atopoietic system that are inherited, acquired, or resulted from myeloablative treatment. [See Dosage and Administration (2), Adverse Reactions (6), and Clinical Studies (14)]
8.5 Geriatric Use
Clinical studies of HPC-C did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently to HEMACORD than younger subjects. In general, administration of HEMACORD to patients over age 65 should be cautious, reflecting their greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
8.6 Renal Disease
HEMACORD contains Dextran 40 which is eliminated by the kidneys. The safety of HEMACORD has not been established in patients with renal insufficiency or renal failure.
10 OVERDOSAGE
10.1 Human Overdosage Experience
There has been no experience with overdosage of HPC-C in human clinical trials. Single doses of HEMACORD up to 57.6 x 107 TNC/kg have been administered. HPC-C prepared for infusion may contain dimethyl sulfoxide (DMSO). The maximum tolerated dose of DMSO has not been established, but it is customary not to exceed a DMSO dose of 1 gm/kg/day when given intravenously. Several cases of altered mental status and coma have been reported with higher doses of DMSO.
10.2 Management of Overdose
For DMSO overdosage, general supportive care is indicated. The role of other interventions to treat DMSO overdosage has not been established.
11 DESCRIPTION
HEMACORD consists of hematopoietic progenitor cells, monocytes, lymphocytes, and granulocytes from human cord blood. Blood recovered from umbilical cord and placenta is volume reduced and partially depleted of red blood cells and plasma.
The active ingredient is hematopoietic progenitor cells which express the cell surface marker CD34. The potency of cord blood is determined by measuring the numbers of total nucleated cells (TNC) and CD34+ cells, and cell viability. Each unit of HEMACORD contains a minimum of 5 x 108 total nucleated cells with at least 1.25 x 106 viable CD34+ cells at the time of cryopreservation. The cellular composition of HEMACORD depends on the composition of cells in the blood recovered from the umbilical cord and placenta of the donor. The actual nucleated cell count, the CD34+ cell count, the ABO group, and the HLA typing are listed on the container label and/or accompanying records sent with each individual unit.
HEMACORD has the following inactive ingredients: dimethyl sulfoxide (DMSO) and Dextran 40. When prepared for infusion according to instructions, the infusate contains the following inactive ingredients: Dextran 40, human serum albumin, and residual DMSO.
12. CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
Hematopoietic stem/progenitor cells from HPC-C migrate to the bone marrow where they divide and mature. The mature cells are released into the bloodstream, where some circulate and others migrate to tissue sites, partially or fully restoring blood counts and function, including immune function, of blood-borne cells of marrow origin. [See Clinical Studies (14)]
In patients with enzymatic abnormalities due to certain severe types of storage disorders, mature leukocytes resulting from HPC-C transplantation may synthesize enzymes that may be able to circulate and improve cellular functions of some native tissues. However, the precise mechanism of action is unknown.
14 CLINICAL STUDIES
The effectiveness of HPC-C, as defined by hematopoieti |
