Myleran (busulfan)

The manufacturer suggests the use of therapeutic drug monitoring to adjust the dosage of IV busulfan in children following administration of the initial dose.

The busulfan AUC should be calculated based on blood samples collected at specified time points; actual sampling times should be recorded. When measuring serum busulfan concentrations with the initial dose of the drug, blood samples should be collected at 2 hours (the end of the infusion), 4 hours, and 6 hours (immediately prior to the next scheduled busulfan dose). For doses other than the first dose, blood samples should be collected prior to the infusion (baseline), and then at 2 hours (the end of the infusion), 4 hours, and 6 hours (immediately prior to the next scheduled busulfan dose). Calculations based on fewer samples than specified may result in inaccurate AUC determinations.

Special instructions for drug administration and blood sample collection should be followed to ensure accurate therapeutic drug monitoring. An administration set with minimal residual hold-up (priming) volume (1-3 mL) should be used for drug infusion to ensure accurate delivery of the entire prescribed dose and to ensure accurate collection of blood samples for the measurement of serum busulfan concentrations. The administration set tubing should be primed with drug solution to allow accurate documentation of the start time of the busulfan infusion. The blood sample should be collected from a peripheral IV line to avoid contamination with the infusing drug solution. If the blood sample is taken directly from the existing central venous catheter, it is important that the blood samplenot be collected while the drug is infusing to ensure that the end of the infusion sample is not contaminated with any residual drug. At the end of the infusion (2 hours), the administration tubing should be disconnected and the central venous catheter line should be flushed with 5 mL of normal saline prior to the collection of the blood sample from the central venous catheter port. The blood samples should be collected from a different port than that used for the busulfan infusion. The time required to flush the indwelling catheter line should not be included when recording the busulfan infusion stop time. The administration tubing should be discarded at the end of the 2-hour infusion.

Collection of the blood samples should be performed by collecting 1-3 mL of blood into heparinized (Na or Li heparin) Vacutainer(R) tubes. The blood samples should be placed on wet ice immediately after collection and should be centrifuged (at 4degreesC) within 1 hour. The plasma should be harvested into appropriate cryovial storage tubes and frozen immediately at -20degreesC. All plasma samples should be sent in a frozen state (i.e., on dry ice) to the assay laboratory for the determination of plasma busulfan concentrations.

Busulfan AUC following the initial dose may be calculated using the following equation where AUC0-6hr is estimated using the linear trapezoidal rule and AUCextrapolated is the ratio of the busulfan concentration at hour 6 and the terminal elimination rate constant, lambdaz. The terminal elimination rate constant must be calculated from the terminal elimination phase of the busulfan concentration versus time curve. A pre-dose busulfan concentration of zero is assumed and should be used in calculating the AUC.

When busulfan AUC for dose 1 has been calculated, the following formula may be used for the adjustment of subsequent busulfan doses to achieve the target busulfan AUC of 1125 mcM*minute:

For the determination of AUC following subsequent doses of IV busulfan, determination of steady-state busulfan AUC (AUC0-6hr) should be estimated from the trough, 2 hour, 4 hour, and 6 hour concentrations using the linear trapezoidal rule.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

Additive myelosuppression may occur with concomitant administration of busulfan with other myelosuppressive agents. In addition, additive pulmonary toxicity may occur when busulfan is administered in combination with other cytotoxic agents.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

No enhanced messaging available.

Busulfan may cause fetal harm when administered to pregnant women, but potential benefits from use of the drug may be acceptable in certain conditions despite the possible risks to the fetus. Fetal malformation early in pregnancy, bone marrow depression late in gestation, fetal growth retardation, and fetal deaths have been reported in pregnant women who received therapeutic doses of busulfan or other alkylating agents. Mild anemia and neutropenia were present in one neonate whose mother had received busulfan from the eighth week of pregnancy until parturition.

Busulfan has been shown to be teratogenic in mice, rats, and rabbits; teratogenic effects included abnormalities in the musculoskeletal system, body weight, and size. Sterility in male and female offspring secondary to an absence of germinal cells in the testes and ovaries also was observed in reproduction studies in rats.

Dimethylacetamide (DMA), the solvent used in commercially available busulfan for injection concentrate, also may cause fetal harm when administered to pregnant women. When administered to pregnant rats at a dose of 400 mg/kg daily (about 40% of the amount present on a mg/m2 basis in the recommended daily dose of IV busulfan), dimethylacetamide caused developmental abnormalities, including anasarca, cleft palate, vertebral anomalies, rib malformation, and serious anomalies of the vessels of the heart.

There are no adequate and well-controlled studies using busulfan or dimethylacetamide in pregnant women. Busulfan should be used during pregnancy only in conditions such as life-threatening situations or severe disease for which safer drugs cannot be used or are ineffective. Women of childbearing potential should be advised to avoid becoming pregnant during busulfan therapy. If the drug is administered during pregnancy or if the patient becomes pregnant while receiving the drug, the patient should be informed of the potential hazard to the fetus.

It is not known whether busulfan is distributed into milk. Because of the potential for serious adverse reactions from busulfan in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No enhanced messaging available.