DABIFIB 150

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 a disintegrant in tablet formulations
• Improves dissolution of active pharmaceutical ingredients
• Facilitates the breakdown of solid dosage forms

Dosage

Children: Refer to specific product information for dosing guidelines, as croscarmelose is used as an excipient and not dosed independently.

Adults: Refer to specific product information for dosing guidelines, as croscarmelose is used as an excipient and not dosed independently.

Mechanism of action

Croscarmelose functions by rapidly absorbing water and swelling upon hydration. This swelling action creates pressure within the tablet, leading to disintegration into smaller particles. The increased surface area of the drug particles enhances dissolution and absorption in the gastrointestinal tract, ultimately improving the pharmacokinetic profile of the active ingredients.

Pharmacodynamics

As a disintegrant, croscarmelose does not exert a pharmacological effect on its own but plays a critical role in the formulation of oral solid dosage forms. Its pharmacodynamic properties are primarily related to its ability to facilitate the release of active ingredients from their dosage forms, thereby influencing the onset and duration of action of the administered medication.

Pharmacokinetics

Croscarmelose is not absorbed systemically when ingested, as it functions primarily within the gastrointestinal tract. It is excreted unchanged in the feces following its role in aiding the dissolution and disintegration of solid dosage forms. Its safety profile is well-established, and it is considered non-toxic, with minimal adverse effects when used in recommended amounts.

Pregnancy

Croscarmelose is generally considered safe for use during pregnancy as it is an inert substance and does not have systemic effects.

Breast-feeding

Croscarmelose is not absorbed systemically and is considered safe for use during breastfeeding.

Storage

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

Formulations

• Tablet
• Capsule
• Powder

Indications

• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
• Treatment of deep vein thrombosis (DVT)
• Treatment of pulmonary embolism (PE)
• Prevention of recurrent DVT and PE

Dosage

Adults: Refer

Mechanism of action

Dabigatran and its acyl glucuronides act as competitive, direct inhibitors of thrombin, a serine protease crucial in the coagulation cascade. By inhibiting thrombin, dabigatran prevents the conversion of fibrinogen into fibrin, which is essential for clot formation. This action not only inhibits thrombin-induced platelet aggregation but also enhances fibrinolysis by affecting the viscoelastic properties of clots, leading to more permeable and less rigid fibrin structures, thereby promoting clot lysis.

Pharmacodynamics

Dabigatran's pharmacodynamic profile is characterized by its ability to provide rapid and predictable anticoagulation without the need for routine monitoring. The drug exhibits a dose-dependent effect on thrombin inhibition, leading to an anti-coagulant effect that is evident shortly after administration. Its effects are influenced by renal function, as dabigatran is primarily eliminated through the kidneys, and dosage adjustments may be necessary in patients with renal impairment.

Pharmacokinetics

Dabigatran has a bioavailability of approximately 3-7% when taken orally due to extensive first-pass metabolism. Peak plasma concentrations are achieved within 1-2 hours after administration. The drug is primarily excreted unchanged via the kidneys, with renal clearance being a significant pathway for its elimination. The half-life of dabigatran ranges from 12 to 17 hours in healthy individuals but can be prolonged in patients with renal impairment.

Contra-indications

• Active bleeding
• Severe renal impairment (creatinine clearance < 30 mL/min)
• Hypersensitivity to dabigatran or any of its excipients
• Mechanical prosthetic heart valves

Adverse effects

• Bleeding complications
• Gastrointestinal disturbances (e.g., dyspepsia, nausea)
• Increased liver enzymes
• Skin reactions (e.g., rash, pruritus)
• Anemia

Interactions

• Dronedarone - severe (increases exposure)
• Carbamazepine - severe (decreases exposure)
• Phenytoin - severe (decreases exposure)
• Ciclosporin - severe (increases exposure)
• Cobicistat - severe (increases exposure)
• Glecaprevir with pibrentasvir - severe (increases exposure)
• Ritonavir - severe (increases exposure)
• HIV-protease inhibitors boosted with ritonavir - severe (increases exposure)
• Letermovir - severe (decreases concentration)

Precautions

• Monitor renal function regularly
• Use with caution in patients with a history of gastrointestinal bleeding
• Discontinue prior to surgical procedures based on bleeding risk
• Consider the risk of bleeding in elderly patients

Pregnancy

Not recommended during pregnancy due to potential risks to the fetus.

Breast-feeding

Not recommended as dabigatran may be excreted in breast milk.

Storage

Store in the original package to protect from moisture. Keep out of reach of children.

Formulations

• Capsules: 75 mg, 110 mg, 150 mg

Indications

• Prevention of venous thromboembolism in patients undergoing elective orthopedic surgery
• Treatment of venous thromboembolism
• Prevention of recurrent venous thromboembolism

Dosage

Children: Refer to the BNF for Children for appropriate dosages as paediatric dosing information is not provided here.

Adults: Refer to the relevant dosage guidelines in clinical practice or the BNF as dosing may vary based on indication and patient-specific factors.

Mechanism of action

Etexilate exerts its anticoagulant effect by selectively inhibiting Factor Xa, a key enzyme in the coagulation cascade that converts prothrombin to thrombin. By inhibiting Factor Xa, etexilate effectively prevents the conversion of fibrinogen to fibrin, thereby inhibiting clot formation and promoting anticoagulation.

Pharmacodynamics

The pharmacodynamic effects of etexilate include dose-dependent anticoagulation, measured by assays such as anti-factor Xa activity. The onset of action is typically rapid, with peak effects occurring within a few hours of administration. The anticoagulant response is maintained as long as the drug is present in the system, allowing for predictable dosing regimens without the need for routine monitoring of coagulation parameters in most patients.

Pharmacokinetics

Etexilate is well absorbed following oral administration, with bioavailability being influenced by food intake. It undergoes extensive first-pass metabolism to its active form. The elimination half-life is approximately 9-13 hours, allowing for once-daily dosing in most clinical scenarios. The drug is primarily excreted via the kidneys, necessitating dose adjustments in patients with renal impairment. Additionally, etexilate is metabolized by cytochrome P450 enzymes, which may lead to potential drug interactions.

Contra-indications

• Severe hypersensitivity to etexilate or any of its components
• Active bleeding disorders
• Severe hepatic impairment

Adverse effects

• Bleeding complications
• Thrombocytopenia
• Gastrointestinal disturbances such as nausea and diarrhea
• Headache
• Elevated liver enzymes

Interactions

• Anticoagulants may have additive effects leading to increased bleeding risk
• Strong CYP3A4 inducers may decrease the efficacy of etexilate
• Strong CYP3A4 inhibitors may increase the concentration and effects of etexilate

Precautions

• Use with caution in patients with a history of bleeding disorders
• Monitor liver function regularly in patients with pre-existing liver conditions
• Consider renal function when prescribing, as adjustments may be necessary

Pregnancy

Etexilate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines and clinical judgment.

Breast-feeding

Etexilate is excreted in breast milk. Caution should be exercised when administered to nursing mothers.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Tablets
• Oral suspension

Mechanism of action

The hydroxyl group acts as a nucleophile, participating in various biochemical reactions, including the degradation of reactive oxygen species. It helps in the detoxification of oxidized guanosine triphosphate (GTP) and deoxyguanosine triphosphate (dGTP), which is critical for maintaining cellular integrity and function.

Pharmacodynamics

The presence of hydroxyl groups in compounds can significantly alter their pharmacological effects, enhancing solubility and reactivity. Hydroxyl groups can stabilize reactive intermediates, leading to increased efficacy in biochemical pathways, particularly in processes involving oxidative stress and cellular detoxification.

Pharmacokinetics

Hydroxyl-containing compounds typically exhibit variable absorption, distribution, metabolism, and excretion profiles depending on their specific structure. The pharmacokinetics of hydroxyl as a standalone entity is not well-defined, but its presence in larger molecules often influences their bioavailability and elimination.

Pregnancy

There is insufficient data to determine the safety of hydroxyl in pregnancy. Caution is advised.

Breast-feeding

There is no specific information available regarding the excretion of hydroxyl in human milk. Caution is advised.

Storage

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

Indications

• Allergic conditions
• Autoimmune diseases
• Asthma and chronic obstructive pulmonary disease (COPD)
• Certain cancers (e.g., leukemia, lymphoma)
• Skin conditions (e.g., dermatitis)
• Inflammatory bowel disease
• Multiple sclerosis exacerbations
• Severe infections requiring immunosuppression

Dosage

Children: Refer to BNF for Children for specific dosing; doses vary significantly based on the child's age, weight, and condition being treated.

Adults: Refer to BNF for specific dosing; typically, initial doses range from 4 to 48 mg depending on the severity of the condition.

Mechanism of action

Methylprednisolone exerts its effects by binding to glucocorticoid receptors, leading to the modulation of gene expression. This interaction influences the transcription of anti-inflammatory proteins while suppressing the expression of pro-inflammatory genes, ultimately resulting in reduced inflammation and immune response.

Pharmacodynamics

The pharmacodynamic effects of methylprednisolone are characterized by its ability to decrease inflammation, suppress the immune response, and affect carbohydrate metabolism. Therapeutic doses lead to various systemic effects, including modification of leukocyte distribution and inhibition of cytokine production.

Pharmacokinetics

Methylprednisolone is well absorbed after oral administration, with a bioavailability of approximately 50%. It has a volume of distribution that reflects extensive tissue binding. The drug is metabolized primarily in the liver through conjugation and reduction, and its metabolites are excreted in urine. The half-life varies based on the route of administration but is generally around 18 to 36 hours.

Adverse effects

• Increased blood pressure
• Hyperglycemia
• Weight gain
• Mood changes
• Insomnia
• Gastrointestinal disturbances
• Increased susceptibility to infections

Interactions

• methylphenidate+apraclonidine: Severe (decreases effects)
• methylthioninium chloride+bupropion: Severe (increases risk of severe hypertension)
• methylphenidate+linezolid: Severe (increases risk of elevated blood pressure)
• rasagiline+methylphenidate: Severe (increases risk of a hypertensive crisis)
• mao-inhibitors+methylphenidate: Severe (increases risk of a hypertensive crisis)
• dronedarone+methylprednisolone: Moderate (increases exposure)
• miconazole+methylprednisolone: Moderate (increases concentration)
• antifungals, azoles+methylprednisolone: Moderate (increases exposure)
• crizotinib+methylprednisolone: Moderate (increases exposure)

Precautions

• Use with caution in patients with hypertension
• Monitor blood glucose levels in diabetic patients
• Consider potential for infection risk due to immunosuppression
• Evaluate for psychiatric effects in susceptible individuals

Pregnancy

Corticosteroids may be used during pregnancy if the potential benefit justifies the risk to the fetus. Careful monitoring is advised.

Breast-feeding

Corticosteroids are excreted in breast milk; caution is advised. Monitor the infant for potential effects.

Storage

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

Formulations

• Tablets
• Injectable solutions
• Topical preparations

Mechanism of action

Methylsulphate functions as a methylating agent, transferring a methyl group to nucleophiles. This process involves the formation of a sulfonium ion, which is highly reactive and can readily react with nucleophilic sites on various substrates, leading to methylation reactions.

Pharmacodynamics

The pharmacodynamics of methylsulphate is primarily related to its role as a methylating agent in biochemical reactions. It can alter the structure and function of biological molecules, potentially affecting cellular processes and signaling pathways. However, detailed pharmacodynamic studies specific to therapeutic use are limited.

Pharmacokinetics

There is limited information on the pharmacokinetics of methylsulphate, given its typical use as a reagent in laboratory settings rather than a clinical drug. When used in chemical reactions, its reactivity and transformation into other compounds would dictate its pharmacokinetic profile, which could vary significantly based on the specific context of use.

Pregnancy

There is limited data on the use of methylsulphate in pregnancy. Consult relevant guidelines.

Breast-feeding

Data on the excretion of methylsulphate in human milk is not available. Caution is advised.

Storage

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

Indications

• Hyperthyroidism
• Graves' disease
• Thyroid storm

Dosage

Children: Refer to the BNF

Adults: The usual initial dose of propylthiouracil in adults is 300 mg per day, divided into 3 doses. The maintenance dose is typically 100-150 mg per day, adjusted based on thyroid function tests.

Mechanism of action

Propylthiouracil acts by inhibiting the enzyme thyroid peroxidase, which is involved in the iodination of tyrosine residues in thyroglobulin, a precursor of thyroid hormones. By blocking this enzyme, PTU reduces the production of thyroxine (T4) and triiodothyronine (T3), leading to decreased thyroid hormone levels in circulation. Additionally, PTU inhibits the conversion of T4 to T3 in peripheral tissues, further contributing to its antithyroid effects.

Pharmacodynamics

The pharmacodynamic effects of propylthiouracil are primarily centered around its ability to lower thyroid hormone levels, which helps alleviate symptoms of hyperthyroidism such as increased heart rate, weight loss, and anxiety. The onset of action can vary, but therapeutic effects may be observed within several weeks of initiation. Monitoring thyroid function tests is essential to assess the efficacy and adjust dosing as needed.

Pharmacokinetics

Propylthiouracil is well absorbed from the gastrointestinal tract, though its bioavailability can be affected by factors such as food intake. The drug is extensively metabolized in the liver, and its elimination half-life averages around 1-2 hours. Most of the drug is excreted in urine as metabolites. It is important to note that due to its rapid metabolism, multiple daily doses may be required to maintain therapeutic levels.

Interactions

• propylthiouracil+metyrapone: Severe (decreases effects)

Indications

• Used as an excipient in drug formulations
• Pleurodesis for the management of recurrent pleural effusions

Dosage

Children: Refer to specific guidelines for paediatric use, as dosing may differ based on age and clinical condition.

Adults: Refer to specific guidelines for the appropriate dosage in pleurodesis and other applications, as it may vary based on clinical context.

Mechanism of action

Talc exhibits very good absorptive properties, allowing it to absorb moisture and other substances effectively. This characteristic is particularly useful in pharmaceutical formulations, where it may enhance the stability and texture of the drug product.

Pharmacodynamics

Talc's primary pharmacodynamic effect is its ability to act as an inert filler and bulking agent in pharmaceutical preparations. It does not have any intrinsic pharmacological activity but serves to improve the physical properties of formulations, such as flowability and compressibility.

Pharmacokinetics

Talc is not absorbed systemically when used as an excipient or in medical procedures. Its effects are local, and it remains in the site of application, where it functions primarily as a mechanical agent. The pharmacokinetics of talc in the context of its use in pleurodesis involves its ability to promote adhesion of the pleural surfaces, thereby preventing fluid accumulation.

Pregnancy

Talc is classified as a substance with minimal systemic absorption, but safety during pregnancy has not been well established. Consult relevant guidelines.

Breast-feeding

Talc is not expected to be absorbed in significant amounts; however, caution is advised and consult guidelines.

Storage

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

Indications

• Used as an acidulant in food and beverages
• Utilized in pharmaceutical formulations to enhance stability
• Serves as a buffering agent in various preparations

Dosage

Children: Refer to specific formulation guidelines for dosage; no standard dose established.

Adults: Refer to specific formulation guidelines for dosage; no standard dose established.

Mechanism of action

Tartaric acid acts primarily as a mild acid, contributing to the acidity of solutions and influencing the solubility and stability of compounds. It can also play a role in stabilizing the pH of formulations, which can enhance the bioavailability of specific drugs. The precise molecular interactions of tartaric acid in biological systems are not fully elucidated but involve the modulation of pH and ionic strength.

Pharmacodynamics

Tartaric acid does not exhibit significant pharmacological activity on its own but influences the properties of other compounds when used in pharmaceutical preparations. Its role as an acidulant can enhance the solubility of certain drugs, thereby improving their absorption and therapeutic efficacy. The acid's buffering capacity can also help maintain a stable environment for drug stability.

Pharmacokinetics

Tartaric acid is absorbed in the gastrointestinal tract, although specific pharmacokinetic parameters such as half-life, peak plasma concentration, and elimination pathways are not well-defined in the literature. It is generally metabolized in the body to various metabolites, primarily through normal metabolic pathways, with renal excretion of its conjugates. Its effects are more related to its role in formulations rather than systemic pharmacodynamics.

Pregnancy

Tartaric acid is generally recognized as safe when used in food and beverages. However, specific safety during pregnancy has not been extensively studied, thus caution is advised.

Breast-feeding

There is limited information on the safety of tartaric acid during breastfeeding, but it is considered to be safe in normal dietary amounts.

Storage

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

Formulations

• Tartaric acid powder
• Tartaric acid solution

Mechanism of action

Dabigatran and its acyl glucuronides are competitive, direct thrombin inhibitors. Because thrombin (serine protease) enables the conversion of fibrinogen into fibrin during the coagulation cascade, its inhibition prevents the development of a thrombus. Both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited by the active moieties. ... To evaluate the profibrinolytic effect of dabigatran, a new, direct thrombin inhibitor, using different in vitro models. The resistance of tissue factor-induced plasma clots to fibrinolysis by exogenous tissue-type plasminogen activator (t-PA) (turbidimetric method) was reduced by dabigatran in a concentration-dependent manner, with > or = 50% shortening of lysis time at clinically relevant concentrations (1-2 um). A similar effect was observed in the presence of low (0.1 and 1 nm) but not high (10 nm) concentrations of thrombomodulin. Acceleration of clot lysis by dabigatran was associated with a reduction in TAFI activation and thrombin generation, and was largely, although not completely, negated by an inhibitor of activated TAFI, potato tuber carboxypeptidase inhibitor. The assessment of the viscoelastic properties of clots showed that those generated in the presence of dabigatran were more permeable, were less rigid, and consisted of thicker fibers. The impact of these physical changes on fibrinolysis was investigated using a model under flow conditions, which demonstrated that dabigatran made the clots markedly more susceptible to flowing t-PA, by a mechanism that was largely TAFI-independent. Dabigatran, at clinically relevant concentrations, enhances the susceptibility of plasma clots to t-PA-induced lysis by reducing TAFI activation and by altering the clot structure. These mechanisms might contribute to the antithrombotic activity of the drug.

Mechanism of action

It has very good absorptive properties.