ADPLATIN

Indications

• Treatment of metastatic colorectal cancer in combination with fluorouracil and folinic acid
• Adjuvant treatment of colon cancer after resection of the primary tumor

Dosage

Children: Refer to the BNF for Children for appropriate dosing in the paediatric population, as specific doses for children are not provided in the BNF for Adults.

Adults: Consult product literature for specific dosing guidelines. The typical adult dose is often around 85 mg/m² administered intravenously every two weeks, but this may vary based on the specific regimen and patient condition.

Mechanism of action

Oxaliplatin exerts its cytotoxic effects by forming DNA cross-links, which inhibit DNA replication and transcription. The drug is converted within the body to reactive platinum species that bind to DNA, leading to the formation of interstrand cross-links and ultimately triggering apoptosis in rapidly dividing cancer cells. This mechanism is particularly effective in targeting cancerous tissues that are highly proliferative.

Pharmacodynamics

The pharmacodynamics of oxaliplatin involve its ability to induce apoptosis in cancer cells through DNA damage. This damage activates several cellular pathways, including the p53 pathway, which is critical for cell cycle regulation and apoptosis. Additionally, oxaliplatin's unique structure allows it to bypass some resistance mechanisms that cancer cells develop against other platinum compounds, making it a valuable option in chemotherapy regimens.

Pharmacokinetics

Oxaliplatin is administered intravenously and has a distribution volume of approximately 16 L/m². Its plasma protein binding is around 95%. The drug undergoes rapid biotransformation in the liver, resulting in several metabolites, with the active form being the platinum-DNA adducts. The elimination half-life is approximately 1-2 hours, and it is primarily excreted via the urine as metabolites and unchanged drug. Dose adjustments may be necessary in patients with hepatic impairment.

Contra-indications

• Peripheral neuropathy with functional impairment

Adverse effects

• Alopecia
• Anaemia
• Appetite decrease
• Arthralgia
• Asthenia
• Chills
• Conjunctivitis
• Constipation
• Cough
• Decreased leukocytes
• Dehydration
• Depression
• Diarrhoea
• Dizziness
• Dyspnoea
• Electrolyte imbalance
• Embolism
• Thrombosis
• Fever
• Flushing
• Gastrointestinal discomfort
• Gastrointestinal disorders
• Haemorrhage
• Headache
• Hiccups
• Hyperglycaemia
• Hyperhidrosis
• Hypersensitivity
• Hypertension
• Increased risk of infection
• Insomnia
• Meningism
• Mucositis
• Nail disorders
• Peripheral neuropathy
• Skin reactions
• Stomatitis
• Taste alteration
• Thrombocytopenia
• Urinary disorders
• Vision disorders
• Vomiting
• Weight changes

Pregnancy

Manufacturer advises to avoid due to toxicity in animal studies.

Breast-feeding

Discontinue breastfeeding.

Storage

Store below 25 degrees Celsius. Protect from light.

Formulations

• Oxaliplatin 50mg/10ml concentrate for solution for infusion vials
• Oxaliplatin 100mg/100ml solution for infusion vials
• Oxaliplatin 200mg/40ml concentrate for solution for infusion vials

Indications

• Energy metabolism disorders
• Neuroprotection
• Potential adjunct therapy in mitochondrial dysfunction
• Investigational uses in ischemic conditions

Dosage

Children: Refer to specific guidelines and clinical recommendations for paediatric dosing as it may vary based on the therapeutic context.

Adults: Refer to specific guidelines and clinical recommendations for adult dosing as it may vary based on the therapeutic context.

Mechanism of action

Succinic acid acts primarily as a substrate in the citric acid cycle, where it is converted to fumarate by the enzyme succinate dehydrogenase. This reaction is part of the electron transport chain, which is vital for ATP production. Additionally, succinic acid can influence cellular signaling pathways, contributing to the regulation of mitochondrial function and energy homeostasis. It also has effects on GABA receptors, which may modulate neuronal excitability and contribute to its neuroprotective properties.

Pharmacodynamics

The pharmacological effects of succinic acid are related to its role in metabolism and energy production. By participating in the citric acid cycle, it helps maintain the balance of energy substrates in cells. Succinic acid may also have antioxidant properties, reducing oxidative stress and mitigating cellular damage. In the context of neuroprotection, it may enhance neuronal survival in conditions of hypoxia or ischemia.

Pharmacokinetics

Succinic acid is rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It is metabolized in the liver and can be converted to various metabolites that enter the citric acid cycle. The elimination of succinic acid occurs primarily through renal excretion. The half-life and specific pharmacokinetic parameters may vary based on the formulation and method of administration.

Pregnancy

There is limited information on the safety of succinic acid during pregnancy. Consult healthcare professionals before use.

Breast-feeding

It is not known whether succinic acid is excreted in human milk. Caution is advised.

Storage

Store in a cool, dry place, away from direct sunlight. Keep out of reach of children.