Exorum, vial, 50mg

Composition

of 1 fl. – oxaliplatin 50 mg.

Excipients: lactose monohydrate.

Pharmacological action

antitumor drug derived from platinum, in the molecular structure of which the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane. Exorum exhibits a broad spectrum of cytotoxic activity, and is also active in vitro and in vivo in various cisplatin-resistant tumor models.

The mechanism of action of the drug is due to the interaction of biotransformed aqueous oxaliplatin derivatives with DNA by forming inter-and intra-helical bridges and suppressing DNA synthesis.

Indications

Disseminated colorectal cancer (as monotherapy or combination therapy in combination with fluoropyrimidines).

Use during pregnancy and lactation

Exorum is contraindicated for use during pregnancy and lactation (breastfeeding).

Women and men of childbearing age should use reliable methods of contraception when using the drug.

Contraindications

— myelosuppression prior to the first course of therapy at the level of neutrophils <2000/µl and/or platelets <100 000/µl;

peripheral sensory neuropathy with functional impairment prior to first course of therapy;

— severe renal dysfunction (CC <30 ml/min);

— pregnancy;

— lactation (breastfeeding);

— hypersensitivity to oxaliplatin or other components of the drug.

Side effects

the Frequency of adverse reactions listed below were determined according to the following criteria: very common (>1/10), often (>1/100, <1/10), sometimes (>1/1000, <1/100); rare (>1/10 000, <1/1000); very rare (<1/10 000), including individual messages.

From the hematopoietic system:  very often-anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often-febrile neutropenia (including grade 3-4), sepsis on the background of neutropenia; rarely-hemolytic anemia, immune thrombocytopenia.

From the digestive system: very often-nausea, vomiting, diarrhea, stomatitis, mucositis, stomach pain, constipation, loss of appetite, increased alkaline phosphatase, liver enzyme activity, bilirubin, LDH; often – dyspepsia, gastro-esophageal reflux, hiccups; sometimes – intestinal obstruction; rarely – colitis, including cases of pseudomembranous colitis.

From the central nervous system and peripheral nervous system:  very often – peripheral sensorineural neuropathy, sensory disturbances, headache, asthenia; often-dizziness, meningism, depression, insomnia; sometimes-increased nervousness; rarely-dysarthria. Neurotoxicity is a dose-limiting factor. Often, the symptoms of sensory neuropathy are triggered by cold. The duration of these symptoms, which are usually relieved between courses, increases depending on the total dose of oxaliplatin. Functional disorders in the form of difficulty performing precise movements are possible consequences of sensory damage. The risk of functional impairment at a total dose of about 850 mg/m2 (10 cycles) is about 10%, reaching 20% in the case of a total dose of 1020 mg/m2 (12 cycles). After discontinuation of treatment, in most cases, the severity of neurological symptoms decreases or they are completely stopped.

In 3% of patients,3 years after the end of treatment, either sustained local paresthesias of moderate intensity (2.3%) or paresthesias affecting functional activity (0.5%) were observed.

Against the background of oxaliplatin treatment, acute sensorineural manifestations were noted, which usually occurred within a few hours after use of the drug and were most often provoked by exposure to cold. They were characterized by transient paresthesia, dysesthesia or hypesthesia, rarely (1-2%) – acute laryngopharyngeal dysesthesia syndrome. The latter was manifested by a subjective feeling of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or laryngeal spasm, or bronchospasm (without stridor or wheezing). There were also symptoms such as jaw muscle spasms, tongue dysesthesia, dysarthria, and chest pressure. Usually, these symptoms were quickly relieved both without the use of medication, and with the introduction of antihistamines and bronchodilators. Increasing the duration of the infusion during subsequent cycles of oxaliplatin therapy reduces the frequency of this syndrome.

Musculoskeletal disorders:  very often-back pain; often-arthralgia, bone pain.

Respiratory system disorders:  very often – cough, shortness of breath; often-rhinitis, upper respiratory tract infections; rarely-pulmonary fibrosis.

From the cardiovascular system:  often – pain behind the sternum, deep vein thrombophlebitis, pulmonary embolism.

From the urinary system: often-hematuria, dysuria.

Dermatological reactions:  very often – alopecia, skin rashes; often-peeling of the skin of the palms and feet, erythematous rashes, increased sweating, nail disorders.

From the side of the organs of vision and hearing:  often-conjunctivitis, visual disturbances; rarely-transient decrease in visual acuity, loss of visual fields, hearing loss, neuritis of the auditory nerve.

Allergic reactions: rarely (when used as monotherapy) or often (in combination with 5-fluorouracil +/- calcium folinate), bronchospasm, angioedema, hypotension, anaphylactic shock may occur. Allergic reactions such as rash (especially urticaria), conjunctivitis or rhinitis were frequently reported.

Local reactions:  with extravasation of the drug-pain and inflammatory reactions at the injection site.

From the side of laboratory parameters:  very often – hypokalemia, violations of the content of sodium and glucose in the blood serum; often-increased creatinine levels.

Other services:  very often-increased body temperature, increased fatigue, increased body weight, taste disorders.

Interaction

No significant changes in the binding of oxaliplatin to plasma proteins were observed when co-administered with erythromycin, salicylates, granisetron, paclitaxel, and sodium valproate.

Pharmaceutical interaction

The drug is incompatible with alkaline solutions or solutions containing chlorides.

When interacting with aluminum, it is possible to form a precipitate and reduce the activity of oxaliplatin.

How to take, course of use and dosage

Exorum is prescribed only for adults in the form of intravenous infusions for 2-6 hours.

Hyperhydration is not required when using oxaliplatin. If oxaliplatin is used in combination with 5-fluorouracil, the oxaliplatin infusion should precede the use of 5-fluorouracil.

The drug is administered at a dose of 85 mg / m2 once every 2 weeks as monotherapy or in combination with 5-fluorouracil.

Repeated use of oxaliplatin is performed only when the number of neutrophils >1500/µl and platelets > > 50 000/µl.

Recommendations for adjusting the dose and mode of use of oxaliplatin.

With hematological disorders (neutrophil count <1500 / µl and / or platelets

With the development of diarrhea of 4 degrees of toxicity (according to the WHO scale), neutropenia of 3-4 degrees (neutrophil count <1000/µl), thrombocytopenia of 3-4 degrees (platelet count

Patients who develop acute laryngopharyngeal paresthesia during infusions or within a few hours after 2-hour infusions, the next oxaliplatin infusion should be performed within 6 hours.

If there is pain (as a sign of neurotoxicity) lasting more than 7 days or if paresthesia without functional disorders persists until the next cycle, the subsequent dose of oxaliplatin should be reduced by 25%.

If paresthesia with functional disorders persists until the next cycle, oxaliplatin should be discontinued.

If the severity of neurotoxicity symptoms decreases after discontinuation of oxaliplatin, you can consider resuming treatment.

With the development of stomatitis and / or mucositis of the 2nd or higher degree of toxicity, treatment with oxaliplatin should be suspended until they stop or reduce the manifestations of toxicity to the 1st degree.

There are no data on the use of the drug in patients with severe renal impairment. Due to limited data on the safety and tolerability of the drug in patients with moderate renal impairment, the patient’s benefit-risk ratio should be weighed before using oxaliplatin. Therapy in this category of patients can be started with the recommended dose, under careful monitoring of renal function. In patients with mild renal impairment, no dose adjustment of oxaliplatin is required.

Changes in the dosage regimen in patients with mild or moderate hepatic insufficiency are not required. There are no data on the use of oxaliplatin in patients with severe hepatic impairment.

The safety profile of oxaliplatin as monotherapy or in combination with 5-fluorouracil in patients over 65 years of age is similar to that observed in patients under 65 years of age.

Rules for preparation and use of the solution

Do not use needles or other equipment containing aluminum when preparing and administering Exorum.

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

Water for injection or a 5% dextrose solution should be used to dissolve the lyophilized powder. At the same time,10 ml of solvent is added to the bottle with 50 mg of Exorum, and 20 ml is added to the bottle with 100 mg to obtain a solution at a concentration of 5 mg / ml.

Immediately after dissolving the lyophilized powder, you should start preparing the solution for infusions.

To prepare an infusion solution, the dissolved preparation Exorum is diluted in 250-500 ml of 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml. The solution for infusions is recommended to be used immediately after preparation. The infusion solution remains stable for 24 hours at a temperature of 2° to 8°C.

The solution with signs of precipitation must be destroyed. You can only use a clear solution.

Oxaliplatin solution should not be mixed in the same infusion system with other medications, especially 5-fluorouracil and calcium folinate. The drug should not be administered undiluted.

Overdose

Symptoms: in case of overdose, the described side effects may increase.

Treatment: careful monitoring of the patient’s condition (including hematological control); conduct symptomatic therapy. The antidote is unknown.

Special instructions

Exorum should only be used in specialized oncology departments and under the supervision of a qualified oncologist. Constant monitoring of possible toxic effects during treatment with Exorum is mandatory.

Regularly (once a week), as well as before each use of Exorum, peripheral blood, liver and kidney function indicators should be examined.

A neurological examination should be performed before each use and during treatment. Patients should be informed about the possibility of persistent symptoms of peripheral sensory neuropathy after the end of treatment. Localized moderate paresthesias with functional disorders can last up to 3 years after the end of treatment according to the adjuvant drug use scheme.

If respiratory symptoms appear (dry cough, dyspnoea, wheezing, or detection of pulmonary infiltrates during X-ray examination), treatment with Exorum should be suspended until the presence of interstitial pneumonitis is excluded.

Symptoms such as dehydration, paralytic ileus, intestinal obstruction, hypokalemia, metabolic acidosis, and renal failure may be due to severe diarrhea or vomiting, especially when Exorum is used in combination with 5-fluorouracil.

Patients with a history of allergic reactions to other platinum compounds should be monitored for allergic symptoms. In the event of an anaphylactic-like reaction to oxaliplatin, the infusion should be stopped immediately and appropriate symptomatic treatment should be prescribed. Further use of oxaliplatin in case of allergic reactions is contraindicated.

In case of extravasation, the infusion should be stopped immediately and local symptomatic treatment should be initiated. The remaining dose of the drug should be injected into another vein.

When using the drug, all the usual instructions adopted for the use of cytotoxic drugs should be followed. If Exorum lyophilizate or solution gets on the skin or mucous membranes, they should be immediately and thoroughly rinsed with water.

Form of production

Lyophilizate for the preparation of an infusion solution in the form of a porous mass of white or almost white color.

Active ingredient

Oxaliplatin

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Cancer