levoleucovorin calcium

Absorption: IV administration results on complete bioavailability.

Distribution: Transported actively and passively across cell membranes; enters CSF.

Metabolism/Excretion: Extensively converted to tetrahydrofolic derivatives.

Half-Life: Total tetrahydrofolic acid: 5.1 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
IV	unknown	end of infusion	3–6 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to folic acid or folinic acid.

Use Cautiously in:

Concurrent use of anticonvulsants (may ↑ risk of seizures);
OB: Safety not established in pregnancy (administered with methotrexate or fluorouracil, both of which are teratogenic);
Lactation: Safety not established in breastfeeding (administered with methotrexate or fluorouracil, both of which are teratogenic);
Pedi: Safety and effectiveness not established in children 6 yr (for osteosarcoma or for reducing the toxicity associated with overdosage of folic acid antagonists or impaired methotrexate elimination) or children 18 yr (for colorectal cancer).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: dermatitis

GI: nausea, stomatitis, vomiting, altered taste, diarrhea, dyspepsia

GU: renal impairment

Neuro: confusion, neuropathy

Resp: dyspnea

Interactions ⬆ ⬇

Drug-drug:

↑risk of toxicity from fluorouracil.
May ↓ effectiveness of phenobarbital , phenytoin, or primidone, leading to ↑ risk of seizures.
May ↓ effectiveness of trimethoprim-sulfamethoxazole when used to treat
Pneumocystis jiroveci
pneumonia in patients with HIV.

Route/Dosage ⬆ ⬇

Levoleucovorin Rescue Following High-Dose Methotrexate—Based on a Methotrexate Dose of 12 g/m2 IV Over 4 hr and Concurrent with Hydration and Maintenance of Urine pH 7.0

IV (Adults and Children ≥6 yr): Normal methotrexate elimination: 7.5 mg (5 mg/m²) every 6 hr for 10 doses starting 24 hr after the start of the methotrexate infusion; Delayed late methotrexate elimination: 7.5 mg (5 mg/m²) every 6 hr starting 24 hr after the start of the methotrexate infusion; continue until methotrexate level <5 × 10^–8 (0.05 micromolar); Delayed early methotrexate elimination and/or evidence of acute renal injury: 75 mg (5 mg/m²) every 3 hr starting 24 hr after the start of the methotrexate infusion; continue until methotrexate level is <1 micromolar; then 7.5 mg every 3 hr until 0.05 micromolar).

Levoleucovorin Rescue Following Inadvertent Overdosage of Methotrexate

IV (Adults and Children ≥6 yr): 7.5 mg (approximately 5 mg/m²) every 6 hr until serum methotrexate level <10⁻⁸ M. Determine serum creatinine and methotrexate levels at 24-hr intervals. If 24-hr serum creatinine has ↑ 50% over baseline or 24-hr methotrexate level is >5 × 10⁻⁶ M or 48-hr level is >9 × 10⁻⁷ M, ↑ dose to 50 mg/m² IV every 3 hr until methotrexate level is <10⁻⁸ M. Maintain hydration and urinary alkalinization (pH ≥7.0). Initiate as soon as possible and within 24 hr of methotrexate when there is delayed excretion; as time interval increases, effectiveness ↓.

Palliative Treatment of Advanced Metastatic Colorectal Cancer

IV (Adults ): 100 mg/m² followed by 5-fluorouracil 370 mg/m²; regimen should be given daily for 5 days; repeat regimen every 4 wk for 2 courses (may then repeat course every 4–5 wk if patient tolerates) or levoleucovorin 10 mg/m² followed by 5-fluorouracil 425 mg/m²; regimen should be given daily for 5 days; repeat regimen every 4 wk for 2 courses (may then repeat course every 4–5 wk if patient tolerates).

Availability ⬆ ⬇

(Generic available)

Lyophilized powder for injection: 50 mg/vial (contains mannitol); 175 mg/vial (contains mannitol)
Solution for injection: 10 mg/mL

Assessment ⬆ ⬇

Assess patient for nausea and vomiting secondary to methotrexate therapy or folic acid antagonists (pyrimethamine and trimethoprim) overdose.
- Monitor for development of allergic reactions (rash, urticaria, wheezing). Notify health care professional if these occur.
- Assess for GI toxicities of stomatitis and diarrhea, especially in older adults receiving weekly combination therapy; closely monitor patients with diarrhea until it has resolved. Promptly treat dehydration.

Lab Test Considerations:

Monitor serum methotrexate and creatinine levels at least once daily to determine dose and effectiveness of therapy. Leucovorin calcium levels should be greater than or equal to methotrexate level. Rescue continues until serum methotrexate level is <5 × 10⁻⁸ M.
- Monitor electrolytes, hydration status, and urine pH every 6 hr during therapy; pH should be maintained >7 to ↓ nephrotoxic effects of high-dose methotrexate.

Implementation ⬆ ⬇

Do not confuse levoleucovorin calcium with leucovorin calcium.

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute 50-mg vial with 5.3 mL of 0.9% NaCl without preservatives for a concentration of 10 mg/mL. Reconstitute 175 mg vial with 3.6 mL of 0.9% NaCl for a concentration of 50 mg/mL. Solution is clear, colorless to yellowish; do not administer solutions that are cloudy, discolored, or contain a precipitate.Diluent: Dilute reconstituted solution or solution for injection further immediately with 0.9% NaCl or D5W. Concentration: 0.55 mg/mL. Initial reconstitution or dilutions in 0.9% NaCl are stable at room temperature for 12 hr. Dilutions in D5W are stable for 4 hr at room temperature. Do not administer solutions that are cloudy or contain a precipitate.
Rate: Administer at no more than 16 mL of reconstituted solution (160 mg levoleucovorin) per min due to calcium content of solution.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of levoleucovorin to patient. Do not stop receiving drug without consulting health care professional. Advise patient to read Medication Guidebefore starting and periodically during therapy in case of changes.
Explain need for continued medical follow-up to assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
Recommend adequate hydration during therapy; vomiting, diarrhea, and nausea may occur. Report persistent or severe diarrhea right away.
Educate about consistent oral hygiene and mouth care; stomatitis (sores, ulcers, white spots on the lips, tongue, or mouth) may occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. There are limited data on levoleucovorin calcium; however, methotrexate or fluorouracil administered with levoleucovorin calcium are both teratogenic. Avoid pregnancy and breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇