REDIRUNO 50 XR

Indications

• Food preservative
• Treatment of urea cycle disorders
• Metabolic disorders involving benzoyl-CoA

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines based on condition.

Adults: Refer to the BNF for specific dosing guidelines based on condition.

Mechanism of action

Benzoate acts mainly by inhibiting the growth of bacteria and fungi through its ability to lower the pH, creating an environment that is less favorable for microbial growth. It is also involved in metabolic pathways where it helps in the conjugation of toxic substances, facilitating their excretion from the body.

Pharmacodynamics

Benzoate is known for its antimicrobial properties, which are particularly effective against a wide range of fungi and bacteria. Its efficacy as a preservative is due to its ability to penetrate microbial cell membranes and disrupt their metabolic processes. Additionally, it has been observed to modulate various metabolic pathways, particularly those associated with aromatic compound degradation.

Pharmacokinetics

After ingestion, benzoate is rapidly absorbed in the gastrointestinal tract. It is metabolized primarily in the liver, where it undergoes conjugation with glycine to form hippurate, which is then excreted in the urine. The half-life of benzoate varies depending on individual metabolic rates but is generally short due to its efficient conversion and excretion.

Pregnancy

There is limited data on the use of benzoate in pregnancy. Consultation with healthcare professionals is advised before use.

Breast-feeding

Limited data is available on the excretion of benzoate in breast milk. Caution is recommended when administering to nursing mothers.

Storage

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

Indications

• Major depressive disorder
• Generalized anxiety disorder

Dosage

Adults: The usual starting dose for adults is 50 mg once daily. The dose may be adjusted based on clinical response and tolerability, with a maximum recommended dose of 400 mg per day.

Mechanism of action

The exact mechanism of the antidepressant action of desvenlafaxine is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system through inhibition of their reuptake. Desvenlafaxine inhibits the serotonin transporters with 10 times the affinity of norepinephrine transporters, and it has the lowest affinity for dopamine transporters. It does not inhibit monoamine oxidase and has minimal interaction with other receptor types, such as muscarinic cholinergic and H1-histaminergic receptors.

Pharmacodynamics

Desvenlafaxine is characterized as a selective serotonin and norepinephrine reuptake inhibitor. It does not exhibit significant activity against muscarinic-cholinergic, H1-histaminergic, or alpha1-adrenergic receptors in vitro, nor does it show inhibitory activity against monoamine oxidase. Clinical studies have demonstrated that desvenlafaxine does not cause clinically relevant changes in cardiac conduction parameters, indicating a favorable cardiovascular safety profile.

Pharmacokinetics

Desvenlafaxine is absorbed after oral administration, with peak plasma concentrations typically occurring within 7.5 hours. It has a half-life of approximately 11 hours, allowing for once-daily dosing. The drug undergoes extensive metabolism primarily through conjugation, with renal excretion of both unchanged drug and metabolites. The pharmacokinetics can be affected by renal impairment, necessitating caution in dosage adjustments for patients with compromised renal function.

Contra-indications

• Hypersensitivity to desvenlafaxine or any of its excipients
• Uncontrolled hypertension
• Severe renal impairment

Adverse effects

• Nausea
• Dry mouth
• Dizziness
• Insomnia
• Somnolence
• Constipation
• Increased blood pressure
• Sweating
• Fatigue
• Anxiety

Interactions

• Monoamine oxidase inhibitors (MAOIs) - risk of serotonin syndrome
• Serotonergic drugs - increased risk of serotonin syndrome
• Antihypertensives - may reduce their effectiveness
• Alcohol - may increase side effects of desvenlafaxine

Precautions

• Monitor blood pressure regularly, especially in patients with pre-existing hypertension
• Use with caution in patients with a history of seizures
• Evaluate for potential risk of serotonin syndrome when used with other serotonergic agents
• Consider risk of withdrawal symptoms upon discontinuation

Pregnancy

Desvenlafaxine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Consult healthcare provider for individual assessment.

Breast-feeding

Desvenlafaxine is excreted in human breast milk. Caution is advised when administering to nursing mothers.

Storage

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

Formulations

• Tablets: 50 mg, 100 mg

Mechanism of action

The exact mechanism of the antidepressant action of desvenlafaxine is unknown but is thought to be related to the potentiation of serotonin and norepinephrine in the central nervous system, through inhibition of their reuptake. Particularly, desvenlafaxine has been found to inhibit the serotonin, norepinephrine, and dopamine transporters with varying degrees of affinity. Desvenlafaxine inhibits serotonin transporters with 10 times the affinity of norepinephrine transporters, and dopamine transporters with the lowest affinity. The exact mechanism of antidepressant action of desvenlafaxine has not been fully elucidated but appears to be associated with the drug's potentiation of serotonergic and noradrenergic activity in the CNS. Like venlafaxine and duloxetine, desvenlafaxine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake; however, inhibition of dopamine reuptake at concentrations that inhibit serotonin and norepinephrine reuptake appears unlikely in most patients. The drug does not inhibit monoamine oxidase (MAO) and has not demonstrated significant affinity for muscarinic cholinergic, H1-histaminergic, alpha1-adrenergic, dopaminergic, gamma-aminobutyric acid (GABA), glutamate, and opiate receptors in vitro.

Pharmacodynamics

Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor. It lacks significant activity on muscarinic-cholinergic, H₁-histaminergic, or &alpha;₁-adrenergic receptors <i>in vitro</i>, or inhibitory activity against monoamine oxidase. Desvenlafaxine does not appear to exert activity against calcium, chloride, potassium and sodium ion channels and also lacks monoamine oxidase (MAO) inhibitory activity. It was also shown to lack significant activity against the cardiac potassium channel, hERG, <i>in vitro</i>. Electrocardiograms were obtained from 1,492 desvenlafaxine treated patients with major depressive disorder and 984 placebo-treated patients in clinical studies lasting up to 8 weeks. No clinically relevant differences were observed between desvenlafaxine treated and placebo-treated patients for QT, QTc, PR, and QRS intervals. In a thorough QTc study with prospectively determined criteria, desvenlafaxine did not cause QT prolongation. No difference was observed between placebo and desvenlafaxine treatments for the QRS interval.