Keytruda

Indications

• Melanoma
• Non-small cell lung cancer
• Urothelial carcinoma
• Classical Hodgkin lymphoma
• Head and neck squamous cell carcinoma
• Renal cell carcinoma
• Colorectal cancer
• Oesophageal carcinoma
• Breast cancer
• Endometrial carcinoma
• Cervical cancer
• Gastric cancer
• Small intestine cancer
• Biliary cancer

Dosage

Children: For paediatric dosing

Adults: The dosage of pembrolizumab is typically 200 mg administered every 3 weeks or 400 mg every 6 weeks, depending on the specific indication and clinical context. Refer to the BNF for specific dosing recommendations based on the patient's condition and response.

Mechanism of action

Pembrolizumab binds to the programmed death-1 (PD-1) receptor on T cells, inhibiting its interaction with PD-L1 and PD-L2, which are ligands that normally downregulate immune responses. By blocking this pathway, pembrolizumab enhances the activation and proliferation of T cells, promoting a more robust immune response against tumor cells.

Pharmacodynamics

The pharmacodynamics of pembrolizumab are primarily related to its role in the modulation of T cell activity. By inhibiting PD-1, pembrolizumab increases T cell activation, which can lead to improved anti-tumor activity. Clinical outcomes include enhanced immune-mediated tumor destruction and improved survival rates in patients with certain types of cancer.

Pharmacokinetics

Pembrolizumab has a half-life of approximately 26 days, allowing for convenient dosing schedules. The drug is administered via intravenous infusion, and its pharmacokinetics can be affected by various factors, including the patient's body weight. It is primarily eliminated through the reticuloendothelial system, and its clearance is linear across the therapeutic dose range.

Contra-indications

• History of interstitial pulmonary disease
• Severe dry eye
• History of keratitis
• History of ulcerative keratitis

Adverse effects

• Immune-mediated adverse reactions
• Skin reactions
• Pneumonitis
• Colitis
• Hepatitis
• Endocrinopathies
• Nephritis
• Infusion-related reactions

Interactions

• Corticosteroids may reduce the effectiveness of pembrolizumab
• Other immunosuppressive agents may interfere with its therapeutic effect

Precautions

• Monitor for immune-related adverse effects
• Patients with a history of keratitis should be observed closely
• Evaluate for underlying pulmonary disease prior to treatment

Pregnancy

Avoid use during pregnancy due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises to avoid breastfeeding during and for 2 months after treatment.

Storage

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

Formulations

• Pembrolizumab 50 mg/ml solution for infusion
• Pembrolizumab 100 mg/4 ml concentrate for solution for infusion

Indications

• Rheumatoid arthritis
• Allergic diseases
• Ulcers
• Anemia

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

The exact actions of supplemental L-histidine are not fully understood, but it is postulated to have immunomodulatory and antioxidant properties. It serves as the precursor for histamine, which can enhance suppressor T cell activity and potentially down-regulate the production of reactive oxygen species in immune cells. This may confer benefits in conditions like rheumatoid arthritis, where oxidative stress is a concern.

Pharmacodynamics

L-histidine is abundant in hemoglobin and contributes to various bodily functions. It has been clinically associated with treating rheumatoid arthritis, allergic diseases, ulcers, and anemia. Deficiencies in L-histidine can lead to complications such as impaired hearing. Its metabolites, particularly histamine, exhibit immunomodulatory effects and antioxidant capabilities.

Pharmacokinetics

L-histidine is absorbed through the gastrointestinal tract, and its bioavailability can be influenced by dietary intake. Once ingested, it is incorporated into proteins and utilized in various metabolic pathways, including histidine biosynthesis and tRNA charging. The metabolism of L-histidine involves its conversion to histamine, which subsequently participates in numerous physiological processes.

Pregnancy

There is limited data on the use of L-histidine during pregnancy. Consult healthcare professionals.

Breast-feeding

Limited information is available on the excretion of L-histidine in human milk. Consult healthcare professionals before use.

Storage

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

Formulations

• L-histidine powder
• L-histidine capsules
• L-histidine tablets

Indications

• Cancer (various types)
• Rheumatoid arthritis
• Multiple sclerosis
• Inflammatory bowel disease
• Psoriasis
• Hypercholesterolemia
• Infectious diseases (e.g., COVID-19)

Dosage

Children: Refer to the BNF for Children for paediatric dosing information, as it varies based on the specific monoclonal antibody and the condition being treated.

Adults: Refer to the specific monoclonal antibody product information for adult dosage, as it varies based on indication and specific agent used.

Mechanism of action

Monoclonal antibodies work by binding to specific proteins on the surface of cells. This binding can block the activity of certain proteins, mark cells for destruction by the immune system, or deliver cytotoxic agents directly to target cells. The mechanism of action varies depending on the specific monoclonal antibody but often involves modulation of immune response, inhibition of cell proliferation, and induction of apoptotic pathways.

Pharmacodynamics

The pharmacodynamics of monoclonal antibodies is primarily characterized by their specificity and affinity for targeted antigens. This leads to a variety of effects, including neutralization of pathogens, blockade of receptor-ligand interactions, and antibody-dependent cellular cytotoxicity. The clinical effects depend on the disease being treated and the specific antibody's action, such as inducing tumor regression in cancer or reducing inflammation in autoimmune diseases.

Pharmacokinetics

Monoclonal antibodies typically have a long half-life, allowing for less frequent dosing. They are generally administered intravenously or subcutaneously, with absorption and distribution influenced by the antibody's size and charge. The elimination occurs primarily through proteolytic degradation and intracellular recycling. Factors such as patient-specific variables, including immunogenicity and the presence of antibodies against the monoclonal antibody, can impact pharmacokinetics.

Interactions

• abatacept+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anakinra+monoclonalantibodies: Severe (increases risk of generalised infection (possibly life-threatening))
• anthracyclines+monoclonalantibodies: Severe (increases risk of cardiotoxicity)
• filgotinib+monoclonalantibodies: Severe (increases risk of immunosuppression)
• monoclonalantibodies+fingolimod: Severe (increases risk of generalised infection (possibly life-threatening))
• normal immunoglobulin+monoclonalantibodies: Severe (affects effects)
• monoclonalantibodies+ozanimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+siponimod: Severe (increases risk of generalised infection (possibly life-threatening))
• monoclonalantibodies+vemurafenib: Severe (increases risk of hepatotoxicity)
• monoclonalantibodies+aminophylline: Moderate (decreases exposure)

Mechanism of action

The biological activity of hydrogen chloride is primarily due to its high solubility in water. Upon dissolution, it dissociates to form hydronium ions, which act as proton donors, facilitating catalytic reactions with organic molecules. This capability may lead to cellular injury and necrosis.

Pharmacodynamics

As a strong acid, monohydrochloride can lower pH levels in biological systems, influencing numerous biochemical pathways. Its reactive nature allows it to interact with proteins, lipids, and nucleic acids, potentially leading to cellular damage and influencing metabolic processes.

Pharmacokinetics

Monohydrochloride is rapidly dissociated in aqueous environments, leading to immediate biological effects. The rapid formation of hydronium ions plays a crucial role in its pharmacokinetic profile, as these ions can affect local pH and influence the activity of various enzymes and cellular pathways. Specific absorption, distribution, metabolism, and excretion profiles are not detailed in the provided data.

Pregnancy

There is limited data on the use of monohydrochloride during pregnancy. Consult local guidelines and consider risk versus benefit.

Breast-feeding

Consult local guidelines regarding the use of monohydrochloride while breastfeeding, as data is limited.

Storage

Store in a cool, dry place, away from direct sunlight. Ensure it is kept in a tightly closed container.

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

• Sweetening agent in food and beverages
• Ingredient in pharmaceutical formulations
• Source of quick energy

Dosage

Children: Refer to specific formulations and clinical guidelines for dosing, as sucrose does not have a standardized dosage. Typically used as needed for sweetening.

Adults: Refer to specific formulations and clinical guidelines for dosing, as sucrose does not have a standardized dosage. Typically used as needed for sweetening.

Mechanism of action

Sucrose is metabolized in the body to glucose and fructose, which are then used as energy sources. It does not have a specific pharmacological mechanism of action but contributes to energy metabolism via the glycolytic and citric acid pathways.

Pharmacodynamics

Upon ingestion, sucrose is hydrolyzed by the enzyme sucrase into its constituent monosaccharides, glucose and fructose. These monosaccharides are absorbed in the small intestine and enter the bloodstream, leading to a rise in blood glucose levels. This process provides a quick source of energy for cellular functions.

Pharmacokinetics

Sucrose is rapidly absorbed in the gastrointestinal tract after hydrolysis. Its absorption depends on the presence of sucrase in the intestine. Once in the bloodstream, glucose can be utilized by cells or stored as glycogen in the liver and muscles. The elimination half-life of sucrose itself is not well-defined as it is quickly broken down and utilized.

Pregnancy

Sucrose is generally regarded as safe during pregnancy when consumed in moderation as part of a balanced diet.

Breast-feeding

Sucrose is considered safe during breastfeeding when consumed in normal dietary amounts.

Storage

Store in a cool, dry place, away from direct sunlight.

Formulations

• Oral solution
• Granules
• Tablets

Mechanism of action

Since the actions of supplemental L-histidine are unclear, any postulated mechanism is entirely speculative. However, some facts are known about L-histidine and some of its metabolites, such as histamine and trans-urocanic acid, which suggest that supplemental L-histidine may one day be shown to have immunomodulatory and/or antioxidant activities. Low free histidine has been found in the serum of some rheumatoid arthritis patients. Serum concentrations of other amino acids have been found to be normal in these patients. L-histidine is an excellent chelating agent for such metals as copper, iron and zinc. Copper and iron participate in a reaction (Fenton reaction) that generates potent reactive oxygen species that could be destructive to tissues, including joints. L-histidine is the obligate precursor of histamine, which is produced via the decarboxylation of the amino acid. In experimental animals, tissue histamine levels increase as the amount of dietary L-histidine increases. It is likely that this would be the case in humans as well. Histamine is known to possess immunomodulatory and antioxidant activity. Suppressor T cells have H2 receptors, and histamine activates them. Promotion of suppressor T cell activity could be beneficial in rheumatoid arthritis. Further, histamine has been shown to down-regulate the production of reactive oxygen species in phagocytic cells, such as monocytes, by binding to the H2 receptors on these cells. Decreased reactive oxygen species production by phagocytes could play antioxidant, anti-inflammatory and immunomodulatory roles in such diseases as rheumatoid arthritis. This latter mechanism is the rationale for the use of histamine itself in several clinical trials studying histamine for the treatment of certain types of cancer and viral diseases. In these trials, down-regulation by histamine of reactive oxygen species formation appears to inhibit the suppression of natural killer (NK) cells and cytotoxic T lymphocytes, allowing these cells to be more effective in attacking cancer cells and virally infected cells.

Pharmacodynamics

Is found abundantly in hemoglobin; has been used in the treatment of rheumatoid arthritis, allergic diseases, ulcers and anemia. A deficiency can cause poor hearing.

Mechanism of action

The biological activity of hydrogen chloride is associated with its high solubility in water i.e., 23 moles/L at 0 °C. ... The hydrogen chloride in water dissociates almost completely, with the hydrogen ion captured by the water molecules to form the hydronium ion. The hydronium ion becomes a donor of a proton that possesses catalytic properties and thus is capable of reacting with organic molecules. This may explain the ability of hydrogen chloride to induce cellular injury and necrosis.