Folinic acid rescue

LEUCOVORIN. When leucovorin is administered after a large dose of methotrexate, the timing of tiie administration is outlined by tiie primary health care provider. It is essential that the leucovorin be given at tiie exact time ordered because tiie purpose of folinic acid rescue is to allow a high dose of a toxic drug to remain in tiie body for only a limited time... 

Folinic acid rescue—Take this drug at the exact prescribed intervals. If nausea and vomiting, occur, contact the primary health care provider immediately. 

These are pyrimidine derivatives and are effective because of differences in susceptibility between the enzymes in humans and in the infective organism. Anticancer agents based on folic acid, e.g. methotrexate, inhibit dihydrofolate reductase, but they are less selective than the antimicrobial agents and rely on a stronger binding to the enzyme than the natural substrate has. They also block pyrimidine biosynthesis. Methotrexate treatment is potentially lethal to the patient, and is usually followed by rescue with folinic acid (A -formyl-tetrahydrofolic acid) to counteract the folate-antagonist action. The rationale is that folinic acid rescues normal cells more effectively than it does tumour cells. 

Toxic effects common when concentration > 4.5 pg/ml at 24 hours or > 0.45 xg/ml at 48 hours after injection folinic acid rescue is indicated. 

Methotrexate is used widely as a DMARD for rheumatoid arthritis, psoriatic arthritis, and for its steroid-sparing effects in many other conditions, especially if azathioprine is not tolerated. In high dose, with folinic acid rescue, methotrexate is used to treat solid and haematological malignancies (see p. 612). Low dose methotrexate slows the progression of rheumatoid arthritis. The evidence for a true disease-modifying effect on psoriatic arthritis is less definite, but methotrexate is often preferred to other DMARDs for its beneficial effect on the skin lesions. 

Acute lymphocytic leukaemia (ALL) nducii on vincristine + prednisolone + asparaginase z doxorubicin CNS prophyfajeis intrathecal methotrexate with cranial irradiation z systemic high-dose methotrexate with folinic acid rescue intrathecal cytarabine intrathecal hydrocortisone / d<11 fIterance, methotrexate mercapcopurineibone marrow transplant... 

When serum methotrexate concentrations are high, leu-covorin (folinic acid) rescue may protect against renal damage. Methotrexate concentrations are only transiently lowered by hemoperfusion, and they are unaffected by peritoneal dialysis once there is acute renal insufficiency. Sustained reductions in drug concentrations and recovery of renal function have been reported after charcoal hemoperfusion followed by hemodialysis (63,64). 

Central nervous system toxicity is unusual with vinca alkaloids, because they do not readily cross the blood-brain barrier. However, fatal myeloencephalopathy can occur a few hours after accidental intrathecal drug administration (58,59), with severe bilateral leg pain, and over the next 36 hours progressive leg weakness, urinary retention, meningism, fever, and somnolence. Other effects include absence of deep tendon and gag reflexes and disappearance of rectal tone. In spite of high-dose folinic acid rescue, patients became comatose, for example by the fourth day after injection, with loss of brain stem function a few days later. 

Methotrexate (CCS) Antimetabolite—inhibits DHF reductase (S phase) Leukemias, lymphomas, breast CA RA, psoriasis BMS, mucositis, crystal] aria leucovorin (folinic acid) rescue... 

When 2 patients with osteosarcoma, treated with high-dose methotrexate 12 give per course, were given ciprofloxacin 500 mg twice daily, either during or 2 days before the start of the methotrexate course, methotrexate elimination was delayed, resulting in raised serum levels, severe cutaneous toxicity and renal impairment. The first patient also had hepatic injury and haematological toxicity. Following increased folinic acid rescue, methotrexate levels normalised after several days. In earlier courses without ciprofloxacin in the first patient and subsequent courses without ciprofloxacin in the second patient, methotrexate elimination was normal. This preliminary report has subsequently been published in full. ... 

High-dose regimen (with folinic acid rescue) ... 

Intravenous bolus 15 to 60 mg/m s then 15 to 60 mg/m intravenous infusion over 36 hours Dicloxacillin (not stated) (Indometacin ako given) Oesophageal cancer (1) 93% reduction in methotrexate clearance prolonged folinic acid rescue necessary 3... 

The picture is not totally clear but it seems possible that the previous use of cisplatin causes kidney damage that may not necessarily be detectable with the usual creatinine clearance tests, llie effect is to cause a marked reduction in the clearance of the methotrexate. The serum methotrexate levels of such patients should be closely monitored so that any delay in its clearance is detected early and folinic acid rescue therapy can be given. This appears to prevent serious toxicity. " ... 

---