Sertraline Oral Solution

Sertraline hydrochloride oral solution is indicated for the treatment of the following [See Clinical Studies (14)]:

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

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

The recommended initial dosage and maximum sertraline hydrochloride oral solution 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 sertraline hydrochloride oral solution, the recommended interval between dose changes is one week.

Dosage in Patients with PMDD

The recommended starting sertraline hydrochloride oral solution dosage in adult women with PMDD is 50 mg per day. Sertraline hydrochloride oral solution 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 Sertraline Hydrochloride Oral Solution

Prior to initiating treatment with sertraline hydrochloride oral solution or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania [See Warnings and Precautions (5.4)].

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 [See Dosage and Administration (2.1, 2.2)]. The use of sertraline hydrochloride oral solution in patients with moderate (Child Pugh scores 7 to 9) or severe hepatic impairment (Child Pugh scores 10 to 15) is not recommended [See Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].

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 sertraline hydrochloride oral solution. In addition, at least 14 days must elapse after stopping sertraline hydrochloride oral solution before starting an MAOI antidepressant [See Contraindications (4), Warnings and Precautions (5.2)].

Discontinuation of Treatment with Sertraline Hydrochloride Oral Solution

Adverse reactions may occur upon discontinuation of sertraline hydrochloride oral solution [See Warnings and Precautions (5.5)]. Gradually reduce the dosage rather than stopping sertraline hydrochloride oral solution abruptly whenever possible.

Preparation of Sertraline Hydrochloride Oral Solution

Sertraline hydrochloride oral solution must be diluted before use.

• Use the supplied calibrated dispensing syringe to measure the amount of sertraline hydrochloride oral solution needed
• Note: The supplied calibrated dispensing syringe 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.

Sertraline hydrochloride oral solution 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 [See Warnings and Precautions (5.2), Drug Interactions (7.1)].
• Taking pimozide [See Drug Interactions (7.1)].
• With known hypersensitivity to sertraline (e.g., anaphylaxis, angioedema) [See Adverse Reactions (6.1, 6.2)].

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

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

Suicidal Thoughts and Behaviors in Pediatric and Young Adult Patients

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant classes) that included approximately 77,000 adult patients and over 4,400 pediatric patients, the incidence of suicidal thoughts and behaviors in pediatric and young adult patients was greater in antidepressant-treated patients than in placebo-treated patients. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 2.

No suicides occurred in any of the pediatric studies. There were suicides in the adult studies, but the number was not sufficient to reach any conclusion about antidepressant drug effect on suicide.

Table 2: Risk Differences of the Number of Cases of Suicidal Thoughts or Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients

It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adult patients extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression.

Monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. Consider changing the therapeutic regimen, including possibly discontinuing sertraline hydrochloride, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

Serotonin Syndrome

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and SSRIs, including sertraline hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that impair metabolism of serotonin, i.e., MAOIs [See Contraindications (4), Drug Interactions (7.1)]. Serotonin syndrome can also occur when these drugs are used alone.

Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

The concomitant use of sertraline hydrochloride with MAOIs is contraindicated. In addition, do not initiate sertraline hydrochloride in a patient being treated with MAOIs such as linezolid or intravenous methylene blue. No reports involved the administration of methylene blue by other routes (such as oral tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or intravenous methylene blue in a patient taking sertraline hydrochloride, discontinue sertraline hydrochloride before initiating treatment with the MAOI [See Contraindications (4), Drug Interactions (7.1)].

Monitor all patients taking sertraline hydrochloride for the emergence of serotonin syndrome. Discontinue treatment with sertraline hydrochloride and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of sertraline hydrochloride with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.

Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including sertraline hydrochloride, increase the risk of bleeding events. Concomitant use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), other antiplatelet drugs, warfarin, and other anticoagulants may add to this risk. Case reports and epidemiological studies (case-control and cohort design) have demonstrated an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to drugs that interfere with serotonin reuptake have ranged from ecchymosis, hematoma, epistaxis, and petechiae to life-threatening hemorrhages.

Inform patients of the increased risk of bleeding associated with the concomitant use of sertraline hydrochloride and antiplatelet agents or anticoagulants. For patients taking warfarin, carefully monitor the international normalized ratio.

Activation of Mania or Hypomania

In patients with bipolar disorder, treating a depressive episode with sertraline hydrochloride or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials, patients with bipolar disorder were generally excluded; however, symptoms of mania or hypomania were reported in 0.4% of patients treated with sertraline hydrochloride. Prior to initiating treatment with sertraline hydrochloride, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.

Discontinuation Syndrome

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesia, such as electric shock sensations), tremor, anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. A gradual reduction in dosage rather than abrupt cessation is recommended whenever possible [See Dosage and Administration (2.6)].

Seizures

Sertraline hydrochloride has not been systematically evaluated in patients with seizure disorders. Patients with a history of seizures were excluded from clinical studies. Sertraline hydrochloride should be prescribed with caution in patients with a seizure disorder.

Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs including sertraline hydrochloride may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy. Avoid use of antidepressants, including sertraline hydrochloride, in patients with untreated anatomically narrow angles.

Hyponatremia

Hyponatremia may occur as a result of treatment with SNRIs and SSRIs, including sertraline hydrochloride. Cases with serum sodium lower than 110 mmol/L have been reported. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH).

In patients with symptomatic hyponatremia, discontinue sertraline hydrochloride and institute appropriate medical intervention. Elderly patients, patients taking diuretics, and those who are volume-depleted may be at greater risk of developing hyponatremia with SSRIs and SNRIs [See Use in Specific Populations (8.5)].

False-Positive Effects on Screening Tests for Benzodiazepines

False-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline hydrochloride. This finding is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline hydrochloride. Confirmatory tests, such as gas chromatography/mass spectrometry, will help distinguish sertraline hydrochloride from benzodiazepines [See Drug Interactions (7.3)].

Sertraline hydrochloride oral solution USP 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 molecular formula C17H17NCl2•HCl is represented by the following structural formula:

Sertraline hydrochloride USP is a white crystalline powder that is slightly soluble in water and isopropyl alcohol, and sparingly soluble in ethanol.

Sertraline hydrochloride oral solution USP is available in a multidose 60 mL bottle. Each mL of solution contains sertraline hydrochloride USP equivalent to 20 mg of sertraline. The solution contains the following inactive ingredients: alcohol (12%), natural peppermint flavor, propylene glycol and purified water. The oral solution must be diluted prior to administration [See Dosage and Administration (2.7)].

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Suicidal Thoughts and Behaviors

Advise patients and caregivers to look for the emergence of suicidality, especially early during treatment and when the dosage is adjusted up or down, and instruct them to report such symptoms to the healthcare provider [See Boxed Warning and Warnings and Precautions (5.1)].

Important Administration Instructions for Oral Solution

For patients prescribed sertraline hydrochloride oral solution, inform them that:

•  Sertraline hydrochloride oral solution must be diluted before use. Do not mix in advance.
•  Use the dispensing syringe to remove the required amount of sertraline hydrochloride oral solution and mix with 4 ounces (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. Do not mix sertraline hydrochloride oral solution with anything other than the liquids listed.
•  Take the dose immediately after mixing. At times, a slight haze may appear after mixing; this is normal.

Disulfiram Contraindication for Sertraline Hydrochloride Oral Solution

Inform patients not to take disulfiram when taking sertraline hydrochloride oral solution. Concomitant use is contraindicated due the alcohol content of the oral solution [See Contraindication (4)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of sertraline hydrochloride with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort, and with drugs that impair metabolism of serotonin (in particular, MAOIs, both those intended to treat psychiatric disorders and also others, such as linezolid). Patients should contact their health care provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome [See Warnings and Precautions (5.2), Drug Interactions (7.1)].

Increased Risk of Bleeding

Inform patients about the concomitant use of sertraline hydrochloride with aspirin, NSAIDs, other antiplatelet drugs, warfarin, or other anticoagulants because the combined use has been associated with an increased risk of bleeding. Advise patients to inform their health care providers if they are taking or planning to take any prescription or over-the­-counter medications that increase the risk of bleeding [See Warnings and Precautions (5.3)].

Activation of Mania/Hypomania

Advise patients and their caregivers to observe for signs of activation of mania/hypomania and instruct them to report such symptoms to the healthcare provider [See Warnings and Precautions (5.4)].

Discontinuation Syndrome

Advise patients not to abruptly discontinue sertraline hydrochloride and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when sertraline hydrochloride is discontinued [See Warnings and Precautions (5.5)].

Allergic Reactions

Advise patients to notify their healthcare provider if they develop an allergic reaction such as rash, hives, swelling, or difficulty breathing [See Adverse Reactions (6.2)].

Pregnancy

Inform pregnant women that sertraline hydrochloride may cause withdrawal symptoms in the newborn or persistent pulmonary hypertension of the newborn (PPHN) [See Use in Specific Populations (8.1)].

Medication Guides available at www.northstarrxllc.com/products or call 1-800-206-7821.

PATIENT INSTRUCTIONS

USING YOUR SERTRALINE HYDROCHLORIDE DISPENSING SYRINGE AND BOTTLE

Use this product as indicated below, unless directed otherwise by your Physician.

IMPORTANT: Please read these instructions before using Sertraline hydrochloride oral solution.

1.    Push the plastic screw-cap on the bottle down while turning it counter clockwise. Remove the unscrewed cap (see Figure 1).
2.    Hold the pull tab of the seal and remove (see Figure 2).
3.    Insert the adaptor into the mouth of the bottle and push down until it is completely seated in the neck of the bottle (leave adaptor inserted in the
       bottle after use) (see Figure 3).

4.    Remove the secure tip from orifice of the dispensing syringe (see Figure 4).

5.    Insert the dispensing syringe into the adaptor fixed to the bottle neck (see Figure 5).

6.    After inserting the syringe into the adaptor, make the bottle upside down and pull the plunger up to the level (see markings on side) that equals 
       the dosage prescribed by your physician (see Figure 6).

7.    Turn the bottle to original position and remove the dispensing syringe from the bottle (see Figure 7) and then empty the entire contents of the 
       dispensing syringe and mix with 4 oz (1/2 cup) of water, ginger ale, lemon/lime soda, lemonade or orange juice ONLY. Do not mix sertraline 
       hydrochloride oral solution with anything other than the liquids listed. The dose should be taken immediately after mixing. Do not mix in advance. 
       At times, a slight haze may appear after mixing; this is normal.

8.    Replace the plastic cap on the bottle by screwing it clockwise; rinse the empty dispensing syringe with water. And close the orifice of the 
       dispensing syringe by fixing the secure tip (see Figure 8).

Rx only                         
NDC 16714-601-02
Sertraline Hydrochloride
Oral Solution USP
20 mg/mL*
Contains 12% alcohol.
DILUTE BEFORE USE
PHARMACIST: PLEASE DISPENSE WITH
MEDICATION GUIDE PROVIDED SEPARATELY
60 mL
Northstar Rx LLC

Side effects that you should report to your doctor or health care professional as soon as possible:

• allergic reactions like skin rash, itching or hives, swelling of the face, lips, or tongue
• black or bloody stools, blood in the urine or vomit
• fast, irregular heartbeat
• feeling faint or lightheaded, falls
• hallucination, loss of contact with reality
• seizures
• suicidal thoughts or other mood changes
• unusual bleeding or bruising
• unusually weak or tired
• vomiting

Side effects that usually do not require medical attention (report to your doctor or health care professional if they continue or are bothersome):

• change in appetite
• change in sex drive or performance
• diarrhea
• indigestion, nausea
• increased sweating
• tremors