Xaloplat5 mg/ml

Xaloplat is a platinum-based chemotherapy agent used in combination with other anticancer drugs for the treatment of colorectal cancer. It is FDA-approved for use only in combination regimens; it is not used as a single agent for its labeled indications.

Established (FDA-approved) uses, always in combination therapy

• Adjuvant treatment of stage III colon cancer — used with infusional 5-fluorouracil (5-FU) and leucovorin (the "FOLFOX" regimen) after complete surgical resection of the primary tumor.
• Treatment of advanced/metastatic colorectal cancer — used with infusional 5-FU and leucovorin, typically as part of first-line or later-line combination chemotherapy.

Off-label / guideline-supported uses (not FDA-approved indications)

Xaloplat-containing regimens (e.g., FOLFOX, FOLFIRINOX) are also used off-label, based on oncology guideline and clinical-trial evidence, in select cases of gastric cancer, esophageal/gastroesophageal junction cancer, and pancreatic cancer, always under specialist oncology supervision and always as part of combination chemotherapy.

Xaloplat must only be prescribed and administered by, or under the supervision of, a qualified oncologist in a facility equipped to manage severe chemotherapy-related reactions.

Each vial of Oxaliplatin for injection contains oxaliplatin as the active ingredient, supplied either as a lyophilized (freeze-dried) powder for reconstitution or as a ready-to-dilute concentrated solution, depending on the manufacturer's formulation. Oxaliplatin is available in single-use vials of various strengths (commonly 50 mg and 100 mg per vial) for intravenous use after reconstitution/dilution. It does not contain any antimicrobial preservative.

Xaloplat is a third-generation platinum-based antineoplastic (chemotherapy) agent structurally related to cisplatin and carboplatin but with a distinct diaminocyclohexane (DACH) carrier ligand that gives it a different toxicity profile — notably a lack of significant nephrotoxicity and ototoxicity, but a characteristic, dose-limiting peripheral sensory neuropathy. Xaloplat is administered only by intravenous infusion under specialist supervision, always in combination with other chemotherapy agents, and is a cornerstone of modern colorectal cancer treatment protocols.

Xaloplat belongs to the class of platinum-based antineoplastic agents (alkylating-like agents). It is classified as a cytotoxic chemotherapy drug used in combination oncology regimens.

Mechanism of Action

Oxaliplatin undergoes non-enzymatic conversion in the body to reactive platinum derivatives that form both inter-strand and intra-strand DNA cross-links (platinum-DNA adducts). These cross-links block DNA replication and transcription, ultimately triggering apoptosis (programmed cell death) in rapidly dividing cancer cells. Oxaliplatin's DACH-platinum adducts are less easily recognized and repaired by cellular mismatch-repair mechanisms than cisplatin adducts, which contributes to its activity even in some cisplatin-resistant tumor cells.

Pharmacokinetics

Following intravenous infusion, Oxaliplatin is extensively and irreversibly bound to plasma proteins and red blood cells; only the unbound (ultrafilterable) platinum fraction is pharmacologically active. It is eliminated mainly through the kidneys via glomerular filtration, with a long terminal half-life due to tissue and protein binding. Oxaliplatin is not significantly metabolized by hepatic cytochrome P450 enzymes.

Xaloplat must be administered only by intravenous infusion, never as an intramuscular, subcutaneous, or intra-arterial injection, and never as an undiluted bolus. Key administration points:

• Infuse over 2 hours through a peripheral line or central venous catheter, using an infusion pump.
• Administer Xaloplat before 5-fluorouracil in the same treatment session; leucovorin may be given concurrently in a separate line (Y-site) or sequentially, per protocol.
• Do not use needles, IV administration sets, or other equipment containing aluminum parts that may contact Xaloplat, as this can cause degradation of the drug and loss of potency.
• Advise patients to avoid cold drinks, ice, and exposure to cold air or objects during and for several days after infusion, as this can trigger or worsen acute peripheral neuropathy symptoms.
• Premedication with antiemetics is recommended, and facilities/staff for managing acute hypersensitivity/anaphylactic reactions must be immediately available during administration (see Precautions and Warnings).

Xaloplat has no clinically significant interactions with the cytochrome P450 enzyme system. However, the following interactions are clinically relevant:

• 5-Fluorouracil: Xaloplat is used deliberately in combination with 5-fluorouracil/leucovorin as standard therapy; this combination increases cumulative gastrointestinal and hematologic toxicity and requires close monitoring of blood counts and GI symptoms.
• Nephrotoxic or ototoxic drugs (e.g., aminoglycosides): theoretical additive risk of impaired platinum clearance or added toxicity when co-administered with other nephrotoxic agents; use with caution and monitor renal function.
• Live/live-attenuated vaccines: avoid during and for a period after treatment with Xaloplat, because chemotherapy-induced immunosuppression increases the risk of vaccine-strain infection; inactivated vaccines may be given but the immune response may be reduced.
• Anticoagulants (e.g., warfarin): Xaloplat-induced thrombocytopenia and hepatotoxicity can increase bleeding risk; monitor INR/PT and coagulation status more frequently.
• QT-prolonging drugs: caution is needed when Xaloplat is combined with other drugs known to prolong the QT interval, due to postmarketing reports of QT prolongation and arrhythmia (see Precautions and Warnings).

Xaloplat commonly causes the following adverse effects; severe reactions require immediate medical attention (see Precautions and Warnings for full detail on serious reactions).

Very Common (may affect more than 1 in 10 people)

• Peripheral sensory neuropathy — the hallmark side effect of Xaloplat: numbness, tingling, or pain in the hands, feet, mouth, or throat, often acutely triggered or worsened by cold exposure (cold drinks, cold air, touching cold objects); may also become chronic and cumulative with repeated cycles.
• Nausea and vomiting
• Diarrhea and abdominal pain
• Myelosuppression: low white blood cell count (neutropenia), low platelet count (thrombocytopenia), anemia
• Fatigue and weakness
• Mouth sores (stomatitis)
• Elevated liver enzymes

Less Common but Serious

• Hypersensitivity/anaphylactic-like reactions — rash, hives, itching, low blood pressure, difficulty breathing, which can occur within minutes of infusion (see Precautions and Warnings)
• Serious infection or sepsis due to low white blood cell counts
• Bleeding due to low platelet counts
• Signs of liver damage (yellowing of skin/eyes, dark urine)
• Cough, shortness of breath (possible lung toxicity)
• Irregular heartbeat

Patients should promptly report any of the above serious symptoms to their treating physician.

Pregnancy: Xaloplat can cause fetal harm and is a cytotoxic chemotherapy agent; it should not be used during pregnancy unless the treating oncologist determines that the potential benefit to the mother clearly justifies the potential risk to the fetus, and only after full discussion with the patient. Women of childbearing potential should use effective contraception during treatment with Xaloplat and for a period after the last dose; men being treated should also use effective contraception, as advised by their physician. Pregnancy testing before starting treatment is recommended where pregnancy is possible.

Breastfeeding: It is not known whether Xaloplat or its metabolites pass into human breast milk. Because of the potential for serious adverse effects in a nursing infant, breastfeeding should be discontinued during treatment with Xaloplat and is not recommended; consult a physician regarding when it may be safe to resume breastfeeding after treatment ends.

Anaphylactic and Hypersensitivity Reactions

Xaloplat can cause anaphylactic-like reactions, which may occur within minutes of starting the infusion, particularly with repeated treatment cycles. Signs include rash, hives, itching, flushing, bronchospasm, low blood pressure, and, rarely, severe anaphylactic shock. Xaloplat must only be given where emergency equipment and medications (epinephrine, corticosteroids, antihistamines) and trained staff are immediately available, and patients must be closely monitored during and after each infusion. Treatment with Xaloplat should generally not be restarted after a severe hypersensitivity reaction.

Peripheral Sensory Neuropathy

Peripheral sensory neuropathy is a hallmark, dose-limiting toxicity of Xaloplat and occurs in the majority of patients. It has two distinct patterns: an acute form, appearing within hours to a couple of days of infusion, often triggered or markedly worsened by exposure to cold (cold drinks, cold air, cold objects), and usually reversible within about two weeks; and a chronic, cumulative form that develops with repeated cycles and may persist or worsen after treatment ends, sometimes interfering with fine motor tasks and daily activities. Patients should be counseled to avoid cold drinks, ice, and cold exposure around the time of each infusion. The dose of Xaloplat is reduced, delayed, or discontinued based on the severity and persistence of neuropathy.

Myelosuppression and Infection

Xaloplat can cause significant bone marrow suppression, including severe neutropenia, thrombocytopenia, and anemia, which can lead to serious infection, sepsis, or bleeding — rarely fatal. Complete blood counts must be checked before each treatment cycle, and treatment withheld until adequate recovery.

Hepatotoxicity

Xaloplat combination therapy can cause liver enzyme elevations and, uncommonly, more serious liver injury including veno-occlusive disease and nodular regenerative hyperplasia. Liver function should be monitored regularly during treatment.

Pulmonary Toxicity

Interstitial lung disease and pulmonary fibrosis, rarely fatal, have been reported with Xaloplat. Unexplained cough, shortness of breath, or new lung findings should be promptly evaluated, and treatment with Xaloplat discontinued if pulmonary toxicity is confirmed.

Cardiac Effects

QT interval prolongation and, rarely, serious ventricular arrhythmias have been reported with Xaloplat. Electrolyte abnormalities (low potassium or magnesium) should be corrected before starting treatment, and periodic ECG monitoring should be considered, especially in patients with heart failure, slow heart rhythms, or those taking other QT-prolonging medicines. Xaloplat should be used with particular caution, or avoided, in patients with congenital long QT syndrome.

Other Warnings

• Rare cases of rhabdomyolysis, including fatal cases, have been reported with Xaloplat; discontinue immediately if muscle pain, weakness, or dark urine occurs.
• Rare cases of reversible posterior leukoencephalopathy syndrome (headache, confusion, seizures, visual changes) have been reported with Xaloplat; confirm with brain imaging if suspected.
• Xaloplat should be handled and disposed of according to institutional cytotoxic-drug handling procedures; avoid skin/eye contact and inhalation.

There is no specific antidote for Xaloplat overdose. An overdose may be expected to worsen known adverse effects, particularly severe myelosuppression (low blood counts), severe peripheral neuropathy, and gastrointestinal toxicity (severe nausea, vomiting, diarrhea), and may increase the risk of hypersensitivity reactions. If an overdose of Xaloplat is suspected, seek immediate medical attention; the patient should be closely monitored in a hospital setting with supportive care (including blood count monitoring and management of complications), as there is no specific reversal agent.

Store unopened Xaloplat vials at controlled room temperature (below 30°C), protected from light, and out of the reach of children, unless the product label specifies otherwise. Once reconstituted, the solution may be stored refrigerated (2-8°C) for up to 24 hours; after further dilution for infusion, use within 6 hours at room temperature or up to 24 hours if refrigerated. Do not freeze. Reconstitution/dilution of Xaloplat must never be performed with sodium chloride (saline) or other chloride-containing solutions, and the drug must not contact aluminum parts of needles or infusion equipment, as both cause degradation of the medicine. Xaloplat should be prepared and handled only by trained healthcare personnel using appropriate cytotoxic-drug precautions.

Renal Impairment

No dose adjustment of Xaloplat is needed in mild-to-moderate renal impairment. In severe renal impairment (creatinine clearance below 30 mL/min), a reduced dose is used with close monitoring, as Xaloplat is primarily eliminated by the kidneys.

Hepatic Impairment

No formal dose adjustment of Xaloplat has been established for hepatic impairment; use with caution and monitor liver function closely (see Precautions and Warnings).

Elderly Patients

No specific dose reduction of Xaloplat is required based on age alone, but elderly patients may have a higher risk of severe neutropenia, diarrhea, dehydration, low potassium, and fatigue, and should be monitored closely.

Pregnancy, Breastfeeding and Children

See Pregnancy and Lactation and Pediatric Uses for detailed guidance on the use of Xaloplat in these populations.

In the adjuvant setting (stage III colon cancer after surgery), Xaloplat-based combination therapy is typically given for a total of 12 cycles (approximately 6 months). In advanced or metastatic colorectal cancer, Xaloplat combination therapy is generally continued until disease progression, unacceptable toxicity (especially persistent severe peripheral neuropathy), or until the treating oncologist determines that further treatment is no longer appropriate. The exact duration of treatment with Xaloplat is individualized based on treatment response, tolerability, and overall clinical judgment.

Xaloplat for injection (lyophilized powder) must be reconstituted only with Water for Injection or 5% Dextrose Injection — never with sodium chloride (saline) or any other chloride-containing solution, as this causes degradation of Xaloplat. A 50 mg vial is typically reconstituted with 10 mL of diluent, and a 100 mg vial with 20 mL, to give a solution containing 5 mg/mL. The reconstituted solution must then be further diluted in 250-500 mL of 5% Dextrose Injection before intravenous infusion. Do not use any equipment containing aluminum parts during preparation or administration of Xaloplat, as contact with aluminum causes degradation of the drug. Some ready-to-dilute liquid formulations of Xaloplat do not require reconstitution and only need dilution in 5% Dextrose — always follow the specific manufacturer's instructions for the product being used.

Oxaliplatin is classified as a platinum-based antineoplastic (alkylating-like) agent, a third-generation platinum compound within the broader class of cytotoxic chemotherapy drugs.

Oxaliplatin is converted in the body to active platinum derivatives that bind to DNA and form platinum-DNA cross-links, blocking DNA replication and transcription and triggering cell death (apoptosis) in cancer cells. Its unique diaminocyclohexane carrier ligand allows it to remain active against some tumor cells that have become resistant to other platinum agents such as cisplatin.

D

The safety and effectiveness of Xaloplat have not been established in pediatric patients. Clinical trials of Xaloplat in children and adolescents (including infants) with various solid tumors did not demonstrate meaningful anti-tumor activity, and peripheral sensory neuropathy was the main dose-limiting toxicity observed, similar to adults. Xaloplat is therefore not recommended for routine use in children outside of a clinical trial setting, and should only be considered by a pediatric oncology specialist in exceptional circumstances.