Flutamide

276.21

276.21

236-341-9

76W6J0943E

757817|147834|215876

DTXSID7032004

C509

L02BB01|L - Antineoplastic and immunomodulating agents

29242990

74.9

3.3

Solid

1.3649 (estimate)

110-111 °C

400.3±45.0 °C(Predicted)

195.9±28.7 °C

1.521

>41.4 [ug/mL]

Store at RT

160 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

NONH for all modes of transport

3

20/21/22-63-36/37/38

22-36-36/37/39-27-26

UG5700000

Xn,Xi

Stable at normal temperatures and pressures.

P261-P280-P301 + P312 + P330

H302 + H312 + H332-H361

|Warning|H302 (92.9%): Harmful if swallowed [Warning Acute toxicity, oral]|P201, P202, P261, P264, P270, P271, P280, P281, P301+P312, P302+P352, P304+P312, P304+P340, P308+P313, P312, P322, P330, P363, P405, and P501|Aggregated GHS information provided by 155 companies from 13 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|Danger|H361: Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]|P201, P202, P260, P264, P270, P273, P281, P308+P313, P314, P391, P405, and P501

In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.

Chronic therapy with flutamide is associated with elevations in serum aminotransferase levels in up to 62% of patients, but marked elevations (above 5 times ULN) in only 3% to 5%. Most of these abnormalities are transient, asymptomatic and do not require dose adjustment or drug discontinuation. However, in 0.1% to 1% of patients, acute liver injury with symptoms and jaundice arises which can be prolonged, severe and even fatal. The latency of onset ranges widely from 1 to 10 months, averaging 3 months. Allergic manifestations are rare as are autoantibodies. The pattern of liver enzyme elevations is most commonly hepatocellular, but many cases with cholestatic and mixed patterns have been described. Liver failure with a requirement for emergency liver transplantation or fatality has been described in many publications with 20 fatal cases reported from the FDA MedWatch program during the first 5 years of its availability. Fatal cases have been reported in children and young women being treated for hirsutism or acne (Case 1).

94-96%

For the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate|FDA Label|Drug: Flutamide

Flutamide is a nonsteroidal antiandrogen that acts by binding to and blocking intracellular androgen receptors in target tissues including testes, prostate, skin, and hair follicle. Flutamide is frequently associated with minor serum aminotransferase elevations and has been linked to numerous cases of acute liver injury, which are frequently severe and can be fatal.

Antineoplastic Agents

Flutamide is a nonsteroidal antiandrogen. In animal studies, flutamide demonstrates potent antiandrogenic effects. It exerts its antiandrogenic action by inhibiting androgen uptake and/or by inhibiting nuclear binding of androgen in target tissues or both. Prostatic carcinoma is known to be androgen-sensitive and responds to treatment that counteracts the effect of androgen and/or removes the source of androgen, e.g. castration. Elevations of plasma testosterone and estradiol levels have been noted following flutamide administration.

Compounds which inhibit or antagonize the biosynthesis or actions of androgens. (See all compounds classified as Androgen Antagonists.)|Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079) (See all compounds classified as Antineoplastic Agents, Hormonal.)

Rapidly and completely absorbed.|Flutamide and its metabolites are excreted mainly in the urine with only 4.2% of a single dose excreted in the feces over 72 hours.

Flutamide is rapidly and extensively metabolized, with flutamide comprising only 2.5% of plasma radioactivity 1 hour after administration.|Flutamide has known human metabolites that include 2-hydroxy-flutamide.

The plasma half-life for the alpha-hydroxylated metabolite of flutamide (an active metabolite) is approximately 6 hours.

Flutamide is a nonsteroidal antiandrogen that blocks the action of both endogenous and exogenous testosterone by binding to the androgen receptor. In addition Flutamide is a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen.

Apimid

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients