Oxaliplatin - Instructions For Use, Price, Reviews, Side Effects

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Oxaliplatin

Oxaliplatin: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. Drug interactions
13. 13. Analogs
14. 14. Terms and conditions of storage
15. 15. Terms of dispensing from pharmacies
16. 16. Reviews
17. 17. Price in pharmacies

Latin name: Oxaliplatin

ATX code: L01XA03

Active ingredient: oxaliplatin (Oxaliplatin)

Manufacturer: concentrate for solution for infusion - Oxford Laboratories, Pvt. Ltd. (Oxford Laboratories, Pvt. Ltd.) (India); lyophilisate for the preparation of a concentrate for the preparation of a solution for infusion - RUE "Belmedpreparaty" (Republic of Belarus)

Description and photo update: 2019-04-10

Prices in pharmacies: from 1649 rubles.

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Oxaliplatin is an antitumor drug.

Release form and composition

Oxaliplatin is available in the following dosage forms:

• concentrate for preparation of solution for infusion: colorless transparent liquid (25 ml each in dark transparent glass vials with a capacity of 30 ml, sealed with a rubber stopper and sealed with aluminum caps with flip-off discs, in a cardboard box 1 bottle; 50 ml each in dark transparent glass vials with a capacity of 60 ml, sealed with a rubber stopper and sealed with aluminum caps with flip-off discs, in a cardboard box 1 bottle; for hospitals - in cardboard boxes with cardboard dividers for 20, 25, 35 or 100 bottles);
• lyophilisate for the preparation of a concentrate for the preparation of a solution for infusion: a porous mass or powder from white to almost white (50 mg in glass vials with a capacity of 20 ml or 50 ml, in a cardboard box 1 bottle; 100 mg each in glass vials with a capacity of 50 ml or 100 ml, in a cardboard box 1 bottle; for hospitals - in cardboard boxes of 15 or 40 bottles with a dosage of 50 mg; 12 or 15 bottles with a dosage of 100 mg).

Each pack also contains instructions for the use of Oxaliplatin.

Composition for 1 ml of concentrate:

• active substance: oxaliplatin - 2 mg;
• auxiliary components: water for injection.

Composition for 1 bottle with lyophilisate:

• active substance: oxaliplatin - 50 mg or 100 mg;
• auxiliary components: lactose monohydrate.

Pharmacological properties

Pharmacodynamics

Oxaliplatin is an antineoplastic agent that belongs to the class of platinum derivatives. In this substance, platinum atoms form a complex with 1,2-diaminocyclohexane and oxalate. The drug has a wide range of cytotoxic effects. It exhibits its activity in various tumor models that are resistant to cisplatin both in vivo and in vitro. As part of the combined treatment with fluorouracil, synergism of cytotoxic action is manifested.

The hypothesis of the interaction of biotransformed aqueous derivatives of oxaliplatin with DNA (deoxyribonucleic acid) through the formation of interstranded and intrastranded bridges was confirmed by studying the mechanism of action of the drug. As a result of the formation of such bridges, DNA synthesis is suppressed, which causes cytotoxicity and antitumor effect.

Pharmacokinetics

Under conditions in vivo oxaliplatin actively biotransformed and the end of a dose of 85 mg / m ² (after 2 hours) no longer detectable in blood plasma. About 15% of the administered dose is present in the blood through binding to albumin, the rest of the platinum (approximately 85%) is rapidly distributed to tissues or excreted in the urine during the first 48 hours.

On the 5th day, approximately 54% of the total dose of the drug is found in the urine, less than 3% is present in the feces.

In patients with renal insufficiency, oxaliplatin clearance is significantly reduced (from 17.6 ± 2.18 l / h to 9.95 ± 1.91 l / h). There are no data on the effect of severe renal failure on the value of platinum clearance.

Indications for use

• Colorectal cancer with metastases (in combination with calcium folinate / fluorouracil);
• Colorectal cancer with metastases (as first-line drug in combination with bevacizumab and calcium folinate / fluorouracil);
• Colon cancer stage III (according to Duke's classification - stage C) - adjuvant treatment after radical resection of the primary tumor (as part of combination therapy with calcium folinate / fluorouracil);
• ovarian cancer (as a second-line drug).

Contraindications

Absolute:

• peripheral neuropathy with functional impairment before the start of the first course of therapy;
• myelosuppression (platelet count less than 100,000 / μl and / or neutrophils less than 2000 / μl) before the start of the first course of therapy;
• children and adolescents up to 18 years old;
• period of pregnancy;
• breast-feeding;
• hypersensitivity to drug components or other platinum derivatives.

Relative (Oxaliplatin is used with caution):

• severe renal dysfunction (with creatinine clearance less than 30 ml / min);
• the presence of risk factors for prolongation of the QT interval or a history of a prolongation of the QT interval;
• concomitant use of drugs that have the potential to cause rhabdomyolysis.

Oxaliplatin, instructions for use: method and dosage

Oxaliplatin solution is administered by intravenous drip in the form of infusions lasting from 2 to 6 hours. Additional overhydration is not required.

If the drug is used in combination treatment with fluorouracil, then oxaliplatin is administered first, and if in combination with bevacizumab, then oxaliplatin infusion is performed after the administration of bevacizumab.

The drug is used only for the treatment of adult patients.

Recommended dosage regimen:

• metastatic colorectal cancer: 85 mg / m ² of body surface intravenously once every 2 weeks (in combination with calcium folinate, fluorouracil or bevacizumab). the solution is administered before the disease progresses or unacceptable toxicity occurs;
• adjuvant treatment of colon cancer: 85 mg / m ² body surface intravenously once every 2 weeks (in combination with calcium folinate or fluorouracil) for 6 months (12 cycles);
• ovarian cancer: 85 mg / m2 ^of body surface once every 2 weeks as part of a combination treatment with other chemotherapeutic agents or as monotherapy.

Dosage regimens for calcium folinate, fluorouracil, and bevacizumab are established in accordance with the instructions for use of these drugs.

Recommendations for the regimen of administration and dose adjustment of Oxaliplatin

In case of hematological disorders (if the number of platelets is less than 5000 / μl and / or neutrophils is less than 1500 / μl), the next course of treatment is postponed until laboratory values are restored.

In patients with grade 3-4 thrombocytopenia (platelet count less than 50,000 / μl), grade 3-4 neutropenia (neutrophil count less than 1000 / μl), and grade 4 diarrhea, the dose of Oxaliplatin with subsequent injections is reduced from 85 mg / m ² up to 65 mg / m ² (in the treatment of ovarian cancer and disseminated colorectal cancer) and from 85 mg / m ² to 75 mg / m ² (in the adjuvant treatment of colorectal cancer, in addition to the standard dose reduction of fluorouracil, if combined therapy is used).

Patients who have acute laryngeal-pharyngeal dysesthesia during the infusion of the solution or within a few hours after the end of the 2-hour infusion are advised to increase the time of the next procedure to 6 hours.

Recommendations for adjusting the dose of Oxaliplatin in the event of neurotoxicity:

• presence of neurotoxicity symptoms of pain lasting longer than 7 days, and paresthesia without functional disturbances continued until the next cycle to be reduced subsequent dose oxaliplatin with 85 mg / m ² to 65 mg / m ² (in the treatment of ovarian cancer and metastatic colorectal cancer), and from 85 mg / m ² to 75 mg / m ² (with adjuvant treatment of colorectal cancer);
• paresthesia with functional impairment, persisting until the next cycle: oxaliplatin should be canceled (resumption of therapy is possible after the severity of symptoms of neurotoxicity has been reduced).

In the event of mucositis and / or stomatitis of the 2nd degree of toxicity and higher, treatment with the drug should be suspended until the manifestations of toxicity decrease or their complete relief.

In case of mild impairment of renal function, as well as mild and moderate impairment of liver function, dose adjustment of Oxaliplatin is not required. In patients with moderate renal insufficiency, drug treatment is started with a dose of 65 mg / m ², carefully monitoring renal function. There are no data on the use of oxaliplatin in severe renal and / or liver dysfunction.

In elderly patients (over 65 years old), Oxaliplatin is used in usual doses.

Instructions for preparing solution for infusion

When preparing the solution, as well as during its introduction, do not use equipment and needles containing aluminum.

Oxaliplatin should not be diluted and dissolved in 0.9% sodium chloride solution and mixed with chloride-containing and other alkaline (saline) solutions.

To prepare a solution for infusion, add 250-500 ml of 5% dextrose solution to the concentrate. The concentration of the resulting solution should be at least 0.2 mg / ml.

When using Oxaliplatin in the form of a lyophilisate, the following dilution scheme is used:

• dosage 50 mg: vials with a capacity of 20 ml - 10 ml of solvent; vials with a capacity of 50 ml - 20 ml of solvent;
• dosage 100 mg: vials with a capacity of 50 ml - 20 ml of solvent; vials with a capacity of 100 ml - 40 ml of solvent.

The solvent can be 5% dextrose solution or water for injection. Then the reconstituted preparation is diluted according to the scheme described above (add 250-500 ml of 5% dextrose solution).

It is recommended to use the prepared solution immediately. It remains stable for 24 hours at a temperature of + 2 … + 8 ° C. If sediment or turbidity appears, the solution should be disposed of.

Oxaliplatin solution should not be mixed in the same infusion set with other drugs, especially calcium folinate and fluorouracil. It is forbidden to inject undiluted concentrate.

Side effects

When using Oxaliplatin as part of a combination therapy with calcium folinate / fluorouracil, side effects from the following systems and organs may occur:

• digestive system: very often - vomiting, nausea, constipation or diarrhea, abdominal pain, mucositis or stomatitis; often - gastroesophageal reflux disease, dyspeptic disorders, bleeding from the rectum, gastrointestinal bleeding; rarely - pancreatitis, colitis, including pseudomembranous;
• hepatobiliary system: very rarely - veno-occlusive liver disease and associated nodular regenerative hyperplasia, peliotic hepatitis (bacillary purpuric hepatitis) and fibrosis of the perisinusoidal spaces (manifested by portal hypertension and / or increased activity of liver enzymes);
• metabolism and nutrition: very often - hyperglycemia, anorexia; often - low blood calcium levels;
• cardiovascular system: very often - nosebleeds; often - increased blood pressure, flushing, thromboembolism, deep vein thrombosis;
• respiratory system: very often - shortness of breath, cough; often - pulmonary embolism, hiccups; rarely - pulmonary fibrosis, acute interstitial lung damage (in extremely rare cases, fatal);
• lymphatic system and blood: very often - leukopenia, thrombocytopenia, anemia, neutropenia, lymphopenia; often - febrile neutropenia (including grade 3-4); rarely - disseminated intravascular coagulation, hemolytic anemia;
• nervous system: very often - headache, violation of taste sensations, acute neurosensory symptoms (transient dysesthesia, hypesthesia and paresthesia; double vision, dysphonia and aphonia, ptosis, hoarseness, decreased visual acuity, eye pain, narrowing of visual fields, facial pain, trigeminal neuralgia; muscle spasms, muscle twitching, masticatory muscle spasm, myoclonus, involuntary muscle contractions; ataxia, impaired coordination, imbalance and gait; discomfort / pressure sensation / pain / feeling of pressure in the chest or pharynx; peripheral sensory neuropathy, paresthesia or dysesthesia of the extremities); often - meningism, dizziness; rarely - the disappearance of deep tendon reflexes, dysarthria, posterior reversible leukoencephalopathy syndrome, Lermitt's symptom;
• psyche: often - insomnia, depression; infrequently - nervousness;
• sense organs: rarely - narrowing of the visual fields, transient loss of vision, transient decrease in visual acuity, optic neuritis, deafness; infrequently - ototoxicity;
• musculoskeletal system: very often - back pain; often - bone pain, arthralgia;
• urinary system: often - dysuria, the appearance of blood in the urine; very rarely - acute renal failure, acute interstitial nephritis, acute tubular necrosis;
• skin and subcutaneous fat: very often - skin lesions; often - erythematous rash, hyperhidrosis, pathological hair loss, changes in the nails, palmar-plantar erythrodysesthesia;
• immune system: very often - rhinitis, skin rash (including nettle), conjunctivitis; often - Quincke's edema, bronchospasm, a feeling of pain in the chest, a drop in blood pressure, anaphylactic shock;
• parasitic and infectious diseases: very often - various infections; often - neutropenic sepsis, upper respiratory tract infections; infrequently - sepsis (including fatal);
• data from instrumental and laboratory studies: very often - hyperbilirubinemia, increased body weight, increased activity of alkaline phosphatase, liver enzymes and lactate dehydrogenase; often - a decrease in body weight, an increase in the content of creatinine in the blood;
• other reactions: very often - fever, asthenia, increased fatigue, chills, reactions at the injection site (hyperemia, pain, thrombosis, edema, inflammation and necrosis of surrounding tissues).

In the course of post-marketing use, side effects of Oxaliplatin from the following systems and organs have been reported:

• digestive system: frequency unknown - duodenal ulcer with potential complications (ulcer perforation, ulcerative bleeding), intestinal ischemia (including fatal);
• cardiovascular system: frequency unknown - prolongation of the QT interval on the ECG with the development of severe ventricular arrhythmia;
• respiratory system: frequency unknown - laryngospasm;
• lymphatic system and blood: frequency unknown - hemolytic uremic syndrome;
• nervous system: frequency unknown - convulsions;
• musculoskeletal system: frequency unknown - cases of rhabdomyolysis, including fatal cases;
• parasitic and infectious diseases: frequency unknown - septic shock.

When using oxaliplatin and calcium folinate / fluorouracil in combination with bevacizumab, in addition to the side effects listed above, the following adverse reactions have been identified: gastrointestinal perforation, bleeding, arterial hypertension, impaired wound healing, proteinuria.

Overdose

With an overdose of oxaliplatin, an increase in the severity of side effects can be expected.

Treatment is symptomatic. The antidote is unknown. The patient should be closely monitored. A strict control of hematological parameters is established.

special instructions

The introduction of Oxaliplatin should be carried out under the supervision of an experienced physician. It is necessary to constantly monitor the possible toxic effects of the drug.

Once a week and before each infusion of the solution, the peripheral blood picture should be determined and the indicators of liver and kidney function should be assessed.

Before starting each cycle of treatment, the patient should undergo a neurological examination in order to timely detect symptoms of neurotoxicity. Signs of peripheral sensory neuropathy, in particular local mild paresthesias with functional impairments, can be observed for another 3 years after the end of adjuvant therapy (patients should be warned about this).

If dyspnea, dry cough, wheezing or pulmonary infiltrates are detected on X-ray, drug treatment should be suspended (until the diagnosis is clarified and interstitial pneumonitis is excluded).

Severe vomiting or diarrhea, especially when oxaliplatin is used in combination with fluorouracil, can cause dehydration, bowel obstruction, renal failure, hypokalemia, paralytic ileus, and metabolic acidosis.

If the patient's history indicates allergic reactions to platinum compounds, it is necessary to especially carefully monitor the appearance of allergic symptoms. In case of anaphylactoid and anaphylactic reactions, the administration of oxaliplatin should be discontinued immediately and appropriate symptomatic therapy should be initiated. Further use of the drug is contraindicated.

With the development of sepsis, intestinal ischemia, duodenal ulcer, neutropenic sepsis, disseminated intravascular coagulation, septic shock, hemolytic uremic syndrome, prolongation of the QT interval and rhabdomyolysis, the administration of Oxaliplatin should be discontinued.

Men and women should use reliable methods of contraception during treatment with the drug.

If the solution for infusion gets on the mucous membranes and skin, they should be urgently rinsed with water (since the drug is cytotoxic).

Influence on the ability to drive vehicles and complex mechanisms

During the period of treatment with Oxaliplatin, side reactions may occur that affect the speed of psychomotor reactions and coordination of movements (for example, dizziness, transient loss of vision, etc.). When these adverse events occur, patients should refrain from driving vehicles and other potentially dangerous and complex mechanisms.

Application during pregnancy and lactation

Oxaliplatin is contraindicated in pregnant women, since the results of clinical studies suggest that at therapeutic doses it will have a teratogenic effect and / or lead to fetal death.

During treatment, as well as for 6 (for men) and 4 (for women) months after the end of therapy, it is necessary to use reliable methods of contraception.

There are no data on the penetration of oxaliplatin into breast milk. If it is necessary to carry out therapy during lactation, breastfeeding should be discontinued.

Pediatric use

Oxaliplatin is contraindicated in patients under the age of 18.

With impaired renal function

In patients with severely impaired renal function, Oxaliplatin is used with caution and at lower initial doses.

Drug interactions

Salicylates, paclitaxel, erythromycin, sodium valproate and granisetron do not significantly affect the binding of the drug to plasma proteins in vitro.

A combination with aluminum is not recommended, as the formation of a precipitate and a decrease in the activity of oxaliplatin is possible.

The drug is pharmaceutically incompatible with chloride-containing and alkaline (saline) solutions, including isotonic sodium chloride solution.

Analogs

Analogues of Oxaliplatin are Gessedil, Oxatera, Oksitan, Oxaliplatin Medak, Oxaliplatin-Teva, Oxaliplatin-Ebeve, Oxaliplatin-Russian Cancer Research Center, Oxaliplatin-Filaxis, Oxyplat, Platikad, Plaksat, Flatiplat, Texalokz, Elorumatin, Ecological.

Terms and conditions of storage

Store in a dark place at a temperature not exceeding 25 ° C. The concentrate for preparation of solution for infusion must not be frozen.

Keep the drug away from children.

Shelf life: concentrate for preparation of solution for infusion - 2 years; lyophilisate for preparing a concentrate for preparing a solution for infusion - 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Oxaliplatin

In reviews of Oxaliplatin, patients share their experience of using an antineoplastic agent in the treatment of ovarian cancer and colorectal cancer. In almost all cases, the dynamics are positive. However, almost always during the administration of the drug or after the infusion, side effects of Oxaliplatin occurred (nausea, headache, weakness, lethargy, bronchospasm, bone pain, tingling in the hands, taste disturbances, etc.).

Price for Oxaliplatin in pharmacies

The maximum selling prices for Oxaliplatin, registered by the manufacturer and indicated in the VED (Essential and Essential Medicines) register:

• lyophilisate for the preparation of a concentrate for the preparation of a solution for infusion, 1 bottle per package: 50 mg per bottle - 4900 rubles; 100 mg in a bottle - 9800 rubles;
• concentrate for the preparation of solution for infusion, 2 mg / ml, 1 bottle per package: 25 ml per bottle - 6441.5 rubles; 50 ml per bottle - 12883 rubles.

The actual retail price of Oxaliplatin is currently unknown. Similar drugs, for example, Oxaliplatin Medak, can be bought for 1600-1700 rubles. (bottles of 50 mg) and 3380-3400 rubles. (bottles of 100 mg).

Oxaliplatin: prices in online pharmacies

Drug name Price Pharmacy

Oxaliplatin medak 50 mg lyophilisate for preparation of solution for infusion 1 pc. 1649 RUB Buy

Oxaliplatin ebeve conc. d / prigot. solution for inf. 5mg / ml vial No. 10ml No. 1 1849 RUB Buy

Oxaliplatin medak 100 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 2999 Buy

Oxaliplatin ebeve conc. d / prigot. solution for inf. 5mg / ml vial 20ml No. 1 RUB 3735 Buy

Oxaliplatin medak 150 mg lyophilisate for preparation of solution for infusion 1 pc. 4759 RUB Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!