neutrexin- Trimetrexate glucuronate injection, powder, lyophilized, for solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

trimetrexate glucuronate (UNII: L137U4A79K) (trimetrexate - UNII:UPN4ITI8T4)

Available from:

MedImmune Oncology, Inc.

INN (International Name):

Trimetrexate glucuronate

Pharmaceutical form:

INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

Composition:

200 mg in 16 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Neutrexin (trimetrexate glucuronate for injection) with concurrent leucovorin administration (leucovorin protection) is indicated as an alternative therapy for the treatment of moderate-to-severe Pneumocystis carinii pneumonia (PCP) in immunocompromised patients, including patients with the acquired immunodeficiency syndrome (AIDS), who are intolerant of, or are refractory to, trimethoprim-sulfamethoxazole therapy or for whom trimethoprim-sulfamethoxazole is contraindicated. This indication is based on the results of a randomized, controlled double-blind trial comparing Neutrexin with concurrent leucovorin protection (TMTX/LV) to trimethoprim‑sulfamethoxazole (TMP/SMX) in patients with moderate-to-severe Pneumocystis carinii pneumonia, as well as results of a Treatment IND. These studies are summarized below: This double-blind, randomized trial initiated by the AIDS Clinical Trials Group (ACTG) in 1988 was designed to compare the safety and efficacy of TMTX/LV to that of TMP/SMX for the treatment of histol

Product summary:

Neutrexin (trimetrexate glucuronate for injection) is supplied as a sterile lyophilized powder in either 5 mL or 30 mL vials. Each 5 mL vial contains trimetrexate glucuronate equivalent to 25 mg of trimetrexate. Each 30 mL vial contains trimetrexate glucuronate equivalent to 200 mg of trimetrexate. The 5 mL vials are packaged and available in two market presentations as listed below: 10 Pack - 10 vials in a white chip-board carton (NDC 58178-020-10) 50 Pack - 2 trays of 25 vials per shrink-wrapped tray (NDC 58178-020-50) The 30 mL vials are packaged and available as listed below: Single Pack - 1 vial (NDC 58178-021-01) Store at controlled room temperature 20° to 25°C (68° to 77°F). Protect from exposure to light. U.S. Patents 4,376,858; 4,694,007; 6,017,922

Summary of Product characteristics

NEUTREXIN- TRIMETREXATE GLUCURONATE INJECTION, POWDER, LYOPHILIZED,
FOR SOLUTION
MEDIMMUNE ONCOLOGY, INC.
----------
NEUTREXIN (TRIMETREXATE GLUCURONATE FOR INJECTION)
WARNINGS
NEUTREXIN (TRIMETREXATE GLUCURONATE FOR INJECTION) MUST BE USED
WITH CONCURRENT LEUCOVORIN (LEUCOVORIN PROTECTION) TO AVOID
POTENTIALLY SERIOUS OR LIFE-THREATENING TOXICITIES (SEE
PRECAUTIONS AND DOSAGE AND ADMINISTRATION).
DESCRIPTION
Neutrexin is the brand name for trimetrexate glucuronate.
Trimetrexate, a 2,4-diaminoquinazoline, non-
classical folate antagonist, is a synthetic inhibitor of the enzyme
dihydrofolate reductase (DHFR).
Neutrexin is available as a sterile lyophilized powder, containing
trimetrexate glucuronate equivalent to
either 200mg or 25mg of trimetrexate without any preservatives or
excipients. The powder is
reconstituted prior to intravenous infusion (see DOSAGE AND
ADMINISTRATION,
RECONSTITUTION AND DILUTION).
Trimetrexate glucuronate is chemically known as
2,4-diamino-5-methyl-6-[(3,4,5-
trimethoxyanilino)methyl] quinazoline mono-D-glucuronate, and has the
following structure:
The empirical formula for trimetrexate glucuronate is C
H N O • C H O with a molecular weight
of 563.56. The active ingredient, trimetrexate free base, has an
empirical formula of C
H N O with
a molecular weight of 369.42. Trimetrexate glucuronate for injection
is a pale greenish-yellow powder
or cake. Trimetrexate glucuronate is soluble in water (>50 mg/mL),
whereas trimetrexate free base is
practically insoluble in water (<0.1 mg/mL). The pKa of trimetrexate
free base in 50% methanol/water is
8.0. The logarithm of the partition coefficient of trimetrexate free
base between octanol and water is
1.63.
CLINICAL PHARMACOLOGY
MECHANISM OF ACTION
®
19
23
5
3
6
10
7
19
23
5
3
10
_In vitro_ studies have shown that trimetrexate is a competitive
inhibitor of dihydrofolate reductase
(DHFR) from bacterial, protozoan, and mammalian sources. DHFR
catalyzes the reduction of
intracellular dihydrofolate to the active coenzyme tetrahydrofolate.
Inhibition