Paroxetine

Registered South African indications:

• Depression
• Obsessive compulsive disorder
• Social phobia
• Panic disorder
• Generalised anxiety disorder

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to aspirin
• Hypersensitivity to peanuts
• Coadministration with monoamine oxidase inhibitors or within 14 days of their use
• Coadministration with thioridazine
• Coadministration with pimozide

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Children
• History of mania
• History of epilepsy
• History of suicidal thoughts or behaviour
• Diabetes mellitus
• Electroconvulsive therapy
• Glaucoma
• Cardiac conditions
• Hyponatraemia or risk factors thereof
• History of bleeding disorders
  - Von Willebrand disease
  - Haemophilia A
  - Deficiency in F VIII
  - Haemophilia B
• Comorbid bleeding disorders
  - Multiple pregnancy
  - Gestational hypertension
  - Preeclampsia
• Abrupt withdrawal

Forms avail. in SA and covered in this monograph: tab, controlled release tab (CR tab)

Depression

• Oral (tab): 20mg, dly; Titrate by 10mg at 1 week intervals; Max: 50mg/24hrs 
• Oral (CR tab): 25mg, dly; Titrate by 12.5mg at 1 week intervals; Max: 62.5mg/24hrs 

Panic disorder

• Oral (tab): Initial: 10mg, dly; Titrate by 10mg at 1 week intervals; Usual dose: 40mg; Max: 60mg/24hrs
• Oral (CR tab): Initial: 12.5mg, dly; Titrate by 12.5mg at 1 week intervals; Max: 75mg/24hrs

Obsessive compulsive disorder

• Oral (tab): 20mg, dly; Titrate by 10mg at 1 week intervals; Usual dose: 40mg, dly; Max: 60mg/24hrs 

Social anxiety disorder

• Oral (tab): 20mg, dly; Titrate by 10mg at 1 week intervals to response; Max: 40-60mg/24hrs
• Oral (CR tab): 12.5mg, dly; Titrate by 12.5mg at 1 week intervals; Max: 37.5mg/24hrs

Generalised anxiety disorder

• Oral (tab): 20mg, dly; Titrate by 10mg at 1 week intervals; Max: 50mg/24hrs

Post-traumatic stress disorder

• Oral (tab): 20mg, dly; Titrate by 10mg at 1 week intervals; Max: 50mg/24hrs

Not established for children below 17 years

Pregnancy

• Caution; positive evidence of risk
• Some epidemiological studies suggest an increased risk of congenital malformations, particularly cardiovascular (e.g. ventricular and atrial septum defects), associated with the use of paroxetine during the first trimester. The mechanism is unknown. The data suggest that the risk of having an infant with a cardiovascular defect following maternal paroxetine exposure is less than 2/100 compared with an expected rate for such defects of approximately 1/100 in the general population
• Paroxetine should only be used during pregnancy when strictly indicated. Women planning a pregnancy and those becoming pregnant during therapy should be asked to consult their physician. Abrupt discontinuation should be avoided during pregnancy
• Neonates should be observed if maternal use of paroxetine continues into the later stages of pregnancy, particularly the third trimester
• The following symptoms may occur in the neonate after maternal paroxetine use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty in sleeping. These symptoms could be due to either serotonergic effects or withdrawal symptoms. In a majority of instances, the complications begin immediately or soon (<24 hours) after delivery
• Epidemiological data have suggested that the use of SSRIs in pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population, 1 to 2 cases of PPHN per 1000 pregnancies occur
• Animal studies showed reproductive toxicity but did not indicate direct harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development
• Postpartum haemorrhage (PPH) is a leading cause of maternal mortality. Treatment with SSRIs and SNRIs within one month prior to birth may increase the risk of PPH
• Observational data indicate an increased risk of PPH following SSRI/ SNRI exposure within the month prior to delivery. Healthcare professionals should be aware of the potential risk of PPH while making treatment decisions for prescribing SSRI/ SNRI towards the end of pregnancy

Breastfeeding

• Caution
• Small amounts of paroxetine are excreted into breast milk. In published studies, serum concentrations in breastfed infants were undetectable (<2ng/ml) or very low (<4ng/ml). No signs of drug effects were observed in these infants. Since no effects are anticipated, breastfeeding can be considered

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended  
• Severe: Caution; dose adjustment recommended
  Oral (tab): Initial: 10mg daily; Titrate by 10mg at 1 week intervals; Max dose: 40mg/day
  Oral (CR tab): Initial: 12.5mg daily; Titrate by 12.5mg at 1 week intervals; Max dose: 50mg/day

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended 
• Severe: Caution; dose adjustment recommended
  Oral (tab): Initial: 10mg daily; Titrate by 10mg at 1 week intervals; Max dose: 40mg/day
  Oral (CR tab): Initial: 12.5mg daily; Titrate by 12.5mg at 1 week intervals; Max dose: 50mg/day

Elderly

• Caution; dose adjustment recommended
  Oral (tab): Initial: 10mg daily; Titrate by 10mg at 1 week intervals; Max dose: 40mg/day
  Oral (CR tab): Initial: 12.5mg daily; Titrate by 12.5mg at 1 week intervals; Max dose: 50mg/day

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Impaired concentration
• Dizziness
• Tremor
• Headache
• Extrapyramidal disorders
• Seizures 
• Restless legs syndrome
• Serotonin syndrome
• Somnolence
• Insomnia
• Agitation
• Abnormal dreams
• Confusion
• Hallucinations
• Manic reactions
• Anxiety
• Depersonalisation
• Panic attacks
• Akathisia
• Suicidal ideation

Cardiovascular Disorders

• Sinus tachycardia
• Bradycardia
• Postural hypotension

Respiratory Disorders

•  Yawning

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Diarrhoea 
• Dry mouth
• Gastrointestinal bleeding

Hepatobiliary disorders

• Hepatitis
• Increased hepatic enzymes

Genitourinary Disorders

• Urinary retention
• Urinary incontinence
• Sexual dysfunction
• Priapism

Endocrine and Metabolic Disorders

• Syndrome of inappropriate anti-diuretic hormone secretion
• Increased serum cholesterol
• Decreased appetite
• Altered glycaemic control
• Hyponatraemia
• Hyperprolactinaemia
• Galactorrhoea

Musculoskeletal Disorders

• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Sweating
• Skin rashes
• Pruritus
• Erythema multiforme
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Urticaria
• Photosensitivity reactions

Immune, Blood and Lymphatic System Disorders

• Abnormal bleeding
• Thrombocytopenia
• Allergic reactions

Sensory Disorders

• Blurred vision
• Mydriasis
• Acute glaucoma
• Tinnitus

• Serotonergic drugs
• Pimozide
• Thioridazine
• Monoamine oxidase inhibitors
• CYP3A4 inducers
• Fosamprenavir
• Ritonavir
• Procyclidine
• CYP2D6 inhibitors
• Tamoxifen
• Alcohol
• Oral anticoagulants
• Non-steroidal anti-inflammatory drugs
• Antiplatelet agents
• Pravastatin

None routine. Specific cases may require

• Blood pressure
• Vital signs

Additional observations

• Blood loss
• Signs of anaemia
  - Fatigue
  - Shortness of breath
  - Chest pain
  - Lactation problems

Risk of postpartum haemorrhage (PPH)

• PPH is a leading cause of maternal mortality. Treatment with SSRIs and SNRIs within one month prior to birth may increase the risk of PPH
• Observational data indicate an increased risk of PPH following SSRI/ SNRI exposure within the month prior to delivery
• Healthcare professionals should be aware of the potential risk of PPH while making treatment decisions for prescribing SSRI/ SNRI towards the end of pregnancy
• Patients should be advised to inform their doctors before taking SSRI/ SNRI containing medicines if they have history of bleeding disorders (e.g von Willebrand disease, haemophilia A, deficiency in F VIII, and haemophilia B); and comorbid bleeding disorders (e.g multiple pregnancy, gestational hypertension or preeclampsia)

Paroxetine is a selective inhibitor of neuronal serotonin reuptake. It inhibits the reuptake of serotonin at the neuronal membrane, enhances serotonergic neurotransmission by reducing turnover of the neurotransmitter, therefore it prolongs its activity at synaptic receptor sites and potentiates serotonin in the central nervous system.

Tablet 20mg

• Adco Paroxetine (Adcock)
• Aropax (GSK) originator
• Austell Paroxetine (Austell)
• Deparoc (Pharmacare)
• Hexal-Paroxetine (Sandoz) Discontinued: 01/04/2018
• Lenio (Aurobindo)
• Parax (Sandoz)
• Paroxetine Unicorn (Pharma Dynamics)
• Paxil (GSK) originator
• Sandoz Paroxetine (Sandoz)
• Sedarin (Xixia)
• Serrapress (Pharma Dynamics)
• Texine (Novagen)
• Xet (Zydus)
• Zydus-Paroxetine (Zydus)

Tablet 30mg

• Aropax (GSK) originator
• Austell Paroxetine (Austell)

Tablet 40mg

• Parax (Sandoz)

Tablet cr 12.5mg

• Aropax CR (GSK) originator

Tablet cr 25mg

• Aropax CR (GSK) originator