Leucovorin Calcium

Class: Antidotes
VA Class: VT102
CAS Number: 6035-45-6
Brands: Wellcovorin

Introduction

Folic acid derivative; antidote for folic acid antagonists.^{b c}

Uses for Leucovorin Calcium

Toxicity Associated with Folic Acid Antagonists

Antidote for unintentional overdosage of methotrexate (e.g., resulting from impaired elimination) and other folic acid antagonists (e.g., pyrimethamine, trimethoprim).^{b c}

IV rescue therapy after high-dose methotrexate regimen (to control duration of exposure of sensitive cells to methotrexate) in the treatment of osteosarcoma^{a c} (designated an orphan drug by FDA for this use).^d

Prevention of hematologic toxicity† associated with pyrimethamine, trimethoprim, or trimetrexate therapy.^{160 a}

Megaloblastic Anemia

IV treatment of folate deficient megaloblastic anemias (e.g., serum folate concentration <0.002 mcg/mL) of infancy, pregnancy, sprue, and nutritional deficiencies when oral folic acid therapy is not feasible.^{a c} No advantage over folic acid injection since ability to convert folic acid to tetrahydrofolic acid (THF) is not impaired in these anemias.^a

Effective in the treatment of megaloblastic anemia resulting from congenital dihydrofolate reductase deficiency†.^a

Not effective in the treatment of pernicious anemia and other megaloblastic anemias secondary to lack of vitamin B₁₂; avoid such use.^{101 102 106} (See Contraindications under Cautions.)

Colorectal Cancer

Adjunct to fluorouracil to prolong survival in the palliative treatment of advanced colorectal cancer^{102 108 112 114 116 118 124 125 126 127 128 129 131 140 146 153 154 155} (designated an orphan drug by FDA for this use).¹⁶⁴

First-line therapy for management of advanced colorectal cancer in a combination regimen consisting of fluorouracil, leucovorin, and either irinotecan or oxaliplatin.^{e f}

Leucovorin Calcium Dosage and Administration

General

Toxicity Associated with Folic Acid Antagonists

Methotrexate Overdosage or Rescue after High-dose Methotrexate Therapy

• 
  

  Monitoring of serum methotrexate concentration required to determine optimum dose and duration of leucovorin therapy.^{b c}

  
  


• 
  

  Maintain adequate hydration (3 L daily) and administer sodium bicarbonate to maintain urinary pH at ≥7 during therapy.^{b c}

  
  


• 
  

  Monitor fluid and electrolyte status in patients experiencing delayed early methotrexate elimination and nonoliguric renal failure until methotrexate concentration declines to <0.023 mcg/mL (0.05 μM) and renal failure has resolved.^{b c}

  
  

Prevention of Pyrimethamine Toxicity†

• 
  

  Dosage of leucovorin necessary to prevent hematologic toxicity varies depending on the dosage of the folic acid antagonist and patient’s clinical status.¹⁵⁹

  
  

Prevention of Trimetrexate Toxicity†

• 
  

  Monitoring of neutrophil counts and platelet counts required; modify dosage of trimetrexate and leucovorin based on the worst of the two blood cell counts.¹⁶⁰ (See Table 4.)

  
  

Administration

Administer orally or by IV or IM injection.^{b c}

Administer parenterally rather than orally in patients with GI toxicity (e.g., nausea, vomiting) and in those receiving individual doses >25 mg.^{101 b c} Parenteral administration also preferred if possibility of vomiting and/or decreased GI absorption exists.^{b c}

Do not administer intrathecally (potentially harmful or fatal).^{102 b c}

Oral Administration

Saturable absorption; administration of doses >25 mg not recommended.^b (See Absorption under Pharmacokinetics.)

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

If used concomitantly with fluorouracil, administer separately to avoid possible formation of a precipitate.^c However, no visually apparent precipitate was detected when the drugs were injected sequentially (with no flush between) into Y-site.^HID (See Compatibility under Stability.)

Reconstitution

Add 5, 10, or 20 mL of sterile water for injection or bacteriostatic water for injection (benzyl alcohol-preserved) to vial containing 50, 100, or 200 mg of leucovorin, respectively, to provide a solution containing 10 mg/mL.^c

For vial containing 350 mg of leucovorin, reconstitute with 17.5 mL of sterile water for injection or bacteriostatic water for injection to provide a solution containing 20 mg/mL.^c

Due to benzyl alcohol content in bacteriostatic water for injection, reconstitute with sterile water for injection when preparing doses >10 mg/m².^{102 106 c}

Rate of Administration

Due to calcium content, administer no more than 160 mg per minute (16 mL of a 10-mg/mL solution or 8 mL of a 20-mg/mL solution per minute).^{102 106 c}

For prevention of trimetrexate toxicity†, administer dose over 5–10 minutes.¹⁶⁰

Dosage

Available as leucovorin calcium; dosage expressed in terms of leucovorin.^{b c}

Pediatric Patients

Toxicity Associated with Folic Acid Antagonists

Prevention of Pyrimethamine Toxicity†

Oral

For pyrimethamine dosages of 25–100 mg daily or 1–2 mg/kg daily (for treatment of toxoplasmosis): 10–25 mg administered with each pyrimethamine dose.¹⁶¹

For pyrimethamine dosages of 25–50 mg once daily (given with clindamycin or sulfadiazine for secondary prophylaxis of toxoplasmosis in adolescents): 10–25 mg once daily.¹⁰⁵

For pyrimethamine dosage of 1 mg/kg once daily (given with dapsone or clindamycin for primary or secondary prophylaxis of toxoplasmosis, respectively, in HIV-infected children): 5 mg once every 3 days.¹⁰⁵

For pyrimethamine dosage of 25 mg once daily (given with atovaquone for primary or secondary prophylaxis against toxoplasmosis in HIV-infected adolescents): 10 mg daily, administered concomitantly with pyrimethamine.¹⁰⁵

For pyrimethamine dosage of 50 or 75 mg once weekly (given with dapsone for primary prevention of Pneumocystis jiroveci [formerly Pneumocystis carinii] pneumonia or toxoplasmosis or for secondary prophylaxis of P. jiroveci pneumonia in HIV-infected adolescents): 25 mg once weekly, administered concomitantly with pyrimethamine.^{105 161}

Adults

Toxicity Associated with Folic Acid Antagonists

Methotrexate Overdosage

Dosage is approximately twice that of levoleucovorin (the active l-isomer).¹⁶²

Oral, IV, or IM

15 mg (approximately 10 mg/m²) every 6 hours until serum methotrexate concentration declines to <0.005 mcg/mL (0.01 μM); initiate administration as soon as possible after overdosage and within 24 hours following methotrexate administration if delayed elimination is detected.^{b c} (See Table 1 and Table 2 under Dosage and Administration.)

If 24-hour S_cr increases 50% over baseline, 24-hour methotrexate concentration is >2.27 mcg/mL (5 μM, or 48-hour methotrexate concentration is >0.409 mcg/mL (0.9 μM), increase dosage immediately to 150 mg (approximately 100 mg/m²) IV every 3 hours until serum methotrexate concentration declines to <0.005 mcg/mL (0.01 μM).^{b c}

Pyrimethamine or Trimethoprim Overdosage

Oral

5–15 mg daily is recommended by some clinicians.^b

Rescue after High-dose Methotrexate Therapy

Dosage is approximately twice that of levoleucovorin (the active l-isomer).¹⁶²

Oral, IV, or IM

15 mg (approximately 10 mg/m²) every 6 hours for 10 doses, starting at 24 hours after initiation of methotrexate (12–15 g/m²) infusion for patients with normal methotrexate elimination (i.e., serum methotrexate concentration approximately 4.54 mcg/mL [10 μM] at 24 hours after administration, 0.454 mcg/mL [1 μM] at 48 hours, and <0.091 mcg/mL [0.2 μM] at 72 hours).^c

Continue therapy and maintain adequate hydration and urinary alkalization (pH ≥7) until methotrexate concentration declines to <0.023 mcg/mL (0.05 μM).^c

If substantial clinical toxicity occurs in patients with mild abnormalities in methotrexate elimination or renal function, extend rescue therapy for an additional 24 hours (i.e., 14 doses over 84 hours) for subsequent methotrexate courses.^{b c}

Monitor S_cr and methotrexate concentration at least once daily.^c Adjust dosage and duration of therapy based on methotrexate elimination pattern and patient’s renal function.^c (See Tables 1 and 2.)

Table 1. Guidelines for Leucovorin Dosage Adjustment in Patients with Delayed Late Methotrexate Elimination

Serum Methotrexate Concentration	Leucovorin Dosage Adjustment
>0.091 mcg/mL (0.2 μM) at 72 hours and >0.023 mcg/mL (0.05 μM) at 96 hours following methotrexate administration	Continue leucovorin 15 mg every 6 hours until methotrexate concentration declines to <0.023 mcg/mL (0.05 μM)b c

Table 2. Guidelines for Leucovorin Dosage Adjustment in Patients with Delayed Early Methotrexate Elimination and/or Evidence of Acute Renal Injury

Serum Methotrexate and/or Scr Concentration	Leucovorin Dosage Adjustment and Monitoring
≥22.7 mcg/mL (50 μM) at 24 hours or ≥2.27 mcg/mL (5 μM) at 48 hours after methotrexate administration and/or ≥100% increase in Scr at 24 hours after administration	Leucovorin 150 mg IV every 3 hours until methotrexate concentration declines to <0.454 mcg/mL (1 μM), then leucovorin 15 mg IV every 3 hours until methotrexate concentration declines to <0.023 mcg/mL (0.05 μM)b c If nonoliguric renal failure develops, monitor fluid and electrolyte status until methotrexate concentration declines to 0.023 mcg/mL (0.05 μM) and renal failure has resolvedb c

Prevention of Pyrimethamine Toxicity†

Oral

For pyrimethamine dosages of 25–100 mg daily or 1–2 mg/kg daily (for treatment of toxoplasmosis): 10–25 mg administered with each pyrimethamine dose.¹⁶¹

For pyrimethamine dosages of 25–50 mg once daily (given with clindamycin or sulfadiazine for secondary prophylaxis of toxoplasmosis): 10–25 mg once daily.¹⁰⁵

For pyrimethamine dosage of 25 mg once daily (given with atovaquone for primary or secondary prophylaxis of toxoplasmosis in HIV-infected individuals): 10 mg daily, administered concomitantly with pyrimethamine.¹⁰⁵

For pyrimethamine dosage of 50 or 75 mg once weekly (given with dapsone for primary prevention of P. jiroveci pneumonia or toxoplasmosis or for secondary prophylaxis of P. jiroveci pneumonia in HIV-infected individuals): 25 mg once weekly, administered concomitantly with pyrimethamine.^{105 161}

Prevention of Trimetrexate Toxicity†

Oral or IV

For trimetrexate dose of 45 mg/m²: 20 mg/m² every 6 hours (total daily dose: 80 mg/m²).^{160 161}

Alternatively, dose may be based on body weight.¹⁶⁰ (See Table 3.)

Table 3. Leucovorin Dosage Based on Body Weight160

Body Weight (kg)	Trimetrexate Dosage (mg/kg/day)	Leucovorin Dosage (mg/kg Every 6 Hours)
<50	1.5	0.6
50–80	1.2	0.5
>80	1.0	0.5

Round calculated oral dose up to the next 25-mg increment.¹⁶⁰

Continue leucovorin therapy for at least 72 hours after last trimetrexate dose (usual duration: 24 days).¹⁶⁰

Adjust dosage if hematologic toxicities occur, based on the worst of the two blood cell counts.¹⁶⁰ (See Table 4.)

Adjust dosage based on the worse of the two blood counts

Table 4. Dosage Adjustments for Hematologic Toxicities160

Toxicity Grade	ANC (cells/mm3)	Platelets (cells/mm3)	Dosage Adjustments
1	>1000	>75,000	No adjustment in trimetrexate or leucovorin dosages
2	750–1000	50,000–75,000	No adjustment in trimetrexate dosage; increase leucovorin to 40 mg/m2 every 6 hours
3	500–749	25,000–49,999	Decrease trimetrexate dose to 22 mg/m2 once daily; increase leucovorin to 40 mg/m2 every 6 hours
4	<500	<25,000	Day 1–9: Discontinue trimetrexate; increase leucovorin to 40 mg/m2 every 6 hours for an additional 72 hours Day 10–21: Discontinue trimetrexate; increase leucovorin to 40 mg/m2 every 6 hours for an additional 72 hours. If hematologic toxicity improves within 96 hours to grade 3 or grade 2, reinitiate trimetrexate at 22 mg/m2 or 45 mg/m2, respectively, once daily; continue leucovorin for 72 hours after the last trimetrexate dose

Megaloblastic Anemia

IM

Up to 1 mg daily; no evidence that doses >1 mg daily are more effective.^{a c}

Duration of therapy depends on hematologic response.^a In general, improved sense of well-being occurs within first 24 hours; bone marrow begins to become normoblastic within 48 hours; and reticulocytosis begins within 2–5 days after initiation of therapy.^a

Colorectal Cancer

IV

Leucovorin 20 mg/m² followed by IV fluorouracil (425 mg/m²) daily for 5 days^{102 126 130 131 132 144 c} or leucovorin 200 mg/m² by slow IV injection (over a minimum of 3 minutes) followed by IV fluorouracil (370 mg/m²) daily for 5 days;^{102 116 126 130 131 132 144 156 c} no evidence of superiority of either regimen.¹³¹

Repeat either regimen at 4-week intervals for 2 additional courses, then at 4- to 5-week intervals provided toxicity from the previous course has subsided.^{102 126 c}

Do not administer repeat courses until WBC >4000/mm³ and platelet count >130,000/mm³.^c If blood counts do not return to these levels within 2 weeks, discontinue therapy.^{102 c} Discontinue therapy when there is clear evidence of tumor progression.^{102 c} (See Patient Evaluation and Monitoring under Cautions.)

If WBC and platelet count return to >4000/mm³ and >130,000/mm³, respectively, within 2 weeks, adjust subsequent fluorouracil dosages based on severity of GI toxicity and nadir blood counts from previous course; leucovorin dosage generally not adjusted according to toxicity.^{102 c} (See Table 5.) If no toxicity occurred in the prior course, increase subsequent fluorouracil dosage by 10%.^{102 c}

Adjust dosage based on the most severe toxicity.

Table 5. Fluorouracil Dosage Adjustments for Hematologic or GI Toxicities102126133c

Toxicity after Prior Dose	Fluorouracil Daily Dosage for Subsequent Course
If moderate diarrhea and/or stomatitis or WBC nadir of 1000–1900/mm3 or Platelet nadir of 25,000–75,000/mm3 occurs	Reduce dosage by 20%
If severe diarrhea and/or stomatitis or WBC nadir of <1000/mm3 or Platelet nadir of <25,000/mm3 occurs	Reduce dosage by 30%

Prescribing Limits

Pediatric Patients

Oral

Administration of doses >25 mg not recommended.^b (See Absorption under Pharmacokinetics.)

Adults

Oral

Administration of doses >25 mg not recommended.^b (See Absorption under Pharmacokinetics.)

Special Populations

Patients with Delayed Methotrexate Elimination

Higher dosages and extended duration of therapy may be required if delayed methotrexate excretion is caused by third space fluid accumulation (i.e., ascites, pleural effusion), renal impairment, or inadequate hydration.^{b c}

Cautions for Leucovorin Calcium

Contraindications

• 
  

  Pernicious anemia or other megaloblastic anemias secondary to lack of vitamin B₁₂;^{101 102 106} such use may obscure diagnosis of pernicious anemia by alleviating hematologic manifestations while allowing neurologic complications to progress.^{a b c}

  
  

Warnings/Precautions

Warnings

Use as Antidote

Administer as soon as possible following unintentional overdosage.^{b c} Delayed administration may reduce effectiveness in counteracting hematologic toxicity associated with folic acid antagonists.^{b c}

Toxicity Potentiation with Concomitant Therapy

When used concomitantly with other chemotherapeutic agents (e.g., fluorouracil, methotrexate), administer only under the supervision of a qualified clinician experienced in the use of cancer chemotherapeutic agents.^{a c}

Possible potentiation of fluorouracil toxicity.^c GI toxicities (particularly stomatitis and diarrhea) observed more frequently, and possibly more severe and prolonged, compared with fluorouracil monotherapy.^c Diarrhea may result in clinical deterioration, leading to death;^{102 143 155 c} if diarrhea occurs, monitor patients until manifestations have completely resolved.^c Do not initiate or continue combination therapy in patients with manifestations of GI toxicity until such manifestations have completely resolved.^{102 114 126 c} Increased risk of severe GI toxicity in debilitated or geriatric patients; use with extreme caution.^{102 143 c} (See Geriatric Use under Cautions.)

Concomitant use with co-trimoxazole for treatment of P. jiroveci pneumonia in HIV-infected patients associated with increased rates of treatment failure, morbidity, and mortality.^{b c}

Seizures and/or syncope reported rarely, usually following concomitant therapy with fluoropyrimidines; most commonly reported in cancer patients with CNS metastases or other predisposing factors.^c

Sensitivity Reactions

Anaphylactoid Reactions

Anaphylactoid reactions and urticaria reported.^{b c}

General Precautions

Patient Evaluation and Monitoring

Treatment of advanced colorectal cancer: When used in combination with fluorouracil, perform physical examination prior to each treatment course and appropriate radiological examination as needed; discontinue therapy when there is clear evidence of tumor progression.^{102 c} Monitor CBC (with differential) and platelet count prior to initiation of therapy.^c During first 2 courses, monitor CBC (with differential) and platelet count weekly; thereafter, monitor once each cycle at time of anticipated WBC nadir.^{102 c} Monitor electrolytes and liver function tests prior to each course for the first 3 courses, then prior to every other course.^c

Specific Populations

Pregnancy

Category C.^{b c}

Lactation

Not known whether distributed into milk.^{b c} Use with caution.^{b c}

Pediatric Use

Possible decreased anticonvulsant effect in pediatric patients receiving anticonvulsant therapy concomitantly with large amounts of folic acid; possible increased frequency of seizures in susceptible patients.^{b c} (See Interactions.)

Geriatric Use

Treatment of advanced colorectal cancer: Increased risk of severe GI toxicity when used in combination with fluorouracil.^c Death secondary to severe enterocolitis, diarrhea, and dehydration reported in geriatric patients receiving weekly leucovorin and fluorouracil therapy;^{102 143 c} concomitant granulocytopenia and fever observed in some patients.^c Use with extreme caution.^{102 143 c}

Common Adverse Effects

Leucovorin in combination with fluorouracil: leukopenia, nausea, vomiting, diarrhea, stomatitis, lethargy/malaise/fatigue, alopecia, dermatitis, anorexia.^c

Interactions for Leucovorin Calcium

Specific Drugs

Drug	Interaction
Anticonvulsants (phenobarbital, phenytoin, primidone)	Decreased anticonvulsant effect if used concomitantly with large amounts of folic acid; possible increased frequency of seizures in susceptible pediatric patientsb c
Co-trimoxazole	Increased rates of treatment failure, morbidity, and mortality in HIV-infected patients receiving combination therapy for treatment of P. jiroveci pneumoniac
Fluorouracil	Possible potentiation of fluorouracil antineoplastic activity and toxicity102 119 128 141 144 146 147 148 149 150 b c
Methotrexate, intrathecal	Possible decreased methotrexate efficacy if used concomitantly with high doses of leucovorinb c

Leucovorin Calcium Pharmacokinetics

Absorption

Bioavailability

Peak serum concentrations of leucovorin (5-formyl-THF), active metabolite (5-methyl-THF), or total reduced folates attained within several hours.^c (See Table 6.)

Dose studied: 25 mg

Doses studied: 15 and 25 mg

Table 6. Time to Peak Serum Concentrations of Leucovorin, 5-Methyl-THF, and Total Reduced Folatesbc

Route	Leucovorin	5-Methyl-THF	Total Reduced Folates
Oral	1.2 hours	2.4 hours	1.72 and 2.3 hours
IV	10 minutes	1.3 hours	10 minutes
IM	28 minutes	2.8 hours	40 and 52 minutes

Oral absorption saturable at doses >25 mg.^{b c} Apparent bioavailability is 97, 75, or 37% for 25-, 50-, or 100-mg dose, respectively.^{b c}

AUC of leucovorin, 5-methyl-THF, and total reduced folates is similar following IV and IM administration.^c AUC of total reduced folates following oral administration of 25-mg dose is 92% of that following IV administration.^c AUC is 8% less following IM injection in gluteal region than in deltoid region.^a

Distribution

Extent

THF and derivatives distributed to all body tissues; liver contains about one-half of total body folate stores.^a

Small amounts of 5-methyl-THF distributed into CSF.^{b c}

Elimination

Metabolism

Rapidly metabolized to active metabolite 5-methyl-THF (major transport and storage form of folate in body).^{a c}

Elimination Route

Excreted in urine, mainly as 10-formyl-THF and 5,10-methenyl-THF.^a

Urinary excretion of folate becomes approximately logarithmic at doses >1 mg.^c

Half-life

Oral administration: 3.5–5.7 hours.^{b c}

IV or IM administration: 6.2 hours (for total reduced folates).^c

Stability

Storage

Oral

Tablets

15–30°C.^b Protect from light and moisture.^b

Parenteral

Injection

2–8°C.^c Protect from light; retain in original carton until time of use.^c Discard unused portion.^c

Powder for Injection

15–30°C.^{a c} Protect from light.^{a c}

Following reconstitution with sterile water for injection, use immediately and discard unused portion.^{102 c}

Following reconstitution with bacteriostatic water for injection, use within 7 days.^{102 c}

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility^HID

Compatible
Dextrose 10% in sodium chloride 0.9%
Dextrose 5 or 10% in water
Ringer’s injection
Ringer’s injection, lactated
Variable
Sodium chloride 0.9%

Drug Compatibility

Admixture CompatibilityHID

Compatible
Cisplatin
Cisplatin with floxuridine
Floxuridine
Incompatible
Fluorouracil

Y-Site CompatibilityHID

Compatible
Amifostine
Aztreonam
Bleomycin sulfate
Cefepime HCl
Cisplatin
Cladribine
Cyclophosphamide
Docetaxel
Doxorubicin HCl
Doxorubicin HCl liposome injection
Etoposide phosphate
Filgrastim
Fluconazole
Fluorouracil
Furosemide
Gemcitabine HCl
Granisetron HCl
Heparin sodium
Linezolid
Methotrexate sodium
Metoclopramide HCl
Mitomycin
Oxaliplatin
Pemetrexed disodium
Piperacillin sodium–tazobactam sodium
Tacrolimus
Teniposide
Thiotepa
Vinblastine sulfate
Vincristine sulfate
Incompatible
Amphotericin B cholesteryl sulfate complex
Droperidol
Foscarnet sodium
Lansoprazole
Sodium bicarbonate

ActionsActions

• 
  

  Racemic mixture of diastereoisomers of 5-formyl-THF; reduced form of folic acid.^{b c} Consists of equal amounts of d- and l-isomers; l-isomer (levoleucovorin) is the pharmacologically active isomer.^{162 163} Does not require reduction by dihydrofolate reductase to participate in reactions utilizing folates.^{b c}

  
  


• 
  

  Counteracts therapeutic and toxic effects (e.g., hematologic toxicity) of folic acid antagonists (e.g., methotrexate).^{b c} No effect on other established toxicities of methotrexate resulting from drug and/or metabolite precipitation in kidneys (e.g., nephrotoxicity).^{b c}

  
  


• 
  

  Enhances therapeutic and toxic effects of fluoropyrimidines (e.g., fluorouracil) by stabilizing binding of fluorouracil metabolite (fluorodeoxyridylic acid) to thymidylate synthase (enzyme responsible for DNA repair and replication), thus enhancing inhibition of this enzyme.^{102 119 128 141 144 146 147 148 149 150 c}

  
  

Advice to Patients

• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.^{b c}

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.^{b c}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{b c} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Leucovorin Calcium

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	5 mg (of leucovorin)*	Leucovorin Calcium Tablets (scored)	Barr, Roxane, UDL, Xanodyne
		10 mg (of leucovorin)*	Leucovorin Calcium Tablets (scored)	Roxane
		15 mg (of leucovorin)*	Leucovorin Calcium Tablets (scored)	Roxane, Xanodyne
		25 mg (of leucovorin)*	Leucovorin Calcium Tablets (scored)	Barr, Roxane, UDL
Parenteral	For injection	50 mg (of leucovorin)*	Leucovorin Calcium for Injection	Bedford
		100 mg (of leucovorin)*	Leucovorin Calcium for Injection	Bedford
		200 mg (of leucovorin)*	Leucovorin Calcium for Injection (preservative-free)	American Pharmaceutical Partners, Bedford
		350 mg (of leucovorin)*	Leucovorin Calcium for Injection	Bedford, Xanodyne
		500 mg (of leucovorin)*	Leucovorin Calcium for Injection (preservative-free)	American Pharmaceutical Partners
	Injection	10 mg (of leucovorin) per mL (500 mg)*	Leucovorin Calcium Injection (preservative-free)	Bedford

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Leucovorin Calcium 10MG Tablets (ROXANE): 24/$152.99 or 72/$439.95

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions February 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

101. Immunex. Leucovorin calcium tablets prescribing information. Seattle, WA; 1994 May.

102. Immunex. Leucovorin calcium for injection prescribing information. Seattle, WA; 1994 May.

103. Engel SI (Lederle Laboratories, Pearl River, NY): personal communication; 1987 Jun.

104. Benvenuto JA, Anderson RW, Kerkof K et al. Stability and compatibility of antitumor agents in glass and plastic containers. Am J Hosp Pharm. 1981; 38:1914-8. [PubMed 7325172]

105. US Public Health Service (USPHS) and Infectious Diseases Society of America (IDSA) Prevention of Opportunistic Infections Working Group. 2001 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons with human immunodeficiency virus. From HIV/AIDS Treatment Information Services (ATIS) website ()

106. Quad Pharmaceuticals. Leucovorin calcium for injection prescribing information. Indianapolis, IN; 1987 Mar.

107. Machover D, Schwarzenberg L, Goldschmidt E et al. Treatment of advanced colorectal and gastric adenocarcinomas with 5-FU combined with high-dose folinic acid: a pilot study. Cancer Treat Rep. 1982; 66:1803-7. [IDIS 160753] [PubMed 6982099]

108. Budd GT, Fleming TR, Bukowski RM et al. 5-fluorouracil and folinic acid in the treatment of metastatic colorectal cancer: a randomized comparison: a Southwest Oncology Group study. J Clin Oncol. 1987; 5:272-7. [PubMed 3543246]

109. Panasci L, Ford J, Margolese R. A phase II study of sequential methotrexate and fluorouracil in advanced colorectal cancer. Cancer Chemother Pharmacol. 1985; 15:164-6. [PubMed 4017165]

110. Glimelius B, Ginman C, Graffman S et al. Sequential methotrexate-5-FU-leucovorin (MFL) in advanced colorectal cancer. Eur J Cancer Clin Oncol. 1986; 22:295-300. [PubMed 3486768]

111. Hansen RM, Ritch PS, Anderson T. Sequential methotrexate, 5-fluorouracil, and calcium leucovorin in colorectal carcinoma. Am J Clin Oncol. 1986; 9:352-4. [PubMed 3489407]

112. Machover D, Goldschmidt E, Chollet P et al. Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil and high-dose folinic acid. J Clin Oncol. 1986; 4:685-96. [PubMed 3517242]

113. Leone BA, Romero A, Rabinovich MG et al. Sequential therapy with methotrexate and 5-fluorouracil in the treatment of advanced colorectal carcinoma. J Clin Oncol. 1986; 4:23-7. [PubMed 3941331]

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