Pfizer Limited

Calcium levofolinate should not be mixed together with 5‑FU in the same intravenous injection or infusion.

In addition to 5-FU, iIncompatibilities have also been reported between injectable forms of calcium levofolinate and injectable forms of droperidol, foscarnet and methotrexate.

Discard any unused product.

Text relocated to section 6.6: 

When ISOVORIN Solution for Injection is diluted with the recommended infusion fluids, the resulting solutions are intended for immediate use but may be stored for up to 24 hours under refrigerated conditions (2 – 8 °C).  Because of the risk of degradation, reconstituted solutions should be protected from light prior to use if necessary.

Type I amber glass vials each containing the equivalent of 25 mg, 50 mg or 175 mg of calcium levofolinate in 2.5 ml, 5 ml or 17.5 ml of solution respectively. Isovorin ISOVORIN Solution for Injection is packed in boxes of 1 vial.

For intravenous infusion, calcium levofolinate may be diluted with 0.9% sodium chloride solution or 5% glucose solution before use.

For intravenous infusion, the 175 mg in 17.5 ml Solution for Injection may be diluted with any of the following infusion fluids before use: Sodium Chloride 0.9%; Glucose 5%; Glucose 10%; Glucose 10% and Sodium Chloride 0.9% Injection; Compound Sodium Lactate Injection.

When ISOVORIN Solution for Injection is diluted with the recommended infusion fluids, the resulting solutions are intended for immediate use but may be stored for up to 24 hours under refrigerated conditions (2 - 8ºC).  Because of the risk of degradation, reconstituted solutions should be protected from light prior to use if necessary.

Prior to administration, calcium levofolinate should be inspected visually. The solution for injection or infusion should be a clear and yellowish solution. If cloudy in appearance, or if particles are observed, the solution should be discarded. Calcium levofolinate solution for injection or infusion is intended only for single use.

Any unused product or waste material should be disposed of in accordance with local requirements.

• In section 4.4 (Special warnings and precautions for use), new paragraphs have been added and information expanded on Calcium levofolinate
• In section 4.5 (Interaction with other medicinal products and other forms of interaction), interactions with Calcium levofolinate have been detailed
• In section 4.8 (Undesirable effects), changed to table template with additions
• In section 4.9, (Overdose ) information on antidote changed

Known hypersensitivity to calcium levofolinate, or to any components of the excipients.

Calcium levofolinate should not be used for the treatment of pernicious anaemia or other megaloblastic anaemias where due to vitamin B₁₂ is deficient deficiency.

Regarding the use of calcium levofolinate with methotrexate or 5-FU during pregnancy and lactation, see section 4.6, and the Summaries of Product Characteristics for methotrexate and 5-FU-containing medicinal products.

Reproduction studies have been performed in rats and rabbits at doses of at least 50 times the human dose.  These studies have revealed no evidence of harm to the foetus due to calcium levofolinate.  There are, however, no adequate and well controlled studies in pregnant women.  Because animal reproduction studies are not always predictive of human response, calcium levofolinate should only be used in pregnant women if the potential benefit justifies the potential risk to the foetus.

It is not known whether calcium levofolinate is excreted in human milk.  Because many drugs are excreted in human milk, caution should be exercised when calcium levofolinate is administered to a nursing mother.

There are no adequate and 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. Calcium levofolinate can be used during breast-feeding when considered necessary according to the therapeutic indications.

None.

There is no evidence that calcium levofolinate has an effect on the ability to drive or use machines.

18 March 2008  17 March 2009

In Section 1 - "10mg/ml" has been added

In section 4.8 - The word "cheilitis" has been added

In Section 6.3 - Has been changed from 24 months to 2 years

Section 9 - The Renewal date format only has been changed from 12/6/1998 to 12 June 1998