Stricarb

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT STERICARB (STRICARB)

Composition:

Active substance: carboplatin;

1 ml of solution contains carboplatin 10 mg;

Excipient: water for injections.

Pharmaceutical form. Infusion solution.

Main physico-chemical properties: clear solution, colorless to pale yellow.

Pharmacotherapeutic group. Antineoplastic agents. Platinum compounds. Carboplatin.

ATC code L01XA02.

Pharmacological properties.

Pharmacodynamics.

Carboplatin is an antitumor agent that is an inorganic platinum complex. The antitumor activity of carboplatin is comparable to that of cisplatin against a broad spectrum of tumors regardless of their localization. Its antitumor mechanism of action is associated with inhibition of nucleic acid synthesis, leading to cell death. The ability of the drug to induce regression of primary tumors and metastases is also related to its effect on the body's immune system.

Studies using DNA alkaline elution and DNA binding assays have demonstrated qualitative similarities in the mechanisms of action of carboplatin and cisplatin. Like cisplatin, carboplatin causes alterations in the superhelical conformation of DNA, associated with a DNA shortening effect. It also induces interstrand and intrastrand cross-links in DNA.

Pharmacokinetics.

After intravenous administration, plasma concentrations of carboplatin and free platinum decline according to a biphasic kinetic pattern. The initial half-life of free platinum is approximately 1–2 hours, and the terminal half-life is 3–6 hours; total platinum exhibits a similar initial half-life, but a longer terminal half-life (approximately 24 hours). With repeated daily dosing over four consecutive days, no accumulation of platinum in plasma is observed. Approximately 85% of the platinum dose in plasma is protein-bound within 24 hours after administration.

In plasma, the concentration of platinum as part of the carboplatin molecule significantly exceeds that of free platinum. Carboplatin binds to plasma proteins and is slowly eliminated from the body, primarily via the kidneys. About 30% of the administered dose is excreted unchanged. In patients with creatinine clearance above 60 ml/min, approximately 60–80% of the administered dose is excreted in urine within 12 hours after administration.

Clinical characteristics.

Indications.

Indicated as monotherapy or in combination with other antineoplastic agents for the treatment of the following diseases:

• Epithelial ovarian cancer;
• Small cell lung cancer.

Contraindications.

Hypersensitivity to carboplatin or to other platinum compounds.

Severe myelosuppression.

Recent significant blood loss.

Renal impairment (creatinine clearance < 30 mL/min).

Hearing impairment.

Pregnancy and breastfeeding period.

Pediatric age.

Concomitant administration of yellow fever vaccine.

Special safety precautions.

Carboplatin treatment must be administered under supervision of an oncologist in a hospital setting with adequate patient monitoring facilities.

When handling the drug, follow the safety procedures for working with cytostatic agents.

Interaction with other medicinal products and other forms of interaction.

Due to increased risk of thrombosis in cancer patients, anticoagulant therapy is often prescribed. High interindividual variability in coagulation parameters during the disease, as well as possible interaction between oral anticoagulants and chemotherapy agents, necessitate regular monitoring of INR values.

Concomitant use with yellow fever vaccine is contraindicated due to the risk of developing fatal generalized infection.

Combination with live attenuated vaccines (except yellow fever vaccine) is not recommended because of the risk of systemic, potentially fatal disease. This risk is increased in patients with immunosuppression due to underlying disease. Inactivated vaccines should be used if available (e.g. polio vaccine).

When used in combination with other myelosuppressive agents, carboplatin enhances bone marrow suppression.

Concomitant use of carboplatin and loop diuretics may increase the risk of renal and auditory dysfunction.

When carboplatin is combined with other agents that suppress bone marrow function, the myelosuppressive effects of carboplatin and/or the co-administered drugs may be enhanced. Concurrent use with other nephrotoxic agents may result in severe and prolonged myelotoxicity due to reduced renal clearance of carboplatin.

Concomitant administration of carboplatin and warfarin should be approached with caution, as cases of increased INR have been observed.

Concomitant use with phenytoin or fosphenytoin is not recommended due to the risk of convulsions, since cytotoxic agents reduce gastrointestinal absorption of phenytoin, and due to the risk of increased toxicity or reduced efficacy of cytotoxic agents resulting from enhanced hepatic metabolism of phenytoin.

Carboplatin should not be administered simultaneously with agents containing chelating components, as they may theoretically reduce the antitumor activity of carboplatin. However, experimental and clinical studies have shown that diethyldithiocarbamate does not affect the antitumor activity of carboplatin.

Concomitant use of cyclosporine, tacrolimus, and sirolimus may lead to lymphoproliferative disorders due to enhanced immunosuppression.

Experimental studies have demonstrated that carboplatin acts synergistically with etoposide and vindesine.

Carboplatin reacts with aluminum, forming a black precipitate. Therefore, when using the drug Stricarb, both during solution preparation and administration, avoid using needles, syringes, catheters, and infusion systems containing aluminum.

Special precautions for use.

Warnings.

Carboplatin therapy should be administered under the supervision of an experienced oncologist. Diagnostic facilities must be available in the hospital to ensure proper patient monitoring and prevention of complications.

Regular blood tests, as well as functional tests to assess kidney and liver function, must be performed. If significant bone marrow suppression or abnormal kidney or liver function is detected, the use of the medicinal product should be discontinued.

Patients who have undergone extensive prior therapy (especially with cisplatin), patients with poor general health status or aged 65 years and older, or patients receiving concomitant treatment with nephrotoxic medicinal products may, like patients with severe renal impairment, experience severe or prolonged myelosuppression.

For these patient groups, initial dosing should be reduced accordingly (see section "Dosage and administration").

Regular blood monitoring is necessary to observe the effects of carboplatin. Myelosuppressive effects of carboplatin are closely related to renal clearance. Patients with impaired renal function require monitoring of renal function parameters before and during treatment. Therapy should be discontinued if significant deviations from normal bone marrow function or abnormal kidney or liver function occur.

The usual interval between treatment cycles should be at least 4 weeks. Administration of carboplatin causes thrombocytopenia, leukopenia, and anemia.

Hematological toxicity. Hemolytic anemia with serological antibodies induced by the drug has been reported in patients treated with carboplatin. Such reactions may lead to fatal outcomes.

Leukopenia, neutropenia, and thrombocytopenia are dose-dependent and represent dose-limiting factors during treatment. Frequent monitoring of peripheral blood parameters is required during and after carboplatin therapy, and treatment with carboplatin should be discontinued if toxic effects occur until parameters return to normal. In patients receiving carboplatin monotherapy, the nadir of neutrophil counts typically occurs on day 21, whereas in patients receiving combination therapy, it occurs on day 15. Frequent monitoring of peripheral blood parameters is required during and after treatment. Subsequent treatment cycles should not be initiated until leukocyte and platelet counts have normalized. The following thresholds apply: leukocyte count ≥2000/mm³ and platelet count ≥100,000/mm³.

Anemia may be cumulative and may require blood transfusions in some cases.

Myelosuppressive effects may be cumulative when combined with other chemotherapy. Patients with severe and persistent myelosuppression are at high risk of infectious complications, including fatal outcomes. Therapy with carboplatin should be discontinued immediately if such effects occur.

To minimize additive effects, combined therapy including carboplatin and other myelosuppressive agents must be carefully planned, particularly regarding dosage and treatment schedule. Supportive transfusion therapy may be required in patients experiencing severe bone marrow suppression.

Cases of acute promyelocytic leukemia and myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) have been reported several years after treatment with carboplatin and other antineoplastic agents.

Hemolytic-uremic syndrome (HUS) is a life-threatening adverse effect. Carboplatin should be discontinued at the first signs of microangiopathic hemolytic anemia, such as rapid decrease in hemoglobin accompanied by thrombocytopenia, increased serum bilirubin, serum creatinine, blood urea nitrogen, or LDH. Renal failure may be irreversible after discontinuation of therapy and may require dialysis.

Allergic reactions. Allergic reactions, such as erythema, unexplained fever, and pruritus, may occur during carboplatin administration. In some cases, anaphylaxis, angioedema, and anaphylactoid reactions, including bronchospasm, urticaria, and facial swelling, have occurred, and very rarely, treatment has resulted in fatal outcomes. Treatment must be discontinued immediately and appropriate therapeutic measures initiated. These reactions are similar to those observed with other platinum-containing compounds and may occur within minutes after administration. The frequency of allergic reactions may increase with prior exposure to platinum-containing agents, even if reactions occurred only after carboplatin administration. Close monitoring for possible allergic reactions is required, and supportive treatment, including administration of antihistamines, adrenaline, and/or glucocorticoids, should be provided.

Hypersensitivity reactions progressing to Kounis syndrome (acute allergic coronary artery spasm that may lead to myocardial infarction) have been reported (see section "Adverse reactions").

Nephrotoxicity and effects on liver function. Carboplatin may cause kidney and liver dysfunction. Very high doses of carboplatin (exceeding the recommended dose by five times in monotherapy) have led to severe abnormalities in liver and kidney function. It has not yet been established whether adequate hydration can prevent this effect on kidney function. Dose reduction or treatment interruption is required in cases of moderate to severe kidney or liver dysfunction (see section "Adverse reactions").

Patients with pre-existing renal impairment are at higher risk of more frequent and severe nephrotoxic effects. Additionally, kidney dysfunction is more likely in patients who previously experienced nephrotoxicity with cisplatin. Although there are no clinical data indicating increased nephrotoxicity, carboplatin is not recommended to be combined with aminoglycosides or other nephrotoxic substances.

Veno-occlusive liver disease. Cases of hepatic venous obstruction (sinusoidal obstruction syndrome of the liver), some with fatal outcomes, have been reported. Patients should be monitored for signs and symptoms of liver dysfunction or portal hypertension, which are unlikely to be due to liver metastases.

Neurological toxicity. Regular neurological examinations and hearing tests should be performed, especially in patients receiving high doses of carboplatin. Neurotoxicity may manifest as paresthesia, reduced deep tendon reflexes, and ototoxicity, which are generally mild. These symptoms are more likely in patients aged 65 years and older, or in those previously treated with platinum-containing agents or other ototoxic drugs. Visual disturbances, including vision loss, have been reported with high-dose carboplatin. Vision typically recovers fully or with minor limitations within several weeks after completion of high-dose therapy.

Cases of reversible posterior leukoencephalopathy syndrome (RPLS) have been reported in patients receiving carboplatin as part of combination chemotherapy. RPLS is a rare, reversible neurological disorder that develops rapidly after discontinuation of treatment and may include seizures, hypertension, headache, confusion, blindness, and other visual and neurological disturbances. Diagnosis of RPLS is confirmed by brain imaging, preferably MRI (magnetic resonance imaging).

Tumor lysis syndrome (TLS). Post-marketing experience has reported cases of tumor lysis syndrome in patients treated with carboplatin as monotherapy or in combination with other chemotherapeutic agents. Patients at high risk of TLS—those with tumors characterized by high proliferative activity, extensive tumor burden, or high sensitivity to cytotoxic agents—should be closely monitored and appropriate preventive measures implemented.

Studies investigating combination therapy with carboplatin and cyclophosphamide have shown that thrombocytopenia occurs more frequently in elderly patients than in younger patients. Since renal function is often reduced in elderly patients, this factor must be considered when determining the drug dosage (see section "Dosage and administration").

Administration of live or live-attenuated vaccines in patients with impaired immune function during chemotherapy, including carboplatin therapy, may lead to severe or fatal infections. Therefore, live vaccination should be avoided during carboplatin treatment. Inactivated or non-live vaccines may be administered, although the immune response to such vaccines may be reduced (see also section "Interaction with other medicinal products and other forms of interaction").

The carcinogenic potential of carboplatin has not been studied, but compounds with similar mechanisms of action and mutagenicity have been reported to be carcinogenic. Secondary malignancies have been reported in association with multiple drug therapies.

The safety and efficacy of carboplatin in children and adolescents have not been established.

Carboplatin may cause nausea and vomiting. Prophylactic antiemetic premedication has been reported to reduce the frequency and intensity of these adverse effects.

Aluminum-containing instruments must not be used during the preparation and administration of carboplatin (see section "Incompatibilities").

Use during pregnancy or breastfeeding.

The drug is contraindicated during pregnancy and breastfeeding due to its high toxicity. Female patients of reproductive age must use effective contraception during carboplatin therapy and must inform their physician immediately if pregnancy occurs. Breastfeeding must be discontinued during treatment with Strikarbe.

Fertility. Women of reproductive age should use reliable contraception methods to prevent pregnancy during carboplatin therapy and for at least 6 months after completion of treatment. Pregnant patients or those who become pregnant during treatment should be referred for genetic counseling.

Carboplatin is genotoxic. Male patients are advised to avoid fathering a child during carboplatin therapy and for at least 6 months after completion of treatment. Sperm cryopreservation should be considered prior to starting therapy, as carboplatin treatment may lead to infertility.

Ability to affect reaction speed when driving or operating machinery.

Studies on the effect of the drug on the ability to drive or operate machinery have not been conducted.

Given that adverse reactions (e.g., hallucinations, bone marrow dysfunction) may occur in sensitive patients during treatment, such patients should refrain from driving or operating machinery requiring concentration during treatment.

Dosage and Administration

For intravenous use only.

Stricarb may be used in combination with other antineoplastic agents.

For adult patients who have not previously been treated with this medicinal product, carboplatin should be administered at a dose of 400 mg/m² body surface area as short intravenous infusions lasting 15–60 minutes, provided normal renal function.

Doses may also be calculated using the Calvert formula based on the patient's glomerular filtration rate (GFR) and the desired area under the pharmacokinetic concentration-time curve (AUC). It is important to note that doses calculated by the Calvert formula are expressed in milligrams, not milligrams per square meter.

Dose (mg) = desired AUC (mg/mL × min) × [GFR (mL/min) + 25]

Table 1

Treatment courses may be repeated with intervals of 4 weeks and/or when neutrophil count is at least 2,000/mm³ and platelet count is at least 100,000/mm³.

For patients in the risk group (those previously treated with myelosuppressive drugs and/or radiation therapy, as well as patients with poor general health status), the initial dose of carboplatin is 300–320 mg/m² of body surface area.

In patients with impaired renal function, carboplatin doses should be reduced according to glomerular filtration rate (GFR), as recommended in Table 2.

Table 2

In the treatment of elderly patients, doses of carboplatin should be adjusted according to the patient's general health status.

Preparation of solutions

Solutions must be prepared immediately before use.

Prior to administration, the drug should be diluted with 5% dextrose solution or 0.9% sodium chloride solution to a concentration of 0.4 mg/mL.

Freshly prepared solutions are physically and chemically stable for 24 hours when stored refrigerated (2–8 °C).

From a microbiological standpoint, the diluted solution should be administered immediately.

Strikarbu must not be administered through infusion systems containing aluminum or via needles containing aluminum (precipitate may form).

Before administration, the Strikarbu solution should be visually inspected for the presence of particulate matter and discoloration; if either is observed, the drug must not be used.

The solution should be drawn from the vial immediately before use.

Only a single withdrawal of the drug from the vial is permitted.

Appropriate handling procedures for cytotoxic agents should be followed when manipulating the drug.

Children

Contraindicated.

Overdose.

Symptoms of overdose. During initial clinical studies, carboplatin was administered at doses up to 1600 mg/m² per course. At these doses, life-threatening hematological adverse reactions such as granulocytopenia, thrombocytopenia, and anemia were observed. The lowest levels of granulocytes, platelets, and hemoglobin were recorded between days 9 and 25 (on average, on days 12–17). Granulocyte counts returned to ≥500/µL within 8–14 days (on average, by day 11), and platelet counts returned to ≥25,000/µL within 3–8 days (on average, by day 7).

Additionally, the following non-hematological adverse reactions were observed: renal dysfunction with a 50% reduction in glomerular filtration rate, neuropathies, ototoxicity, vision loss, alopecia, hyperbilirubinemia, mucositis, diarrhea, nausea and vomiting with headache, erythema, and severe infection. Hearing disturbances were mostly transient and reversible in most cases.

Treatment of overdose. There is no specific antidote for carboplatin overdose. Possible complications of overdose may include bone marrow suppression, as well as liver and kidney dysfunction. In the management of hematological adverse reactions, effective measures may include bone marrow transplantation and transfusions (platelets, blood).

Side effects.

Most adverse reactions are due to the drug's therapeutic effect, as it is not selective for malignant cells and affects all rapidly dividing cells. Consequently, adverse reactions may be expected in tissues and organs where normal cell division occurs at a relatively high rate, such as in the bone marrow, lymphoreticular tissue, gastrointestinal mucosa, skin, gonads, and in the fetus. Adverse effects may not manifest for days or even weeks, depending on the drugs used and the rate of cell division in a particular tissue, and may have a cumulative nature. The most serious adverse effect, which also limits the possibility of continuing therapy, is myelosuppression. Treatment with Strikarb must be administered in specialized centers with the involvement of qualified personnel.

The frequency of adverse reactions is classified as follows:

Very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), unknown (cannot be estimated from available data).

Infections and infestations.
Common: infections*.
Unknown: pneumonia.

Benign, malignant and unspecified neoplasms (including cysts and polyps).
Uncommon: development of secondary malignancies (including promyelocytic leukemia, which occurred 6 years after monotherapy with carboplatin and prior radiotherapy) has been observed after completion of carboplatin monotherapy and combination therapy (causal relationship not established).

Blood and lymphatic system disorders.
Very common: thrombocytopenia, neutropenia, leukopenia, anemia; the dose-limiting factor in carboplatin therapy is bone marrow suppression. In patients with impaired renal function, prior radiotherapy, poor general health status, and age ≥ 65 years, myelosuppression may be more severe and prolonged. Furthermore, bone marrow suppression is enhanced when carboplatin is combined with other agents having similar myelosuppressive effects. When carboplatin is used as monotherapy at the recommended dose and according to indications (frequency of administration), bone marrow suppression is usually reversible and non-cumulative.

When maximum tolerated doses of carboplatin are used in monotherapy, thrombocytopenia with platelet counts dropping below 50,000/mm³ was observed in approximately 25% of patients. The nadir usually occurs on days 14–21, with recovery within 35 days after initiation of treatment. Leukopenia with leukocyte concentration > 2,000/mm³ was observed in approximately 14% of patients; recovery begins from the day of reaching the nadir (days 14–28) and proceeds more slowly, usually within 42 days after the start of therapy. Neutropenia with granulocyte count < 1,000/mm³ was observed in approximately 18% of patients. In 15% of patients with normal baseline values, hemoglobin levels dropped below 8 g/dL. Anemia frequently occurs and may be cumulative. In a small number of patients, leukopenia and thrombocytopenia led to symptomatic reactions such as infections and bleeding.

Common: hemorrhage*, infectious complications in patients with poor general condition (< 1% leading to fatal outcome).
Unknown: blood dyscrasias, febrile neutropenia, hemolytic-uremic syndrome.

Immune system disorders.
Common: hypersensitivity reactions, anaphylactoid reactions. Anaphylactoid reactions, which rarely lead to fatal outcomes, may occur within minutes after injection. Symptoms include bronchospasm, pruritus, urticaria, angioedema, hives, facial flushing and swelling, dyspnea, hypotension, dizziness, anaphylactic shock, wheezing, and tachycardia (see section "Special precautions").

Metabolism and nutrition disorders.
Very common: following carboplatin therapy, decreased serum electrolytes (magnesium, potassium, sodium, and calcium) have been reported; however, these manifestations were not severe enough to cause clinical signs or symptoms. Early hyponatremia has also been reported.
Rare: anorexia, hyponatremia.
Unknown: dehydration, tumor lysis syndrome.

Nervous system disorders.
Common: peripheral neuropathy, paresthesia, decreased deep tendon reflexes, sensory disturbances, dysgeusia.

The incidence of peripheral neuropathy after carboplatin therapy is 4%. In most patients, neurotoxicity is limited to paresthesia and decreased deep tendon reflexes. The frequency and severity of adverse effects are increased in patients aged ≥ 65 years or those previously treated with cisplatin. Paresthesia present before starting carboplatin therapy, primarily due to prior cisplatin treatment, may persist or worsen during carboplatin therapy.

In isolated cases, symptoms from the central nervous system have been reported, although these are often attributable to concomitant use of antiemetic drugs.

Clinically significant sensory disturbances (e.g., visual disturbances, taste changes) were observed in 1% of patients.

The incidence of neurological adverse effects was higher in patients receiving carboplatin as part of combination therapy, possibly due to cumulative effects.

Very rare: cerebral stroke*.
Unknown: reversible posterior leukoencephalopathy syndrome. Hallucinations, anxiety, and nightmares are possible.

Eye disorders.
Common: transient visual disturbances, up to complete vision loss, have been rarely reported during treatment with platinum-containing agents. These disturbances usually occur only with high-dose therapy in patients with impaired renal function. In post-marketing surveillance studies, cases of optic neuritis have been reported.

Ear and labyrinth disorders.
Very common: subclinical hearing impairments in the high-frequency range (4000–8000 Hz) were observed audiometrically in 15% of patients after carboplatin therapy.
Common: clinical ototoxicity. Clinical symptoms occurred in only 1% of patients and were predominantly manifested as tinnitus. In patients with pre-existing hearing loss due to cisplatin therapy, hearing impairment may persist or worsen.

Clinically significant hearing loss has been observed in children who received higher-than-recommended doses of carboplatin in combination with other ototoxic drugs.

Cardiac disorders.
Common: cardiovascular disorders*.
Very rare: isolated cases of cardiovascular disorders (heart failure, embolism), cerebrovascular disorders (strokes) (causal relationship with carboplatin use not established), arrhythmia. Isolated cases of hypertension have been reported.
Unknown: Kounis syndrome.

Vascular disorders.
Uncommon: hemorrhagic complications.
Unknown: embolism*, hypertension, hypotension.

Respiratory, thoracic and mediastinal disorders.
Common: pulmonary fibrosis with constrictive chest pain and dyspnea, interstitial lung disease, bronchospasm; these should be considered if pulmonary hypersensitivity cannot be excluded.

Gastrointestinal disorders.
Very common: vomiting, nausea, colic, abdominal pain; nausea without vomiting occurred in approximately 15% of patients. 65% of patients reported vomiting, with one-third experiencing severe vomiting. Nausea and vomiting typically occur 6–12 hours after carboplatin administration. These symptoms usually resolve with antiemetic treatment and generally disappear within the first 24 hours after therapy. One-quarter of patients experience neither nausea nor vomiting. Only 1% of patients experienced vomiting refractory to medical treatment. Patients previously treated, especially with cisplatin, experience vomiting more frequently.

17% of patients reported gastrointestinal pain.

Common: diarrhea (8%), constipation (6%), mucositis, esophagitis.
Unknown: stomatitis, pancreatitis.

Hepatobiliary disorders.
Very common: mild to moderate liver function abnormalities were reported in approximately one-third of patients with normal baseline values receiving carboplatin therapy. Alkaline phosphatase increases more frequently (in 24% of patients) than serum glutamic oxaloacetic transaminase (in 15% of patients), alanine aminotransferase in serum, or total bilirubin (in 5% of patients). Most abnormalities spontaneously normalize during the treatment course. In half of the patients, these changes were predominantly mild and reversible.

In a limited group of patients receiving high-dose carboplatin injections and undergoing autologous bone marrow transplantation, liver function test abnormalities were observed.

Unknown: severe liver dysfunction (including acute liver necrosis) may occur after administration of higher-than-recommended doses of carboplatin.

Skin and subcutaneous tissue disorders.
Common: alopecia, skin disorders.
Unknown: urticaria, erythema, pruritus.

Musculoskeletal and connective tissue disorders.
Common: musculoskeletal disorders, asthenia.

Reproductive system and breast disorders.
Unknown: azoospermia and amenorrhea.

Renal and urinary disorders.
Common: renal function impairment with creatinine clearance < 60 mL/min was observed in 27% of patients. In patients with pre-existing renal impairment before starting carboplatin therapy, nephrotoxic effects may occur more frequently or be more severe.

It is unknown whether adequate hydration can compensate for this effect. In cases of moderate (creatinine clearance 41–59 mL/min) or severe (creatinine clearance 21–40 mL/min) renal impairment, dose reduction or discontinuation of the drug is required.

Common: urogenital disorders.

Uncommon: overall, nephrotoxic effects do not require dose reduction or prophylactic measures such as high-volume fluid administration or forced diuresis.

Nevertheless, increased blood urea nitrogen (in 5% of patients) and increased serum urea or serum creatinine (in 6% of patients), hemolytic-uremic syndrome, hematuria, and edema have been reported.

Dose reduction or discontinuation of carboplatin therapy and symptomatic treatment are required in case of significant deviations in renal function tests.

Administration site reactions.
Common: asthenia.
Unknown: fever and chills without signs of infection, pain, erythema, swelling, urticaria, necrosis, malaise. Necrosis due to extravasation.

General disorders and administration site conditions.
Common: chills, urticaria, headache.

Investigations.
Very common: decreased creatinine clearance, increased blood urea, increased alkaline phosphatase, increased aspartate aminotransferase, liver function test abnormalities, decreased blood sodium, potassium, calcium, and magnesium levels.
Common: increased blood bilirubin, increased creatinine and blood urea levels.

* Leads to fatal outcome in < 1% of patients; fatal cardiovascular disorders, including heart failure, in < 1% of patients; embolism and cerebrovascular disorders.

Other adverse reactions: reports of secondary acute malignant tumors after cytostatic combination therapy. Cases of alopecia, fever and chills, mucositis, asthenia, malaise, and dysgeusia have been observed. Hemolytic-uremic syndrome has been reported in isolated cases. There are reports of isolated cardiovascular events (heart failure, embolism) and isolated stroke cases.

Cases of hypertension have been recorded.

Shelf life. 2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C.

Keep out of reach of children.

Incompatibilities.

Carboplatin reacts with aluminum, forming a black precipitate. Therefore, when using Strikarb, avoid using needles, syringes, catheters, and infusion systems containing aluminum, both during solution preparation and administration.

Do not use solvents not specified in the section "Dosage and administration."

Do not mix with other drugs in the same container.

Packaging.

5 ml, 15 ml, 45 ml, or 60 ml of the drug in a glass vial stoppered with a rubber plug and sealed with an aluminum crimp cap equipped with a flip-off cap ensuring tamper-evidence.

One vial with the instruction for medical use in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

MYLAN LABORATORIES LIMITED (OTL)

Manufacturer's address.

Plot No. 284-B, Bommasandra Jigani Link Road, Industrial Area, Anekal Taluk, Bangalore, Karnataka 560105, India

Marketing authorization holder.

m.biotech ltd

Address of marketing authorization holder.

Gladstone House, 77-79 High Street, Egham TW20 9HY, Surrey, United Kingdom