Paraplatin

Name: Paraplatin

What is carboplatin (paraplatin)?

Carboplatin is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.

Carboplatin is used together with other cancer medications to treat ovarian cancer.

Carboplatin may also be used for other purposes not listed in this medication guide.

What should i discuss with my healthcare provider before receiving carboplatin (paraplatin)?

You should not receive this medication if you are allergic to carboplatin or similar medications such as oxaliplatin (Eloxatin) or cisplatin (Platinol). You should not receive carboplatin if you have severe bleeding or bone marrow suppression.

If you have any of these other conditions, you may need a dose adjustment or special tests:

  • liver disease;
  • kidney disease;
  • a weak immune system; or
  • if you have received carboplatin in the past.

FDA pregnancy category D. Do not use carboplatin if you are pregnant. It could harm the unborn baby. Use effective birth control, and tell your doctor if you become pregnant during treatment.

It is not known whether carboplatin passes into breast milk or if it could harm a nursing baby. You should not breast-feed while being treated with carboplatin.

What happens if i miss a dose (paraplatin)?

Contact your doctor if you miss an appointment for your carboplatin injection.

Paraplatin and Lactation

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if Paraplatin crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using Paraplatin.

Paraplatin Usage

Only a professional experienced in the use of cancer drugs should give you this medication. Paraplatin is given by dripping the medicine slowly and directly into a vein (intravenous infusion) for 15 minutes or longer. Your doctor will determine the dose of Paraplatin for you based on your weight, height, and kidney function. Paraplatin may be given alone or with other drugs. Treatment is usually repeated every 4 weeks for a number of cycles.

Before and after Paraplatin treatment, your doctor may give you medication to lessen the nausea and vomiting associated with this cancer treatment.

Paraplatin Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

More common
  • Pain at place of injection
Less common
  • Black, tarry stools
  • blood in urine or stools
  • cough or hoarseness, accompanied by fever or chills
  • fever or chills
  • lower back or side pain, accompanied by fever or chills
  • numbness or tingling in fingers or toes
  • painful or difficult urination, accompanied by fever or chills
  • pinpoint red spots on skin
  • skin rash or itching
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Rare
  • Blurred vision
  • ringing in ears
  • sores in mouth and on lips
  • wheezing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Nausea and vomiting
  • unusual tiredness or weakness
Less common
  • Constipation or diarrhea
  • loss of appetite

This medicine may cause a temporary loss of hair in some people. After treatment with carboplatin has ended, normal hair growth should return.

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Paraplatin - Clinical Pharmacology

Carboplatin, like cisplatin, produces predominantly interstrand DNA cross-links rather than DNA-protein cross-links. This effect is apparently cell-cycle nonspecific. The aquation of carboplatin, which is thought to produce the active species, occurs at a slower rate than in the case of cisplatin. Despite this difference, it appears that both carboplatin and cisplatin induce equal numbers of drug-DNA cross-links, causing equivalent lesions and biological effects. The differences in potencies for carboplatin and cisplatin appear to be directly related to the difference in aquation rates.

In patients with creatinine clearances of about 60 mL/min or greater, plasma levels of intact carboplatin decay in a biphasic manner after a 30-minute intravenous infusion of 300 mg/m2 to 500 mg/m2 of carboplatin. The initial plasma half-life (alpha) was found to be 1.1 to 2 hours (n=6), and the postdistribution plasma half-life (beta) was found to be 2.6 to 5.9 hours (n=6). The total body clearance, apparent volume of distribution and mean residence time for carboplatin are 4.4 L/hour, 16 L and 3.5 hours, respectively. The Cmax values and areas under the plasma concentration versus time curves from 0 to infinity (AUC inf) increase linearly with dose, although the increase was slightly more than dose proportional. Carboplatin, therefore, exhibits linear pharmacokinetics over the dosing range studied (300 mg/m2 to 500 mg/m2).

Carboplatin is not bound to plasma proteins. No significant quantities of protein-free, ultrafilterable platinum-containing species other than carboplatin are present in plasma. However, platinum from carboplatin becomes irreversibly bound to plasma proteins and is slowly eliminated with a minimum half-life of 5 days.

The major route of elimination of carboplatin is renal excretion. Patients with creatinine clearances of approximately 60 mL/min or greater excrete 65% of the dose in the urine within 12 hours and 71% of the dose within 24 hours. All of the platinum in the 24-hour urine is present as carboplatin. Only 3% to 5% of the administered platinum is excreted in the urine between 24 and 96 hours. There are insufficient data to determine whether biliary excretion occurs.

In patients with creatinine clearances below 60 mL/min, the total body and renal clearances of carboplatin decrease as the creatinine clearance decreases. Paraplatin dosages should therefore be reduced in these patients (see DOSAGE AND ADMINISTRATION).

The primary determinant of Paraplatin clearance is glomerular filtration rate (GFR) and this parameter of renal function is often decreased in elderly patients. Dosing formulas incorporating estimates of GFR (see DOSAGE AND ADMINISTRATION) to provide predictable Paraplatin plasma AUCs should be used in elderly patients to minimize the risk of toxicity.

Contraindications

Paraplatin (carboplatin aqueous solution) INJECTION is contraindicated in patients with a history of severe allergic reactions to cisplatin or other platinum-containing compounds.

Paraplatin should not be employed in patients with severe bone marrow depression or significant bleeding.

Precautions

General

Needles or intravenous administration sets containing aluminum parts that may come in contact with Paraplatin (carboplatin aqueous solution) INJECTION should not be used for the preparation or administration of the drug. Aluminum can react with carboplatin causing precipitate formation and loss of potency.

Drug Interactions

The renal effects of nephrotoxic compounds may be potentiated by Paraplatin.

Carcinogensis, Mutagenesis, Impairment of Fertility

The carcinogenic potential of carboplatin has not been studied, but compounds with similar mechanisms of action and mutagenicity profiles have been reported to be carcinogenic. Carboplatin has been shown to be mutagenic both in vitro and in vivo. It has also been shown to be embryotoxic and teratogenic in rats receiving the drug during organogenesis. Secondary malignancies have been reported in association with multi-drug therapy.

Pregnancy

Pregnancy Category D

See WARNINGS.

Nursing Mothers

It is not known whether carboplatin is excreted in human milk. Because there is a possibility of toxicity in nursing infants secondary to Paraplatin treatment of the mother, it is recommended that breast feeding be discontinued if the mother is treated with Paraplatin (carboplatin aqueous solution) INJECTION.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established (see WARNINGS; “audiologic toxicity”).

Geriatric Use

Of the 789 patients in initial treatment combination therapy studies (NCIC and SWOG), 395 patients were treated with carboplatin in combination with cyclophosphamide. Of these, 141 were over 65 years of age and 22 were 75 years or older. In these trials, age was not a prognostic factor for survival. In terms of safety, elderly patients treated with carboplatin were more likely to develop severe thrombocytopenia than younger patients. In a combined database of 1,942 patients (414 were ≥65 years of age) that received single-agent carboplatin for different tumor types, a similar incidence of adverse events was seen in patients 65 years and older and in patients less than 65. Other reported clinical experience has not identified differences in responses between elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Because renal function is often decreased in the elderly, renal function should be considered in the selection of Paraplatin dosage (see DOSAGE AND ADMINISTRATION).

How is Paraplatin Supplied

Paraplatin® (carboplatin aqueous solution) INJECTION

NDC 0015-3210-30   50 mg/5 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.

NDC 0015-3211-30   150 mg/15 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.

NDC 0015-3212-30   450 mg/45 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.

NDC 0015-3216-30   600 mg/60 mL aqueous solution in multidose vials (with white flip-off seals), individually cartoned.

Storage

Unopened vials of Paraplatin (carboplatin aqueous solution) INJECTION are stable to the date indicated on the package when stored at 25°C (77°F);excursions permitted from 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from light.

Paraplatin (carboplatin aqueous solution) INJECTION multidose vials maintain microbial, chemical, and physical stability for up to 14 days at 25°C following multiple needle entries.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Solutions for infusion should be discarded 8 hours after preparation.

Handling and Disposal

Procedures for proper handling and disposal of anti-cancer drugs should be considered. Several guidelines on this subject have been published.1-8 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

To minimize the risk of dermal exposure, always wear impervious gloves when handling vials containing Paraplatin (carboplatin aqueous solution) Injection. This includes all handling activities in clinical settings, pharmacies, storerooms, and home healthcare settings, including during unpacking and inspection, transport within a facility, and dose preparation and administration.

References

  1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society; 1999:32-41.
  2. Recommendations for the safe handling of cytotoxic drugs. Washington, DC: Division of Safety, Clinical Center Pharmacy Department and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of Health and Human Services, Public Health Service Publication NIH 92-2621.
  3. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA. 1985;253:1590-1592.
  4. National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longwood Avenue, Boston, MA 02115.
  5. Clinical Oncological Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Aust. 1983;1:426-428.
  6. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from The Mount Sinai Medical Center. CA Cancer J Clin. 1983;33:258-263.
  7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049.
  8. Controlling occupational exposure to hazardous drugs. (OSHA Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.

US Patent No. 4,657,927

Bristol-Myers Squibb Company
Princeton, New Jersey 08543 USA

Rev March 2007

Paraplatin 
carboplatin injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0015-3210
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
carboplatin (carboplatin) carboplatin 10 mg  in 1 mL
Packaging
# Item Code Package Description
1 NDC:0015-3210-30 1 VIAL, MULTI-DOSE (1 VIAL) in 1 CARTON
1 5 mL (5 MILLILITER) in 1 VIAL, MULTI-DOSE
Paraplatin 
carboplatin injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0015-3211
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
carboplatin (carboplatin) carboplatin 10 mg  in 1 mL
Packaging
# Item Code Package Description
1 NDC:0015-3211-30 1 VIAL, MULTI-DOSE (1 VIAL) in 1 CARTON
1 15 mL (15 MILLILITER) in 1 VIAL, MULTI-DOSE
Paraplatin 
carboplatin injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0015-3212
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
carboplatin (carboplatin) carboplatin 10 mg  in 1 mL
Packaging
# Item Code Package Description
1 NDC:0015-3212-30 1 VIAL, MULTI-DOSE (1 VIAL) in 1 CARTON
1 45 mL (45 MILLILITER) in 1 VIAL, MULTI-DOSE
Paraplatin 
carboplatin injection, solution
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0015-3216
Route of Administration INTRAVENOUS DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
carboplatin (carboplatin) carboplatin 10 mg  in 1 mL
Packaging
# Item Code Package Description
1 NDC:0015-3216-30 1 VIAL, MULTI-DOSE (1 VIAL) in 1 CARTON
1 60 mL (60 MILLILITER) in 1 VIAL, MULTI-DOSE
Labeler - Bristol-Myers Squibb
Revised: 06/2008   Bristol-Myers Squibb

What should I avoid?

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Paraplatin can cause side effects that may impair your vision. Be careful if you drive or do anything that requires you to be able to see clearly.

Paraplatin can pass into body fluids (urine, feces, vomit). For at least 48 hours after you receive a dose, avoid allowing your body fluids to come into contact with your hands or other surfaces. Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

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