Platinol

PLATINOL® (cisplatin for injection, USP)

NDC xxxxx-xxx-xx—Each amber vial contains 50 mg of cisplatin

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling occupational exposure to hazardous drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html.

3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006;63:1172-1193.

4. Polovich M, White JM, Kelleher LO, eds. 2005. Chemotherapy and biotherapy guidelines and recommendations for practice. 2nd ed. Pittsburgh, PA: Oncology Nursing Society.

Manufactured by: Corden Pharma Latina S.p.A. Sermoneta-Latina 04013 Italy. Rev December 2011

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

If Platinol is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

• Platinol 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 diagnostic and treatment facilities are readily available.
• Cumulative renal toxicity associated with Platinol is severe. Other major dose-related toxicities are myelosuppression, nausea and vomiting.
• Ototoxicity, which may be more pronounced in children, and is manifested by tinnitus, and/or loss of high frequency hearing and occasionally deafness, is significant.
• Anaphylactic-like reactions to Platinol have been reported. Facial edema, bronchoconstriction, tachycardia, and hypotension may occur within minutes of Platinol administration. Epinephrine, corticosteroids, and antihistamines have been effectively employed to alleviate symptoms.
• Exercise caution to prevent inadvertent Platinol overdose. Doses greater than 100 mg/m2/cycle once every 3 to 4 weeks are rarely used. Care must be taken to avoid inadvertent Platinol overdose due to confusion with carboplatin or prescribing practices that fail to differentiate daily doses from total dose per cycle.

This medicine 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.

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

Cisplatin 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.

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

Call your doctor at once if you have:

• hearing or vision problems, pain behind your eyes;

• trouble with walking or daily activities;

• numbness, tingling, or cold feeling in your hands or feet;

• drowsiness, mood changes, increased thirst, little or no urinating;

• swelling, weight gain, feeling short of breath;

• pale skin, 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;

• chest pain or heavy feeling, pain spreading to the jaw or arm, nausea, sweating, general ill feeling;

• sudden numbness or weakness (especially on one side of the body), sudden severe headache, problems with speech or balance;

• low calcium (numbness or tingly feeling around your mouth, muscle tightness or contraction, overactive reflexes);

• high or low potassium (confusion, tingly feeling, slow or uneven heart rate, weak pulse, extreme thirst, increased urination, leg discomfort, muscle weakness or limp feeling); or

• low sodium (slurred speech, hallucinations, vomiting, severe weakness, muscle cramps, loss of coordination, feeling unsteady, fainting, seizure, shallow breathing or breathing that stops).

Common side effects may include:

• decreased sense of taste;

• tired feeling;

• temporary hair loss; or

• pain, swelling, burning, or irritation around the IV needle.

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.

Platinol® (cisplatin for injection, USP) is a white to light yellow lyophilized powder. Each vial of Platinol contains 50 mg cisplatin, 450 mg Sodium Chloride, USP, and 500 mg Mannitol, USP.

The active ingredient, cisplatin, is a yellow to orange crystalline powder with the molecular formula PtCl2H6N2, and a molecular weight of 300.1. Cisplatin is a heavy metal complex containing a central atom of platinum surrounded by two chloride atoms and two ammonia molecules in the cis position. It is soluble in water or saline at 1 mg/mL and in dimethylformamide at 24 mg/mL. It has a melting point of 207° C.

Peripheral blood counts should be monitored weekly. Liver function should be monitored periodically. Neurologic examination should also be performed regularly (see ADVERSE REACTIONS).

Drug Interactions

Plasma levels of anticonvulsant agents may become subtherapeutic during cisplatin therapy.

In a randomized trial in advanced ovarian cancer, response duration was adversely affected when pyridoxine was used in combination with altretamine (hexamethylmelamine) and Platinol.

Carcinogenesis, Mutagenesis, Impairment of Fertility

See WARNINGS.

Pregnancy

Category D. See WARNINGS.

Nursing Mothers

Cisplatin has been reported to be found in human milk; patients receiving Platinol should not breast-feed.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established. Variants in the thiopurine S-methyltransferase (TPMT) gene are associated with an increased risk of ototoxicity in children treated with cisplatin (see CLINICAL PHARMACOLOGY).

All children should have audiometric monitoring performed prior to initiation of therapy prior to each subsequent dose, and for several years post therapy. Advanced testing methods may allow for earlier detection of hearing loss in an attempt to facilitate the rapid initiation of interventions that can limit the potential adverse impact of hearing impairment on a child's cognitive and social development.

Geriatric Use

Insufficient data are available from clinical trials of cisplatin in the treatment of metastatic testicular tumors or advanced bladder cancer to determine whether elderly patients respond differently than younger patients. In four clinical trials of combination chemotherapy for advanced ovarian carcinoma, 1484 patients received cisplatin either in combination with cyclophosphamide or paclitaxel. Of these, 426 (29%) were older than 65 years. In these trials, age was not found to be a prognostic factor for survival. However, in a later secondary analysis for one of these trials, elderly patients were found to have shorter survival compared with younger patients. In all four trials, elderly patients experienced more severe neutropenia than younger patients. Higher incidences of severe thrombocytopenia and leukopenia were also seen in elderly compared with younger patients, although not in all cisplatin-containing treatment arms. In the two trials where nonhematologic toxicity was evaluated according to age, elderly patients had a numerically higher incidence of peripheral neuropathy than younger patients. Other reported clinical experience suggests that elderly patients may be more susceptible to myelosuppression, infectious complications, and nephrotoxicity than younger patients.

Cisplatin is known to be substantially excreted by the kidney and is contraindicated in patients with preexisting renal impairment. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and renal function should be monitored.

Caution should be exercised to prevent inadvertent overdosage with Platinol. Acute overdosage with this drug may result in kidney failure, liver failure, deafness, ocular toxicity (including detachment of the retina), significant myelosuppression, intractable nausea and vomiting and/or neuritis. In addition, death can occur following overdosage.

No proven antidotes have been established for Platinol overdosage. Hemodialysis, even when initiated four hours after the overdosage, appears to have little effect on removing platinum from the body because of Platinol's rapid and high degree of protein binding. Management of overdosage should include general supportive measures to sustain the patient through any period of toxicity that may occur.

Preparation Precautions

Caution should be exercised in handling the powder and preparing the solution of cisplatin. Procedures for proper handling and disposal of anticancer drugs should be utilized. Several guidelines on this subject have been published.1-4 To minimize the risk of dermal exposure, always wear impervious gloves when handling vials and IV sets containing Platinol for injection.

Skin reactions associated with accidental exposure to cisplatin may occur. The use of gloves is recommended. If Platinol powder or Platinol solution contacts the skin or mucosa, immediately and thoroughly wash the skin with soap and water and flush the mucosa with water. More information is available in the references listed below.

Instructions for Preparation

The 50 mg vials should be reconstituted with 50 mL of Sterile Water for Injection, USP. Each mL of the resulting solution will contain 1 mg of Platinol.

Reconstitution as recommended results in a clear, colorless to slight yellow solution.

The reconstituted solution should be used intravenously only and should be administered by IV infusion over a 6- to 8-hour period (see DOSAGE AND ADMINISTRATION).

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

NOTE TO PHARMACIST: Exercise caution to prevent inadvertent Platinol overdosage. Please call prescriber if dose is greater than 100 mg/m2 per cycle. Aluminum and flip-off seal of vial have been imprinted with the following statement:

CALL DR. IF DOSE>100 MG/M2/CYCLE.