کربوپلاتین
Carboplatin (Paraplatin)
کربوپلاتین

نام ژنریک

Carboplatin

شکل دارویی

اشكال دارويي:


Injection: 10 mg/ml , 15ml, 10 mg/ml, 5ml


Injection, Solution : 50 ,150 mg


Injection, Solution, Concentrate : 10 mg/ml, 45ml

موارد مصرف

موارد و مقدار مصرف


درمان اوليه و ثانويه (Palliative) كارسينوم تخمدان، رتينوبلاستوما، سرطان پيشرفته مثانه، سرطان ريه، سرطان سر و گردن، تومور ويلمز، تومور اوليه مغز، نئوپلاسم بيضه، سرطان سرويكس.


بزرگسالان: مقدار توصيه شده اوليه براي منوتراپي mg/m2 360 است كه در روز اول از راه وريدي تزريق مي‌شود. اين مقدار هر چهار هفته تكرار مي‌شود. هنگامي كه همراه با سيكلوفسفاميد تجويز مي‌شود، ميزان mg/m2 300 از راه وريدي، در روز اول و هر 4 هفته براي 6 دوره مصرف مي‌شود.


تنظيم دوز: تنظيم دوز دارو براساس كمترين ميزان پلاكت يا نوتروفيل پس از درمان، كه به صورت هفتگي شمارش مي‌گردند، انجام مي‌شود (به جدول توجه كنيد.)


در صورتي كه كليرانس كراتي‌نين ml/min 59-41 باشد، دوز اوليه mg/m2 250 خواهد بود؛ اگر ml/min 40-16 باشد دوز اوليه به mg/m2 200 كاهش مي‌يابد.


در بيماراني كه كليرانس كراتي‌نين آنها ml/min 15 يا كمتر مي‌باشد، استفاده از اين دارو توصيه نمي‌گردد.





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كمترين تعداد پلاكتها




(در


mm3
)




كمترين تعداد نوتروفيلها




 (در


mm3
)




مقدار مصرف




تنظيم شده




بيش از 100000




بيش از 2000




125 درصد




100000-50000




2000-500




بدون تنظيم




كمتر از 50000




كمتر از 500




75 درصد



موارد منع مصرف

موارد منع مصرف و احتياط


موارد منع مصرف: در سابقه حساسيت مفرط به سيس پلاتين، تركيبات حاوي پلاتينيوم، مانيتول، خونريزي يا كاهش شديد فعاليت مغز استخوان (در طول درمان ممكن است انتقال خون به بيمار به دليل كم‌خوني تجمعي ضروري باشد. كاهش فعاليت مغز استخوان ممكن است در بيماران داراي كليرانس كرآتينين كمتر از ml/min 60 شديدتر باشد. بيماران بزرگتر از 65 سال در معرض خطر بيشتر مسموميت عصبي قرار دارند). منع مصرف دارد.


موارد احتياط: الف) در صورت كاهش عملكرد كليوي، دارو بايد با احتياط تجويز شده و مقدار مصرف تنظيم شود.


ب) هنگام تهيه يا مصرف كاربوپلاتين بايد احتياط فراوان رعايت شود تا از بروز خطرات موتاژنيك، تراتوژنيك و كارسينوژنيك دارو جلوگيري شود.


به هنگام تهيه بايد از دستكش، ماسك و سرنگهاي مخصوصي كه از نشت دارو جلوگيري مي‌كنند، استفاده شود. همچنين سوزنها، ويالها و داروهاي استفاده نشده بايد به طرز صحيح از بين بروند و از آلوده كردن محل كار خودداري گردد. از استنشاق گرد و بخار دارو و از تماس دارو با پوست و غشاهاي مخاطي بايد خودداري شود.

عوارض جانبی دارو

عوارض جانبي


اعصاب مرکزي: نوروپاتي محيطي، ضعف، گيجي، نوروتوكسيسيته مركزي.


دستگاه گوارش: يبوست، اسهال، استفراغ، از دست دادن الكتروليت‌ها، حساسيت مفرط، تهوع، تغيير حس چشايي.


خون: كاهش فعاليت مغز استخوان (ترومبوسيتوپني، لكوپني، نوتروپني، كم‌خوني، ضعف).


كبدي: مسموميت كبدي، درد.


ساير عوارض: آلوپسي، حساسيت مفرط، اتوتوكسيسيته، درد، آنافيلاكسي، نارسايي قلبي، آمبولي، اختلالات بينايي.


مسموميت و درمان


تظاهرات باليني: مسموميت كبدي يا كاهش فعاليت مغز استخوان.


درمان: هيچ نوع پادزهري براي مصرف بيش از حد كاربوپلاتين شناخته نشده است.

موارد قابل توجه

-

تداخل دارویی

تداخل دارويي


مصرف همزمان كاربوپلاتين با داروهاي نفروتوكسيك موجب بروز اثرات اضافي مسموميت كليوي ناشي از كاربوپلاتين مي‌شود و بايد با احتياط مصرف شوند.


آسپيرين ممكن است منجر به افزايش ريسك خونريزي شود و بايد از مصرف همزمان آنها پرهيز گردد.


سركوب كننده‌هاي مغز استخوان (شامل راديوتراپي) مي‌توانند منجر به افزايش سميت هماتولوژيك شوند.

مکانیزم اثر

تداخل دارويي


مصرف همزمان كاربوپلاتين با داروهاي نفروتوكسيك موجب بروز اثرات اضافي مسموميت كليوي ناشي از كاربوپلاتين مي‌شود و بايد با احتياط مصرف شوند.


آسپيرين ممكن است منجر به افزايش ريسك خونريزي شود و بايد از مصرف همزمان آنها پرهيز گردد.


سركوب كننده‌هاي مغز استخوان (شامل راديوتراپي) مي‌توانند منجر به افزايش سميت هماتولوژيك شوند.

فارماكوكینتیك

فارماكوكينتيك


جذب: از راه وريدي تزريق مي‌شود.


پخش: حجم توزيع اين دارو تقريباً معادل تمام آب بدن است. پيوند پروتئيني قابل ملاحظه نيست. ولي دارو مي‌تواند به محصولات حاوي پلاتينيوم تبديل شود كه 87% به پروتئين باند مي‌شوند. نيمه‌ عمر خود دارو 3-2 ساعت بوده در حاليكه نيمه‌ عمر نهايي پلاتينيوم 6-4 ساعت مي‌باشد.


متابوليسم: هيدروليز شده و انواع هيدروكسيله و آبي (aquated) را تشكيل مي‌دهد.


دفع: 65 درصد دارو طي 12 ساعت و 71 درصد آن طي 24 ساعت از طريق كليه دفع مي‌شود. گردش مجدد روده‌اي ـ كبدي ممكن است اتفاق افتد.

سایر اطلاعات

طبقه‌بندي فارماكولوژيك: تركيب آلكيله كننده (غير اختصاصي چرخه سلولي).


طبقه‌بندي درماني: ضد نئوپلاسم.


طبقه‌بندي مصرف در بارداري: رده D


نام‌هاي تجاري: Ebecarbo


ملاحظات اختصاصي


علاوه بر موارد مربوط به تمامي داروهاي آلكيله كننده، رعايت موارد زير نيز توصيه مي‌شود:


1- محلول دارو با استفاده از دكستروز پنج درصد در آب، محلول نمكي نرمال، يا آب استريل تزريقي تا غلظت mg/ml 10 تهيه مي‌شود.


2- كاربوپلاتين را مي‌توان با محلول نمكي نرمال يا دكستروز پنج درصد در آب رقيق كرد.


3- ويالهاي باز نشده بايد در دماي اتاق نگهداري شود. بعد از تهيه و رقيق كردن دارو، محلول به مدت هشت ساعت در دماي اتاق پايدار است. از آنجايي كه كاربوپلاتين حاوي مواد نگهدارنده ضد باكتري نيست، داروي استفاده نشده بايد بعد از هشت ساعت دور ريخته شود.


4- از وسايل تزريقي يا سوزنهاي ساخته شده از آلومينيوم نبايد استفاده كرد، زيرا كاربوپلاتين ممكن است رسوب كرده و كارايي خود را از دست بدهد.


5- اگرچه احتمال بروز تهوع و استفراغ با كاربوپلاتين كمتر از سيس‌پلاتين است، ولي اين دارو مي‌تواند موجب بروز استفراغ شديد شود. داروي ضد استفراغ بايد تجويز شود.


6- كاربوپلاتين بايد تحت نظر پزشك آشنا به داروهاي سرطاني مصرف شود.


توجه: سركوب مغز استخوان ناشي از دارو شديد بوده و مي‌تواند منجر به بروز خونريزي يا عفونت شود.


آنمي مي‌تواند تجمعي باشد و حتي نياز به تزريق خون داشته باشد. بايد تست‌هاي آزمايشگاهي بيمار به دقت پيگيري شود.


واكنش‌هاي شبه آنافيلاكتيك به كاربوپلاتين طي چندين دقيقه اول پس از تزريق رخ مي‌دهد.


ممكن است اپي‌نفرين، كورتيكوستروئيدها و آنتي‌هيستامين‌ها باعث تخفيف علائم شوند.


نكات قابل توصيه به بيمار


1- مصرف مايعات كافي براي افزايش دفع ادرار، جهت تسهيل دفع اسيداوريك ضروري مي‌باشد.


2- در صورت بروز وزوز گوش فوراً به پزشك اطلاع دهيد تا از كاهش دائمي شنوايي جلوگيري شود. آزمون شنوايي بايد قبل از شروع درمان و نوبت بعدي مصرف دارو انجام گيرد.


3- از تماس با افراد مبتلا به عفونت خودداري كنيد.


4- بروز هرگونه خونريزي يا كبودي غيرمعمول را فوراً اطلاع دهيد.


مصرف در سالمندان: بيماران بزرگتر از 65 سال در معرض خطر بيشتر مسموميت عصبي قرار دارند.


مصرف در كودكان: بي‌ضرري مصرف دارو ثابت نشده است.


مصرف در شيردهي: ترشح دارو در شير مشخص نيست ولي به دليل خطر ايجاد سميت در نوزاد، بايستي از شيردهي در طي درمان خودداري شود.


مصرف در بارداري: اين دارو مي‌تواند باعث آسيب به جنين شود. در مواردي كه فوايد كربوپلاتين از مضرات آن بيشتر بوده يا در مواردي كه جان بيمار در خطر باشد، ممكن است در طي دوران بارداري استفاده گردد.


توجه: براي كسب آگاهي بيشتر درباره اين دارو، به اطلاعات مربوط به Alkylating Agents مراجعه كنيد.


اثر بر آزمايشهاي تشخيصي


مقادير زياد كاربوپلاتين ممكن است موجب افزايش غلظت بيلي‌روبين، آلكالين فسفاتاز، آسپارتات آمينوترانسفراز (AST)، كراتينين سرم و BUN شود. همچنين مي‌تواند سطوح هموگلوبين، هماتوكريت و الكتروليت‌ها را كاهش دهد. ممكن است تعداد RBC, WBC، نوتروفيل‌ها و پلاكت‌ها كاهش يابند.

Carboplatin (Paraplatin)

PARAPLATIN®
(carboplatin aqueous solution) Injection

WARNING

PARAPLATIN (carboplatin aqueous solution) INJECTION should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate treatment facilities are readily available.

Bone marrow suppression is dose related and may be severe, resulting in infection and/or bleeding. Anemia may be cumulative and may require transfusion support. Vomiting is another frequent drug-related side effect.

Anaphylactic-like reactions to carboplatin have been reported and may occur within minutes of PARAPLATIN (carboplatin) administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms.

DRUG DESCRIPTION

PARAPLATIN® (carboplatin aqueous solution) INJECTION is supplied as a sterile, pyrogen-free, 10 mg/mL aqueous solution of carboplatin. Carboplatin is a platinum coordination compound. The chemical name for carboplatin is platinum, diammine[1,1-cyclobutanedicarboxylato(2-)-O,O′]-, (SP-4-2), and carboplatin has the following structural formula:

PARAPLATIN®
   (carboplatin) Structural Formula Illustration

Carboplatin is a crystalline powder with the molecular formula of C6H12N2O4Pt and a molecular weight of 371.25. It is soluble in water at a rate of approximately 14 mg/mL, and the pH of a 1% solution is 5 to 7. It is virtually insoluble in ethanol, acetone, and dimethylacetamide.

What are the possible side effects of carboplatin (Paraplatin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • severe or ongoing...

Read All Potential Side Effects and See Pictures of Paraplatin »

What are the precautions when taking carboplatin (Paraplatin)?

Before using carboplatin, tell your doctor or pharmacist if you are allergic to it, or to cisplatin; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: decreased bone marrow function/blood cell disorders (e.g., anemia, leukopenia, thrombocytopenia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, mineral imbalance (low blood levels of sodium, potassium, magnesium, calcium).

Do not have immunizations/vaccinations without the...

Read All Potential Precautions of Paraplatin »

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

Initial Treatment of Advanced Ovarian Carcinoma

PARAPLATIN (carboplatin aqueous solution) INJECTION is indicated for the initial treatment of advanced ovarian carcinoma in established combination with other approved chemotherapeutic agents. One established combination regimen consists of PARAPLATIN (carboplatin) and cyclophosphamide. Two randomized controlled studies conducted by the NCIC and SWOG with carboplatin versus cisplatin, both in combination with cyclophosphamide, have demonstrated equivalent overall survival between the two groups (see Clinical Studies).

There is limited statistical power to demonstrate equivalence in overall pathologic complete response rates and long-term survival ( ≥ 3 years) because of the small number of patients with these outcomes: the small number of patients with residual tumor < 2 cm after initial surgery also limits the statistical power to demonstrate equivalence in this subgroup.

Secondary Treatment of Advanced Ovarian Carcinoma

PARAPLATIN (carboplatin) is indicated for the palliative treatment of patients with ovarian carcinoma recurrent after prior chemotherapy, including patients who have been previously treated with cisplatin.

Within the group of patients previously treated with cisplatin, those who have developed progressive disease while receiving cisplatin therapy may have a decreased response rate.

DOSAGE AND ADMINISTRATION

NOTE: Aluminum reacts with carboplatin causing precipitate formation and loss of potency, therefore, needles or intravenous sets containing aluminum parts that may come in contact with the drug must not be used for the preparation or administration of PARAPLATIN (carboplatin) .

Single-Agent Therapy

PARAPLATIN (carboplatin aqueous solution) INJECTION, as a single agent, has been shown to be effective in patients with recurrent ovarian carcinoma at a dosage of 360 mg/m2 IV on day 1 every 4 weeks (alternatively see Formula Dosing). In general, however, single intermittent courses of PARAPLATIN (carboplatin) should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.

Combination Therapy with Cyclophosphamide

In the chemotherapy of advanced ovarian cancer, an effective combination for previously untreated patients consists of:

PARAPLATIN (carboplatin) —300 mg/m2 IV on day 1 every 4 weeks for 6 cycles (alternatively see Formula Dosing).

Cyclophosphamide—600 mg/m2 IV on day 1 every 4 weeks for 6 cycles. For directions regarding the use and administration of cyclophosphamide please refer to its package insert. (See Clinical Studies.)

Intermittent courses of PARAPLATIN (carboplatin) in combination with cyclophosphamide should not be repeated until the neutrophil count is at least 2,000 and the platelet count is at least 100,000.

Dose Adjustment Recommendations

Pretreatment platelet count and performance status are important prognostic factors for severity of myelosuppression in previously treated patients.

The suggested dose adjustments for single agent or combination therapy shown in the table below are modified from controlled trials in previously treated and untreated patients with ovarian carcinoma. Blood counts were done weekly, and the recommendations are based on the lowest post-treatment platelet or neutrophil value.

Platelets Neutrophils Adjusted Dose * (From Prior Course)
> 100,000 > 2,000 125%
50-100,000 500-2,000 No Adjustment
< 50,000 < 500 75%
* Percentages apply to PARAPLATIN (carboplatin aqueous solution) INJECTION as a single agent or to both PARAPLATIN and cyclophosphamide in combination. In the controlled studies, dosages were also adjusted at a lower level (50% to 60%) for severe myelosuppression. Escalations above 125% were not recommended for these studies.

PARAPLATIN (carboplatin) is usually administered by an infusion lasting 15 minutes or longer. No pre- or post-treatment hydration or forced diuresis is required.

Patients with Impaired Kidney Function

Patients with creatinine clearance values below 60 mL/min are at increased risk of severe bone marrow suppression. In renally-impaired patients who received single-agent carboplatin therapy, the incidence of severe leukopenia, neutropenia, or thrombocytopenia has been about 25% when the dosage modifications in the table below have been used.

Baseline Creatinine Clearance Recommended Dose on Day 1
41-59 mL/min 250 mg/m2
16-40 mL/min 200 mg/m2

The data available for patients with severely impaired kidney function (creatinine clearance below 15 mL/min) are too limited to permit a recommendation for treatment.

These dosing recommendations apply to the initial course of treatment. Subsequent dosages should be adjusted according to the patient's tolerance based on the degree of bone marrow suppression.

Formula Dosing

Another approach for determining the initial dose of PARAPLATIN (carboplatin) is the use of mathematical formulae, which are based on a patient's pre-existing renal function or renal function and desired platelet nadir. Renal excretion is the major route of elimination for carboplatin. (See CLINICAL PHARMACOLOGY.) The use of dosing formulae, as compared to empirical dose calculation based on body surface area, allows compensation for patient variations in pretreatment renal function that might otherwise result in either underdosing (in patients with above average renal function) or overdosing (in patients with impaired renal function).

A simple formula for calculating dosage, based upon a patient's glomerular filtration rate (GFR in mL/min) and PARAPLATIN (carboplatin) target area under the concentration versus time curve (AUC in mg/mL•min), has been proposed by Calvert. In these studies, GFR was measured by 51Cr-EDTA clearance.

CALVERT FORMULA FOR CARBOPLATIN DOSING

Total Dose (mg) = (target AUC) x (GFR + 25)

Note: With the Calvert formula, the total dose of PARAPLATIN (carboplatin) is calculated in mg, not mg/m2.

The target AUC of 4 mg/mL•min to 6 mg/mL•min using single-agent carboplatin appears to provide the most appropriate dose range in previously treated patients. This study also showed a trend between the AUC of single-agent carboplatin administered to previously treated patients and the likelihood of developing toxicity.

AUC (mg/mL•min) % Actual Toxicity in Previously Gr 3 or Gr 4 Thrombocytopenia Treated Patients Gr 3 or Gr 4 Leukopenia
4 to 5 16% 13%
6 to 7 33% 34%

Geriatric Dosing

Because renal function is often decreased in elderly patients, formula dosing of PARAPLATIN (carboplatin) based on estimates of GFR should be used in elderly patients to provide predictable plasma PARAPLATIN (carboplatin) AUCs and thereby minimize the risk of toxicity.

PREPARATION OF INTRAVENOUS SOLUTIONS

PARAPLATIN (carboplatin aqueous solution) INJECTION is a premixed aqueous solution of 10 mg/mL carboplatin.

PARAPLATIN (carboplatin) aqueous solution can be further diluted to concentrations as low as 0.5 mg/mL with 5% Dextrose in Water (D5W) or 0.9% Sodium Chloride Injection, USP.

When prepared as directed, PARAPLATIN (carboplatin) aqueous solutions are stable for 8 hours at room temperature (25°C). Since no antibacterial preservative is contained in the formulation, it is recommended that PARAPLATIN (carboplatin) aqueous solutions be discarded 8 hours after dilution.

HOW 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.

Bristol-Myers Squibb Company Princeton, New Jersey 08543 USA. Rev March 2007

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

For a comparison of toxicities when carboplatin or cisplatin was given in combination with cyclophosphamide, see Clinical Studies: Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer: Comparative Toxicity.

ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER

    First Line Combination Therapy* Percent Second Line Single-Agent Therapy** Percent
Bone Marrow
   Thrombocytopenia < 100,000/mm3 66 62
< 50,000/mm3 33 35
  Neutropenia < 2000 cells/mm3 96 67
< 1000 cells/mm3 82 21
  Leukopenia < 4000 cells/mm3 97 85
< 2000 cells/mm3 71 26
  Anemia < 11 g/dL 90 90
< 8 g/dL 14 21
  Infections   16 5
  Bleeding   8 5
  Transfusions   35 44
Gastrointestinal
  Nausea and vomiting   93 92
  Vomiting   83 81
  Other GI side effects   46 21
Neurologic
  Peripheral neuropathies   15 6
  Ototoxicity   12 1
  Other sensory side effects   5 1
  Central neurotoxicity   26 5
Renal
  Serum creatinine elevations   6 10
  Blood urea elevations   17 22
Hepatic
  Bilirubin elevations   5 5
  SGOT elevations   20 19
  Alkaline phosphatase elevations   29 37
Electrolytes loss
  Sodium   10 47
  Potassium   16 28
  Calcium   16 31
  Magnesium   61 43
Other side effects
  Pain   44 23
  Asthenia   41 11
  Cardiovascular   19 6
  Respiratory   10 6
  Allergic   11 2
  Genitourinary   10 2
  Alopecia   49 2
  Mucositis   8 1
* Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer: Data are based on the experience of 393 patients with ovarian cancer (regardless of baseline status) who received initial combination therapy with carboplatin and cyclophosphamide in two randomized controlled studies conducted by SWOG and NCIC (see Clinical Studies).
Combination with cyclophosphamide as well as duration of treatment may be responsible for the differences that can be noted in the adverse experience table.
** Single Agent Use for the Secondary Treatment of Ovarian Cancer: Data are based on the experience of 553 patients with previously treated ovarian carcinoma (regardless of baseline status) who received single-agent carboplatin.

In the narrative section that follows, the incidences of adverse events are based on data from 1,893 patients with various types of tumors who received carboplatin as single-agent therapy.

Hematologic Toxicity

Bone marrow suppression is the dose-limiting toxicity of PARAPLATIN (carboplatin) . Thrombocytopenia with platelet counts below 50,000/mm3 occurs in 25% of the patients (35% of pretreated ovarian cancer patients); neutropenia with granulocyte counts below 1,000/mm3 occurs in 16% of the patients (21% of pretreated ovarian cancer patients); leukopenia with WBC counts below 2,000/mm3 occurs in 15% of the patients (26% of pretreated ovarian cancer patients). The nadir usually occurs about day 21 in patients receiving single-agent therapy. By day 28, 90% of patients have platelet counts above 100,000/mm3; 74% have neutrophil counts above 2,000/mm3; 67% have leukocyte counts above 4,000/mm3.

Marrow suppression is usually more severe in patients with impaired kidney function. Patients with poor performance status have also experienced a higher incidence of severe leukopenia and thrombocytopenia.

The hematologic effects, although usually reversible, have resulted in infectious or hemorrhagic complications in 5% of the patients treated with carboplatin, with drug-related death occurring in less than 1% of the patients. Fever has also been reported in patients with neutropenia.

Anemia with hemoglobin less than 11 g/dL has been observed in 71% of the patients who started therapy with a baseline above that value. The incidence of anemia increases with increasing exposure to PARAPLATIN (carboplatin) . Transfusions have been administered to 26% of the patients treated with carboplatin (44% of previously treated ovarian cancer patients).

Bone marrow depression may be more severe when PARAPLATIN (carboplatin) is combined with other bone marrow suppressing drugs or with radiotherapy.

Gastrointestinal Toxicity

Vomiting occurs in 65% of the patients (81% of previously treated ovarian cancer patients) and in about one-third of these patients it is severe. Carboplatin, as a single agent or in combination, is significantly less emetogenic than cisplatin; however, patients previously treated with emetogenic agents, especially cisplatin, appear to be more prone to vomiting. Nausea alone occurs in an additional 10% to 15% of patients. Both nausea and vomiting usually cease within 24 hours of treatment and are often responsive to antiemetic measures. Although no conclusive efficacy data exist with the following schedules, prolonged administration of carboplatin, either by continuous 24-hour infusion or by daily pulse doses given for 5 consecutive days, was associated with less severe vomiting than the single-dose intermittent schedule. Emesis was increased when carboplatin was used in combination with other emetogenic compounds. Other gastrointestinal effects observed frequently were pain, in 17% of the patients; diarrhea, in 6%; and constipation, also in 6%.

Neurologic Toxicity

Peripheral neuropathies have been observed in 4% of the patients receiving carboplatin (6% of pretreated ovarian cancer patients) with mild paresthesias occurring most frequently. Carboplatin therapy produces significantly fewer and less severe neurologic side effects than does therapy with cisplatin. However, patients older than 65 years and/or previously treated with cisplatin appear to have an increased risk (10%) for peripheral neuropathies. In 70% of the patients with pre-existing cisplatin-induced peripheral neurotoxicity, there was no worsening of symptoms during therapy with carboplatin. Clinical ototoxicity and other sensory abnormalities such as visual disturbances and change in taste have been reported in only 1% of the patients. Central nervous system symptoms have been reported in 5% of the patients and appear to be most often related to the use of antiemetics.

Although the overall incidence of peripheral neurologic side effects induced by carboplatin is low, prolonged treatment, particularly in cisplatin pretreated patients, may result in cumulative neurotoxicity.

Nephrotoxicity

Development of abnormal renal function test results is uncommon, despite the fact that carboplatin, unlike cisplatin, has usually been administered without high-volume fluid hydration and/or forced diuresis. The incidences of abnormal renal function tests reported are 6% for serum creatinine and 14% for blood urea nitrogen (10% and 22%, respectively, in pretreated ovarian cancer patients). Most of these reported abnormalities have been mild and about one-half of them were reversible.

Creatinine clearance has proven to be the most sensitive measure of kidney function in patients receiving carboplatin, and it appears to be the most useful test for correlating drug clearance and bone marrow suppression. Twenty-seven percent of the patients who had a baseline value of 60 mL/min or more demonstrated a reduction below this value during carboplatin therapy.

Hepatic Toxicity

The incidences of abnormal liver function tests in patients with normal baseline values were reported as follows: total bilirubin, 5%; SGOT, 15%; and alkaline phosphatase, 24%; (5%, 19%, and 37%, respectively, in pretreated ovarian cancer patients). These abnormalities have generally been mild and reversible in about one-half of the cases, although the role of metastatic tumor in the liver may complicate the assessment in many patients. In a limited series of patients receiving very high dosages of carboplatin and autologous bone marrow transplantation, severe abnormalities of liver function tests were reported.

Electrolyte Changes

The incidences of abnormally decreased serum electrolyte values reported were as follows: sodium, 29%; potassium, 20%; calcium, 22%; and magnesium, 29%; (47%, 28%, 31%, and 43%, respectively, in pretreated ovarian cancer patients). Electrolyte supplementation was not routinely administered concomitantly with carboplatin, and these electrolyte abnormalities were rarely associated with symptoms.

Allergic Reactions

Hypersensitivity to carboplatin has been reported in 2% of the patients. These allergic reactions have been similar in nature and severity to those reported with other platinum-containing compounds, ie, rash, urticaria, erythema, pruritus, and rarely bronchospasm and hypotension. Anaphylactic reactions have been reported as part of postmarketing surveillance (see WARNINGS). These reactions have been successfully managed with standard epinephrine, corticosteroid, and antihistamine therapy.

Injection Site Reactions

Injection site reactions, including redness, swelling, and pain, have been reported during postmarketing surveillance. Necrosis associated with extravasation has also been reported.

Other Events

Pain and asthenia were the most frequently reported miscellaneous adverse effects; their relationship to the tumor and to anemia was likely. Alopecia was reported (3%). Cardiovascular, respiratory, genitourinary, and mucosal side effects have occurred in 6% or less of the patients. Cardiovascular events (cardiac failure, embolism, cerebrovascular accidents) were fatal in less than 1% of the patients and did not appear to be related to chemotherapy. Cancer-associated hemolytic uremic syndrome has been reported rarely.

Malaise, anorexia, hypertension, dehydration, and stomatitis have been reported as part of postmarketing surveillance.

Read the Paraplatin (carboplatin) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

The renal effects of nephrotoxic compounds may be potentiated by PARAPLATIN (carboplatin) .

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Bone marrow suppression (leukopenia, neutropenia, and thrombocytopenia) is dose-dependent and is also the dose-limiting toxicity. Peripheral blood counts should be frequently monitored during PARAPLATIN (carboplatin) treatment and, when appropriate, until recovery is achieved. Median nadir occurs at day 21 in patients receiving single-agent carboplatin. In general, single intermittent courses of PARAPLATIN (carboplatin) should not be repeated until leukocyte, neutrophil, and platelet counts have recovered.

Since anemia is cumulative, transfusions may be needed during treatment with PARAPLATIN (carboplatin) , particularly in patients receiving prolonged therapy.

Bone marrow suppression is increased in patients who have received prior therapy, especially regimens including cisplatin. Marrow suppression is also increased in patients with impaired kidney function. Initial PARAPLATIN (carboplatin) dosages in these patients should be appropriately reduced (see DOSAGE AND ADMINISTRATION) and blood counts should be carefully monitored between courses. The use of PARAPLATIN (carboplatin) in combination with other bone marrow suppressing therapies must be carefully managed with respect to dosage and timing in order to minimize additive effects.

Carboplatin has limited nephrotoxic potential, but concomitant treatment with aminoglycosides has resulted in increased renal and/or audiologic toxicity, and caution must be exercised when a patient receives both drugs. Clinically significant hearing loss has been reported to occur in pediatric patients when carboplatin was administered at higher than recommended doses in combination with other ototoxic agents.

PARAPLATIN (carboplatin) can induce emesis, which can be more severe in patients previously receiving emetogenic therapy. The incidence and intensity of emesis have been reduced by using premedication with antiemetics. Although no conclusive efficacy data exist with the following schedules of PARAPLATIN (carboplatin) , lengthening the duration of single intravenous administration to 24 hours or dividing the total dose over 5 consecutive daily pulse doses has resulted in reduced emesis.

Although peripheral neurotoxicity is infrequent, its incidence is increased in patients older than 65 years and in patients previously treated with cisplatin. Pre-existing cisplatin-induced neurotoxicity does not worsen in about 70% of the patients receiving carboplatin as secondary treatment.

Loss of vision, which can be complete for light and colors, has been reported after the use of carboplatin with doses higher than those recommended in the package insert. Vision appears to recover totally or to a significant extent within weeks of stopping these high doses.

As in the case of other platinum-coordination compounds, allergic reactions to carboplatin have been reported. These may occur within minutes of administration and should be managed with appropriate supportive therapy. There is increased risk of allergic reactions including anaphylaxis in patients previously exposed to platinum therapy. (See CONTRAINDICATIONS and ADVERSE REACTIONS: Allergic Reactions.)

High dosages of carboplatin (more than 4 times the recommended dose) have resulted in severe abnormalities of liver function tests.

PARAPLATIN (carboplatin aqueous solution) INJECTION may cause fetal harm when administered to a pregnant woman. Carboplatin has been shown to be embryotoxic and teratogenic in rats. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.

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.

Carcinogenesis, 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 (carboplatin) 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).

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There is no known antidote for PARAPLATIN (carboplatin aqueous solution) INJECTION overdosage. The anticipated complications of overdosage would be secondary to bone marrow suppression and/or hepatic 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 (carboplatin) should not be employed in patients with severe bone marrow depression or significant bleeding.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

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 (carboplatin) dosages should therefore be reduced in these patients (see DOSAGE AND ADMINISTRATION).

The primary determinant of PARAPLATIN (carboplatin) 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 (carboplatin) plasma AUCs should be used in elderly patients to minimize the risk of toxicity.

Clinical Studies

Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer

In two prospectively randomized, controlled studies conducted by the National Cancer Institute of Canada, Clinical Trials Group (NCIC), and the Southwest Oncology Group (SWOG), 789 chemotherapy naive patients with advanced ovarian cancer were treated with carboplatin or cisplatin, both in combination with cyclophosphamide every 28 days for 6 courses before surgical reevaluation. The following results were obtained from both studies:

Comparative Efficacy

Overview of Pivotal Trials

  NCIC SWOG
Number of patients randomized 447 342
Median age (years) 60 62
Dose of cisplatin 75 mg/m2 100 mg/m2
Dose of carboplatin 300 mg/m2 300 mg/m2
Dose of cyclophosphamide 600 mg/m2 600 mg/m2
Residual tumor < 2 cm (number of patients) 39% (174/447) 14% (49/342)

Clinical Response in Measurable Disease Patients

  NCIC SWOG
Carboplatin (number of patients) 60% (48/80) 58% (48/83)
Cisplatin (number of patients) 58% (49/85) 43% (33/76)
95% CI of difference (Carboplatin-Cisplatin) (-13.9%, 18.6%) (-2.3%, 31.1%)

Pathologic Complete Response*

  NCIC SWOG
Carboplatin (number of patients) 11% (24/224) 10% (17/171)
Cisplatin (number of patients) 15% (33/223) 10% (17/171)
95% CI of difference (Carboplatin-Cisplatin) (-10.7%, 2.5%) (-6.9%, 6.9%)
* 114 Carboplatin and 109 Cisplatin patients did not undergo second look surgery in NCIC study. 90 Carboplatin and 106 Cisplatin patients did not undergo second look surgery in SWOG study.

Progression-Free Survival (PFS)

  NCIC SWOG
Median
  Carboplatin 59 weeks 49 weeks
  Cisplatin 61 weeks 47 weeks
2-year PFS*
  Carboplatin 31% 21%
  Cisplatin 31% 21%
  95% CI of difference (Carboplatin-Cisplatin) (-9.3, 8.7) (-9.0, 9.4)
3-year PFS*
  Carboplatin 19% 8%
  Cisplatin 23% 14%
  95% CI of difference (Carboplatin-Cisplatin) (-11.5, 4.5) (-14.1, 0.3)
Hazard Ratio** 1.10 1.02
  95% CI (Carboplatin-Cisplatin) (0.89, 1.35) (0.81, 1.29)
* Kaplan-Meier EstimatesUnrelated deaths occurring in the absence of progression were counted as events (progression) in thisanalysis.
** Analysis adjusted for factors found to be of prognostic significance were consistent with unadjustedanalysis.

Survival

  NCIC SWOG
Median
  Carboplatin 110 weeks 86 weeks
  Cisplatin 99 weeks 79 weeks
2-year Survival*
  Carboplatin 51.9% 40.2%
  Cisplatin 48.4% 39.0%
  95% CI of difference (Carboplatin-Cisplatin) (-6.2, 13.2) (-9.8, 12.2)
3-year Survival*
  Carboplatin 34.6% 18.3%
  Cisplatin 33.1% 24.9%
  95% CI of difference (Carboplatin-Cisplatin) (-7.7, 10.7) (-15.9, 2.7)
Hazard Ratio** 0.98 1.01
  95% CI (Carboplatin-Cisplatin) (0.78, 1.23) (0.78, 1.30)
* Kaplan-Meier Estimates
** Analysis adjusted for factors found to be of prognostic significance were consistent with unadjusted analysis.

Comparative Toxicity

The pattern of toxicity exerted by the carboplatin-containing regimen was significantly different from that of the cisplatin-containing combinations. Differences between the two studies may be explained by different cisplatin dosages and by different supportive care.

The carboplatin-containing regimen induced significantly more thrombocytopenia and, in one study, significantly more leukopenia and more need for transfusional support. The cisplatin-containing regimen produced significantly more anemia in one study. However, no significant differences occurred in incidences of infections and hemorrhagic episodes.

Non-hematologic toxicities (emesis, neurotoxicity, ototoxicity, renal toxicity, hypomagnesemia, and alopecia) were significantly more frequent in the cisplatin-containing arms.

ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER NCIC STUDY

    Carboplatin Arm Percent* Cisplatin Arm Percent* P-Values**
Bone Marrow
  Thrombocytopenia < 100,000/mm3 70 29 < 0.001
< 50,000/mm3 41 6 < 0.001
  Neutropenia < 2000 cells/mm3 97 96 ns
< 1000 cells/mm3 81 79 ns
  Leukopenia < 4000 cells/mm3 98 97 ns
< 2000 cells/mm3 68 52 0.001
  Anemia < 11 g/dL 91 91 ns
< 8 g/dL 18 12 ns
  Infections   14 12 ns
  Bleeding   10 4 ns
  Transfusions   42 31 0.018
Gastrointestinal
  Nausea and vomiting   93 98 0.010
  Vomiting   84 97 < 0.001
  Other GI side effects   50 62 0.013
Neurologic
  Peripheral neuropathies   16 42 < 0.001
  Ototoxicity   13 33 < 0.001
  Other sensory side effects   6 10 ns
  Central neurotoxicity   28 40 0.009
Renal
  Serum creatinine elevations   5 13 0.006
  Blood urea elevations   17 31 < 0.001
Hepatic
  Bilirubin elevations   5 3 ns
  SGOT elevations   17 13 ns
  Alkaline phosphatase elevations   - - -
Electrolytes loss
  Sodium   10 20 0.005
  Potassium   16 22 ns
  Calcium   16 19 ns
  Magnesium   63 88 < 0.001
Other side effects
  Pain   36 37 ns
  Asthenia   40 33 ns
  Cardiovascular   15 19 ns
  Respiratory   8 9 ns
  Allergic   12 9 ns
  Genitourinary   10 10 ns
  Alopecia +   50 62 0.017
  Mucositis   10 9 ns
* Values are in percent of evaluable patients.
** ns=not significant, p > 0.05.
+ May have been affected by cyclophosphamide dosage delivered.

ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER SWOG STUDY

    Carboplatin Arm Percent* Cisplatin Arm Percent* P-Values**
Bone Marrow
  Thrombocytopenia < 100,000/mm3 59 35 < 0.001
< 50,000/mm3 22 11 0.006
  Neutropenia < 2000 cells/mm3 95 97 ns
< 1000 cells/mm3 84 78 ns
  Leukopenia < 4000 cells/mm3 97 97 ns
< 2000 cells/mm3 76 67 ns
  Anemia < 11 g/dL 88 87 ns
< 8 g/dL 8 24 < 0.001
  Infections   18 21 ns
  Bleeding   6 4 ns
  Transfusions   25 33 ns
Gastrointestinal
  Nausea and vomiting   94 96 ns
  Vomiting   82 91 0.007
  Other GI side effects   40 48 ns
Neurologic
  Peripheral neuropathies   13 28 0.001
  Ototoxicity   12 30 < 0.001
  Other sensory side effects   4 6 ns
  Central neurotoxicity   23 29 ns
Renal
  Serum creatinine elevations   7 38 < 0.001
  Blood urea elevations   - - -
Hepatic
  Bilirubin elevations   5 3 ns
  SGOT elevations   23 16 ns
  Alkaline phosphatase elevations   29 20 ns
Electrolytes loss
  Sodium   - - -
  Potassium   - - -
  Calcium   - - -
  Magnesium   58 77 < 0.001
Other side effects
  Pain   54 52 ns
  Asthenia   43 46 ns
  Cardiovascular   23 30 ns
  Respiratory   12 11 ns
  Allergic   10 11 ns
  Genitourinary   11 13 ns
  Alopecia +   43 57 0.009
  Mucositis   6 11 ns
* Values are in percent of evaluable patients.
** ns=not significant, p > 0.05.
+ May have been affected by cyclophosphamide dosage delivered.

Use as a Single Agent for Secondary Treatment of Advanced Ovarian Cancer

In two prospective, randomized controlled studies in patients with advanced ovarian cancer previously treated with chemotherapy, carboplatin achieved 6 clinical complete responses in 47 patients. The duration of these responses ranged from 45 to 71+ weeks.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Last reviewed on RxList: 6/30/2009
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Paraplatin Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

CARBOPLATIN - INJECTION

(CAR-bow-plah-tin)

COMMON BRAND NAME(S): Paraplatin

WARNING: Carboplatin can cause severe blood disorders (e.g., anemia, bone marrow suppression) that can result in infection and bleeding problems. Your risk of developing these problems increases with higher doses or longer treatment with carboplatin. Also, an unlikely but very serious allergic reaction to this drug may occur within minutes of receiving a dose. Tell your doctor immediately if you develop any of the following symptoms: easy bruising/bleeding, signs of infection (e.g., persistent sore throat, fever), unusual tiredness, rash, itching, swelling, severe dizziness, or trouble breathing.

Vomiting is a common side effect of this medication. See the Side Effects section for more information.

USES: Carboplatin is used to treat various types of cancer. It is a chemotherapy drug that contains platinum. It is used alone or in combination with other medications to slow or stop cancer cell growth.

HOW TO USE: Carboplatin is usually given by infusion into a vein (intravenously-IV) over at least 15 minutes by a healthcare professional.

The dosage is based on your medical condition, body size, and response to therapy. In general, courses of carboplatin treatment should not be given more often than once every 4 weeks. Consult your doctor or pharmacist for more details.

Disclaimer

Paraplatin Consumer (continued)

SIDE EFFECTS: Stomach pain, body aches/pain, diarrhea, constipation, weakness, nausea, and vomiting may occur. Nausea and vomiting can be severe in some patients but usually go away within 24 hours of treatment. Drug therapy may be needed to prevent or relieve nausea and vomiting. Not eating before your treatment may help relieve vomiting. Changes in diet such as eating several small meals or limiting activity may help lessen some of these effects. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Temporary hair loss may occur. Normal hair growth should return after treatment has ended.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor right away if you have any serious side effects, including: numbness or tingling in the hands/feet, mouth sores, yellowing eyes/skin, dark urine, unusual tiredness, change in the amount of urine, pain/swelling/redness at the injection site, hearing problems (e.g., ringing in the ears, hearing loss), easy bruising/bleeding, blood in the urine, black/bloody stools, fast/irregular heartbeat.

Rarely, temporary vision loss may occur with high doses of carboplatin. Normal vision usually returns within several weeks after the end of treatment. Consult your doctor or pharmacist for more details and report this side effect immediately if it occurs.

This medication can lower your body's ability to fight an infection. Notify your doctor promptly if you develop any signs of an infection such as fever, chills or persistent sore throat.

A very serious allergic reaction to this drug is unlikely, but get medical help right away if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Paraplatin (carboplatin) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using carboplatin, tell your doctor or pharmacist if you are allergic to it, or to cisplatin; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: decreased bone marrow function/blood cell disorders (e.g., anemia, leukopenia, thrombocytopenia).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, mineral imbalance (low blood levels of sodium, potassium, magnesium, calcium).

Do not have immunizations/vaccinations without the consent of your doctor, and avoid contact with people who have recently received oral polio vaccine.

Use caution with sharp objects like safety razors or nail cutters and avoid activities such as contact sports to lower the chance of getting cut, bruised or injured.

Wash your hands well to prevent the spread of infections.

The elderly may be more sensitive to the side effects of this drug, especially to bleeding problems and numbness/tingling of the hands/feet.

Children may be at greater risk for hearing loss when carboplatin is used at higher-than-recommended doses in combination with other medications that may affect hearing.

This medication is not recommended for use during pregnancy. It may cause harm to an unborn baby. Women of childbearing age should use reliable form(s) of birth control during treatment and for some time afterwards. Consult your doctor for more details.

It is not known whether this drug passes into breast milk. Because of the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Disclaimer

Paraplatin Consumer (continued)

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: aminoglycoside antibiotics (e.g., gentamicin, neomycin), amphotericin B, certain anti-seizure medications (hydantoins such as phenytoin), certain "water pills" (loop diuretics such as furosemide, bumetanide, ethacrynic acid), nalidixic acid.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly.

NOTES: Laboratory and/or medical tests (e.g., complete blood counts, kidney function tests, blood mineral levels) should be performed to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist immediately to establish a new dosing schedule.

STORAGE: Not applicable. This medication is given in a clinic and will not be stored at home.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854-1166 (USA), or 1-800-668-1507 (Canada).

Information last revised September 2010. Copyright(c) 2010 First Databank, Inc.

Paraplatin Patient Information Including Side Effects

Brand Names: Paraplatin

Generic Name: carboplatin (Pronunciation: KAR boe PLA tin)

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 are the possible side effects of carboplatin (Paraplatin)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • pale skin, feeling light-headed or short of breath, rapid heart rate, trouble concentrating;
  • easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;
  • fever, chills, body aches, flu symptoms, sores in your mouth and throat;
  • severe or ongoing vomiting;
  • stomach pain, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);
  • numbness or tingly feeling in your hands or feet;
  • hearing or vision problems;
  • skin changes where the medicine was injected; or
  • low magnesium (confusion, uneven heart rate, jerking muscle movements, muscle weakness or limp feeling).

Less serious side effects may include:

  • nausea, vomiting, loss of appetite;
  • tired feeling;
  • temporary hair loss; or
  • pain, swelling or redness where the medicine was injected.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Paraplatin (carboplatin) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about 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.

Before receiving carboplatin, tell your doctor if you have liver or kidney disease, or if you have received carboplatin in the past.

Carboplatin can harm your kidneys, and this effect is increased when you also use certain other medicines harmful to the kidneys. Before you receive carboplatin, tell your doctor about all other medications you use. Many other drugs (including some over-the-counter medicines) can be harmful to the kidneys.

Carboplatin can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Visit your doctor regularly.

Call your doctor if you have a serious side effect such as pale skin, easy bruising or bleeding, fever, chills, body aches, flu symptoms, mouth sores, hearing or vision problems, numbness or tingling, feeling short of breath, or muscle weakness.

You may need to receive blood transfusions while you are being treated with carboplatin.

Side Effects Centers

Paraplatin Patient Information including How Should I Take

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.

How is carboplatin given (Paraplatin)?

Carboplatin is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.

Carboplatin is usually given once every 4 weeks. Follow your doctor's instructions.

You may be given other medications to prevent nausea or vomiting while you are receiving carboplatin.

Carboplatin can lower blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Your blood may need to be tested often. Your kidney and liver function may also need to be tested. Visit your doctor regularly.

You may need to receive blood transfusions while you are being treated with carboplatin.

Side Effects Centers

Paraplatin Patient Information including If I Miss a Dose

What happens if I miss a dose (Paraplatin)?

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

What happens if I overdose (Paraplatin)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include pale skin, easy bruising or bleeding, severe weakness, fever, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes).

What should I avoid while using carboplatin (Paraplatin)?

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

Carboplatin 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.

What other drugs will affect carboplatin (Paraplatin)?

Carboplatin can harm your kidneys. This effect is increased when you also use other medicines harmful to the kidneys. You may need dose adjustments or special tests if you have recently used:

  • medicines to treat a bowel disorder;
  • medication to prevent organ transplant rejection;
  • antiviral medications;
  • pain or arthritis medicines; or
  • any injected antibiotics.

This list is not complete and other drugs may interact with carboplatin. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your doctor or pharmacist can provide more information about carboplatin.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 5.03. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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