Levoleucovorin is the pharmacologically active enantiomer of leucovorin, also known as folinic acid. It is used as an adjunct in the treatment of certain types of cancer and in some cases of high-dose methotrexate therapy.

LEVOleucovorin is the active form of leucovorin calcium. It is used in patients with methotrexate toxicity or overdose and in patients on anti-folate chemotherapy.

LEVOleucovorin Uses:

• Metastatic Colorectal Cancer:
  • Treatment of advanced, metastatic colorectal cancer (in combination with fluorouracil)
• Folic acid antagonist overdose:
  • As an antidote to diminish toxicity in inadvertent overdosage of folic acid antagonists
• High-dose methotrexate rescue:
  • Rescue agent after high-dose methotrexate therapy in osteosarcoma treatment
• Impaired methotrexate elimination:
  • As an antidote to diminish the toxicity and counteract effects of impaired methotrexate elimination
• Limitations of use:
  • Levoleucovorin is not indicated for the treatment of pernicious anemia or megaloblastic anemias secondary to the lack of vitamin B12 (due to the risk of progressive neurologic manifestations despite hematologic remission).

LEVOleucovorin Dose in Adults:

Note:

• Levoleucovorin is a medicine that's used to help treat certain types of cancer. When it's used instead of another form called leucovorin calcium, you only need to take half as much of it. It works by assisting in the treatment of cancer and counteracting the side effects of certain cancer drugs.

LEVOleucovorin Dose in the treatment of metastatic Colorectal Cancer:

Levoleucovorin in Colorectal Cancer Treatment:

• It's used with another drug called fluorouracil.
• There are different ways to take it:
  • 100 mg for each square meter of body surface area (mg/m^2) daily, followed by a specific dose of fluorouracil, for 5 days. This cycle is repeated every month for 2 months, and then once every 4 or 5 weeks.
  • Alternatively, 10 mg/m^2 daily, with another dose of fluorouracil, for 5 days. This is again repeated in the same way as the previous method.
• When replacing another drug called leucovorin calcium with levoleucovorin, you use half the usual dose of leucovorin calcium.

Levoleucovorin for Methotrexate Issues:

• High-dose methotrexate rescue:
  • Start with 7.5 mg every 6 hours for 10 times, 24 hours after methotrexate starts.
  • If methotrexate is clearing from the body normally, continue the 7.5 mg dose.
  • If it's not clearing fast enough or if there are kidney problems, the dose may need to increase or the frequency of doses may change.
  • If someone is having serious side effects and methotrexate isn't clearing properly, they might need levoleucovorin for a longer time in the next treatments.
• Methotrexate Overdose:
  • Start with 7.5 mg every 6 hours. Keep taking this until methotrexate levels in the body are very low.
  • The dose might need to be increased if methotrexate levels remain high or if there are signs of kidney problems.
  • Along with this, the patient should drink a lot of water and may need to take other medicines to make their urine less acidic.
• If Methotrexate Isn't Clearing Properly:
  • Similar to overdose, start with 7.5 mg every 6 hours until methotrexate levels are low.
  • Increase the dose if needed, based on methotrexate levels or kidney problems.
  • Again, drinking lots of water and other treatments might be necessary.

LEVOleucovorin Dose in Childrens:

Note:

•  Levoleucovorin, when substituted in place of leucovorin calcium (the racemic form), is dosed at one-half the usual dose of leucovorin calcium.

High-dose methotrexate rescue:

For High-dose Methotrexate Rescue in Kids and Teens:

• Start Treatment:
  • 24 hours after methotrexate is given, start levoleucovorin at 7.5 mg every 6 hours.
  • This is based on a methotrexate dose of 12 g/m^2 given over 4 hours.
  • Also, give the patient lots of fluids and make sure their urine is not too acidic.
  • This treatment has been tested in kids as young as 4 to 6 years old.
• Adjust Treatment Based on Methotrexate Levels:
  • Normal Clearing: If methotrexate levels drop as expected (10 micromolar at 24 hours, 1 micromolar at 48 hours, and less than 0.2 micromolar at 72 hours), keep giving 7.5 mg every 6 hours for a total of 10 doses.
  • Slow Clearing: If the levels are still above 0.2 micromolar at 72 hours and above 0.05 micromolar at 96 hours, continue the 7.5 mg every 6 hours until the level drops below 0.05 micromolar.
  • Very Slow Clearing or Kidney Problems: If the levels are really high (like 50 micromolar at 24 hours or if they double within 24 hours), give a higher dose of 75 mg every 3 hours. Once the levels drop a bit, go back to 7.5 mg every 3 hours until they're below 0.05 micromolar.
  • Serious Side Effects: If the patient has big side effects but not the worst methotrexate levels or kidney problems, they might need levoleucovorin for an extra day the next time they're treated.
  • Other Issues Slowing Clearing: If the patient has other problems like fluid build-up, kidney issues, or isn't drinking enough water, they might need more levoleucovorin or need to take it for longer.

For Accidental Methotrexate Overdose in Kids and Teens:

• Start Treatment:
  • Begin with 7.5 mg every 6 hours. Continue this until methotrexate levels are very low (below 0.01 micromolar).
  • Begin this treatment as soon as possible after the overdose.
• Adjust Treatment if Needed:
  • If kidney function gets worse (like if a blood test called serum creatinine goes up a lot) or if methotrexate levels stay high, the dose might need to go up to 50 mg every 3 hours. Keep this up until methotrexate levels are below 0.01 micromolar.
  • As with the rescue treatment, make sure the patient drinks lots of water and keep their urine from getting too acidic. Use sodium bicarbonate to help with this.

Pregnancy Risk Category: C

• Levoleucovorin is a specific type of a substance called leucovorin.
• Leucovorin is like a useful form of folic acid, which is important, especially during pregnancy.
• Folic acid is recommended for pregnant women.
• However, when it comes to treating colorectal cancer during pregnancy, there's not a lot of information available about using levoleucovorin.

Use of LEVOleucovorin during breastfeeding

• We're not sure if levoleucovorin goes into breast milk.
• It's a specific type of leucovorin, which is related to folic acid.
• Folic acid is important and recommended for women who are breastfeeding.
• But, when levoleucovorin is used as a medicine, it's often given with other drugs like methotrexate or fluorouracil.
• So, if you're thinking about its use during breastfeeding, you'd also need to consider the effects of those other drugs.

LEVOleucovorin Dose in Kidney Disease:

• The manufacturer doesn't give any starting dose changes for levoleucovorin.
• However, if the patient has problems getting rid of methotrexate from their body, adjust the levoleucovorin amount based on how much methotrexate is in their system.

LEVOleucovorin Dose in Liver disease:

• No initial dosage adjustments provided in the manufacturer’s labeling.

• Adverse reactions reported with levoleucovorin either as a part of combination chemotherapy or following chemotherapy.

Common Side Effects of LEVOleucovorin:

• Central nervous system:
  • Fatigue
  • Malaise
• Dermatologic:
  • Dermatitis
  • Alopecia
• Gastrointestinal:
  • Stomatitis
  • Diarrhea
  • Nausea
  • Vomiting
  • Anorexia
  • Decreased appetite
  • Abdominal pain
• Neuromuscular & skeletal:
  • Asthenia

Less Common Side Effects of LEVOleucovorin:

• Central nervous system:
  • Confusion
  • Neuropathy
• Gastrointestinal:
  • Dysgeusia
  • Dyspepsia
  • Typhlitis
• Renal:
  • Renal insufficiency
• Respiratory:
  • Dyspnea

Contraindications to LEVOleucovorin:

• Don't use levoleucovorin if someone has had a serious allergic reaction to leucovorin, folinic acid, folic acid, or any ingredient in the levoleucovorin product.

Warnings and precautions

Gastrointestinal toxicities:

• When used together, levoleucovorin and leucovorin calcium can increase the side effects of a drug called fluorouracil.
• This has led to severe stomach issues and even death, especially in older patients.
• Because of this risk, when levoleucovorin is combined with fluorouracil to treat colorectal cancer, the dose of fluorouracil is reduced.
• Common stomach-related side effects like diarrhea or mouth sores can be worse and last longer when these two drugs are used together.
• It's crucial to wait until any stomach-related symptoms are gone before starting or restarting this combination treatment.

Syncope and seizure:

• Seizures or fainting episodes have been noted in patients using leucovorin calcium.
• These incidents are more common in individuals with brain tumor spread or other conditions that increase their risk.

LEVOleucovorin: Drug Interaction

Monitoring parameters:

High-dose Methotrexate & Overdose:

• Check methotrexate and kidney (creatinine) levels in the blood at least every 24 hours.
• Monitor the acidity (pH) of the urine.
• Watch hydration and salt balance, especially if methotrexate isn't leaving the body quickly (this can cause kidney problems).

For Colorectal Cancer Treatment:

• Keep an eye out for:
  • Diarrhea
  • Mouth sores (stomatitis)

How to administer LEVOleucovorin?

How to Administer:

• Only use through an IV (in the vein).
• Do NOT give directly into the spinal fluid (intrathecally).

Rate of Administration:

• Give it slowly, either directly (push) or diluted over at least 3 minutes.
• For products that have calcium: don't go faster than 160 mg per minute.

For Colorectal Cancer Treatment (Off-label use):

• Some studies have given levoleucovorin over 2 hours as an IV infusion.

Mechanism of action of LEVOleucovorin:

• Levoleucovorin helps reduce the harmful effects of drugs like methotrexate, which work by blocking a specific process in the body.
• It's a special version of leucovorin, which supports the body when methotrexate is blocking its normal functions.
• Additionally, leucovorin can boost the effectiveness (and side effects) of another drug called fluorouracil, by helping it better stop a certain enzyme in the body.

How it works:

• Levoleucovorin changes in the body to become a useful form called 5-methyl-tetrahydrofolate (active).

How long it lasts in the body:

• For total-tetrahydrofolate: About 5.1 hours.
• For a specific form, (6S)-5-methyl-5,6,7,8-tetrahydrofolate: About 6.8 hours.

How quickly it shows up in the blood:

• After getting it through an IV, it reaches its highest level in the blood in about 0.9 hours (or roughly 54 minutes).

International Brands of LEVOleucovorin:

• Fusilev
• Khapzory
• Elvorine
• Isovorin

LEVOleucovorin Brand Names in Pakistan:

Not Available.