Interacting drugs- summary

Leucovarin + Anticonvulsants decrease  folic acid in large amounts counteract the antiepileptic effect of phenobarbital, phenytoin and primidone and increase the frequency of seizures in susceptible children.

 Consider the possibility when using these drugs concomittantly

5-Fluorouracil -  leucovorin may enhance the toxicity of 5-FU 

Methotrexate-  small quantites of systemically administered leucovorin enter the CSF primarily as 5-methyltertrahydrofolate and remain 1 to 3 orders of magnitude lower than the usual MTX concentrations following intrathecal administration.

However, high doses of leucovorin may reduce the efficacy of intrathecally administerd MTX 

Reduces methoxtrexate toxicity. Enhances cytotoxic effect of fluorocil. Should not be co-administered with a folic acid antagonist.

After high dose methotrexate therapy in osteosarcoma

Allergic sensitization, nausea, vomiting, pyrexia.

Others reported- Leukopenia, thrombocytoipenia, infection, nausea, vomiting, diarrhea, stomatitis, constipation, lethargy/malaise/fatigue alopecia, dematitis, anorexia, hospitilization for toxicity

Hypersens Special precautions:

Undiagonosed megaloblastic anaemia, folate dependent tumors. Parentral administartion- preferable to ral dosin it there is a possibility that may patient may vomit or not absorb the leukovorin.

Monitoring-

obtain a CBC with differential and platelets prior to eacxh treatment with leucovorin/5-FU combination.

Warnings- Anemia- leucovorin is improper therapy for pernicious anemia and other megaloblastic anemia secondary to lack of Vitamin B12.

5-Flurouracil dosage toxicity - leucovorin enhances the toxicity of 5-FU , when these drugs are administered concurrently.

Administer the combination for use of colrectal cancer under the supervision of a physician expereienced in the use of antimetabolite cancer therapy.

Take particular care in the treatment of elderly or debilitated colorectal cancer patients,as these patients may be at increased risk of severity.

Mothotrexate concentrations- monitoring of serum MTX concentration is essential in detremining the optimal dose and duration of treatment of leukovorin.

Calcium content- because of the calcium content of the leucovorin solution, inject no more than 160mg/min IV of a 10mg/ml or 8ml of a 20mg/ml solution per minute.

Folic acid antagonist overdosage- in the accidental overdosage of folic acid antagonists (eg pyramethamine,trimethoprim ) administer leucovorin as promptly as possible.

Pregnancy- give to pregnant woman only if clearly needed.

Lactation- excercise caution when administering to a nursing woman.

Indications:

After high dose methotrexate therapy in osteosarcoma

Dosage:

Oral - doses more than 25mg is not recommended.

Overdosage

Excessive amounts of leucovorin may nullify the chemotherapeutic effect of folic acid antagonists eg. pyrimethamine , trimethoprim.

Missed dose

1. If you miss a dose of this medicine, or vomit after taking the dose,check with your doctor right away.

2. Your doctor may want you to to take extra leucovorin to make up for what you missed

3. Do not take more medicine on your own,however since it is very important that you just receive the right dose at the right time.

Pharmacology

Leucovorin is one of the several active chemically reduced derivatives of folic acid.it is useful as an antidote to drugs which as folic acid antagonists. Administratin of leucovorin can counteract the therapeutic and toxic effects of folic acid antagonists such as methotrexate MTX which act by inhibiting dihydrofolate reductase.

Pharmacokinetics

Following oral administratin of leucovorin israpidly absorbed and expands the serum pool of reduced folates. At a dose of 25mg almost 100%of I-isomer but only 20% of d-iosmer is absorbed.

Pregnancy

Give to pregnant woman only if clearly needed.

Lactation

Excercise caution when administering to a nursing woman.