Paraplatin Side Effects

Generic Name: carboplatin

Please note - some side effects for Paraplatin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Paraplatin - for the Consumer

Paraplatin

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Paraplatin:

Constipation; diarrhea; hair loss; loss of appetite; nausea; stomach pain or upset; vomiting; weakness.

Seek medical attention right away if any of these SEVERE side effects occur when using Paraplatin:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); change in the amount of urine produced; cough; dark urine; decreased hearing or hearing loss; fever, chills, or sore throat; injection-site reactions (eg, redness, swelling, pain); numbness, tingling, or pain of the hands or feet; pain, irritation, or sores in the mouth; ringing in the ears; severe or persistent tiredness or weakness; unusual bruising or bleeding; vision changes or loss; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Paraplatin Side Effects - for the Professional

Paraplatin

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
*  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. 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.
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

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. 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. 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 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. 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.

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Side Effects by Body System - for Healthcare Professionals

Hematologic

Bone marrow suppression is the dose limiting toxicity of carboplatin. Marrow suppression is usually more severe in patients with impaired kidney function. Anemia with a hemoglobin count less than 11 g/dL has been observed in 71% of patients who started therapy with a baseline above that value. The incidence of anemia increases with increasing exposure. Bone marrow depression may be more severe when carboplatin is combined with other bone marrow suppressing drugs or with radiotherapy. One study has suggested that myelotoxicity could be minimized by the use of regimes based on the circadian rhythm of the bone marrow.

Hematologic side effects have been reported to include thrombocytopenia with platelet counts below 50,000/mm3 in 25% of patients and in 35% of previously treated ovarian cancer patients (PTOCP), neutropenia with granulocyte counts below 1,000/mm3 in 16% of patients (21% of PTOCP), and leukopenia with WBC counts below 2,000/mm3 in 15% of patients (26% of PTOCP).

Gastrointestinal

Gastrointestinal side effects have included vomiting which occurred in 65% of patients and in 81% of PTOCP. In approximately one third of these patients, the vomiting was reported as severe. Other gastrointestinal side effects have included pain (17%), diarrhea (6%), constipation (6%), and stomatitis.

Patients previously treated with emetogenic agents (especially cisplatin) have been more prone to vomiting. Nausea alone occurs in an additional 10% to 15% of patients. Prolonged administration of carboplatin (either by continuous 24 hour infusion or daily pulse doses given for 5 consecutive days) was associated with less severe vomiting than the single dose intermittent schedule.

Nervous system

Nervous system side effects have included peripheral neuropathies which have been reported in 4% of patients and 6% of PTOCP, with mild paresthesias occurring most frequently. Patients older than 65 years of age or previously treated with cisplatin have a been reported to have a 10% risk for peripheral neuropathies. Prolonged treatment, particularly in cisplatin-pretreated patients, may result in cumulative neurotoxicity.

Hepatic

Hepatic side effects have included abnormal liver function tests reported in patients with normal baseline values receiving standard dosages including total bilirubin (5%), SGOT (15%), and alkaline phosphatase (24%), and 5%, 19%, and 37% respectively in PTOCP. These abnormalities were mild and reversible in about one-half of the cases.

In patients receiving very high dosages of carboplatin and autologous bone marrow transplantation, severe abnormalities of liver function tests have been reported.

Renal

Renal side effects have included abnormalities in 6% of serum creatinine test results (10% for PTOCP) and 14% of blood urea nitrogen test results (22% for PTOCP). Most of these reported abnormalities have been mild and about one-half of them were reversible. There have been at least two case reports in the literature of patients with preexisting renal dysfunction deteriorating into renal failure due to intravenous carboplatin therapy. In one of the cases, renal failure followed high-dose therapy. In the other patient, acute renal failure was reversible. There have also been at least two reports in the literature of acute renal failure associated with the use of intraperitoneal carboplatin. Neither patient had a full return of renal function to baseline.

Creatinine clearance is the most sensitive measure of renal function in patients receiving carboplatin. Creatinine clearance also appears to be the most useful test for correlating drug clearance and bone marrow suppression.

Other

Other side effects have included abnormally decreased serum electrolyte values such as sodium (29%), magnesium (29%), calcium (22%), and potassium (20%), 47%, 43%, 31%, and 28% respectively in PTOCP. Electrolyte abnormalities were rarely associated with symptoms.

Ototoxicity has been reported with the use of high-dose carboplatin.

The most frequently reported miscellaneous side effects were pain and asthenia.

Hypersensitivity

One study has noted that approximately 40 instances of hypersensitivity have been reported. The study further notes that there is generally a slow development of hypersensitivity, with reactions evolving only after several cycles of therapy.

Allergic reactions have generally been manageable with standard epinephrine, corticosteroid, and antihistamine therapy.

Hypersensitivity side effects have been reported to include rash, urticaria, erythema, pruritus, and rarely bronchospasm and hypotension. Hypersensitivity reactions may be common in patients with gynecological malignancies.

Metabolic

Metabolic side effects have included dehydration.

Ocular

Ocular side effects including a case of blindness associated with the use of high dose carboplatin have been reported.

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