Sertraline

Sertraline may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• nausea
• diarrhea
• constipation
• vomiting
• difficulty falling asleep or staying asleep
• dry mouth
• heartburn
• loss of appetite
• weight changes
• dizziness
• excessive tiredness
• headache
• nervousness
• uncontrollable shaking of a part of the body
• changes in sex drive or ability
• excessive sweating

Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING or SPECIAL PRECAUTIONS section, call your doctor immediately:

• seizures
• abnormal bleeding or bruising
• agitation, hallucinations, fever, sweating, confusion, fast heartbeat, shivering, severe muscle stiffness or twitching, loss of coordination, nausea, vomiting, or diarrhea
• rash
• hives
• swelling
• difficulty breathing

Sertraline may decrease appetite and cause weight loss in children. Your child's doctor will watch his or her growth carefully. Talk to your child's doctor if you have concerns about your child's growth or weight while he or she is taking this medication. Talk to your child's doctor about the risks of giving sertraline to your child.

Sertraline may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Keep all appointments with your doctor.

Before having any laboratory test, tell your doctor and the laboratory personnel that you are taking sertraline.

Do not let anyone else take your medication. Ask your pharmacist any questions you have about refilling your prescription.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

Sertraline belongs to a class of drugs called selective serotonin reuptake inhibitors (SSRIs). Other drugs in this class are:

• fluoxetine (Prozac, Sarafem)
• paroxetine (Brisdelle, Paxil, Paxil CR, Pexeva)
• citalopram (Celexa)
• fluvoxamine (Luvox CR)

Pregnancy

Pregnancy category: C

Use late in the third trimester associated with complications in newborns and may require prolonged hospitalization, respiratory support, and tube feeding

Persistent pulmonary hypertension of the newborn

• Potential risk of persistent pulmonary hypertension of the newborn (PPHN) when used during pregnancy
• Initial public health advisory in 2006 was based on a single published study; since then, there have been conflicting findings from new studies, making it unclear whether use of SSRIs during pregnancy can cause PPHN
• FDA has reviewed the additional new study results and has concluded that, given the conflicting results from different studies, it is premature to reach any conclusion about a possible link between SSRI use in pregnancy and PPHN
• FDA recommendation: FDA advises healthcare professionals not to alter their current clinical practice of treating depression during pregnancy and to report any adverse events to the FDA MedWatch program
• A meta-analysis of 7 observational studies, found exposure to SSRIs in late pregnancy (ie, >20 weeks' gestation) more than doubled the risk of PPHN that could not be explained by other etiologies (eg, congenital malformations, meconium aspiration) (BMJ 2014;348:f6932)

Lactation

Distributed into milk; use caution (AAP states effect on nursing infants is unknown but may be of concern)

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Sertraline is part of the drug class:

• Selective serotonin reuptake inhibitors

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• anticoagulants ('blood thinners') such as warfarin (Coumadin, Jantoven);
• antidepressants ('mood elevators') such as amitriptyline (Elavil), amoxapine (Asendin), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Adapin, Sinequan), imipramine (Tofranil), nortriptyline (Aventyl, Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil);
• aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen (Advil, Motrin) and naproxen (Aleve, Naprosyn);
• cimetidine (Tagamet);
• diazepam (Valium);
• digoxin (Lanoxin);
• linezolid ;
• lithium (Eskalith, Lithobid);
• medications for anxiety, mental illness, Parkinson's disease, and seizures;
• medications for irregular heartbeat such as flecainide (Tambocor) and propafenone (Rythmol);
• methylene blue;
• oral medications for diabetes such as tolbutamide (Orinase);
• medications for migraine headaches such as almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), rizatriptan (Maxalt), sumatriptan (Imitrex), and zolmitriptan (Zomig);
• sedatives;
• sibutramine (Meridia);
• sleeping pills; 
• tranquilizers.

This is not a complete list of sertraline drug interactions. Ask your doctor for more information.

Grapefruit and grapefruit juice may interact with sertraline and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor.

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of sertraline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Sertraline hydrochloride is not approved for use in pediatric patients except for patients with obsessive compulsive disorder (OCD).

You should not use sertraline if you are allergic to it, or if you also take pimozide. Do not use the liquid form of sertraline if you are taking disulfiram (Antabuse) or you could have a severe reaction to the disulfiram.

Do not take sertraline within 14 days before or 14 days after you take an MAO inhibitor. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

To make sure sertraline is safe for you, tell your doctor if you have ever had:

• heart disease, high blood pressure, or a stroke;

• liver or kidney disease;

• a seizure;

• bleeding problems, or if you take warfarin (Coumadin, Jantoven);

• bipolar disorder (manic depression); or

• low levels of sodium in your blood.

Some medicines can interact with sertraline and cause a serious condition called serotonin syndrome. Be sure your doctor knows if you also take stimulant medicine, opioid medicine, herbal products, other antidepressants, or medicine for mental illness, Parkinson's disease, migraine headaches, serious infections, or prevention of nausea and vomiting. Ask your doctor before making any changes in how or when you take your medications.

Some young people have thoughts about suicide when first taking an antidepressant. Your doctor should check your progress at regular visits. Your family or other caregivers should also be alert to changes in your mood or symptoms.

Taking an SSRI antidepressant during pregnancy may cause serious lung problems or other complications in the baby. However, you may have a relapse of depression if you stop taking your antidepressant. Tell your doctor right away if you become pregnant. Do not start or stop taking this medicine during pregnancy without your doctor's advice.

It is not known whether sertraline passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Do not give sertraline to anyone younger than 18 years old without the advice of a doctor. Sertraline is FDA-approved for children with obsessive-compulsive disorder (OCD). It is not approved for treating depression in children.

Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Sertraline may be taken with or without food. Try to take the medicine at the same time each day.

The liquid (oral concentrate) form of sertraline must be diluted before you take it. To be sure you get the correct dose, measure the liquid with the medicine dropper provided. Mix the dose with 4 ounces (one-half cup) of water, ginger ale, lemon/lime soda, lemonade, or orange juice. Do not use any other liquids to dilute the medicine. Stir this mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

This medicine can cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking sertraline.

It may take up to 4 weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

Do not stop using sertraline suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using sertraline.

Store at room temperature away from moisture and heat.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Do not drink alcohol.

Ask your doctor before taking a nonsteroidal anti-inflammatory drug (NSAID) for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), diclofenac, indomethacin, meloxicam, and others. Using an NSAID with sertraline may cause you to bruise or bleed easily.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Taking sertraline with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking a sleeping pill, narcotic medication, muscle relaxer, or medicine for anxiety, depression, or seizures.

Other drugs may interact with sertraline, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all your current medicines and any medicine you start or stop using.

In the U.S.

• Zoloft

Available Dosage Forms:

• Tablet
• Solution
• Capsule

Therapeutic Class: Antidepressant

Pharmacologic Class: Serotonin Reuptake Inhibitor

Sertraline is used to treat depression, obsessive-compulsive disorder (OCD), panic disorder, premenstrual dysphoric disorder (PMDD), posttraumatic stress disorder (PTSD), and social anxiety disorder (SAD).

Sertraline belongs to a group of medicines known as selective serotonin reuptake inhibitors (SSRIs). It works by increasing the activity of a chemical called serotonin in the brain.

sertraline is available only with your doctor's prescription.

It is very important that your doctor check your or your child's progress at regular visits. This is to allow for changes in your dose and to help reduce any side effects.

Do not take sertraline with a monoamine oxidase (MAO) inhibitor (eg, isocarboxazid [Marplan®], phenelzine [Nardil®], selegiline [Eldepryl®], tranylcypromine [Parnate®]). Do not start taking sertraline during the 2 weeks after you stop a MAO inhibitor and wait 2 weeks after stopping sertraline before you start taking a MAO inhibitor. If you take them together or do not wait 2 weeks, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, a sudden high body temperature, an extremely high blood pressure, or severe convulsions.

Do not use pimozide (Orap®) while you are taking sertraline. Do not use the oral liquid form of sertraline if you are also using disulfiram (Antabuse®). Using these medicines together can cause serious problems.

Sertraline may cause a serious condition called serotonin syndrome if taken together with some medicines. Do not use sertraline with buspirone (Buspar®), fentanyl (Abstral®, Duragesic®), linezolid (Zyvox®), lithium (Eskalith®, Lithobid®), methylene blue injection, tryptophan, St. John's wort, or some pain or migraine medicines (eg, rizatriptan, sumatriptan, tramadol, Frova®, Imitrex®, Maxalt®, Relpax®, Ultram®, Zomig®). Check with your doctor first before taking any other medicines with sertraline.

For some children, teenagers, and young adults, sertraline can increase thoughts of suicide. Tell your doctor right away if you or your child start to feel more depressed and have thoughts about hurting yourselves. Report any unusual thoughts or behaviors that trouble you or your child, especially if they are new or get worse quickly. Make sure the doctor knows if you or your child have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Also tell the doctor if you or your child have sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let the doctor know if you, your child, or anyone in your family has bipolar disorder (manic-depressive) or has tried to commit suicide.

Sertraline may increase your risk for bleeding problems. Make sure your doctor knows if you or your child are also using other medicines that thin the blood, such as aspirin, NSAID pain or arthritis medicines (eg, diclofenac, ibuprofen, naproxen, Advil®, Aleve®, Celebrex®, Voltaren®), or warfarin (Coumadin®, Jantoven®).

sertraline may cause hyponatremia (low sodium in the blood). This is more common in elderly patients, those who are taking diuretic medicines for high blood pressure, or those who have decreased amounts of fluid in the body due to severe diarrhea or vomiting. Check with your doctor right away if you or your child have headache, trouble concentrating, memory problems, confusion, weakness, or unsteadiness.

sertraline may affect blood sugar levels. If you are diabetic and notice a change in the results of your blood or urine sugar tests, talk with your doctor.

The use of alcohol is not recommended in patients who are taking sertraline. .

sertraline may cause some people to become drowsy, to have trouble thinking, or to have problems with movement. Make sure you know how you react to sertraline before you drive, use machines, or do anything else that could be dangerous if you are not alert or well-coordinated.

The dropper dispenser for the oral liquid contains dry natural rubber (a derivative of latex). This may cause allergic reactions in people who are sensitive to latex. Tell your doctor if you or your child have a latex allergy before you start using sertraline.

Do not stop taking sertraline without checking first with your doctor. Your doctor may want you to gradually reduce the amount you are taking before stopping it completely. This is to decrease the chance of having side effects such as agitation, anxiety, dizziness, a feeling of constant movement of self or surroundings, headache, increased sweating, nausea, trembling or shaking, trouble with sleeping or walking, or unusual tiredness when you stop the medicine.

Before you have any medical tests, tell the medical doctor in charge that you or your child are taking sertraline. The results of some tests may be affected by sertraline.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

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

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

Dosage in Patients with PMDD

The recommended starting Sertraline hydrochloride dosage in adult women with PMDD is 50 mg per day. Sertraline hydrochloride tablets 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 Tablets

Prior to initiating treatment with Sertraline hydrochloride tablets 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 tablets 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 tablets. In addition, at least 14 days must elapse after stopping Sertraline hydrochloride tablets before starting an MAOI antidepressant [See Contraindications (4), Warnings and Precautions (5.2)].

Discontinuation of Treatment with Sertraline Hydrochloride Tablets

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

25 mg Tablets

Green colored, capsule shaped, biconvex, film-coated tablets, debossed with 'L' and 'U' on either side of the breakline on one side and 'D01' on the other side.

50 mg Tablets

Blue colored, capsule shaped, biconvex, film-coated tablets, debossed with 'L' and 'U' on either side of the breakline on one side and 'D02' on the other side.

100 mg Tablets

Yellow colored, capsule shaped, biconvex, film-coated tablets, debossed with 'L'and 'U' on either side of the breakline on one side and 'D03' on the other side.

Mechanism of Action

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

Pharmacodynamics

Studies at clinically relevant doses have demonstrated that Sertraline blocks the uptake of serotonin into human platelets. In vitro studies in animals also suggest that Sertraline is a potent and selective inhibitor of neuronal serotonin reuptake and has only very weak effects on norepinephrine and dopamine neuronal reuptake. In vitro studies have shown that Sertraline has no significant affinity for adrenergic (alpha1, alpha2, beta), cholinergic, GABA, dopaminergic, histaminergic, serotonergic (5HT1A, 5HT1B, 5HT2), or benzodiazepine receptors. The chronic administration of Sertraline was found in animals to down regulate brain norepinephrine receptors. Sertraline does not inhibit monoamine oxidase.

Alcohol

In healthy subjects, the acute cognitive and psychomotor effects of alcohol were not potentiated by Sertraline hydrochloride.

Pharmacokinetics

Absorption

Following oral once-daily Sertraline hydrochloride dosing over the range of 50 to 200 mg for 14 days, mean peak plasma concentrations (Cmax) of Sertraline occurred between 4.5 to 8.4 hours post-dosing. The average terminal elimination half-life of plasma Sertraline is about 26 hours. Consistent with the terminal elimination half-life, there is an approximately two-fold accumulation up to steady-state concentrations, which are achieved after one week of once-daily dosing. Linear dose-proportional pharmacokinetics were demonstrated in a single dose study in which the Cmax and area under the plasma concentration time curve (AUC) of Sertraline were proportional to dose over a range of 50 to 200 mg. The single dose bioavailability of Sertraline hydrochloride tablets is approximately equal to an equivalent dose of Sertraline hydrochloride oral solution. Administration with food causes a small increase in Cmax and AUC.

Metabolism

Sertraline undergoes extensive first pass metabolism. The principal initial pathway of metabolism for Sertraline is N-demethylation. N-desmethylSertraline has a plasma terminal elimination half-life of 62 to 104 hours. Both in vitro biochemical and in vivo pharmacological testing have shown N-desmethylSertraline to be substantially less active than Sertraline. Both Sertraline and N-desmethylSertraline undergo oxidative deamination and subsequent reduction, hydroxylation, and glucuronide conjugation. In a study of radiolabeled Sertraline involving two healthy male subjects, Sertraline accounted for less than 5% of the plasma radioactivity. About 40 to 45% of the administered radioactivity was recovered in urine in 9 days. Unchanged Sertraline was not detectable in the urine. For the same period, about 40 to 45% of the administered radioactivity was accounted for in feces, including 12 to 14% unchanged Sertraline.

DesmethylSertraline exhibits time-related, dose dependent increases in AUC (0 to 24-hour), Cmax and Cmin, with about a 5- to 9-fold increase in these pharmacokinetic parameters between day 1 and day 14.

Protein Binding

In vitro protein binding studies performed with radiolabeled 3H-Sertraline showed that Sertraline is highly bound to serum proteins (98%) in the range of 20 to 500 ng/mL. However, at up to 300 and 200 ng/mL concentrations, respectively, Sertraline and N-desmethylSertraline did not alter the plasma protein binding of two other highly protein bound drugs, warfarin and propranolol.

Studies in Specific Populations

Pediatric Patients:

Sertraline pharmacokinetics were evaluated in a group of 61 pediatric patients (29 aged 6 to 12 years, 32 aged 13 to 17 years) including both males (N=28) and females (N=33). Relative to the adults, pediatric patients aged 6 to 12 years and 13 to 17 years showed about 22% lower AUC (0 to 24 hr) and Cmax values when plasma concentration was adjusted for weight. The half-life was similar to that in adults, and no gender-associated differences were observed [See Dosage and Administration (2.1), Use in Specific Populations (8.4)].

Geriatric Patients:

Sertraline plasma clearance in a group of 16 (8 male, 8 female) elderly patients treated with 100 mg/day of Sertraline hydrochloride for 14 days was approximately 40% lower than in a similarly studied group of younger (25 to 32 year old) individuals. Steady-state, therefore, was achieved after 2 to 3 weeks in older patients. The same study showed a decreased clearance of desmethylSertraline in older males, but not in older females [See Use in Specific Populations (8.5)].

Hepatic Impairment:

In patients with chronic mild liver impairment (N=10: 8 patients with Child-Pugh scores of 5 to 6; and 2 patients with Child-Pugh scores of 7 to 8) who received 50 mg of Sertraline hydrochloride per day for 21 days, Sertraline clearance was reduced, resulting in approximately 3-fold greater exposure compared to age-matched volunteers with normal hepatic function (N=10). The exposure to desmethylSertraline was approximately 2-fold greater in patients with mild hepatic impairment compared to age-matched volunteers with normal hepatic function. There were no significant differences in plasma protein binding observed between the two groups. The effects of Sertraline hydrochloride in patients with moderate and severe hepatic impairment have not been studied [See Dosage and Administration (2.4), Use in Specific Populations (8.6)].

Renal Impairment:

Sertraline is extensively metabolized and excretion of unchanged drug in urine is a minor route of elimination. In volunteers with mild to moderate (CLcr=30 to 60 mL/min), moderate to severe (CLcr=10 to 29 mL/min) or severe (receiving hemodialysis) renal impairment (N=10 each group), the pharmacokinetics and protein binding of 200 mg Sertraline per day maintained for 21 days were not altered compared to age-matched volunteers (N=12) with no renal impairment. Thus Sertraline multiple dose pharmacokinetics appear to be unaffected by renal impairment [See Use in Specific Populations (8.7)].

Drug Interaction Studies

Pimozide:

In a controlled study of a single dose (2 mg) of pimozide, 200 mg Sertraline hydrochloride (once daily) co-administration to steady state was associated with a mean increase in pimozide AUC and Cmax of about 40%, but was not associated with any changes in ECG. The highest recommended pimozide dose (10 mg) has not been evaluated in combination with Sertraline hydrochloride. The effect on QT interval and PK parameters at doses higher than 2 mg of pimozide are not known [See Drug Interactions (7.1)].

Drugs Metabolized by CYP2D6

Many antidepressant drugs (e.g., SSRIs, including Sertraline hydrochloride, and most tricyclic antidepressant drugs) inhibit the biochemical activity of the drug metabolizing isozyme CYP2D6 (debrisoquin hydroxylase), and, thus, may increase the plasma concentrations of co-administered drugs that are metabolized by CYP2D6. The drugs for which this potential interaction is of greatest concern are those metabolized primarily by CYP2D6 and that have a narrow therapeutic index (e.g., tricyclic antidepressant drugs and the Type 1C antiarrhythmics propafenone and flecainide). The extent to which this interaction is an important clinical problem depends on the extent of the inhibition of CYP2D6 by the antidepressant and the therapeutic index of the co-administered drug. There is variability among the drugs effective in the treatment of MDD in the extent of clinically important 2D6 inhibition, and in fact Sertraline hydrochloride at lower doses has a less prominent inhibitory effect on 2D6 than some others in the class. Nevertheless, even Sertraline hydrochloride has the potential for clinically important 2D6 inhibition [See Drug Interactions (7.1)].

Phenytoin

Clinical trial data suggested that Sertraline hydrochloride may increase phenytoin concentrations [See Drug Interactions (7.1)].

Cimetidine

In a study assessing disposition of Sertraline hydrochloride (100 mg) on the second of 8 days of cimetidine administration (800 mg daily), there were increases in Sertraline hydrochloride mean AUC (50%), Cmax (24%) and half-life (26%) compared to the placebo group [See Drug Interactions (7.2)].

Diazepam

In a study comparing the disposition of intravenously administered diazepam before and after 21 days of dosing with either Sertraline hydrochloride (50 to 200 mg/day escalating dose) or placebo, there was a 32% decrease relative to baseline in diazepam clearance for the Sertraline hydrochloride group compared to a 19% decrease relative to baseline for the placebo group (p<0.03). There was a 23% increase in Tmax for desmethyldiazepam in the Sertraline hydrochloride group compared to a 20% decrease in the placebo group (p<0.03) [See Drug Interactions (7.2)].

Lithium

In a placebo-controlled trial in normal volunteers, the administration of two doses of Sertraline hydrochloride did not significantly alter steady-state lithium levels or the renal clearance of lithium [See Drug Interactions (7.2)].

Tolbutamide

In a placebo-controlled trial in normal volunteers, administration of Sertraline hydrochloride for 22 days (including 200 mg/day for the final 13 days) caused a statistically significant 16% decrease from baseline in the clearance of tolbutamide following an intravenous 1000 mg dose. Sertraline hydrochloride administration did not noticeably change either the plasma protein binding or the apparent volume of distribution of tolbutamide, suggesting that the decreased clearance was due to a change in the metabolism of the drug [See Drug Interactions (7.2)].

Atenolol

Sertraline hydrochloride (100 mg) when administered to 10 healthy male subjects had no effect on the beta-adrenergic blocking ability of atenolol [See Drug Interactions (7.2)].

Digoxin

In a placebo-controlled trial in normal volunteers, administration of Sertraline hydrochloride for 17 days (including 200 mg/day for the last 10 days) did not change serum digoxin levels or digoxin renal clearance [See Drug Interactions (7.2)].

Drugs Metabolized by CYP3A4

In three separate in vivo interaction studies, Sertraline hydrochloride was co-administered with CYP3A4 substrates, terfenadine, carbamazepine, or cisapride under steady-state conditions. The results of these studies indicated that Sertraline hydrochloride did not increase plasma concentrations of terfenadine, carbamazepine, or cisapride. These data indicate that Sertraline hydrochloride's extent of inhibition of CYP3A4 activity is not likely to be of clinical significance. Results of the interaction study with cisapride indicate that Sertraline hydrochloride 200 mg (once daily) induces the metabolism of cisapride (cisapride AUC and Cmax were reduced by about 35%) [See Drug Interactions (7.2)].

Microsomal Enzyme Induction

Preclinical studies have shown Sertraline hydrochloride to induce hepatic microsomal enzymes. In clinical studies, Sertraline hydrochloride was shown to induce hepatic enzymes minimally as determined by a small (5%) but statistically significant decrease in antipyrine half-life following administration of 200 mg of Sertraline hydrochloride per day for 21 days. This small change in antipyrine half-life reflects a clinically insignificant change in hepatic metabolism.

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)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of Sertraline hydrochloride tablets 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 tablets 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 tablets and to discuss any tapering regimen with their healthcare provider. Adverse reactions can occur when Sertraline hydrochloride tablets are 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 tablets may cause withdrawal symptoms in the newborn or persistent pulmonary hypertension of the newborn (PPHN) [See Use in Specific Populations (8.1)].

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

MADE IN INDIA

Revised: September 2017                                                                               ID#: 252896

Medication Guide

Sertraline Hydrochloride (ser' tra leen hye'' droe klor' ide) Tablets

What is the most important information I should know about Sertraline hydrochloride tablets?

Sertraline hydrochloride tablets and other antidepressant medicines may cause serious side effects. Call your healthcare provider right away if you have any of the following symptoms, or call 911 if there is an emergency.

1.      Suicidal thoughts or actions:

• Sertraline hydrochloride tablets and other antidepressant medicines may increase suicidal thoughts or actions in some people 24 years of age and younger, especially within thefirst few months of treatment or when the dose is changed.
• Depression or other serious mental illnesses are the most important causes of suicidal thoughts or actions.
• Watch for these changes and call your healthcare provider right away if you notice new or sudden changes in mood, behavior, actions, thoughts, or feelings, especially if severe.
  • Pay particular attention to such changes when Sertraline hydrochloride tablets are started or when the dose is changed.
  • Keep all follow-up visits with your healthcare provider and call between visits if you are worried about symptoms.

Call your healthcare provider right away if you have any of the following symptoms, or call 911 if an emergency, especially if they are new, worse, or worry you:

• attempts to commit suicide
• acting aggressive or violent
• new or worse depression
• feeling agitated, restless, angry or irritable
• an increase in activity or talking more than what is normal for you
• acting on dangerous impulses
• thoughts about suicide or dying
• new or worse anxiety or panic attacks
• trouble sleeping
• other unusual changes in behavior or mood

2.      Serotonin Syndrome. This condition can be life-threatening and symptoms may include:

• agitation, hallucinations, coma, or other changes in mental status
• racing heartbeat, high or low blood pressure
• coordination problems or muscle twitching (overactive reflexes)
• nausea, vomiting, or diarrhea
• sweating or fever
• muscle rigidity

3.      Increased chance of bleeding: Sertraline hydrochloride tablets and other antidepressant medicines may increase your risk of bleeding or bruising, especially if you take the blood thinner warfarin (Coumadin®, Jantoven®), a non-steroidal anti-inflammatory drug (NSAIDs, like ibuprofen or naproxen), or aspirin.

4.      Manic episodes. Symptoms may include:

• greatly increased energy
• racing thoughts
• unusually grand ideas
• severe trouble sleeping
• reckless behavior
• excessive happiness or irritability
• talking more or faster than usual

5.      Seizures or convulsions.

6.      Glaucoma (angle-closure glaucoma). Many antidepressant medicines including Sertraline hydrochloride tablets may cause a certain type of eye problem called angle-closure glaucoma. Call your healthcare provider if you have eye pain, changes in your vision, or swelling or redness in or around the eye. Only some people are at risk for these problems. You may want to undergo an eye examination to see if you are at risk and receive preventative treatment if you are.

7.      Changes in appetite or weight. Children and adolescents should have height and weight monitored during treatment.

8.      Low salt (sodium) levels in the blood. Elderly people may be at greater risk for this. Symptoms may include:

• Headache
• weakness or feeling unsteady
• confusion, problems concentrating or thinking, memory problems

Do not stop Sertraline hydrochloride tablets without first talking to your healthcare provider. Stopping Sertraline hydrochloride tablets too quickly may cause serious symptoms including:

• anxiety, irritability, high or low mood, feeling restless or changes in sleep habits
• headache, sweating, nausea, dizziness
• electric shock-like sensations, shaking, confusion

What are Sertraline hydrochloride tablets?

Sertraline hydrochloride tablet is a prescription medicine used to treat:

• Major Depressive Disorder (MDD)
• Panic Disorder
• Social Anxiety Disorder
• Obsessive Compulsive Disorder (OCD)
• Posttraumatic Stress Disorder (PTSD)
• Premenstrual Dysphoric Disorder (PMDD)

It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider.

Sertraline hydrochloride tablets are safe and effective in treating children with OCD age 6 to 17 years.

It is not known if Sertraline hydrochloride tablets are safe and effective for use in children under 6 years of age with OCD or children with other behavior health conditions.

Talk to your healthcare provider if you do not think that your condition is getting better with Sertraline hydrochloride tablets treatment.

Who should not take Sertraline hydrochloride tablets?

Do not take Sertraline hydrochloride tablets if you:

• take a monoamine oxidase inhibitor (MAOI). Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic linezolid.
• have taken an MAOI within 2 weeks of stopping Sertraline hydrochloride tablets unless directed to do so by your healthcare provider.
• have stopped taking an MAOI in the last 2 weeks unless directed to do so by your healthcare provider.
• take any other medicines that contain Sertraline (such as Sertraline HCl or Sertraline hydrochloride).
• take the antipsychotic medicine pimozide (Orap®) because this can cause serious heart problems.
• are allergic to Sertraline or any of the ingredients in Sertraline hydrochloride tablets. See the end of this Medication Guide for a complete list of ingredients in Sertraline hydrochloride tablets.
• take Antabuse®(disulfiram) (if you are taking the liquid form of Sertraline hydrochloride tablets) due to the alcohol content.

People who take Sertraline hydrochloride tablets close in time to an MAOI may have serious or even life-threatening side effects. Get medical help right away if you have any of these symptoms:

• high fever
• rapid changes in heart rate or blood pressure
• uncontrolled muscle spasms
• confusion
• stiff muscles
• loss of consciousness (pass out)

What should I tell my healthcare provider before taking Sertraline hydrochloride tablets?

Before starting Sertraline hydrochloride tablets, tell your healthcare provider:

• if you have:
  • liver problems
  • heart problems
  • bipolar disorder or mania
  • kidney problems.
  • or have had seizures or convulsions
  • low sodium levels in your blood
  • a history of a stroke
  • high blood pressure
  • or have had bleeding problems
• are pregnant or plan to become pregnant . Your baby may have withdrawal symptoms after birth or may be at increased risk for a serious lung problem at birth. Talk to your healthcare provider about the benefits and risks of taking Sertraline hydrochloride tablets during pregnancy.
• are breastfeeding or plan to breastfeed . A small amount of Sertraline hydrochloride may pass into your breast milk. Talk to your healthcare provider about the best way to feed your baby while taking Sertraline hydrochloride tablets.

Tell your healthcare provider about all the medicines that you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Sertraline hydrochloride tablets and some medicines may interact with each other, may not work as well, or may cause serious side effects.

Your healthcare provider or pharmacist can tell you if it is safe to take Sertraline hydrochloride tablets with your other medicines. Do not start or stop any medicine while taking Sertraline hydrochloride tablets without talking to your healthcare provider first.

How should I take Sertraline hydrochloride tablets?

• Take Sertraline hydrochloride tablets exactly as prescribed. Your healthcare provider may need to change the dose of Sertraline hydrochloride tablets until it is the right dose for you.
• Sertraline hydrochloride tablets may be taken with or without food.
• If you miss a dose of Sertraline hydrochloride tablets, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of Sertraline hydrochloride tablets at the same time.

If you take too much Sertraline hydrochloride tablets, call your healthcare provider or poison control center right away, or go to the nearest hospital emergency room right away.

What should I avoid while taking Sertraline hydrochloride tablets?

Sertraline hydrochloride tablets can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You should not drive, operate heavy machinery, or do other dangerous activities until you know how Sertraline hydrochloride tablets affect you. Do not drink alcohol while you take Sertraline hydrochloride tablets.

What are the possible side effects of Sertraline hydrochloride tablets?

Sertraline hydrochloride tablets may cause serious side effects, including:

• See "What is the most important information I should know about Sertraline hydrochloride tablets?"
• The most common side effects in adults who take Sertraline hydrochloride tablets include:
  • nausea, loss of appetite, diarrhea, or indigestion
  • increased sweating
  • tremor or shaking
  • agitation
  • change in sleep habits including increased sleepiness or insomnia
  • sexual problems including decreased libido and ejaculation failure
  • feeling tired or fatigued
  • anxiety

The most common side effects in children and adolescents who take include abnormal increase in muscle movement or agitation, nose bleeds, urinary incontinence, aggressive reaction, possible slowed growth rate, and weight change. Your child's height and weight should be monitored during treatment with Sertraline hydrochloride tablets.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of Sertraline hydrochloride tablets. For more information, ask your healthcare provider or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

How should I store Sertraline hydrochloride tablets? 

• Store Sertraline hydrochloride tablets at room temperature, 68°F to 77°F (20°C to 25°C).
• Keep Sertraline hydrochloride tablets bottle closed tightly.

Keep Sertraline hydrochloride tablets and all medicines out of the reach of children.

General information about the safe and effective use of Sertraline hydrochloride tablets

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Sertraline hydrochloride tablets for a condition for which it was not prescribed. Do not give Sertraline hydrochloride tablets to other people, even if they have the same condition. It may harm them.

This Medication Guide summarizes the most important information about Sertraline hydrochloride tablets. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about Sertraline hydrochloride tablets that is written for healthcare professionals.

For more information about Sertraline hydrochloride tablets call Lupin Pharmaceuticals, Inc. at 1-800-399-2561 or visit at www.lupinpharmaceuticals.com.

What are the ingredients in Sertraline hydrochloride tablets?

Active ingredient: Sertraline hydrochloride

Inactive ingredients: 

D&C Yellow #10 (in 25 mg tablet), dibasic calcium phosphate anhydrous, FD&C Blue #1 (in 25 mg tablet), FD&C Blue #2 (in 50 mg tablet), FD&C Red #40 (in 25 mg tablet), hydroxypropyl cellulose, hypromellose, iron oxide yellow (in 100 mg tablet), magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, sodium starch glycolate and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration

The brands listed are trademarks of their respective owners and are not trademarks of Lupin Pharmaceuticals, Inc. The makers of these brands are not affiliated with and do not endorse Lupin Pharmaceuticals, Inc. or its products.

Manufactured for:

Lupin Pharmaceuticals, Inc.

Baltimore, Maryland 21202

United States

MADE IN INDIA

Revised: September 2017                                                                               ID#: 252898

Sertraline Tablets USP, 25 mg

Rx only

90 Tablets

NDC 68180-351-09

Sertraline Tablets USP, 50 mg

Rx only

90 Tablets

NDC 68180-352-09

Sertraline Tablets USP, 100 mg

Rx only

90 Tablets

NDC 68180-353-09

• Zoloft

Depression: The onset of action is within a week, however, individual response varies greatly and full response may not be seen until 8 to 12 weeks after initiation of treatment (APA [Gelenberg 2010]).

Time to Peak

Plasma: Sertraline: 4.5 to 8.4 hours

Half-Life Elimination

Sertraline: Mean: 26 hours; N-desmethylsertraline: 62 to 104 hours

Children 6 to 12 years: Mean: 26.2 hours (Alderman 1998)

Children 13 to 17 years: Mean: 27.8 hours (Alderman 1998)

Adults 18 to 45 years: Mean: 27.2 hours (Alderman 1998)

Protein Binding

98%

Binge-eating disorder

Data from two small double-blind, randomized, controlled trials support the use of sertraline to improve weight loss, binge frequency, and binge behaviors in patients with binge-eating disorder [Leombruni 2008], [McElroy 2000]. Additional trials may be necessary to further define the role of sertraline for this condition.

Bulimia nervosa

Data from one small randomized controlled trial and another study of lower quality (open-label, flexible dose study) in patients with bulimia nervosa supports the use of sertraline to reduce the number of binge eating crises and purging in these patients [Milano 2004], [Sloan 2004]. Additional trials may be necessary to further define the role of sertraline for this condition.

Cholestatic pruritus

Data from one small controlled trial and one small prospective cohort study suggest that sertraline may be beneficial in the management of cholestatic pruritus. Additional data may be necessary to further define the role of sertraline in this condition.

American Association for the Study of Liver Diseases (AASLD) practice guidelines for primary biliary cirrhosis recommend the use of sertraline for cholestatic pruritus when other therapies (ie, bile acid sequestrants, naltrexone, rifampin) have failed.

Generalized anxiety disorder

Data from several double-blind randomized, controlled trials in patients with generalized anxiety disorder, supports the use of sertraline to reduce anxiety symptoms in these patients [Ball 2005], [Brawman-Mintzer 2006], [Dahl 2005].

No dosage adjustment necessary.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy

Alcohol (Ethyl): May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Management: Patients receiving selective serotonin reuptake inhibitors should be advised to avoid alcohol. Monitor for increased psychomotor impairment in patients who consume alcohol during treatment with selective serotonin reuptake inhibitors. Consider therapy modification

Amifampridine: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Monitor therapy

Amodiaquine: CYP2C8 Inhibitors may increase the serum concentration of Amodiaquine. Avoid combination

Analgesics (Opioid): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Antidepressants (Serotonin Reuptake Inhibitor/Antagonist): Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Antidepressants (Serotonin Reuptake Inhibitor/Antagonist). This may cause serotonin syndrome. Management: Consider alternatives, and use conservative initial dosing. Monitor patients receiving these combinations for signs/symptoms of serotonin toxicity. Consider therapy modification

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Apixaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely. Monitor therapy

ARIPiprazole: Sertraline may enhance the adverse/toxic effect of ARIPiprazole. Sertraline may increase the serum concentration of ARIPiprazole. Management: See full interaction monograph. Aripiprazole dose adjustment may not be required when used as adjunctive therapy for major depressive disorder. Consider therapy modification

Aspirin: Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of Aspirin. Monitor therapy

Beta-Blockers: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Beta-Blockers. Exceptions: Acebutolol; Atenolol; Betaxolol (Ophthalmic); Betaxolol (Systemic); Bisoprolol; Carteolol (Ophthalmic); Esmolol; Labetalol; Levobunolol; Metipranolol; Nadolol; Penbutolol; Sotalol. Monitor therapy

Blood Glucose Lowering Agents: Selective Serotonin Reuptake Inhibitors may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

BusPIRone: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Selective Serotonin Reuptake Inhibitors may decrease the metabolism of BusPIRone. Management: The combination of a selective serotonin reuptake inhibitor and buspirone should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Sertraline. Monitor therapy

Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy

Cimetidine: May decrease the metabolism of Selective Serotonin Reuptake Inhibitors. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and/or bleeding may be increased. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Sertraline. Monitor therapy

Cyproheptadine: May diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

Dabigatran Etexilate: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Dabigatran Etexilate. Agents with Antiplatelet Properties may increase the serum concentration of Dabigatran Etexilate. This mechanism applies specifically to clopidogrel. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Darunavir: May decrease the serum concentration of Sertraline. Monitor therapy

Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Monitor therapy

Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Monitor therapy

Desmopressin: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dextromethorphan: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Dextromethorphan. Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dextromethorphan. Management: Avoid the concurrent use of dextromethorphan and SSRIs, particularly fluoxetine and paroxetine, when possible. The risk for this interaction may persist for several weeks following discontinuation of fluoxetine or paroxetine. Consider therapy modification

Disulfiram: May enhance the adverse/toxic effect of Sertraline. This is specifically related to sertraline oral concentrate due to its alcohol content (12%). Management: Sertraline Oral Concentrate contains 12% alcohol, and its use should be avoided with disulfiram. Avoid combination

Dosulepin: Selective Serotonin Reuptake Inhibitors may increase the serum concentration of Dosulepin. Avoid combination

Edoxaban: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Monitor therapy

Efavirenz: May decrease the serum concentration of Sertraline. Monitor therapy

Erythromycin (Systemic): May enhance the adverse/toxic effect of Sertraline. Monitor therapy

Fosphenytoin: May decrease the serum concentration of Sertraline. Sertraline may increase the serum concentration of Fosphenytoin. Monitor therapy

Galantamine: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of Galantamine. Monitor therapy

Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Grapefruit Juice: May increase the serum concentration of Sertraline. Monitor therapy

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Consider therapy modification

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Ibritumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Monitor therapy

Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy

Iobenguane I 123: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Selective Serotonin Reuptake Inhibitors may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Linezolid: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could result in serotonin syndrome. Avoid combination

Lithium: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This could increase the risk of serotonin toxicity/serotonin syndrome. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

MAO Inhibitors: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methylene Blue: Selective Serotonin Reuptake Inhibitors may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

MetyroSINE: May enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Mivacurium: Sertraline may increase the serum concentration of Mivacurium. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

NSAID (COX-2 Inhibitor): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). NSAID (COX-2 Inhibitor) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Monitor therapy

NSAID (Nonselective): Selective Serotonin Reuptake Inhibitors may enhance the antiplatelet effect of NSAID (Nonselective). NSAID (Nonselective) may diminish the therapeutic effect of Selective Serotonin Reuptake Inhibitors. Management: Consider using alternative analgesics, when appropriate, and/or addition of a gastroprotective agent. Monitor patients closely for signs/symptoms of bleeding, and for evidence of diminished SSRI effectiveness with concurrent use. Consider therapy modification

Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Monitor therapy

Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Monitor therapy

Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy

Phenytoin: Sertraline may increase the serum concentration of Phenytoin. Phenytoin may decrease the serum concentration of Sertraline. Monitor therapy

Pimozide: Selective Serotonin Reuptake Inhibitors may enhance the adverse/toxic effect of Pimozide. Avoid combination

Propafenone: Sertraline may enhance the QTc-prolonging effect of Propafenone. Sertraline may increase the serum concentration of Propafenone. Monitor therapy

Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

RisperiDONE: Selective Serotonin Reuptake Inhibitors may decrease the metabolism of RisperiDONE. Monitor therapy

Rivaroxaban: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Rivaroxaban. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Monitor therapy

Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Succinylcholine: Sertraline may increase the serum concentration of Succinylcholine. Monitor therapy

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Selective Serotonin Reuptake Inhibitors may enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy

Thyroid Products: Selective Serotonin Reuptake Inhibitors may diminish the therapeutic effect of Thyroid Products. Thyroid product dose requirements may be increased. Monitor therapy

Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Tositumomab and Iodine I 131 Tositumomab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Tositumomab and Iodine I 131 Tositumomab. Specifically, the risk of bleeding-related adverse events may be increased. Monitor therapy

TraMADol: Serotonin Modulators may enhance the adverse/toxic effect of TraMADol. The risk of seizures may be increased. TraMADol may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Tricyclic Antidepressants: Sertraline may enhance the adverse/toxic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with sertraline. Consider therapy modification

Tryptophan: May enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination

Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination

Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Selective Serotonin Reuptake Inhibitors may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Sertraline crosses the human placenta. Available studies evaluating teratogenic effects following maternal use of sertraline in the first trimester have not shown an overall increased risk of major birth defects. Studies evaluating specific birth defects have provided inconsistent results. Nonteratogenic effects in the newborn following SSRI/SNRI exposure late in the third trimester include respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypo- or hypertonia, hyper-reflexia, jitteriness, irritability, constant crying, and tremor. Symptoms may be due to the toxicity of the SSRIs/SNRIs or a discontinuation syndrome and may be consistent with serotonin syndrome associated with SSRI treatment. Persistent pulmonary hypertension of the newborn (PPHN) has also been reported with SSRI exposure. The long-term effects of in utero SSRI exposure on infant development and behavior are not known.

Due to pregnancy-induced physiologic changes, women who are pregnant may require adjusted doses of sertraline to achieve euthymia. The ACOG recommends that therapy with SSRIs or SNRIs during pregnancy be individualized; treatment of depression during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. According to the American Psychiatric Association (APA), the risks of medication treatment should be weighed against other treatment options and untreated depression. For women who discontinue antidepressant medications during pregnancy and who may be at high risk for postpartum depression, the medications can be restarted following delivery. Treatment algorithms have been developed by the ACOG and the APA for the management of depression in women prior to conception and during pregnancy (ACOG 2008; APA 2010; Yonkers 2009).

Pregnant women exposed to antidepressants during pregnancy are encouraged to enroll in the National Pregnancy Registry for Antidepressants (NPRAD). Women 18 to 45 years of age or their health care providers may contact the registry by calling 844-405-6185. Enrollment should be done as early in pregnancy as possible.

Commonly reported side effects of sertraline include: diarrhea, dizziness, drowsiness, dyspepsia, fatigue, insomnia, loose stools, nausea, tremor, headache, paresthesia, anorexia, decreased libido, delayed ejaculation, diaphoresis, ejaculation failure, and xerostomia. Other side effects include: abdominal pain, agitation, pain, vomiting, anxiety, hypouricemia, and malaise. See below for a comprehensive list of adverse effects.

Continuous regimen:
-Initial dose: 50 mg orally once a day during the menstrual cycle
-Maintenance dose: 50 to 150 mg orally once a day during the menstrual cycle

Cyclic regimen:
-Initial dose: 50 mg orally once a day starting 14 days prior to the anticipated start of menstruation through to the first full day of menses, and repeated with each new cycle
-Maintenance dose: 50 to 100 mg orally once a day

Comments:
-The dose may be increased in increments of 50 mg per menstrual cycle, increased at the onset of each new cycle; dosage adjustments may also include changes between regimens.
-If a 100 mg once daily dose has been established with the cyclic regimen, a titration step of 50 mg per day for three days should be used at the beginning of each dosing period (luteal phase of the menstrual cycle).
-The effectiveness of sertraline for longer than three months has not been systematically evaluated in controlled trials.

Treatment of premenstrual dysphoric disorder (PMDD)

This dosage information is for sertraline oral tablet. All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Generic: sertraline

• Form: Oral tablet
• Strengths: 25 mg, 50 mg, 100 mg

• Form: Oral solution
• Strengths: 20 mg/mL

Brand: Zoloft

• Form: Oral tablet
• Strengths: 25 mg, 50 mg, 100 mg

• Form: Oral solution
• Strengths: 20 mg/mL

Dosage for major depressive disorder

Adult dosage (ages 18–64 years)

• The typical starting dose is 50 mg per day.
• Your doctor will slowly increase your dose every week, as needed.
• The maximum dose is 200 mg per day.

Child dosage (ages 0–17 years)

The use of this drug to treat children with this condition has not been studied. It should not be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for obsessive-compulsive disorder

Adult dosage (ages 18–64 years)

• The typical starting dose is 50 mg per day.
• Your doctor will slowly increase your dose every week, as needed.
• The maximum dose is 200 mg per day.

Child dosage (ages 0–5 years)

The use of this drug to treat children with this condition has not been studied. It should not be used in people younger than 6 years.

Child dosage (ages 6–12 years)

25 mg once daily

Child dosage (ages 0–5 years)

50 mg once daily

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for panic disorder

Adult dosage (ages 18–64 years)

• The typical starting dose is 25 mg per day. This is usually increased to 50 mg per day after 1 week.
• Your doctor will slowly increase your dose every week, as needed.
• The maximum dose is 200 mg per day.

Child dosage (ages 0–17 years)

The use of this drug to treat children with this condition has not been studied. It should not be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for posttraumatic stress disorder

Adult dosage (ages 18–64 years)

• The typical starting dose is 25 mg per day. This is usually increased to 50 mg per day after 1 week.
• Your doctor will slowly increase your dose every week, as needed.
• The maximum dose is 200 mg per day.

Child dosage (ages 0–17 years)

The use of this drug to treat children with this condition has not been studied. It should not be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for social anxiety disorder

Adult dosage (ages 18–64 years)

• The typical starting dose is 25 mg per day. This is usually increased to 50 mg per day after 1 week.
• Your doctor will slowly increase your dose every week, as needed.
• The maximum dose is 200 mg per day.

Child dosage (ages 0–17 years)

The use of this drug to treat children with this condition has not been studied. It should not be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Dosage for premenstrual dysphoric disorder

Adult dosage (ages 18–64 years)

The typical starting dose is 50 mg per day, throughout your menstrual cycle.

Child dosage (ages 0–17 years)

The use of this drug to treat children with this condition has not been studied. It should not be used in people younger than 18 years.

Senior dosage (ages 65 years and older)

The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects. Your doctor may start you on a lowered dose or a different dosing schedule. This can help keep levels of this drug from building up too much in your body.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always to speak with your doctor or pharmacist about dosages that are right for you.