Ridmal

Indications

• Methemoglobinemia
• Urinary tract infections
• Surgical marking
• Treatment of certain types of cyanide poisoning

Dosage

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

Adults: Refer to the relevant clinical guidelines or the BNF for specific dosing recommendations.

Mechanism of action

Methylene blue acts as a reducing agent, converting methemoglobin back to its functional form, hemoglobin. This is primarily achieved through its action as an electron donor, facilitating the reduction of ferric iron (Fe3+) in hemoglobin to ferrous iron (Fe2+), thereby restoring its oxygen-carrying capacity. It also exhibits antimicrobial properties through its ability to generate reactive oxygen species when exposed to light, which can inhibit bacterial growth.

Pharmacodynamics

The pharmacodynamics of methylene blue involve its role in enhancing oxygen delivery in patients suffering from methemoglobinemia. By converting methemoglobin back to hemoglobin, it effectively increases the amount of hemoglobin available for oxygen transport. The drug also shows effects on the vascular system, where it can induce vasodilation and influence blood pressure.

Pharmacokinetics

Methylene blue is rapidly absorbed after intravenous administration, with peak plasma concentrations occurring within 1 to 3 hours. It is extensively distributed in body tissues and fluids, including the liver, kidneys, and lungs. The drug undergoes hepatic metabolism, primarily through the cytochrome P450 system, and is excreted mainly through urine. The half-life ranges from 5 to 24 hours, depending on the dosage and individual patient factors.

Pregnancy

Consult healthcare provider before use, as safety in pregnancy is not established.

Breast-feeding

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

Storage

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

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
• Enhances the bioavailability of active pharmaceutical ingredients

Dosage

Children: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Adults: Refer to the specific formulation guidelines, as dosage will vary based on the active ingredient and formulation type.

Mechanism of action

Croscarmellose sodium works by swelling and absorbing water when it comes into contact with gastrointestinal fluids. This swelling leads to the rapid disintegration of the tablet or capsule matrix, facilitating the release and absorption of the active pharmaceutical ingredients.

Pharmacodynamics

Croscarmellose sodium is classified as a superdisintegrant. Its ability to rapidly disintegrate solid dosage forms can significantly enhance the dissolution rate of the active ingredient, which is crucial for achieving therapeutic effects in a timely manner.

Pharmacokinetics

Croscarmellose sodium is not absorbed in the gastrointestinal tract and does not exert pharmacological effects in the body. It is considered non-toxic and is excreted unchanged. Its main role is as an excipient, influencing the formulation's characteristics rather than the pharmacokinetics of the active ingredients.

Precautions

• Use with caution in patients with known hypersensitivity to croscarmellose or its components.

Pregnancy

Safety in pregnancy has not been established. Use only if clearly needed.

Breast-feeding

Caution is advised when using during breastfeeding, as safety has not been established.

Storage

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

Formulations

• Powder
• Granules

Indications

• Uncomplicated malaria caused by Plasmodium falciparum
• Malaria in combination with other antimalarial medications

Dosage

Children: Refer to BNF for Children for age-appropriate dosing recommendations.

Adults: Refer to BNF for specific dosing guidelines based on the severity of malaria and combination therapy used. Commonly used doses may vary.

Mechanism of action

Dihydroartemisinin acts by binding to haem within the Plasmodium falciparum parasite. It is believed to bind to haem produced during the parasite's haem biosynthesis pathway in the early ring stage, and later to haem released from haemoglobin digestion. This binding triggers a reductive scission of the endoperoxide bridge, leading to the generation of a reactive oxygen species. This species further leads to the formation of a reactive carbon radical, which alkylates multiple protein targets within the parasite, contributing to its antimalarial activity. Notably, it irreversibly inhibits the sarco/endoplasmic reticulum Ca2+ ATPase pump of Plasmodium falciparum.

Pharmacodynamics

Dihydroartemisinin forms a reactive carbon radical intermediate that is instrumental in killing Plasmodium falciparum through the alkylation of diverse proteins. This mechanism is thought to disrupt various cellular functions within the parasite, ultimately leading to its death.

Pharmacokinetics

Dihydroartemisinin is rapidly absorbed following oral administration, with peak plasma concentrations typically reached within 1 to 2 hours. It is extensively metabolized in the liver, primarily through cytochrome P450 enzymes, leading to the formation of several metabolites. The elimination half-life is relatively short, ranging from 1 to 3 hours. The drug is primarily excreted in urine and bile, making it effective for short-term treatment but necessitating multiple doses for sustained efficacy.

Adverse effects

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

Precautions

• Use with caution in patients with a history of hypersensitivity to artemisinin derivatives.
• Monitor for signs of malaria treatment failure, especially in cases of severe malaria.
• Assess liver function prior to and during treatment, as hepatic impairment can affect drug metabolism.

Pregnancy

Dihydroartemisinin is classified as category C. Animal studies have shown adverse effects on the fetus, but there are no adequate and well-controlled studies in pregnant women. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Dihydroartemisinin is excreted in breast milk. Caution should be exercised when administering to nursing mothers. The effects on the infant are unknown.

Storage

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

Formulations

• Oral tablets
• Injectable solution

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

• 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.

Indications

• Plasmodium falciparum malaria
• Uncomplicated malaria
• Treatment of malaria in combination with other antimalarials

Dosage

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

Adults: Refer to the BNF for specific dosing information based on the treatment regimen and patient condition.

Mechanism of action

The mechanism of piperaquine inhibition of the haem detoxification pathway is unknown but is expected to be similar to that of other antimalarial agents. It is thought to interfere with the parasite's ability to detoxify haem, leading to toxic accumulation within the parasite, thereby inhibiting its growth and replication.

Pharmacodynamics

Piperaquine exhibits a mechanism of action that inhibits the Plasmodium falciparum parasite's haem detoxification pathway. This action is crucial in preventing the survival of the parasite within the host, leading to a reduction in parasitemia and clinical symptoms associated with malaria.

Pharmacokinetics

Piperaquine displays a relatively long half-life, allowing for once-daily dosing in treatment regimens. It is well absorbed following oral administration, with peak plasma concentrations achieved within several hours. The drug is extensively distributed in body tissues, and its elimination involves hepatic metabolism and renal excretion. The pharmacokinetics may be influenced by various drug interactions.

Interactions

• grapefruit juice: Severe (increases concentration)
• mitotane: Severe (decreases concentration)
• St John's Wort: Severe (decreases concentration)
• rifampicin: Severe (decreases concentration)
• dronedarone: Unknown (increases concentration)
• cobicistat: Unknown (increases concentration)
• crizotinib: Unknown (increases concentration)
• idelalisib: Unknown (increases concentration)
• imatinib: Unknown (increases concentration)
• letermovir: Unknown (increases concentration)

Pregnancy

Data on the use of piperaquine in pregnancy are limited. Consult local guidelines for the management of malaria in pregnant women.

Breast-feeding

Piperaquine is excreted in breast milk; caution should be exercised when administering to breastfeeding women.

Storage

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

Formulations

• Piperaquine phosphate tablet

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

Mechanism of action

Artemisinins, including Artenimol which is a major active metabolite of many artemisinins, are thought to act via a common mechanism. While the exact mechanism of action is not certain, theories exist as to how artemisinins produce their antimalarial effect. Artemisinins are believed to bind to haem within the *P. falciparum* parasite. The source of this haem varies with the life stage of the parasite. When the parasite is in the early ring stage artemisinins are believed to bind haem produced by the parasite's haem biosynthesis pathway. In later stages artemisinins likely bind to haem released by haemoglobin digestion. Once bound to haem, artemisinins are thought to undergo activation involving ferrous iron via reductive scission which splits the endoperoxide bridge to produce a reactive oxygen. This reactive oxygen is thought to undergo a subsequent intramolecular hydrogen abstraction to produce a reactive carbon radical. The carbon radical is believed to be the source of the drugs potent activity against *P. falciparum* by alkylating a wide array of protein targets. The nature and magnitude of the effect on specific protein function as a result of this alkylation is unknown. One target which has been the focus of research is the sarco/endoplasmic reticulum Ca2+ ATPase pump of *P. falciparum*. Artemisinins have been found to irreversably bind to and inhibit this protein at a binding site similar to that of Thapsigargin. The mechanism is likely the same as for other proteins, namely alkylation via the carbon radical intermediate. Artemisinins appear to preferentially collect in infected erythrocytes, concentrating the drug by several hundred-fold compared to uninfected cells. This may play a role in why little alkylation is seen in uninfected erythrocytes. A 2025 systematic review notes Dihydroartemisinine's pharmacological activities as being antimalarial and anticancer, and that it has shown promise in improving nonalcoholic steatohepatitis (NASH) by reducing  liver fat, inflammation, and fibrosis via Inhibition of  lipogenesis (SREBP-1c, FASN, SCD1) and promotion of  lipolysis (PGC1α, CPT-1a).

Pharmacodynamics

Artenimol is thought to form a reactive carbon radical intermediate which kills *P. falciparum* through alkylation of a wide array of proteins.

Mechanism of action

The mechanism of piperaquine inhibition of the haem detoxification pathway is unknown but is expected to be similar to that of [DB00608].

Pharmacodynamics

Piperaquine inhibits the P. Falciparum parasite's haem detoxification pathway.