinib is a P-gp inhibitor.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is a moderate inhibitor of CYP3A4 and should be used with caution in patients receiving concomitant medications that are primarily metabolized through CYP3A4, such as vincristine. The plasma concentrations of CYP3A4 substrates can increase when co-administered with netupitant. The inhibitory effect on CYP3A4 can last for multiple days. If coadministration is necessary, use caution and monitor for chemotherapeutic related adverse reactions.
Nifedipine: (Major) Use caution if coadminsitration of nifedipine is necessary with vincristine and monitor for vincristine toxicity. In a pharmacokinetic study of 26 patients with solid tumors and normal renal and hepatic function, vincristine 2 mg IV was administered alone (n = 14) or with nifedipine 10 mg by mouth three times daily for 3 days before and 7 days after (n = 12). Coadministration of nifedipine significantly increased vincristine AUC (10 +/- 2.91 mcg x min/ml vs 2.9 +/- 0.86 mcg x min/ml; p = < 0.001) and terminal half-life (85.56 +/- 23.51 hours vs 21.72 +/- 9.61 hours; p < 0.05) compared with vincristine alone; additionally, the plasma clearance was significantly reduced in patients treated with nifedipine (309.54 +/- 95.46 vs 985.06 +/- 258.6 ml/min/m2; p < 0.01). The mechanism of this interaction is poorly understood.
Nilotinib: (Moderate) Monitor for increased severity or earlier onset of vincristine-related adverse reactions (e.g., periipheral, autonomic and central neuropathy; low blood counts) if coadministration with nilotinib is necessary. Nilotinib may increase vincristine exposure. Vincristine is a CYP3A4 substrate and nilotinib is a moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Norethindrone; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Norgestimate; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifabutin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Oritavancin: (Minor) Vincristine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of vincristine may be reduced if these drugs are administered concurrently.
Osimertinib: (Moderate) Monitor for an increase in vincristine-related adverse reactions if coadministration with osimertinib is necessary. Vincristine is a P-glycoprotein (P-gp) substrate and osimertinib is a P-gp inhibitor.
Oxcarbazepine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, include oxcarbazepine. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Pacritinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of pacritinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and pacritinib is a P-gp inhibitor.
Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and vincristine, a CYP3A4 substrate, may cause an increase in systemic concentrations of vincristine. Use caution when administering these drugs concomitantly.
Pegaspargase: (Major) Administration of pegaspargase concurrently or prior to vincristine may result in decreased hepatic metabolism of vincristine and cause additive neurotoxicity. Administration of L-asparaginase after vincristine may lessen this effect; vincristine should be given 12 to 24 hours prior to L-asparaginase or pegaspargase.
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.
Pentobarbital: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Perampanel: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including perampanel (in vitro). Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Phenobarbital: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Phenytoin: (Major) Avoid the concomitant use of phenytoin and vincristine. Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 such as phenytoin may increase the metabolism of vincristine and decrease the efficacy of drug. Also, simultaneous oral or intravenous administration of phenytoin and antineoplastic chemotherapy combinations that included non-liposomal vincristine sulfate have been reported to reduce blood levels of phenytoin and to increase seizure activity. Concurrent treatment with vinca alkaloids and phenytoin has resulted in 50% decreases in phenytoin concentrations and seizures. Reduced phenytoin concentrations may be noted within 24 hours and continue for up to 10 days.
Pirtobrutinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of pirtobrutinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and pirtobrutinib is a P-gp inhibitor.
Posaconazole: (Major) Avoid coadministration of posaconazole with vincristine due to increased plasma concentrations of vincristine. Vincristine is a CYP3A4 substrate and posaconazole is a strong CYP3A4 inhibitor. Concomitant administration of azole antifungals, including posaconazole, with another vinca alkaloid has been associated with neurotoxicity and other serious adverse reactions, including seizures, peripheral neuropathy, syndrome of inappropriate antidiuretic hormone secretion, and paralytic ileus.
Pretomanid: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of pretomanid is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and pretomanid is a P-gp inhibitor.
Primidone: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Propafenone: (Major) Propafenone inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Protease inhibitors: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Quinidine: (Major) Quinidine inhibits P-glycoprotein (P-gp), and vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Quinine: (Moderate) Quinine inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Ribociclib: (Major) Avoid coadministration of vincristine with ribociclib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Major) Avoid coadministration of vincristine with ribociclib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Rifabutin: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifabutin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Rifampin: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of the drug, including rifampin. Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Rifapentine: (Major) Avoid coadministration of vincristine and rifapentine due to the risk of decreased vincristine exposure which may reduce its efficacy. Vincristine is a CYP3A substrate and rifapentine is a strong CYP3A inducer.
Ritonavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Rolapitant: (Moderate) Use caution if vincristine and rolapitant are used concurrently, and monitor for vincristine-related adverse effects. Vincristine is a P-glycoprotein (P-gp) substrate, where an increase in exposure may significantly increase adverse effects; rolapitant is a P-gp inhibitor. When rolapitant was administered with another P-gp substrate, digoxin, the day 1 Cmax and AUC were increased by 70% and 30%, respectively; the Cmax and AUC on day 8 were not studied.
Saquinavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp 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.
Secobarbital: (Major) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP 3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including barbiturates. Patients receiving these drugs concurrently should be monitored for possible loss of vincristine efficacy.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) In vitro, ethinyl estradiol is a mild CYP3A4 inhibitor, and vincristine is a CYP3A substrate. Theoretically, coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.
Selpercatinib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of selpercatinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and selpercatinib is a P-gp inhibitor.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of taurursodiol is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and taurursodiol is a P-gp inhibitor.
Sorafenib: (Moderate) Monitor for an earlier onset or increased severity of vincristine-related adverse reactions if coadministration with sorafenib is necessary. Vincristine is a P-glycoprotein (P-gp) substrate and sorafenib is a P-gp inhibitor in vitro. The effect of concomitant use of P-gp inhibitors with vincristine has not been investigated; however, it is likely that these agents will alter the pharmacokinetics or pharmacodynamics of vincristine.
Sotorasib: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of sotorasib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and sotorasib is a P-gp inhibitor.
Sparsentan: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of sparsentan is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and sparsentan is a P-gp inhibitor.
St. John's Wort, Hypericum perforatum: (Moderate) St. John's Wort, Hypericum perforatum induces both CYP3A4 and P-glycoprotein (P-gp), and may decrease serum concentrations of drugs metabolized by this enzyme, such as vincristine. If these drugs are used together, monitor for possible decreased efficacy of vincristine.
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.
Temsirolimus: (Major) Avoid coadministration of temsirolimus with vincristine due to increased plasma concentrations of vincristine. Vincristine is a P-glycoprotein (P-gp) substrate and temsirolimus is a P-gp inhibitor. The effect of concomitant use of P-gp inhibitors has not been investigated, but it is likely that these agents will alter the pharmacokinetics or pharmacodynamics of vincristine.
Teniposide: (Moderate) Use teniposide and vincristine together with caution; neurotoxicity including cases of severe neuropathy have been reported.
Tepotinib: (Major) Monitor for vincristine-related adverse reactions if coadministration of tepotinib is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and tepotinib is a P-gp inhibitor.
Thalidomide: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as vincristine should be used cautiously due to the potential for additive effects.
Ticagrelor: (Moderate) Ticagrelor is a mild CYP3A4 and P-glycoprotein (P-gp) inhibitor, and vincristine is a CYP3A and P-gp substrate. Coadministration may increase vincristine concentrations; monitor patients for vincristine to

xicity if these drugs are used together.
Tipranavir: (Major) The plasma concentrations of vincristine may be significantly elevated when administered concurrently with protease inhibitors. Consideration should be given to temporarily withholding the regimen in patients who develop significant hematological or gastrointestinal toxicity when protease inhibitors are coadministered with vincristine. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; protease inhibitors are CYP3A4 inhibitors and some also inhibit P-gp. If the antiretroviral regimen needs to be withheld for a prolonged period, consider use of a revised regimen that does not include a CYP3A4 and P-gp inhibitor.
Trandolapril; Verapamil: (Major) Verapamil inhibits CYP3A4 and P-glycoprotein (P-gp); vincristine is a CYP3A and P-gp substrate. Coadministration could increase exposure to vincristine; however, verapamil must be given in toxic doses to achieve this effect. An in vitro study has shown that verapamil competes with vincristine for protein binding sites, specifically 1-acid glycoprotein. Verapamil reduced the binding of vincristine to various proteins by 27 to 60%. The clinical significance of this interaction is not known. The absorption of verapamil may also be reduced by coadministration with the cyclophosphamide, vincristine, procarbazine, prednisone (COPP) chemotherapeutic drug regimen. Monitor for increased side effects of vincristine and loss of blood pressure control during coadministration.
Trifluoperazine: (Major) Trifluoperazine inhibits P-glycoprotein (P-gp), which is a mechanism of resistance to naturally occurring (non-synthetic) chemotherapy agents; vincristine is a P-gp substrate. Coadministration could increase exposure to vincristine; however, trifluoperazine must be given in toxic doses to achieve this effect.
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: (Major) Avoid coadministration of vincristine with tucatinib due to increased plasma concentrations of vincristine, resulting in an earlier onset and/or increased severity of neuromuscular side effects. Vincristine is a CYP3A4 and P-glycoprotein (P-gp) substrate; tucatinib is a strong CYP3A4 inhibitor and P-gp 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.
Valproic Acid, Divalproex Sodium: (Moderate) In vitro, Valproic Acid, Divalproex Sodium is a mild CYP3A4 inhibitor and inducer, as well as a mild P-glycoprotein (P-gp) inducer; vincristine is a substrate of both CYP3A and P-gp. Theoretically, concentrations of vincristine may be affected by coadministration. Monitor patients for changes in vincristine efficacy and toxicity if these drugs are used together.
Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust the dose of vasopressin as needed when used concomitantly with drugs suspected of causing syndrome of inappropriate antidiuretic hormone (SIADH), such as vincristine. Use together may increase the pressor and antidiuretic effects of vasopressin.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and vincristine may result in altered concentrations of vincristine. Vemurafenib is an inhibitor of P-glycoprotein (PGP) and an inducer of CYP3A4. Vincristine is a substrate of PGP and CYP3A4. Use caution and monitor patients for toxicity and efficacy.
Verapamil: (Major) Verapamil inhibits CYP3A4 and P-glycoprotein (P-gp); vincristine is a CYP3A and P-gp substrate. Coadministration could increase exposure to vincristine; however, verapamil must be given in toxic doses to achieve this effect. An in vitro study has shown that verapamil competes with vincristine for protein binding sites, specifically 1-acid glycoprotein. Verapamil reduced the binding of vincristine to various proteins by 27 to 60%. The clinical significance of this interaction is not known. The absorption of verapamil may also be reduced by coadministration with the cyclophosphamide, vincristine, procarbazine, prednisone (COPP) chemotherapeutic drug regimen. Monitor for increased side effects of vincristine and loss of blood pressure control during coadministration.
Voclosporin: (Moderate) Monitor for vincristine-related adverse reactions if coadministration of voclosporin is necessary as concurrent use may increase vincristine exposure. Vincristine is a P-gp substrate and voclosporin is a P-gp inhibitor.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Increased concentrations of vincristine are likely. Consider if alternative antibiotic therapy is appropriate. Monitor for vincristine-related side effects, including neurotoxicity, if these drugs must be used together. Clarithromycin is a potent inhibitor of CYP3A4 and also inhibits P-gp. Vincristine is a CYP3A4 and P-gp substrate. Postmarketing reports of interactions, including serious toxicity, between clarithromycin or similar macrolides and vinca alkaloids have been noted.
Voriconazole: (Major) Avoid coadministration of voriconazole with vincristine due to increased plasma concentrations of vinorelbine. Vincristine is a CYP3A4 substrate and voriconazole is a strong CYP3A4 inhibitor. Although no studies have been conducted, vincristine exposure is likely to be increased.
Zafirlukast: (Major) Zafirlukast inhibits CYP3A4, and vincristine is a CYP3A substrate. Coadministration could increase exposure to vincristine; monitor patients for increased side effects if these drugs are given together.

Oncovin/Vincasar PFS/Vincristine/Vincristine Sulfate Intravenous Inj Sol: 1mg, 1mL

Adults

1.4 mg/m2 per week; due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg in some clinical studies.

Geriatric

1.4 mg/m2 per week; due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 mg in some clinical studies.

Adolescents

2 mg/m2 IV per week; due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 or 2.5 mg in some pediatric studies.

Children

2 mg/m2 IV per week; due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 or 2.5 mg in some pediatric studies.

Infants

greater than 10 kg: 2 mg/m2 IV per week; due to the risk of vincristine-induced peripheral neuropathy, weekly doses were capped at 2 or 2.5 mg in some pediatric studies.
10 kg or less: 0.05 mg/kg IV per week.

Mechanism of Action: Vincristine, 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.

Vincristine 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 red blood cells and platelets. Vincristine has a high volume of distribution and rapid distribution half-life of <5 minutes due to extensive tissue binding. Vincristine 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. Approximately 50% of a dose is hepatically metabolized, and most of a dose is excreted as metabolites or the parent drug in the bile and feces. Seventy-six percent of a dose is eliminated through the biliary tree over 72 hours. The beta-half-life of vincristine ranges between 50—155 minutes and the final elimination half-life is between 23—85 hours. The long terminal half-life, AUC and cumulative dose of vincristine are thought to contribute to its increased incidence of neurotoxicity. Because of the extensive biliary elimination, patients with significant biliary obstruction may need a dosage reduction. One commonly used method is to reduce the dose by 75% for a direct bilirubin of 3 mg/dl or greater.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters:
Vincristine is a substrate for the cytochrome P450 (CYP) 3A4 isoenzyme and P-glycoprotein (P-gp).

Intravenous Route

The cytotoxicity of vincristine is associated with intracellular concentration above certain critical threshold for a certain period of time. Most bolus schedules obtain high peak concentrations (200—400 nM) for a short period of time (< 2 hours). Exposure to 100nM of vincristine for 3 hours or exposure to 10 nM for 6—12 hours are required to kill 50% of leukemia or lymphoma cell lines in culture. Despite lower peak concentrations, continuous infusion dosage schedules are associated with longer tissue exposure to vincristine concentrations above the critical cytotoxic level. The long terminal half-life, AUC and cumulative dose of vincristine are thought to contribute to its increased incidence of neurotoxicity.

Pregnancy

Vincristine is contraindicated for use during pregnancy; it may cause fetal harm based on data from animal studies. Females of reproductive potential should avoid pregnancy during vincristine therapy. Apprise the patient of the hazard to the fetus if vincristine is used during pregnancy or if pregnancy occurs during therapy. Teratogenesis (e.g., fetal malformations) and embryo death (e.g., resorption) have been reported in several animal species who received vincristine at doses that were nontoxic to the pregnant animal.

Do not breastfeed during vincristine therapy. It is not known if vincristine is excreted in human milk. Because of the potential for serious adverse reactions from vincristine in the nursing infant, discontinue either vincristine or breast-feeding.