Desvenlafaxine

: All SNRIs, including desvenlafaxine, should not be taken with any of the monoamine oxidase inhibitor (MAOI) class of antidepressants, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), selegiline (Eldepryl), and procarbazine (Matulane) or other drugs that inhibit monoamine oxidase [for example, linezolid (Zyvox)]. Such combinations may lead to confusion, high blood pressure, tremor, hyperactivity, coma, and death. Desvenlafaxine should not be administered within 14 days after stopping MAOIs and MAOIs should not be administered within 7 days of stopping desvenlafaxine.

Similar reactions may occur if desvenlafaxine is combined with other SNRIs, selective serotonin reuptake inhibitors (for example, fluoxetine [Prozac] or paroxetine [Paxil]) or other drugs that increase serotonin in the brain, for example, tryptophan, St. John's wort, meperidine (Demerol) or tramadol (Ultram).

SNRIs may increase the effect of warfarin (Coumadin), leading to excessive bleeding. Warfarin therapy should be monitored more frequently in patients who are also taking desvenlafaxine. Combining SNRIs with aspirin, nonsteroidal antiinflammatory drugs (NSAIDs) or other drugs that affect bleeding may increase the likelihood of upper gastrointestinal bleeding.

Ketoconazole (Nizoral, Extina, Xolegel, Kuric) may reduce the breakdown of desvenlafaxine, therefore increasing concentrations of desvenlafaxine in the body and the risk of adverse effects. Desvenlafaxine may reduce the concentration of midazolam (Versed).

The recommended dosage for Pristiq is 50 milligrams (mg) once daily, with or without food.

In clinical studies, doses of 50 mg to 400 mg per day were shown to be effective, although no additional benefit was demonstrated at doses greater than 50 mg per day, and adverse reactions and discontinuations were more frequent at higher doses.

Pristiq should be taken at approximately the same time each day. Swallow tablets whole. Do not divide, crush, chew, or dissolve them.

The recommended dose in patients with moderate to severe hepatic (liver) impairment is 50 mg per day. Dose increases above 100 mg per day is not recommended.

Pristiq Overdose

If you experience any of the below symptoms of a Pristiq overdose, call your doctor or go to the closest emergency room immediately.

• Severe drowsiness
• Seizures
• Fast/irregular heartbeat

Missed Dose of Pristiq

If you miss a dose of Pristiq, wait to take the next dose at your scheduled time.

Do not "double up" and take more than one dose at the same time.

Black Box Warnings

Antidepressants increase risk of suicidal thinking and behavior in children, adolescents, and young adults (18-24 years) in short-term studies

Increased risk not observed in patients >24 years; slight decrease observed in patients >65 years

In children and young adults, initiate only if benefits greatly outweigh risks

Monitor closely for changes in behavior, clinical worsening, and suicidal tendencies during initial 1-2 months of therapy and dosage adjustments

Patient’s family should communicate any abrupt behavioral changes to healthcare provider

Worsening behavior and suicidal tendencies that are not part of presenting symptoms may necessitate discontinuance of therapy

Not approved for use in pediatric patients

Contraindications

Hypersensitivity

Coadministration with serotonergic drugs

• Coadministration with MAOIs increases risk of serotonin syndrome
• Use of MAOIs concomitantly within 14 days before initiating desvenlafaxine or within 7 days after discontinuing desvenlafaxine
• Symptoms include tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, hyperthermia with features resembling neuroleptic malignant syndrome (NMS), seizures, rigidity, autonomic instability with possible rapid fluctuations of vital signs, and mental status changes that include extreme agitation progressing to delirium and coma
• Starting desvenlafaxine in patient being treated with linezolid or IV methylene blue is contraindicated because of increased risk of serotonin syndrome
• If linezolid or IV methylene blue must be administered, discontinue desvenlafaxine immediately and monitor for central nervous system (CNS) toxicity; therapy may be resumed 24 hours after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first

Cautions

Suicidality; monitor for clinical worsening and suicide risk (especially in children, adolescents, and young adults aged 18-24 years), during early phases of treatment and alterations in dosages

Consider risk of serotonin syndrome if administered concomitantly with other serotonergic drugs including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s Wort

Serotonin syndrome or NMS-like reactions may occur; discontinue and initiate supportive therapy; closely monitor patients concomitantly receiving triptans, antipsychotics, or serotonin precursors

Neonates exposed to SNRIs or SSRIs late in 3rd trimester of pregnancy have developed complications necessitating prolonged hospitalization, respiratory support, and tube feeding

Control hypertension before initiating treatment; monitor blood pressure regularly during treatment; if sustained hypertension is observed, consider dosage reduction or discontinuance

SSRIs and SNRIs may impair platelet aggregation and increase the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis, petechiae, and GI hemorrhage to life-threatening hemorrhage; concomitant use of aspirin, NSAIDs, warfarin, other anticoagulants, or other drugs known to affect platelet function may add to this risk

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Seizure disorder

Screen patients for bipolar disorder; risk of mixed or manic episodes is increased in patients treated with antidepressants

Activation of mania or hypomania

Cardiovascular, cerebrovascular or lipid metabolism disorders; monitor patients who have history of or are at risk for these disorders

Monitor serum lipids periodically; risk of elevations in fasting serum total cholesterol, low-density lipoprotein (LDL) and triglycerides is increased

Hyponatremia due to syndrome of inappropriate antidiuretic hormone (SIADH); cases of serum sodium ≤110 mmol/L have been reported; monitor patients who are taking diuretics or at risk for volume depletion

Rare reports of interstitial lung disease and eosinophilic pneumonia; monitor patients for progressive dyspnea, cough, or chest discomfort

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

Dosages >50 mg/day offer no additional benefit but have worse adverse effects

Prescriptioin should be written for smallest quantity consistent with good patient care

May cause anxiety, nervousness, and insomnia

May impair congnitive abilities; use caution operating heavy machinery

Bone fractures reported with antidepressant treatment; consider possibility of  fracture if antidepressant-treated patient presents with unexplained bone pain

May cause or exacerbate sexual dysfunction

Taper dose when possible and monitor for discontinuation symptoms

Desvenlafaxine is a prescription medication used to treat depression. Desvenlafaxine belongs to a group of drugs called serotonin norepinephrine reuptake inhibitors (SNRIs), which work by increasing serotonin and norepinephrine levels in the brain to maintain mental balance and improve mood.

This medication comes as an extended release tablet and is taken once a day, with or without food.

Do not divide, crush, chew, or dissolve tablets. Swallow desvenlafaxine tablets whole.

Common side effects of desvenlafaxine include nausea, constipation, trouble falling asleep or staying asleep, and increased sweating. Desvenlafaxine can also cause dizziness and make you feel tired. Do not drive or operate heavy machinery until you know how desvenlafaxine affects you.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of desvenlafaxine there are no specific foods that you must exclude from your diet when receiving this medication.

Suicidality and Antidepressant Drugs

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, teens, and young adults. 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. Desvenlafaxine is not approved for use in children under 18.

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.

Usual Adult Dose for Depression:

50 mg orally once a day, with or without food
Maximum dose: 400 mg orally per day

Comments:
-There is no evidence that doses greater than 50 mg per day provide additional benefit.
-Side effects and discontinuations were more common at higher doses.

Use: Treatment of major depressive disorder (MDD)

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For desvenlafaxine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to desvenlafaxine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of desvenlafaxine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of desvenlafaxine in the elderly. However, elderly patients are more likely to have low blood pressure, hyponatremia (low sodium in the blood), and age-related kidney problems, which may require an adjustment in the dose for patients receiving desvenlafaxine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking desvenlafaxine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using desvenlafaxine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bromopride
• Furazolidone
• Iproniazid
• Isocarboxazid
• Linezolid
• Methylene Blue
• Metoclopramide
• Moclobemide
• Phenelzine
• Procarbazine
• Rasagiline
• Safinamide
• Selegiline
• Tranylcypromine

Using desvenlafaxine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Abciximab
• Aceclofenac
• Acemetacin
• Acenocoumarol
• Alfentanil
• Almotriptan
• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Ancrod
• Anisindione
• Antithrombin III Human
• Apixaban
• Aspirin
• Benzphetamine
• Bivalirudin
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buspirone
• Butorphanol
• Carbamazepine
• Celecoxib
• Chlorpheniramine
• Choline Salicylate
• Cilostazol
• Citalopram
• Clomipramine
• Clonixin
• Clopidogrel
• Cocaine
• Cyclobenzaprine
• Danaparoid
• Defibrotide
• Dermatan Sulfate
• Desipramine
• Desirudin
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Dibenzepin
• Diclofenac
• Dicumarol
• Diflunisal
• Dihydrocodeine
• Dipyridamole
• Dipyrone
• Dolasetron
• Donepezil
• Doxepin
• Droxicam
• Duloxetine
• Edoxaban
• Eletriptan
• Epoprostenol
• Eptifibatide
• Escitalopram
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Frovatriptan
• Granisetron
• Heparin
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Ibuprofen
• Iloprost
• Imipramine
• Indomethacin
• Iobenguane I 123
• Ketoprofen
• Ketorolac
• Lamifiban
• Levomilnacipran
• Levorphanol
• Lexipafant
• Lisdexamfetamine
• Lithium
• Lofepramine
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Melitracen
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Milnacipran
• Mirtazapine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nalbuphine
• Naproxen
• Naratriptan
• Nefazodone
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Nortriptyline
• Opipramol
• Oxaprozin
• Oxycodone
• Oxymorphone
• Oxyphenbutazone
• Palonosetron
• Parecoxib
• Paroxetine
• Pentazocine
• Pentosan Polysulfate Sodium
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Pranoprofen
• Proglumetacin
• Propyphenazone
• Proquazone
• Protriptyline
• Remifentanil
• Rivaroxaban
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sertraline
• Sibrafiban
• Sibutramine
• Sodium Salicylate
• St John's Wort
• Sufentanil
• Sulfinpyrazone
• Sulindac
• Sulodexide
• Sumatriptan
• Tapentadol
• Tenoxicam
• Tianeptine
• Tiaprofenic Acid
• Ticlopidine
• Tirofiban
• Tolfenamic Acid
• Tolmetin
• Tramadol
• Trazodone
• Trimipramine
• Tryptophan
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vortioxetine
• Warfarin
• Xemilofiban
• Ziprasidone
• Zolmitriptan

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using desvenlafaxine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use desvenlafaxine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of desvenlafaxine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bipolar disorder (mood disorder with mania and depression), or risk of or
• Bleeding problems or
• Glaucoma (angle-closure type) or
• Heart or blood vessel disease or
• Hyperlipidemia (high cholesterol or triglycerides in the blood) or
• Hypertension (high blood pressure) or
• Hyponatremia (low sodium levels in the blood) or
• Interstitial lung disease, or history of or
• Mania or hypomania, history of or
• Seizures, history of or
• Stroke, history of or
• Tachycardia (fast heart rate)—Use with caution. May make these conditions worse.

• Kidney disease or
• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Use desvenlafaxine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take with or without food. Take with food if it causes an upset stomach.
• Swallow whole. Do not chew, break, or crush.
• To gain the most benefit, do not miss doses.
• Take this medicine at the same time of day.
• Keep taking desvenlafaxine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Desvenlafaxine is a potent and selective serotonin and norepinephrine reuptake inhibitor.

Distribution

Vd: 3.4 L/kg

Metabolism

Hepatic via conjugation (major pathway), and oxidation via CYP3A4 (minor pathway)

Excretion

Urine (45% as unchanged drug; ~24% as metabolites)

Half-Life Elimination

~10 to 11 hours; prolonged in renal failure and hepatic failure

Protein Binding

30%

Average AUC is increased by about 31% and 35% in patients with moderate and severe hepatic impairment, respectively. Clearance is decreased about 20% and 36% in patients with moderate and severe hepatic impairment, respectively. The mean half-life increased from 10 hours in healthy subjects to 13 and 14 hours in patients with moderate and severe hepatic impairment, respectively. Average AUC, clearance and mean half-life is similar in patients with mild hepatic impairment and healthy subjects.

Hot flashes

In meta-analyses of trials evaluating the treatment of hot flashes in post-menopausal women, the use of desvenlafaxine was shown to be safe and effective (Berhan 2014; Sun 2013).

Based on the American College of Obstetricians and Gynecologists, the American Association of Clinical Endocrinologists, and the Society of Obstetricians and Gynaecologists of Canada guidelines, serotonin and norepinephrine reuptake inhibitors such as desvenlafaxine given for hot flashes are an effective and recommended treatment for patients who cannot take hormone replacement therapy.

Major depressive disorder (MDD): Oral: 50 mg once daily; doses up to 400 mg once daily have been studied and have shown to be effective; however, the manufacturer states there is no additional benefit at doses >50 mg per day.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. The 25 mg tablet is intended for a gradual reduction in dose when discontinuing treatment. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA 2010; Bauer 2002; Haddad 2001; NCCMH 2010; Schatzberg 2006; Shelton 2001; Warner 2006).

Hot flashes (off-label use): 100 mg once daily; 150 mg once daily has also been studied and has shown to be effective, but has been associated with treatment discontinuation (Berhan 2014; Sun 2013). Titration during the first 1 to 2 weeks of therapy may help manage adverse effects at therapy initiation (Gallagher 2012).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of desvenlafaxine.

Allow 7 days to elapse between discontinuing desvenlafaxine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Reported for 50 to 100 mg/day.

>10%:

Central nervous system: Dizziness (10% to 13%), insomnia (9% to 12%)

Dermatologic: Hyperhidrosis (10% to 11%)

Gastrointestinal: Nausea (22% to 26%), xerostomia (11% to 17%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (elderly 8%), syncope (<2%), tachycardia (<2%), hypertension (dose related; ≤1% of patients taking 50 to 100 mg daily had sustained diastolic BP ≥90 mm Hg)

Central nervous system: Drowsiness (≤9%), fatigue (7%), anxiety (3% to 5%), delayed ejaculation (1% to 5%), abnormal dreams (2% to 3%), anorgasmia (males ≤3%; females 1%), jitteriness (2%), depersonalization (<2%), dystonia (<2%), vertigo (≤2%), yawning (1%), disturbance in attention (≤1%), male sexual disorder (≤1%)

Dermatologic: Alopecia (<2%), skin photosensitivity (<2%), skin rash (<2%)

Endocrine & metabolic: Decreased libido (males 4% to 5%), increased serum cholesterol (increased by ≥50 mg/dL and ≥261 mg/dL: 3% to 4%), increased serum prolactin (<2%), weight gain (<2%), hot flash (1%), increased LDL cholesterol (increased by ≥50 mg/dL and ≥190 mg/dL: ≤1%)

Gastrointestinal: Constipation (9%), decreased appetite (5% to 8%), vomiting (≤4%), bruxism (<2%)

Genitourinary: Proteinuria (6% to 8%), erectile dysfunction (3% to 6%), urinary retention (<2%), ejaculation failure (≤1%), urinary hesitancy (≤1%)

Hepatic: Abnormal hepatic function tests (<2%)

Hypersensitivity: Angioedema (<2%)

Neuromuscular & skeletal: Tremor (≤3%), stiffness (<2%), weakness (<2%)

Ophthalmic: Blurred vision (3% to 4%), mydriasis (2%)

Otic: Tinnitus (≤2%)

Frequency not defined: Cardiovascular: Coronary occlusion, ischemic heart disease, myocardial infarction

<1% (Limited to important or life-threatening): Acute pancreatitis, angle-closure glaucoma, seizure, Stevens-Johnson syndrome

Applies to desvenlafaxine: oral tablet extended release

Along with its needed effects, desvenlafaxine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking desvenlafaxine:

• Chills
• cold sweats
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fast, pounding, or irregular pulse
• headache
• numbness or tingling in the arms or legs
• shakiness in the legs, arms, hands, or feet
• trembling or shaking of the hands or feet
• trouble thinking, speaking, or walking
• weakness

• Blistering, peeling, or loose skin
• blood in the stool or urine
• chest tightness
• convulsions (seizures)
• cough
• diarrhea
• dilated or enlarged pupils (black part of the eye)
• feeling irritated
• fever
• hives, itching, or rash
• hoarseness
• joint pain, stiffness, or swelling
• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
• loss of bladder control
• muscle pain
• muscle spasm or jerking of all extremities
• nosebleeds
• red skin lesions, often with a purple center
• red, irritated eyes
• red skin
• sore throat
• sores, ulcers, or white spots in the mouth or on the lips
• sudden loss of consciousness
• swelling of the eyelids, face, lips, hands, or feet
• talking, feeling, or acting with excitement
• trouble breathing or swallowing
• unusual bruising
• unusual tiredness or weakness
• vomiting blood

Some side effects of desvenlafaxine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bigger, dilated, or enlarged pupils (black part of the eye)
• decreased appetite
• inability to have an orgasm
• inability to have or keep an erection
• increased sensitivity of the eyes to light
• loss of sexual ability, desire, drive, or performance
• sleepiness or unusual drowsiness
• sleeplessness

• Change in taste
• continuous ringing, buzzing, or other unexplained noise in the ears
• decreased weight
• difficult urination
• fear or nervousness
• hearing loss
• increased sensitivity of the eyes to light
• jitteriness
• lack or loss of strength
• loss of taste

-Moderate renal impairment (CrCl 30 to 50 mL/min): 50 mg per day
-Severe renal impairment (CrCl less than 30 mL/min) or end-stage renal disease (CrCl less than 15 mL/min): 50 mg every other day

Supplemental doses should not be administered after dialysis.

Animal studies have revealed no teratogenic effects. There are no adequate and well-controlled studies in pregnant women. Additionally, neonates exposed to SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors), late in the third trimester required prolonged hospitalization, respiratory support, and tube feeding. Other reported clinical findings have included: respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. This clinical picture is consistent with either a direct toxic effect of SSRIs and SNRIs, a drug discontinuation syndrome, or a serotonin syndrome. AU TGA pregnancy category B2: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

This drug should be used during pregnancy only if the potential benefits justify the potential risks to the fetus. AU TGA pregnancy category: B2 US FDA pregnancy category: C Comments: Women who discontinued antidepressant use during pregnancy were more likely to experience a relapse of major depression than women who continued antidepressant use.