ARTEFAN 80/480

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Malaria treatment in combination with lumefantrine

Dosage

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

Adults: Refer to specific guidelines; typically, artemether is administered in a combination therapy regimen with lumefantrine.

Mechanism of action

Artemether interacts with ferriprotoporphyrin IX (heme) in the acidic vacuole of malaria parasites, leading to the generation of cytotoxic radical species. This interaction involves the activation of the drug by reduced heme or ferrous iron, resulting in the formation of oxygen-centered radicals that subsequently convert into carbon-centered radicals. These radicals are toxic to the parasites, thereby inhibiting their growth and reproduction.

Pharmacodynamics

Artemether is rapidly metabolized to its active metabolite, dihydroartemisinin. It primarily targets the erythrocytic stages of Plasmodium falciparum by inhibiting nucleic acid and protein synthesis. The drug has a rapid onset of action, providing quick symptomatic relief by significantly reducing the number of circulating malarial parasites. In combination therapy with lumefantrine, artemether enhances overall treatment effectiveness and contributes to a higher clinical cure rate.

Pharmacokinetics

Artemether is absorbed quickly, with a rapid onset of action. It is metabolized in the liver to dihydroartemisinin, which is the active form responsible for its antimalarial effects. The drug is eliminated from the body relatively quickly, while lumefantrine, which has a longer half-life, aids in clearing any residual parasites. This pharmacokinetic profile supports the use of artemether in combination therapies for malaria.

Adverse effects

• nausea
• vomiting
• dizziness
• headache
• fatigue
• abdominal pain
• anemia
• QT prolongation

Interactions

• mitotane+artemether with lumefantrine: Severe (decreases exposure)
• mitotane+artemether: Severe (decreases exposure)
• rifampicin+artemether: Severe (decreases exposure)
• grapefruit juice+artemether: Unknown (increases exposure)
• efavirenz+artemether: Unknown (decreases concentration)
• etravirine+artemether: Unknown (decreases exposure)

Precautions

• Monitor for signs of hypersensitivity reactions
• Use with caution in patients with pre-existing QT prolongation
• Assess liver function before use, as hepatic impairment may alter drug metabolism

Pregnancy

Artemether is categorized as pregnancy category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Artemether is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• artemether/lumefantrine combination tablets
• artemether oral solution

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

• Hypovolemic shock
• Severe burns
• Postoperative fluid replacement
• Sepsis
• Trauma management

Dosage

Children: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Adults: Refer to established guidelines for specific dosing, as it varies based on the type of colloidal solution used and the clinical condition being treated.

Mechanism of action

Colloidal solutions work by maintaining oncotic pressure in the blood, thus helping to retain fluid within the vascular system. This is primarily due to the large molecular weight of the colloidal particles, which cannot easily pass through capillary walls. The presence of colloids in the blood helps to draw water into the circulation, increasing blood volume and improving tissue perfusion.

Pharmacodynamics

The pharmacodynamics of colloidal solutions are centered on their ability to exert osmotic pressure, which helps maintain blood volume and pressure. This effect is particularly important in conditions such as hypovolemia and shock, where fluid replacement is necessary to restore hemodynamic stability. The efficacy of colloidal solutions can vary depending on the type of colloid used, as well as the underlying clinical condition being treated.

Pharmacokinetics

Colloidal solutions are typically administered intravenously and their pharmacokinetics can vary based on the specific formulation. Generally, colloids are distributed throughout the vascular compartment and have a longer duration of action compared to crystalloids, as they remain in circulation longer. The elimination of colloids is primarily through the reticuloendothelial system, where they are metabolized or eliminated by the liver and spleen. Factors such as particle size and composition can influence their distribution and clearance.

Adverse effects

• Allergic reactions
• Injection site reactions
• Nausea
• Vomiting
• Headache
• Fever

Precautions

• Use with caution in patients with known allergies to any component of the formulation
• Monitor for signs of hypersensitivity during administration
• Consider volume overload in patients with cardiac or renal impairment

Pregnancy

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

Breast-feeding

It is not known whether colloidal solutions are excreted in human milk. Caution should be exercised when administering to breastfeeding mothers.

Storage

Store at room temperature, protect from light, and do not freeze. Keep out of reach of children.

Formulations

• Colloidal silver
• Colloidal gold
• Colloidal iron
• Other metal colloids

Indications

• Used as a disintegrant in tablet formulations
• Facilitates the release of active pharmaceutical ingredients in oral dosage forms

Dosage

Children: Refer to specific formulation guidelines as dosing is based on the formulation and not typically provided for excipients like crosspovidone.

Adults: Refer to specific formulation guidelines as dosing is based on the formulation and not typically provided for excipients like crosspovidone.

Mechanism of action

Crosspovidone functions as a disintegrant by absorbing water and swelling upon contact with moisture, which disrupts the tablet structure and leads to rapid disintegration. This mechanism increases the surface area of the active ingredient, allowing for faster dissolution and absorption in the gastrointestinal tract.

Pharmacodynamics

The pharmacodynamics of crosspovidone are primarily related to its physical properties rather than specific biochemical interactions. It aids in the disintegration and dissolution processes of tablets, enhancing the bioavailability of the active pharmaceutical ingredients. The effectiveness of crosspovidone as a disintegrant can depend on factors such as the formulation, the presence of other excipients, and the manufacturing process.

Pharmacokinetics

Crosspovidone is not absorbed systemically as it is used in formulations as an excipient. It remains in the gastrointestinal tract where it performs its function as a disintegrant. Its elimination is not applicable as it does not enter the systemic circulation. The biocompatibility of crosspovidone is well established, and it is generally recognized as safe for use in pharmaceuticals.

Pregnancy

Crosspovidone is generally considered safe for use in pregnancy as it is not systemically absorbed, but clinical judgement should be applied.

Breast-feeding

Crosspovidone is not systemically absorbed and is unlikely to pose a risk to a breastfeeding infant.

Storage

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

Indications

• Monitoring respiratory function
• Assessment of metabolic status
• Management of respiratory acidosis
• Management of respiratory alkalosis

Dosage

Children: Dosing for interventions related to carbon dioxide levels in pediatric patients should be guided by clinical protocols and the BNF for Children.

Adults: Dosing for interventions related to carbon dioxide levels is typically based on clinical assessment and individual patient needs. Refer to clinical guidelines for specific scenarios.

Mechanism of action

Carbon dioxide acts primarily as a signaling molecule in the body, influencing respiratory drive and blood pH. It is produced during cellular respiration and is a critical component of the bicarbonate buffering system, which helps maintain acid-base homeostasis. Elevated levels of CO2 in the blood stimulate ventilation in the lungs, increasing the rate of gas exchange and facilitating the removal of excess CO2.

Pharmacodynamics

The pharmacodynamic effects of dioxides, particularly carbon dioxide, are closely related to its concentration in the blood. As CO2 levels increase, it leads to respiratory acidosis, which can stimulate the respiratory centers in the brain to increase ventilation. Conversely, low levels of CO2 can cause respiratory alkalosis, potentially leading to decreased respiratory drive. CO2 also plays a role in vasodilation and can affect blood flow and pressure through its influence on smooth muscle tone.

Pharmacokinetics

Carbon dioxide is produced endogenously during metabolic processes and is transported in the bloodstream primarily in three forms: dissolved in plasma, as bicarbonate ions (HCO3-), and bound to hemoglobin. The half-life of CO2 in the bloodstream is very short due to its rapid exchange with alveolar gas in the lungs. The elimination of CO2 occurs through exhalation, making it a dynamic component of respiratory physiology.

Pregnancy

Data on the effects of dioxide during pregnancy are limited. Caution is advised due to potential risks associated with exposure.

Breast-feeding

Limited data are available regarding the excretion of dioxide in human milk. Caution is recommended.

Storage

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

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

• Uncomplicated malaria due to Plasmodium falciparum
• Coartem (lumefantrine and artemether) for rapid malaria treatment

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, it is suggested that lumefantrine inhibits the formation of beta-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamics

Lumefantrine is active against the erythrocytic stages of Plasmodium falciparum. When administered with artemether, it is believed to have cooperative antimalarial effects, with artemether providing rapid symptom relief and lumefantrine clearing residual parasites due to its longer half-life.

Pharmacokinetics

Lumefantrine has a long half-life, allowing for sustained effects after administration. It is absorbed from the gastrointestinal tract and is extensively metabolized in the liver. Its pharmacokinetic profile supports its use in combination therapy with rapidly acting agents like artemether.

Adverse effects

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Headache
• Fatigue
• Dizziness
• Palpitations

Interactions

• Drug interactions with artemether; co-administration may enhance antimalarial effects
• Potential interactions with drugs that affect liver enzymes, which may alter lumefantrine metabolism

Precautions

• Use with caution in patients with a history of cardiac arrhythmias
• Monitor for signs of hepatotoxicity in patients with pre-existing liver disease
• Consider potential for drug interactions in patients receiving multiple medications

Pregnancy

Lumefantrine should only be used in pregnancy if clearly needed; consult guidelines for specific considerations.

Breast-feeding

Use with caution while breastfeeding; consult healthcare provider for recommendations.

Storage

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

Formulations

• Tablets
• Oral suspension

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.

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.

Indications

• Potential role in bone health
• Support for connective tissue formation
• May aid in mineral metabolism

Dosage

Children: There is no established clinical dosage for silicon in paediatric populations, as it is not classified as an essential nutrient.

Adults: There is no established clinical dosage for silicon in adults, as it is not classified as an essential nutrient.

Mechanism of action

Silicon is believed to enhance the synthesis of glycosaminoglycans and collagen, which are important for the structural integrity of connective tissues. It may also influence the activity of certain enzymes involved in bone mineralization, thus playing a role in maintaining bone density and health.

Pharmacodynamics

The pharmacodynamics of silicon is not fully elucidated; however, it is thought to involve the modulation of bone metabolism and the promotion of connective tissue health. Silicon may have a synergistic effect with other minerals, such as calcium and magnesium, aiding in their utilization and metabolism in the body.

Pharmacokinetics

The pharmacokinetics of silicon is complex, as it is not absorbed through typical gastrointestinal pathways. Instead, silicon is thought to be taken up in the form of silicates and then distributed throughout the body, particularly in connective tissues. The elimination of silicon occurs primarily through renal excretion, with some variations depending on dietary intake and individual metabolism.

Pregnancy

Silicon is generally considered safe during pregnancy, as it is a naturally occurring element in the human body. However, specific recommendations regarding supplementation should be followed based on the advice of a healthcare provider.

Breast-feeding

Silicon is present in breast milk in small amounts. Its safety during breastfeeding is generally regarded as acceptable, although supplementation should be approached with caution and under medical advice.

Storage

Silicon should be stored in a cool, dry place, protected from light and moisture. Follow specific storage recommendations provided by the manufacturer if available.

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.

Mechanism of action

Involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals. Artemether (AM) is an antimalarial drug derived from artemisinin (Qinghaosu), an extract of the herb Artemisia annua L., sweet wormwood. Its antiparasitic effect is that of a schizontocide and is explained by rapid uptake by parasitized erythrocytes and interaction with a component of hemoglobin degradation resulting in formation of free radicals. It has been shown to exhibit a high clinical cure rate. Two theories have been put forward for the mode of antimalarial action of the artemisinin antimalarials, in accodance with the known properties of peroxides with medicinal activity. The first assumes that the artemisinins must be activated by contact with either reduced haem (ferrous haem, Fe(ll)PPIX) or non-haem ferrous iron (exogenous iron), causing cleavage of the peroxide to generate oxygen-centered radicals (alkoxy radicals') which are then presumed to be converted into carbon-centered radicals by transfer of proximate hydrogen atoms from the periphery of the peroxide molecule. These carbon-centered radicals are then thought to alkylate sensitive, yet unspecified, biomolecules in the parasite. A second theory argues for a process in which the intact artemisinin binds to a site within a vital protein in the parasite. The act of binding causes the peroxide to be converted to hydroperoxide or similar open peroxide, which in accordance with known properties of such compounds, generates one or more active chemical entities, either oxidizing agents or oxygen transfer agents per se, or oxygen-centered free radicals. This would be associated with the binding process. In such a way, the artemisinins might act as (irreversibile) inhibitors. Iron may, or may not, be associated with the activation process. No specific biological target in the parasite has yet been identified in support of this theory, but it may be membrane-bound proteins. A 2025 systematic review notes Artemether's pharmacological activity is antimalarial.

Pharmacodynamics

In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of <i>P. falciparum</i> by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

Mechanism of action

The exact mechanism by which lumefantrine exerts its antimalarial effect is unknown. However, available data suggest that lumefantrine inhibits the formation of &beta;-hematin by forming a complex with hemin and inhibits nucleic acid and protein synthesis.

Pharmacodynamics

Lumefantrine is a blood schizonticide active against erythrocytic stages of <i>Plasmodium falciparum</i>. It is thought that administration of lumefantrine with artemether results in cooperate antimalarial clearing effects. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thus thought to provide rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

Mechanism of action

It has very good absorptive properties.