Bavencio

Indications

• Merkel cell carcinoma (specialist use only)
• Renal cell carcinoma (specialist use only)
• Urothelial carcinoma (specialist use only)

Dosage

Children: Paediatric dosing information is not provided in the BNF; refer to the BNF for Children for guidance.

Adults: The recommended dosage of avelumab for adults is 800 mg administered every 2 weeks by intravenous infusion.

Mechanism of action

Avelumab binds to the programmed death-ligand 1 (PD-L1), preventing its interaction with programmed death-1 (PD-1) receptors on T-cells. This blockade enhances T-cell activation and proliferation, leading to a robust anti-tumor immune response.

Pharmacodynamics

The binding of avelumab to PD-L1 results in the inhibition of PD-L1-mediated immune suppression, allowing T-cells to exert their cytotoxic effects on tumor cells. This mechanism is crucial in enhancing the immune response against various malignancies, leading to potential tumor regression.

Pharmacokinetics

Avelumab is administered via intravenous infusion. The pharmacokinetics profile of avelumab includes a half-life of approximately 12 to 20 days. The drug is primarily eliminated through the reticuloendothelial system, and its plasma concentration increases proportionally with dose. It is not extensively metabolized by cytochrome P450 enzymes, making it less susceptible to drug-drug interactions.

Adverse effects

• Infusion-related reactions
• Immune-related reactions
• Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)
• Fatigue

Precautions

• Monitor for signs and symptoms of infusion-related and immune-related reactions
• Patients with a history of severe SCAR associated with other immunostimulant antineoplastic drugs should be treated with caution
• Pre-medication may be required to mitigate infusion-related reactions

Pregnancy

Manufacturer advises avoid unless essential-no information available.

Breast-feeding

Manufacturer advises avoid during treatment and for at least 1 month after stopping treatment-no information available.

Storage

Store in a refrigerator (2–8 °C). Consult product literature for storage conditions after preparation of the infusion.

Formulations

• Solution for infusion: 800 mg/14 ml

Indications

• Infections (topical treatment)
• Wound care (as an antiseptic)
• Ear infections (as an ear drop solution)
• Acid-base balance in metabolic acidosis

Dosage

Children: Refer to established guidelines as dosage may vary based on the formulation and indication.

Adults: Refer to established guidelines as dosage may vary based on the formulation and indication.

Mechanism of action

Acetic acid exerts its effects primarily through its ability to lower pH levels, creating an acidic environment which is inhospitable to many pathogens. It can disrupt the integrity of microbial cell membranes, leading to cell lysis and death. Additionally, acetic acid can promote the healing of wounds and enhance the absorption of certain medications when used as a solvent.

Pharmacodynamics

The pharmacodynamics of acetic acid involve its interaction with biological systems, leading to changes in cellular functions. Its acidic nature helps in the denaturation of proteins and disruption of microbial metabolism. This contributes to its antibacterial and antifungal activities, making it effective against a range of pathogens.

Pharmacokinetics

Acetic acid is rapidly absorbed in the gastrointestinal tract when ingested. It is metabolized primarily in the liver, converting to acetyl CoA and subsequently entering various metabolic pathways including the citric acid cycle. The elimination half-life varies but is generally short, with excretion occurring mainly via urine. When applied topically, absorption is minimal, and local effects are predominant.

Pregnancy

The safety of acetic acid during pregnancy has not been established. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

There is no specific information available regarding the use of acetic acid during breastfeeding. Caution is advised.

Storage

Store in a cool, dry place away from direct sunlight. Keep tightly closed in a well-ventilated area.

Indications

• Cerebral edema
• Elevated intracranial pressure

Mechanism of action

Mannitol elevates blood plasma osmolality, enhancing the flow of water from tissues into interstitial fluid and plasma. This effect reduces cerebral edema and intracranial pressure. It is not reabsorbed in the renal tubule, increasing glomerular filtrate osmolality and promoting diuresis. Mannitol aids in the urinary excretion of toxins and serves as a renal function diagnostic aid by allowing measurement of glomerular filtration rate (GFR). In inhaled form, it is thought to create an osmotic gradient across the airway epithelium, although its exact mechanism in cystic fibrosis treatment is unclear.

Pharmacodynamics

Mannitol is a sugar alcohol, structurally similar to other polyols like xylitol and sorbitol. Its solutions can become acidic due to the loss of a hydrogen ion in water. Mannitol is primarily used as a diuretic to increase urine production and to manage conditions associated with fluid retention, including cerebral edema and glaucoma. It is often co-administered with other diuretics and IV fluids. Caution is advised with inhaled mannitol as it may cause bronchospasm and hemoptysis.

Pharmacokinetics

Mannitol is freely filtered by the glomeruli, with less than 10% being reabsorbed in the renal tubules. Its urinary excretion rate can be used to evaluate glomerular filtration rate (GFR). The drug's pharmacokinetics are influenced by its osmotic properties, which dictate its effects on fluid distribution in the body. Mannitol does not undergo significant metabolism and is excreted unchanged in the urine.

Contra-indications

• Severe renal impairment
• Severe pulmonary congestion
• Anuria
• Cerebral hemorrhage

Adverse effects

• Electrolyte imbalance
• Dehydration
• Hypotension
• Headache
• Nausea
• Vomiting
• Diarrhea
• Thirst
• Pulmonary edema
• Bronchospasm (inhaled form)

Interactions

• May enhance the effects of other diuretics
• Caution with nephrotoxic medications

Precautions

• Monitor renal function during treatment
• Use cautiously in patients with heart failure
• Assess for signs of fluid overload

Pregnancy

Mannitol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether mannitol is excreted in human milk. Caution should be exercised when administered to a nursing woman.

Storage

Store at room temperature, away from light and moisture. Protect from freezing.

Formulations

• Injectable solution (e.g., 20% mannitol)

Indications

• Topical treatment of localized infections
• Antiseptic for skin and mucous membrane applications
• Astringent in certain dermatological conditions

Dosage

Children: Refer to professional resources for specific dosing information, as it can vary based on formulation and condition treated.

Adults: Refer to professional resources for specific dosing information, as it can vary based on formulation and condition treated.

Mechanism of action

Glacial acetic acid exerts its effects primarily through its acidic properties, leading to protein denaturation and cell lysis in microbial cells. This action disrupts cellular integrity, promoting the death of bacteria and fungi. Additionally, it can alter the pH of tissues, which may contribute to its antiseptic effects.

Pharmacodynamics

The pharmacodynamic effects of glacial acetic acid are largely attributed to its ability to lower the pH in the local environment, which can inhibit the growth of certain pathogens. Its astringent properties help to reduce secretions and promote tissue contraction, which can be beneficial in managing conditions that involve inflammation or excessive exudation.

Pharmacokinetics

Glacial acetic acid is absorbed through the skin and mucous membranes when applied topically. Once absorbed, it can be metabolized by the liver, with elimination primarily occurring through urine. The exact pharmacokinetic parameters can vary based on the route of administration and the formulation used, but detailed data on half-life and volume of distribution are not well-characterized in standard references.

Pregnancy

Glacial acetic acid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is classified as a category C drug.

Breast-feeding

It is not known whether glacial acetic acid is excreted in human milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a tightly closed container, in a cool, dry place away from incompatible substances.

Dosage

Children: Refer to specific guidelines for pediatric dosing; consult the BNF for Children for accurate dosage information.

Adults: Refer to specific guidelines for use; dosage may vary based on the context of use.

Mechanism of action

Hydroxide ions act primarily as bases, neutralizing acids to form water and salts. They participate in various biochemical pathways, including selenium metabolism and the degradation of reactive oxygen species. Hydroxide can influence enzyme activity and stability by altering the pH of the environment, thereby affecting metabolic reactions.

Pharmacodynamics

Hydroxide ions can impact biological processes by changing the local pH, which influences enzyme activity, ion transport, and the solubility of other compounds. Their ability to neutralize acids can help regulate physiological pH, contributing to homeostasis in living organisms.

Pharmacokinetics

As an inorganic ion, hydroxide does not undergo traditional pharmacokinetic processes like absorption, distribution, metabolism, or excretion. Instead, it is rapidly equilibrated in biological fluids and participates in acid-base reactions, having immediate effects on the local environment.

Pregnancy

There is limited information regarding the use of hydroxide during pregnancy. Consult a healthcare professional for advice.

Breast-feeding

Limited data is available on the excretion of hydroxide in breast milk. Consult a healthcare professional before use.

Storage

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

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

Mechanism of action

Mannitol is an osmotic diuretic that is metabolically inert in humans and occurs naturally, as a sugar or sugar alcohol, in fruits and vegetables. Mannitol elevates blood plasma osmolality, resulting in enhanced flow of water from tissues, including the brain and cerebrospinal fluid, into interstitial fluid and plasma. As a result, cerebral edema, elevated intracranial pressure, and cerebrospinal fluid volume and pressure may be reduced. As a diurectic mannitol induces diuresis because it is not reabsorbed in the renal tubule, thereby increasing the osmolality of the glomerular filtrate, facilitating excretion of water, and inhibiting the renal tubular reabsorption of sodium, chloride, and other solutes. Mannitol promotes the urinary excretion of toxic materials and protects against nephrotoxicity by preventing the concentration of toxic substances in the tubular fluid. As an Antiglaucoma agent mannitol levates blood plasma osmolarity, resulting in enhanced flow of water from the eye into plasma and a consequent reduction in intraocular pressure. As a renal function diagnostic aid mannitol is freely filtered by the glomeruli with less than 10% tubular reabsorption. Therefore, its urinary excretion rate may serve as a measurement of glomerular filtration rate (GFR). The exact mechanism of action of inhaled mannitol in the symptomatic maintenance treatment of cystic fibrosis remains unclear. It is hypothesized that mannitol produces an osmotic gradient across the airway epithelium that draws fluid into the extracellular space and alters the properties of the airway surface mucus layer, allowing easier mucociliary clearance. MANNITOL IS.../USED/ IN PROPHYLAXIS OF ACUTE RENAL FAILURE. IT IS USED FOR THIS PURPOSE IN CONDITIONS AS DIVERSE AS CARDIOVASCULAR OPERATIONS, SEVERE TRAUMATIC INJURY, OPERATIONS IN THE PRESENCE OF SEVERE JAUNDICE, AND MGMNT OF HEMOLYTIC TRANSFUSION REACTIONS. IN EACH OF THESE CONDITIONS, A PRECIPITOUS FALL IN THE FLOW OF URINE MAY BE ANTICIPATED EITHER AS THE RESULT OF AN ACUTELY REDUCED FILTRATION RATE OR FROM ACUTE CHANGES IN TUBULAR PERMEABILITY. THE LATTER MAY BE CONSEQUENCE OF THE PRESENCE OF NOXIOUS AGENT WITHIN THE TUBULAR FLUID IN EXCESSIVELY HIGH CONCN, IN SOME INSTANCES SUFFICIENT TO RESULT IN ACTUAL PRECIPITATION. IN THESE SITUATIONS, MANNITOL EXERTS OSMOTIC EFFECT WITHIN THE TUBULAR FLUID, INHIBITS WATER REABSORPTION, & MAINTAINS THE RATE OF URINE FLOW. ...CONCN OF TOXIC AGENT WITHIN TUBULAR FLUID DOES NOT REACH EXCESSIVELY HIGH LEVELS THAT OTHERWISE WOULD HAVE BEEN ACHIEVED BY MORE COMPLETE REABSORPTION OF WATER. ...EVEN THOUGH /GLOMERULAR/ FILTRATION RATE IS REDUCED, MANNITOL IS STILL FILTERED @ GLOMERULUS. THE TUBULAR IMPERMEABILITY TO MANNITOL IS NOT ALTERED BY ACUTE RENAL ISCHEMIA OF SHORT DURATION. HENCE, THE MANNITOL THAT IS FILTERED IS ALSO EXCRETED IN THE VOIDED URINE. UNREABSORBED SOLUTE LIMITS BACK DIFFUSION OF WATER. ...URINE VOL CAN BE MAINTAINED EVEN IN PRESENCE OF DECR GLOMERULAR FILTRATION.

Pharmacodynamics

Chemically, mannitol is an alcohol and a sugar, or a polyol; it is similar to xylitol or sorbitol. However, mannitol has a tendency to lose a hydrogen ion in aqueous solutions, which causes the solution to become acidic. For this reason, it is not uncommon to add a substance to adjust its pH, such as sodium bicarbonate. Mannitol is commonly used to increase urine production (diuretic). It is also used to treat or prevent medical conditions that are caused by an increase in body fluids/water (e.g., cerebral edema, glaucoma, kidney failure). Mannitol is frequently given along with other diuretics (e.g., furosemide, chlorothiazide) and/or IV fluid replacement. Inhaled mannitol has the possibility to cause bronchospasm and hemoptysis; the occurrence of either should lead to discontinuation of inhaled mannitol.