Platinox

Each vial contains Oxaliplatin, USP 50 mg.

Pharmacology: Pharmacodynamics: Mechanism of Action: Oxaliplatin undergoes nonenzymatic conversion in physiologic solutions to active derivatives via displacement of the labile oxalate ligand. Several transient reactive species are formed, including monoaquo and diaquo DACH platinum, which covalently bind with macromolecules. Both inter and intrastrand Pt-DNA crosslinks are formed. Crosslinks are formed between the N7 positions of two adjacent guanines (GG), adjacent adenine-guanines (AG), and guanines separated by an intervening nucleotide (GNG). These crosslinks inhibit DNA replication and transcription. Cytotoxicity is cell-cycle nonspecific. In vivo studies have shown antitumor activity of oxaliplatin against colon carcinoma. In combination with 5-fluorouracil, oxaliplatin exhibits in vitro and in vivo antiproliferative activity greater than either compound alone in several tumor models [HT29 (colon), GR (mammary), and L1210 (leukemia)].
Pharmacokinetics: The reactive oxaliplatin derivatives are present as a fraction of the unbound platinum in plasma ultrafiltrate. The decline of ultrafilterable platinum levels following oxaliplatin administration is triphasic, characterized by two relatively short distribution phases (t_½α; 0.43 hours and t_½β; 16.8 hours) and a long terminal elimination phase (t_½γ; 391 hours). Pharmacokinetic parameters obtained after a single 2-hour intravenous infusion of Oxaliplatin at a dose of 85 mg/m² expressed as ultrafilterable platinum were Cmax of 0.814 mcg/mL and volume of distribution of 440 L.
Interpatient and intrapatient variability in ultrafilterable platinum exposure (AUC_0-48hr) assessed over 3 cycles was moderate to low (23% and 6%, respectively). A pharmacodynamic relationship between platinum ultrafiltrate levels and clinical safety and effectiveness has not been established.
Distribution: At the end of a 2-hour infusion of Oxaliplatin, approximately 15% of the administered platinum is present in the systemic circulation. The remaining 85% is rapidly distributed into tissues or eliminated in the urine. In patients, plasma protein binding of platinum is irreversible and is greater than 90%. The main binding proteins are albumin and gamma-globulins. Platinum also binds irreversibly and accumulates (approximately 2-fold) in erythrocytes, where it appears to have no relevant activity. No platinum accumulation was observed in plasma ultrafiltrate following 85 mg/m² every two weeks.
Metabolism: Oxaliplatin undergoes rapid and extensive nonenzymatic biotransformation. There is no evidence of cytochrome P450-mediated metabolism in vitro. Up to 17 platinum-containing derivatives have been observed in plasma ultrafiltrate samples from patients, including several cytotoxic species (monochloro DACH platinum, dichloro DACH platinum, and monoaquo and diaquo DACH platinum) and a number of noncytotoxic, conjugated species.
Elimination: The major route of platinum elimination is renal excretion. At five days after a single 2-hour infusion of Oxaliplatin, urinary elimination accounted for about 54% of the platinum eliminated, with fecal excretion accounting for only about 2%. Platinum was cleared from plasma at a rate (10-17 L/h) that was similar to or exceeded the average human glomerular filtration rate (GFR; 7.5 L/h). There was no significant effect of gender on the clearance of ultrafilterable platinum. The renal clearance of ultrafilterable platinum is significantly correlated with GFR.

Oxaliplatin, in combination with fluorouracil and leucovorin, is used for the treatment of metastatic cancer of the colon or rectum as first-line therapy.
Oxaliplatin is indicated for adjuvant treatment of stage III colon cancer patients who have undergone complete resection of the primary tumor.

Therapy in Previously Treated Metastatic Cancer of the Colon or Rectum: Oxaliplatin dosage of 85 mg/m² is administered by IV infusion on day 1 as part of a 2-day combination regimen that includes fluorouracil and leucovorin. The 2-day regimen may be repeated at intervals of 2 weeks.
Therapy in Previously Untreated and Previously Treated Patients with Advanced Colorectal Cancer: The recommended dose schedule given every two weeks is as follows:
Day 1: Oxaliplatin 85 mg/m2 IV infusion in 250-500 mL D5W and leucovorin 200 mg/m² IV infusion in D5W both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by 5-FU 600 mg/m² IV infusion in 500 mL D5W (recommended) as a 22-hour continuous infusion.
Day 2: Leucovorin 200 mg/m² IV infusion over 120 minutes, followed by 5-FU 400 mg/m² IV bolus given over 2-4 minutes, followed by 5-FU 600 mg/m² IV infusion in 500 mL D5W (recommended) as a 22-hour continuous infusion.

There is no known antidote for oxaliplatin overdose. In addition to thrombocytopenia, the anticipated complications of an oxaliplatin overdose include myelosuppression, nausea and vomiting, diarrhea, and neurotoxicity. Patients suspected of receiving an overdose should be monitored, and supportive treatment should be administered.

Oxaliplatin should not be administered to patients with a history of known allergy to oxaliplatin or other platinum compounds.

Oxaliplatin 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.
The safety and effectiveness of the combination of oxaliplatin and 5-FU/LV in patients with renal impairment have not been evaluated. The combination of oxaliplatin and 5-FU/LV should be used with caution in patients with preexisting renal impairment since the primary route of platinum elimination is renal. Clearance of ultrafilterable platinum is decreased in patients with mild, moderate, and severe renal impairment. A pharmacodynamic relationship between platinum ultrafiltrate levels and clinical safety and effectiveness has not been established.
If nausea, vomiting, or loss of appetite occurs, ask your doctor or pharmacist for ways to lessen these effects. Also, other medicines may be given before and after therapy with oxaliplatin to help reduce these effects.
It is important to take each dose as scheduled. If you must miss a dose, contact your doctor who will establish a new dose schedule. Do not take 2 doses at once.
Oxaliplatin may cause drowsiness, dizziness, or vision changes. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to oxaliplatin.
Do not reuse needles, syringes, or other materials. Dispose of properly after use. Ask your doctor, nurse, or pharmacist to explain local regulations for selecting an appropriate container and properly disposing of the container when full.
Oxaliplatin reduces the number of blood cells needed for clotting. To prevent bleeding, avoid situations in which bruising or injury may occur.
Oxaliplatin lowers your resistance to infection. To prevent infection, avoid contact with people who have colds or other infections. Do not touch your eyes or the inside of your nose unless you have thoroughly washed your hands first.
Check with your doctor before having vaccinations while you are using oxaliplatin.
Oxaliplatin may affect how your nerves feel and may cause sensitivity to cold temperatures. Avoid drinking cold drinks and using ice while receiving oxaliplatin. Cover exposed skin before exposing yourself to cold temperatures or cold objects.
Lab tests, including complete blood cell and hemoglobin counts, may be performed to monitor your progress. Be sure to keep all doctor and lab appointments.
If oxaliplatin contains particles or is discolored, or if the vial is cracked or damaged in any way, do not use it.
Use in Pregnancy & Lactation: Oxaliplatin has not been studied in pregnant women. However, studies in animals have shown that oxaliplatin causes miscarriages, decreased weight or death of the fetus, and problems with bone formation.
It is not known whether oxaliplatin passes into human breast milk. Oxaliplatin may cause serious side effects in the nursing infant, breast-feeding is not recommended while taking the medicine.

Oxaliplatin has not been studied in pregnant women. However, studies in animals have shown that oxaliplatin causes miscarriages, decreased weight or death of the fetus, and problems with bone formation.
It is not known whether oxaliplatin passes into human breast milk. Oxaliplatin may cause serious side effects in the nursing infant, breast-feeding is not recommended while taking the medicine.

Gastrointestinal System: One of the most common side effects from receiving oxaliplatin is nausea, vomiting, and/or diarrhea. Patients should be given medicines known as antiemetics before receiving oxaliplatin to help prevent, or decrease this side effect. Diarrhea and mouth sores have also been known to occur. These chances increase if oxaliplatin is given along with the chemotherapy drug fluorouracil.
Nerves and Nervous System: Oxaliplatin can commonly cause damage to nerves and nervous system tissues. Patients may feel tingling, numbness, and sometimes burning of the fingers and toes (neuropathy, both an acute, reversible sensitivity to cold and numbness in the hands and feet and a chronic, possibly irreversible foot/leg, hand/arm numbness, often with deficits in proprioception). This side effect is common, can be severe, and gets worse in the cold. The patient must inform the doctor if any of these symptoms are present. In addition, the patient may experience a tightness or spasm in their throat. The chance that this will happen increases if the patient is exposed to cold food or drinks while receiving oxaliplatin.
Hematological: Low blood counts, referred to as myelosuppression, are expected due to oxaliplatin. The extent to which the blood counts fall due to oxaliplatin has been minimal. When the white blood cell count is low, this is called neutropenia and patients are at an increased risk of developing a fever and infections. There is a drug called filgrastim that can be used to increase the white blood cell count. Platelets are blood cells in the body that allow for the formation of clots. When the platelet count is low, patients are at an increased risk for bruising and bleeding. If the platelet count remains too low a platelet blood transfusion is an option. Low red blood cell counts, referred to as anemia, may also occur due to cisplatin administration. Low red counts make people feel tired and lacking energy. There is a drug called erythropoietin that can be used to increase the red blood cell count.
Allergic Reactions: Oxaliplatin has caused severe allergic reactions known as anaphylaxis. The symptoms include difficulty breathing, drop in blood pressure, sweating, redness of the face, dizziness, headache, and a fast heart beat. This appears to be more common after several treatments with the drug oxaliplatin.
Others: Less common side effects include hair loss (alopecia), fever, rash on hands and feet when given with fluorouracil, and Fatigue. Oxaliplatin rarely causes kidney damage or hearing damage, unlike cisplatin chemotherapy. In addition, some patients may experience an allergic reaction to platinum-containing drugs.

No specific cytochrome P-450-based drug interaction studies have been conducted. No pharmacokinetic interaction between 85 mg/m² oxaliplatin and 5-FU/LV has been observed in patients treated every 2 weeks. Increases of 5-FU plasma concentrations by approximately 20% have been observed with doses of 130 mg/m² oxaliplatin dosed every 3 weeks. Since platinum containing species are eliminated primarily through the kidney, clearance of these products may be decreased by coadministration of potentially nephrotoxic compounds; although, this has not been specifically studied.

Store at temperatures not exceeding 30°C.

Cytotoxic Chemotherapy

L01XA03 - oxaliplatin ; Belongs to the class of platinum-containing antineoplastic agents. Used in the treatment of cancer.

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