Calcium Folinate

Registered South African indications:

• Antidote to folic acid antagonists

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pernicious anaemia
• Megaloblastic anaemias where vitamin B12 is deficient
• Galactose intolerance (tab)
• Lapp lactase deficiency (tab)  
• Glucose-galactose malabsorption (tab)
• Lactose allergy (tab)

Cautions

• Pregnancy
• Breastfeeding
• Elderly
• Patients with a low physical performance due to illness
• Excessive calcium folinate doses
• Pre-existing or methotrexate-induced renal insufficiency
• Do not administer intrathecally (inj) 

Forms avail. in SA and covered in this monograph: tab, inj

Folinic acid rescue

Depending upon the dose of methotrexate administered, dosage regimens of calcium folinate vary

• IV/IM: 15 mg (6-12 mg/m²), 6hrly, for 72 hrs

Dose to be given 12-24 hours (24 hours at the latest) after the beginning of the methotrexate infusion

Followed by

• IM: 12-15mg, 6hrly, for 48hrs

OR

• Oral (tab): 15mg, 6hrly, for 48hrs

48hrs after the start of the methotrexate infusion, the residual methotrexate-level should be measured. If the residual methotrexate-level is > 0.5µmol/l, calcium folinate dosages should be adapted according to the following table: 

Advanced or metastatic colorectal cancer

• Consult specialist for dosages

Calcium folinate should not be administered intrathecally

See additional prescribing points

Forms avail. in SA and covered in this monograph: tab, inj

Folinic acid rescue

• See adult dosage

Pregnancy

• Caution
• 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 folinate. There are, however, no adequate and well-controlled studies in pregnant women
• Because animal studies are not always predictive of human response, calcium folinate should only be used in pregnant women if the potential benefit justifies the potential risk to the foetus

Breastfeeding

• Caution
• It is unknown if calcium folinate is distributed into breastmilk; therefore it should be used with caution in breastfeeding women

Renal Impairment

• Caution; no information available 

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no dose adjustment recommended

Porphyria Information

• Not porphyrinogenic (NP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Agitation
• Depression
• Increased seizure frequency (epileptics)

Immune, Blood and Lymphatic System Disorders

• Allergic reactions
• Anaphylactoid reactions
• Urticaria

Others

• Fever

• Folic acid antagonists
• Cotrimoxazole
• Pyrimethamine
• Phenobarbitone
• Phenytoin
• Primidone
• Fluoropyrimidine
• Succinimides 
• 5-Fluorouracil 

None routine

Excretion of methotrexate as part of folinic acid rescue 

• Measures to ensure the prompt excretion of methotrexate are important as part of folinic acid rescue. These measures include:
  - Alkalinisation of urine so that the urinary pH is >7.0 before methotrexate infusion
  - Maintenance of urine output of 1800-2000 ml/m²/24 hr by increased oral or IV fluids on days 2, 3 and 4 following methotrexate therapy
  - Plasma methotrexate concentration, BUN and creatinine should be measured on days 2, 3 and 4
  - These measures must be continued until the plasma methotrexate level is less than 10^-7 molar (0.1μM)

Special precautions for handling (inj)

• From a microbial point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally mot be longer than 24 hours at 2 to 8°C
• Prior to administration, calcium folinate should be inspected visually. The solution for injection or infusion should be a clear and yellowish solution. If cloudy in appearance or particles are observed, the solution should be discarded

Incompatibilities (inj)

• Incompatibilities have been reported between injectable forms of calcium folinate and injectable forms of droperidol, fluorouracil, foscarnet and methotrexate

Folinate is a derivative of tetrahydrofolic acid, the reduced form of folic acid, which is involved as a cofactor for 1-carbon transfer reactions in the biosynthesis of purine and pyrimidines of nucleic acids. It is postulated that folinate enters and "rescues" normal cells from the toxic effects of folic acid antagonists, in preference to tumour cells, because of a difference in membrane transport mechanisms. 

Tablet 15mg

• Rescuvolin (Cipla)
• Rescuvolin (Teva Pharmaceuticals)

Injection (per ml) 10mg

• Leucovorin-Faulding (Pharmaplan)

Injection (per vial) 50mg

• Rescuvolin (Cipla)

Injection (per 10ml) 100mg

• Abic leucovorin (Teva)

Injection (per 20ml) 200mg

• Abic leucovorin (Teva)

Injection (per 30ml) 300mg

• Abic leucovorin (Teva)