Universal reference book for medicines
Product name: EXOURUM (EXORUM)

Active substance: oxaliplatin

Type: Antitumor preparation

Manufacturer: ЛЭНС-ФАРМ (Russia)
Composition, form of production and packaging
Lyophilizate for the preparation of a solution for infusions
in the form of a porous mass of white or almost white color.

1 f.

oxaliplatin 50 mg

- "- 100 mg

Excipients: lactose monohydrate.

Vials of colorless glass (1) - packs cardboard.

INSTRUCTION FOR THE SPECIALIST.

The product description was approved by the manufacturer for the 2009 print edition.

PHARMACHOLOGIC EFFECT

An antineoplastic agent, a derivative of platinum, in whose molecular structure the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane.
Exorum exhibits a wide range of cytotoxic effects, and also exhibits in vitro and in vivo activity on various models of cisplatin-resistant tumors.
The mechanism of action of the drug is due to the interaction of biotransformed aqueous derivatives of oxaliplatin with DNA by formation of inter- and intraspiral bridges and suppression of DNA synthesis.

PHARMACOKINETICS

Distribution and Metabolism

In vivo, oxaliplatin is actively biotransformed and not detected in the plasma by the end of a 2-hour dose of 85 mg / m 2 , with 15% of the administered dose in the blood, and the remaining 85% are rapidly distributed into tissues (or excreted in the urine).
Platinum binds to plasma albumin.
Excretion

It is excreted in the urine for the first 48 hours. By the fifth day about 54% of the entire dose is found in the urine and less than 3% in the stool.

Pharmacokinetics in special clinical cases

A significant decrease in clearance from 17.6 ± 2.18 l / h to 9.95 ± 1.91 l / h was observed in renal failure together with a statistically significant decrease in V d from 330 ± 40.9 to 241 ± 36.1 l.
The effect of severe renal failure on the clearance of platinum has not been studied.
INDICATIONS

- disseminated colorectal cancer (as monotherapy or combined therapy in combination with fluoropyrimidines).

DOSING MODE

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

Hyperhydration with oxaliplatin is not required.
If oxaliplatin is used in combination with 5-fluorouracil, oxaliplatin infusion should precede the administration of 5-fluorouracil.
The drug is given in a dose of 85 mg / m 2 once or twice a week as monotherapy or in combination with 5-fluorouracil.

Repeated administration of oxaliplatin is only performed with neutrophil count> 1500 / μL and platelets> 50,000 / μL.

Recommendations for dose adjustment and administration of oxaliplatin.

When hematological disorders (neutrophil count <1500 / μL and / or platelets <50,000 / μL), the next course is postponed until the laboratory parameters are restored.

With the development of diarrhea 4 degrees of toxicity (according to the WHO scale), neutropenia 3-4 degrees (neutrophil count <1000 / μl), thrombocytopenia 3-4 degrees (platelet count <50,000 / μl) dose of oxaliplatin in subsequent injections should be reduced from 85 mg / m 2 to 65 mg / m 2 for the treatment of disseminated colorectal cancer and ovarian cancer;
and up to 75 mg / m 2 with adjuvant therapy for colorectal cancer in addition to the usual reduction in the dose of 5-fluorouracil in the case of their combined use.
Patients who, during infusions or within a few hours after 2-hour infusions develop acute laryngeal-pharyngeal paresthesia, the next infusion of oxaliplatin should be performed within 6 hours.

When pain (as a sign of neurotoxicity) lasts more than 7 days or when paresthesia without functional impairment persists until the next cycle, the subsequent dose of oxaliplatin should be reduced by 25%.

In paresthesia with functional impairment, which persists until the next cycle, oxaliplatin should be discontinued.

With a decrease in the severity of the symptoms of neurotoxicity after the withdrawal of oxaliplatinum, treatment resumption may be considered.

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

Data on the use of the drug in patients with severe renal impairment are not present.
Due to the limited data on safety and tolerability of the drug in patients with moderate renal impairment , the ratio of benefit to risk should be weighed against the use of oxaliplatin. Therapy in this category of patients can be initiated with the recommended dose, under careful control of kidney function. With a mild degree of impaired renal function, dosage adjustment of oxaliplatin is not required.
Changes in the dosing regimen in patients with hepatic insufficiency of mild or moderate severity are not required.
Data on the use of oxaliplatin in patients withsevere impairment of liver function are absent.
The safety profile of oxaliplatin as a monotherapy or in combination with 5-fluorouracil in patients over the age of 65 is similar to that observed in patients under 65 years of age.

Rules for the preparation and administration of a solution

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

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

To dissolve the lyophilized powder, use water for injection or a 5% dextrose solution.
At the same time, 10 ml of the solvent is added to the bottle containing 50 mg of the Exorum preparation, and to the bottle with 100 mg - 20 ml to obtain a solution at a concentration of 5 mg / ml.
Immediately after dissolving the lyophilized powder, the solution for infusion should be prepared.

To prepare the infusion solution, the dissolved preparation of Exorum is diluted in 250-500 ml of 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml.
It is recommended to use the infusion solution immediately after preparation. The infusion solution remains stable for 24 hours at a temperature of 2 ° to 8 ° C.
A solution with signs of precipitation is subject to destruction.
Use only a clear solution.
The solution of oxaliplatin should not be mixed in the same infusion system with other drugs, especially with 5-fluorouracil and calcium folinate.
The drug should not be administered undiluted.
SIDE EFFECT

The incidence of adverse reactions listed below was determined according to the following criteria: very often (> 1/10), often (> 1/100, <1/10);
sometimes (> 1/1000, <1/100); rarely (> 1/10 000, <1/1000); very rarely (<1/10 000), including individual messages.
From the hemopoietic system: very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia;
often - febrile neutropenia (including grade 3-4), sepsis against neutropenia; rarely - hemolytic anemia, immune thrombocytopenia.
On the part of the digestive system : very often - nausea, vomiting, diarrhea, stomatitis, mucositis, pain in the stomach, constipation, loss of appetite, increased level of alkaline phosphatase, activity of liver enzymes, bilirubin, LDH;
often - dyspepsia, gastro-esophageal reflux, hiccough; sometimes - intestinal obstruction; rarely - colitis, including cases of pseudomembranous colitis.
From the side of the central nervous system and peripheral nervous system: very often - peripheral neurosensory neuropathy, sensitivity disorders, 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 provoked by cold. The duration of these symptoms, which are usually docked in the interval between courses, increases depending on the total dose of oxaliplatin. Functional disorders in the form of difficulty in performing accurate movements are possible consequences of sensory damage. The risk of functional disorders at a total dose of about 850 mg / m 2 (10 cycles) is about 10%, reaching 20% ​​in the case of a total dose of 1020 mg / m 2 (12 cycles). After cessation of treatment in most cases, the severity of neurologic symptoms decreases or they completely stop.
In 3% of patients 3 years after the end of treatment, either stable local paresthesias of moderate intensity (2.3%) or paresthesia affecting functional activity (0.5%) were observed.

On the background of treatment with oxaliplatin, acute neurosensory manifestations were noted, which usually occurred within a few hours after the administration of the drug and were most often provoked by exposure to cold.
They were characterized by transient paresthesia, dysesthesia or hypoesthesia, rarely (1-2%) - an acute syndrome of laryngeal pharyngeal dysesthesia. The latter manifested itself as a subjective feeling of dysphagia and dyspnea without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or spasm of the larynx, or bronchospasm (without stridor or wheezing). Also observed were such phenomena as spasm of the jaw muscles, dysesthesia of the tongue, dysarthria and a feeling of pressure in the chest. Usually, these symptoms were quickly stopped both without the use of drug therapy, and with the administration of antihistamines and bronchodilators. Increasing the duration of infusion during subsequent cycles of oxaliplatin therapy can reduce the incidence of this syndrome.
From the musculoskeletal system: very often - pain in the back;
often - arthralgia, pain in the bones.
From the respiratory system: very often - cough, shortness of breath;
often - rhinitis, infections of the upper respiratory tract; rarely - pulmonary fibrosis.
From the cardiovascular system: often - chest pain, thrombophlebitis of deep veins, thromboembolism of pulmonary arteries.

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, excessive sweating, violations from the nails.
On the part of the organs of sight and hearing: often - conjunctivitis, visual impairment;
rarely - transient reduction in visual acuity, loss of vision, 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, arterial hypotension, anaphylactic shock can be observed.
Often there have been cases of allergic manifestations, such as a rash (especially hives), conjunctivitis or rhinitis.
Local reactions: with extravasation of the drug - pain and inflammatory reactions at the site of administration.

From laboratory indicators: very often - hypokalemia, violations of sodium and glucose in the blood serum;
often - increasing the level of creatinine.
Other: very often - increased body temperature, increased fatigue, weight gain, impaired taste.

CONTRAINDICATIONS

- myelosuppression before the first course of therapy with a neutrophil count <2000 / μL and / or platelets <100,000 / μL;

- peripheral sensory neuropathy with functional disorders before the start of the first course of therapy;

- severe renal dysfunction (CK <30 ml / min);

- Pregnancy;

- lactation (breastfeeding);

- Hypersensitivity to oxaliplatinum or other components of the drug.

PREGNANCY AND LACTATION

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

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

APPLICATION FOR FUNCTIONS OF THE LIVER

Data on the use of the drug in patients with severe renal impairment are not present.
The drug is contraindicated in severe violations of kidney function (creatinine clearance less than 30 ml / min ).
Due to the limited data on safety and tolerability of the drug in patients with moderate renal impairment , the ratio of benefit to risk should be weighed against the use of oxaliplatin.
Therapy in this category of patients can be initiated with the recommended dose, under careful control of kidney function. With a mild degree of impaired renal function, dosage adjustment of oxaliplatin is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Changes in the dosing regimen in patients with hepatic insufficiency of mild or moderate severity are not required.
Data on the use of oxaliplatin in patients with severe impairment of liver function are absent.
APPLICATION IN ELDERLY PATIENTS

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

SPECIAL INSTRUCTIONS

Exorcum should be used only in specialized departments of oncology and under the supervision of a qualified oncologist.
Continuous monitoring of possible toxic effects in the treatment with Exorum is mandatory.
Regularly (once a week), as well as before each introduction of the Exorum, it is necessary to conduct a study of peripheral blood, liver function and kidney function.

Before the start of each treatment and during treatment, a neurological examination should be performed.
Patients should be informed about the possibility of persistent symptoms of peripheral sensory neuropathy after the end of the course of treatment. Localized mild paresthesias with functional disorders can last up to 3 years after the end of treatment according to the adjuvant treatment regimen.
If respiratory symptoms (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 kidney failure may be due to severe diarrhea or vomiting, especially when using Exorum in combination with 5-fluorouracil.

Patients with allergic reactions to other platinum compounds in the anamnesis should be monitored for allergic symptoms.
In the case of a reaction to oxaliplatin, anaphylactic, infusion should be immediately discontinued and appropriate symptomatic treatment should be prescribed. Further use of oxaliplatin in the case of allergic reactions is contraindicated.
With extravasation, the infusion should be stopped immediately and local symptomatic treatment started.
The remaining dose of the drug should be injected into another vein.
When using the drug should be observed all the usual instructions adopted for the use of cytotoxic drugs.
If you get lyophilizate or a solution of Exorum on the skin or mucous membranes, they should be washed immediately and thoroughly with water.
OVERDOSE

Symptoms: In case of an 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.
DRUG INTERACTION

There was no significant change in the binding of oxaliplatin to blood plasma proteins with simultaneous use with erythromycin, salicylates, granisetron, paclitaxel, 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.

TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

TERMS AND CONDITIONS OF STORAGE

List B. The drug should be stored in a dry, protected from light and out of reach of children at a temperature of no higher than 25 ° C.
Shelf life - 2 years.
Alphabetical index of medicines:
A  B  V  G  D  E  J
Z  I  Y  K  L  M  N
O  P  R  S  T  U  F
H  C  CH  SH  E  U  Y
Rambler's Top100
Privacy policy:
Copyright 2009 - 2017. Universal reference book of medicines. All rights reserved.
When using site materials, an active hyperlink is required!