ii. Folinic acid (as calcium salt in water) 

50mg/ampoule: injection 10 amps pack: 4700.00 TP (Price could not be revised).

Levofolinate is the pharmacologically active isomer of 5-formyltetrahydrofolic acid. It is available as levofolinic acid (as calcium salt) BP 25mg in 2.5ml vial: solution for injection.

Mode of action: Levofolinate does not require reduction by the enzyme dihydrofolate reductase in order to participate in reactions utilising folates as a source of “one carbon” moieties. Levofolinate is actively and passively transported across cell membranes. Administration of levofolinate can “rescue” normal cells and thereby prevent toxicity of folic acid-antagonists such as methotrexate which act by inhibiting dihydrofolate reductase. Levofolinate can enhance the therapeutic and toxic effects of fluoropyrimidines used in cancer therapy such as 5-fluorouracil. 5-fluorouracil is metabolised to 5- fluoro-2’ deoxyuridine-5’ monophosphate (FDUMP), which binds to and inhibits thymidylate synthase. Levofolinate is readily converted to another reduced folate, 5, 10- methylenetetrahydrofolate, which acts to stabilise the binding of FDUMP to thymidylate synthase & thereby enhances the inhibition of this enzyme. Ind: Levofolinic acid is indicated- i. to diminish the toxicity and counteract the action of folic acid antagonists such as methotrexate in cytotoxic therapy & overdose in adults and children; ii. to increases the thymine depleting effects of 5-FU resulting in enhanced cytotoxic activity. Combination regimens of 5-fluorouracil & levofolinate give greater efficacy compared to 5- FU given alone.

C/I: Known hypersensitivity to calcium levofoli¬nate or to any components of the excipients. Calcium levofolinate should not be used for the treatment of pernicious anemia or other megalo¬blastic anemias due to vitamin Bl2 deficiency. S/E: Very common: Vomiting and nausea, diarrhoea. Uncommon: Anaphylactoid/ anaphylactic reactions (including shock).

Rare: Insomnia, agitation and depression. Precautions: Please see the manufacturer’s literature.

Pregnancy & lactation: There are no adequateand well controlled clinical studies conducted in pregnant or breast feeding women. Calcium levofolinate may be excreted in human milk and should only be administered where the benefits of the drug to the mother outweigh possible hazards to the infant.

Dosage & admin: For single use only,

Adults, children & the elderly:

Calcium levofolinate therapy should commence 24 hours after the beginning of methotrexate infusion. Dosage regimen vary depending upon the dose of methotrexate administered.

In general, the calcium levofolinate should be administered at a dose of 7.5mg (approximate¬ly 5mg/m2) every 6 hours for 10 doses by i.m injection, bolus i.v injection or i.v infusion. Where overdose of methotrexate is suspected, the dose of calcium levofolinate should be at least 50% of the offending dose of methotrex¬ate and should be administered in the first hour. In the case of i.v administration, no more than 160mg of calcium levofolinate should be injected per minute due to the calci¬um content of the solution. In addition to cal¬cium levofolinate administration, measures to ensure the prompt excretion of methotrexate are important as part of calcium levofolinate rescue therapy. These measures include:

a. Alkalinisation of urine so that the urinary pH is greater than 7,0 before methotrexate infusion (to increase solubility of methotrexate and its metabolites).

b. Maintenance of urine output of 1800- 2000ml/m2/24 hours by increased oral or intravenous fluids on days 2, 3 and 4 following methotrexate therapy.

c. Plasma methotrexate concentration, BUN and creatinine should be measured on days 2,

3 & 4,

These measures must be continued until the plasma methotrexate level is less than 10-7 molar (0.1 jiM).

Based on the available clinical evidence, the following regimen is effective in advanced colorectal carcinoma; Calcium levofolinate given at a dose of 100mg/m2 by slow i.v injection, followed immediately by 5-FU at an initial dose of 370mg/rn2 by i.v injection. The injection of levofolinate should not be given more rapidly than over 3 minutes because of the calcium content of the solution. This treatment is repeated daily for 5 consecutive days. Subsequent courses may be given after a treatment-free interval of 21-28 days. For the above regimen, modification of the 5-FU dosage and the treatment-free interval may be necessary depending on patient condition, clinical response and dose limiting toxicity. Children: There are no data available on the use of this combination in children. Administration: Do not administer calcium levofolinate intrathecally.

The 175mg in 17.5ml vial of calcium levofoli¬nate solution for injection should be used to administer the high doses of calcium levofoli¬nate required in combination regimens. When used in combination regimens with 5-FU, cal¬cium levofolinate should only be given by the i.v route. Each vial of calcium levofolinate (175mg) contains 0.7mEq (0.35 mmol) of calci¬um per vial and it is recommended that the solution is administered over not less than 3 minutes. For i.v infusion, the 175mg in 17.5ml solution for injection may be diluted with any of the following infusion fluids before use. Sodium chloride 0.9%; glueose 5%; glucose 10%; glucose 10% and sodium chloride 0.9% injection; compound sodium lactate injection. Calcium levofolinate should not be mixed together with 5-FU in the same infusion and, because of the risk of degradation, the giving set should be protected from light.

Drug inter: When calcium levofolinate is given in conjunction with a folic acid antagonist (e g cotrimoxazole, pyrimethamine), the efficacy of the folic acid antagonist may either be reduced or completely neutralised. Calcium levofolinate may diminish the antiepileptic effect of phenobarbital, phenytoin, primidone and succinimides, and may increase the frequency of seizures in susceptible patients.

Price: 25mg (2.5ml) vial x l’s pack: 430.00 IP