Oxaliplatin LAHEMA

Active material: Oxaliplatin
When ATH: L01XA03
CCF: Anticancer drug
ICD-10 codes (testimony): C18, C19, C20
When CSF: 22.01.02
Manufacturer: PLIVA-LACHEMA a.s. (Czech Republic)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Valium for solution for infusion in the form of a powder of white color.

Excipients: mannitol.

Bottles of colorless glass (1) – packs cardboard.

Pharmacological action

Anticancer drug. Belongs to a new class of platinum-based compounds, which Atom forms a complex relationship with Platinum 1.2-diaminociklogeksanom (DACG) and oksalatnoj group.

Oxaliplatin has anti-tumor activity in different types of tumors,including colorectal cancer. Effective in the treatment of tumors, resistant to cisplatinu. Seen regardless of the phase of the cell cycle. Mechanism of Antitumor effect of Oxaliplatin is based on stroma and not completely studied. Presumably, Oxaliplatin forms international- and vnutritjazhevye connection with DNA, thereby inhibiting its replication and transcription phase.

When applied with 5-fluorouracil has been observed synergy zitotoksicski.

The drug may be fetotoxic, teratogenic, cardiotoksicescoe and neurotoxic action. Possible manifestation of nefrotoksicnosti in applying the drug in high doses.

Pharmacokinetics

Pharmacokinetics of Oxaliplatin after 2-hour infusions in the dose 130 mg / m² with the 3-week intervals for plasma, ultrafiltrate of plasma and erythrocytes are presented in table.

C_Cohn – Oxaliplatin concentration at the end of infusion;

NA-not applicable

Distribution

In the body of Oxaliplatin is as follows: as Platinum, associated with the plasma protein, as a free Platinum in plasma, as well as Platinum, related cell. Platinum binding to plasma proteins by the end of the 2-hour infusion 70%, through 5 days increases to 95%. About 37% introduced Platinum penetrates into erythrocytes. As a result of the irreversible binding of Platinum erythrocytes and plasma protein, duration T_1/2 Platinum from the blood of approaching natural speed updates of erythrocytes and serum proteins.

Great cumulation Oxaliplatin was not observed, even after 7 cycles of chemotherapy.

Metabolism

The main metabolites of Oxaliplatin are (TRANS-1.2-diaminociklogeksan) dihloroplatina, (TRANS-1.2-diaminociklogeksan) monohloromonoakvaplatina and Glutathione (TRANS-1.2-diaminociklogeksan) Platinum. These metabolites are excreted from the body in urine.

Deduction

Process of elimination long: 33% Oxaliplatin is displayed during 48 hours after the 2-hour infusions in the dose 130 mg / m²; about half of the total dose is excreted in the urine within 3 days, a small number of displays with faeces.

Pharmacokinetics in special clinical situations

Clearance of platinum in patients with severe renal insufficiency not studied.

Testimony

— disseminated colorectal cancer (as monotherapy or combination therapy in combination with ftorpirimidinami).

Dosage regimen

The drug used only in adults. The recommended dose is 85 mg / m² 1 once every 2 weeks as monotherapy or in combination with 5-fluorouracil. Give/drip in the form 2-6-hour infusions. Gipergidratace when applying Oxaliplatin does not require.

If Oxaliplatin is used in combination with 5-fluorouracil, the Oxaliplatin infusion should precede the introduction of 5-fluorouracil.

Repeated introduction of Oxaliplatin is produced only when the number of neutrophils > 1500/l and platelet > 50 000/l.

Recommendations for the correction of the dose and regimen of Oxaliplatin

When Hematologic violations (the number of neutrophils <1500/MKL and/or thrombocytes <50 000/l) the appointment of the next course lay before the restoration laboratory indicators.

With the development of diarrhea 4 toxicity (on a scale of who), neutropenia 3-4 degrees (the number of neutrophils <1000/l), thrombocytopenia 3-4 degrees (platelet count <50000/l) dose of Oxaliplatin on subsequent introductions should be reduced from 85 mg / m² to 65 mg / m² In addition to the usual lower-dose 5-fluorouracil in case their combined application.

Patients, which during infusion or within a few hours after the 2-hour infusion develops acute gortanno-glotocnaya paresthesia, the next Oxaliplatin infusion should be conducted over a 6 hours.

Recommendations for dose adjustment of Oxaliplatin in the development neurotoxicity:

— the symptoms of neurotoxicity, causing pain, of more than, than 7 days or when parestesia without functional disorders, continued to next cycle, the subsequent Oxaliplatin dose should be reduced to 25%;

— parestesia with functional impairment, continued to next cycle, Oxaliplatin should be abolished;

— reduction of symptoms of neurotoxicity after canceling Oxaliplatin, You can consider resuming treatment.

With the development of stomatitis and/or mukozitov 2 and more toxicity, treatment of Oxaliplatin should be suspended until their cupping or reduce the manifestations of toxicity to 1 degrees.

Due to limited data on the safety and acceptability of the drug in patients with moderate kidney dysfunction, before applying Oxaliplatin should weigh the benefits and risks of therapy. This category of patients therapy can be started with the recommended dose, under the close supervision of the kidney. At light violations of kidney function correction dose of Oxaliplatin Lahem does not require.

Patients with mild or moderate hepatic insufficiency dose adjustment is not required. Data on the use of Oxaliplatin in patients with severely impaired hepatic function no.

The safety profile of Oxaliplatin alone or in combination with 5-fluorouracil at older patients 65 years similar to, What is observed in patients before 65 years.

The homemade infuzing solution rules and treatment with drug

When cooking and with the introduction of the drug cannot be used needles and other equipment, aluminum-containing.

Do not dissolve and do not dilute 0.9% solution of sodium chloride and do not mix with other salt (alkaline) solutions or solutions, containing chlorides.

For dissolution liofilizata should use water for injection or 5% glucose. In a bottle 50 mg drug Oxaliplatin Lahema add 10 mL of solvent, and into the vial with 100 mg – 20 ml to obtain a solution with concentration 5 mg / ml.

Directly after dissolution liofilizata should proceed with the preparation of infusions.

The homemade infuzing solution dissolved the drug diluted in 250 ml (for the bottles with 50 mg) or in 500 ml (for the bottles with 100 mg) 5% glucose solution (the concentration of the obtained solution is not less 0.2 mg / ml). Infusion solution recommended for use immediately after cooking. Infusion solution remains stable for 24 hours at a temperature of from 2 ° to 8 ° C..

Solution showing signs of falling sludge should be destroyed. You can use only transparent solution.

Oxaliplatin solution should not be mixed in the same infusion system with other drugs, especially with 5-fluorouracil and calcium folinatom.

The drug cannot enter straight.

Side effect

Gradation of frequency of adverse reactions: Often (>1/10), often (>1/100, <1/10); sometimes (>1/1000, <1/100); rarely (>1/10 000, <1/1000); rarely (< 1/10 000), including individual messages.

With blood system: Often – anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often – febrile neutropenia (including 3-4 degree), sepsis amid neutropenia; rarely – gemoliticheskaya anemia, immune thrombocytopenia.

From the digestive system: Often – nausea, vomiting, diarrhea, stomatitis, mukozit, pain in the stomach, constipation, loss of appetite; often – dyspepsia, hastroэzofahealnыy reflux, Ikotech; sometimes – ileus; rarely – colitis, including cases psevdomembranoznogo colitis.

From the central and peripheral nervous system: Often – peripheral sensory neuropathy, sensory disturbances, headache, asthenia; often – dizziness, meningism, depression, insomnia; sometimes excessive nervousness; rarely – dysarthria.

Neurotoxicity was dose-limiting side-phenomenon. Often symptoms of sensory neuropathy caused by cold. The duration of these symptoms, which usually stopped between courses, increases depending on the total dose of Oxaliplatin. Functional disorders, expressed difficulty performing precise movements, are the possible effects of touch damage. The risk of impairment to total dose about 850 mg / m² (10 cycles) is about 10%, reaching 20% in the case of total dose 1020 mg / m² (12 cycles). In most cases the neurological symptoms improve or disappear after discontinuation of treatment. However, 3% patients through 3 a year after the end of treatment were observed or persistent localized paraesthesia moderate intensity (2.3%) or paresthesia, affect the functional activity (0.5%). Treatment with Oxaliplatin marked acute manifestations of nejrosensornye, that usually occurred within a few hours after the injection and most often provoked by cold. They were characterized by transient paresteziej, dizesteziej or gipesteziej, rarely (1-2%) acute gortanno syndrome-pharyngeal dizestezii. The latter showed a subjective sense of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or spasm of the larynx or bronchospasm (No stridor or wheezing). Also experienced such phenomenon, as jaw spasm, dizestesia language, dysarthria and pressure sensation in the chest. Usually these symptoms quickly stoped as without the use of drug therapy, and with the introduction of antihistamine and expanding tools. Infusion time subsequent cycles of Oxaliplatin therapy can reduce the frequency of this syndrome.

On the part of the musculoskeletal system: Often – back pain; often – arthralgia, ostealgias.

The respiratory system: Often – cough, breathlessness; often – rhinitis, upper respiratory tract infection; rarely – fibrosis lyegkikh.

Cardio-vascular system: often – chest pain, deep vein thrombophlebitis, tromboembolia pulmonary artery.

From the urinary system: often – hematuria, dizurija.

Dermatological reactions: Often – alopecia, skin rashes; often – skin peeling palms and feet, erythematous rash, increased sweating, violations by nails.

From the senses: Often – taste disturbances; often – conjunctivitis, visual impairment; rarely – the transitory reduction of Visual acuity, the fields of vision loss, hearing loss, neuritis of the auditory nerve.

Allergic reactions: often – rash (especially hives), conjunctivitis or rhinitis; rarely (When applying alone) or often (in combination with 5-fluorouracil ± calcium folinate) – bronchospasm, angioedema, arterial hypotension and anaphylactic shock.

Local reactions: When drug extravasation – pain and inflammatory reactions at the injection.

From the laboratory parameters: Often – increase in AP , liver enzymes, the content of bilirubin, LDH, kaliopenia, violations of sodium and glucose in serum; often – elevation of serum creatinine.

Other: Often – fever, increased fatigue, weight gain.

Contraindications

-neutropenia (<2000/l) and / or thrombocytopenia (<100 000/l), before the start of therapy;

-peripheral neuropathy and functional disorders, identified before the first course of therapy;

- Severe renal insufficiency (CC less than 30 ml / min);

- Pregnancy;

- Lactation (breast-feeding);

- Up to 18 years;

- Hypersensitivity to the drug;

-hypersensitivity to Platinum or other derivative mannitolu in history.

FROM caution You should use the drug in the human kidney.

Pregnancy and lactation

Contraindicated for use in pregnancy and lactation (breast-feeding).

Women of childbearing age and men during treatment with Oxaliplatin should use reliable methods of contraception.

Cautions

Introduction of Oxaliplatin should be carried out under the supervision of a physician, with experience of cytotoxic drugs. Constant monitoring of possible toxic effects in the treatment of Oxaliplatin is required.

Regularly (1 once a week), and also before every introduction drug Oxaliplatin Lahema should undertake monitoring of peripheral blood and uniform indicators of kidney and liver.

Before each cycle of therapy with Oxaliplatin Lahema neurological examination should be performed to identify signs of neurotoxicity.

Patients should be informed about the possibilities of sustainable symptoms of peripheral sensory neuropathy after treatment. Localized moderate paresthesias with functional impairment can hold up to 3 years after the end of treatment with the drug adjuvantny schema.

With the emergence of respiratory symptoms (dry cough, dyspnoea, wheezing or identifying pulmonary infiltrates with x-ray study), treatment with Oxaliplatin Lahema exceptions should be suspended until the existence of interstitial pnevmonita.

Symptoms such as dehydration, paralytic ileus, bowel obstruction, kaliopenia, metabolic acidosis and renal failure can be caused by diarrhoea or vomiting expressed, especially when using the drug Oxaliplatin Lahem in combination with 5-fluorouracil.

Patients with allergic reactions to other Platinum compounds in history should be monitored for the presence of allergic symptoms. In the case of reaction to Oxaliplatin, such anaphylactic, infuziu should immediately suspend and appoint appropriate symptomatic treatment. Continued use of the drug Oxaliplatin Lahem in case of allergic reactions is contraindicated.

In the case of extravasation infuziu should immediately stop and start local symptomatic treatment. The remainder of the dose of the drug should enter into another vein.

When using the drug Oxaliplatin Lahema should observe all the usual instructions, taken for the application of cytotoxic drugs. When hit or liofilizata solution of the drug Oxaliplatin Lahema on the skin or mucous membranes, they should be immediately and thoroughly with water.

Overdose

Symptoms: increased side effects medication, such as peripheral neuropathy, mielosuprescia, diarrhea and mucositis.

Treatment: symptomatic therapy, regular monitoring picture blood. No specific antidote.

Drug Interactions

A significant change in linking Oxaliplatin with plasma proteins in vitro application of erythromycin, salicylates, granisetronom, paclitaxel and valproatom sodium were not observed.

When interacting with aluminum possibly education sludge and reduced activity of Oxaliplatin.

Pharmaceutical interaction

Farmatsevticeski incompatible with 0.9% solution of sodium chloride and other salt (alkaline) solutions or solutions, containing chlorides.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature no higher than 25 ° C. Shelf life – 2 year.