The prescribing information states that paroxetine should "not be used in combination with an MAOI (including linezolid, an antibiotic which is a reversible non-selective MAOI), or within 14 days of discontinuing treatment with an MAOI", and should not be used in combination with pimozide, thioridazine, tryptophan, or warfarin.Paroxetine interacts with the following cytochrome P450 enzymes:
CYP2D6 for which it is both a substrate and a potent inhibitor. CYP2B6 (strong) inhibitor. CYP3A4 (weak) inhibitor. CYP1A2 (weak) inhibitor. CYP2C9 (weak) inhibitor. CYP2C19 (weak) inhibitor.Paroxetine has been shown to be an inhibitor of G protein-coupled receptor kinase 2 (GRK2). Pharmacology
Pharmacodynamics
Paroxetine is the most potent and one of the most specific selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors (SSRIs). It also binds to the allosteric site of the serotonin transporter, similarly, but less potently, than escitalopram. Paroxetine also inhibits the reuptake of norepinephrine to a lesser extent (<50 nmol/L). Based on evidence from four weeks of administration in rats, the equivalent of 20 mg paroxetine taken once daily occupies approximately 88% of serotonin transporters in the prefrontal cortex. Pharmacokinetics
Paroxetine is well-absorbed following oral administration. It has an absolute bioavailability of about 50%, with evidence of a saturable first pass effect. When taken orally, it achieves maximum concentration in about 6–10 hours and reaches steady-state in 7–14 days. Paroxetine exhibits significant interindividual variations in volume of distribution and clearance. Less than 2% of an oral dose is excreted in urine unchanged.Paroxetine is a mechanism-based inhibitor of CYP2D6.
Use in pregnancy is not recommended while use during breastfeeding is relatively safe.Paroxetine shares many of the common adverse effects of SSRIs, including (with the corresponding rates seen in people treated with placebo in parentheses):

nausea 26% (9%)
diarrhea 12% (8%)
constipation 14% (9%)
dry mouth 18% (12%)
somnolence 23% (9%)
insomnia 13% (6%)
headache 18% (17%)
hypomania 1% (0.3%)
blurred vision 4% (1%)
loss of appetite 6% (2%)
nervousness 5% (3%)
paraesthesia 4% (2%)
dizziness 13% (6%)
asthenia (weakness; 15% (6%))
tremor 8% (2%)
sweating 11% (2%)
sexual dysfunction (≥10% incidence).Most of these adverse effects are transient and go away with continued treatment. Central and peripheral 5-HT3 receptor stimulation is believed to result in the gastrointestinal effects observed with SSRI treatment. Compared to other SSRIs, it has a lower incidence of diarrhea, but a higher incidence of anticholinergic effects (e.g., dry mouth, constipation, blurred vision, etc. ), sedation/somnolence/drowsiness, sexual side effects, and weight gain.Due to reports of adverse withdrawal reactions upon terminating treatment, the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency recommends gradually reducing over several weeks or months if the decision to withdraw is made. See also Discontinuation syndrome (withdrawal). Mania or hypomania may occur in 1% of patients with depression and up to 12% of patients with bipolar disorder. This side effect can occur in individuals with no history of mania but it may be more likely to occur in those with bipolar or with a family history of mania. Suicide
Like other antidepressants, paroxetine may increase the risk of suicidal thinking and behaviour in people under the age of 25.