Duloxetine Hcl (duloxetine HCl)

Dosage of duloxetine hydrochloride is expressed in terms of duloxetine.

Because withdrawal effects may occur, abrupt discontinuance of duloxetine should be avoided. When duloxetine therapy is discontinued, dosage should be tapered gradually and the patient carefully monitored to reduce the risk of withdrawal symptoms. If intolerable symptoms occur following dosage reduction or upon discontinuance of treatment, duloxetine therapy may be reinstituted at the previously prescribed dosage until such symptoms abate. Clinicians may resume dosage reductions at that time but at a more gradual rate.

Duloxetine hydrochloride is administered orally without regard to meals. The delayed-release capsules should be swallowed whole and not chewed or crushed; the contents should not be sprinkled on food or mixed with liquids.

If a dose is missed, take the missed dose as soon as it is remembered. If it is almost time for the next scheduled dose, skip the missed dose and resume regular dosing. Do not take 2 doses of duloxetine at the same time.

Store duloxetine capsules at 25degreesC; excursions are permitted to 15--30degreesC.

No dosing information is available for this tab.

No dosing information is available for this tab.

Duloxetine is metabolized by cytochrome P-450 (CYP) isoenzymes, principally CYP2D6 and CYP1A2. Duloxetine is a moderate inhibitor of CYP2D6 and also inhibits CYP1A2. In vitro studies indicate that duloxetine does not inhibit CYP2C9, CYP3A, or CYP2C19. In vitro studies indicate that duloxetine does not induce CYP1A2 or CYP3A.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Concurrent or recent (i.e., within 14 days) therapy with a monoamine oxidase (MAO) inhibitor intended to treat psychiatric disorders. Use of an MAO inhibitor intended to treat psychiatric disorders within 5 days of duloxetine discontinuance.

*Initiation of duloxetine in a patient receiving MAO inhibitors such as linezolid or IV methylene blue.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in 5% or more of adults receiving duloxetine include nausea, dry mouth, somnolence, constipation, decreased appetite, and increased sweating.

Adverse effects reported in 5% or more of pediatric patients receiving duloxetine include decreased weight, decreased appetite, nausea, vomiting, fatigue, and diarrhea.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of duloxetine have been established in children 7-17 years of age for the treatment of generalized anxiety disorder, and in adolescents 13-17 years of age for the treatment of juvenile fibromyalgia syndrome. Safety and efficacy of duloxetine have not been established in pediatric patients with major depressive disorder, diabetic peripheral neuropathic pain, or chronic musculoskeletal pain.

Use of duloxetine for the treatment of generalized anxiety disorder in children 7-17 years of age is supported by one 10-week, placebo-controlled clinical trial. Safety and efficacy of duloxetine for the treatment of generalized anxiety disorder in children <7 years of age have not been established.

Use of duloxetine for the treatment of fibromyalgia in adolescents 13-17 years of age is supported by one 13-week, placebo-controlled clinical trial. Safety and efficacy of duloxetine for the treatment of fibromyalgia in pediatric patients <13 years of age have not been established.

Safety and efficacy of duloxetine for major depressive disorder have not been established in pediatric patients. In two 10-week, placebo-controlled trials, duloxetine failed to establish superiority for major depressive disorder compared to placebo.

A greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants). No suicides occurred in these pediatric trials.

Monitor all pediatric patients receiving antidepressant therapy for clinical worsening and the development of suicidal thinking or behavior, especially during the first few months of treatment and during dosage changes. Decreased appetite and loss of weight have been observed with use of SSRIs and SNRIs. Regular monitoring of weight and growth is also recommended in pediatric patients receiving duloxetine.

A National Pregnancy Registry for Antidepressants is available that monitors pregnancy outcomes in women exposed to antidepressants, including duloxetine, during pregnancy. Clinicians are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388.

Available evidence has not identified a clear drug-associated risk of major birth defects or adverse developmental outcomes with duloxetine. There are risks associated with untreated depression and fibromyalgia and also the exposure to SNRIs or SSRIs during pregnancy. A prospective, longitudinal study of 201 euthymic women receiving antidepressants with a history of major depressive disorder showed that the discontinuation of antidepressants during pregnancy or the postpartum period was associated with a greater likelihood of a relapse of major depression. The risks of untreated depression when discontinuing or adjusting treatment during pregnancy or during the postpartum period should be considered. Fibromyalgia during pregnancy is also associated with an increased risk of adverse maternal and infant outcomes (preterm premature rupture of membranes, preterm birth, small for gestational age, intrauterine growth restriction, placental disruption, venous thrombosis), although it is not known if these outcomes are directly associated with fibromyalgia or other comorbid factors.

Data from a post-marketing cohort study suggests that duloxetine use in the month before delivery is associated with an increased risk of postpartum hemorrhage.

Some neonates exposed to SNRIs or SSRIs late in the third trimester of pregnancy have developed complications that have sometimes been severe and required prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Clinical findings reported to date in these neonates have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These clinical features appear to be consistent with either a direct toxic effect of the SNRI or SSRI or, possibly, a drug withdrawal syndrome. It should be noted that, in some cases, the clinical picture was consistent with serotonin syndrome.

Duloxetine is distributed into human milk. Because exposure to duloxetine through breast milk has resulted in cases of sedation, poor feeding, and poor weight gain in breast-fed infants, breast-fed infants exposed to duloxetine should be monitored for these symptoms.

Following the administration of duloxetine 40 mg once daily in 6 lactating women for 3.5 days, the resulting amount of duloxetine in the breast milk was approximately 7 mcg/day, which is an estimated daily infant dose of approximately 2 mcg/kg/day, less than 1% of the maternal dose. Peak concentrations of duloxetine in the breast milk occurred a median of 3 hours after the dose was administered. The presence of duloxetine metabolites in the breast milk has not been evaluated.

It is not known if duloxetine affects milk production. Consider the developmental and health benefits of breast-feeding, the mother's clinical need for the drug, and the potential for adverse effects on the nursing infant from exposure to duloxetine or to the untreated underlying maternal condition.

The manufacturer recommends initiating duloxetine therapy at a dosage of 30 mg once daily for 2 weeks before considering a dosage increase when treating generalized anxiety disorder in geriatric patients >=65 years of age.

Consider dosage reduction or discontinuation if symptomatic orthostatic hypotension, falls, or syncope occur. Geriatric patients typically have a greater fall risk due to the use of multiple medications and increased presence of comorbid conditions and gait disturbances.

Approximately 6, 21, 41, 33, and 8% of patients studied in clinical trials of duloxetine for major depressive disorder, chronic low back pain, osteoarthritis, diabetic peripheral neuropathy, and fibromyalgia, respectively, were 65 years of age or older. Although no overall differences in efficacy or safety were observed between geriatric and younger adult patients in the major depressive disorder, generalized anxiety disorder, diabetic peripheral neuropathic pain, fibromyalgia, osteoarthritis, and chronic low back pain clinical trials, and other clinical experience has not revealed any evidence of age-related differences, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out.

Clinically important hyponatremia has been reported in geriatric patients, who may be at greater risk for this adverse effect.

In placebo-controlled trials, patients receiving duloxetine reported a higher rate of falls. Fall risk appears to be proportional to the patient's underlying fall risk, and appears to increase with increasing age. The impact of age itself on fall risk is unknown, as geriatric patients typically have greater underlying fall risk due to the increased prevalence of multiple medications and the increased presence of comorbid conditions and gait disturbances. Falls with serious consequences (fractures, hospitalization) have been reported with duloxetine.