Clebopride malate / Simeticone, (0.68 mg clebopride 200 mg simeticone)

Indications

• Dyspepsia
• Colic
• Wind pains

Dosage

Children: For children aged 1 month to 1 year: 0.5–1 mL, to be taken before feeds. For children aged 5–11 years: 5–10 mL three times a day, alternatively as required. For children aged 12–17 years: 10–20 mL three times a day, alternatively as required.

Adults: 10–20 mL three times a day, alternatively as required, to be made up with water.

Mechanism of action

Simeticone acts as a surfactant, decreasing the surface tension of gas bubbles in the gastrointestinal tract. This action facilitates the coalescence of mucus-covered gas bubbles, leading to their expulsion. The clinical efficacy of simeticone is attributed to these antifoam properties, which help alleviate discomfort caused by trapped gas.

Pharmacodynamics

Simeticone effectively decreases the surface tension of gas bubbles within the gastrointestinal tract, thereby facilitating their expulsion. It has a short duration of action, as it is typically administered on an as-needed basis, and possesses a wide therapeutic index because it is not absorbed systemically, making it generally safe for use.

Pharmacokinetics

Simeticone is not absorbed into the systemic circulation and is excreted unchanged. It has a localized effect within the gastrointestinal tract, where it acts to alleviate symptoms related to gas. Due to its lack of systemic absorption, the pharmacokinetics of simeticone are characterized by rapid action following administration, with effects lasting only as long as the drug is present in the gastrointestinal tract.

Contra-indications

• Hypophosphataemia
• Severe renal impairment
• Hepatic coma

Adverse effects

• Diarrhoea
• Nephrolithiasis (long term use)

Interactions

• Magnesium salts may interact with other medications and should be avoided in patients with renal impairment.

Precautions

• Use with caution in patients with heart failure, hypermagnesaemia, metabolic alkalosis, or respiratory alkalosis.
• Avoid antacids containing large amounts of sodium in patients with fluid retention.

Pregnancy

Simeticone is generally considered safe during pregnancy as it is not systemically absorbed.

Breast-feeding

Simeticone is considered safe during breastfeeding as it is not systemically absorbed.

Storage

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

Formulations

• Oral suspension (Infacol 40mg/ml, Dentinox Infant colic drops)
• Chewable tablets (Dentinox)
• Liquid form (sugar-free options available)

Indications

• Nausea
• Vomiting
• Postoperative nausea and vomiting
• Chemotherapy-induced nausea and vomiting

Dosage

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

Adults: Refer to the BNF for specific dosing information.

Mechanism of action

Clebopride exerts its effects by antagonizing the D2 dopamine receptors in the central nervous system, particularly in the chemoreceptor trigger zone (CTZ) of the medulla oblongata. This blockade reduces the stimulus for vomiting. Additionally, it has effects on serotonin receptors, contributing to its antiemetic action.

Pharmacodynamics

Clebopride demonstrates a high affinity for dopamine receptors, effectively inhibiting the action of dopamine, which is a neurotransmitter known to induce nausea and vomiting. The drug's antiemetic effect is evident in its ability to prevent or alleviate symptoms of nausea and vomiting in patients undergoing treatments that provoke these conditions, such as chemotherapy.

Pharmacokinetics

Clebopride is absorbed after oral administration, with peak plasma concentrations typically reached within one to two hours. The drug is metabolized in the liver, primarily through conjugation processes, and excreted mainly via urine. The half-life of clebopride is approximately 8 to 10 hours, allowing for once or twice daily dosing in clinical practice.

Contra-indications

• Hypersensitivity to clebopride or any of its components
• Pheochromocytoma
• Gastrointestinal hemorrhage
• Mechanical obstruction of the gastrointestinal tract
• Severe hepatic impairment
• Cardiac arrhythmias

Adverse effects

• Drowsiness
• Fatigue
• Nausea
• Diarrhea
• Dry mouth
• Extrapyramidal symptoms
• Tardive dyskinesia
• Hyperprolactinemia
• Allergic reactions such as rash or urticaria

Interactions

• Caution when used with other central nervous system depressants
• May enhance the effects of anticholinergic drugs
• Can interfere with the action of dopaminergic agents
• Caution with concomitant use of drugs that prolong the QT interval

Precautions

• Monitor for signs of extrapyramidal symptoms and tardive dyskinesia
• Use with caution in patients with a history of seizures
• Consider dose adjustments in patients with renal impairment
• Assess risk versus benefit in patients with a history of depression

Pregnancy

Clebopride should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Data on its use in pregnancy are limited.

Breast-feeding

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

Storage

Store below 25°C, protect from light. Keep out of reach of children.

Formulations

• Tablets: 50 mg
• Injection: 10 mg/2 ml

Indications

• Support in energy metabolism
• Management of metabolic disorders
• Potential role in exercise performance enhancement

Dosage

Children: Refer to specific guidance in the BNF for Children.

Adults: Refer to specific guidance in the BNF.

Mechanism of action

Malate participates in the malate-aspartate shuttle, which is essential for transferring reducing equivalents across the mitochondrial membrane. This shuttle allows for the conversion of NADH produced during glycolysis to NADH within the mitochondria, thus facilitating ATP production. Additionally, malate is involved in gluconeogenesis, where it contributes to the synthesis of glucose from non-carbohydrate precursors.

Pharmacodynamics

Malate aids in energy metabolism, particularly in the conversion of nutrients to ATP. It supports the regeneration of NAD+, which is crucial for numerous metabolic reactions. By participating in the TCA cycle, malate enhances aerobic respiration and plays a role in maintaining the balance of metabolic intermediates necessary for cellular function.

Pharmacokinetics

Malate is readily absorbed in the gastrointestinal tract and is distributed throughout the body, where it enters various metabolic pathways. It is primarily metabolized in the liver and muscle tissues. The elimination of malate is through metabolic conversion, with its metabolites being further processed in the TCA cycle.

Pregnancy

There are no well-controlled studies of malate in pregnant women. Use only if clearly needed.

Breast-feeding

Malate is considered to be safe during breastfeeding, though limited data are available.

Storage

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

Formulations

• Malate salts
• Malic acid

Mechanism of action

Simethicone is a surfactant that decreases the surface tension of gas bubbles in the gastrointestinal tract, more easily allowing gas to exit the body. The clinical use of simethicone is based on its antifoam properties. Silicone antifoams spread on the surface of aqueous liquids, forming a film of low surface tension and thus causing collapse of foam bubbles. Simethicone reportedly allows mucus-surrounded gas bubbles in the GI tract to coalesce and be expelled.

Pharmacodynamics

Simethicone decreases the surface tension of gas bubbles in the gastrointestinal tract, facilitating their expulsion. It has a short duration of action as it is generally given as needed, and a wide therapeutic index as it is not systemically absorbed.