Levoleucovorin

Trade Names:
Fusilev
- Injection, lyophilized powder for solution 50 mg

Pharmacology

User Reviews & Ratings As a treatment for... Avg User Ratings [?] Methotrexate Rescue Be the first to rate it 0 reviews Methotrexate Overdosage Be the first to rate it 0 reviews Compare with other drugs.

Counteracts the therapeutic and toxic effects of folic acid antagonists such as methotrexate.

Pharmacokinetics

Absorption

After rapid IV administration, C _max of total tetrahydrofolate (THF) is 1,722 ng/mL. Serum (6S)-5,6,7,8-THF reached a C _max of 275 ng/mL in 0.9 hours.

Elimination

Mean terminal t _½ of total-THF and (6S)-5-methyl-5,6,7,8-THF is 5.1 and 6.8 h, respectively.

Indications and Usage

Rescue after high-dose methotrexate therapy in osteosarcoma; diminish the toxicity and counteract the effects of impaired methotrexate elimination and of inadvertent overdosage of folic acid antagonists.

Contraindications

Previous allergic reactions to folic acid or folinic acid.

Dosage and Administration

IV Recommendations for levoleucovorin rescue are based on a methotrexate dose of 12 g/m ² infused over 4 h. Levoleucovorin rescue at a dose of 7.5 mg (approximately 5 mg/m ² ) every 6 h for 10 doses starts 24 h after beginning of methotrexate infusion. Determine serum creatinine and methotrexate levels at least once daily. Continue levoleucovorin administration, hydration, and urinary alkalinization (pH 7 or more) until the methotrexate level is below 5 × 10 ⁻⁸ M (0.05 micromolar). Adjust the levoleucovorin dose as follows:

If serum methotrexate level is about 10 micromolar at 24 h after administration, 1 micromolar at 48 h, and less than 0.2 micromolar at 72 h, administer levoleucovorin 7.5 mg every 6 h for 60 h (10 doses starting at 24 h after the start of methotrexate infusion).

If serum methotrexate level remains above 0.2 micromolar at 72 h and more than 0.05 micromolar at 96 h after administration, continue levoleucovorin 7.5 mg every 6 h until methotrexate level is less than 0.05 micromolar.

If serum methotrexate level is 50 micromolar or more at 24 h or 5 micromolar or more at 48 h after administration, or if there is a 100% or greater increase in serum creatinine level at 24 h after methotrexate administration (eg, an increase from 0.5 mg/dL to a level of 1 mg/dL or more), give levoleucovorin 75 mg every 3 h until methotrexate level is less than 1 micromolar, then administer levoleucovorin 7.5 mg every 3 h until methotrexate level is less than 0.05 micromolar.

Patients experiencing delayed early methotrexate elimination are likely to develop reversible renal failure. In addition to appropriate levoleucovorin therapy, these patients require continuing hydration and urinary alkalinization and close monitoring of fluid and electrolyte status, until the serum methotrexate level falls below 0.05 micromolar and renal failure resolves.

If clinically important methotrexate toxicity is observed, extend levoleucovorin rescue for an additional 24 h (total of 14 doses over 84 h) in subsequent courses of therapy.

Delayed methotrexate excretion may be caused by accumulation in a third space fluid collection (eg, ascites), renal function impairment, or inadequate hydration. Under such circumstances, higher doses of levoleucovorin or prolonged administration may be indicated.

Although levoleucovorin may ameliorate hematologic toxicity associated with high-dose methotrexate, levoleucovorin has no effect on other established methotrexate toxicities (eg, nephrotoxicity).

IV Start levoleucovorin rescue as soon as possible after an inadvertent overdosage and within 24 h of methotrexate administration when there is delayed excretion. Administer levoleucovorin 7.5 mg (approximately 5 mg/m ² ) every 6 h until the serum methotrexate level is less than 10 ⁻⁸ M. Determine serum creatinine and methotrexate levels at 24 h intervals. If the 24 h serum creatinine increases 50% over baseline or if the 24 h methotrexate level is greater than 5 × 10 ⁻⁶ M, or if the 48 h level is greater than 9 × 10 ⁻⁷ M, increase the levoleucovorin dose to 50 mg/m ² every 3 h until the methotrexate level is less than 10 ⁻⁸ M. Concomitantly employ hydration (3 L/day) and urinary alkalinization with sodium bicarbonate. Adjust the bicarbonate dose to maintain the urine pH at 7 or more.

General Advice

• Do not administer intrathecally.
• Do not coadminister with other agents in the same admixture.
• Do not inject more than 16 mL of reconstituted solution (levoleucovorin 160 mg) IV/min because of the calcium content of the solution.

Storage/Stability

Store at 59° to 86°F. Protect from light. Initial reconstitution of levoleucovorin or additional dilution using sodium chloride 0.9% injection may be stored at room temperature for not more than 12 h. Dilutions with dextrose injection 5% may be stored at room temperature for not more than 4 h.

Drug Interactions

Use with caution because of possible decreased anticonvulsant activity.

Risk of fluorouracil toxicity (eg, dehydration, diarrhea, enterocolitis) may be increased.

Efficacy of intrathecal methotrexate may be decreased.

In HIV-infected patients with acute Pneumocystis carinii pneumonia, the risk of TMP-SMZ treatment failure and morbidity may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Confusion, neuropathy (6%).

Dermatologic

Dermatitis (6%); pruritus, rash (postmarketing).

GI

Stomatitis, vomiting (38%); nausea (19%); diarrhea, dyspepsia, taste perversion, typhlitis (6%).

Genitourinary

Abnormal renal function (6%).

Respiratory

Dyspnea (6%).

Miscellaneous

Rigors and temperature changes (postmarketing).

Precautions

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy of levoleucovorin rescue following high-dose methotrexate have been evaluated in a limited number of patients 6 to 21 years of age.

Elderly

Studies of treatment of osteosarcoma did not include subjects 65 years of age and older.

Overdosage

Symptoms

No data are available.

Link to Page

Print Page

Email Page

Add to List