Venlafaxine (Dosage)
Venlafaxine potentiates monoaminergic activity in the central nervous system (CNS). In preclinical studies it has been proven that venlafaxine and its main metabolite, O-desmetilvenlafaxina, are potent inhibitors of the reuptake of serotonin and noradrenaline (SNRI). It also weakly inhibits dopamine reuptake.
CONTRAINDICATIONS
Hypersensitivity to venlafaxine.
Concomitant prescription with MAOI antidepressants is contraindicated. Do not initiate the treatment with venlafaxine until 14 days after the interruption of MAOI treatment and stop treatment with venlafaxine for at least 7 days before initiating the MAOI treatment.
CAUTIONS
Precautions should be taken when prescribing venlafaxine in patients with a recent history of infarction or unstable heart disease, a history of seizures, in patients whose conditions may be compromised by increases in heart rate, in patients with IOP (elevated intraocular pressure) or at risk of sharp angle glaucoma. Caution in patients with a family history or background of bipolar disorder, history of aggression.
In patients with bleeding disorders or predisposition to them extreme precautions when prescribing venlafaxine together with anticoagulants, drugs that affect platelet function or increase the risk of bleeding. Caring for individuals with kidney failure, liver failure, elderly patients, children under 18 years old and diabetics.
Periodic control of blood pressure is recommended when taking venlafaxine. Hyponatremia and/or syndrome of inappropriate secretion of ADH (antidiuretic hormone) may occur, usually in volume depleted or dehydrated patients.
It is necessary to carry out a rigorous control in patients with a history of suicidal behavior and those who present a significant degree of suicidal ideation prior to start the treatment, since the risk of suicidal thoughts or suicide attempts during the treatment is greater. Gradually reduce the dose over a period of weeks or months to avoid withdrawal reactions.
Assess benefit/risk if akathisia/psychomotor agitation appears. It is recommended to monitor cholesterol levels. Risk of serotonin syndrome, particularly with the concomitant use of other serotonergic agents or that affect the metabolism of serotonin. If the concomitant treatment is clinically justified, is mandatory a strict monitoring of the patient, especially at the beginning and when increasing the dose. Concomitant use with serotonergic precursors (tryptophan supplements), with antipsychotics or with other dopamine antagonists is not recommended.
Consider risk/benefit in patients with high risk of severe cardiac arrhythmia or prolongation of the QTc interval. Avoid concomitant administration with medications that prolong the QTc interval.
SIDE EFFECTS
Asthenia, chills, fatigue, hypertension, vasodilation, palpitations, decreased appetite, constipation, nausea, vomiting, xerostomia, dyspepsia, hypercholesterolemia, weight loss, abnormal dreams, decreased libido, dizziness, dry mouth, headache, hypertonia, insomnia, nervousness, paresthesia, sedation, somnolence, tremor, confusion, depersonalization, yawning, sweating, accommodation abnormalities, mydriasis, visual disturbances, tinnitus, ejaculation/abnormal orgasms in males, anorgasmia, erectile dysfunction, involvement in urination, disorders menstrual, dysuria, and pollakiuria.
PHARMACOLOGIC INTERACTIONS
Potentiation of toxicity with risk of serotonin syndrome if venlafaxine is administered together with triptans, SSRI antidepressants, ISRN antidepressants, lithium, sibutramine, fentanyl and its analogues, dextromethorphan, tapentadol, pethidine, methadone, pentazocine, St. John's wort and drugs that affect the metabolism or serotonin precursors.
Venlafaxine potentiates the effect of warfarin.
The action of venlafaxine is increased by cimetidine.
Venlafaxine potentiates the action and toxicity of haloperidol.
Caution in co-administration with imipramine and metoprolol.
There is an increased risk of QTc prolongation and/or ventricular arrhythmias if venlafaxine is administered together with drugs that prolong the QTc interval (class Ia and III antiarrhythmics: quinidine, amiodarone, sotalol, dofetilide, some antipsychotics such as thioridazine, some macrolide antibiotics, some antihistamines; some quinolone antibiotics such as moxifloxacin).
Avoid alcohol consumption during the treatment.
BRAND NAMES
- Arafaxina Retard ®
- Conervin Retard ®
- Dislaven Retard ®
- Dobupal ®
- Flaxen ®
- Levest ®
- Vandral ®
- Venlabrain Retard ®
- Venlamylan ®
- Venlapine ®
- Zarelis ®
Genes analyzed
Bibliography
Venlafaxine is an antidepressant used in the treatment of major depressive disorder (MDD), anxiety and panic disorders. Venlafaxine belongs to the serotonin and norepinephrine reuptake inhibitor (SNRI) class of drugs, increasing its concentration in the synaptic space and thus enhancing neurotransmission. However, venlafaxine also weakly inhibits dopamine reuptake, which is why it is also known as a serotonin-norepinephrine-dopamine reuptake inhibitor (SNRI).
Cytochrome CYP2D6 converts venlafaxine in the liver to the active metabolite, O-desmethylvenlafaxine (ODV), which also has antidepressant activity. People with two inactive copies of the CYP2D6 gene (poor metabolizers, PM) may have an impaired ability to metabolize venlafaxine, resulting in a lower concentration of ODV in the bloodstream. Conversely, individuals with more than two copies of functional CYP2D6 alleles (ultrarapid metabolizers, UM) may have an increased ability to metabolize venlafaxine, resulting in an increased ODV metabolite in the bloodstream.
CYP2D6 alleles or gene variants with decreased or non-functional activity are CYP2D6*3, *4, *6, *7, *8, *11 and *12; partially functional alleles are CYP2D6*9, *10, *29 and *41. The allele called CYP2D6*5 is an inactive allele consisting of a complete gene deletion, so sequencing or PCR technology is required for the analysis of this isoform. The same is true for variants that are duplications of the CYP2D6 gene, such as the variants of ultrarapid metabolizers.
Few studies have investigated the effect of CYP2D6 variants on response to venlafaxine or the risk of adverse reactions during its treatment. These studies usually have small sample sizes or are case studies, so in general, the evidence on the relationship between the plasma level of the drug and its efficacy or tolerability is low.
