Sertraline

Registered South African indications:

• Major depressive illness
  - Single episodes and recurrent depression
• Obsessive-compulsive disorder (OCD)
• Panic disorder with or without agoraphobia

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of its excipients
• Coadministration with monoamine oxidase inhibitors (MAOIs)
• Pregnancy
• Breastfeeding
• Coadministration with pimozide
• Hepatic impairment
• Renal impairment
• Porphyria
• Children under the age of 18 years, except for patients with OCD aged 13 - 17 years old

Contraindications registered in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Coadministration with irreversible monoamine oxidase inhibitors (MAOIs) or within 14 days of their use
  - Sertraline must be discontinued for at least 7 days before starting treatment with an irreversible MAOI
• Coadministration with pimozide

South African recommendations

• Women of childbearing potential not on effective contraception
• Elderly
• Children and adolescents below 18 years
• Suicidal thoughts and clinical worsening
• Major depressive disorder (Adults and children)
• Other psychiatric and non-psychiatric disorders
• History of bleeding disorders
• Risk factors for QTc prolongation/Torsade de Pointes (TdP)
  - Cardiac disease
  - Hypokalaemia
  - Hypomagnesemia
  - Family history of QTc prolongation
  - Bradycardia
  - Coadministration of agents which prolong QTc interval
• History of mania/hypomania
• Schizophrenia
• Unstable epilepsy
• Controlled epilepsy
• Volume depletion
• Risk of developing hyponatraemia
• Abrupt withdrawal
• Extrapyramidal disorders
• Risk of bone fractures
• Recent history of myocardial infarction or unstable heart disease
• Diabetes mellitus
• Risk of postpartum haemorrhage
• Diseases or conditions that could affect metabolism or haemodynamic processes
• Combined use with electroconvulsive therapy
• Angle-closure glaucoma
• History of glaucoma
• Switching from SSRIs, antidepressants or anti-obsessional agents, particularly from long-acting agents such as fluoxetine
• Coadministration with diuretics
• May impair ability to drive and operate machinery

Recommendations in other jurisdictions

• Pregnancy
• Breastfeeding
• Hepatic impairment
• Elderly
• Children and adolescents below 18 years
• History of bleeding disorders
• Major depressive disorder
• Risk of postpartum haemorrhage
• Risk factors for QTc prolongation/Torsade de Pointes (TdP) 
  - Cardiac disease 
  - Hypokalaemia 
  - Hypomagnesemia 
  - Family history of QTc prolongation 
  - Bradycardia 
  - Coadministration of agents which prolong QTc interval
• History of mania or hypomania
• Schizophrenia
• Unstable epilepsy
• Controlled epilepsy
• History of suicide-related events or exhibiting a significant degree of suicidal ideation
• Other psychiatric disorders
• Risk of developing hyponatraemia
• Volume depletion
• Abrupt withdrawal
• Diabetes mellitus 
• Angle closure glaucoma
• History of glaucoma
• Switching from SSRIs, antidepressants or anti-obsessional agents, particularly from long-acting agents such as fluoxetine
• Combined use with electroconvulsive therapy
• Coadministration with diuretics
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: fct, tab

Dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Major depressive illness
- Single episodes and recurrent depression

• Oral (fct, tab): Initial: 50mg, dly; In patients with incomplete response but good toleration at lower doses: Titrate by 50mg at intervals of 2 weeks, to 150-200mg daily; Maintenance: 50-200mg, dly; Max: 150-200mg/24hrs

Obsessive-compulsive disorder (OCD)

• Oral (fct, tab): Initial: 50mg, dly; Maintenance: 50-100mg, dly

---

Doses above 100mg did not have any additional benefit. The onset of therapeutic effect may be seen within 7 days, although 2-4 weeks (and even longer in OCD) are usually necessary for full activity

---

Panic disorders with or without agoraphobia 

• Oral (tab): Initial: 25mg, dly; Increase to 50mg after 1 week; Maintenance: 50mg, dly 

---

This dosage regimen has been demonstrated to reduce the frequency of early treatment emergent side effects characteristic of panic disorder 

---

Sertraline should be given as a single daily dose with or without food

---

If sertraline therapy has to be discontinued, sertraline should be tapered

Forms avail. in SA and covered in this monograph: fct, tab

Paed. dosages below include:

• South African registered indications and dosages

South African registered indications and dosages

Obsessive-compulsive disorder (OCD)

Younger than 13 years

• Not established for use

Between 13-17 years

• Oral (fct, tab): Initial: 50mg, dly; In case of lack of response: Titrate by 50mg at intervals of at least 1 week; Maintenance: 50-200mg, dly; Max: 200mg/24hrs

---

Sertraline is contraindicated in children under the age of 18 years with both OCD and a major depressive disorder

---

The generally lower body weights of children compared to adults should be taken into consideration in advancing the dose from 50mg, in order to avoid excessive dosing. Given the 24hr elimination half-life of sertraline, dose changes should not occur at intervals of <1 week

---

See additional prescribing points

Pregnancy

South African recommendations

• Contraindicated
• The safety of sertraline during pregnancy has not been established
• Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to birth
• Women of childbearing potential should employ an adequate method of contraception when taking sertraline

Recommendations in other jurisdictions

• Caution; not recommended
• There are no well-controlled studies in pregnant women. However, a substantial amount of data did not reveal evidence of induction of congenital malformations by sertraline. Animal studies showed evidence for effects on reproduction probably due to maternal toxicity caused by the pharmacodynamic action of the compound and/or direct pharmacodynamic action of the compound on the foetus
• Use of sertraline during pregnancy has been reported to cause symptoms, compatible with withdrawal reactions, in some neonates, whose mothers had been on sertraline. This phenomenon has also been observed with other SSRI antidepressants. Sertraline is not recommended in pregnancy unless the clinical condition of the woman is such that the benefit of the treatment is expected to outweigh the potential risk
• Neonates should be observed if maternal use of sertraline continues into the later stages of pregnancy, particularly the third trimester. The following symptoms may occur in the neonate after maternal sertraline 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
• SSRIs/SNRIs may increase the risk of postpartum haemorrhage. Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following SSRI/SNRI exposure within the month prior to delivery 

Breastfeeding

South African recommendations

• Contraindicated
• The safety of sertraline during breastfeeding has not been established
• Women using sertraline should not breastfeed their infants

Recommendations in other jurisdictions

• Caution; not recommended
• Published data concerning sertraline levels in breast milk show that small quantities of sertraline and its metabolite N-desmethylsertraline are excreted in milk. Generally negligible to undetectable levels were found in infant serum, with one exception of an infant with serum levels about 50% of the maternal level (but without a noticeable health effect in this infant)
• To date, no adverse effects on the health of infants breastfed by mothers using sertraline have been reported, but risk cannot be excluded. Use in breastfeeding mothers is not recommended unless the benefit outweighs the risk

Fertility

South African recommendations

• There is no clinical trial data on fertility. In animal studies, no effect on fertility parameters was observed

Recommendations in other jurisdictions

• Animal data did not show an effect of sertraline on fertility parameters
• Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far

Renal Impairment

South African recommendations

• Contraindicated
  Sertraline should not be used in patients with renal impairment

Recommendations in other jurisdictions

• No dose adjustment recommended

Hepatic Impairment

South African recommendations

• Contraindicated
  The metabolism of sertraline is delayed in patients with impaired liver function
  The use of sertraline in patients with hepatic disease must be avoided

Recommendations in other jurisdictions

• Mild to moderate (Child-Pugh class A): Caution; dose adjustment recommended   
  A lower or less frequent dose should be used
  Recommended dose: 50% of the usual dose; Max: 100mg/24hrs
• Severe (Child-Pugh class B or C): Caution; not recommended

Elderly

• Caution; no dose adjustment recommended
  Elderly should be dosed carefully, as they are at greater risk for hyponatraemia

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Insomnia 
• Anxiety
• Depression
• Agitation
• Decreased libido
• Nervousness
• Depersonalisation
• Nightmares
• Bruxism
• Suicidal ideation/behaviour
• Psychotic disorder
• Abnormal thinking
• Apathy
• Hallucinations
• Aggression
• Euphoric mood
• Paranoia
• Conversion disorder
• Paroniria
• Drug dependence
• Sleep walking
• Dizziness
• Headache
• Somnolence
• Tremor
• Movement disorders
  - Extrapyramidal symptoms such as hyperkinesia, hypertonia, dystonia, teeth grinding or gait abnormalities
• Hypertonia
• Attention disturbances
• Amnesia
• Involuntary muscle contractions
• Syncope
• Hyperkinesia
• Migraine
• Seizures
• Postural dizziness
• Abnormal coordination
• Speech disorder
• Coma
• Akathisia
• Dyskinesia
• Cerebrovascular spasm
• - Cerebral vasoconstriction syndrome
  - Call-Fleming syndrome
• Psychomotor restlessness
• Choreoathetosis
• Yawning
• Fatigue

Cardiovascular Disorders 

• Palpitations
• Tachycardia
• Cardiac disorder
• Myocardial infarction
• Bradycardia
• QTc prolongation
• Torsade de pointes
• Hot flushes
• Hypertension
• Flushing
• Peripheral ischaemia
• Procedure vasodilation

Respiratory Disorders 

• Bronchospasm
• Dyspnoea
• Epistaxis
• Laryngospasm
• Hyperventilation
• Hypoventilation
• Stridor
• Dysphonia
• Hiccups
• Interstitial lung disease
• Pharyngitis
• Upper respiratory tract infection
• Rhinitis

Gastrointestinal Disorders 

• Diarrhoea
• Nausea and vomiting
• Dry mouth
• Abdominal pain
• Constipation
• Dyspepsia
• Flatulence
• Oesophagitis
• Dysphagia
• Haemorrhoids
• Salivary hypersecretion
• Eructation
• Melaena
• Haematochezia
• Stomatitis
• Glossitis
• Mouth ulceration
• Pancreatitis
• Diverticulitis
• Gastroenteritis
• Tooth disorder
• Microscopic colitis
• Thirst

Hepatobiliary Disorders 

• Abnormal hepatic function
• Serious hepatic events
  - Hepatitis
  - Jaundice
  - Hepatic failure
• Increased alanine aminotransferase
• Increased aspartate aminotransferase

Genitourinary Disorders 

• Premature ejaculation
• Haematuria
• Pollakiuria
• Micturition disorder
• Urinary retention
• Urinary incontinence
• Polyuria
• Nocturia
• Urinary hesitation
• Oliguria
• Ejaculation failure
• Irregular menstruation
• Erectile dysfunction
• Sexual dysfunction
• Menorrhagia
• Vaginal hemorrhage
• Female sexual dysfunction
• Atrophic vulvovaginitis
• Genital discharge
• Balanoposthitis
• Priapism
• Postpartum hemorrhage
• Abnormal semen

Endocrine and Metabolic Disorders 

• Hypothyroidism
• Hyperprolactinaemia
• Syndrome of inappropriate antidiuretic hormone secretion
• Decreased appetite
• Increased appetite
• Diabetes mellitus
• Hypercholesterolaemia
• Increased blood cholesterol
• Hypoglycaemia
• Hyponatraemia
• Hyperglycaemia
• Galactorrhoea
• Gynaecomastia
• Increased weight
• Decreased weight

Musculoskeletal Disorders 

• Arthralgia
• Myalgia
• Osteoarthritis
• Muscular weakness
• Back pain
• Muscle twitching
• Muscle cramps
• Rhabdomyolysis
• Bone disorder
• Trismus

Skin and Subcutaneous Tissue Disorders 

• Rash
• Hyperhidrosis
• Periorbital oedema
• Face oedema
• Purpura
• Alopecia
• Cold sweat
• Dry skin
• Urticaria
• Pruritus
• Dermatitis
• Follicular rash
• Severe cutaneous adverse reactions (SCAR)
  - Stevens-Johnson syndrome
  - Epidermal necrolysis
• Angioedema
• Photosensitivity
• Bullous dermatitis
• Abnormal hair texture
• Abnormal skin odour

Immune, Blood and Lymphatic System Disorders 

• Neoplasm
• Abnormal bleeding
  - Gastrointestinal bleeding
• Lymphadenopathy
• Thrombocytopenia
• Leukopenia
• Hypersensitivity
• Seasonal allergy
• Anaphylactoid reaction
• Fever
• Peripheral oedema
• Altered platelet function

Sensory Disorders 

• Visual disturbance
• Mydriasis
• Scotoma
• Glaucoma
• Diplopia
• Photophobia
• Hyphaema
• Unequal pupils
• Abnormal vision
• Lacrimal disorder
• Maculopathy
• Paraesthesia
• Dysgeusia
• Hypoaesthesia
• Hyperaesthesia
• Sensory disturbance
• Otitis media
• Tinnitus
• Ear pain
• Tongue disorder
• Tongue ulceration
• Chills

Others

• Signs and symptoms associated with serotonin syndrome or neuroleptic malignant syndrome: In some cases associated with coadministration of serotonergic agents
  - Agitation
  - Confusion
  - Diaphoresis
  - Diarrhoea
  - Fever
  - Hypertension
  - Rigidity
  - Tachycardia
• Chest pain
• Hernia
• Injury
• Abnormal clinical laboratory results

• Monoamine oxidase inhibitors (MAOIs)
  - Irreversible MAOIs
  - Reversible, selective MAO-A inhibitors
  - Reversible, non-selective MAOIs
• Selegiline
• Moclobemide
• Linezolid
• Methylene blue
• Pimozide
• Central nervous system depressants
• Serotonergic agents
• Fenfluramine
• Rifampicin
• Fentanyl
• Serotonergic antidepressants
• Amphetamines
• Triptans
• Sumatriptan
• Opiates
• Buprenorphine
• Agents that prolong QTc interval
• Lithium
• Phenytoin
• CYP3A4 inducers
• Phenobarbital
• Carbamazepine
• Warfarin
• Cimetidine
• Agents acting on platelet function
• Non-steroidal anti-inflammatory drugs
• Acetylsalicylic acid
• Ticlopidine
• Agents that increase risk of bleeding
• Neuromuscular blockers
• Mivacurium
• Desipramine
• CYP2D6 substrates
• Class 1C antiarrhythmics 
• Propafenone
• Flecainide
• Tricyclic antidepressants
• Typical antipsychotics
• Potent CYP3A4 inhibitors
• Protease inhibitors
• Ketoconazole
• Itraconazole
• Posaconazole
• Voriconazole
• Clarithromycin
• Telithromycin
• Nefazodone
• Moderate CYP3A4 inhibitors
• Aprepitant
• Erythromycin
• Fluconazole
• Verapamil
• Diltiazem
• Strong CYP2C19 inhibitors
• Omeprazole
• Lansoprazole
• Pantoprazole
• Rabeprazole
• Fluoxetine
• Fluvoxamine
• Metamizole

Other interactions

• Urine immunoassay screening test (See additional prescribing points)
• Grapefruit juice
• St John's wort
• Alcohol

• Weight
• Height
• Body mass index (longitudinal monitoring)

Specific cases may require

• Serum sodium
• Growth (paediatric patients)

Additional observations

• Depression
• Clinical worsening
• Suicidality
• Psychosis
• Unusual changes in behaviour (particularly during the initial 1-2 months of therapy or during periods of dosage adjustments)
  - Anxiety
  - Agitation
  - Panic attacks
  - Insomnia
  - Irritability
  - Hostility
  - Impulsivity
  - Akathisia
  - Hypomania
  - Mania
  - Social functioning
• Signs and symptoms of serotonin syndrome
  - Mental status changes (e.g agitation, hallucinations, delirium, coma)
  - Autonomic instability (e.g tachycardia, labile BP, diaphoresis)
  - Neuromuscular changes (e.g tremor, rigidity, myoclonus)
  - Gastrointestinal symptoms (e.g nausea, vomiting, diarrhoea)
  - Seizures
• Signs and symptoms of neuroleptic malignant syndrome

Panic disorder

• Panic disorder is characterised by the occurrence of unexpected panic attacks and associated concern about having additional attacks, worry about the implications or consequences of the attacks, and /or a significant change in behaviour related to the attacks
• Panic disorder is characterised by recurrent unexpected panic attacks, i.e., a discrete period of intense fear or discomfort in which four (or more) of the following symptoms develop abruptly and reach a peak within 10 minutes: palpitations, pounding heart, or accelerated heart rate; sweating; trembling or shaking; sensations of shortness of breath or smothering; feeling of choking; chest pain or discomfort; nausea or abdominal distress; feeling dizzy, unsteady, light-headed, or faint; derealisation (feelings of unreality) or depersonalisation (being detached from oneself); fear of losing control; fear of dying; paraesthesias (numbness or tingling sensations); chills or hot flushes
• The effectiveness of sertraline in long-term use, (>12 weeks), has not been systematically evaluated. Therefore, the physician who elects to use sertraline for extended periods should periodically re-evaluate the long-term usefulness of the medicine for the individual patient

Interference with urine screening tests

• False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline
• This is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline therapy
• Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines

Uricosuric effect

• Sertraline is associated with a mean decrease in serum uric acid of approximately 7%. The clinical significance of this weak uricosuric effect is unknown

Bone fractures

• Epidemiological studies show an increased risk of bone fractures in patients receiving serotonin reuptake inhibitors (SRIs) including sertraline. The mechanism leading to this risk is not fully understood 

Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) uptake in vitro, which results in the potentiation of the effects of 5-HT in animals. It has only very weak effects on norepinephrine and dopamine neuronal reuptake. At clinical doses, sertraline blocks the uptake of serotonin into human platelets. It is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals. In controlled studies in normal volunteers, sertraline did not cause sedation and did not interfere with psychomotor performance. In accord with its selective inhibition of 5-HT uptake, sertraline does not enhance catecholaminergic activity. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. The chronic administration of sertraline in animals was associated with down-regulation of brain norepinephrine receptors as observed with other clinically effective antidepressants and antiobsessional agents.

Tablet 50mg

• Arrow Sertraline (Arrow)
• Arysert 50 (Zydus Healthcare SA)
• Austell Sertraline (Austell)
• Dyna Sertraline (Pharma Dynamics)
• Serdep (Cipla Medpro)
• Serlife (Ranbaxy)
• Sermax (Be-Tabs)
• Sertra (UpJohn) originator
• Sertraline Winthrop (Zentiva)
• Sertzol (Ranbaxy)
• Zolid (Novagen)
• Zoloft (UpJohn) originator
• Zosert (Ranbaxy)
• Zylin (Zydus Healthcare SA)

Tablet 100mg

• Arrow Sertraline (Arrow)
• Austell Sertraline (Austell)
• Dyna Sertraline (Pharma Dynamics)
• Serdep (Cipla Medpro)
• Serlife (Ranbaxy)
• Sermax (Be-Tabs)
• Sertzol (Ranbaxy)
• Zolid (Novagen)