VENIZ XR 37.5MG CAPSULES

Indications

• Major depressive disorder
• Generalized anxiety disorder
• Social anxiety disorder

Dosage

Adults: The usual adult dose for major depressive disorder is 75 mg daily, which may be increased to a maximum of 375 mg daily, depending on clinical response. For generalized anxiety disorder and social anxiety disorder, the starting dose

Mechanism of action

Venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) inhibit the reuptake of serotonin and norepinephrine at presynaptic terminals. This inhibition increases the levels of these neurotransmitters in the synapse, promoting their action on postsynaptic receptors. At lower doses, venlafaxine predominantly inhibits serotonin reuptake, while at higher doses, it also inhibits norepinephrine reuptake. Additionally, both venlafaxine and ODV have weak effects on dopamine reuptake, but do not significantly interact with muscarinic, histaminergic, or adrenergic receptors.

Pharmacodynamics

Venlafaxine acts as an antidepressant by increasing neurotransmitter levels in the central nervous system, thus alleviating symptoms associated with psychiatric disorders. The drug does not exhibit significant activity at muscarinic, histaminergic, or adrenergic receptors, minimizing side effects commonly associated with other psychotropic medications.

Pharmacokinetics

Venlafaxine is well absorbed after oral administration, with peak plasma concentrations typically occurring within 2 hours for immediate-release formulations and 6 hours for extended-release formulations. The drug undergoes extensive metabolism in the liver, primarily via the cytochrome P450 system, resulting in the active metabolite O-desmethylvenlafaxine. The elimination half-life of venlafaxine is approximately 5 hours, while that of ODV is longer, around 11 hours. The drug and its metabolites are excreted mainly through the urine.

Contra-indications

• Hypersensitivity to venlafaxine or any of its excipients
• Concomitant use with monoamine oxidase inhibitors (MAOIs)
• Severe renal impairment

Adverse effects

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

Interactions

• Monoamine oxidase inhibitors (MAOIs)
• Other serotonergic drugs (e.g., SSRIs, SNRIs, triptans)
• CYP2D6 inhibitors (e.g., paroxetine, fluoxetine)
• Alcohol
• Antihypertensive agents

Precautions

• Monitor blood pressure regularly due to risk of increased blood pressure
• Caution in patients with a history of seizures
• Use with caution in patients with bipolar disorder
• Risk of serotonin syndrome when combined with other serotonergic agents
• Discontinuation syndrome may occur with abrupt withdrawal

Pregnancy

Venlafaxine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited human data are available.

Breast-feeding

It is not known if venlafaxine is excreted in human breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Tablets
• Extended-release capsules

Mechanism of action

The exact mechanism of action of venlafaxine in the treatment of various psychiatric conditions has not been fully elucidated; however, it is understood that venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) potently and selectively inhibits the reuptake of both serotonin and norepinephrine at the presynaptic terminal. This results in increased levels of neurotransmitters available at the synapse that can stimulate postsynaptic receptors. It is suggested that venlafaxine has a 30-fold selectivity for serotonin compared to norepinephrine: venlafaxine initially inhibits serotonin reuptake at low doses, and with higher doses, it inhibits norepinephrine reuptake in addition to serotonin. Venlafaxine and ODV are also weak inhibitors of dopamine reuptake. The mechanism of the antidepressant action of venlafaxine in humans is believed to be associated with its potentiation of neurotransmitter activity in the CNS. Preclinical studies have shown that venlafaxine and its active metabolite, O-desmethylvenlafaxine, are potent inhibitors of neuronal serotonin and norepinephrine reuptake and weak inhibitors of dopamine reuptake. Venlafaxine and O-desmethylvenlafaxine have no significant affinity for muscarinic cholinergic, H1-histaminergic, or a1-adrenergic receptors in vitro. Pharmacologic activity at these receptors is hypothesized to be associated with the various anticholinergic, sedative, and cardiovascular effects seen with other psychotropic drugs. Venlafaxine and O-desmethylvenlafaxine do not possess monoamine oxidase (MAO) inhibitory activity. /The antinociceptive effects of the novel phentylethylamine antidepressant drug venlafaxine and its interaction with various opioid, noradrenaline and serotonin receptor subtypes were evaluated. When mice were tested with a hotplate analgesia meter, venlafaxine induced a dose-dependent antinociceptive effect following i.p. administration with an ED50 of 46.7 mg/kg (20.5; 146.5; 95% CL). Opioid, adrenergic and serotoninergic receptor antagonists were tested for their ability to block venlafaxine antinociception. Venlafaxine-induced antinociception was significantly inhibited by naloxone, nor-BNI and naltrindole but not by beta-FNA or naloxonazine, implying involvement of kappa1- and delta-opioid mechanisms. When adrenergic and serotoninergic antagonists were used, yohimbine (P < 0.005) but not phentolamine or metergoline, decreased antinociception elicited by venlafaxine, implying a clear alpha2- and a minor alpha1-adrenergic mechanism of antinociception. When venlafaxine was administered together with various agonists of the opioid and alpha2- receptor subtypes, it significantly potentiated antinociception mediated by kappa1- kappa3- and delta-opioid receptor subtypes. The alpha2-adrenergic agonist clonidine significantly potentiated venlafaxine-mediated antinociception. Summing up these results, we conclude that the antinociceptive effect of venlafaxine is mainly influenced by the kappa- and delta-opioid receptor subtypes combined with the alpha2-adrenergic receptor. These results suggest a potential use of venlafaxine in the management of some pain syndromes. However, further research is needed in order to establish both the exact clinical indications and the effective doses of venlafaxine when prescribed for pain. /Salt not specified/ Venlafaxine ... causes selective inhibition of neuronal reuptake of serotonine and norepinephrine with little effect on other neurotransmitter systems. Cases of seizures, tachycardia, and QRS prolongation have been observed following drug overdose in humans. The clinical manifestations of cardiac toxicity suggest that venlafaxine may exhibit cardiac electrophysiological effects on fast conducting cells. Consequently, studies were undertaken to characterize effects of venlafaxine on the fast inward sodium current (I(Na)) of isolated guinea pig ventricular myocytes. Currents were recorded with the whole-cell configurati

Pharmacodynamics

Venlafaxine is an antidepressant agent that works to ameliorate the symptoms of various psychiatric disorders by increasing the level of neurotransmitters in the synapse. Venlafaxine does not mediate muscarinic, histaminergic, or adrenergic effects.