TERBIFORTE

Indications

• Prevention of postoperative nausea and vomiting
• Treatment of nausea and vomiting
• Premedication for surgical procedures

Dosage

Children: Refer to the BNF for Children for age-appropriate dosing guidelines.

Adults: Refer to the BNF for specific dosing recommendations based on the clinical context and patient condition.

Mechanism of action

Droperidol primarily acts as an antagonist at dopamine D2 receptors in the central nervous system. This blockade of dopamine receptors leads to a decrease in nausea and vomiting, as dopamine is a key neurotransmitter involved in these processes. Furthermore, droperidol may also have some affinity for other receptor types, including adrenergic and serotonin receptors, contributing to its sedative and antiemetic effects.

Pharmacodynamics

The pharmacodynamic profile of droperidol includes its ability to reduce the incidence of nausea and vomiting through central action. It can also produce sedation and anxiolytic effects, making it useful in preoperative settings. The onset of action is typically rapid, with effects observed shortly after administration. Droperidol has a dose-dependent relationship, where higher doses may lead to increased sedation and potential extrapyramidal side effects due to its dopamine antagonism.

Pharmacokinetics

Droperidol is well-absorbed after parenteral administration, with peak plasma concentrations occurring within 30 minutes to 1 hour. It is metabolized in the liver, primarily via cytochrome P450 enzymes, and has a relatively short half-life, generally ranging from 1 to 3 hours. Droperidol is excreted mainly in urine as metabolites, with less than 1% of the dose excreted unchanged. The drug's pharmacokinetic profile can be influenced by factors such as age, liver function, and concurrent medications.

Interactions

• droperidol + dopaminereceptor agonists: Severe (decreases effects)
• droperidol + levodopa: Unknown (decreases effects)

Indications

• Tinea pedis (athlete's foot)
• Tinea cruris (jock itch)
• Tinea corporis (ringworm)
• Onychomycosis (fungal nail infections)

Dosage

Adults: For adults, the typical oral dosage for tinea infections is 250 mg once daily for 2 to

Mechanism of action

Terbinafine inhibits the enzyme squalene monooxygenase, preventing the conversion of squalene to 2,3-oxydosqualene, a vital step in ergosterol synthesis. This leads to reduced ergosterol levels, which are essential for fungal cell membrane integrity, and causes an accumulation of squalene, contributing to cell death.

Pharmacodynamics

As an allylamine antifungal, terbinafine disrupts fungal cell membrane synthesis by inhibiting squalene epoxidase. This action results in weakening of the cell wall and the formation of squalene-rich vesicles within the fungal cells. It has a long duration of action due to extensive tissue distribution and a long terminal elimination half-life. The therapeutic index is wide, making overdose uncommon, but liver function tests are recommended prior to treatment to mitigate the risk of hepatotoxicity.

Pharmacokinetics

Terbinafine is well absorbed after oral administration, with peak plasma concentrations occurring within 2 hours. It is extensively distributed in body tissues, particularly in skin and nails, where it accumulates. The elimination half-life ranges from 25 to 30 hours, allowing for once-daily dosing. Terbinafine is primarily metabolized by the liver and excreted in urine, with less than 5% of the dose excreted unchanged.

Adverse effects

• Nausea
• Diarrhea
• Abdominal pain
• Headache
• Rash
• Taste disturbance
• Liver function abnormalities

Interactions

• Moderate (increases exposure) with galantamine
• Moderate (increases exposure) with risperidone
• Moderate (increases exposure) with atomoxetine
• Moderate (increases exposure) with eliglustat
• Moderate (increases exposure) with fesoterodine
• Moderate (decreases exposure) with rifampicin
• Moderate (increases exposure) with fluoxetine
• Moderate (increases exposure) with centrally acting anticholinesterases
• Moderate (increases exposure) with second-generation antipsychotics
• Moderate (increases exposure) with tricyclic antidepressants

Precautions

• Use with caution in individuals with liver dysfunction
• Monitor liver function tests before and during therapy
• Avoid use in patients with a history of hypersensitivity to terbinafine or its components
• Caution in patients with renal impairment

Pregnancy

Manufacturer advises avoiding use unless potential benefit outweighs risk.

Breast-feeding

Manufacturer advises avoiding use unless potential benefit outweighs risk.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets (250 mg)
• Cream (1%)
• Solution (1%)

Mechanism of action

Terbinafine inhibits the enzyme squalene monooxygenase (also called squalene epoxidase), preventing the conversion of squalene to 2,3-oxydosqualene, a step in the synthesis of ergosterol. This inhibition leads to decreased ergosterol, which would normally be incorporated into the cell wall, and accumulation of squalene. Generation of a large number of squalene containing vesicles in the cytoplasm may leach other lipids away from, and further weaken, the cell wall.

Pharmacodynamics

Terbinafine is an allylamine antifungal that inhibits squalene epoxidase (also known as squalene monooxygenase) to prevent the formation of ergosterol and cause an accumulation of squalene, weakening the cell wall of fungal cells. Terbinafine distributes into tissues and has a long terminal elimination half life, so the duration of action is long. Overdose with terbinafine is rare, even above the therapeutic dose, so the therapeutic index is wide. Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.