Karboplatin-Amedart (Concentrate) Instructions for Use

Marketing Authorization Holder

Amedart LLC (Russia)

ATC Code

L01XA02 (Carboplatin)

Active Substance

Carboplatin (Rec.INN registered by WHO)

Dosage Form

Carboplatin-Amedart

Concentrate for solution for infusion 10 mg/ml

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion

15 ml – vials – cardboard packs – Prescription only
25 ml – vials – cardboard packs – Prescription only
45 ml – vials – cardboard packs – Prescription only
5 ml – vials – cardboard packs – Prescription only
60 ml – vials – cardboard packs – Prescription only

Clinical-Pharmacological Group

Antineoplastic drug

Pharmacotherapeutic Group

Antineoplastic agent, alkylating compound

Pharmacological Action

Antineoplastic agent with alkylating action, contains platinum. The mechanism of action is associated with the formation of cross-links between adjacent guanine base pairs in DNA, which leads to suppression of nucleic acid biosynthesis and cell death.

Pharmacokinetics

It is metabolized by hydrolysis to form active compounds that interact with DNA. Protein binding is very low. However, platinum derived from carboplatin is irreversibly bound to plasma proteins and is slowly excreted with a minimum T_1/2 of 5 days.

The T_1/2 of carboplatin in the initial phase is 1.1-2 hours, in the terminal phase – 2.6-5.9 hours. It is excreted by the kidneys – 71% within 24 hours with a CrCl of 60 ml/min or more.

Indications

Ovarian cancer (primary treatment as part of combination chemotherapy and secondary – palliative for advanced stages); germ cell tumors in men and women; malignant tumors of the head and neck; lung cancer; cancer of the cervix and uterine body; transitional cell carcinoma of the bladder.

ICD codes

Dosage Regimen

Calculate the dose using the Calvert formula: Dose (mg) = Target AUC x (GFR + 25).

Use the patient’s glomerular filtration rate (GFR), calculated from serum creatinine, for the calculation.

For previously untreated ovarian cancer, administer a target AUC of 5-7 mg/ml/min every 4 weeks, in combination with other chemotherapeutic agents.

For monotherapy in recurrent disease, administer a target AUC of 4-6 mg/ml/min every 4 weeks.

Adjust the dose for patients with impaired renal function; do not administer to patients with severe renal impairment.

Administer as an intravenous infusion over 15-60 minutes.

Pre-medicate with effective antiemetics to prevent nausea and vomiting.

Do not use needles or intravenous sets containing aluminum parts for preparation or administration.

Dilute the concentrate with 5% Dextrose Solution or 0.9% Sodium Chloride Solution to a final concentration as low as 0.5 mg/ml.

Withhold subsequent cycles until platelet count recovers to at least 100,000/µl and neutrophil count to at least 2,000/µl.

Consider dose reduction for subsequent cycles based on the severity of hematologic toxicity from the prior dose.

Monitor complete blood count, renal function, and audiological function prior to each treatment cycle.

Adverse Reactions

From the hematopoietic system: bone marrow suppression, anemia, clinical complications are possible (infectious diseases, sepsis/septic shock and bleeding).

From the digestive system: nausea, vomiting, stomatitis, diarrhea or constipation, abdominal pain, decreased appetite.

From the liver and biliary tract: increased activity of AST, ALP and serum bilirubin concentration, significant liver dysfunction.

From the nervous system: asthenia, peripheral polyneuropathy (paresthesia, decreased deep tendon reflexes); long-term therapy may lead to cumulative neurotoxicity.

From the organ of vision: decreased visual acuity up to complete loss of vision or loss of the ability to distinguish colors (improvement or complete restoration of vision, as a rule, occurs within a few weeks after discontinuation of carboplatin; cortical blindness was observed in patients with impaired renal function who were treated with high doses of carboplatin).

From the organ of hearing: hearing loss, tinnitus.

From the urinary system: increased serum creatinine and urea concentrations, acute kidney damage is possible, the risk of nephrotoxicity while taking carboplatin increases with increasing carboplatin dose, as well as in patients who have previously been treated with cisplatin.

From the water and electrolyte balance : hypokalemia, hypocalcemia, hyponatremia and hypomagnesemia.

Allergic reactions: erythematous rash, fever, itching, urticaria, bronchospasm, arterial hypotension, anaphylactic reactions; rarely – exfoliative dermatitis.

Other: taste changes, alopecia, flu-like symptoms (fever, pyrexia), hemolytic-uremic syndrome, myalgia/arthralgia, heart failure, cerebrovascular disorders.

Local reactions: pain at the injection site, allergic reactions.

Contraindications

Hypersensitivity to carboplatin and platinum-containing drugs; severe renal impairment, previous severe myelodepression, recent significant blood loss; pregnancy, lactation (breastfeeding); childhood.

With caution in acute infectious diseases of viral, fungal or bacterial nature (including chickenpox, herpes zoster), hearing impairment; bone marrow suppression (including against the background of concomitant radiation or chemotherapy); with previous therapy with nephrotoxic drugs, for example, cisplatin; in the post-vaccination period.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Women of childbearing potential receiving carboplatin therapy should use reliable methods of contraception.

In experimental studies, it has been established that Carboplatin has teratogenic and embryotoxic effects.

Use in Renal Impairment

Contraindicated in severe renal impairment.

Pediatric Use

Contraindicated for use in children (safety and efficacy have not been sufficiently studied).

Geriatric Use

Periodic neurological examinations are recommended for patients over 65 years of age.

Special Precautions

Carboplatin should be used only under the supervision of a physician experienced in chemotherapy. Before starting treatment and during its course, it is necessary to monitor renal function, peripheral blood count, neurological status, and perform audiometry. Changes in biochemical parameters are possible: increased serum urea and creatinine levels, decreased concentrations of magnesium, potassium, calcium.

It should be used with caution in bone marrow suppression (including against the background of concomitant radiation or chemotherapy), previous therapy with nephrotoxic drugs (for example, cisplatin), hearing impairment, acute infectious diseases of viral, fungal or bacterial nature, in patients with ascites or exudative pleurisy, in the post-vaccination period.

Caution should be exercised when using carboplatin in patients after a course of radiation therapy.

Periodic neurological examinations are recommended, especially in patients previously treated with cisplatin and in patients over 65 years of age.

Since Carboplatin can cause cumulative ototoxic effects, patients are recommended to undergo audiographic examinations before and during treatment. In case of clinically significant hearing impairment, appropriate dose adjustment of carboplatin or discontinuation of treatment may be required.

Women and men during treatment with carboplatin should use reliable methods of contraception.

In the presence of concomitant ascites or exudative pleurisy, the toxicity of carboplatin increases.

Subsequent doses of carboplatin should not be administered until the platelet count reaches 100 thousand/µl and neutrophils – 2 thousand/µl.

In patients with thrombocytopenia that developed while taking carboplatin, special precautions must be taken to prevent bleeding and hemorrhage: caution when performing invasive procedures; regular examination of intravenous injection sites, skin and mucous membranes for bleeding and hemorrhage; limiting the frequency of venipuncture and avoiding intramuscular injections; analysis of urine, vomit, feces and secretions for occult blood; caution when using toothbrushes and floss, toothpicks, safety razors and scissors; prevention of constipation; prevention of falls or other injuries; ethanol and ASA intake should be avoided.

It is necessary to avoid contact with patients with bacterial infections, especially against the background of developed leukopenia.

If body temperature rises or chills, cough or hoarseness, pain in the lower back or side, painful or difficult urination appear, you should immediately consult a doctor.

During treatment, it is not recommended to vaccinate patients or their family members, and it is also necessary to avoid contact with people who have received the polio vaccine, or to wear a protective mask.

Effect on the ability to drive vehicles and mechanisms

Considering that the use of carboplatin in patients may cause peripheral neuropathy, visual impairment and color perception, during treatment, patients should avoid driving vehicles and other activities that require high concentration and speed of psychomotor reactions.

Drug Interactions

With simultaneous use with drugs that have myelodepressive, nephrotoxic effects, mutual enhancement of toxic effects is possible.

Enhances (mutually) the nephrotoxicity of aminoglycosides and other nephrotoxic drugs.

Reduces the production of antibodies to the administration of inactivated viral vaccine and live viral vaccine (in addition, intensification of the process of replication of the vaccine virus and enhancement of its side effects are possible). The interval between discontinuation of carboplatin treatment and vaccination should be from 3 to 12 months (depends on the dose and type of the drug, the underlying disease and other factors).

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.