Patizra solution for injection

Indications

• Neovascular (wet) age-related macular degeneration
• Diabetic macular edema

Dosage

Children: Dosage information for pediatric patients is not established; refer to the BNF for Children for specific guidelines.

Adults: The recommended dose for adults is usually 0.5 mg (0.05 ml) administered as an intravitreal injection, with treatment intervals typically every month or as directed by a specialist based on the patient's response.

Mechanism of action

Ranibizumab binds to and inhibits the activity of VEGF-A, preventing it from interacting with its receptors on the surface of endothelial cells. This action reduces vascular permeability and neovascularization, stabilizing the retinal tissue and improving visual function.

Pharmacodynamics

The pharmacodynamic effects of ranibizumab include the reduction of fluid leakage from retinal vessels and the regression of newly formed blood vessels, which improves the visual acuity in patients with retinal disorders. The effects are generally seen within a few weeks of administration.

Pharmacokinetics

Ranibizumab is administered via intravitreal injection, leading to localized concentrations in the eye. Systemic absorption is minimal due to the large molecular weight of the drug. It has a half-life of approximately 9 days in the vitreous humor. Clearance is primarily via retinal and choroidal mechanisms.

Contra-indications

• Intra-ocular inflammation (active)
• Ocular or periocular infection
• Previous retinal detachment or macular hole with visual impairment due to diabetic macular oedema

Adverse effects

• Endophthalmitis
• Intra-ocular pressure increase
• Retinal detachment
• Vitreous hemorrhage
• Cataract formation

Interactions

• Danaparoid: Unknown (increases risk of bleeding events)
• Phenindione: Unknown (increases risk of bleeding events)
• Thrombin inhibitors: Unknown (increases risk of bleeding events)
• Argatroban: Unknown (increases risk of bleeding events)
• Bivalirudin: Unknown (increases risk of bleeding events)

Precautions

• Monitor intra-ocular pressure and perfusion of the optic nerve head following injection
• Counsel patients or their carers to report symptoms suggestive of endophthalmitis, retinal detachment or intra-ocular inflammation
• Use with caution in patients with a history of ocular or periocular infections

Pregnancy

Avoid unless potential benefit outweighs risk-systemic exposure very low; limited information available.

Breast-feeding

Specialist sources indicate use with caution-no information available. Large molecular weight suggests limited excretion into milk and likely partial destruction in the infant’s gastrointestinal tract.

Storage

Store in a refrigerator (2–8°C). May be stored unopened at room temperature (20–25°C) for up to 24 hours before use; protect from light.

Formulations

• Solution for injection (pre-filled disposable injection)

Indications

• Rheumatoid arthritis
• Allergic diseases
• Peptic ulcers
• Anemia

Dosage

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

Adults: Refer to BNF for specific dosing information based on condition and individual patient factors.

Mechanism of action

The specific actions of supplemental L-histidine are not completely understood, but it is known that L-histidine serves as a precursor for histamine through the process of decarboxylation. Histamine is associated with immunomodulatory and antioxidant effects, which may help in conditions such as rheumatoid arthritis by activating suppressor T cells and reducing reactive oxygen species production in immune cells. Additionally, L-histidine can chelate metals that participate in oxidative reactions, potentially protecting tissues from oxidative damage.

Pharmacodynamics

Histidine is essential for the synthesis of proteins and is found in high concentrations in hemoglobin. Its metabolites, including histamine, play significant roles in immune response regulation and oxidative stress management. A deficiency in histidine can lead to various health issues, including impaired hearing and reduced immune function.

Pharmacokinetics

Histidine is readily absorbed in the intestines and distributed throughout the body. It undergoes metabolic conversion primarily in the liver, where it is transformed into histamine and other metabolites. The elimination of histidine occurs through various metabolic pathways, and it is excreted in urine primarily as metabolites.

Pregnancy

Histidine is generally regarded as safe during pregnancy when consumed in food. However, the safety of high-dose supplementation has not been established.

Breast-feeding

Histidine is considered safe during breastfeeding in dietary amounts. The effects of high-dose supplementation are not well studied.

Storage

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

Formulations

• L-histidine capsules
• L-histidine powder

Dosage

Children: Refer to specific drug monographs for dosing information, as monohydrate does not represent a specific active ingredient.

Adults: Refer to specific drug monographs for dosing information, as monohydrate does not represent a specific active ingredient.

Mechanism of action

The mechanism of action of a monohydrate compound is dependent on the active pharmaceutical ingredient it contains. Typically, the monohydrate form improves the dissolution and absorption of the drug, thereby enhancing its bioavailability. This can lead to more effective therapeutic outcomes compared to anhydrous forms.

Pharmacodynamics

Pharmacodynamics of a monohydrate drug will vary based on the specific active ingredient. Generally, the pharmacodynamic profile includes the drug's effects on physiological systems and its mechanism of action at the cellular level. Monohydrate forms may show altered pharmacodynamic properties due to differences in solubility and absorption rates.

Pharmacokinetics

The pharmacokinetics of a monohydrate drug formulation will also depend on the specific drug. Typically, pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion can be influenced by the presence of water molecules in the hydrated form. Monohydrates may exhibit enhanced absorption rates due to increased solubility, which can lead to faster onset of action.

Pregnancy

Safety in pregnancy has not been established. Use only if potential benefits justify the risks.

Breast-feeding

Caution is advised when using during breastfeeding, as effects on the nursing infant are unknown.

Storage

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

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.

Indications

• Used as an emulsifier in pharmaceutical formulations
• Improving the solubility of poorly soluble drugs
• Stabilizing emulsions in topical and oral medications
• Used in laboratory settings as a surfactant

Dosage

Children: Dosage varies based on formulation and intended use, refer to specific product guidelines.

Adults: Dosage varies based on formulation and intended use, refer to specific product guidelines.

Mechanism of action

Tween works by reducing the surface tension of the liquid it is mixed with, allowing for better mixing of hydrophilic and hydrophobic substances. This property makes it effective in enhancing the delivery of drugs that are poorly soluble in water. Tween can also stabilize emulsions by forming a protective layer around droplets, preventing them from coalescing.

Pharmacodynamics

As a surfactant, Tween enhances the solubility of lipophilic compounds and improves the absorption of drugs through biological membranes. Its application in drug formulation can lead to increased bioavailability and improved therapeutic effects, especially for poorly soluble drugs.

Pharmacokinetics

Tween is generally not absorbed significantly in the gastrointestinal tract when ingested. Instead, it has a local effect in the gastrointestinal tract and may influence the absorption of other compounds. The metabolism of Tween is not well characterized, and its excretion primarily occurs through feces. The overall pharmacokinetic profile is influenced by the specific formulation in which it is used.

Pregnancy

Tween (polysorbate 20) is generally considered safe for use during pregnancy. However, it should be used only when clearly needed and after consultation with a healthcare provider.

Breast-feeding

Tween is considered safe for use during breastfeeding. Its absorption and systemic exposure are minimal, but it is advisable to consult a healthcare provider.

Storage

Store at room temperature, away from moisture and heat. Keep tightly closed in a cool, dry place.

Indications

• Rheumatoid arthritis
• Atopic dermatitis
• Psoriatic arthritis
• Ulcerative colitis

Dosage

Children: Refer to the BNF for Children for dosing information in pediatric patients.

Adults: Refer to the prescribing information for specific dosing guidelines based on the condition being treated.

Mechanism of action

Upto exerts its therapeutic effects by selectively inhibiting Janus kinase 1 (JAK1). This inhibition prevents the phosphorylation and activation of signal transducer and activator of transcription (STAT) proteins, which are crucial for the signaling of numerous pro-inflammatory cytokines. Consequently, the reduced activity of these pathways leads to decreased inflammation and immune response.

Pharmacodynamics

The pharmacodynamics of Upto are characterized by its ability to inhibit the JAK-STAT signaling pathway, leading to a decrease in the production of inflammatory mediators. This results in reduced symptoms of inflammation, such as pain and swelling, and improved clinical outcomes in patients with autoimmune diseases. The onset of action can vary, with some patients reporting improvements within weeks of starting therapy.

Pharmacokinetics

Upto is rapidly absorbed following oral administration, with peak plasma concentrations typically reached within a few hours. It undergoes extensive metabolism primarily via the cytochrome P450 system, particularly CYP3A4. The elimination half-life is approximately 10 hours, allowing for once-daily dosing. Upto is excreted mainly through urine and feces, with a significant portion of the drug being eliminated unchanged.

Contra-indications

• Hypersensitivity to the active substance or any of the excipients
• Severe hepatic impairment
• Severe renal impairment

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness
• Fatigue
• Allergic reactions including rash and itching

Interactions

• May interact with other central nervous system depressants, increasing sedation
• Potential interactions with drugs metabolized by the liver
• May affect the pharmacodynamics of anticoagulants

Precautions

• Use with caution in patients with hepatic or renal impairment
• Monitor for signs of sedation or respiratory depression
• Consider potential for abuse and dependence

Pregnancy

Limited data is available. Use only if clearly needed and the benefits justify the risks to the fetus.

Breast-feeding

Excreted in breast milk. Use with caution and consider alternative treatments.

Storage

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

Formulations

• Tablets
• Capsules
• Oral solution

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.