· Breast carcinomas.

· Sarcoma of the bones and soft parts.

· Hodgkin's disease, non-Hodgkin's lymphoma.

· Solid tumors of the child.

· Lung cancers.

· Acute and chronic leukemias.

· Cancers of the bladder, ovary, stomach.

The mean dosage is from 40 to 75 mg / m 2 per cycle.
Each cycle is separated from the previous cycle by an interval of 3 to 4 weeks Cycles are repeated up to a maximum total dose of 550 mg / m 2. >
The dose of Adriblastin should be injected within 3 to 5 minutes in the tubing, venous perfusion of sodium chloride solution, 0.9% isotonic or 5% glucose solution, Br>

· Or in a single time

· Or in twice during the day

· Be spread over 2 or 3 days.

It is not necessary to carry out a long perfusion, which can be installed shortly before the administration of Adriblastine and stopped a few minutes after.

ATTENTION

It is extremely important to ensure that the administration is endovenous. Any extravasation could produce necrosis of the surrounding tissues. In this case, the injection should be discontinued immediately.

Modalities of handling

The preparation of injectable cytotoxic solutions must be carried out by specialized and trained personnel with knowledge of the medicines used, under conditions ensuring the protection of the environment and especially the protection of the personnel who handle them. It requires a preparation room reserved for this purpose. It is forbidden to smoke, eat or drink in this room.) Handlers must have a set of equipment suitable for handling including blouses, long sleeves, protective masks, cap, goggles, gloves Single use, sterile, work area protection, containers and garbage collection bags. Excreta and vomit should be handled with care. Pregnant women should be warned and avoid the manipulation of cytotoxics. Any broken container shall be treated with the same precautions and considered as contaminated waste The disposal of the contaminated waste is carried out by incineration in rigid containers labeled for this purpose

These provisions may be considered within the framework of the Cancerology Network (Circular DGS / DH / 98 No. 98/188 of 24 March 1998) in collaboration with any suitable and meeting the requirements. >

No information in the marketing authorization.

Pharmacotherapeutic group: ANTHRACYCLINES AND RELATIVES

ATC code: L01DB01.

Cytostatic antineoplastic agent, antibiotic of the anthracycline family

Basic studies have shown that doxorubicin rapidly binds to the nuclear structures of the cell, blocking the synthesis of A.D.N. And A.R.N. As an intercalating agent, at the level of the A.D.N.

The effects on the ability to drive and use machines have not been studied. However, on the basis of reported adverse reactions (including nausea, vomiting, ECG changes, electrolytic disorders), patients should be warned not to drive and not use machinery without prior notice A health professional.

· Its prescription should be avoided in subjects with cardiac disease with myocardial insufficiency

· Pregnancy.

· Breastfeeding.

· Yellow fever vaccine: risk of vaccine disease, generalized fatal

Special warnings

Strict haematological and cardiac monitoring should enable effective control of possible toxic changes

· ADRIBLASTINE in injectable form administered intravenously, strictly

Precautions for use

· It seems essential to reduce doses in subjects with severe hepatic insufficiency: in these subjects, indeed, the blood levels of Adriblastin and the plasma half-life of this product are increased, Increase in side-effects (then administer 15 to 30 mg / m 2 every 4 weeks).
· Dose administration in one injection reduces considerably the incidence of stomatitis

· The spacing of the cycles by an interval of 3 or 4 weeks allows the repair of blood cells and cells, immune-competent

· Compliance with the maximum total dose of 550 mg / m 2 limits the occurrence of congestive myocarditis

It is evident, however, that the number, blood count, and electrocardiogram should be monitored regularly before each cycle (Cardiovascular assessment should be carried out before administration of the product, especially in subjects subjected to it; To thoracic radiotherapy).

· Cytolysis causes hyperuricemia to be monitored and prevented

· Certain leukemias secondary to anti-cancer agents (see section 4.4) may be curable, provided early and appropriate management. Accordingly, any patient treated with doxorubicin should be monitored hematologically.


Doxorubicin is mainly used in combination with other cytotoxic drugs.
Additive toxicity may occur, especially for medullary / haematological, and gastrointestinal (see Warnings and Precautions for Use). The use of doxorubicin in chemotherapy combining other potentially cardiotoxic products (eg cyclophosphamide), as well as the concomitant use of other cardiac products (eg, calcium channel blockers); Require cardiac function monitoring throughout the treatment.

Changes in hepatic function induced by concomitant therapies may affect the metabolism, pharmacokinetics, efficacy and / or toxicity of doxorubicin.



When paclitaxel is administered, prior to doxorubicin, it may increase plasma levels of doxorubicin and / or its metabolites. Some data indicate that this effect is minor when anthracycline is administered before paclitaxel.
Associations to be taken into account

+; Sorafénib

If combined with sorafenib, risk of increased plasma concentrations of doxorubicin

+; Verapamil

Risk of increased toxicity of doxorubicin by increasing its plasma concentrations

Common interactions with all cytotoxic drugs

Associations contraindicated (see section Contraindications)

+ Yellow fever vaccine

Risk of vaccine disease, generalized fatal.

Associations, not recommended (see Warnings and precautions for use)

+, Phenytoin (and, by extrapolation, fosphenytoin)

Risk of convulsions occurring by decreased digestive absorption of phenytoin alone by cytotoxic, or increased risk of toxicity or loss of efficacy, cytotoxic by increased metabolism, hepatic by phenytoin Or fosphenytoin.

+ Live attenuated vaccines except yellow fever

Risk of illness, generalized vaccination possibly fatal. This risk is increased in subjects already immunocompromised by the underlying disease

Use an inactivated vaccine when it exists (poliomyelitis).

Associations to be taken into account

+ Antivitamins K (AVK)

The high variability of coagulability and increased thrombotic and haemorrhagic risks in tumor affections, coupled with the potential for interaction between AVK and anticancer chemotherapy, Is decided to treat the patient by AVK, increase the frequency of INR checks.

+ Immunosuppressants (ciclosporin, everolimus, sirolimus, tacrolimus)

Excessive immunodepression with risk of lymphoproliferative syndrome

In the absence of compatibility studies, this medicinal product should not be mixed with other medicinal products (eg, heparin or alkaline solutions), except those specified in Dosage and Mode of Administration .

Doxorubicin should not be mixed with fluorouracil (for example, in the same infusion bag or at the IV injection site of IV infusion tubing) since it has been reported that these drugs are Incompatible because a precipitate could form. If a combination of doxorubicin with fluorouracil is necessary it is advisable to rinse the tubing IV between the administration of these two drugs

· Hemodialysis is unnecessary because doxorubicin is excreted mainly by the biliary and intestinal route.


Pregnancy

Doxorubicin is likely to cause severe malformations in the child when administered during pregnancy and therefore should not be used during pregnancy unless Absolute necessity. Women should avoid pregnancy if they or their partner are being treated with doxorubicin and within six months of the end of treatment.
Breastfeeding

Data on the excretion of doxorubicin in human milk are not available. Because many drugs, including anthracyclines, are excreted in breast milk, and because of the potential for adverse reactions, which are serious in the breast-fed infant, women should therefore discontinue breast-feeding before starting Treatment with doxorubicin.

ADRIBLASTINE may give rise to undesirable effects

· Stomatitis

· Medullary hypoplasia in about 2/3 of patients

· Immunodeficiency rapidly regressive

· Alopecia in 90% of cases, but reversible at discontinuation of treatment.

· Amenorrhea, azoospermia.

There have also been reports of febrile, nausea, vomiting, abdominal pain, and diarrhea. But these manifestations are transient and do not pose a problem, serious therapeutic.

Some changes in the ECG may appear: rhythm disorders, QT prolongation in particular, disturbances, acute rhythm may occur within hours after injection. Frequent ECG checks, possibly supplemented by a recording, over 24 hours (Holter methods) must make it possible to specify its meaning.

Possible associated electrolyte disorders (hypokalaemia, hyponatremia) should be corrected. In some cases, severe heart failure, resistant to the usual treatments, may occur. These reactions are rare in patients who have received a total dose of less than 550 mg / m 2, are more frequent beyond this dose and can reach 27% of the patients in this case. >

As with other DNA-altering anti-cancer agents, syndromes, myelodysplastic syndromes and acute leukemias, myeloid lesions have been observed, after combined therapy including doxorubicin.
With topoisomerase II inhibitors, there has been reported a higher than expected incidence of secondary leukemias presenting as de novo leukemias, LAM2, LAM3, LAM4. Such forms may have a short latency period (1 to 3 years). These forms, which are available for curative treatment, require early diagnosis and curative treatment (see Warnings and Precautions).
< Br>
Reporting suspected adverse reactions

Reporting suspected adverse reactions after authorization of the drug is important. It permits continuous monitoring of the benefit / risk ratio of the drug. Health professionals report any suspected adverse reactions via the national reporting system: National Agency for the Safety of Medicines and Health Products (Ansm) and network of Regional Pharmacovigilance Centers -
· Hodgkin's disease, non-Hodgkin's lymphoma · Solid tumors of the child · Lung cancers · Acute leukemias And Chronic Cancers of the bladder, ovary, stomach.