Kyxata Drug Information

Initial Treatment of Advanced Ovarian Carcinoma

KYXATA, as part of a combination regimen, is indicated for the initial treatment of adults with advanced ovarian carcinoma.

Recurrent Advanced Ovarian Carcinoma KYXATA is indicated for treatment of adults with ovarian carcinoma recurrent after prior chemotherapy.

Premedication and Supportive Medications Administer KYXATA in a setting where cardiopulmonary resuscitation medication and equipment are available. Premedicate patients with antiemetics prior to each infusion of KYXATA for the prevention of nausea and vomiting. Glomerular filtration rate (GFR) is commonly calculated as estimated creatinine clearance (CLcr) using the Cockroft-Gault formula.

Administer up to six cycles or until disease progression or unacceptable toxicity occurs. Refer to cyclophosphamide prescribing information for additional information. For older adults, calculate the dose based on AUC to reduce risk of severe adverse reactions.

Individualize the dose and dosing schedule of KYXATA based on the specific regimen administered, response to treatment, and patient risk factors.

Dosage Modifications for Adverse Reactions For a patients administered a dose based on body surface area as a single agent or combination, dosage modifications are shown in Table 1. Monitor complete blood counts prior to treatment, weekly during treatment, and as clinically indicated.

Dosage Recommendations for Patients with Renal Impairment

For patients administered a dose based on AUC, no dose modification is recommended for renal impairment. For patients administered a dose based on body surface area, the recommended doses for renal impairment are described in Table 2. A recommended dose has not been established for patients with creatinine clearance <16 mL/min.

Preparation and Administration Preparation KYXATA is a hazardous drug. Follow applicable handling and disposal procedures. 1 Do not use needles or intravenous infusion sets containing aluminum; aluminum reacts with carboplatin causing precipitate formation and a loss of potency. Visually inspect KYXATA vials prior to use.

Discard solution if particulate matter or discoloration are observed. KYXATA is supplied as a multiple-dose vial. After first use, store the partially used vial in the original carton at 20°C to 25°C (68°F to 77°F) and then discard after 28 days.

Withdraw the calculated dose of KYXATA from the vial. Prior to administration, KYXATA can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose Injection, USP or 0.9% Sodium Chloride Injection, USP. Diluted carboplatin solution for infusion when prepared as directed in an infusion bag should be used immediately, but may be stored at room temperature (20°C to 25°C) for a maximum of 8 hours.

Discard KYXATA infusion solution 8 hours after dilution. Administration Administer KYXATA by intravenous infusion over 30 to 60 minutes.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Initial Treatment of Advanced Ovarian Cancer The safety of KYXATA in combination with cyclophosphamide for initial treatment of advanced ovarian cancer was evaluated in two randomized controlled studies conducted by NCIC and SWOG. Patients in the carboplatin arm received carboplatin in combination with cyclophosphamide and patients in the active-comparator arm received cisplatin in combination with cyclophosphamide.

Tables 3 and 4 summarize the adverse reactions and laboratory abnormalities in the NCIC study, respectively. Table 5: Adverse Reactions (≥ 5%) in Patients with Ovarian Cancer – SWOG Study - 6 Table 6: Laboratory Abnormalities in Patients with Advanced Ovarian Cancer - SWOG Study 5 - Recurrent Ovarian Cancer The safety of carboplatin as a single agent for patients with ovarian carcinoma recurrent after prior chemotherapy was evaluated in two prospective, randomized controlled studies. Tables 7 and 8 summarize the adverse reactions and laboratory abnormalities from these studies, respectively Table 7: Adverse Reactions (≥5%) in Patients Treated with Carboplatin (Single-agent) for Advanced Ovarian Cancer in Two Controlled Studies 5 Clinically relevant adverse reactions in < 5% of patients who received carboplatin included allergic reactions, alopecia, mucositis, ototoxicity, and sensory disorders.

Table 8: Laboratory Abnormalities in Patients Treated with Carboplatin as a Single-agent for Secondary Treatment of Advanced Ovarian Cancer in Two Prospective, Randomized Controlled Studies 5 Other Clinical Trials Experience The following adverse reactions occurred in patients treated with carboplatin for ovarian cancer as a single agent or in combination with chemotherapy in clinical trials: The following adverse reactions occurred in patients (n=1893) with solid tumors or hematological malignancies treated with single agent carboplatin in clinical trials: Gastrointestinal Disorders: diarrhea (6%), constipation (6%), dysgeusia (1%) Ocular Disorders: visual disturbances (1%). The following adverse reactions occurred in patients treated with carboplatin for ovarian cancer in combination with chemotherapy in clinical trials: Cardiovascular: arterial thromboembolic event, venous thromboembolic event General: fatigue, febrile neutropenia Musculoskeletal and Connective Tissue Disorders: fistula, wound-healing complication Renal and Urinary Disorders: proteinuria Respiratory: dyspnea

Postmarketing Experience

The following adverse reactions have been identified during post approval use of carboplatin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Allergic reactions: anaphylaxis, bronchospasm, erythema, hypotension, pruritus, rash, urticaria Blood and Lymphatic System: hemolytic uremic syndrome, secondary acute myeloid leukemia Cardiovascular: cardiac failure, cerebrovascular accident, embolism, hemorrhage, hypertension Gastrointestinal: stomatitis General disorders: anorexia, dehydration, injection site reactions (including redness, pain, swelling, extravasation, and necrosis), malaise Infection: sepsis/septic shock Renal and Urinary Disorders: acute kidney injury

Use with Aminoglycosides

Avoid concomitant use of aminoglycosides with KYXATA. Concomitant use of KYXATA with aminoglycosides increased renal toxicity and ototoxicity.

Pregnancy Risk Summary Based on findings from animals and its mechanism of action, KYXATA can cause fetal harm when administered to a pregnant woman. Available data from case reports with carboplatin use in pregnant women are insufficient to inform a drug-associated risk. Administration of carboplatin to pregnant rats caused adverse developmental outcomes, including embryo-lethality and structural abnormalities (see Data).

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Data Animal Data Carboplatin administered to pregnant rats was embryo-lethal and teratogenic.

Pediatric Use The safety and effectiveness of KYXATA in pediatric patients have not been established. Pediatric patients may be at risk of hearing loss if KYXATA is administered at higher than recommended dosages or in combination with other ototoxic agents.

There is no known antidote for KYXATA overdosage. The anticipated complications of overdosage would be secondary to bone marrow suppression and/or hepatic toxicity. Patients receiving overdosages of carboplatin experienced severe liver function test abnormalities.

Loss of vision, which can be complete for light and colors, has been reported after the use of carboplatin at doses higher than the recommended approved dosage for KYXATA. Vision recovers totally or to a significant extent after discontinuation of carboplatin. Clinically significant hearing loss has been reported to occur in pediatric patients when carboplatin was administered at higher than approved recommended doses for KYXATA and in combination with other ototoxic agents.

KYXATA is removed by dialysis. Closely monitor patients suspected of receiving an overdose, including for the adverse reactions described above, and administer appropriate supportive treatment.