Sertraline Flashcards
What are the FDA approved uses of sertraline?
Major depressive disorder
obsessive compulsive disorder
Panic disorder
Post traumatic stress disorder
Social phobia/anxiety
Premenstrual dysphoric disorder
What are the side effects of sertraline?
Gastrointestinal side effects:
- Constipation
- Diarrhoea
- Indegestion
- Nausea/vomiting
neurologic side effects
- dizziness
- Headache
- Somnolence
- Tremor
Reproductive side effects:
- Abnormal ejaculation
- Reduced Labido
What are some precautions to be wary of when taking sertraline ?
Angle-Closure glaucoma
SSRIs including sertraline may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Sertraline should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.
Sexual dysfunction
Selective serotonin reuptake inhibitors (SSRIs)/serotonin norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section 4.8). There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs/SNRI.
Grapefruit juice
The administration of sertraline with grapefruit juice is not recommended
Suicide/suicidal thoughts/suicide attempts or clinical worsening
Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS)
Switching from Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants or antiobsessional drugs
Abnormal bleeding/Haemorrhage
There have been reports of bleeding abnormalities with SSRIs including cutaneous bleeding (ecchymoses and purpura) and other haemorrhagic events such as gastrointestinal or gynaecological bleeding, including fatal haemorrhages. Caution is advised in patients taking SSRIs, particularly in concomitant use with drugs known to affect platelet function (e.g. anticoagulants, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs)) as well as in patients with a history of bleeding disorders (see section
Drugs where co-administration with sertraline is not recommended
CNS depressants and alcohol
The co-administration of sertraline 200 mg daily did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor performance in healthy subjects; however, the concomitant use of sertraline and alcohol is not recommended.
Other serotonergic drugs
See section 4.4.
Caution is also advised with fentanyl (used in general anaesthesia or in the treatment of chronic pain), other serotonergic drugs (including other serotonergic antidepressants, amphetamines, triptans), and with other opiate drugs.
Sertraline should be used cautiously when co-administered with buprenorphine/ opioids as the risk of serotonin syndrome, a potentially life-threatening condition, is increased (see section 4.4).
Special Precautions
Drugs that Prolong the QT Interval
The risk of QTc prolongation and/or ventricular arrhythmias (e.g. TdP) may be increased with concomitant use of other drugs which prolong the QTc interval (e.g. some antipsychotics and antibiotics) (see section 4.4).
Lithium
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.
Phenytoin
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.
Triptans
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 (see section 4.4).
Warfarin
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.
Other drug interactions, digoxin, atenolol, cimetidine
Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline had no effect on the beta-adrenergic blocking ability of atenolol. No interaction of sertraline 200 mg daily was observed with digoxin.
Drugs affecting platelet function
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 (see section 4.4).
Neuromuscular Blockers
SSRIs may reduce plasma cholinesterase activity resulting in a prolongation of the neuromuscular blocking action of mivacurium or other neuromuscular blockers.
Drugs Metabolized by Cytochrome P450 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.
Sertraline does not act as an inhibitor of CYP 3A4, CYP 2C9, CYP 2C19, and CYP 1A2 to a clinically significant degree. This has been confirmed by in-vivo interaction studies with CYP3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate diazepam, and CYP2C9 substrates tolbutamide, glibenclamide and phenytoin. In vitro studies indicate that sertraline has little or no potential to inhibit CYP 1A2.
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 (see section 4.4).
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 (see section 5.2). Interaction with strong inhibitors of CYP2C19, e.g. omeprazole, lansoprazole, pantoprazole, rabeprazole, fluoxetine, fluvoxamine cannot be excluded.
