ZOLOFT (Sertraline hydrochloride, USP)

ZOLOFT (Sertraline hydrochloride, USP)

ZOLOFT contains sertraline hydrochloride, an SSRI. Sertraline hydrochloride has a molecular weight of 342.7 and has the following chemical name: (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride. The empirical formula C17H17NCl2●HCl

INDICATIONS AND USAGE

ZOLOFT is indicated for the treatment of the following:

  • Major depressive disorder (MDD)
  • Obsessive-compulsive disorder (OCD)
  • Panic disorder (PD)
  • Posttraumatic stress disorder (PTSD)
  • Social anxiety disorder (SAD)
  • Premenstrual dysphoric disorder (PMDD)

Mechanism of Action

Sertraline potentiates serotonergic activity in the central nervous system through inhibition of neuronal reuptake of serotonin (5-HT).

Dosage and administration

Dosage in Patients with MDD, OCD, PD, PTSD, and SAD

The recommended initial dosage and maximum ZOLOFT dosage in patients with MDD, OCD, PD, PTSD, and SAD are displayed in Table 1 below. A dosage of 25 mg or 50 mg per day is the initial therapeutic dosage.

For adults and pediatric patients, subsequent dosages may be increased in case of an inadequate response in 25 to 50 mg per day increments once a week, depending on tolerability, up to a maximum of 200 mg per day. Given the 24-hour elimination half-life of ZOLOFT, the recommended interval between dose changes is one week.

Table 1: Recommended Daily Dosage of ZOLOFT in Patients with MDD, OCD, PD, PTSD, and SAD
IndicationStarting DoseTherapeutic Range
Adults
MDD50 mg50-200 mg
OCD50 mg50-200 mg
PD, PTSD, SAD25 mg50-200 mg
Pediatric Patients
OCD (ages 6-12 years old)25 mg50-200 mg
OCD (ages 13-17 years old)50 mg50-200 mg

Dosage in Patients with PMDD

The recommended starting ZOLOFT dosage in adult women with PMDD is 50 mg per day. ZOLOFT may be administered either continuously (every day throughout the menstrual cycle) or intermittently (only during the luteal phase of the menstrual cycle, i.e., starting the daily dosage 14 days prior to the anticipated onset of menstruation and continuing through the onset of menses). Intermittent dosing would be repeated with each new cycle.

  • When dosing continuously, patients not responding to a 50 mg dosage may benefit from dosage increases at 50 mg increments per menstrual cycle up to 150 mg per day.
  • When dosing intermittently, patients not responding to a 50 mg dosage may benefit from increasing the dosage up to a maximum of 100 mg per day during the next menstrual cycle (and subsequent cycles) as follows: 50 mg per day during the first 3 days of dosing followed by 100 mg per day during the remaining days in the dosing cycle.

Screen for Bipolar Disorder Prior to Starting ZOLOFT: Prior to initiating treatment with ZOLOFT or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania.

Dosage Modifications in Patients with Hepatic Impairment: Both the recommended starting dosage and therapeutic range in patients with mild hepatic impairment (Child Pugh scores 5 or 6) are half the recommended daily dosage. The use of ZOLOFT in patients with moderate (Child Pugh scores 7 to 9) or severe hepatic impairment (Child Pugh scores 10-15) is not recommended.

Switching Patients to or from a Monoamine Oxidase Inhibitor Antidepressant: At least 14 days must elapse between discontinuation of a monoamine oxidase inhibitor (MAOI) antidepressant and initiation of ZOLOFT. In addition, at least 14 days must elapse after stopping ZOLOFT before starting an MAOI antidepressant.

Discontinuation of Treatment with ZOLOFT: Adverse reactions may occur upon discontinuation of ZOLOFT. Gradually reduce the dosage rather than stopping ZOLOFT abruptly whenever possible.

Preparation of ZOLOFT Oral Solution

ZOLOFT oral solution must be diluted before use.

  • Use the supplied calibrated dropper to measure the amount of ZOLOFT oral solution needed
  • Note: The supplied calibrated dropper has 25 mg and 50 mg graduation marks only
  • Mix with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. After mixing, a slight haze may appear, which is normal.

Instruct patients or caregivers to immediately take the dose after mixing.

CONTRAINDICATIONS

ZOLOFT is contraindicated in patients:

  • Taking, or within 14 days of stopping, MAOIs, (including the MAOIs linezolid and intravenous methylene blue) because of an increased risk of serotonin syndrome.
  • Taking pimozide.
  • With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema).

In addition to the contraindications for all ZOLOFT formulations listed above, ZOLOFT oral solution is contraindicated in patients:

  • Taking disulfiram. ZOLOFT oral solution contains alcohol, and concomitant use of ZOLOFT and disulfiram may result in a disulfiram-alcohol reaction.

Warnings and precautions

  • Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI, triptans), but also when taken alone. If it occurs, discontinue ZOLOFT and initiate supportive treatment.
  • Increased Risk of Bleeding: Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may increase this risk.
  • Activation of Mania/Hypomania: Screen patients for bipolar disorder.
  • Seizures: Use with caution in patients with seizure disorders.
  • Angle Closure Glaucoma: Avoid use of antidepressants, including
  • ZOLOFT, in patients with untreated anatomically narrow angles. 
  • QTc Prolongation: ZOLOFT should be used with caution in patients with risk factors for QTc prolongation.
  • Sexual Dysfunction: ZOLOFT may cause symptoms of sexual dysfunction.
  • Antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients
  • Closely monitor for clinical worsening and emergence of suicidal thoughts and behaviors

ADVERSE REACTIONS

Most common adverse reactions (>5% and twice placebo) in pooled placebo-controlled MDD, OCD, PD, PTSD, SAD and PMDD clinical trials were nausea, diarrhea/loose stool, tremor, dyspepsia, decreased appetite, hyperhidrosis, ejaculation failure, and decreased libido.

DRUG INTERACTIONS

Monoamine Oxidase Inhibitors (MAOIs)
Clinical Impact:The concomitant use of SSRIs including ZOLOFT and MAOIs increases the risk of serotonin syndrome.
Intervention:ZOLOFT is contraindicated in patients taking MAOIs, including MAOIs such as linezolid or intravenous methylene blue.
Examples:selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue
Pimozide
Clinical Impact:Increased plasma concentrations of pimozide, a drug with a narrow therapeutic index, may increase the risk of QTc prolongation and ventricular arrhythmias.
Intervention:Concomitant use of pimozide and ZOLOFT is contraindicated.
Other Serotonergic Drugs
Clinical Impact:The concomitant use of serotonergic drugs with ZOLOFT increases the risk of serotonin syndrome.
Intervention:Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of ZOLOFT and/or concomitant serotonergic drugs.
Examples:other SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort
Drugs that Interfere with Hemostasis (antiplatelet agents and anticoagulants)
Clinical Impact:The concurrent use of an antiplatelet agent or anticoagulant with ZOLOFT may potentiate the risk of bleeding.
Intervention:Inform patients of the increased risk of bleeding associated with the concomitant use of ZOLOFT and antiplatelet agents and anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.
Examples:aspirin, clopidogrel, heparin, warfarin
Drugs Highly Bound to Plasma Protein
Clinical Impact:ZOLOFT is highly bound to plasma protein. The concomitant use of ZOLOFT with another drug that is highly bound to plasma protein may increase free concentrations of ZOLOFT or other tightly-bound drugs in plasma.
Intervention:Monitor for adverse reactions and reduce dosage of ZOLOFT or other protein-bound drugs as warranted.
Examples:warfarin
Drugs Metabolized by CYP2D6
Clinical Impact:ZOLOFT is a CYP2D6 inhibitor. The concomitant use of ZOLOFT with a CYP2D6 substrate may increase the exposure of the CYP2D6 substrate.
Intervention:Decrease the dosage of a CYP2D6 substrate if needed with concomitant ZOLOFT use. Conversely, an increase in dosage of a CYP2D6 substrate may be needed if ZOLOFT is discontinued.
Examples:propafenone, flecainide, atomoxetine, desipramine, dextromethorphan, metoprolol, nebivolol, perphenazine, thoridazine, tolterodine, venlafaxine
Phenytoin
Clinical Impact:Phenytoin is a narrow therapeutic index drug. ZOLOFT may increase phenytoin concentrations.
Intervention:Monitor phenytoin levels when initiating or titrating ZOLOFT. Reduce phenytoin dosage if needed.
Examples:phenytoin, fosphenytoin
Drugs that Prolong the QTc Interval
Clinical Impact:The risk of QTc prolongation and/or ventricular arrhythmias (e.g., TdP) is increased with concomitant use of other drugs which prolong the QTc interval.
Intervention:Pimozide is contraindicated for use with sertraline. Avoid the concomitant use of drugs known to prolong the QTc interval.
Examples:Specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus).

USE IN SPECIFIC POPULATIONS

Pregnancy: Overall, available published epidemiologic studies of pregnant women exposed to sertraline in the first trimester suggest no difference in major birth defect risk compared to the background rate for major birth defects in comparator populations. Some studies have reported increases for specific major birth defects; however, these study results are inconclusive. There are clinical considerations regarding neonates exposed to SSRIs and SNRIs, including ZOLOFT, during the third trimester of pregnancy.

Disease-associated maternal and/or embryo/fetal risk

A prospective longitudinal study followed 201 pregnant women with a history of major depression who were euthymic taking antidepressants at the beginning of pregnancy. The women who discontinued antidepressants during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressants. Consider the risks of untreated depression when discontinuing or changing treatment with antidepressant medication during pregnancy and postpartum.

Fetal/Neonatal adverse reactions

Exposure to SSRIs and SNRIs, including ZOLOFT in late pregnancy may lead to an increased risk for neonatal complications requiring prolonged hospitalization, respiratory support, and tube feeding, and/or persistent pulmonary hypertension of the newborn (PPHN).

When treating a pregnant woman with ZOLOFT during the third trimester, carefully consider both the potential risks and benefits of treatment. Monitor neonates who were exposed to ZOLOFT in the third trimester of pregnancy for PPHN and drug discontinuation syndrome.

Lactation: Available data from published literature demonstrate low levels of sertraline and its metabolites in human milk. There are no data on the effects of sertraline on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ZOLOFT and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Pediatric Use: The safety and efficacy of ZOLOFT have been established in the treatment of OCD in pediatric patients aged 6 to 17.

Hepatic Impairment: The recommended dosage in patients with mild hepatic impairment (Child-Pugh score 5 or 6) is half the recommended dosage due to increased exposure in this patient population. The use of ZOLOFT in patients with moderate (Child-Pugh score 7 to 10) or severe hepatic impairment (Child-Pugh score 10-15) is not recommended, because ZOLOFT is extensively metabolized, and the effects of ZOLOFT in patients with moderate and severe hepatic impairment have not been studied.

Renal Impairment: No dose adjustment is needed in patients with mild to severe renal impairment. Sertraline exposure does not appear to be affected by renal impairment.

OVERDOSAGE

The following have been reported with sertraline tablet overdosage:

  • Seizures, which may be delayed, and altered mental status including coma.
  • Cardiovascular toxicity, which may be delayed, including QRS and QTc interval prolongation. Hypertension most commonly seen, but rarely can see hypotension alone or with co-ingestants including alcohol.
  • Serotonin syndrome (patients with a multiple drug overdosage with other proserotonergic drugs may have a higher risk).

Gastrointestinal decontamination with activated charcoal should be considered in patients who present early after a sertraline overdose.

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