HELIGO KIT

Indications

• Gastro-oesophageal reflux disease
• Duodenal ulcer
• Benign gastric ulcer
• NSAID-associated gastric or duodenal ulcer
• Zollinger-Ellison syndrome

Dosage

Adults: 30 mg once daily for 4 weeks for duodenal ulcers, 30 mg once daily for 8 weeks for gastric ulcers, and 15 mg once daily for maintenance treatment. For gastro-oesophageal reflux disease, the usual dose is 15 mg

Mechanism of action

Lansoprazole is a prodrug that becomes activated in an acidic environment. Once protonated, it forms stable disulfide bonds with cysteine residues on the H+,K+-ATPase enzyme in parietal cells. This covalent binding leads to prolonged inhibition of gastric acid secretion, affecting both basal and stimulated acid production regardless of the stimulus.

Pharmacodynamics

Lansoprazole decreases gastric acid secretion by specifically targeting the H+,K+-ATPase enzyme, which catalyzes the final step in gastric acid secretion. It effectively heals duodenal ulcers and alleviates symptoms associated with acid secretion, such as heartburn, while also reducing pepsin secretion. Its action is effective in both daytime and nocturnal acid secretion, making it useful in treating various acid-related disorders.

Pharmacokinetics

Lansoprazole is absorbed after oral administration, with peak plasma concentrations usually occurring within 1-2 hours. It is extensively metabolized in the liver primarily via cytochrome P450 enzymes, leading to various metabolites that are excreted in urine. The half-life of lansoprazole is approximately 1.5 hours, but its acid-suppressive effects last longer due to its mechanism of action. The presence of food can affect the absorption rate, so it is typically recommended to take lansoprazole before meals.

Contra-indications

• Hypersensitivity to lansoprazole or any of its excipients
• Concurrent use with rilpivirine-containing products

Adverse effects

• Headache
• Diarrhoea
• Nausea
• Abdominal pain
• Constipation
• Flatulence
• Dizziness
• Fatigue
• Skin rash
• Elevated liver enzymes
• Acute interstitial nephritis
• Clostridium difficile-associated diarrhoea
• Bone fractures
• Hypomagnesemia

Interactions

• Increased risk of gastrointestinal infections due to reduced gastric acidity
• Apalutamide may decrease exposure when used with lansoprazole
• May alter the absorption of drugs that require an acidic environment for optimal absorption

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for signs of Clostridium difficile infection in patients with prolonged therapy
• Consider risk of hypomagnesemia and associated complications

Pregnancy

Manufacturer advises to avoid use during pregnancy due to lack of adequate human data.

Breast-feeding

Specialist sources indicate use with caution, as lansoprazole is likely to be present in human milk, but in small amounts probably too low to be harmful.

Storage

Store below 25°C in a dry place, protect from light.

Formulations

• Gastro-resistant capsules
• Oral suspension
• Gastro-resistant tablets
• Gastro-resistant granules

Indications

• Intestinal amoebiasis
• Urogenital trichomoniasis
• Giardiasis

Dosage

Children: For children aged 1 month to 11 years, the dosage is 50–75 mg/kg once, with a maximum of 2 g per dose. For children aged 12 to 17 years, the dosage is 2 g for a single dose, which may be repeated once if necessary.

Adults: The usual adult dosage is 2 g taken orally as a single dose for urogenital trichomoniasis or giardiasis, and 1.5 g to 2 g once daily for 3 to 6 days for intestinal amoebiasis.

Mechanism of action

Tinidazole acts as a prodrug and antiprotozoal agent. Its nitro group is reduced in Trichomonas by a ferredoxin-mediated electron transport system, generating free nitro radicals that covalently bind to DNA, causing DNA damage and cell death. The exact mechanism of action against Giardia and Entamoeba species is not fully understood but is believed to be similar to that of Trichomonas.

Pharmacodynamics

Tinidazole demonstrates in vitro and clinical activity against Trichomonas vaginalis, Giardia duodenalis (also known as G. lamblia), and Entamoeba histolytica. It does not exhibit significant activity against most strains of vaginal lactobacilli, which are beneficial bacteria in the vaginal flora.

Pharmacokinetics

Tinidazole is well absorbed following oral administration, with peak plasma concentrations occurring within 0.5 to 3 hours. It is extensively distributed throughout body tissues and fluids. The drug undergoes hepatic metabolism and is eliminated primarily through the urine, with a half-life of approximately 12 to 14 hours. Clinical and laboratory monitoring is advised if treatment extends beyond 10 days.

Adverse effects

• Abdominal pain
• Decreased appetite
• Diarrhoea
• Headache
• Nausea
• Skin reactions
• Vertigo
• Vomiting

Precautions

• Clinical and laboratory monitoring is advised if treatment exceeds 10 days

Pregnancy

Manufacturer advises avoiding use in the first trimester.

Breast-feeding

Present in milk; the manufacturer advises avoiding breastfeeding during and for 3 days after stopping treatment.

Storage

Store below 25°C, protect from moisture.

Formulations

• Tinidazole 500 mg tablets
• Tinidazole oral suspension

Indications

• Community-acquired pneumonia
• Chronic bronchitis exacerbation
• Sinusitis
• Skin and soft tissue infections
• Helicobacter pylori eradication
• Pharyngitis and tonsillitis
• Otitis media

Dosage

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

Adults: Refer to the BNF for specific adult dosing information.

Mechanism of action

Clarithromycin binds to the 50S ribosomal subunit of susceptible bacteria, inhibiting the translocation of peptides during protein synthesis. This action ultimately leads to a decrease in bacterial growth and replication.

Pharmacodynamics

Clarithromycin exhibits bacteriostatic activity against many gram-positive and some gram-negative bacteria. It is particularly effective against strains of Streptococcus pneumoniae, Staphylococcus aureus, and Haemophilus influenzae. The drug's action is concentration-dependent, with higher concentrations leading to greater antibacterial effects.

Pharmacokinetics

Clarithromycin is well absorbed from the gastrointestinal tract, with bioavailability typically around 50%. It is extensively metabolized in the liver, primarily by cytochrome P450 enzymes, producing an active metabolite, 14-hydroxyclarithromycin. The elimination half-life ranges from 3 to 4 hours, and the drug is excreted mainly in urine. Dose adjustments may be necessary in patients with renal impairment.

Contra-indications

• Hypersensitivity to clarithromycin or any macrolide antibiotic
• History of cholestatic jaundice or hepatic dysfunction associated with prior use of clarithromycin
• Concurrent use of certain medications that can lead to serious drug interactions, such as astemizole, cisapride, pimozide, or terfenadine

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Dysgeusia (taste disturbance)
• Headache
• Rash
• Elevations in liver enzymes
• QT prolongation
• Hearing loss

Interactions

• Increased risk of myopathy or rhabdomyolysis when used with statins
• Increased plasma concentrations of warfarin, leading to enhanced anticoagulant effect
• Potentially increased effects of certain benzodiazepines, such as midazolam
• Clarithromycin may inhibit CYP3A4, affecting the metabolism of various drugs

Precautions

• Caution in patients with renal impairment, as dosage adjustment may be necessary
• Use with caution in patients with pre-existing liver disease
• Monitoring for signs of hepatotoxicity is recommended
• Consider potential for drug interactions when prescribing

Pregnancy

Clarithromycin is classified as category C. It should only be used if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Clarithromycin is excreted in human milk. Caution should be exercised when administering to breastfeeding women.

Storage

Store below 25 degrees Celsius. Keep the product in its original packaging to protect from moisture.

Formulations

• Tablets (250 mg, 500 mg)
• Oral suspension (125 mg/5 mL, 250 mg/5 mL)
• Injection (500 mg)

Mechanism of action

As a PPI, lansoprazole is a prodrug and requires protonation via an acidic environment to become activated. Once protonated, lansoprazole is able to react with cysteine residues, specifically Cys813 and Cys321, on parietal H+,K+-ATPase resulting in stable disulfides. PPI's in general are able to provide prolonged inhibition of acid secretion due to their ability to bind covalently to their targets. Lansoprazole is a selective and irreversible proton pump inhibitor. In the acidic environment of the gastric parietal cell, lansoprazole is converted to active sulphenamide derivatives that bind to the sulfhydryl group of (H+, K+)-adenosine triphosphatase ((H+,K+)-ATPase), also known as the proton pump (H+,K+)-ATPase catalyzes the final step in the gastric acid secretion pathway. Lansoprazole's inhibition of (H+,K+)-ATPase results in inhibition of both centrally and peripherally mediated gastric acid secretion. The inhibitory effect is dose-related. Lansoprazole inhibits both basal and stimulated gastric acid secretion regardless of the stimulus.

Pharmacodynamics

Lansoprazole decreases gastric acid secretion by targeting H+,K+-ATPase, which is the enzyme that catalyzes the final step in the acid secretion pathway in parietal cells. Conveniently, lansoprazole administered any time of day is able to inhibit both daytime and nocturnal acid secretion. The result is that lansoprazole is effective at healing duodenal ulcers, reduces ulcer-related pain, and offers relief from symptoms of heartburn Lansoprazole also reduces pepsin secretion, making it a useful treatment option for hypersecretory conditions such as Zollinger-Ellison syndrome.

Mechanism of action

Tinidazole is a prodrug and antiprotozoal agent. The nitro group of tinidazole is reduced in <i>Trichomonas</i> by a ferredoxin-mediated electron transport system. The free nitro radical generated as a result of this reduction is believed to be responsible for the antiprotozoal activity. It is suggested that the toxic free radicals covalently bind to DNA, causing DNA damage and leading to cell death. The mechanism by which tinidazole exhibits activity against <i>Giardia</i> and <i>Entamoeba</i> species is not known, though it is probably similar. The nitro group of tinidazole is reduced by cell extracts of Trichomonas. As a result of this reduction a free nitro radical is generated which may be responsible for the antiprotozoal activity. The mechanism by which tinidazole exhibits activity against Giardia and Entamoeba species is not known.

Pharmacodynamics

Tinidazole is a synthetic antiprotozoal agent. Tinidazole demonstrates activity both in vitro and in clinical infections against the following protozoa: <i>Trichomonas vaginalis</i>, <i>Giardia duodenalis</i> (also termed <i>G. lamblia</i>), and <i>Entamoeba histolytica</i>. Tinidazole does not appear to have activity against most strains of vaginal lactobacilli.