Pristiq

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

• constipation
• loss of appetite
• dry mouth
• dizziness
• extreme tiredness
• unusual dreams
• yawning
• sweating
• uncontrollable shaking of a part of the body
• pain, burning, numbness, or tingling in part of the body
• enlarged pupils (black circles in the centers of the eyes)
• changes in sexual desire or ability
• difficulty urinating

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

• rash
• hives
• swelling
• difficulty breathing
• fast heartbeat
• cough
• chest pain
• fever
• coma (loss of consciousness for a period of time)
• seizures
• hallucinations (seeing things or hearing voices that do not exist)
• fever, sweating, confusion, fast or irregular heartbeat, and severe muscle stiffness
• unusual bleeding or bruising
• nosebleeds
• small red or purple dots on the skin
• nausea
• vomiting
• diarrhea
• headache
• difficulty concentrating
• memory problems
• confusion
• weakness
• problems with coordination
• increased falls
• fainting

Desvenlafaxine 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).

Take Pristiq exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. Your doctor will determine the best dose for you. The dosage of Pristiq must be individualized.

The recommended dose for Pristiq is 50 mg once daily, with or without food. Pristiq should be taken at approximately the same time each day. Tablets should be swallowed whole with fluid and not divided, crushed, chewed, or dissolved.

Desvenlafaxine is a selective serotonin and norepinephrine reuptake inhibitor (SNRIs) antidepressant. Desvenlafaxine affects chemicals in the brain that may be unbalanced in people with depression.

Desvenlafaxine is used to treat major depressive disorder.

Desvenlafaxine may also be used for purposes not listed in this medication guide.

Major Depressive Disorder

Treatment of major depressive disorder in adults.1 3 5 6

Efficacy of long-term use (i.e., >8 weeks) not established by controlled studies.1 If desvenlafaxine is used for extended periods, the need for continued therapy should be reassessed periodically.1

General

• Allow at least 14 days to elapse between discontinuance of an MAO inhibitor and initiation of desvenlafaxine and at least 7 days to elapse between discontinuance of desvenlafaxine and initiation of an MAO inhibitor.1

• If switching from another antidepressant (including venlafaxine) to desvenlafaxine, may be necessary to taper dosage of the previous antidepressant to minimize discontinuance symptoms.a

• Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.1 7 8 9 (See Worsening of Depression and Suicidality Risk under Cautions.)

• Avoid abrupt discontinuance.1 Taper dosage gradually and monitor for withdrawal symptoms.1 25 26 If intolerable symptoms occur following dosage reduction or discontinuance, consider reinstituting previously prescribed dosage, then resume more gradual dosage reductions.1 (See Worsening of Depression and Suicidality Risk and also see Withdrawal of Therapy under Cautions.)

• If used during pregnancy, consider cautiously tapering dosage during third trimester prior to delivery.1 2 15 (See Pregnancy under Cautions.)

• Sustained therapy may be required; periodically reassess need for continued therapy.1 28

Administration

Oral Administration

Administer orally with or without food at approximately the same time each day.1

Swallow extended-release tablets whole with fluid; do not divide, crush, chew, or dissolve.1

Dosage

Available as desvenlafaxine succinate; dosage expressed in terms of desvenlafaxine.1

Adults

50 mg once daily.1 Although efficacy established at dosages of 50–400 mg once daily in clinical studies, no additional benefit observed with dosages >50 mg once daily; adverse effects and discontinuances were more frequent at higher dosages.1

Optimum duration not established; may require several months or longer of sustained antidepressant therapy.1 28 Long-term efficacy (i.e., >8 weeks) of desvenlafaxine at a dosage of 50 mg once daily not studied.1 Periodically reassess need for continued therapy.1 28

Special Populations

Hepatic Impairment

Initially, 50 mg once daily.a Dosage increases to >100 mg daily not recommended.a

Renal Impairment

Mild renal impairment (Clcr 50–80 mL/minute): No dosage adjustment needed.1

Moderate renal impairment (Clcr 30–50 mL/minute): 50 mg once daily.1 Do not increase dosage.a

Severe renal impairment (Clcr< 30 mL/minute) or end-stage renal disease: 50 mg every other day.1 Do not increase dosage and do not give supplemental doses after dialysis.a

Geriatric Patients

No specific dosage recommendations at this time, but consider possibility of age-related decreases in renal function when selecting dosage.1 May administer drug every other day if poorly tolerated.1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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 this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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 this medicine, 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 this medicine 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 this medicine 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 this medicine 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 this medicine, 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 this medicine. 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.

This section provides information on the proper use of a number of products that contain desvenlafaxine. It may not be specific to Pristiq. Please read with care.

Take this medicine only as directed by your doctor to benefit your condition as much as possible. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered.

This medicine should come with a Medication Guide. Read and follow these instructions carefully. Ask your doctor if you have any questions.

You may have to take desvenlafaxine for several weeks before you begin to feel better.

Take the tablet with or without food, and at the same time every day.

Swallow the extended-release tablet whole with water. Do not dissolve, crush, break, or chew it.

Part of the tablet may pass into your stools. This is normal and nothing to worry about.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • For depression:
    • Adults—50 milligrams (mg) once a day. Your doctor may adjust your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Desvenlafaxine succinate administered by oral gavage to mice and rats for 2 years did not increase the incidence of tumors in either study.

Mice received desvenlafaxine succinate at dosages up to 500/300 mg/kg/day (dosage lowered after 45 weeks of dosing). The 300 mg/kg/day dose is 15 times a human dose of 100 mg per day on a mg/m2 basis.

Rats received desvenlafaxine succinate at dosages up to 300 mg/kg/day (males) or 500 mg/kg/day (females). The highest dose is 29 (males) or 48 (females) times a human dose of 100 mg per day on a mg/m2 basis.

Mutagenesis

Desvenlafaxine was not mutagenic in the in vitro bacterial mutation assay (Ames test) and was not clastogenic in an in vitro chromosome aberration assay in cultured CHO cells, an in vivo mouse micronucleus assay, or an in vivo chromosome aberration assay in rats. Additionally, desvenlafaxine was not genotoxic in the in vitro CHO mammalian cell forward mutation assay and was negative in the in vitro BALB/c-3T3 mouse embryo cell transformation assay.

Impairment of fertility

When desvenlafaxine succinate was administered orally to male and female rats, fertility was reduced at the high dose of 300 mg/kg/day, which is 30 times a human dose of 100 mg per day (on a mg/m2 basis). There was no effect on fertility at 100 mg/kg/day, approximately 10 times a human dose of 100 mg per day (on a mg/m2 basis).

See FDA-approved patient labeling (Medication Guide).

Advise patients, their families, and their caregivers about the benefits and risks associated with treatment with Pristiq and counsel them in its appropriate use.

Advise patients, their families, and their caregivers to read the Medication Guide and assist them in understanding its contents. The complete text of the Medication Guide is reprinted at the end of this document.

Suicide Risk

Advise patients, their families and caregivers to look for the emergence of suicidality, especially early during treatment and when the dose is adjusted up or down [see Boxed Warning and Warnings and Precautions (5.1)].

Concomitant Medication

Advise patients taking Pristiq not to use concomitantly other products containing desvenlafaxine or venlafaxine. Healthcare professionals should instruct patients not to take Pristiq with an MAOI or within 14 days of stopping an MAOI and to allow 7 days after stopping Pristiq before starting an MAOI [see Contraindications (4)].

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome, particularly with the concomitant use of Pristiq with other serotonergic agents (including triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, amphetamines, tryptophan, buspirone, and St. John's Wort supplements) [see Warnings and Precautions (5.2)].

Elevated Blood Pressure

Advise patients that they should have regular monitoring of blood pressure when taking Pristiq [see Warnings and Precautions (5.3)].

Abnormal Bleeding

Patients should be cautioned about the concomitant use of Pristiq and NSAIDs, aspirin, warfarin, or other drugs that affect coagulation since combined use of psychotropic drugs that interfere with serotonin reuptake and these agents has been associated with an increased risk of bleeding [see Warnings and Precautions (5.4)].

Angle Closure Glaucoma

Patients should be advised that taking Pristiq can cause mild pupillary dilation, which in susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a prophylactic procedure (e.g., iridectomy), if they are susceptible. [see Warnings and Precautions (5.5)]

Activation of Mania/Hypomania

Advise patients, their families and caregivers to observe for signs of activation of mania/hypomania [see Warnings and Precautions (5.6)].

Discontinuation

Advise patients not to stop taking Pristiq without talking first with their healthcare professional. Patients should be aware that discontinuation effects may occur when stopping Pristiq, and a dose of 25 mg per day is available for discontinuing therapy [see Warnings and Precautions (5.7) and Adverse Reactions (6.1)].

Switching Patients From Other Antidepressants to Pristiq

Discontinuation symptoms have been reported when switching patients from other antidepressants, including venlafaxine, to Pristiq. Tapering of the initial antidepressant may be necessary to minimize discontinuation symptoms.

Interference with Cognitive and Motor Performance

Caution patients about operating hazardous machinery, including automobiles, until they are reasonably certain that Pristiq therapy does not adversely affect their ability to engage in such activities.

Alcohol

Advise patients to avoid alcohol while taking Pristiq [see Drug Interactions (7.7)].

Allergic Reactions

Advise patients to notify their physician if they develop allergic phenomena such as rash, hives, swelling, or difficulty breathing.

Pregnancy

Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations (8.1)].

Nursing

Advise patients to notify their physician if they are breastfeeding an infant [see Use in Specific Populations (8.3)].

Residual Inert Matrix Tablet

Patients receiving Pristiq may notice an inert matrix tablet passing in the stool or via colostomy. Patients should be informed that the active medication has already been absorbed by the time the patient sees the inert matrix tablet.

LAB-0452-16.0

You should not use Pristiq if you are allergic to desvenlafaxine or venlafaxine (Effexor).

Do not use Pristiq within 7 days before or 14 days after you have used an MAO inhibitor, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine. A dangerous drug interaction could occur.

Some medicines can interact with desvenlafaxine and cause a serious condition called serotonin syndrome. Be sure your doctor knows if you also take opioid medicine, herbal products, or medicine for depression, 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.

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

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

• bipolar disorder (manic depression);

• depression, suicidal thoughts;

• liver or kidney disease;

• glaucoma;

• seizures or epilepsy;

• a bleeding or blood clotting disorder; or

• low levels of sodium in your blood.

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.

Pristiq may cause problems in a newborn baby if the mother takes the medication late in pregnancy (during the third trimester). Tell your doctor if you are pregnant or plan to become pregnant during treatment.

Desvenlafaxine can pass into breast milk and may harm a nursing baby. You should not breast-feed while using this medicine.

Pristiq is not approved for use by anyone younger than 18 years old.

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)

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.

Taking Pristiq 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.

Many drugs can interact with desvenlafaxine. Not all possible interactions are listed here. Tell your doctor about all your current medicines and any you start or stop using, especially:

• any other antidepressant;

• sibutramine;

• St. John's wort;

• tramadol;

• tryptophan (sometimes called L-tryptophan);

• lithium, or other medicine to treat mood disorders, thought disorders, or mental illness; or

• migraine headache medicine - sumatriptan, zolmitriptan, and others.

This list is not complete and many other drugs can interact with desvenlafaxine. This includes prescription and over-the-counter medicines, vitamins, and herbal products. Give a list of all your medicines to any healthcare provider who treats you.