G Out Plus

Indications

• Acute gout
• Prophylaxis of familial Mediterranean fever (recurrent polyserositis)
• Short-term prophylaxis during initial therapy with allopurinol and uricosuric drugs

Dosage

Children: Refer to the BNF for Children for specific dosing information in children.

Adults: 500 micrograms two to three times daily for acute gout. For prophylaxis of familial Mediterranean fever, 1.0-2.0 mg once daily. Adjustments may be needed based on renal and hepatic function.

Mechanism of action

Colchicine likely interferes with the intracellular assembly of the inflammasome complex in neutrophils and monocytes, mediating activation of interleukin-1β. It also reduces neutrophil adhesion, recruitment, and superoxide production, while disrupting cytoskeletal functions by inhibiting β-tubulin polymerization into microtubules. This action prevents neutrophil activation and migration, mitigating symptoms of gout and reducing inflammatory responses.

Pharmacodynamics

Colchicine exhibits anti-inflammatory properties, effectively ameliorating symptoms of gout and Familial Mediterranean fever. It also demonstrates anti-fibrotic and cardiovascular protective effects, with potential anticancer properties, such as inhibiting cancer cell migration and angiogenesis. However, it is important to note that colchicine has a narrow therapeutic index, which requires careful dosing.

Pharmacokinetics

Colchicine is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is extensively metabolized in the liver, primarily via cytochrome P450 enzymes, and has a half-life of about 9-16 hours. The drug is primarily eliminated via biliary excretion, with renal clearance being significant in patients with renal impairment.

Contra-indications

• Severe renal impairment
• Severe hepatic impairment
• Hypersensitivity to colchicine

Adverse effects

• Abdominal pain
• Diarrhoea
• Nausea
• Vomiting
• Agranulocytosis
• Alopecia
• Bone marrow disorders
• Gastrointestinal haemorrhage
• Kidney injury
• Liver injury
• Menstrual cycle irregularities
• Myopathy
• Nerve disorders
• Rash
• Sperm abnormalities
• Thrombocytopenia

Interactions

• Moderate interaction with berotralstat (increases concentration)
• Moderate interaction with sotorasib (increases exposure)
• Moderate interaction with tucatinib (increases exposure)
• Moderate interaction with venetoclax (increases exposure)
• Unknown interaction with apalutamide (decreases exposure)
• Unknown interaction with amiodarone (increases exposure)
• Unknown interaction with dronedarone (increases exposure)
• Unknown interaction with antifungals, azoles (increases exposure)
• Unknown interaction with ceritinib (increases exposure)
• Unknown interaction with ciclosporin (increases exposure)

Precautions

• Use with caution in elderly patients
• Patients with gastrointestinal, cardiac disease
• Patients with renal or hepatic impairment
• Monitor for signs of toxicity or blood disorders

Pregnancy

Use with caution; specialist sources indicate potential risks.

Breast-feeding

No adverse effects reported in breast-fed infants; consider delaying breastfeeding for 6–8 hours after maternal dose.

Storage

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

Formulations

• Colchicine 500 microgram tablets

Indications

• Constipation
• Dietary fiber supplementation
• Irritable bowel syndrome
• Diverticular disease
• Weight management

Dosage

Children: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Adults: Refer to appropriate guidelines for specific dosage; generally taken with adequate fluid intake.

Mechanism of action

Cellulose acts primarily as a bulk-forming laxative. It absorbs water in the intestines, which increases stool bulk and stimulates peristalsis, thus facilitating bowel movements. Additionally, cellulose is not digestible by human enzymes, leading to fermentation by gut bacteria, which may enhance gut health and alter gut microbiota composition.

Pharmacodynamics

Cellulose increases stool weight and frequency of bowel movements. It works by retaining water in the intestines, leading to softer stools and improved passage through the gastrointestinal tract. The bulking effect of cellulose can help alleviate constipation and promote overall digestive health. It may also play a role in cholesterol reduction and glycemic control through its effects on digestion and absorption of nutrients.

Pharmacokinetics

Cellulose is not absorbed into the bloodstream due to its indigestible nature. Instead, it passes through the gastrointestinal tract, where it adds bulk to the stool. Its fermentation by colonic bacteria produces short-chain fatty acids, which may have beneficial effects on colon health. The onset of action for cellulose as a laxative can vary but is generally within 24 to 72 hours after ingestion.

Adverse effects

• Bloating
• Flatulence
• Diarrhea
• Abdominal discomfort

Precautions

• Use with caution in patients with a history of gastrointestinal disorders.
• Monitor for potential allergic reactions in sensitive individuals.

Pregnancy

Cellulose is generally considered safe during pregnancy as it is a non-toxic, indigestible fiber.

Breast-feeding

Cellulose is also considered safe during breastfeeding; it is excreted in breast milk in negligible amounts.

Storage

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

Formulations

• Powder
• Capsules
• Tablets
• Granules

Indications

• Used as an excipient in solid dosage forms
• Facilitates drug disintegration and dissolution

Dosage

Children: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Adults: Refer to specific product formulation guidelines as crospovidone is used as an excipient and does not have a direct dosage.

Mechanism of action

Crospovidone acts by rapidly absorbing water and swelling upon contact with moisture. This action leads to the disintegration of solid dosage forms, thus increasing the surface area of the active ingredients and promoting their dissolution and subsequent absorption in the gastrointestinal tract. It does not affect the pH of the formulation, ensuring that the active ingredients remain stable.

Pharmacodynamics

Crospovidone exhibits properties that enhance the bioavailability of active ingredients in pharmaceutical formulations. Its ability to rapidly disintegrate tablets and capsules leads to quicker release and absorption of the drug into systemic circulation. As a disintegrant, it aids in the effective delivery of drugs that may otherwise be poorly soluble.

Pharmacokinetics

Crospovidone itself is not absorbed systemically when administered orally. It remains in the gastrointestinal tract, where it performs its function as a disintegrant. The pharmacokinetic profile of drugs formulated with crospovidone may be influenced by the enhanced dissolution and absorption rates provided by this excipient.

Pregnancy

Crospovidone is considered to have low toxicity and is generally regarded as safe for use during pregnancy, but specific studies are limited.

Breast-feeding

There is insufficient data on the excretion of crospovidone in human milk, but it is deemed safe for use during breastfeeding.

Storage

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

Formulations

• Powder
• Tablets

Indications

• Skin irritation
• Minor cuts
• Abrasions
• Superficial skin lesions

Dosage

Children: Apply a thin layer to the affected area as needed, following the manufacturer's instructions.

Adults: Apply a thin layer to the affected area as needed, following the manufacturer's instructions.

Mechanism of action

The specific mechanism of action of Instacoat can vary depending on its active ingredients. Generally, topical formulations exhibit local effects by forming a protective layer over the skin, which can help in preventing infection and facilitating the natural healing process. Some ingredients may have anti-inflammatory properties that reduce redness and swelling, while others may promote cellular regeneration and wound healing.

Pharmacodynamics

Instacoat acts locally at the site of application, with minimal systemic absorption. The pharmacodynamic effects are mainly related to the ingredients used in the formulation. These effects can include enhancement of skin hydration, reduction of inflammation, and promotion of tissue regeneration. The overall outcome is improved skin integrity and faster healing of affected areas.

Pharmacokinetics

As a topical agent, Instacoat is primarily applied to the skin, resulting in localized effects. The pharmacokinetics would largely depend on the specific formulation and its active components. Typically, topical medications show limited systemic absorption, ensuring that the primary effects are exerted locally. The onset of action may occur within a few hours following application, with the duration of effect varying based on the formulation and skin characteristics.

Pregnancy

Data on the use of Instacoat during pregnancy is limited. Its use should be considered only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

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

Storage

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

Indications

• Lactose intolerance
• As a filler or excipient in pharmaceutical formulations

Dosage

Children: Refer to the BNF for Children for specific dosing information based on age and clinical context.

Adults: Refer to the BNF for specific dosing information based on clinical context.

Mechanism of action

Lactose is metabolized in the intestine by the enzyme lactase into its constituent monosaccharides, glucose and galactose. In individuals with lactase deficiency, unabsorbed lactose passes into the colon, where it is fermented by bacteria, leading to gas production and osmotic effects that contribute to diarrhea.

Pharmacodynamics

The pharmacodynamics of lactose are primarily related to its effects on gastrointestinal function. In healthy individuals, lactose is effectively broken down into glucose and galactose, which are absorbed and utilized for energy. In individuals with lactose intolerance, the unabsorbed lactose can cause osmotic diarrhea and colonic fermentation, leading to discomfort and symptoms associated with lactose intolerance.

Pharmacokinetics

Lactose is not absorbed in the gastrointestinal tract until it is hydrolyzed into glucose and galactose by lactase. The absorption of glucose and galactose occurs in the small intestine. The half-life is not applicable as lactose is not typically administered as a medication but is rather ingested as a natural component of food. Its metabolism primarily occurs in the intestine.

Adverse effects

• Bloating
• Diarrhea
• Abdominal pain
• Flatulence

Precautions

• Use with caution in patients with lactose intolerance.
• Consider potential for gastrointestinal upset in sensitive individuals.

Pregnancy

Lactose is generally considered safe for use during pregnancy. However, consult a healthcare professional for individual advice.

Breast-feeding

Lactose is safe to use while breastfeeding, as it is a natural sugar present in breast milk.

Storage

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

Formulations

• Powder
• Granules
• Tablets
• Syrup

Indications

• Used as an excipient in tablet formulations
• Acts as a bulking agent in various pharmaceutical preparations

Dosage

Children: Refer to specific product guidelines for dosage as microcrystalline cellulose is used as an excipient and does not have a therapeutic dose.

Adults: Refer to specific product guidelines for dosage as microcrystalline cellulose is used as an excipient and does not have a therapeutic dose.

Mechanism of action

Microcrystalline cellulose acts primarily as a diluent and binder in tablet formulations. It does not exert a pharmacological effect on its own but helps to enhance the physical properties of the drug formulation, improving the flowability, compressibility, and stability of tablets. Its porous structure allows it to absorb moisture, which can help maintain the stability of the active pharmaceutical ingredients.

Pharmacodynamics

As an inert substance, microcrystalline cellulose does not have pharmacodynamic effects. It does not interact with biological systems to produce therapeutic effects. Instead, its role is to improve the physical characteristics of drug formulations, ensuring that active ingredients are effectively delivered to patients.

Pharmacokinetics

Microcrystalline cellulose is not absorbed by the gastrointestinal tract and does not enter systemic circulation. It passes through the digestive system largely unchanged, contributing bulk to the stool. Its inert nature means that it does not undergo metabolism, and its elimination is through feces, contributing to dietary fiber intake.

Pregnancy

There is insufficient data on the use of microcrystalline cellulose during pregnancy. Consult healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is generally considered safe during breastfeeding. However, consult a healthcare provider for personalized advice.

Storage

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

Formulations

• Microcrystalline cellulose powder
• Tablets containing microcrystalline cellulose as an excipient

Dosage

Children: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Adults: Refer to specific drug formulations and product labels as purified substances can vary widely in their use and dosing.

Mechanism of action

The mechanism of action for purified compounds varies widely depending on the specific substance. Generally, purified drugs exert their effects by interacting with specific biological targets, such as receptors, enzymes, or ion channels, leading to a desired therapeutic effect. This interaction can involve binding to receptors to activate or inhibit signaling pathways, modulating enzymatic activity, or altering physiological processes.

Pharmacodynamics

Pharmacodynamics describes the effects of a drug on the body and the relationship between drug concentration and effect. For purified drugs, this can involve dose-response relationships and the time course of their action. The purified form often enhances potency and reduces variability in response among patients, which can lead to more predictable therapeutic outcomes. The overall effect is determined by the drug's affinity for its target, the efficacy of the drug-receptor interaction, and the downstream signaling pathways activated as a result of this interaction.

Pharmacokinetics

Pharmacokinetics involves the absorption, distribution, metabolism, and excretion (ADME) of a drug. For purified substances, absorption can be more efficient due to the absence of impurities that may affect solubility or stability. Distribution may also be enhanced, leading to higher bioavailability. Metabolism can be influenced by the structure of the purified compound, as it may be metabolized more readily by liver enzymes. Excretion typically occurs through the kidneys or liver, depending on the molecular characteristics of the purified drug.

Pregnancy

Consult with a healthcare professional, as the safety of purified forms of medications during pregnancy may vary depending on the specific substance.

Breast-feeding

Consult with a healthcare professional, as the safety of purified forms of medications during breastfeeding may vary depending on the specific substance.

Storage

Store in a cool, dry place, away from light and moisture, and keep out of reach of children.

Dosage

Children: Refer to the specific product information for dosing guidance based on the active ingredient within the supertab formulation.

Adults: Refer to the specific product information for dosing guidance based on the active ingredient within the supertab formulation.

Mechanism of action

The mechanism of action for supertab formulations depends on the active ingredient. Generally, sustained release formulations are designed to maintain therapeutic drug levels over an extended period, reducing the frequency of dosing. This is achieved by controlling the rate of drug release into the systemic circulation, which may involve polymer matrices or osmotic systems that modulate the dissolution and absorption of the drug.

Pharmacodynamics

Pharmacodynamics of supertab formulations will vary according to the specific active ingredient. However, sustained-release medications typically aim to provide a more stable plasma concentration, leading to prolonged therapeutic effects and reduced peak-trough fluctuations. This can enhance patient compliance and therapeutic outcomes, particularly in conditions requiring consistent medication levels.

Pharmacokinetics

The pharmacokinetics of supertab formulations also depends on the active ingredient. Generally, sustained-release formulations exhibit altered absorption profiles, with a gradual release of the drug into circulation. This may result in extended half-lives of the drug compared to immediate-release formulations. Factors such as gastrointestinal pH, motility, and the presence of food can influence the absorption rate.

Pregnancy

Consult healthcare provider before use, as safety during pregnancy has not been established.

Breast-feeding

Consult healthcare provider before use, as safety during breastfeeding has not been established.

Storage

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

Dosage

Children: Refer to specific product information for paediatric dosing, as it will depend on the formulation and indication.

Adults: Refer to specific product information for dosing guidance, as it will vary based on formulation and clinical use.

Mechanism of action

The mechanism of action for a universal drug would depend on its specific formulation and intended targets. Generally, such drugs might act on multiple receptors or pathways, potentially modulating immune responses, inflammatory processes, or neurotransmitter systems. The aim would be to exert a beneficial effect across different physiological systems.

Pharmacodynamics

Pharmacodynamics of a universal drug would involve its effects on the body, including the relationship between drug concentration and therapeutic effect. A universal drug may exhibit dose-dependent responses, with efficacy influenced by receptor affinity, intrinsic activity, and the presence of other competing endogenous substances. Side effects may also vary based on the specific biological pathways affected.

Pharmacokinetics

Pharmacokinetics refers to how a drug is absorbed, distributed, metabolized, and excreted in the body. For a universal drug, this could involve varied absorption rates depending on the route of administration, extensive distribution to various tissues, metabolism by liver enzymes, and renal or biliary excretion. Factors such as age, sex, genetic polymorphisms, and comorbid conditions could influence its pharmacokinetic profile.

Pregnancy

Consult with a healthcare provider to evaluate risks versus benefits.

Breast-feeding

Consult with a healthcare provider to evaluate risks versus benefits.

Storage

Store at room temperature, away from moisture and heat.

Dosage

Children: Refer to the specific drug monograph in the USP NF for paediatric dosing information.

Adults: Refer to the specific drug monograph in the USP NF for adult dosing information.

Mechanism of action

USP NF does not refer to a specific active ingredient or therapeutic agent. Rather, it encompasses a broad range of substances, each with its own unique mechanism of action depending on the specific drug referenced. Generally, drugs listed in the USP NF may act through various pathways, including receptor binding, enzyme inhibition, and modulation of ion channels, among others.

Pharmacodynamics

Pharmacodynamics will vary widely depending on the specific drug. Pharmacodynamics typically involves the study of drug effects and their mechanisms at the cellular level, including receptor interactions, signal transduction pathways, and the resultant physiological response. Each drug will have its own profile based on its chemical structure and target sites.

Pharmacokinetics

Pharmacokinetics also varies depending on the specific drug. It involves the study of the absorption, distribution, metabolism, and excretion (ADME) of drugs. Factors such as the route of administration, solubility, protein binding, and half-life will influence how a drug behaves in the body. For precise pharmacokinetic data, reference should be made to the specific monograph for the drug in question within the USP NF.

Pregnancy

Safety in pregnancy has not been established. Use only if potential benefit justifies the potential risk to the fetus.

Breast-feeding

Caution is advised; it is not known whether this drug is excreted in human milk.

Storage

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

Dosage

Children: Refer to the BNF for Children for appropriate paediatric dosing information.

Adults: Refer to the specific BNF guidelines for dosing information as it may vary based on the condition being treated.

Mechanism of action

The mechanism of action for White involves its interaction with specific biological pathways, leading to the desired pharmacological effects. The precise pathways may include modulation of receptor activity or alteration of enzyme function, although specific details are not provided.

Pharmacodynamics

Pharmacodynamics of White includes its effects on the body, including therapeutic effects and potential side effects. As a compound, it may exert its influence on multiple physiological systems, which can lead to changes in symptoms or disease progression.

Pharmacokinetics

Pharmacokinetics of White involves its absorption, distribution, metabolism, and excretion. Understanding these parameters can help predict how the drug behaves in the body, including onset of action and duration of effect. Detailed pharmacokinetic data is not specified.

Mechanism of action

The exact mechanism of action of colchicine has not been fully established; however, colchicine likely interferes with the intracellular assembly of the inflammasome complex present in neutrophils and monocytes that mediates activation of interleukin-1β, an inflammatory mediator. Colchicine also attenuates neutrophil adhesion and recruitment, as well as superoxide production. Clinical data demonstrate that colchicine reduces high-sensitivity C- reactive protein (hs-CRP). Colchicine is an anti-mitotic drug that disrupts cytoskeletal functions by inhibiting β-tubulin polymerization into microtubules. Consequently, it prevents the activation, degranulation, and migration of neutrophils. This pharmacological action is thought to be related to colchicine ameliorating gout symptoms and preventing major cardiovascular events. Colchicine blocks microtubule growth at low concentrations and causes the depolymerization of microtubules at high concentrations. ... HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 hr. The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. Colchicine, long used to treat gout, arrests microtubule assembly and inhibits many cellular functions. At micromolar concentrations, it suppresses monosodium urate crystal-induced NACHT-LRR-PYD-containing protein-3 (NALP3) inflammasome-driven caspase-1 activation, IL-1beta processing and release, and L-selectin expression on neutrophils. At nanomolar concentrations, colchicine blocks the release of a crystal-derived chemotactic factor from neutrophil lysosomes, blocks neutrophil adhesion to endothelium by modulating the distribution of adhesion molecules on the endothelial cells, and inhibits monosodium urate crystal-induced production of superoxide anions from neutrophils. Cyto-chrome P450 3A4, the multidrug transporter P-glycoprotein, and the drugs that bind these proteins influence its pharmacokinetics and pharmacodynamics. Trial evidence supports its efficacy in acute gout and in preventing gout flares, but it has narrow therapeutic index, and overdosage is associated with gastrointestinal, hepatic, renal, neuromuscular, and cerebral toxicity; bone marrow damage; and high mortality. The actions of colchicine were examined with the two-electrode voltage-clamp technique and radioligand binding assays in mouse and human 5-hydroxytryptamine(3A) receptors (5-HT(3A)Rs) expressed in Xenopus laevis oocytes. Colchicine inhibited 5-hydroxytryptamine (5-HT)-evoked currents in oocytes expressing mouse 5-HT(3A)Rs, with an IC(50) of 59.5 +/- 3 uM. In contrast to the mouse receptor, coapplication of colchicine with 5-HT (<1 uM) strongly enhanced 5-HT-evoked currents in oocytes expressing human 5-HT(3A)Rs. Colchicine applied alone did not induce a detectable current. In the presence of 0.5 microM 5-HT, the potentiation was concentration-dependent and reached the maximum (approximately 100%) when 750 microM colchicine was applied. However, colchicine-dependent inhibition can be observed at 5-HT concentrations > 1 uM. In oocyte membranes

Pharmacodynamics

Colchicine ameliorates the symptoms of gout and Familial Mediterranean fever. It possesses anti-inflammatory, anti-fibrotic, and cardiovascular protective effects. Colchicine was shown to exhibit anticancer properties, such as the inhibition of cancer cell migration and angiogenesis. Colchicine has a narrow therapeutic window.