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Aclarubicin

(British Approved Name, US Adopted Name, rINN)

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

AclarubicinSynonyms: Aclacinomycin A; Aclarubicinum; Aklarubicin; Aklarubisiini; NSC-208734
BAN: Aclarubicin
USAN: Aclarubicin
INN: Aclarubicin [rINN (en)]
INN: Aclarubicina [rINN (es)]
INN: Aclarubicine [rINN (fr)]
INN: Aclarubicinum [rINN (la)]
INN: Акларубицин [rINN (ru)]
Chemical name: Methyl (1R,2R,4S)-4-(O-{2,6-dideoxy-4-O-[(2R,6S)-tetrahydro-6-methyl-5-oxopyran-2-yl]-αl-lyxo-hexopyranosyl}-(1→4)-2,3,6-trideoxy-3-dimethylamino-l-lyxo-hexopyranosyloxy)-2-ethyl-1,2,3,4,6,11-hexahydro-2,5,7-trihydroxy-6,11-dioxonaphthacene-1-carboxylate
Molecular formula: C42H53NO15 =811.9
CAS: 57576-44-0
ATC code: L01DB04

Description. Aclarubicin is an anthracycline antineoplastic antibiotic isolated from Streptomyces galilaeus.

Aclarubicin Hydrochloride

(British Approved Name Modified, US Adopted Name, rINNM)

Drug Nomenclature

BAN: Aclarubicin Hydrochloride [BANM]
INN: Aclarubicin Hydrochloride [rINNM (en)]
INN: Hidrocloruro de aclarubicina [rINNM (es)]
INN: Aclarubicine, Chlorhydrate d’ [rINNM (fr)]
INN: Aclarubicini Hydrochloridum [rINNM (la)]
INN: Акларубицина Гидрохлорид [rINNM (ru)]
Molecular formula: C42H53NO15,HCl =848.3
CAS: 75443-99-1
ATC code: L01DB04

Pharmacopoeias. In Japan.

Stability. In a study of the stability of anthracycline antineoplastic agents in 4 infusion fluids — glucose 5%, sodium chloride 0.9%, lactated Ringer’s injection, and a commercial infusion fluid — stability appeared to be partly related to pH; aclarubicin was most stable in sodium chloride injection, with a pH of 6.2, and any increase or decrease in pH appeared to affect stability adversely.

Adverse Effects, Treatment, and Precautions

As for Doxorubicin Hydrochloride. Alopecia and cardiotoxicity may be less pronounced than with doxorubicin, and extravasation of aclarubicm causes less local tissue inflammation. Bone-marrow depression is dose-limiting, with platelet counts reaching a nadir 1 to 2 weeks after dosage, while leucopenia is greatest after 2 to 3 weeks; recovery generally occurs within 4 weeks. Myelosuppression may be particularly severe in patients who have received mitomycin or a nitrosourea.

Incidence of adverse effects

An early review noted that a strikingly high incidence of ECG changes had been seen with aclarubicm, but that although acute cardiotoxicity occurred, the chronic cardiomyopathy classically associated with the anthracyclines appeared to be rare. Alopecia was also rare, although gastrointestinal disturbances and mucositis were as common or more common than with doxorubicin.

Pharmacokinetics

Aclarubicm is rapidly distributed into tissues after intravenous injection. Clearance is triphasic, with a terminal elimination half-life of about 3 hours; the principal active metabolite has a terminal half-life of about 13 hours. Aclarubicm is extensively metabolised and only about 1 % of the total dose is eliminated unchanged. It is excreted in urine, chiefly as metabolites; some is also eliminated in bile.

Uses and Administration

Aclarubicm is an anthracycline antibiotic with antineoplastic actions similar to those of the other anthracyclines (see Doxorubicin Hydrochloride), although it inhibits RNA synthesis more strongly than DNA synthesis. It has been used as the hydrochloride in the treatment of malignant blood disorders, such as acute myeloid leukaemia. Aclarubicm hydrochloride 104 mg is equivalent to about 100 mg of aclarubicm. The usual initial dose as a single agent has been the equivalent of 175 to 300 mg/m of aclarubicm, divided over 3 to 7 consecutive days, as intravenous infusions over 30 to 60 minutes.

Where appropriate and tolerated, maintenance doses of the equivalent of 25 to 100 mg/m may be given as a single infusion every 3 to 4 weeks. The total dose that can be given over the patient’s life-time depends upon cardiological status but most patients have not received more than 400 mg/m. Dosages may need to be reduced when given as part of a combination regimen.

An early review of studies in patients with relapsed acute myeloid leukaemia confirmed the activity of aclarubicm, with reported complete remission rates of the order of 12 to 24%. Doses varied from 10 to 30 mg/m daily to higher doses of 75 to 120 mg/m for 2 to 4 days; in general a total dose of about 300 mg/m appeared to be necessary to induce remission. Less information was available concerning activity in acute lymphoblastic leukaemia, but response rates were lower than those in acute myeloid leukaemia. Results in the malignant lymphomas were generally disappointing.

Longer-term follow-up has confirmed that remission rates and survival are similar for induction regimens in acute myeloid leukaemia using either aclarubicin or daunorubicin.

Single-ingredient Preparations

The symbol ¤ denotes a preparation which is discontinued or no longer actively marketed.

Austria: Aclaplastin¤;
France: Aclacinomycine¤;
Germany: Aclaplastin¤;
United Kingdom: Aclacin¤

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