KRABEVA 400mg/16mL

Indications

• Colorectal cancer (specialist use only)
• Breast cancer (specialist use only)
• Renal cell carcinoma (specialist use only)
• Non-small cell lung cancer (specialist use only)
• Epithelial ovarian cancer (specialist use only)
• Fallopian tube cancer (specialist use only)
• Primary peritoneal cancer (specialist use only)
• Carcinoma of the cervix (specialist use only)
• Hepatocellular carcinoma (specialist use only)

Dosage

Adults: 2.5 mg/kg every 3 weeks, with adjustments as necessary based on product literature regarding dose interruption or discontinuation due to side effects.

Mechanism of action

Bevacizumab binds to human VEGF-A, preventing it from interacting with its receptors on endothelial cells. This inhibition disrupts the VEGF signaling pathway, leading to decreased vascular permeability and reduced angiogenesis, ultimately resulting in tumor starvation and reduced metastasis.

Pharmacodynamics

The pharmacodynamics of bevacizumab involve its ability to inhibit angiogenesis, which is crucial for tumor growth and metastasis. By blocking VEGF, bevacizumab decreases blood vessel formation, impacts tumor oxygenation, and alters tumor microenvironments, leading to reduced tumor size and progression. The drug's effect on the tumor vasculature can also enhance the efficacy of concurrent chemotherapy.

Pharmacokinetics

Bevacizumab is administered intravenously and has a half-life of approximately 20 days. It is distributed widely in the body, with a volume of distribution of about 3.3 L/kg. The drug undergoes non-specific catabolism, and clearance is influenced by factors such as tumor burden and the presence of antibodies against bevacizumab. Dosage adjustments may be necessary based on patient response and tolerability.

Contra-indications

• Hypersensitivity to bevacizumab or any excipients
• Active bleeding or significant bleeding disorder
• Severe uncontrolled hypertension
• Recent history of arterial thromboembolic events

Adverse effects

• Hypertension
• Proteinuria
• Gastrointestinal perforations
• Wound healing complications
• Hemorrhage
• Thromboembolic events
• Ocular disorders such as vision loss
• Fatigue
• Nausea
• Neutropenia
• Thrombocytopenia

Interactions

• May increase the risk of bleeding when used with anticoagulants
• Risk of osteonecrosis of the jaw when used concurrently with bisphosphonates
• Potentially increased risk of hypertension with other antihypertensive medications

Precautions

• History of dry eyes
• Invasive dental procedures should be avoided if possible
• Monitor blood pressure regularly during treatment
• Ophthalmic examinations are recommended at baseline and during treatment

Pregnancy

Avoid unless potential benefit outweighs risk; embryotoxic in animal studies.

Breast-feeding

Discontinue breastfeeding before starting treatment and for 3 months after last treatment.

Storage

Store in a refrigerator (2°C to 8°C). Do not freeze. Protect from light.

Formulations

• Powder for solution for infusion

Dosage

Children: Refer to specific formulations and clinical guidelines for dosing information as this can vary widely based on the context of use.

Adults: Refer to specific formulations and clinical guidelines for dosing information as this can vary widely based on the context of use.

Mechanism of action

Dibasic compounds often act by providing a buffering effect in biological systems, which helps to maintain physiological pH levels. They may also interact with various biological targets depending on their specific structure, influencing metabolic pathways and cellular functions.

Pharmacodynamics

The pharmacodynamics of dibasic compounds is highly variable and depends on their specific chemical structure and the context of their use. Generally, these compounds may alter the absorption and distribution of other drugs, modulate enzyme activity, or affect cellular signaling pathways through their interactions with biological molecules.

Pharmacokinetics

The pharmacokinetics of dibasic compounds can vary widely. Factors such as solubility, stability, and route of administration influence their absorption, distribution, metabolism, and excretion. Typically, dibasic compounds may be absorbed in the gastrointestinal tract and may undergo various metabolic processes depending on their specific nature.

Pregnancy

Dibasic compounds should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult with a healthcare provider.

Breast-feeding

Caution is advised when administering dibasic compounds to breastfeeding mothers. Consult with a healthcare provider.

Storage

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

Indications

• Vascular health
• Oxidative stress-related conditions
• Anti-aging applications
• Inflammatory disorders

Dosage

Children: Refer to the BNF for Children for pediatric dosing information regarding hydrogen-rich water.

Adults: Refer to the BNF for specific dosages and administration guidelines for hydrogen-rich water.

Mechanism of action

Molecular hydrogen exerts its effects primarily through its antioxidant properties, which involve the activation of the Nrf2 pathway. This pathway regulates the expression of various antioxidant enzymes, thereby reducing oxidative stress and inflammation. In endothelial cells, H2 has been shown to prevent TCDD-induced senescence and promote cellular longevity by maintaining cellular homeostasis and modulating redox status.

Pharmacodynamics

The pharmacodynamics of dihydrogen are characterized by its ability to scavenge free radicals and reduce oxidative stress. It also influences cellular signaling pathways related to inflammation and aging. Specifically, H2 aids in maintaining the balance of NAD+/NADH, which is crucial for cellular metabolism and energy production. The modulation of the Nrf2 pathway leads to enhanced production of endogenous antioxidants, contributing to its protective effects on vascular endothelial cells.

Pharmacokinetics

Dihydrogen is rapidly absorbed and distributed in the body. When administered as hydrogen-rich water, it is absorbed through the gastrointestinal tract. Its concentration decreases over time, becoming nearly undetectable after 12 hours in aqueous solutions. The pharmacokinetic profile indicates that the effects of hydrogen may persist even after the gas has been eliminated, likely due to the activation of protective cellular mechanisms.

Pregnancy

There is insufficient data on the use of dihydrogen during pregnancy. Consult a healthcare provider for guidance.

Breast-feeding

Limited information is available regarding the safety of dihydrogen during breastfeeding. Consult a healthcare provider before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep container tightly closed.

Formulations

• Hydrogen-rich water

Dosage

Children: Refer to the specific drug formulation for dosing recommendations.

Adults: Refer to the specific drug formulation for dosing recommendations.

Mechanism of action

The mechanism of action for a dihydrate compound is dependent on the specific drug it is associated with. Generally, the pharmacological activity may involve interaction with cellular receptors, modification of enzymatic activity, or alteration of biochemical pathways, which leads to therapeutic effects relevant to the condition being treated.

Pharmacodynamics

Pharmacodynamics of dihydrate compounds involves the relationship between drug concentration and its effect on the body. The presence of water molecules can influence the drug's solubility and absorption, which in turn affects its efficacy and potency. Factors such as receptor binding affinity and the resultant physiological responses are key considerations.

Pharmacokinetics

Pharmacokinetics of dihydrate formulations typically encompasses the processes of absorption, distribution, metabolism, and excretion (ADME). The hydration state can impact the rate of absorption, where dihydrate forms may dissolve more readily in the gastrointestinal tract. Distribution patterns may also vary based on the drug's hydrophilicity or lipophilicity, while metabolic pathways and excretion routes will depend on the specific drug.

Pregnancy

Data on the safety of dihydrate during pregnancy is limited. It is recommended to use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

The excretion of dihydrate in human milk is not well studied. Caution should be exercised when administering dihydrate to breastfeeding women.

Storage

Store in a cool, dry place, protected from light, and in tightly closed containers.

Indications

• Emulsifying agent in drug formulations
• Stabilizer for parenteral preparations
• Solubilizer for hydrophobic drug compounds
• Ingredient in topical formulations

Dosage

Children: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Adults: Refer to specific product guidelines, as dosing varies based on formulation and intended use.

Mechanism of action

Polysorbate functions primarily as an emulsifying agent. It reduces the surface tension between immiscible liquids, allowing them to mix more easily. This property is particularly useful in stabilizing emulsions and suspensions, facilitating the delivery of active pharmaceutical ingredients in various formulations.

Pharmacodynamics

Polysorbate does not exert pharmacological effects in the traditional sense, as it does not bind to specific receptors to elicit a physiological response. Instead, it plays a crucial role in modifying the physical properties of drug formulations, thereby enhancing drug delivery and absorption. Its ability to solubilize drugs enhances their bioavailability, particularly for poorly soluble compounds.

Pharmacokinetics

Polysorbate is generally considered to be non-toxic and is not absorbed to a significant extent when administered orally. It is metabolized by the liver and excreted primarily through the gastrointestinal tract. The pharmacokinetic profile may vary depending on the route of administration and the specific formulation in which it is used.

Adverse effects

• Allergic reactions
• Skin irritation
• Gastrointestinal disturbances

Precautions

• Use cautiously in patients with known allergies to polysorbates or related compounds
• Monitor for allergic reactions in susceptible individuals

Pregnancy

Polysorbate is generally considered safe for use during pregnancy, but consult with a healthcare provider for specific cases.

Breast-feeding

Polysorbate is considered safe during breastfeeding, but consult with a healthcare provider for individual advice.

Storage

Store at room temperature, away from direct sunlight and moisture.

Formulations

• Polysorbate 20
• Polysorbate 80

Indications

• Neurodegenerative diseases
• Diabetes management
• Protective agent in stress conditions
• Potential use in rare metabolic disorders

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations, as pediatric dosing should be determined based on age, weight, and clinical condition.

Adults: Refer to the BNF for specific dosing guidelines as they may vary based on indication and formulation.

Mechanism of action

Trehalose acts by modulating cellular processes, particularly by stabilizing proteins and cellular structures under stress conditions. It enhances autophagy, a cellular degradation and recycling process, which plays a critical role in maintaining cellular homeostasis. The modulation of this pathway can lead to neuroprotective effects, making trehalose a compound of interest in neurodegenerative disease research.

Pharmacodynamics

Trehalose is believed to exert its effects by improving cellular resilience to stress and enhancing the clearance of misfolded proteins. It may also influence glucose metabolism and help maintain osmotic balance, reducing cellular damage in conditions such as diabetes and neurodegenerative diseases. The compound has shown promise in preclinical studies for its ability to improve cognitive function and protect against cellular injury.

Pharmacokinetics

Trehalose is absorbed in the intestine and metabolized primarily by trehalase enzymes. It has a relatively low bioavailability, and its metabolism can vary based on dietary intake and individual enzymatic activity. The pharmacokinetics of trehalose are influenced by its solubility and stability in aqueous environments, with a half-life that may vary depending on the dosage form and route of administration.

Mechanism of action

Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2 on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55 +/- 0.07 mmol/L. This concentration gradually decreased, and H2 was almost undetectable in medium after 12 hr. At 24 hr after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated beta-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2 was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2 on HUVECs. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. /Hydrogen-rich water/ Amyloid beta (Abeta) peptides are identified /as a/ cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity /in SK-N-MC cells/. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. /Hydrogen-rich water/ The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1beta, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubi