Chemical formula: C₁₇H₁₇Cl₂N Molecular mass: 306.23 g/mol PubChem compound: 68617
Sertraline interacts in the following cases:
The risk of ventricular arrhythmias (e.g. TdP) may be increased with concomitant use of other drugs which inducing Torsade de Pointes.
The risk of QTc prolongation may be increased with concomitant use of other drugs which prolong the QTc interval (e.g. some antipsychotics and antibiotics).
Due to the risk of serotonin syndrome, the combination of sertraline with a reversible and selective MAOI, such as moclobemide, should not be given. Following treatment with a reversible MAO-inhibitor, a shorter withdrawal period than 14 days may be used before initiation of sertraline treatment. It is recommended that sertraline should be discontinued for at least 7 days before starting treatment with a reversible MAOI.
Sertraline may act as a mild-moderate inhibitor of CYP 2D6. Chronic dosing with sertraline 50 mg daily showed moderate elevation (mean 23%-37%) of steady-state desipramine plasma levels (a marker of CYP 2D6 isozyme activity). Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index like class 1C antiarrhythmics such as propafenone and flecainide, TCAs and typical antipsychotics, especially at higher sertraline dose levels.
The co-administration of sertraline 200 mg daily did not potentiate the effects of alcohol on cognitive and psychomotor performance in healthy subjects; however, the concomitant use of sertraline and alcohol is not recommended.
Intake of three glasses of grapefruit juice daily increased the sertraline plasma levels by approximately 100% in a cross-over study in eight Japanese healthy subjects. Therefore, the intake of grapefruit juice should be avoided during treatment with sertraline.
Intake of three glasses of grapefruit juice daily increased the sertraline plasma levels by approximately 100% in a cross-over study in eight Japanese healthy subjects. Therefore, the intake of grapefruit juice should be avoided during treatment with sertraline.
Based on the interaction study with grapefruit juice, it cannot be excluded that the concomitant administration of sertraline and potent CYP3A4 inhibitors, e.g. protease inhibitors, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin and nefazodone, would result in even larger increases in exposure of sertraline. This also concerns moderate CYP3A4 inhibitors, e.g. aprepitant, erythromycin, fluconazole, verapamil and diltiazem. The intake of potent CYP3A4 inhibitors should be avoided during treatment with sertraline.
Sertraline plasma levels are enhanced by about 50% in poor metabolizers of CYP2C19 compared to rapid metabolizers. Interaction with strong inhibitors of CYP2C19, e.g. omeprazole, lansoprazole, pantoprazole, rabeprazole, fluoxetine, fluvoxamine cannot be excluded.
Caution is also advised with fentanyl (used in general anaesthesia or in the treatment of chronic pain) and with other opiate drugs.
There have been rare post-marketing reports describing patients with weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following the use of sertraline and sumatriptan. Symptoms of serotonergic syndrome may also occur with other products of the same class (triptans). If concomitant treatment with sertraline and triptans is clinically warranted, appropriate observation of the patient is advised.
Caution is also advised in co-administration of sertraline with other serotonergic drugs (including other serotonergic antidepressants, amphetamines, triptans).
Sertraline is extensively metabolised by the liver. A multiple dose pharmacokinetic study in subjects with mild, stable cirrhosis demonstrated a prolonged elimination half life and approximately three-fold greater AUC and Cmax in comparison to normal subjects. There were no significant differences in plasma protein binding observed between the two groups. The use of sertraline in patients with hepatic disease must be approached with caution. If sertraline is administered to patients with hepatic impairment, a lower or less frequent dose should be considered. Sertraline should not be used in patients with severe hepatic impairment.
The risk of bleeding may be increased when medicines acting on platelet function (e.g. NSAIDs, acetylsalicylic acid and ticlopidine) or other medicines that might increase bleeding risk are concomitantly administered with SSRIs, including sertraline.
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.
Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown.
The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients treated with sertraline.
In a placebo-controlled trial in normal volunteers, the co-administration of sertraline with lithium did not significantly alter lithium pharmacokinetics, but did result in an increase in tremor relative to placebo, indicating a possible pharmacodynamic interaction. When co-administering sertraline with lithium, patients should be appropriately monitored.
SSRIs may reduce plasma cholinesterase activity resulting in a prolongation of the neuromuscular blocking action of mivacurium or other neuromuscular blockers.
A placebo-controlled trial in normal volunteers suggests that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonetheless, as some case reports have emerged of high phenytoin exposure in patients using sertraline, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline therapy, with appropriate adjustments to the phenytoin dose. In addition, co-administration of phenytoin may cause a reduction of sertraline plasma levels. It cannot be excluded that other CYP3A4 inducers, e.g. phenobarbital, carbamazepine, St. John’s Wort, rifampicin may cause a reduction of sertraline plasma levels.
Co-administration of sertraline 200 mg daily with warfarin resulted in a small but statistically significant increase in prothrombin time, which may in some rare cases unbalance the INR value. Accordingly, prothrombin time should be carefully monitored when sertraline therapy is initiated or stopped.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Sertraline should be used with caution in patients with a history of mania/hypomania. Close surveillance by the physician is required. Sertraline should be discontinued in any patient entering a manic phase.
Sertraline should be used with caution in patients with angle-closure glaucoma or history of glaucoma.
Psychotic symptoms might become aggravated in schizophrenic patients.
In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Sertraline plasma levels are enhanced by about 50% in poor metabolizers of CYP2C19 compared to rapid metabolizers.
Seizures may occur with sertraline therapy. Sertraline should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Sertraline should be discontinued in any patient who develops seizures.
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, particular 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.
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 nursed by mothers using sertraline have been reported, but a risk cannot be excluded. Use in nursing mothers is not recommended unless, in the judgment of the physician, the benefit outweighs the risk.
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.
Clinical pharmacology studies have shown that sertraline has no effect on psychomotor performance. However, as psychotropic drugs may impair the mental or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery, the patient should be cautioned accordingly.
Nausea is the most common undesirable effect. In the treatment of social anxiety disorder, sexual dysfunction (ejaculation failure) in men occurred in 14% for sertraline vs 0% in placebo. These undesirable effects are dose dependent and are often transient in nature with continued treatment.
The undesirable effects profile commonly observed in double-blind, placebo-controlled studies in patients with OCD, panic disorder, PTSD and social anxiety disorder was similar to that observed in clinical trials in patients with depression.
The following list displays adverse reactions observed from postmarketing experience (frequency not known) and placebo-controlled clinical trials (comprising a total of 2542 patients on sertraline and 2145 on placebo) in depression, OCD, panic disorder, PTSD and social anxiety disorder.
Some adverse drug reactions listed below may decrease in intensity and frequency with continued treatment and do not generally lead to cessation of therapy.
Frequency of adverse reactions observed from placebo-controlled clinical trials in depression, OCD, panic disorder, PTSD and social anxiety disorder. Pooled analysis and postmarketing experience (frequency not known).
Common: upper respiratory tract infection, pharyngitis, rhinitis
Uncommon: gastroenteritis, otitis media
Rare: diverticulitis§
Uncommon: neoplasm
Rare: lymphadenopathy, thrombocytopenia∗§, leukopenia∗§
Uncommon: hypersensitivity∗, seasonal allergy∗
Rare: anaphylactoid reaction∗
Uncommon: hypothyroidism∗
Rare: hyperprolactinaemia∗§, inappropriate antidiuretic hormone secretion∗§
Common: decreased appetite, increased appetite∗
Rare: hypercholesterolaemia, diabetes mellitus∗, hypoglycaemia∗, hyperglycaemia∗§, hyponatraemia∗§
Very Common: insomnia
Common: anxiety*, depression*, agitation*, libido decreased*, nervousness, depersonalisation, nightmare, bruxism*
Uncommon: suicidal ideation/behaviour, psychotic disorder∗, thinking abnormal, apathy, hallucination*, aggression*, euphoric mood*, paranoia
Rare: conversion disorder∗§, paroniria∗§, drug dependence, sleep walking, premature ejaculation
Very Common: dizziness, headache*, somnolence
Common: tremor, movement disorders (including extrapyramidal symptoms such as hyperkinesia, hypertonia, dystonia, teeth grinding or gait abnormalities), paraesthesia*, hypertonia*, disturbance in attention, dysgeusia
Uncommon: amnesia, hypoaesthesia*, muscle contractions involuntary*, syncope*, hyperkinesia*, migraine*, convulsion*, dizziness postural, coordination abnormal, speech disorder
Rare: coma*, akathisia, dyskinesia, hyperaesthesia, cerebrovascular spasm (including reversible cerebral vasoconstriction syndrome and Call-Fleming syndrome)∗§, psychomotor restlessness∗§, sensory disturbance, choreoathetosis§, also reported were signs and symptoms associated with serotonin syndrome∗ or neuroleptic malignant syndrome: In some cases associated with concomitant use of serotonergic drugs that included agitation, confusion, diaphoresis, diarrhoea, fever, hypertension, rigidity and tachycardia§
Common: visual disturbance∗
Uncommon: mydriasis∗
Rare: scotoma, glaucoma, diplopia, photophobia, hyphaema∗§, pupils unequal∗§, vision abnormal§, lacrimal disorder
Common: tinnitus∗
Uncommon: ear pain
Common: palpitations∗
Uncommon: tachycardia∗,cardiac disorder
Rare: myocardial infarction∗§, Torsade de Pointes∗§, bradycardia, QTc prolongation∗
Common: hot flush∗
Uncommon: abnormal bleeding (such as gastrointestinal bleeding)∗, hypertension∗, flushing, haematuria∗
Rare: eripheral ischaemia
Common: yawning∗
Uncommon: dyspnoea, epistaxis∗, bronchospasm*
Rare: hyperventilation, interstitial lung disease∗§, laryngospasm, dysphonia, stridor∗§, hypoventilation, hiccups
Very Common: nausea, diarrhoea, dry mouth
Common: dyspepsia, constipation*, abdominal pain*, vomiting*, flatulence
Uncommon: melaena, tooth disorder, oesophagitis, glossitis, haemorrhoids, salivary hypersecretion, dysphagia, eructation, tongue disorder
Rare: mouth ulceration, pancreatitis∗§, haematochezia, tongue ulceration, stomatitis
Rare: hepatic function abnormal, serious liver events (including hepatitis, jaundice and hepatic failure)
Common: hyperhidrosis, rash*
Uncommon: periorbital oedema*, urticaria*, alopecia*, pruritus*, purpura*, dermatitis, dry skin, face oedema, cold sweat
Rare: rare reports of severe cutaneous adverse reactions (SCAR): e.g. Stevens-Johnson syndrome∗ and epidermal necrolysis∗§, skin reaction∗§, photosensitivity§, angioedema, hair texture abnormal, skin odour abnormal, dermatitis bullous, rash follicular
Common: back pain, arthralgia∗, myalgia
Uncommon: osteoarthritis, muscle twitching, muscle cramps∗, muscular weakness
Rare: rhabdomyolysis∗§, bone disorder
Frequency Not Known: trismus*
Uncommon: pollakiuria, micturition disorder, urinary retention, urinary incontinence*, polyuria, nocturia
Rare: urinary hesitation*, oliguria
Very Common: ejaculation failure
Common: menstruation irregular∗, erectile dysfunction
Uncommon: sexual dysfunction, menorrhagia, vaginal haemorrhage, female sexual dysfunction
Rare: galactorrhoea*, atrophic vulvovaginitis, genital discharge, balanoposthitis∗§, gynaecomastia∗, priapism*
Very Common: fatigue*
Common: malaise*, chest pain*, asthenia∗, pyrexia∗
Uncommon: oedema peripheral*, chills, gait disturbance∗, thirst
Rare: hernia, drug tolerance decreased
Common: weight increased∗
Uncommon: alanine aminotransferase increased*, aspartate aminotransferase increased*, weight decreased*
Rare: blood cholesterol increased∗, abnormal clinical laboratory results, semen abnormal, altered platelet function∗§
Common: injury
Rare: vasodilation procedure
=∗== ADR identified post-marketing
§ ADR frequency represented by the estimated upper limit of the 95% confidence interval using “The Rule of 3”.
Discontinuation of sertraline (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported. Generally these events are mild to moderate and are self-limiting; however, in some patients they may be severe and/or prolonged. It is therefore advised that when sertraline treatment is no longer required, gradual discontinuation by dose tapering should be carried out.
SSRIs or SNRIs including sertraline have been associated with cases of clinically significant hyponatraemia in elderly patients, who may be at greater risk for this adverse event.
In over 600 paediatric patients treated with sertraline, the overall profile of adverse reactions was generally similar to that seen in adult studies. The following adverse reactions were reported from controlled trials (n=281 patients treated with sertraline):
Very common (≥1/10): Headache (22%), insomnia (21%), diarrhoea (11%) and nausea (15%).
Common (≥1/100 to <1/10): Chest pain, mania, pyrexia, vomiting, anorexia, affect lability, aggression, agitation, nervousness, disturbance in attention, dizziness, hyperkinesia, migraine, somnolence, tremor, visual disturbance, dry mouth, dyspepsia, nightmare, fatigue, urinary incontinence, rash, acne, epistaxis, flatulence.
Uncommon (≥1/1000 to <1/100): ECG QT prolonged, suicide attempt, convulsion, extrapyramidal disorder, paraesthesia, depression, hallucination, purpura, hyperventilation, anaemia, hepatic function abnormal, alanine aminotransferase increased, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, haematuria, rash pustular, rhinitis, injury, weight decreased, muscle twitching, abnormal dreams, apathy, albuminuria, pollakiuria, polyuria, breast pain, menstrual disorder, alopecia, dermatitis, skin disorder, skin odour abnormal, urticaria, bruxism, flushing.
Frequency not known: enuresis
Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.
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