Oksaliplatin

General characteristics. Structure:

Active ingredient: oxaliplatin;

1 ml of solution contains 2 mg of an oksaliplatin, in terms of 100% substance, on 25 ml (50 mg) or 50 ml (100 mg) in a bottle;

auxiliary a veshchestva:kislota hydrochloric, water for injections.

Pharmacological properties:

Pharmacodynamics. Antineoplastic drug, derivative platinum in which molecular structure atom of platinum forms a complex with oxalate and 1,2 diaminocyclohexane. Active agent is an enantiomer. Oksaliplatin shows a wide range of cytotoxic action of in vitro and antineoplastic action of in vivo in various models of tumors. Also shows activity of in vitro and        in vivo on various models steady against Cisplatinum. The mechanism of action is caused by Oksaliplatin's interaction with DNA by formation of boundaries - and intra spiral chains and DNA synthesis oppression.

Pharmacokinetics. After intravenous administration Oksaliplatin, mainly, accumulates in erythrocytes and ​​ does not pass into plasma. 85-88% of platinum contact proteins in the first 5 hours after introduction. Oksaliplatin is exposed to bystry not fermental biotransformation with formation of reactive complexes of platinum. Active metabolites of an oksaliplatin belong to group of DATsG-complexes of platinum.

Removal. Oksaliplatin is brought from an organism mainly by renal excretion. About 50% of the entered dose are excreted with urine during the first 3 days. Excretion with a stake makes about 0,5% a day and reaches 5% of the general dose for the 11th days. The elimination half-life of ultrafiltrovany platinum (оксалиплатин and free metabolites of an oksaliplatin) makes 273±19 hours. Removal of platinum from erythrocytes lasts about 48 days.

Pharmacokinetics in special clinical cases. Considerable decrease in clearance from 17,55±2,18 l/hour to 9,95±1,91 l/h is observed at a renal failure together with statistically considerable reduction of Vd from 330±40,9 to 241±36,1 l. Influence of considerable decrease in renal function on clearance of platinum is not studied.

Pharmaceutical characteristics:

main physical and chemical properties: colourless transparent solution.

Incompatibility.

- Oksaliplatin it is impossible to enter together with alkaline medicines (in particular 5-ftoruratsily, trometamoly and the drugs of folinovy acid containing трометамол).
- Oksaliplatin it is impossible to dissolve in 0,9% solution of sodium of chloride or to part 0,9% with chloride sodium solution.

- Oksaliplatin it is impossible to mix with other medicines in one infusional bag / bottle or one infusional line (instructions for simultaneous administration of folinovy acid are provided in the section "Route of administration").
- Oksaliplatin it is impossible to enter by means of infusional systems which part aluminum parts, or through the needles containing aluminum are.

- It is not necessary to part with the saline solutions containing chlorides (including chlorides of Sa, To and Na).

Indications to use:

In a combination with 5-ftoruratsily and foliniyevy acid оксалиплатин it is shown for:

-  adjuvant treatment of a colorectal cancer ІІІ stages (Duke s C) after full removal of primary tumor;

- treatments of a metastatic colorectal cancer.

Route of administration and doses:

Drug is intended only for treatment of adults.

The recommended dose of an oksaliplatin at purpose of adjuvant therapy makes       85 mg/sq.m of a body surface intravenously, to enter the same dose repeatedly each two weeks throughout 12 cycles (6 months).

The recommended dose of an oksaliplatin for treatment of a metastatic colorectal cancer makes 85 mg/sq.m intravenously which is entered repeatedly by each two weeks before regressing of a disease or before emergence of signs of intolerable toxicity.

The dose needs to be adjusted according to individual portability of drug (see the section "Features of Use").

Oksaliplatin it is always necessary to enter earlier, than ftoropirimidina, for example before introduction of a 5-ftoruratsil.

Oksaliplatin enter intravenously kapelno in the form of 2-6-hour infusions (оксалиплатин apply only to adults).

Infusion.

Oksaliplatin it is always necessary to enter before use of ftoropirimidin.

Oksaliplatin apply in the form of intravenous infusion.

Oksaliplatin preferential enter into combinations with continuous infusion                 of a 5-ftoruratsil. Introduction of an oksaliplatin needs to be carried out always earlier, than infusion of a 5-ftoruratsil.

For the scheme of treatment repeating each two weeks the dosage mode in the form of bolyusny introduction and continuous infusion of a 5-ftoruratsil is recommended.

Use of an oksaliplatin does not demand preliminary hydration.

Oksaliplatin divorced in 250–500 ml of 5% of solution of glucose for obtaining concentration from 0,2 to 0,7 mg/ml has to be entered into the central or peripheral vein for 2–6 hours. Concentration of 0,7 mg/ml corresponds to the highest which is applied in clinical practice at a dose of an oksaliplatin of 85 mg/sq.m.

Solution for infusion is stable within 24 hours at storage at a temperature from 2 ˚С to    8 ˚С. From the microbiological point of view solution needs to be applied to infusion immediately. If not to impose drug right after preparation, liability for conditions and storage time are born by the specialist who applies it.

Before use carry out direct vision. It is possible to apply only transparent solution without visible particles.

Drug is intended for single use. The drug remains, unused solution and all objects which were used for dilution and Oksaliplatin's introduction need to be utilized with observance of standard procedures of utilization of cytotoxic drugs, in view of the existing regulations on destruction of dangerous wastes.

Recommendations about dose adjustment and mode of introduction of an oksaliplatin.

In case of hematologic disturbances (quantity of neutrophils <1500/mkl and/or thrombocytes <50000/mkl) purpose of the following course is postponed until recovery of laboratory indicators.

At development of diarrhea of the IV degree of toxicity, a neutropenia of the III-IV degree (quantity of neutrophils <10Õ109/l), thrombocytopenia of the III-IV degree (quantity of thrombocytes              <50Õ109/l) the dose of an oksaliplatin at the subsequent introductions has to be lowered from          85 to 65 mg/sq.m at therapy of the disseminated colorectal cancer and ovarian cancer; and to 75 mg/sq.m at adjuvant therapy of a colorectal cancer in addition to a usual dose decline of a 5-ftoruratsil in case of their combined use.

Patients at whom during infusion or within several hours after 2-hour infusion the acute laryngopharyngeal dizesteziya develops should carry out infusion of an oksaliplatin within 6 hours.

Recommendations about correction of a dose of an oksaliplatin at development of a neurotoxicity:

- at the symptoms of a neurotoxicity causing pain lasting more than 7 days, the subsequent dose of an oksaliplatin has to be lowered from 85 to 65 mg/sq.m at therapy of the disseminated colorectal cancer, to 75 mg/sq.m - at adjuvant therapy of a colorectal cancer;

- at the paresthesia without functional disturbances remaining to the following cycle, the subsequent dose of an oksaliplatin has to be lowered from 85 to 65 mg/sq.m at therapy of the disseminated colorectal cancer, to 75 mg/sq.m - at adjuvant therapy of a colorectal cancer;

- at the paresthesia with functional disturbances remaining to the following cycle оксалиплатин it is necessary to cancel;

- at reduction of expressiveness of symptoms of a neurotoxicity after cancellation of an oksaliplatin it is possible to consider a question of treatment resuming.

At development of stomatitis and/or mukozit II (above) toxicity degrees treatment oksaliplatiny need to be stopped before disappearance or decrease in manifestations of toxicity to the I degree.

Patients with a narushennoyfunktion of kidneys. Oksaliplatin is forbidden to apply to patients with a heavy renal failure.

At patients from a legkoya a medium-weight renal failure the recommended dose of an oksaliplatin makes 85 mg/sq.m.

Patients from a liver nedostatochnostyyufunktion. Change of a dosage with weak or moderate insufficiency of function of a liver is not required from patients. There are no data on use of an oksaliplatin for patients with heavy abnormal liver functions.

Patients of a pozhilogovozrast. The profile of safety of an oksaliplatin as means of monotherapy or in a combination with 5-ftoruratsily at patients is more senior than 65 years is similar to that at patients aged up to 65 years.

Special measures at introduction.

- never to use infusional systems which part aluminum parts, or needles which contain aluminum are.

- never to administer the drug in an undiluted look;

- never to dissolve and not to part with saline solutions (including 0,9% chloride sodium solution);

- never to mix with other medicines in the same package for infusion, not to apply at the same time in one system to infusion (especially with                    5-ftoruratsily, alkaline solutions, trometamoly and the medicines containing foliniyevy acid and трометамол as excipient). Oksaliplatin it is possible to apply along with foliniyevy acid by means of              Y-shaped infusional system, with a fork just before an injection site. Oksaliplatin and foliniyevy acid it is not necessary to mix in the same bottle. Foliniyevy acid should not contain трометамол as excipient, it should be parted only isotonic 5% with glucose solution, but never to part with solution of sodium of chloride or alkaline solutions;

- to apply only the recommended solvent (5% glucose solution);

- after Oksaliplatin's introduction infusional system and a vein it is necessary to wash out 5% glucose solution.

Utilization and safety at use.

Considering toxicity of an oksaliplatin, the following protective measures are recommended:

- The personnel have to have the corresponding qualification and to be informed on technology of work with drug.

- At manipulations with drug it is necessary to follow rules of work with cytostatics.
- Pregnant health workers cannot work with drug.

- During the work with drug the personnel should use protective clothes: dressing gowns, hats, masks, glasses and one-time gloves.

- For manipulations with drug it is necessary to allocate the special place where it is forbidden to smoke, eat and drink. Working surfaces should be closed one-time sheets of the absorbing paper with a protective film covering from a reverse side.

- The drug remains, all things and materials used at dissolution, cultivation and administration of solutions of an oksaliplatin, and also cleaning (including gloves), it is necessary to put in special containers or heavy-duty bags for toxic waste and to destroy according to the standard procedure of recycling of cytotoxic substances according to the existing regulations on destruction of dangerous wastes.

- It is necessary to remove the emetic mass and excrement of patients with care.

- At accidental hit of the lyophilized powder or solutions of an oksaliplatin on skin or their mucous membranes it is necessary to wash away immediately a large amount of water.

Features of use:

Oksaliplatin it is necessary to apply only in specialized oncological departments and under observation of the experienced oncologist.

Renal failure.

With renal failures easy and moderate severity it is necessary to watch patients carefully for the purpose of identification of side reactions and to adjust a dose depending on toxicity level.

Hypersensitivity reactions.

Careful observation of a condition of patients with allergic reactions to other compounds of platinum in the anamnesis is necessary. At emergence of reaction on оксалиплатин, similar anaphylactic, infusion of drug it is necessary to stop and appoint the corresponding symptomatic treatment immediately. Repeated use of an oksaliplatin for treatment of such patients is contraindicated. Arrived сообщенияо cases of cross-reactions with all compounds of platinum which sometimes had a lethal outcome.

In case of an ekstravazation (hit out of a vein) an oksaliplatin infusion it is necessary to stop and begin a usual topical symptomatic treatment immediately.

Neurologic symptoms.

It is necessary to tshchatelnokontrolirovat manifestations of neurologic toxicity of an oksaliplatin, especially if it is combined with other drugs which have neurologic toxicity. Before each introduction, and then it is periodically necessary to conduct neurologic examination of the patient.

Patients at whom during infusion or within several hours after two-hour infusion the acute laryngopharyngeal dizesteziya develops (see the section "Side reactions") should carry out the subsequent introduction of an oksaliplatin within 6 hours.

Peripheral neuropathy.

If there are neurologic symptoms (paresthesia, a dizesteziya), dose adjustment of an oksaliplatin has to be based on duration and severity of these symptoms:

• if symptoms remain more than 7 days and are followed by pain, the following dose of an oksaliplatin should be lowered from 85 to 65 mg/sq.m (treatment of metastasises) or to 75 mg/sq.m (adjuvant therapy);

• if paresthesia without functional disturbances remains to the following cycle, the dose of an oksaliplatin should be lowered from 85 to 65 mg/sq.m (treatment of metastasises) or to 75 mg/sq.m (adjuvant therapy);

• if paresthesia with functional disturbances remains to the following cycle, treatment oksaliplatiny should be stopped;

• if these symptoms disappear after the treatment termination oksaliplatiny, it is possible to consider a question of treatment resuming.

It is necessary to inform patients that symptoms of a touch peripheral neuropathy can remain also after the treatment termination. The moderate localized paresthesias or paresthesias which can disturb functional activity can be observed up to 3 years after the termination of adjuvant therapy.

Syndrome of a reversible back leukoencephalopathy (RPLS).

Cases of emergence of a syndrome of a reversible back leukoencephalopathy (RPLS also known as RPES (a syndrome of reversible back encephalopathy) were recorded at patients who received оксалиплатин as a part of the combined chemotherapy. Rplsyavlyaetsya a rare, reversible, neurologic disease which quickly develops and can be followed by spasms, arterial hypertension, a headache, confusion of consciousness, a blindness and other reversible visual and neurologic frustration (see the section "Side reactions"). The diagnosis of Rplspodtverzhdayetsya by means of methods of visualization of a brain, it is desirable MRT (magnetic and resonant tomography).

Nausea, vomiting, diarrhea, dehydration and hematologic changes.

At gastrointestinal toxicity of an oksaliplatin which is shown in the form of nausea and vomiting it is necessary to apply antiemetics with the preventive and/or medical purpose (see the section "Side reactions").

The severe diarrhea and/or vomiting can lead to dehydration of an organism, paralytic intestinal impassability, obstruction of intestines, a hypopotassemia, a metabolic acidosis and a renal failure, especially at the combined use of an oksaliplatin with 5-ftoruratsily.

In case of development of hematologic toxicity (quantity of neutrophils <1,5 x109/l or quantity of thrombocytes <50x109/l) the beginning of the following course are postponed until establishment of tolerance levels of hematologic indicators. The developed blood test needs to be carried out prior to treatment oksaliplatiny and before each subsequent cycle.

Patients need to be informed on possibility of diarrhea/vomiting, мукозита / stomatitis and a neutropenia after use of an oksaliplatin and a 5-ftoruratsil that they could see immediately a doctor behind necessary treatment.

In case of development мукозита / the stomatitis which is followed or not followed by a neutropenia, the subsequent purpose of drug should be postponed until regression approach мукозита / stomatitis to severity ≤ I and/or until establishment of quantity of neutrophils ≥ 1,5 x109/of l.

If оксалиплатин combine with 5-ftoruratsily (with foliniyevy acid or without it), in connection with toxicity of a 5-ftoruratsil, correction of its dose is usually recommended.

At diarrhea of the IV severity, a neutropenia of the III-IV severity (quantity of neutrophils <1x109/l) or thrombocytopenia of the III-IV degree (quantity of thrombocytes <50x109/l) in addition to a dose decline of a 5-ftoruratsil it is necessary to lower a dose of an oksaliplatin from     85 to 65 mg/sq.m (treatment of metastasises) or to 75 mg/sq.m (adjuvant therapy).

Pulmonary manifestations.

At emergence of respiratory symptoms of the obscure etiology, such as unproductive cough, диспноэ, crepitation or pulmonary infiltrates on the roentgenogram, it is necessary to stop treatment oksaliplatiny to an exception of an intersticial pneumonitis by additional inspections of lungs (see the section "Side reactions").

Hepatic manifestations.

At change of results of functional trials of a liver or at emergence of symptoms of portal hypertensia which, obviously, is not result of metastasises in a liver it is necessary to consider a possibility of development of isolated cases of defeat of the vessels of a liver caused by drug use.

Fertility.

Genotoksichesky effects of an oksaliplatin were revealed. Men are recommended to apply contraceptives during the entire period of reception of an oksaliplatin and 6 months after the therapy termination, and also to consult about a possibility of preservation of sperm prior to therapy as оксалиплатин can cause irreversible infertility.

Women have to avoid pregnancy during administration of drug and apply a well-tried remedy of contraception (see the section "Use during Pregnancy or Feeding by a Breast").

Ability to influence speed of response at control of motor transport or work with other mechanisms. Vliyaniyeoksaliplatina on speed of response at control of motor transport or work with other mechanisms it was not studied, however potentially possible side effects (such as dizziness, nausea, vomiting, vision disorder, in particular the temporary loss of sight which is taking place after the termination of treatment and neurologic symptoms) can influence ability to manage motor transport or work with other mechanisms. Thus, it is necessary to warn patients about a possible negative impact of drug.

Side effects:

At a combination therapy oksaliplatiny and 5-ftoruratsilom/foliniyevy  acid (5-FU/FK) gastrointestinal side effects (diarrhea, nausea, vomiting and mukozit), hematologic disturbances (a neutropenia, thrombocytopenia) and neurologic syndromes (touch peripheral neuropathy, acute and dependent on a cumulative dose) were most often observed. Generally, these side effects are more often observed and characterized by heavier current at a combination of an oksaliplatin with 5-FU/FK, than at therapy only 5-FU/FK.

Side effects on systems of bodies.

Reactions in an injection site. Hypostasis and thrombosis in an injection site, the ekstravazation can lead to feeling of pain and an inflammation in the place of damage which can be heavy and cause complications, including a necrosis, especially at introduction of infusion of an oksaliplatin to a peripheral vein (see. "Features of use").

General disturbances. Fever (fever, a fever owing to an infection (followed or not followed by a febrile neutropenia), or fever, a fever of an immunological origin) fatigue, an adynamy, pain, increase in body weight (adjuvant therapy), a body degrowth (at patients with metastasises), immunoallergic thrombocytopenia, hemolitic anemia.

Disturbances from immune system. The infection, an allergy / allergic reaction (rash on skin (especially a small tortoiseshell), conjunctivitis, rhinitis, are widespread anaphylactic reactions, including a bronchospasm, a Quincke's disease, hypotension and an acute anaphylaxis), immunoallergic thrombocytopenia, hemolitic anemia.

Metabolism disturbances. Hyperglycemia, hypopotassemia, hypernatremia, dehydration, metabolic acidosis.

Mental disturbances. Depression, sleeplessness, annoyance.

Disturbances of the central and peripheral nervous system. Touch peripheral neuropathy, headache, touch disturbances, disturbances of feeling of taste, dizziness, neuritis of a motor nerve, meningism, dysarthtia, syndrome of a reversible back leukoencephalopathy (PRLSorPRES).

Frustration of organs of sight. Conjunctivitis, visual disturbances, disturbances of a field of vision, temporary decrease in visual acuity, temporary loss of sight (passes after the treatment termination), an optic neuritis.

Frustration of acoustic organs. Ototoxicity, deafness.

Vascular disorders. Nasal bleeding, bleeding, reddening, thrombophlebitis of deep veins, embolism of a pulmonary artery, rectal bleeding, arterial hypertension.

Gastrointestinal disturbances. Diarrhea, nausea, vomiting, stomatitis / мукозит, abdominal pain, a lock, anorexia, dyspepsia, a gastroesophageal reflux, gastrointestinal bleeding, Ilheus (impassability of intestines), colitis, including the diarrhea caused by Clostridium difficile, pancreatitis.

Skeletal and muscular disturbances. Dorsodynia, arthralgia, ostealgia.

Damage of skin and hypodermic fabrics. Skin diseases, allopecia skin exfoliation, erythematic rashes, rash, гипергидратоз, defeats of appendages of skin.

Disturbances of respiratory system, bodies of a thorax and mediastinum. Dispnoye, cough a stethalgia, a hiccups, intersticial diseases of lungs, pulmonary fibrosis (See. "Features of use").

Disturbances from ENT organs. Rhinitis, upper respiratory tract infection.

Disturbances of an urinary system. Dysuria, frequent and urodynia, increase in level of creatinine, hamaturia.

Deviations of laboratory indicators from norm.

-      Hematologic: anemia, a neutropenia, thrombocytopenia, a leukopenia, a lymphopenia a febrile neutropenia / нейтропенический sepsis (for example, a neutropenia of the III-IV severity and documentary confirmed infections).

-      Biokhimicheskiye:povysheniye of the level of an alkaline phosphatase and bilirubin, hyperglycemia, increase in level of a lactate dehydrogenase (LDG), hypopotassemia, aberrations of level of enzymes of a liver (ALT/nuclear heating plant), hypernatremia, increase in level of creatinine.

Disturbances gepatobiliarny системы:веноокклюзионноезаболеваниепечени or the histologic anomalies connected with this disease including пелиоз a liver, a nodal regenerative hyperplasia and perisinusoidalny fibrosis. Clinical symptoms can include portal hypertensia and/or increase in level of transaminases.

Disturbances of kidneys and urinary tract. acute tubular necrosis, acute interstitsionny nephrite and acute renal nedostatosnost.

Hematologic toxicity at use of a dose Oksaliplatin of 85 mg/m ² in a combination with 5-FU/FK each 2 nedeli:anemiya, a neutropenia, thrombocytopenia, a febrile neutropenia, neytropenichesky sepsis, a hemolitic uraemic syndrome.

Gastrointestinal toxicity at use of a dose Oksaliplatin of 85 mg/m ² in a combination with 5-FU/FK each 2 weeks: nausea, diarrhea, vomiting, мукозит / stomatitis. Heavy diarrhea and/or vomiting can lead to dehydration, impassability of intestines (including to paralytic), to a hypopotassemia, a metabolic acidosis and a renal failure, especially in case of the combined treatment oksaliplatiny with 5-ftoruratsily (see the section "Features of Use").

Nervous system. Neurologic toxicity of an oksaliplatin depends on a dose. It, mainly, is shown in the form of peripheral touch neyropatiya of which it is characteristic the dizesteziya and/or paresthesia of extremities which are followed, or not followed by spasms which are often caused by cold. Duration of these symptoms which regression usually occurs between treatment cycles increases at increase in quantity of cycles of treatment.

Depending on duration of symptoms, such as pain and/or functional disturbances (see the section "Features of Use"), dose adjustment or even cancellation of treatment is necessary.

It was reported about acute neurosensory manifestations. These manifestations begin within several hours after administration of drug and often arise under the influence of cold. They are characterized by reversible paresthesia, a dizesteziya or a hypesthesia, or shown in the form of an acute syndrome of a laryngopharyngeal dizesteziya. This acute syndrome is characterized by subjective feeling of a dysphagy or диспноэ, without objective signs of respiratory disturbance (is not followed by cyanosis or a hypoxia), either a laryngospasm, or a bronchospasm (without stridor or goose breathing); also it is shown by a jaw spasm, disturbance of sensitivity of language, a dysarthtia and feeling of a sdavlennost in a breast.

Though in such cases antihistaminic drugs and bronchodilators are used, these symptoms quickly pass, even in the absence of treatment. Lengthening of time of infusion during the subsequent cycles promotes reduction of frequency of manifestations of this syndrome (see the section "Features of Use").

Also other symptoms were observed: jaw spasms, muscular spasms, involuntary reductions of muscles, myoclonuses, ataxias, walking disturbances, ataxy, disturbances of balance, sudorga, stesneniyeglotka or thorax, depression, discomfort and pain. There can be a disturbance of cranial nerves in the form of a ptosis a century, diplopias, aphonias, a dysphonia, hoarsenesses which sometimes call as paralysis of phonatory bands, aphasia, an epileptiform neuralgia.

At treatment oksaliplatiny other neurologic symptoms, such as a dysarthtia, loss of a tendon jerk and Lhermitte s sign symptom are also possible. There are data on separate cases of an optic neuritis.

Interaction with other medicines:

Oksaliplatinstimuliruyet development of the cholinergic syndrome connected using an irinotekan through acetylcholinesterase oppression strengthening.

Oksaliplatinne influences pharmacokinetics of a ftoruratsil and topotekan. There are data indicating synergy action with ftoruratsily and SN-38, an active metabolite of an irinotekan. There is information that in the researches invitro essential substitution of the oksaliplatin connected with proteins of plasma, such medicines is not observed: erythromycin, salicylates, гранисетрон, paklitakset also sodium Valproatum.

Contraindications:

-  Hypersensitivity to active substance or excipients of drug;

-  period of pregnancy and feeding by a breast;

- children's age;

- a miyelosupressiya (quantity of neutrophils <2x109/l and/or quantity of thrombocytes <100x109/l) prior to the beginning of the first course of treatment;

-   peripheral touch neuropathy with functional disturbances prior to the beginning of a course of treatment;

- heavy renal failure (clearance of creatinine <30 ml/min.).

Use during pregnancy or feeding by a breast.

Safety of use of an oksaliplatin during pregnancy was not investigated. Preclinical data demonstrate to what оксалиплатин in therapeutic doses can render эмбриолетальноеи / or teratogenic action on a fruit therefore drug is not recommended to be used during pregnancy and to women of reproductive age who do not apply contraceptives.

Purpose of drug is possible only after careful weighing of advantage and risk, and also after informing the patient on risk for a fruit and on condition of her consent. During administration of drug patients need to apply appropriate measures of contraception. It is necessary to continue their use after the end of treatment: to women - within 4 months, to men - within 6 months. Oksaliplatin can have a negative impact on fertility.

Excretion of an oksaliplatin in breast milk was not studied. During treatment oksaliplatiny feeding by a breast contraindicated.

Children. Safety and an effektivnostprimeneniya of drug are not established to children.

Overdose:

In a case peredozirovkimozhno to expect more expressed manifestation of side effects. It is necessary to establish careful control of the patient, in particular hematologic control. If necessary, symptomatic therapy is appointed. The antidote to an oksaliplatin is not known.

Storage conditions:

Period of validity 2 years. To store in original packaging at a temperature up to 25 °C, not to freeze. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Packaging of 25 ml (50 mg) or 50 ml (100 mg) in a glass bottle, 1 bottle in a pack.