Paroxetine Hydrochloride (Page 4 of 9)
6.2 Postmarketing Experience
The following reactions have been identified during post approval use of paroxetine. Because these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Acute pancreatitis, elevated liver function tests (the most severe cases were deaths due to liver necrosis, and grossly elevated transaminases associated with severe liver dysfunction), Guillain-Barré syndrome, Stevens-Johnson syndrome, toxic epidermal necrolysis, priapism, syndrome of inappropriate ADH secretion (SIADH), prolactinemia and galactorrhea; extrapyramidal symptoms which have included akathisia, bradykinesia, cogwheel rigidity, dystonia, hypertonia, trismus; status epilepticus, acute renal failure, pulmonary hypertension, allergic alveolitis, anaphylaxis, eclampsia, laryngismus, optic neuritis, porphyria, restless legs syndrome (RLS), ventricular fibrillation, ventricular tachycardia (including torsade de pointes), hemolytic anemia, events related to impaired hematopoiesis (including aplastic anemia, pancytopenia, bone marrow aplasia, and agranulocytosis), and vasculitic syndromes (such as Henoch-Schönlein purpura).
7 DRUG INTERACTIONS
7.1 Clinically Significant Drug Interactions
Table 6 includes clinically significant drug interactions with Paroxetine.
Table 6: Clinically Significant Drug Interactions with Paroxetine
| Monoamine Oxidase Inhibitors (MAOIs) | |
| Clinical Impact | The concomitant use of SSRIs, including Paroxetine, and MAOIs increases the risk of serotonin syndrome. |
| Intervention | Paroxetine is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue [see Dosage and Administration (2.6), Contraindications (4), Warnings and Precautions (5.2)]. |
| Examples | selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue |
| Pimozide and Thioridazine | |
| Clinical Impact | Increased plasma concentrations of pimozide and thioridazine, drugs with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias. |
| Intervention | Paroxetine is contraindicated in patients taking pimozide or thioridazine [see Contraindications (4)]. |
| Other Serotonergic Drugs | |
| Clinical Impact | The concomitant use of serotonergic drugs with Paroxetine increases the risk of serotonin syndrome. |
| Intervention | Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of Paroxetine and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2)]. |
| Examples | other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort |
| Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants) | |
| Clinical Impact | The concurrent use of an antiplatelet agent or anticoagulant with Paroxetine may potentiate the risk of bleeding. |
| Intervention | Inform patients of the increased risk of bleeding associated with the concomitant use of Paroxetine and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio [see Warnings and Precautions (5.5)]. |
| Examples | aspirin, clopidogrel, heparin, warfarin |
| Drugs Highly Bound to Plasma Protein | |
| Clinical Impact | Paroxetine is highly bound to plasma protein. The concomitant use of Paroxetine with another drug that is highly bound to plasma protein may increase free concentrations of Paroxetine or other tightly-bound drugs in plasma. |
| Intervention | Monitor for adverse reactions and reduce dosage of Paroxetine or other protein-bound drugs as warranted. |
| Examples | warfarin |
| Drugs Metabolized by CYP2D6 | |
| Clinical Impact | Paroxetine is a CYP2D6 inhibitor [see Clinical Pharmacology (12.3)]. The concomitant use of Paroxetine with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate. |
| Intervention | Decrease the dosage of a CYP2D6 substrate if needed with concomitant Paroxetine use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if Paroxetine is discontinued. |
| Examples | propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, tolterodine, venlafaxine, risperidone. |
| Tamoxifen | |
| Clinical Impact | Concomitant use of tamoxifen with Paroxetine may lead to reduced plasma concentrations of the active metabolite (endoxifen) and reduced efficacy of tamoxifen |
| Intervention | Consider use of an alternative antidepressant little or no CYP2D6 inhibition [see Warnings and Precautions (5.11)]. |
| Fosamprenavir/Ritonavir | |
| Clinical Impact | Co-administration of fosamprenavir/ritonavir with paroxetine significantly decreased plasma levels of paroxetine. |
| Intervention | Any dose adjustment should be guided by clinical effect (tolerability and efficacy). |
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