What is Levoleucovorin?
Levoleucovorin can be used to prevent or treat the toxic effects of methotrexate on people who have been treated with methotrexate for bone cancer.Levoleucovorin can also be used to treat the toxic effects of methotrexate in people who do not properly eliminate the drug after it is metabolized. It can also be used to treat the toxic effects caused by an overdose of certain medications or methotrexate.Levoleucovorin can also be used as part of a combination chemotherapy regimen with fluorouracil for colorectal carcinoma that has spread to other areas of the body. Levoleucovorin only treats the symptoms of colorectal carcinoma, not the cancer itself.Levoleucovorin is not recommended for treating anemia caused by a deficiency in vitamin B12.
Warnings
This medication should not be used if you have an allergy to levoleucovorin, folic, or folinic acids.Tell your doctor that you take sulfa medications, seizure medication, or fluorouracil (5FU), a cancer drug.It may not be possible to inform your carers of all your medical conditions or that you are breastfeeding or pregnant in an emergency. Ensure that any doctor who treats you afterwards knows you received levoleucovorin.If you experience fever, chills, or white patches on your lips or inside your mouth, severe diarrhoea, confusion, or urination issues, or if you can't urinate or feel hot or thirsty, tell your doctor immediately.
Before you take this drug
This medicine should not be taken if you have an allergy to levoleucovorin, folic, or folinic acids.
Tell your doctor or carers, if possible, if you are suffering from:
- Kidney disease
- If you are dehydrated.
Levoleucovorin is not known to harm unborn babies. Tell your doctor immediately if you plan to get pregnant.Levoleucovorin may cause problems with breastfeeding. You should consult your doctor if you are concerned about any risks.You may not know if you're pregnant or breastfeeding in an emergency. Be sure to tell any doctor who is caring for you or your baby that you have taken this medication.
How to take Levoleucovorin?
A levoleucovorin infusion is administered into a vein. This injection will be given by a healthcare provider.Levoleucovorin, when used with methotrexate, is typically given every 3 to 4 hours.Levoleucovorin, a daily treatment for colorectal carcinoma, is typically given as a five-day treatment that's repeated every four to five weeks.You will be monitored to ensure that the medicine is working.Your doctor will need to conduct frequent tests in order to determine the duration of your treatment.
What happens if I miss the dose?
You are unlikely to miss a dosage if this medication is administered by a health care professional in a clinical setting.Call your doctor if you forget your appointment for levoleucovorin, if it is given daily over a 4-week period.
What happens if I overdose?
For poison assistance, call 1-800-222-1222 or get immediate medical help.
What should be avoided?
If your doctor prescribes any restrictions regarding food, beverage, or activity, follow their instructions.
Side effects of Levoleucovorin
If you experience any of the following symptoms of an allergic reaction: hives, difficulty breathing, swelling of your lips, face, tongue, or throat,
Tell your doctor and carers immediately if you:
- Blisters or ulcers on your lips, red or swollen gingivae, difficulty swallowing
- Severe or ongoing diarrhoea;
- A feeling of lightheadedness, as if you could pass out.
- Seizure (convulsions);
- Dehydration symptoms include feeling thirsty, hot, or unable to urinate. Other symptoms include heavy sweating or a hot and dry complexion.
- Kidney problems include: little or no urine production; difficulty urinating; swelling of the feet or ankles.
Levoleucovorin may cause side effects such as:
- Diarrhoea, nausea, vomiting;
- You may experience pain or sores on your lips.
There may be other side effects.Call your doctor for medical advice about side effects. To report adverse effects, you can contact the FDA at 1-800-FDA-1088.
Details on dosage
Usual Adult Dose for Methotrexate Rescue:
Levoleucovorin rescue after high-dose methotrexate therapy:
Dose: Start 24 hours after methotrexate is started. Every 6 hours, 7.5mg (approximately 5.0 mg/m2). You can also find out more about the following:recommendations for levoleucovorin are based on a methotrexate dosage of 12 grammes/m2 given by intravenous injection over a period of 4 hours.
At least daily, serum creatinine levels and methotrexate should be measured. Levoleucovorin, hydration, and urinary alkalinization should be administered.
Dosage and Administration Guidelines
Clinical Situation 1: Normal Methotrexate Elimination
Laboratory findings: Serum methotrexate levels are approximately 10 micromolar after 24 hours of administration, 1 micromolar 48 hours later, and less than 0.02 micromolar 72 hours later.
Levoleucovorin Dosage: 7.5 mg IV, every 6 hours. Duration: 60 hours.
Clinical Situation 2: Delayed Late Methotrexate Elimination
Lab Findings: Serum methylate levels remain above 0.2 micromolars for 72 hours and are greater than 0.05 micromolars after 96 hours.
Levoleucovorin Dosage: Continue to administer 7.5 mg intravenously every six hours until the methotrexate concentration is below 0.05 micromoles.
Clinical Situation 3: Evidence of acute renal injury or delayed early elimination of methotrexate
Lab Findings: A serum methotrexate concentration of 50 micromolars or higher at 24 hours or 5 micromolars or higher at 48 hours following administration; or a 100% increase or greater in serum creatinine at 24 hours after methotrexate (e.g., an increase from 0.5 mg/dl to 1 mg/dl or more).
Levoleucovorin Dosage: 75 mg intravenously every 3 hours, until methotrexate is below 1 micromolar. Then 7.5 mg intravenously every 3 hours, until methotrexate is below 0.05 micromolar.
Renal failure can occur in patients who have delayed methotrexate removal. These patients need to continue hydration and urinary alkalinization as well as close monitoring of fluids and electrolytes until the serum level of methotrexate falls below 0.05 micromolar.
Some patients may experience significant but less severe abnormalities of methotrexate metabolism or renal function after methotrexate treatment. These abnormalities can be associated with clinically significant toxicity. In the event of significant clinical toxicity, levoleucovorin should be given for an extra 24 hours in subsequent courses of treatment (totaling 14 doses spread over 84 hours). When laboratory abnormalities and clinical toxicities occur, it is important to consider the possibility that a patient may be taking other medications that interact with methotrexate.
Delays in methotrexate elimination can be caused by renal insufficiency or insufficient hydration. In such cases, higher doses of methotrexate or prolonged administration could be recommended.
Levoleucovorin can reduce the hematologic toxicities associated with high-dose methotrexate. However, it has no effect on the other established toxicities, such as nephrotoxicity caused by drug or metabolite accumulation in the kidney.
Adult Usual Dose of Methotrexate:
Dosing recommendations for an inadvertent methotrexate overdose
Dose: 7.5mg (approximately 5 mg/m2) is administered intravenously every 6 hours, until the serum level of methotrexate is less than 10–8 mM.
When methotrexate is administered with delayed excretion, levoleucovorin should be started as soon as possible. Levoleucovorin's effectiveness at counteracting toxicities may decrease as the time between methotrexate administration and antifolate administration increases.
The levels of methotrexate and serum creatinine should be measured at intervals of 24 hours. The dose of levoleucovorin can be increased by 50 mg/m2 every three hours if the serum creatinine level has increased more than 50% from baseline or if methotrexate levels are greater than 5x10-6M or 9x10-7M at 48 h.Also, hydration (3 L/day) should be used in conjunction with urinary alkalinization using NaHCO3. Bicarbonate should be adjusted so that the pH of the urine is 7.0 or higher.
Adult dose for colorectal cancer:
Use in combination with 5-fluorouracil for palliative chemotherapy in patients with metastatic colorectal carcinoma.
Regimen 1: Slow intravenous infusion of 100 mg/m2 over 3 minutes minimum, followed by intravenous 5-FU injection at 370 mg/m2.
Regimen 2: Intravenous 5-FU injection at 425 mg/m2, followed by 10 mg/m2.
The treatment is repeated five times daily. The five-day treatment course can be repeated twice at intervals of four weeks (28 days) for two courses, and then again at intervals of 4 to 5 weeks (28 to 35 days) if the patient is fully recovered from the toxic side effects.
The dosage of 5-FU in subsequent treatment courses should be adjusted according to the patient's tolerance. Patients who have experienced mild hematologic, gastrointestinal, or other toxicity during the previous treatment course should reduce their daily 5-FU dosage by 20%. Patients who experienced severe toxicity may need to reduce it by 30%. Patients who did not experience any toxicity during the previous treatment course may have their 5-FU dose increased by 10%. The dosage of levoleucovorin is not adjusted for toxicity.
Interaction with other drug
Tell your doctor if you are taking any other medications or if you will stop taking them during treatment with levoleucovorin.
- Seizure medicine: phenobarbital, phenytoin, primidone;
- A multivitamin, mineral, or other supplement that contains folic acids;
- A sulfa medication (bactrim or septra; sulfatrim; smx-tmp; and smztmp, among others).
This list is incomplete. Levoleucovorin may interact with other drugs, such as prescription and over-the-counter medicines, vitamins, and herbal products. The drug guide doesn't list every possible interaction.
