Paroxetine hydrochloride – PAXIL CR® – PAXIL IR®

• PAXIL CR®
• PAXIL IR®

• Selective Serotonin Reuptake Inhibitor

• Tablet: 10 Mg, 20 Mg, 30 Mg, 40 Mg
• Extended release Tablet: 12.5 Mg, 25 Mg, 37.5 Mg
• Capsule: 7.5 Mg
• Oral Suspension: 10Mg/5mL

• Depression: Major Depressive Disorder.
• Panic Disorder: with or without agoraphobia.
• Social Phobia (Social Anxiety Disorder)
• Premenstrual Dysphoric Disorder

• Paroxetine is in category of SSRIs (selective serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitor – responsible for its antidepressant and anxiolytic action- significant affinity for Adrenergic, Dopaminergic, Serotonergic or Histaminergic brain receptors.

• Absorption: The mean elimination half-life of paroxetine was 15 to 20 hours
• Distribution: At therapeutic concentrations, the plasma protein binding of paroxetine is approximately 95%.
• Metabolism: First-pass metabolism is extensive, but may be partially saturable, accounting for the increased bioavailability observed with multiple dosing. The metabolism of paroxetine is accomplished in part by cytochrome P450
• Excretion: 64% of an administered dose eliminated by the kidneys +36% in the feces. Less than 2% >>> parent compound.

1. Depression:
   • Initial Dosage: 25 mg/day
   • Maintenance dosage: 30 mg/day PAXIL IR~ to 37.5 mg/day PAXIL CR- For at least 6 months- Dose changes should be done with an interval of at least one week.
   • Max Dosage: 62.5 mg/day
2. Panic Disorder:
   • Initial Dosage: 12.5 mg/day
   • Maintenance Dosage: Dosage adjustments should be made to maintain the patient on the lowest effective dosage.
   • Max Dosage: 75 mg/day
3. Social Phobia (Social Anxiety Disorder):
   • Initial Dosage: 12.5 mg/day
   • Maintenance Dosage: Dosage adjustments should be made to maintain the patient on the lowest effective dosage.
   • Max Dosage: 37.5 mg/day
4. Premenstrual Dysphoric Disorder:
   • Initial Dosage: 12.5 mg/day- limited to the luteal phase of the menstrual cycle, starting 14 days prior to the expected onset of menses, and terminating on the first day of menses.
   • Maintenance dosage: periodically re-evaluate the long-term usefulness of the drug for the individual patient. (Dose not studied yet)
5. Elderly Patients:
   • Initial Dosage: 12.5 mg/day
   • Max Dosage: 50 mg/day.
6. Renal/Hepatic Impairment:
   • Initial Dosage: 12.5 mg/day
   • Max Dosage: 50 mg/day.

1. Potential for reduced efficacy of Tamoxifen with concomitant SSRI use, including Paroxetine>>> Lowers the effect of Tamoxifen.
2. Monoamine Oxidase Inhibitors: Should not be used in combination >>> Serotonin Syndrome
3. Thioridazine: Associated with serious ventricular arrhythmias >>> torsade de pointes-type arrhythmias, and sudden death (Due to enzyme inhibitor -inhibit P450 2D6- effect of Paroxetin)>>>> Neuroleptic malignant syndrome!
4. Pimozide: QT interval prolongation and severe arrhythmias >>> torsade de pointes-type arrhythmias
5. Antiretroviral (Fosamprenavir/ritonavir): Co-administration with paroxetine significantly decreased plasma levels of paroxetine>>> Do dose adjustment
6. Drugs Highly Bound to Plasma Protein: Paroxetine is highly bound to plasma protein, therefore administration of paroxetine to a patient taking another drug that is highly protein bound may cause increased free concentrations of the other drug, resulting in adverse events. Conversely, adverse effects could result from displacement of paroxetine by other highly bound drugs.
7. Anti-cholinergic Drugs: Synergistic effect >>> Lower the dose of Paroxetine.
8. Anticonvulsants: Paroxetine+Phenytoin>>> Lowers the effect of paroxetine! (enzyme inducer effect):
   • No initial dosage adjustment of PAXIL CR is considered necessary when the drug is to be coadministered with known drug metabolizing enzyme inducers (e.g. carbamazepine, phenytoin, sodium valproate) and any subsequent dosage adjustment should be guided by clinical effect.
9. Antipsychotic Drugs: >>> Neuroleptic Malignant Syndrome
10. Lithium: potential for serotonin syndrome
11. Triptans: potential for serotonin syndrome/ Neuroleptic Malignant Syndrome
12. Tryptophan: potential for serotonin syndrome/ Neuroleptic Malignant Syndrome
13. Cimetidine: Elevated Paroxetine plasma level ( Cimetidine is enzyme inhibitor drug)
14. St. John’s Wort: may result in an increase in undesirable effects.

More Than 5%:

1. Psychomotor Impairment (Dizziness): Avoid Driving although SSRIs are not sedative.
2. Nausea
3. Insomnia
4. Headache
5. Dry Mouth
6. Constipation
7. Diarrhea
8. Ejaculation Disorder
9. Tremor

Less Than 5%:

1. Anxiety
2. Blurred Vision
3. Decreased Appetite
4. Impotence
5. Nervousness

1. Hypersensitivity to paroxetine hydrochloride
2. Monoamine Oxidase Inhibitors: Should not be used in combination>>> Serotonin Syndrome
3. Thioridazine: Associated with serious ventricular arrhythmias>>>torsade de pointes-type arrhythmias, and sudden death ( Due to enzyme inhibitor -inhibit P450 2D6- effect of Paroxetin)>>>> Neuroleptic malignant syndrome!
4. Pimozide: QT interval prolongation and severe arrhythmias >>> torsade de pointes-type arrhythmias
5. Glaucoma: As with other SSRIs, Paroxetine can cause mydriasis>>> Use with caution in patients with high intra ocular pressures/ narrow angle glaucoma.
6. Hyponatremia: Reversible when discontinued.
7. Sexual Function/Reproduction: May affect sperm quality>>> Reversible when discontinued.

• Pregnancy: Category D
• Lactation: Lactating women should not nurse their infants while receiving paroxetine.

1. Pediatrics (<18 years of age): not indicated for use in patients below the age of 18 years.
2. Geriatrics (≥ 65 years of age): Increased plasma levels of Paroxetine.
3. Potential association with behavioural and emotional changes, including selfharm >>> potential for suicidal behaviour
4. NOT be discontinued abruptly, due to risk of discontinuation symptoms. Do a gradual reduction.
5. Bone Fracture Risk: Elderly patients and patients with important risk factors – risk of falls, such as dizziness and orthostatic hypotension, especially at the early stages of treatment
6. Cardiovascular: The usual precautions should be observed in patients with cardiac conditions.
7. Dependence Liability: carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of Paroxetine.
8. Increased LDL-cholesterol levels of ~10% >> Use with caution in Cardiovascular patients.
9. Abnormal Bleeding: SSRIs including Paroxetine may increase the risk of bleeding events by causing abnormal platelet aggregation >>> Caution in concomitant use of acetylsalicylic acid (ASA), nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin and other anticoagulants.
10. Use with caution in patients with hepatic impairment.
11. Use with caution in patients with Epilepsy & Seizure Past history
12. Fatal outcome is approximately 400 mg:
    • Overdose symptoms: somnolence, nausea, tremor, dizziness, vomiting, diarrhea, agitation, aggression, anxiety, confused state, headache, fatigue, insomnia, tachychardia, hyperhydrosis, mydriasis, convulsion, paraethesia, serotonin syndrome, fever, blood pressure changes, involuntary muscle contraction and loss of consciousness
    • No specific antidote is known.
    • Induction of emesis is not recommended. Due to the large volume of distribution of Paroxetine.
    • Do supportive care with frequent monitoring of vital signs and careful observation is indicate