Marqibo

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Marqibo

Classes

Vinca Alkaloids and Analogs

Administration

CAUTION: Observe and exercise usual precautions for handling, preparing, and administering solutions of cytotoxic drugs.

Injectable Administration Intravenous Administration

Call 1-888-292-9617 with any questions about the preparation of liposomal vincristine.
Liposomal vincristine takes approximately 60 to 90 minutes to prepare; the preparer should have uninterrupted time.
Preparation steps that involve mixing should be done in a biological safety cabinet or by other established pharmacy safety procedures for the preparation of hazardous drugs.
The manufacturer will provide the following to the medical facility at the initial order of liposomal vincristine: 1) tongs, and 2) either a water bath, calibrated thermometer, and calibrated electronic timer (replaced every 2 years) or a block heater (replaced every 5 years).
Additional required items prior to drug preparation are 1) liposomal vincristine kit (vincristine sulfate injection 1 mg/mL, sphingomyelin/cholesterol liposome injection 103 mg/mL, and sodium phosphate injection 14.2 mg/mL, flotation ring, overlabel for the final syringe admixture, and the infusion bag label); 2) sterile venting needle or another suitable device equipped with a sterile 0.2-micron filter; 3) 1-mL or 3-mL sterile syringe with needle; and a 5-mL sterile syringe with needle.
Deviations in temperature, time, and preparation procedures may fail to ensure proper encapsulation of vincristine sulfate into the liposomes; the components of the kit should be discarded and a new kit should be used to prepare the dose if the preparation deviates from the instructions.
Preparation Using a Water Bath:
Fill a water bath with water to at least 8 centimeters (3.2 inches) from the bottom and maintain this minimum water level throughout the procedure; the water bath must remain outside of the sterile area.
Place a calibrated thermometer in the water bath to monitor water temperature; leave thermometer in the water bath until the procedure is complete.
Preheat the water bath to 63 to 67 degrees C; maintain this water temperature until the procedure is complete.
Remove the caps on all vials and swab the vials with sterile alcohol pads.
Vent the sodium phosphate injection vial with a sterile venting needle equipped with a sterile 0.2-micron filter (or other suitable venting device); position the venting needle point well above liquid level before adding sphingomyelin/cholesterol liposome injection and vincristine sulfate injection.
Withdraw 1 mL of sphingomyelin/cholesterol liposome injection and inject into the sodium phosphate injection vial.
Withdraw 5 mL of vincristine sulfate injection and inject into the sodium phosphate injection vial; remove the venting needle and gently invert the sodium phosphate injection vial 5 times to mix (do NOT shake).
The final vial admixture contains liposomal vincristine 5 mg/31 mL (0.16 mg/mL).
Fit the flotation ring around the neck of the final vial admixture.
Confirm that the water bath temperature is 63 to 67 degrees C using a calibrated thermometer; remove the final vial admixture from the biological safety cabinet and place into the water bath for 10 minutes using the calibrated electronic timer; monitor to ensure the desired temperature is maintained.
After placing the final vial admixture into the water bath, immediately record the constitution start time and water temperature on the liposomal vincristine overlabel.
Confirm that the water temperature is 63 to 67 degrees C using the calibrated thermometer at the end of the 10 minutes; using tongs (to avoid burns), remove the vial from the water bath and remove the flotation ring.
Record the final constitution time and the water temperature on the liposomal vincristine overlabel.
After drying the exterior of the final vial admixture with a clean paper towel, affix the liposomal vincristine overlabel and gently invert 5 times to mix; do not shake.
Allow the final vial admixture to equilibrate for at least 30 minutes at room temperature (15 to 30 degrees C; 59 to 86 degrees F); swab the top of the vial with a sterile alcohol pad and return the vial back to the biological safety cabinet.
Empty, clean, and dry the water bath after each use.
Storage of the final vial admixture: store at room temperature for up to 12 hours.
Preparation Using a Block Heater:
Do NOT use water with the block heater; additionally, the flotation ring included in the liposomal vincristine kit is not required for the block heater application.
Arrange the 3 heater blocks in the block heater with the block holding the constitution vial centered between the 2 other blank heater blocks.
Place a calibrated thermometer in the block opening adjacent to the vial well to monitor the temperature; leave the thermometer in the block opening until the procedure has been completed.
Turn on the block heater and set the controller to 75 degrees C; verify the block temperature by checking that the thermometer inserted in the block reads within 2 degrees C of this temperature.
Equilibrate the heating block to the 75 degrees C +/- 2 degrees C for 15 minutes; maintain this block temperature until completion of the procedure.
Remove the caps on all vials and swab the vials with sterile alcohol pads.
Vent the sodium phosphate injection vial with a sterile venting needle equipped with a sterile 0.2-micron filter (or other suitable venting device); position the venting needle point well above liquid level before adding sphingomyelin/cholesterol liposome injection and vincristine sulfate injection.
Withdraw 1 mL of sphingomyelin/cholesterol liposome injection and inject into the sodium phosphate injection vial.
Withdraw 5 mL of vincristine sulfate injection and inject into the sodium phosphate injection vial; remove the venting needle and gently invert the final vial admixture 5 times to mix (do NOT shake).
The final vial admixture contains liposomal vincristine 5 mg/31 mL (0.16 mg/mL).
Confirm that the block heater temperature is 73 to 77 degrees C using a calibrated thermometer; remove the final vial admixture from the biological safety cabinet and place into the block heater for 18 minutes using the calibrated electronic timer; monitor to ensure the desired temperature is maintained.
After placing the final vial admixture into the block heater, immediately record the constitution start time and water temperature on the liposomal vincristine overlabel; only use the calibrated thermometer inserted in the block to monitor temperature.
Confirm that the block heater temperature is 73 to 77 degrees C using the calibrated thermometer at the end of the 18 minutes; using tongs (to avoid burns), remove the vial from the block heater.
Record the final constitution time and the block heater temperature on the liposomal vincristine overlabel.
Affix the liposomal vincristine overlabel and gently invert 5 times to mix; do not shake.
Allow the final vial admixture to equilibrate for at least 30 minutes at room temperature (15 to 30 degrees C; 59 to 86 degrees F); swab the top of the vial with a sterile alcohol pad and return the vial back to the biological safety cabinet.
Storage of the final vial admixture: store at room temperature for up to 12 hours.
Dilution:
Withdraw the calculated liposomal vincrisitine dose (based on actual body surface area) from the final vial admixure.
Remove the volume corresponding to the liposomal vincristine dose from an infusion bag containing 100 mL of 5% Dextrose injection or 0.9% Sodium Chloride injection; inject the dose of liposomal vincristine into the infusion bag for a final infusion bag volume of 100 mL.
Complete the information required on the infusion bag label and affix to the infusion bag.
Intravenous (IV) Infusion:
Administer the diluted liposomal vincristine solution IV over 1 hour through a secure and free-flowing venous access line; complete the infusion within 12 hours of drug preparation.
Discontinue the infusion immediately and consider local treatment measures if extravasation is suspected.
Do not use with in-line filters; do not mix with other drugs.

Adverse Reactions
Severe

infection / Delayed / 39.8-39.8
neutropenia / Delayed / 18.1-18.1
thrombocytopenia / Delayed / 16.9-16.9
anemia / Delayed / 16.9-16.9
peripheral neuropathy / Delayed / 16.7-16.7
fever / Early / 14.5-14.5
fatigue / Early / 12.0-12.0
elevated hepatic enzymes / Delayed / 6.0-11.0
abdominal pain / Early / 8.4-8.4
hypotension / Rapid / 6.0-6.0
ileus / Delayed / 6.0-6.0
cardiac arrest / Early / 6.0-6.0
asthenia / Delayed / 4.8-4.8
constipation / Delayed / 4.8-4.8
respiratory arrest / Rapid / 4.8-4.8
weakness / Early / 1.2-1.2
tumor lysis syndrome (TLS) / Delayed / Incidence not known
hyperkalemia / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
tissue necrosis / Early / Incidence not known

Moderate

hyperesthesia / Delayed / Incidence not known
hypocalcemia / Delayed / Incidence not known
hyperuricemia / Delayed / Incidence not known
hyperphosphatemia / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
phlebitis / Rapid / Incidence not known
erythema / Early / Incidence not known

Mild

nausea / Early / 52.0-52.0
diarrhea / Early / 37.0-37.0
anorexia / Delayed / 33.0-33.0
insomnia / Early / 32.0-32.0
hypoesthesia / Delayed / Incidence not known
arthralgia / Delayed / Incidence not known
paresthesias / Delayed / Incidence not known
musculoskeletal pain / Early / Incidence not known
hyporeflexia / Delayed / Incidence not known
myalgia / Early / Incidence not known
skin irritation / Early / Incidence not known
injection site reaction / Rapid / Incidence not known

Boxed Warning
Intrathecal administration


Intrathecal administration of vincristine liposomal is contraindicated. Death has occurred with intrathecal use. Vincristine liposomal is only for intravenous use.

Ensure correct formulation selection

Vincristine liposomal has different dosage recommendations than vincristine sulfate injection. Ensure correct formulation selection and dose before preparation and administration to avoid overdosage.

Common Brand Names

Marqibo

Dea Class

Rx

Description

Liposome-encapsulated formulation of vincristine sulfate, a vinca alkaloid agent
Used for the treatment of adult patients with relapsed Philadelphia chromosome-negative ALL
Neurologic toxicity (e.g., peripheral neuropathy and paralytic ileus) and myelosuppression have been reported

Dosage And Indications
For the treatment of Philadelphia chromosome-negative acute lymphocytic leukemia (ALL) in second or greater relapse or that has progressed after 2 or more anti-leukemia therapies.
NOTE: Vincristine sulfate liposome (Marqibo) has a different dosage than vincristine sulfate; verify drug name and dose prior to administration.
NOTE: FDA approval of vincristine sulfate liposome was based on response rate.
Intravenous dosage Adults

2.25 mg/m2 IV over 1 hour once every 7 days. Avoid concomitant use with strong CYP3A4 inducers or inhibitors. Treatment with vincristine sulfate liposome (median of 4 doses; range, 1—18 doses) led to an overall complete remission rate (CR) rate of 20% (CR, 11%; CR with incomplete blood count recovery (CRi), 9%) and an overall response (CR + CRi + partial response + bone marrow blast response) rate of 35% in a multicenter, single-arm, phase II study in 65 patients with Philadelphia chromosome-negative acute lymphocytic leukemia (ALL) in second or greater relapse or that progressed after 2 or more anti-leukemia therapies (median of 9 prior anti-leukemia agents). Most patients had B-cell ALL (85%). Concomitant hydroxyurea use was permitted for the first 14 days and corticosteroid use was allowed for the first 5 days to control leukocytosis. All patients had received prior vincristine sulfate therapy and 77% of patients had residual neuropathy prior to study entry. Additionally, patients in this study were not eligible for immediate hematopoetic stem-cell transplantation (HSCT) and had achieved a CR from at least 1 previous anti-leukemic therapy (defined as a leukemia-free interval for at least 90 days). The median duration of CR or CRi was 23 weeks (95% CI, 5—66 weeks) and the median overall survival (OS) time was 4.6 months (range, < 1 month to < 25 months); the 6-month and 24-month OS rates were 35% and 4%, respectively. Twelve patients (18.5%) in this study subsequently underwent a HSCT; the median OS time in these patients was 9.3 months (range, 4—25.3 months).

Dosing Considerations
Hepatic Impairment

Baseline mild or moderate hepatic impairment: No initial dose adjustment is necessary.Baseline severe hepatic impairment: Use has not been evaluated.

Renal Impairment

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

Drug Interactions

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.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Acetaminophen; Aspirin: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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.
Albuterol; Budesonide: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Aluminum Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Carbonate: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Aluminum Hydroxide; Magnesium Trisilicate: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
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.
Antacids: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
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: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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. (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Caffeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Carisoprodol: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Dipyridamole: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Omeprazole: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Aspirin, ASA; Oxycodone: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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.
Azelastine; Fluticasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Beclomethasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Betamethasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Bismuth Subsalicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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.
Budesonide: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Budesonide; Formoterol: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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. (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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.
Caffeine: (Major) Sodium phosphates should be used with caution in patients using concomitant medications that lower the seizure threshold like psychostimulants.
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.
Choline Salicylate; Magnesium Salicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
Ciclesonide: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Colchicine: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment.
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.
Corticosteroids: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Cortisone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Deflazacort: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Dexamethasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Diazoxide: (Moderate) Use sodium phosphates cautiously with diazoxide, as concurrent use can cause hypernatremia.
Dichlorphenamide: (Moderate) Use dichlorphenamide and sodium phosphate monobasic monohydrate; sodium phosphate dibasic anhydrous together with caution. Dichlorphenamide increases potassium excretion and can cause hypokalemia and should be used cautiously with other drugs that may cause hypokalemia including laxatives. Measure potassium concentrations at baseline and periodically during dichlorphenamide treatment. If hypokalemia occurs or persists, consider reducing the dichlorphenamide dose or discontinuing dichlorphenamide therapy.
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.
Erdafitinib: (Major) Avoid coadministration of sodium phosphates with erdafitinib before the initial dose increase period (days 14 to 21) which is based on serum phosphate levels. Sodium phosphates increase serum phosphate levels. Erdafitinib causes hyperphosphatemia as a consequence of FGFR inhibition. Changes in serum phosphate levels by sodium phosphate may interfere with the determination of this initial dose increase and may cause additive hyperphosphatemia.
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.
Fludrocortisone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Flunisolide: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Fluticasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Fluticasone; Salmeterol: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Fluticasone; Vilanterol: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Formoterol; Mometasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Hydralazine: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Use sodium phosphates cautiously with hydralazine as concurrent use can cause hypernatremia.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Hydrocortisone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Magnesium Hydroxide: (Major) Antacids may interact with urinary acidifiers by alkalinizing the urine. Frequent use of these high dose antacids should be avoided in patients receiving urinary acidifiers.
Magnesium Salicylate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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.
Methadone: (Minor) As methadone is a weak base, the renal elimination of methadone is increased by urine acidification. Thus acidifying agents may lower the serum methadone concentration. The limited amounts of circulating methadone that undergo glomerular filtration are partially reabsorbed by the kidney tubules, and this reabsorption is pH-dependent. Several studies have demonstrated that methadone is cleared faster from the body with an acidic urinary pH as compared with a more basic pH.
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.
Methyldopa: (Moderate) Use sodium phosphates cautiously with methyldopa, as concurrent use can cause hypernatremia.
Methylprednisolone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Mometasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Olopatadine; Mometasone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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 react

ions 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.
Prednisolone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Prednisone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
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.
Probenecid; Colchicine: (Moderate) Colchicine is an alkaloid that is inhibited by acidifying agents. The colchicine dose may need adjustment.
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.
Salsalate: (Moderate) Acidification of the urine may increase serum concentrations of salicylates by increasing tubular reabsorption of salicylates, however, this interaction is not likely to be clinically significant since the urine is normally acidic.
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 toxicity 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.
Triamcinolone: (Moderate) Use sodium phosphate cautiously with corticosteroids, especially mineralocorticoids or corticotropin, ACTH, as concurrent use can cause hypernatremia.
Trientine: (Major) In general, oral mineral supplements should not be given since they may block the oral absorption of trientine. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine each inhibit oral absorption of the other, 2 hours should elapse between administration of trientine and iron doses.
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.

How Supplied

Marqibo Intravenous Inj Lipos
Marqibo Intravenous Inj Sol

Maximum Dosage
Adults

2.25 mg/m2 IV every 7 days.

Geriatric

2.25 mg/m2 IV every 7 days.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mechanism Of Action

Vincristine sulfate liposome (Marqibo) is a sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate, a vinca alkaloid agent. Vincristine sulfate was developed from the periwinkle plant in 1959. It is a cell cycle specific agent that exerts its cytotoxic effects on the cell by binding to tubulin, interfering with the structure and function of microtubules. By stabilizing spindle fibers, chromosome segregation is prevented which causes metaphase arrest and mitosis inhibition. The sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate is less susceptible to acid hydrolysis. Additionally, this encapsulated formulation may better penetrate the tumor vasculature and allow the drug to be released slowly, exposing it to the tumor over a longer time period.

Pharmacokinetics

Liposomal vincristine is administered by intravenous (IV) infusion. After IV administration of liposomal vincristine 2.25 mg/m2 over 1 hour, the median clearance was 302 mL/hour (range, 148 to 783 mL/hour) in 12 patients with acute lymphocytic leukemia. Urinary excretion was less than 8% of the dose over 96 hours and fecal elimination accounted for 69% of the total dose over 72 hours following IV liposomal vincristine.
Affected cytochrome P450 (CYP) isoenzymes and drug transporters: CYP3A4, P-gp
Vincristine is a substrate of CYP3A4 and P-glycoprotein. Formal drug interaction studies have not been conducted with liposomal vincristine.

Intravenous Route

The liposomal formulation of vincristine may not be immediately bioavailable and cannot be directly comparable with non-liposomal vincristine sulfate. After IV administration of liposomal vincristine 2.25 mg/m2 over 1 hour in 13 patients with acute lymphocytic leukemia, the median Cmax value was 1,230 ng/mL (range, 919 to 1,720 ng/mL) and the median AUC(0 to inf) value was 13,680 ng x hour/mL (range, 7,036 to 26,074 ng x hour/mL).

Pregnancy And Lactation
Pregnancy

Liposomal vincristine may cause fetal harm if used during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid pregnancy while receiving liposomal vincristine. Women who use liposomal vincristine during pregnancy or who become pregnant while taking this drug should be apprised of the potential hazard to a fetus. Fetal malformations (e.g., skeletal and visceral abnormalities), decreased fetal weights, and an increased number of early resorptions and post-implantation losses were observed following the administration of liposomal vincristine at doses of 0.022 to 0.09 mg/kg per day in pregnant rats.

Counsel patients about the reproductive risk and contraception requirements during liposomal vincristine treatment. Females of reproductive potential should receive pregnancy testing prior to starting therapy. These patients should avoid pregnancy and use effective contraception during therapy and for 6 months after the last liposomal vincristine dose. Due to the risk of male-mediated teratogenicity, male patients with a female partner of reproductive potential should use effective contraception during therapy and for 3 months after the last liposomal vincristine dose. There is a risk of infertility in male and female patients who receive liposomal vincristine, based on data from animal studies and in humans  who received non-liposomal vincristine. Gonadal dysfunction has been reported in both male and female post-pubertal patients who received multi-agent chemotherapy, including non-liposomal vincristine sulfate; fertility recover may occur in some patients.