DULOXETINE capsule, delayed release

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DULOXETINE HYDROCHLORIDE (UNII: 9044SC542W) (DULOXETINE - UNII:O5TNM5N07U)

Available from:

St. Mary's Medical Park Pharmacy

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Duloxetine delayed-release capsules are indicated for the treatment of: - Major Depressive Disorder [see Clinical Studies ( 14.1 )] . - Generalized Anxiety Disorder [see Clinical Studies ( 14.2 )] . - Diabetic Peripheral Neuropathy [see Clinical Studies ( 14.3 )] . - Chronic Musculoskeletal Pain [see Clinical Studies ( 14.5 )] .          Monoamine Oxidase Inhibitors (MAOIs)   - The use of MAOIs intended to treat psychiatric disorders with duloxetine or within 5 days of stopping treatment with duloxetine is contraindicated because of an increased risk of serotonin syndrome. The use of duloxetine within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration ( 2.8) and Warnings and Precautions ( 5.4)].          Starting duloxetine in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration ( 2.9) and Warnings and Precautions ( 5.4)].          Pregnancy Category C          Risk Summary — There are no adequate and well-controlled studies of duloxetine administration in pregnant women. In animal studies with duloxetine, fetal weights were decreased but there was no evidence of teratogenicity in pregnant rats and rabbits at oral doses administered during the period of organogenesis up to 4 and 7 times the maximum recommended human dose (MRHD) of 120 mg/day, respectively. When duloxetine was administered orally to pregnant rats throughout gestation and lactation, pup weights at birth and pup survival to 1 day postpartum were decreased at a dose 2 times the MRHD. At this dose, pup behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity were observed. Post-weaning growth was not adversely affected. Duloxetine should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.          Clinical Considerations          Fetal/Neonatal Adverse Reaction — Neonates exposed during pregnancy to serotonin - norepinephrine reuptake inhibitors (SNRIs) or selective serotonin reuptake inhibitors (SSRIs) have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding which can arise immediately upon delivery. 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. These features are consistent with either a direct toxic effect of the SNRIs or SSRIs, or possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome [see Warnings and Precautions ( 5.4)] .          Data          Animal Data — In animal reproduction studies, duloxetine has been shown to have adverse effects on embryo/fetal and postnatal development.          When duloxetine was administered orally to pregnant rats and rabbits during the period of organogenesis, there was no evidence of teratogenicity at doses up to 45 mg/kg/day (4 times the maximum recommended human dose (MRHD) of 120 mg/day on a mg/m 2 basis, in rat; 7 times the MRHD in rabbit). However, fetal weights were decreased at this dose, with a no-effect dose of 10 mg/kg/day approximately equal to the MRHD in rats; 2 times the MRHD in rabbits).          When duloxetine was administered orally to pregnant rats throughout gestation and lactation, the survival of pups to 1 day postpartum and pup body weights at birth and during the lactation period were decreased at a dose of 30 mg/kg/day (2 times the MRHD); the no-effect dose was 10 mg/kg/day. Furthermore, behaviors consistent with increased reactivity, such as increased startle response to noise and decreased habituation of locomotor activity, were observed in pups following maternal exposure to 30 mg/kg/day. Post-weaning growth and reproductive performance of the progeny were not affected adversely by maternal duloxetine treatment.          Risk Summary          Duloxetine is present in human milk. In a published study, lactating women who were weaning their infants were given duloxetine. At steady state, the concentration of duloxetine in breast milk was approximately 25% that of maternal plasma. The estimated daily infant dose was approximately 0.14% of the maternal dose. The developmental and health benefits of human milk feeding should be considered along with the mother’s clinical need for duloxetine and any potential adverse effects on the milk-fed child from the drug or from the underlying maternal condition. Exercise caution when duloxetine is administered to a nursing woman.          Data          The disposition of duloxetine was studied in 6 lactating women who were at least 12 weeks postpartum and had elected to wean their infants. The women were given 40 mg of duloxetine twice daily for 3.5 days. The peak concentration measured in breast milk occurred at a median of 3 hours after the dose. The amount of duloxetine in breast milk was approximately 7 mcg/day while on that dose; the estimated daily infant dose was approximately 2 mcg/kg/day. The presence of duloxetine metabolites in breast milk was not examined. Generalized Anxiety Disorder — In pediatric patients aged 7 to 17 years, efficacy was demonstrated in one 10 week, placebo-controlled trial. The study included 272 pediatric patients with GAD of which 47% were 7 to 11 years of age. Duloxetine demonstrated superiority over placebo as measured by greater improvement in the Pediatric Anxiety Rating Scale (PARS) for GAD severity score [see Clinical Studies ( 14.2)]. The safety and effectiveness in pediatric patients less than 7 years of age have not been established. Major Depressive Disorder — Efficacy was not demonstrated in two 10-week, placebo-controlled trials with 800 pediatric patients with MDD, age 7-17. Neither duloxetine nor an active control (indicated for treatment of pediatric depression) was superior to placebo. The safety and effectiveness in pediatric patients less than 7 years of age have not been established. The most frequently observed adverse reactions in the clinical trials included nausea, headache, decreased weight, and abdominal pain. Decreased appetite and weight loss have been observed in association with the use of SSRIs and SNRIs. Perform regular monitoring of weight and growth in children and adolescents treated with an SNRI such as duloxetine [see Adverse Reactions ( 6.11)]. Use of duloxetine in a child or adolescent must balance the potential risks with the clinical need [see Boxed Warning and Warnings and Precautions ( 5.1)]. Animal Data — Duloxetine administration to young rats from post-natal day 21 (weaning) through post-natal day 90 (adult) resulted in decreased body weights that persisted into adulthood, but recovered when drug treatment was discontinued; slightly delayed (~1.5 days) sexual maturation in females, without any effect on fertility; and a delay in learning a complex task in adulthood, which was not observed after drug treatment was discontinued. These effects were observed at the high dose of 45 mg/kg/day (2 times the MRHD, for a child); the no-effect-level was 20 mg/kg/day (≈1 times the MRHD, for a child). Of the 2,418 patients in premarketing clinical studies of duloxetine for MDD, 5.9% (143) were 65 years of age or over. Of the 1041 patients in CLBP premarketing studies, 21.2% (221) were 65 years of age or over. Of the 487 patients in OA premarketing studies, 40.5% (197) were 65 years of age or over. Of the 1,074 patients in the DPNP premarketing studies, 33% (357) were 65 years of age or over. In the MDD, GAD, DPNP, OA, CLBP, and other studies, no overall differences in safety or effectiveness were generally observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. SSRIs and SNRIs, including duloxetine have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event [see Warnings and Precautions ( 5.13)] . In an analysis of data from all placebo-controlled-trials, patients treated with duloxetine reported a higher rate of falls compared to patients treated with placebo. The increased risk appears to be proportional to a patient’s underlying risk for falls. Underlying risk appears to increase steadily with age. As elderly patients tend to have a higher prevalence of risk factors for falls such as medications, medical comorbidities and gait disturbances, the impact of increasing age by itself on falls during treatment with duloxetine is unclear. Falls with serious consequences including bone fractures and hospitalizations have been reported [see Warnings and Precautions ( 5.3) and Adverse Reactions ( 6.10)] . The pharmacokinetics of duloxetine after a single dose of 40 mg were compared in healthy elderly females (65 to 77 years) and healthy middle-age females (32 to 50 years). There was no difference in the Cmax, but the AUC of duloxetine was somewhat (about 25%) higher and the half-life about 4 hours longer in the elderly females. Population pharmacokinetic analyses suggest that the typical values for clearance decrease by approximately 1% for each year of age between 25 to 75 years of age; but age as a predictive factor only accounts for a small percentage of between-patient variability. Dosage adjustment based on the age of the patient is not necessary.       Duloxetine's half-life is similar in men and women. Dosage adjustment based on gender is not necessary.          Duloxetine bioavailability (AUC) appears to be reduced by about one-third in smokers. Dosage modifications are not recommended for smokers.          No specific pharmacokinetic study was conducted to investigate the effects of race.          Patients with clinically evident hepatic impairment have decreased duloxetine metabolism and elimination. After a single 20 mg dose of duloxetine, 6 cirrhotic patients with moderate liver impairment (Child-Pugh Class B) had a mean plasma duloxetine clearance about 15% that of age- and gender-matched healthy subjects, with a 5-fold increase in mean exposure (AUC). Although C max was similar to normals in the cirrhotic patients, the half-life was about 3 times longer [see Dosage and Administration ( 2.6) and Warnings and Precautions ( 5.14)] .          Limited data are available on the effects of duloxetine in patients with end-stage renal disease (ESRD). After a single 60 mg dose of duloxetine, C max and AUC values were approximately 100% greater in patients with end-stage renal disease receiving chronic intermittent hemodialysis than in subjects with normal renal function. The elimination half-life, however, was similar in both groups. The AUCs of the major circulating metabolites, 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate, largely excreted in urine, were approximately 7- to 9-fold higher and would be expected to increase further with multiple dosing. Population PK analyses suggest that mild to moderate degrees of renal impairment (estimated CrCl 30 to 80 mL/min) have no significant effect on duloxetine apparent clearance [see Dosage and Administration ( 2.6) and Warnings and Precautions ( 5.14)] .          In animal studies, duloxetine did not demonstrate barbiturate-like (depressant) abuse potential.          While duloxetine has not been systematically studied in humans for its potential for abuse, there was no indication of drug-seeking behavior in the clinical trials. However, it is not possible to predict on the basis of premarketing experience the extent to which a CNS active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for a history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of duloxetine (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).          In drug dependence studies, duloxetine did not demonstrate dependence-producing potential in rats.

Product summary:

Duloxetine delayed-release capsules are available in the following strengths, colors, imprints, and presentations: 30MG Capsule, Color- Blue , Imprint- ap; DLX30 NDC 60760-461-30 BOTTLES OF 30 60760-461-60 BOTTLES OF 60 - INACTIVE          Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [ see USP Controlled Room Temperature].

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

DULOXETINE- DULOXETINE CAPSULE, DELAYED RELEASE
St. Mary's Medical Park Pharmacy
----------
MEDICATION GUIDE
Duloxetine Delayed-Release Capsules
(doo lox’ e teen)
Read this Medication Guide before you start taking duloxetine
delayed-release capsules and each time
you get a refill. There may be new information. This information does
not take the place of talking to
your healthcare provider about your medical condition or treatment.
Talk to your healthcare provider about:
•
all risks and benefits of treatment with antidepressant medicines
•
all treatment choices for depression or other serious mental illness
What is the most important information I should know
aboutantidepressant medicines, depression, other
serious mental illnesses, and suicidal thoughts or actions?
1.
Duloxetine delayed-release capsules and other antidepressant medicines
may increase suicidal
thoughts or actions in some children, teenagers, or young adults
within the first few months of
treatment or when the dose is changed.
2.
Depression and other serious mental illnesses are the most important
causes of suicidal thoughts or
actions. Some people may have a particularly high risk of having
suicidal thoughts or actions.
These include people who have (or have a family history of) bipolar
illness (also called manic-
depressive illness).
3.
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 right away if you have any of the
following symptoms or feelings,
especially if they are new, worse, or worr

Summary of Product characteristics

DULOXETINE- DULOXETINE CAPSULE, DELAYED RELEASE
ST. MARY'S MEDICAL PARK PHARMACY
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DULOXETINE DELAYED-
RELEASE CAPSULES SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING
INFORMATION FOR DULOXETINE
DELAYED-RELEASE CAPSULES.
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._
Increased risk of suicidal thinking and behavior in children,
adolescents, and young adults taking
antidepressants ( 5.1)
Monitor for worsening and emergence of suicidal thoughts and behaviors
( 5.1)
RECENT MAJOR CHANGES
None.
INDICATIONS AND USAGE
Duloxetine delayed-release capsules are a serotonin and norepinephrine
reuptake inhibitor (SNRI)
indicated for:
Major Depressive Disorder (MDD) ( 1)
Generalized Anxiety Disorder (GAD) ( 1)
Diabetic Peripheral Neuropathic Pain (DPNP) ( 1)
Chronic Musculoskeletal Pain ( 1)
DOSAGE AND ADMINISTRATION
Take duloxetine delayed-release capsules once daily, with or without
food. Swallow duloxetine delayed-
release capsules whole; do not crush or chew, do not open capsule.
Take a missed dose as soon as it is
remembered. Do not take two doses of duloxetine delayed-release
capsules at the same time. ( 2)
INDICATION
STARTING
DOSE
TARGET DOSE
MAXIMUM
DOSE
MDD ( 2.1)
40 mg/day
to 60 mg/day
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
120 mg/day
GAD ( 2.2)
Adults
60 mg/day
60 mg/day (once daily)
120 mg/day
Elderly
30 mg/day
60 mg/day (once daily)
120 mg/day
Children and Adolescents
(7 to 17 years of age)
30 mg/day
30 to 60 mg/day (once daily)
120 mg/day
DPNP ( 2.3)
60 mg/day
60 mg/day (once daily)
60 mg/day
Chronic
Musculoskeletal
Pain ( 2.5)
30 mg/day
60 mg/day (once daily)
60 mg/day
Some patients may benefit from starting at 30 mg once daily ( 2)
There is no evidence that doses greater than 60