DRIZALMA SPRINKLE- duloxetine capsule, delayed release

United States - English - NLM (National Library of Medicine)

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Active ingredient:
DULOXETINE HYDROCHLORIDE (UNII: 9044SC542W) (DULOXETINE - UNII:O5TNM5N07U)
Available from:
SUN PHARMACEUTICAL INDUSTRIES, INC.
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
DRIZALMA Sprinkle is indicated for the treatment of: Chronic Musculoskeletal Pain in adults [see Clinical Studies (14.4)] Use of MAOIs intended to treat psychiatric disorders with DRIZALMA Sprinkle, or within 5 days of stopping treatment with DRIZALMA Sprinkle, are contraindicated because of an increased risk of serotonin syndrome. The use of DRIZALMA Sprinkle within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.10), Warnings and Precautions (5.4, 5.12), Drug Interactions (7)] . Starting DRIZALMA Sprinkle in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is contraindicated because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.4)] . Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Healthcare providers are encouraged to register patients by calling the Natio
Product summary:
Features Strengths 20 mg a 30 mg a 40 mg a 60 mg a Body color Green White White Green Cap color Green Blue White Blue Cap imprint RG53 RG54 RL85 RG55 Body imprint RG53 RG54 RL85 RG55 Presentations and NDC Codes Bottles of 30 47335-616-30 47335-617-30 47335-618-30 47335-619-30 Bottles of 60 47335-616-60 47335-617-60 47335-618-60 47335-619-60 Bottles of 90 47335-616-90 47335-617-90 47335-618-90 47335-619-90 Bottles of 1000 47335-616-10 47335-617-10 47335-618-10 47335-619-10 Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tightly closed container. For 30, 60, and 90 count bottles only: This package is child-resistant.
Authorization status:
New Drug Application
Authorization number:
47335-616-10, 47335-616-30, 47335-616-60, 47335-616-90, 47335-617-10, 47335-617-30, 47335-617-60, 47335-617-90, 47335-618-10, 47335-618-30, 47335-618-60, 47335-618-90, 47335-619-10, 47335-619-30, 47335-619-60, 47335-619-90

DRIZALMA SPRINKLE- duloxetine capsule, delayed release

SUN PHARMACEUTICAL INDUSTRIES, INC.

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Medication Guide

DRIZALMA Sprinkle (dri zal' mah)

(duloxetine delayed-release capsules)

What is the most important information I should know about DRIZALMA Sprinkle?

DRIZALMA Sprinkle may cause serious side effects, including:

Increased risk of suicidal thoughts or actions in some children, adolescents, and young adults.

DRIZALMA Sprinkle and other antidepressant medicines may increase suicidal thoughts and actions in

some people 24 years of age and younger, especially within the first few months of treatment or when

the dose is changed.

Depression and other serious mental illnesses are the most important causes of suicidal thoughts or

actions. Some people may have a higher risk of having suicidal thoughts or actions. These include

people who have (or have a family history of) depression, bipolar illness (also called manic-depressive

illness) or a history of suicidal thoughts or actions.

How can I watch for and try to prevent suicidal thoughts and actions?

Pay close attention to any changes in mood, behavior, actions, thoughts, or feelings, especially sudden

changes. This is very important when an antidepressant medicine is started or when the dose is

changed.

Call your healthcare provider right away to report new or sudden changes in mood, behavior, thoughts,

or feelings.

Keep all follow-up visits with your healthcare provider as scheduled. Call your healthcare provider

between visits as needed, especially if you have concerns about symptoms.

Call your healthcare provider or get emergency help right away if you or your family member have any

of the following symptoms, especially if they are new, worse, or worry you.

attempts to commit suicide

acting on dangerous impulses

acting aggressive, being angry, or violent

thoughts about suicide or dying

new or worse depression

new or worse anxiety

panic attacks

feeling very agitated or restless

new or worse irritability

trouble sleeping

an extreme increase in activity or talking (mania)

other unusual changes in behavior or mood

What is DRIZALMA Sprinkle?

DRIZALMA Sprinkle is prescription medicine used to treat:

A certain type of depression called Major Depressive Disorder (MDD) in adults

Generalized Anxiety Disorder (GAD) in adults and children 7 to 17 years old

Diabetic Peripheral Neuropathic Pain (DPNP) in adults

Chronic Musculoskeletal Pain in adults

It is not known if DRIZALMA Sprinkle is safe and effective for use to treat GAD in children less than 7

years of age.

It is not known if DRIZALMA Sprinkle is safe and effective for use to treat MDD, DPNP, and Chronic

Musculoskeletal Pain in children.

Do not take DRIZALMA Sprinkle if you:

take a Monoamine Oxidase Inhibitor (MAOI)

have stopped taking an MAOI in the last 14 days

are being treated with the antibiotic linezolid or intravenous methylene blue

Ask your healthcare provider or pharmacist if you are not sure if you take an MAOI, including the antibiotic

linezolid or intravenous methylene blue.

Do not start taking an MAOI for a least 5 days after you stop treatment with DRIZALMA Sprinkle.

Before taking DRIZALMA Sprinkle, tell your healthcare provider about all your medical conditions,

including if you:

have or have a family history of suicide, bipolar disorder, depression, mania or hypomania

have liver or kidney problems

drink alcohol

have or had had bleeding problems

have glaucoma (high pressure in the eye)

have or have had seizures (convulsions)

have high or low blood pressure

have diabetes or high blood sugar

have or have had heart problems or stroke

have low sodium levels in your blood

have problems urinating (hesitation) or emptying your bladder (urinary retention)

are pregnant or plan to become pregnant. DRIZALMA Sprinkle may harm your unborn baby. Talk to

your healthcare provider about the risks to you and your unborn baby if you take DRIZALMA Sprinkle

during pregnancy.

Tell your healthcare provider right away if you become pregnant or think you are pregnant during

treatment with DRIZALMA Sprinkle.

If you become pregnant during treatment with DRIZALMA Sprinkle, talk to your healthcare provider

about registering with the National Pregnancy Registry for Antidepressants. You can register by calling

1-844-405-6185.

are breastfeeding or plan to breastfeed. DRIZALMA Sprinkle passes into your breast milk and may

harm your baby. Talk to your healthcare provider about the best way to feed your baby during

treatment with DRIZALMA Sprinkle.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter

medicines, vitamins, and herbal supplements.

DRIZALMA Sprinkle and other medicines may affect each other causing possible serious side effects.

DRIZALMA Sprinkle may affect the way other medicines work and other medicines may affect the way

DRIZALMA Sprinkle works.

Especially tell your healthcare provider if you take:

other MAOIs

medicines to treat migraine headaches known as triptans

tricyclic antidepressants

fentanyl

lithium

tramadol

tryptophan

buspirone

amphetamines

St. John’s Wort

other medicines containing desvenlafaxine or venlafaxine

medicines that can affect blood clotting such as aspirin, nonsteroidal anti-inflammatory drugs

(NSAIDs), warfarin

Ask your healthcare provider if you are not sure if you are taking any of these medicines. Your healthcare

provider can tell you if it is safe to take DRIZALMA Sprinkle with your other medicines.

Do not start or stop any other medicines during treatment with TREATMENT without talking to your

healthcare provider first. Stopping DRIZALMA Sprinkle suddenly may cause you to have serious side

effects. See, “What are the possible side effects of DRIZALMA Sprinkle?”

Know the medicines you take. Keep a list of them to show to your healthcare provider and pharmacist when

you get a new medicine.

How should I take DRIZALMA Sprinkle?

Take DRIZALMA Sprinkle exactly as your healthcare provider tells you to take it. Do not change your

dose or stop taking DRIZALMA Sprinkle without talking to your healthcare provider.

Your healthcare provider may need to change the dose of DRIZALMA Sprinkle until it is the right

dose for you.

Take DRIZALMA Sprinkle with or without food.

Swallow DRIZALMA Sprinkle whole. Do not chew or crush DRIZALMA Sprinkle.

If you have trouble swallowing DRIZALMA Sprinkle whole, you can open the capsule and take the

contents with applesauce. See the, “Instructions for Use” at the end of this Medication Guide for

instructions on how to take DRIZALMA Sprinkle with applesauce.

See the, “Instructions for Use” at the end of this Medication Guide for instructions on how to mix and

give DRIZALMA Sprinkle through a nasogastric (NG) tube.

If you miss a dose of DRIZALMA Sprinkle, 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 2 doses of DRIZALMA Sprinkle at the same time.

If you take too much DRIZALMA Sprinkle, call your healthcare provider or poison control center at 1800-

222-1222 right away, or go to the nearest hospital emergency room.

What should I avoid while taking DRIZALMA Sprinkle?

Do not drive, operate heavy machinery, or do other dangerous activities until you know how

DRIZALMA Sprinkle affects you. DRIZALMA Sprinkle can make you drowsy.

You should not drink large amounts of alcohol during treatment with DRIZALMA Sprinkle. Drinking large

amounts of alcohol during treatment with DRIZALMA Sprinkle can increase your risk of having serious side

effects.

What are the possible side effects of DRIZALMA Sprinkle?

DRIZALMA Sprinkle may cause serious side effects, including:

See “What is the most important information I should know about DRIZALMA Sprinkle?”

Liver problems. DRIZALMA Sprinkle may cause severe liver problems that may cause death. Tell

your healthcare provider right away if you develop any of the following symptoms of severe liver

problems:

itching

right upper abdominal pain

dark urine

yellow skin or eyes

enlarged liver

increased liver enzymes

Decreased in blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise

too quickly from a sitting or lying position, especially when you start or restart treatment or when the

dose is changed.

Falls and fainting. DRIZALMA Sprinkle may cause you to feel sleepy or dizzy, may cause a decrease

in your blood pressure when you rise to quickly from a sitting or lying position, and can slow your

thinking and motor skills which may lead to falls that have caused fractures or other serious injuries.

Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen

when you take DRIZALMA Sprinkle with certain other medicines. See, “Who should not take

DRIZALMA Sprinkle?” Call your healthcare provider or go to the nearest hospital emergency room

right away if you have any of the following signs and symptoms of serotonin syndrome:

agitation

seeing or hearing things that are not real (hallucinations)

confusion

coma

fast heart beat

blood pressure changes

dizziness

sweating

flushing

high body temperature (hyperthermia)

tremors, stiff muscles, or muscle

twitching

loss of coordination

seizures

nausea, vomiting, diarrhea

Abnormal bleeding. Taking DRIZALMA Sprinkle with aspirin, non-steroidal anti-inflammatory drugs

(NSAIDs), or blood thinners may add to this risk. Tell your healthcare provider right away about any

unusual bleeding or bruising.

Severe skin reactions. DRIZALMA Sprinkle may cause serious skin reactions that may need to be

treated in a hospital and may be life-threating. Stop taking DRIZALMA Sprinkle and call your

healthcare provider or get emergency help right away if you develop skin blisters, peeling rash, sores in

the mouth, hives or any other allergic reactions during treatment with DRIZALMA Sprinkle.

Discontinuation syndrome. Suddenly stopping DRIZALMA Sprinkle when you take higher doses may

cause you to have serious side effects. Your healthcare provider may want to decrease your dose

slowly. Symptoms may include:

dizziness

nausea

headache

irritability and agitation

problems sleeping

diarrhea

anxiety

tiredness

abnormal dreams

sweating

confusion

changes in your mood

seizures

electric shock sensation

(paresthesia)

hypomania

ringing in your ears

(tinnitus)

Manic episodes. Manic episodes may happen in people with bipolar disorder who take DRIZALMA

Sprinkle. Symptoms may include:

greatly increased energy

severe trouble sleeping

racing thoughts

reckless behavior

unusually grand ideas

excessive happiness or irritability

talking more or faster than usual

Eye problems (angle-closure glaucoma). 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.

Seizures (convulsions).

Increases in blood pressure. Your healthcare provider should check your blood pressure regularly

during treatment with DRIZALMA Sprinkle. If you have high blood pressure, it should be controlled

before you start treatment with DRIZALMA Sprinkle.

Low sodium levels in your blood (hyponatremia). Low sodium levels can happen during treatment with

DRIZALMA Sprinkle. Low sodium levels in your blood may be serious and may cause death. Elderly

people may be at greater risk for this. Signs and Symptoms of low sodium levels in your blood may

include:

headache

difficulty concentrating

memory changes

confusion

weakness and unsteadiness on your feet which can lead to falls

In severe or more sudden cases, signs and symptoms include:

hallucinations (seeing or hearing things that are not real)

fainting

seizures

coma

respiratory arrest

death

Problems with urination. DRIZALMA Sprinkle may cause you to have problems with urination

including decreased urine flow and being unable to pass any urine. Tell your healthcare provider if you

develop any problems with urine flow during treatment with DRIZALMA Sprinkle.

Your healthcare provider may tell you to stop taking DRIZALMA Sprinkle if you develop serious side

effects during treatment with DRIZALMA Sprinkle.

The most common side effects of DRIZALMA Sprinkle, include:

nausea

dry mouth

sleepiness

constipation

fatigue

loss of appetite

increased sweating

Height and weight changes in children and adolescents may happen during treatment with DRIZALMA

Sprinkle. Your healthcare provider should check your child’s or adolescent’s height and weight during

treatment with DRIZALMA Sprinkle.

These are not all the possible side effects of DRIZALMA Sprinkle.

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

FDA-1088.

How should I store DRIZALMA Sprinkle?

Store DRIZALMA Sprinkle at room temperature between 68°F to 77°F (20°C to 25°C).

Store DRIZALMA Sprinkle in a tightly closed container.

Keep DRIZALMA Sprinkle and all medicines out of the reach of children.

General information about the safe and effective use of DRIZALMA Sprinkle.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not

use DRIZALMA Sprinkle for a condition for which it was not prescribed. Do not give DRIZALMA

Sprinkle to other people, even if they have the same symptoms that you have. It may harm them. You

may ask your healthcare provider or pharmacist for information about DRIZALMA Sprinkle that is

written for healthcare professionals.

What are the ingredients in DRIZALMA Sprinkle?

Active ingredient: duloxetine hydrochloride

Inactive ingredients: hypromellose, hypromellose phthalate, polyethylene glycol, starch, sucrose, sugar

spheres, talc, titanium dioxide, and triethyl citrate.

The capsule shell ingredients for 20 mg strength are D&C Yellow 10, FD &C Blue 1, FD &C Red 40,

gelatin, sodium lauryl sulfate and titanium dioxide. The capsule shell ingredients for 30 mg strength are

FD &C Blue 1, FD &C Red 40 and FD &C Red 3 (present in cap), gelatin, sodium lauryl sulfate and

titanium dioxide. The capsule shell ingredients for 40 mg strength are gelatin, sodium lauryl sulfate and

titanium dioxide. The capsule shell ingredients for 60 mg strength are D&C Yellow 10 (present in

body), FD &C Blue 1, FD &C Red 40, FD &C Red 3 (present in cap), gelatin, sodium lauryl sulfate

and titanium dioxide.

The imprinting ink for 20 mg, 30 mg, 40 mg, and 60 mg strength capsules was made of ammonia

solution, black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide,

propylene glycol and shellac.

Manufactured by:

Sun Pharmaceutical Industries Limited,

Mohali, INDIA

Distributed by:

Sun Pharmaceutical Industries, Inc.

Cranbury, NJ 08512

FDA-03

For more information call Sun Pharmaceutical Industries, Inc. at 1-800-818-4555.

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: July/2019

Revised: 7/2020

Document Id: 18db1eaf-84ab-4c79-8aa1-a9c66d1ba714

34391-3

Set id: b41423b8-dfec-4d79-ba3c-e43a87803d85

Version: 4

Effective Time: 20200703

SUN PHARMACEUTICAL INDUSTRIES, INC.

DRIZALMA SPRINKLE- duloxetine capsule, delayed release

SUN PHARMACEUTICAL INDUSTRIES, INC.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use DRIZALMA SPRINKLE safely and effectively.

See full prescribing information for DRIZALMA SPRINKLE.

DRIZALMA SPRINKLE™ (duloxetine delayed-release capsules), for oral use.

Initial U.S. Approval: 2004

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

See full prescribing information for complete boxed warning.

RECENT MAJOR CHANGES

INDICATIONS AND USAGE

DRIZALMA Sprinkle is a serotonin and norepinephrine reuptake inhibitor (SNRI) indicated for: (1)

DOSAGE AND ADMINISTRATION

Indication (2)

Starting Dose (2)

Target Dose (2)

Maximum Dose (2)

MDD (2.2) (2)

40 mg/day to (2)

60 mg/day (2)

Acute Treatment: 40 mg/day

(20 mg twice daily) to 60

mg/day (once daily or as 30 mg

twice daily); Maintenance

Treatment: 60 mg/day (2)

120 mg/day (2)

GAD (2.3) (2)

Adults (2)

60 mg/day (2)

60 mg/day (once daily) (2)

120 mg/day (2)

Elderly (2)

30 mg/day (2)

60 mg/day (once daily) (2)

120 mg/day (2)

Children and Adolescents (7 to 17

years old) (2)

30 mg/day (2)

30 to 60 mg/day (once daily)

120 mg/day (2)

DPNP (2.4) (2)

60 mg/day (2)

60 mg/day (once daily) (2)

60 mg/day (2)

Chronic Musculoskeletal Pain (2.5) (2)

30 mg/day (2)

60 mg/day (once daily) (2)

60 mg/day (2)

DOSAGE FORMS AND STRENGTHS

Increased risk of suicidal thinking and behavior in pediatric and young adult patients taking

antidepressants (5.1)

Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal

thoughts and behaviors (5.1)

Warnings and Precautions (5.5) 6/2020

Major Depressive Disorder (MDD) in adults (1)

Generalized Anxiety Disorder (GAD) in adults and pediatric patients ages 7 years to 17 years old (1)

Diabetic Peripheral Neuropathic Pain (DPNP) in adults (1)

Chronic Musculoskeletal Pain in adults (1)

Take DRIZALMA Sprinkle with or without food (2.1)

DRIZALMA Sprinkle may be: swallowed whole (do not crush or chew capsule); opened and sprinkled over

applesauce; or administered via nasogastric tube (2.1)

Take a missed dose as soon as it is remembered. Do not take two doses of DRIZALMA Sprinkle at the same time

(2.1)

There is no evidence that doses greater than 60 mg/day confers additional benefit, while some adverse reactions

were observed to be dose-dependent (2)

Discontinuation: Gradually reduce dosage to avoid discontinuation symptoms (2.9, 5.7)

DOSAGE FORMS AND STRENGTHS

20 mg, 30 mg, 40 mg and 60 mg delayed-release capsules (3) (3)

CONTRAINDICATIONS

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact Sun Pharmaceutical Industries, Inc. at 1-800-818-4555

or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

USE IN SPECIFIC POPULATIONS

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 7/2020

Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with DRIZALMA Sprinkle

or within 5 days of stopping treatment with DRIZALMA Sprinkle. Do not use DRIZALMA Sprinkle

within 14 days of stopping an MAOI intended to treat psychiatric disorders. In addition, do not start DRIZALMA

Sprinkle in a patient who is being treated with linezolid or intravenous methylene blue (4)

Hepatotoxicity: Hepatic failure, sometimes fatal, has been reported in patients treated with duloxetine delayed-release

capsules. Duloxetine delayed-release capsules should be discontinued in patients who develop jaundice or other

evidence of clinically significant liver dysfunction and should not be resumed unless another cause can be

established. DRIZALMA Sprinkle should not be prescribed to patients with substantial alcohol use or evidence of

chronic liver disease (5.2)

Orthostatic Hypotension, Falls and Syncope: Cases have been reported with duloxetine delayed-release capsules

therapy (5.3)

Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents (e.g., SSRI, SNRI,

triptans), but also when taken alone. If it occurs, discontinue DRIZALMA Sprinkle and initiate supportive treatment

(5.4)

Increased Risk of Bleeding: Duloxetine may increase the risk of bleeding events. Concomitant use of NSAIDs,

aspirin, other antiplatelet drugs, warfarin, and anticoagulants may increase this risk (5.5, 7, 8.1)

Severe Skin Reactions: Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS),

can occur with duloxetine. DRIZALMA Sprinkle should be discontinued at the first appearance of blisters, peeling

rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified (5.6)

Discontinuation Syndrome: Taper dose when possible and monitor for discontinuation symptoms (5.7)

Activation of Mania or Hypomania: Use cautiously in patients with bipolar disorder. Cautions patients about the risk of

activation of mania/hypomania (5.8)

Angle-Closure Glaucoma: Avoid use of antidepressants, including DRIZALMA Sprinkle, in patients with untreated

anatomically narrow angles (5.9)

Seizures: Prescribe with care in patients with a history of seizure disorder (5.10)

Blood Pressure: Monitor blood pressure prior to initiating treatment and periodically throughout treatment (5.11)

Hyponatremia: Can occur in association with SIADH. Cases of hyponatremia have been reported (5.13)

Glucose Control in Diabetes: In diabetic peripheral neuropathic pain patients, small increases in fasting blood glucose,

and HbA1 have been observed (5.14)

Most common adverse reactions (≥5% and at least twice the incidence of placebo patients): nausea, dry mouth,

somnolence, constipation, decreased appetite, and hyperhidrosis (6.1).

Potent CYP1A2 Inhibitors: Avoid concomitant use (2.6, 7)

CYP2D6 Substrates: Consider dose reduction with concomitant use (7)

Hepatic Impairment: Avoid use in patients with mild, moderate, or severe hepatic impairment (2.7)

Renal Impairment: Avoid use in patients with severe renal impairment (2.7, 5.14)

Pregnancy: Third trimester use may increase risk for symptoms of poor adaptation (respiratory distress,

temperature instability, feeding difficulty, hypotonia, tremor, irritability) in the neonate (8.1)

FULL PRESCRIBING INFORMATION: CONTENTS*

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Information

2.2 Dosage for Treatment of Major Depressive Disorder

2.3 Dosage for Treatment of Generalized Anxiety Disorder

2.4 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain

2.5 Dosage for Treatment of Chronic Musculoskeletal Pain

2.6 Dosage Recommendations for Concomitant Use with Potent CYP1A2 Inhibitors

2.7 Dosage Recommendations for Patients with Hepatic and Renal Impairment

2.8 Screen for Bipolar Disorder Prior to Starting DRIZALMA Sprinkle

2.9 Discontinuation of Treatment with DRIZALMA Sprinkle

2.10 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat

Psychiatric Disorders

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults

5.2 Hepatotoxicity

5.3 Orthostatic Hypotension, Falls and Syncope

5.4 Serotonin Syndrome

5.5 Increased Risk of Bleeding

5.6 Severe Skin Reactions

5.7 Discontinuation Syndrome

5.8 Activation of Mania/Hypomania

5.9 Angle-Closure Glaucoma

5.10 Seizures

5.11 Elevated Blood Pressure

5.12 Clinically Important Drug Interactions

5.13 Hyponatremia

5.14 Use in Patients with Concomitant Illness

5.15 Urinary Hesitation and Retention

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Drugs Having Clinically Important Interactions with DRIZALMA Sprinkle

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Gender

8.7 Smoking Status

8.8 Race

8.9 Hepatic Impairment

8.10 Severe Renal Impairment

9 DRUG ABUSE AND DEPENDENCE

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

10.1 Signs and Symptoms

10.2 Management of Overdose

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

14.1 Major Depressive Disorder

14.2 Generalized Anxiety Disorder

14.3 Diabetic Peripheral Neuropathic Pain

14.4 Chronic Musculoskeletal Pain

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS

Closely monitor all antidepressant-treated patients for clinical worsening, and for

emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)].

1 INDICATIONS AND USAGE

DRIZALMA Sprinkle is indicated for the treatment of:

Chronic Musculoskeletal Pain in adults [see Clinical Studies (14.4)]

2 DOSAGE AND ADMINISTRATION

2.1 Important Administration Information

Sections or subsections omitted from the full prescribing information are not listed.

Antidepressants increased the risk of suicidal thoughts and behavior in pediatric and

young adult patients in short-term studies.

Major Depressive Disorder in adults [see Clinical Studies (14.1)]

Generalized Anxiety Disorder in adults and pediatric patients 7 years to 17 years old [see Clinical

Studies (14.2)]

Diabetic Peripheral Neuropathy in adults [see Clinical Studies (14.3)]

Administer DRIZALMA Sprinkle with or without food. Swallow DRIZALMA Sprinkle whole (do

not chew or crush the capsule). For patients unable to swallow an intact capsule, refer to the

alternative administration instructions below.

Directions for use with applesauce

2.2 Dosage for Treatment of Major Depressive Disorder

Administer DRIZALMA Sprinkle at a total dose of 40 mg per day (given as 20 mg twice daily) to 60 mg

per day (given either once daily or as 30 mg twice daily). For some patients, it may be desirable to start

at 30 mg once daily for 1 week, to allow patients to adjust to the medication before increasing to 60 mg

once daily. While a 120 mg per day dose was shown to be effective, there is no evidence that doses

greater than 60 mg per day confer any additional benefits. The safety of doses above 120 mg per day

has not been adequately evaluated. Periodically reassess to determine the need for maintenance treatment

and the appropriate dose for such treatment [see Clinical Studies (14.1)].

2.3 Dosage for Treatment of Generalized Anxiety Disorder

Adults - For most patients, initiate DRIZALMA Sprinkle 60 mg once daily. For some patients, it may be

desirable to start at 30 mg once daily for 1 week, to allow patients to adjust to the medication before

increasing to 60 mg once daily. While a 120 mg once daily dose was shown to be effective, there is no

evidence that doses greater than 60 mg per day confer additional benefit. Nevertheless, if a decision is

made to increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily.

The safety of doses above 120 mg once daily has not been adequately evaluated. Periodically reassess

to determine the continued need for maintenance treatment and the appropriate dose for such treatment

[see Clinical Studies (14.2)].

Elderly - Initiate DRIZALMA Sprinkle at a dose of 30 mg once daily for 2 weeks before considering an

increase to the target dose of 60 mg. Thereafter, patients may benefit from doses above 60 mg once

daily. If a decision is made to increase the dose beyond 60 mg once daily, increase dose in increments

of 30 mg once daily. The maximum dose studied was 120 mg per day. Safety of doses above 120 mg

once daily has not been adequately evaluated [see Clinical Studies (14.2)].

Children and Adolescents (7 to 17 years of age) - Initiate DRIZALMA Sprinkle at a dose of 30 mg once

daily for 2 weeks before considering an increase to 60 mg. The recommended dose range is 30 to 60

mg once daily. Some patients may benefit from doses above 60 mg once daily. If a decision is made to

increase the dose beyond 60 mg once daily, increase dose in increments of 30 mg once daily. The

maximum dose studied was 120 mg per day. The safety of doses above 120 mg once daily has not been

evaluated [see Clinical Studies (14.2)].

2.4 Dosage for Treatment of Diabetic Peripheral Neuropathic Pain

Administer DRIZALMA Sprinkle 60 mg once daily. There is no evidence that doses higher than 60 mg

confer additional significant benefit and the higher dose is clearly less well tolerated [see Clinical

Studies (14.3)]. For patients for whom tolerability is a concern, a lower starting dose may be considered.

Since diabetes is frequently complicated by renal disease, consider a lower starting dose and gradual

increase in dose for patients with renal impairment [see Dosage and Administration (2.7), Use in Specific

Populations (8.10), and Clinical Pharmacology (12.3)].

For patients with swallowing difficulty, DRIZALMA Sprinkle can be opened and the contents

sprinkled over applesauce. The contents of the capsules should be swallowed along with a small

amount (tablespoonful) of applesauce. The drug/food mixture should be swallowed immediately

and not stored for future use.

Nasogastric tube administration

Open and add contents of capsule to an all plastic catheter tip syringe and add 50 mL of water.

Gently shake the syringe for approximately 10 seconds. Promptly deliver through a 12 French or

larger nasogastric tube. Ensure no pellets are left in the syringe. Rinse with additional water

(about 15 mL) if needed.

If a dose of DRIZALMA Sprinkle is missed, take the missed dose as soon as it is remembered. If

it is almost time for the next dose, skip the missed dose and take the next dose at the regular time.

Do not take two doses of DRIZALMA Sprinkle at the same time.

2.5 Dosage for Treatment of Chronic Musculoskeletal Pain

Administer DRIZALMA Sprinkle 60 mg once daily. Begin treatment at 30 mg for one week, to allow

patients to adjust to the medication before increasing to 60 mg once daily. There is no evidence that

higher doses confer additional benefit, even in patients who do not respond to a 60 mg dose, and higher

doses are associated with a higher rate of adverse reactions [see Clinical Studies (14.4)].

2.6 Dosage Recommendations for Concomitant Use with Potent CYP1A2 Inhibitors

2.7 Dosage Recommendations for Patients with Hepatic and Renal Impairment

Hepatic Impairment: Avoid use in patients with mild (Child-Pugh A), moderate (Child-Pugh B), or

severe hepatic impairment (Child-Pugh C) [see Warnings and Precautions (5.14) and Use in Specific

Populations (8.9)].

Severe Renal Impairment: Avoid use in patients with severe renal impairment ( CrCl ≥15 to <30 mL/min)

[see Warnings and Precautions (5.14) and Use in Specific Populations (8.10)].

2.8 Screen for Bipolar Disorder Prior to Starting DRIZALMA Sprinkle

Prior to initiating treatment with DRIZALMA Sprinkle or another antidepressant, screen patients for a

personal or family history of bipolar disorder, mania, or hypomania [see Warnings and Precautions

(5.8)].

2.9 Discontinuation of Treatment with DRIZALMA Sprinkle

2.10 Switching a Patient to or from a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat

Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric

disorders and initiation of therapy with DRIZALMA Sprinkle. Conversely, at least 5 days should be

allowed after stopping DRIZALMA Sprinkle before starting an MAOI intended to treat psychiatric

disorders [see Contraindications (4), Warnings and Precautions (5.4)].

3 DOSAGE FORMS AND STRENGTHS

20 mg: hard gelatin capsules with green cap imprinted with “RG53” and green body imprinted with

RG53” containing off-white to pale-yellow colored pellets.

30 mg: hard gelatin capsules with blue cap imprinted with “RG54” and white body imprinted with

RG54” containing off-white to pale-yellow colored pellets.

40 mg: hard gelatin capsules with white cap imprinted with “RL85” and white body imprinted with “RL

85” containing off-white to pale-yellow colored pellets.

60 mg: hard gelatin capsules with blue cap imprinted with “RG55” and green body imprinted with

RG55” containing off-white to pale-yellow colored pellets.

4 CONTRAINDICATIONS

Coadministration with potent CYP1A2 Inhibitors: Avoid concomitant use of DRIZALMA Sprinkle

with potent CYP1A2 inhibitors.

Adverse reactions may occur upon discontinuation of DRIZALMA Sprinkle [see Warnings and

Precautions (5.7)]. Gradually reduce the dosage rather than stopping DRIZALMA Sprinkle

abruptly whenever possible [see Warnings and Precautions (5.7)].

Use of MAOIs intended to treat psychiatric disorders with DRIZALMA Sprinkle, or within 5 days of

stopping treatment with DRIZALMA Sprinkle, are contraindicated because of an increased risk of

serotonin syndrome. The use of DRIZALMA Sprinkle within 14 days of stopping an MAOI intended to

treat psychiatric disorders is also contraindicated [see Dosage and Administration (2.10), Warnings and

Precautions (5.4, 5.12), Drug Interactions (7)].

Starting DRIZALMA Sprinkle in a patient who is being treated with MAOIs such as linezolid or

intravenous methylene blue is contraindicated because of an increased risk of serotonin syndrome [see

Warnings and Precautions (5.4)].

5 WARNINGS AND PRECAUTIONS

5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults

In pooled analyses of placebo-controlled trials of antidepressant drugs (SSRIs and other antidepressant

classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of

suicidal thoughts and behaviors in the antidepressant-treated patients age 24 years and younger was

greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts

and behaviors among drugs, but there was an increased risk identified in young patients for most drugs

studied. There were differences in absolute risk of suicidal thoughts and behaviors across the different

indications, with the highest incidence in MDD. The drug-placebo differences in the number of cases

of suicidal thoughts and behaviors per 1000 patients treated are provided in Table 1.

Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behavior in

the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients

Age Range

Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or

Behaviors per 1000 Patients Treated

Increases Compared to Placebo

<18

14 additional patients

18 to 24

5 additional patients

Decreases Compared to Placebo

25 to 64

1 fewer patients

≥65

6 fewer patients

It is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and

young adults extends to longer-term use, i.e., beyond four months. However, there is substantial

evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants

delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts

5.2 Hepatotoxicity

There have been reports of hepatic failure, sometimes fatal, in patients treated with duloxetine delayed-

release capsules. These cases have presented as hepatitis with abdominal pain, hepatomegaly, and

elevation of transaminase levels to more than twenty times the upper limit of normal with or without

jaundice, reflecting a mixed or hepatocellular pattern of liver injury. Duloxetine delayed-release

capsules should be discontinued in patients who develop jaundice or other evidence of clinically

significant liver dysfunction and should not be resumed unless another cause can be established.

Cases of cholestatic jaundice with minimal elevation of transaminase levels have also been reported.

Other post-marketing reports indicate that elevated transaminases, bilirubin, and alkaline phosphatase

have occurred in patients with chronic liver disease or cirrhosis.

Duloxetine delayed-release capsules increased the risk of elevation of serum transaminase levels in

development program clinical trials. Liver transaminase elevations resulted in the discontinuation of

0.3% (92/34,756) of duloxetine delayed-release capsules-treated patients. In most patients, the median

time to detection of the transaminase elevation was about two months. In adult placebo-controlled trials

in any indication, for patients with normal and abnormal baseline ALT values, elevation of ALT > 3

times the upper limit of normal occurred in 1.25% (144/11,496) of duloxetine delayed-release

capsules-treated patients compared to 0.45% (39/8716) of placebo- treated patients. In adult placebo-

controlled studies using a fixed dose design, there was evidence of a dose response relationship for

ALT and AST elevation of >3 times the upper limit of normal and >5 times the upper limit of normal,

respectively.

Because it is possible that duloxetine and alcohol may interact to cause liver injury or that duloxetine

may aggravate pre-existing liver disease, DRIZALMA Sprinkle should not be prescribed to patients

with substantial alcohol use or evidence of chronic liver disease.

5.3 Orthostatic Hypotension, Falls and Syncope

Orthostatic hypotension, falls and syncope have been reported with therapeutic doses of duloxetine

delayed-release capsules. Syncope and orthostatic hypotension tend to occur within the first week of

therapy but can occur at any time during duloxetine delayed-release capsules treatment, particularly

after dose increases. The risk of falling appears to be related to the degree of orthostatic decrease in

blood pressure as well as other factors that may increase the underlying risk of falls.

In an analysis of patients from all placebo-controlled trials, patients treated with duloxetine delayed-

release capsules reported a higher rate of falls compared to patients treated with placebo. Risk appears

to be related to the presence of orthostatic decrease in blood pressure. The risk of blood pressure

decreases may be greater in patients taking concomitant medications that induce orthostatic hypotension

(such as anti-hypertensives) or are potent CYP1A2 inhibitors [see Warnings and Precautions (5.12) and

Drug Interactions (7.1)] and in patients taking duloxetine delayed-release capsules at doses above 60 mg

daily. Consideration should be given to dose reduction or discontinuation of DRIZALMA Sprinkle in

patients who experience symptomatic orthostatic hypotension, falls and/or syncope during duloxetine

delayed-release capsules therapy.

Risk of falling also appeared to be proportional to a patient’s underlying risk for falls and appeared to

increase steadily with age. As elderly patients tend to have a higher underlying risk for falls due to a

higher prevalence of risk factors such as use of multiple medications, medical comorbidities and gait

and behaviors.

Monitor all antidepressant-treated patients for any indication for clinical worsening and emergence

of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at

times of dosage changes. Counsel family members or caregivers of patients to monitor for

changes in behavior and to alert the healthcare provider. Consider changing the therapeutic

regimen, including possibly discontinuing DRIZALMA Sprinkle, in patients whose depression is

persistently worse, or who are experiencing emergent suicidal thoughts or behaviors.

disturbances, the impact of increasing age by itself is unclear. Falls with serious consequences

including bone fractures and hospitalizations have been reported [see Adverse Reactions (6.1) and Patient

Counseling Information (17)].

5.4 Serotonin Syndrome

Serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective-serotonin reuptake inhibitors

(SSRIs), including duloxetine, can precipitate serotonin syndrome, a potentially life-threatening

condition. The risk is increased with concomitant use of other serotonergic drugs (including triptans,

tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, and St. John’s

Wort) and with drugs that impair metabolism of serotonin [see Contraindications (4), Drug Interactions

(7)]. Serotonin syndrome can also occur when these drugs are used alone.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations,

delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness,

diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus,

hyperreflexia, incoordination), seizures, and gastrointestinal symptoms (e.g., nausea, vomiting,

diarrhea).

The concomitant use of DRIZALMA Sprinkle with MAOIs is contraindicated. In addition, do not initiate

DRIZALMA Sprinkle in a patient who is being treated with MAOIs such as linezolid or intravenous

methylene blue. No reports involved the administration of methylene blue by other routes (such as oral

tablets or local tissue injection). If it is necessary to initiate treatment with an MAOI such as linezolid or

intravenous methylene blue in a patient taking duloxetine delayed-release capsules, discontinue

duloxetine delayed-release before initiating treatment with the MAOI [see Contraindications (4), Drug

Interactions (7)].

Monitor all patients taking DRIZALMA Sprinkle for the emergence of serotonin syndrome. Discontinue

treatment with DRIZALMA Sprinkle capsules immediately if the above symptoms occur and initiate

supportive symptomatic treatment. If concomitant use of DRIZALMA Sprinkle with other serotonergic

drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor

for symptoms.

5.5 Increased Risk of Bleeding

Drugs that interfere with serotonin reuptake inhibition, including duloxetine, may increase the risk of

bleeding events. Concomitant use of aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), warfarin,

and other anti-coagulants may add to this risk. Case reports and epidemiological studies (case-control

and cohort design) have demonstrated an association between use of drugs that interfere with serotonin

reuptake and the occurrence of gastrointestinal bleeding. A post-marketing study showed a higher

incidence of postpartum hemorrhage in mothers taking duloxetine. Other bleeding events related to

SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-

threatening hemorrhages.

Inform patients about the risk of bleeding associated with the concomitant use of DRIZALMA Sprinkle

and NSAIDs, aspirin, or other drugs that affect coagulation [see Drug Interactions (7.1)].

5.6 Severe Skin Reactions

Severe skin reactions, including erythema multiforme and Stevens-Johnson Syndrome (SJS), can occur

with duloxetine. The reporting rate of SJS associated with duloxetine use exceeds the general

population background incidence rate for this serious skin reaction (1 to 2 cases per million person

years). The reporting rate is generally accepted to be an underestimate due to underreporting.

DRIZALMA Sprinkle should be discontinued at the first appearance of blisters, peeling rash, mucosal

erosions, or any other sign of hypersensitivity if no other etiology can be identified.

5.7 Discontinuation Syndrome

Discontinuation symptoms have been systematically evaluated in patients taking duloxetine. Following

abrupt or tapered discontinuation in adult placebo-controlled clinical trials, the following symptoms

occurred at 1% or greater and at a significantly higher rate in duloxetine-treated patients compared to

those discontinuing from placebo: dizziness, headache, nausea, diarrhea, paresthesia, irritability,

vomiting, insomnia, anxiety, hyperhidrosis, and fatigue.

Adverse reactions after discontinuation of serotonergic antidepressants, particularly after abrupt

discontinuation, include: nausea, sweating, dysphoric mood, irritability, agitation, dizziness, sensory

disturbances (e.g., paresthesias, such as electric shock sensations), tremor, anxiety, confusion,

headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures.

Patients should be monitored for these symptoms when discontinuing treatment with DRIZALMA

Sprinkle. A gradual reduction in dosage rather than abrupt cessation is recommended whenever

possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation of

treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician

may continue decreasing the dose but at a more gradual rate [see Dosage and Administration (2.9)].

5.8 Activation of Mania/Hypomania

In patients with bipolar disorder, treating a depressive episode with duloxetine delayed-release

capsules or another antidepressant may precipitate a mixed/manic episode. In controlled clinical trials in

adult patients with major depressive disorder, patients with bipolar disorder were generally excluded;

however, symptoms of mania or hypomania were reported in 0.1% of patients treated with duloxetine

delayed-release capsules. No activation of mania or hypomania was reported in DPNP, GAD, or

chronic musculoskeletal pain placebo-controlled trials.

Prior to initiating treatment with DRIZALMA Sprinkle, screen patients for any personal or family

history of bipolar disorder, mania, or hypomania.

5.9 Angle-Closure Glaucoma

The pupillary dilation that occurs following use of many antidepressant drugs, including duloxetine,

may trigger an angle closure attack in a patient with anatomically narrow angles who does not have a

patent iridectomy. Avoid use of antidepressants, including DRIZALMA Sprinkle, in patients with

anatomically narrow angles.

5.10 Seizures

Duloxetine has not been systematically evaluated in patients with a seizure disorder, and such patients

were excluded from clinical studies. In adult placebo-controlled clinical trials, seizures/convulsions

occurred in 0.02% (3/12,722) of patients treated with duloxetine delayed-release capsules and 0.01%

(1/9513) of patients treated with placebo. DRIZALMA Sprinkle should be prescribed with care in

patients with a history of a seizure disorder.

5.11 Elevated Blood Pressure

In adult placebo-controlled clinical trials across indications from baseline to endpoint, duloxetine

treatment was associated with mean increases of 0.5 mm Hg in systolic blood pressure and 0.8 mm Hg

in diastolic blood pressure compared to mean decreases of 0.6 mm Hg systolic and 0.3 mm Hg diastolic

in placebo-treated patients. There was no significant difference in the frequency of sustained (3

consecutive visits) elevated blood pressure.

Patients receiving duloxetine delayed-release capsules should have regular monitoring of blood

pressure since increases in blood pressure were observed in clinical studies [see Adverse Reactions

(6.1)]. Pre-existing hypertension should be controlled before initiating treatment with DRIZALMA

Sprinkle. Caution should be exercised in treating patients with pre-existing hypertension,

cardiovascular, or cerebrovascular conditions that might be compromised by increases in blood

pressure.

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