Paroxetin (Dosage)

Paroxetine is a drug of the selective serotonin reuptake inhibitor family. It is used in the treatment of depression, obsessive-compulsive disorder, panic disorder, anxiety disorder, among others. The variability in the response to paroxetine includes physical, psychosocial and also genetic factors, such as the presence of certain variants in the CYP2D6 gene, the main cytochrome involved in its metabolization.

Paroxetine is an antidepressant from the group of selective serotonin reuptake inhibitors (SSRIs) with a profile similar to fluoxetine. It specifically inhibits the reuptake of 5-hydroxytryptamine by brain neurons.

CONTRAINDICATIONS

Hypersensitivity to paroxetine

In combination with MAOIs (MonoAmino Oxidase Inhibitor Antidepressants), initiate treatment 2 weeks after interruption of the irreversible MAOI, or 24 h after interruption of the reversible MAOI and allow at least one week between interruption of paroxetine and the initiation of the MAOI; combination with thioridazine or pimozide.

CAUTIONS

Cautions should be taken in patients with a history of mania, severe renal insufficiency, hepatic insufficiency, diabetes (if paroxetine and pravastatin are received concomitantly, it is mandatory to perform a dose adjustment of oral hypoglycaemic agents and / or insulin), epilepsy, seizures, closed angle glaucoma or antecedents, heart disease, situations that cause hyponatremia, history of bleeding disorders or conditions that predispose to bleeding.

Precautions in the prescription to the elderly patients.

Caution in the concomitant use with oral anticoagulants, drugs that affect platelet function and increase the risk of bleeding. Combined with serotonergic and/or neuroleptic risk of NMS (neuroleptic malignant syndrome).

In children and adolescents should not be used; in case it is necessary to prescribe paroxetine, watch out because it increases the risk of suicidal behavior and hostility. There are no clinical studies in children under 7 years of age. Caution should be exercised in the prescribed doses since psychotropic sleepiness / agitation may appear in the first weeks, it is recommended to assess risk / benefit.

There is risk of suicide, so closely monitoring the patient is mandatory until improvement in the patient mood is detected. Even more extreme precautions in patients with a history of suicidal behavior or thoughts, or those who show a significant degree of suicidal ideation before the start of treatment. Abrupt interruption of treatment may cause withdrawal symptoms, should be done gradually over several weeks or months.

SIDE EFFECTS

Increased cholesterol levels, decreased appetite, drowsiness, insomnia, agitation, aggression, abnormal dreams, decreased concentration, dizziness, tremors, headache, altered concentration, blurred vision, yawning; nausea, constipation, diarrhea, vomiting, dry mouth; sweating, sexual dysfunction; asthenia, weight gain.

Short-term clinical trials in children and adolescents showed an increase in suicidal behaviors, self-harm behaviors and increased hostility.

PHARMACOLOGIC INTERACTIONS

Paroxetine potentiates its toxicity (serotonin syndrome) if it is administered together with: MAOI antidepressants, L-tryptophan, triptans, tramadol, linezolid, methylthionine chloride, SSRI antidepressants, lithium, pethidine, Hypericum perforatum.

Plasma paroxetine levels are decreased by fosamprenavir/ritonavir.

Paroxetine increases the plasma levels of: procyclidine, clomipramine, nortriptyline, desipramine, perphenazine, thioridazine, risperidone, atomoxetine, propafenone, flecainide, metoprolol.

Paroxetine may increase the risk of bleeding if it is administered with: oral anticoagulants, NSAIDs/ASAs, and other antiplatelet agents.

Paroxetine reduces the effectiveness of tamoxifen. The administration of paroxetine should be avoided, whenever possible, during the breast cancer prevention treatment with tamoxifen.

Caution if you are taking paroxetine with: fentanyl in general anesthesia or in the treatment of chronic pain.

The co-administration of paroxetine and pravastatin may cause an increase in blood glucose levels.

Avoid alcohol consumption during treatment with paroxetine.

BRAND NAMES

  • Arapaxel ®
  • Casbol ®
  • Daparox ®
  • Frosinor ®
  • Motivan ®
  • Seroxat ®
  • Xetin ®

Genes analyzed

CYP2D6

Bibliography

Bousman CA, Stevenson JM, Ramsey LB, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4, and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants. Clin Pharmacol Ther. 2023 Jul;114(1):51-68.

Hole K, Haslemo T, Molden E.Impact of CYP2D6 Genotype on Paroxetine Serum Concentration. Ther Drug Monit. 2023 Oct 1;45(5):683-688.

Li XL, Huang SQ, Xiao T, et al. Pharmacokinetics of immediate and sustained-release formulations of paroxetine: population pharmacokinetic approach to guide paroxetine personalized therapy in chinese psychotic patients. Front Pharmacol. 2022 Sep 12;13:966622.

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