Rescuvolin 15mg, 50mg Tablets, Powder for Injection

As an antidote to folic acid antagonists, such as methotrexate, which block the conversion of folic acid to tetrahydrofolate by binding the enzyme dihydrofolate reductase.

In cases of inadvertent overdosage of a folic acid antagonist, RESCUVOLIN should be administered as soon as possible; if a period of more than 4 hours intervenes, the treatment may not be effective. Where large doses of methotrexate have been given, RESCUVOLIN may be given by intravenous infusion in a dose equivalent to 75 mg of folinic acid within 12 hours, followed by 12 mg intramuscularly every 6 hours for 4 doses. Doses equal to or greater than the dose of methotrexate have been recommended. In less severe overdosage 6 to 12 mg of RESCUVOLIN intramuscularly every 6 hours for 4 doses may be adequate. RESCUVOLIN is used in conjunction with methotrexate to reduce the toxicity of the methotrexate (u201cfolinic acid rescueu201d; u201ccalcium leucovorin rescueu201d). RESCUVOLIN is given after an appropriate interval, usually of up to 24 hours, has elapsed for methotrexate to exert its antineoplastic effect. Doses of up to 120 mg have been given over 12 to 24 hours by intramuscular injection or intravenous injection or infusion, followed by 12 to 15 mg intramuscularly, or 15 mg by mouth, every 6 hours for the next 48 hours. The required dose of RESCUVOLIN and duration of RESCUVOLIN treatment following high dose methotrexate treatment must be determined by regular (every 12 to 24 hours) measurements of the plasma methotrexate concentration. In general monitoring should continue until the plasma methotrexate concentration is below 5 x 10 -8 Molar. A larger dose and or longer administration may be required in patients with aciduria, ascites, dehydration, gastrointestinal obstruction, renal function impairment or pleural effusions because excretion of methotrexate is slowed and the length of time for plasma methotrexate levels to decrease to non-toxic levels is increased. With lower doses of methotrexate, RESCUVOLIN 15 mg by mouth every 6 hours for 48 to 72 hours may suffice. RESCUVOLIN POWDER FOR INJECTION may be reconstituted with sterile water for injection.

Hypersensitivity to folinic acid or any of the ingredients in RESCUVOLIN. Vitamin B 12 deficiency (see WARNINGS AND SPECIAL PRECAUTIONS). RESCUVOLIN is contraindicated in patients with stomach and bowel complaints (vomiting and diarrhoea).

Warnings: RESCUVOLIN should not be used for the treatment of pernicious anaemia or other megaloblastic anaemias secondary to a deficiency of Vitamin B 12. Its use can result in an apparent response of the haematopoietic system, but neurological damage may occur or progress if already present. Special precautions: This medicinal product contains lactose as an excipient, and patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. RESCUVOLIN has no or negligible influence on the ability to drive and use machines.

RESCUVOLIN enhances the toxicity, as well as the antineoplastic action of fluorouracil, especially on the gastro-intestinal tract. RESCUVOLIN may increase the frequency of seizures in susceptible paediatric patients by counteracting the anticonvulsant effects of barbiturates, hydantoin anticonvulsants and primidone.

The safety of this medicine in pregnant and lactating women has not been established.

Immune system disorders: Less frequent: Allergic reactions may occur; pyrexia has occurred after injections. Central nervous system: Less frequent: Seizures have been reported with use in cancer chemotherapy. RESCUVOLIN should never be given alone or in conjunction with inadequate amounts of hydroxycobalamin for the treatment of pernicious anaemia. Gastro-intestinal disorders: Less frequent: High doses of RESCUVOLIN have given rise to gastro-intestinal complaints.

See SIDE EFFECTS. Treatment is symptomatic and supportive.