Wellcovorin

Wellcovorin (leucovorin) is used to reduce the side effects of large doses or accidental overdose of medications that can reduce the effects of folic acid in the body, for adults. This includes methotrexate (Rheumatrex), pyrimethamine (Daraprim), trimethoprim (Trimpex, Proloprim), and others.

Wellcovorin is also used for cerebral folate transport deficiency with confirmed FOLR1 gene variant (CFD-FOLR1), in adults and children. This condition causes very low folate in the fluid surrounding the brain and spinal cord, which progressively affects development, learning, behavior, movement, and seizures, and in severe cases may lead to loss of mobility. Wellcovorin has been reported to raise levels of active folate called 5-MTHF in the cerebrospinal fluid (CSF) in these patients.

Wellcovorin (leucovorin) is a form of folic acid that helps your body produce and maintain new cells, helps prevent changes to DNA that may lead to cancer, and is essential for nerve and brain function.

Wellcovorin is:

• not recommended for use in patients with a deficiency of methenyltetrahydrofolate synthetase (MTHFS) because MTHFS is a primary enzyme in the metabolism of leucovorin to 5-methenyltetrahydrofolate.
• not indicated for the treatment of pernicious anemia or other megaloblastic anemias, due to the lack of vitamin B12, because of the risk of progression of neurologic manifestations despite hematologic remission.

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Wellcovorin is for oral administration only and can be taken with or without food.

Patients or caregivers may dissolve leucovorin tablets in an age-appropriate liquid (e.g., water, breastmilk, or infant formula) or crush and mix with soft food before administration. If leucovorin is to be administered in this manner, patients or caregivers should administer the dissolved or mixed product immediately after mixing.

Administer Wellcovorin as soon as possible after a folic acid antagonist or dihydrofolate reductase (DHFR) inhibitor overdose and within 24 hours of methotrexate use when there is impaired methotrexate elimination.

You should not take leucovorin if you have pernicious anemia or other types of anemia caused by a lack of vitamin B12.

This medicine should not be used if there is a history of hypersensitivity reaction, depending on the indication, to leucovorin (folinic acid), levoleucovorin, folic acid, or any component of Wellcovorin, including

• folic acid antagonist or DHFR inhibitor toxicity with a history of a severe hypersensitivity reaction
• FOLR1-CFTD with a history of any hypersensitivity reaction.

You should not take Wellcovorin if you have pernicious anemia or other types of anemia caused by a lack of vitamin B12.

If possible, before you receive this medicine, tell your doctor if you have:

• liver disease;
• kidney disease;
• breathing problems; or
• if you are dehydrated.

It is not known whether Wellcovorin will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether this medicine passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breastfeeding a baby.

Wellcovorin side effects include itchy skin, rash, hives, difficulty breathing, hypersensitivity reactions, rigors (shivering and feeling very cold while your body temperature raises), and temperature change.

Get emergency medical help if you have signs of an allergic reaction, including hives, difficulty breathing, or swelling of your face, lips, tongue, or throat.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Wellcovorin dosage for treatment of FOLR1-CFTD

The treatment dose is based on body weight

• For patients who weigh less than 40 kg:
• For patients who weigh 40 kg or more:

Dose frequencey

• The full daily dose may be given once a day or divided into up to 6 doses per day.

Single-dose limits

• Single doses of 25 mg or less are preferred.
• Do not give more than 75 mg at one time.

See the specific Wellcovorin Dosing page for information on the dose for reducing the toxicity of methotrexate in adult patients with impaired methotrexate elimination, and folic acid antagonists or dihydrofolate reductase (DHFR) inhibitors following an overdose in adult patients.

Tell your healthcare providers about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products. Wellcovorin can interact with other medications you take.

• Some seizure medicines (antiepileptic medicines): If a patient taking Wellcovorin is also taking certain seizure medicines, they should be watched more closely for seizures. Some seizure medicines may make Wellcovorin work less well.
• Trimethoprim-sulfamethoxazole (antibiotic): Wellcovorin should not be taken together with trimethoprim-sulfamethoxazole.
• Fluorouracil: Wellcovorin can increase the side effects of fluorouracil. Serious bowel problems, severe diarrhea, dehydration, and even death have been reported, especially in older adults.

Not all possible drug interactions are listed here.

• Store at 15°C to 25°C (59°F to 77°F).
• Protect from light and moisture.

GlaxoSmithKline, Durham, NC 27701