Apigy 2.5

Indications

• Prophylaxis of venous thromboembolism following knee replacement surgery
• Prophylaxis of venous thromboembolism following hip replacement surgery
• Treatment of deep vein thrombosis
• Treatment of pulmonary embolism
• Prophylaxis of recurrent deep vein thrombosis
• Prophylaxis of recurrent pulmonary embolism
• Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation

Dosage

Adults: Initially 10 mg twice daily for 7 days, then maintenance 5 mg twice daily. For the prophylaxis of venous thromboembolism following hip or knee replacement surgery, the recommended dose is 2.5 mg twice daily, to be started 12-24 hours after surgery.

Mechanism of action

Apixaban selectively inhibits factor Xa in both its free and bound forms, independently of antithrombin III. This inhibition prevents the conversion of prothrombin to thrombin, thereby inhibiting thrombus formation.

Pharmacodynamics

The pharmacodynamic effects of apixaban are characterized by its ability to inhibit factor Xa, which plays a crucial role in the coagulation cascade. This leads to decreased thrombin generation, resulting in reduced clot formation. Its anticoagulant effect can be monitored by measuring anti-factor Xa activity.

Pharmacokinetics

Apixaban is rapidly absorbed after oral administration, with peak plasma concentrations reached within 3 to 4 hours. It has a bioavailability of approximately 50% and is primarily metabolized in the liver via cytochrome P450 enzymes, particularly CYP3A4. The elimination half-life ranges from 8 to 15 hours, and the drug is eliminated through both renal and fecal pathways, with about 25% excreted unchanged in urine.

Contra-indications

• Active bleeding
• Severe uncontrolled hypertension
• History of bleeding diathesis
• Significant risk of major bleeding

Adverse effects

• Bleeding complications
• Nausea
• Headache
• Dizziness
• Diarrhea
• Myalgia
• Skin reactions

Interactions

• St. John's Wort (moderate decrease in exposure)
• Antifungals (azoles - potential increased risk of bleeding)
• Calcium channel blockers (unknown effect on exposure)
• Ciclosporin (unknown effect on exposure)
• HIV protease inhibitors boosted with ritonavir or cobicistat (unknown effect on exposure)
• Idelalisib (unknown effect on exposure)
• Lapatinib (unknown effect on exposure)
• Mitotane (unknown decrease in exposure)
• Neratinib (unknown effect on exposure)

Precautions

• Use with caution in the elderly
• Monitor renal function
• Assess risk factors for bleeding before initiation

Pregnancy

Not known to be harmful, but caution is advised.

Breast-feeding

Use only if essential, as small amounts are present in milk.

Storage

Store in the original container with desiccant, discard any remaining capsules 6 weeks after opening.

Formulations

• Tablets: 2.5 mg, 5 mg, and 10 mg
• Modified-release capsules

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 oral solid dosage forms
• Improves the bioavailability of poorly soluble drugs

Dosage

Children: Refer to specific formulation guidelines for dosage instructions, as croscarmellose sodium is used as an excipient.

Adults: Refer to specific formulation guidelines for dosage instructions, as croscarmellose sodium is used as an excipient.

Mechanism of action

Croscarmellose sodium acts by swelling and forming a gel-like consistency upon contact with moisture. This swelling property helps the disintegration of solid dosage forms, enhancing the release of the active pharmaceutical ingredient from the formulation, thereby promoting its absorption in the gastrointestinal tract.

Pharmacodynamics

Croscarmellose sodium enhances the rate of disintegration of solid dosage forms, which is crucial for the effective release of the active drug. The mechanism involves the rapid absorption of water, which leads to an increase in volume and pressure within the tablet matrix, ultimately causing it to break apart. This property improves the dissolution rate and bioavailability of the drug contained within the formulation.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract; therefore, it does not have systemic pharmacokinetics. It functions locally within the gastrointestinal lumen, facilitating the disintegration and dissolution of drugs. Its efficacy is dependent on the formulation composition, including the presence of other excipients and the physical characteristics of the dosage form.

Adverse effects

• Gastrointestinal disturbances
• Allergic reactions
• Bloating
• Abdominal pain

Precautions

• Use with caution in patients with known allergies to cellulose derivatives
• Monitor for gastrointestinal symptoms in predisposed individuals

Pregnancy

Croscarmellose is generally considered safe for use during pregnancy, but should be used under medical supervision.

Breast-feeding

Croscarmellose is not known to be excreted in breast milk and is considered safe during breastfeeding.

Storage

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

Formulations

• Tablets
• Capsules
• Powders

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

• Cleansing agent in topical formulations
• Emulsifying agent in cosmetic products
• Foaming agent in shampoos and body washes

Dosage

Children: Refer to specific product formulations for appropriate concentrations and application methods.

Adults: Refer to specific product formulations for appropriate concentrations and application methods.

Mechanism of action

Lauryl sulfate functions as an anionic surfactant. It reduces the surface tension between different substances, allowing for better spreading and wetting. In the context of cleansing, it facilitates the removal of dirt and oils from the skin and hair by emulsifying these substances, thus making them easier to rinse away with water.

Pharmacodynamics

As a surfactant, lauryl sulfate displays properties that can disrupt cellular membranes and alter permeability. This mechanism is beneficial in enhancing the penetration of other therapeutic agents in topical formulations. However, its irritant potential on skin and mucous membranes should be noted, as it can lead to dryness and irritation with prolonged exposure.

Pharmacokinetics

Lauryl sulfate is primarily applied topically and is not intended for systemic absorption. When used in formulations, it acts locally at the site of application. Its absorption through the skin is minimal, and any systemic exposure is limited. Metabolism and excretion pathways are not well-defined for topical applications, as it is largely washed away after use.

Pregnancy

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

Breast-feeding

Unknown whether lauryl 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

• Used as an excipient in tablet formulations
• Used as a bulking agent in capsule formulations
• Used in food products as a thickener or stabilizer

Dosage

Children: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Adults: Refer to specific product guidelines as dosage will depend on the formulation and the active ingredients.

Mechanism of action

Microcrystalline cellulose acts as a non-digestible filler that enhances the flow properties of powders during the manufacturing of tablets and capsules. It does not have a direct pharmacological action on the body but ensures that the active ingredients are effectively delivered to the patient.

Pharmacodynamics

As a non-active ingredient, microcrystalline cellulose does not exert pharmacodynamic effects typical of active pharmaceutical ingredients. Its primary role is to provide a stable and consistent matrix for the drug, facilitating the release of the active compound once ingested.

Pharmacokinetics

Microcrystalline cellulose is not absorbed in the gastrointestinal tract; it passes through the digestive system largely unchanged. It adds bulk to the stool, which may aid in promoting regular bowel movements. The substance is excreted in feces, where it contributes to dietary fiber intake.

Pregnancy

Data regarding the use of microcrystalline cellulose during pregnancy is limited. It is advisable to consult with healthcare professionals before use.

Breast-feeding

Microcrystalline cellulose is considered safe during breastfeeding, as it is not absorbed systemically.

Storage

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

Mechanism of action

Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin III. Apixaban also inhibits prothrominase. These effects prevent the formation of a thrombus.

Pharmacodynamics

Apixaban selectively inhibits factor Xa in its free and bound forms, independant of antithrombin III. Apixaban also inhibits prothrominase. These effects prevent the formation of a thrombus.