Cymbalta/Duloxetine = some label excerpts

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Excerpts from:

http://www.fda.gov/cder/foi/label/2004/21427lbl.pdf

 

Duloxetine/CymbaltaWARNINGS (Page 4) Clinical Worsening and Suicide Risk -

Patients with major depressive disorder, both adult 171

and pediatric, may experience worsening of their depression

and/or the emergence of suicidal 172 ideation and behavior

(suicidality), whether or not they are taking antidepressant

medications, and 173 this risk may persist until significant

remission occurs.

 

Although there has been a long-standing 174 concern

that antidepressants may have a role in inducing worsening

of depression and the 175 emergence of suicidality in

certain patients, a causal role for antidepressants in inducing

such 176 behaviors has not been established. Nevertheless,

patients being treated with antidepressants should be

observed closely for clinical worsening and suicidality,

especially at the beginning 178 of a course of drug

therapy, or at the time of dose changes, either

increases or decreases. 179

 

Consideration should be given to changing the therapeutic

regimen, including possibly 180 discontinuing the medication,

in patients whose depression is persistently worse or whose

181 emergent suicidality is severe, abrupt in onset, or was

not part of the patient's presenting 182 symptoms. 183

 

Because of the possibility of co-morbidity between major

depressive disorder and other 184 psychiatric and

nonpsychiatric disorders, the same precautions observed

when treating patients 185 with major depressive disorder

should be observed when treating patients with other

psychiatric 186 and nonpsychiatric disorders. 187

 

The following symptoms - anxiety, agitation, panic attacks,

insomnia, irritability, hostility 188 (aggressiveness),

impulsivity, akathisia (psychomotor restlessness), hypomania,

and mania -have 189 been reported in adult and pediatric

patients being treated with antidepressants for major 190

depressive disorder as well as for other indications, both

psychiatric and nonpsychiatric. Although 191 a causal

link between the emergence of such symptoms and either

the worsening of depression 192 and/or the emergence of

suicidal impulses has not been established, consideration

should be given 193 to changing the therapeutic regimen,

including possibly discontinuing the medication, in patients 194

for whom such symptoms are severe, abrupt in onset, or were

not part of the patient's presenting 195 symptoms. 196

 

Families and caregivers of patients being treated with

antidepressants for major depressive 197 disorder or

other indications, both psychiatric and nonpsychiatric,

should be alerted about the 198 need to monitor patients

for the emergence of agitation, irritability, and the other

symptoms 199 described above, as well as the emergence

of suicidality, and to report such symptoms 200 immediately

to health care providers. Prescriptions for Cymbalta should be

written for the 201 smallest quantity of capsules consistent with

good patient management, in order to reduce the risk 202 of

overdose. 203

 

If the decision has been made to discontinue treatment,medication should be tapered, as rapidly 204 as is feasible,

but with recognition that abrupt discontinuation can be

associated with certain 205 symptoms (see PRECAUTIONS

and DOSAGE AND ADMINISTRATION, Discontinuing 206Cymbalta (duloxetine hydrochloride), for a description of the

risks of discontinuation of 207 Cymbalta). 208

 

A major depressive episode may be the initial presentation

of bipolar disorder. It is generally 209 believed (though

not established in controlled trials) that treating such an

episode with an 210 antidepressant alone may increase the

likelihood of precipitation of a mixed/manic episode in 211

patients at risk for bipolar disorder. Whether any of the

symptoms described above represent such 212 a conversion

is unknown. However, prior to initiating treatment with an

antidepressant, patients 213 should be adequately screened

to determine if they are at risk for bipolar disorder; such

screening 214 should include a detailed psychiatric history,

including a family history of suicide, bipolar 215 disorder,

and depression. It should be noted that Cymbalta is not

approved for use in treating 216 bipolar depression. 217

 

PRECAUTIONS (page 6) Discontinuation of Treatment with Cymbalta-

Discontinuation symptoms have been 272 systematically

evaluated in patients taking Cymbalta. Following abrupt

discontinuation in placebo-273 controlled clinical trials

of up to 9-weeks duration, the following symptoms occurred

at a rate 274 greater than or equal to 2% and at a

significantly higher rate in duloxetine-treated patients 275

 

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compared to those discontinuing from placebo: dizziness;

nausea; headache; paresthesia; vomiting; 276 irritability;

and nightmare. 277

 

During marketing of other SSRIs and SNRIs (Serotonin

and Norepinephrine Reuptake 278 Inhibitors), there have

been spontaneous reports of adverse events occurring upon

discontinuation 279 of these drugs, particularly when abrupt,

including the following: dysphoric mood, irritability, 280

agitation, dizziness, sensory disturbances (e.g. paresthesias

such as electric shock sensations), 281 anxiety, confusion,

headache, lethargy, emotional lability, insomnia, hypomania,

tinnitus, and 282 seizures. Although these events are generally

self-limiting, some have bee reported to be severe. 283

 

Patients should be monitored for these symptoms when

discontinuing treatment with Cymbalta. 284 A gradual

reduction in the dose rather than abrupt cessation is

recommended whenever possible. 285 If intolerable

symptoms occur following a decrease in the dose or upon

discontinuation of 286 treatment, then resuming the

previously prescribed dose may be considered. Subsequently,

the 287 physician may continue decreasing the dose but at

a more gradual rate (see DOSAGE AND 288

ADMINISTRATION). 289

 

Information for Patients Physicians 309 are advised to

discuss the following issues with patients for whom they

prescribe 310 Cymbalta. 311

 

Patients and their families should be encouraged to be

alert to the emergence of anxiety,312 agitation, panic

of depression, and suicidal ideation, especially early during

antidepressant treatment. 314 Such symptoms should be

reported to the patient's physician, especially if they are

severe, abrupt 315 in onset, or were not part of the

patient's presenting symptoms. 316

 

Duloxetine should be swallowed whole and should not be

chewed or crushed, nor should the 317 contents be sprinkled

on food or mixed with liquids. All of these might affect the

enteric coating. 318

 

Any psychoactive drug may impair judgment, thinking, or

motor skills. Although in controlled 319 studies duloxetine

has not been shown to impair psychomotor performance,

cognitive function, or 320 memory, it may be associated

with sedation. Therefore, patients should be cautioned

about 321 operating hazardous machinery including

automobiles, until they are reasonably certain that 322

duloxetine therapy does not affect their ability to engage

in such activities. 323

 

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Patients should be advised to inform their physicians if

they are taking, or plan to take, any 324 prescription or

over-the-counter medications, since there is a potential

for interactions.325 Although duloxetine does not increase

the impairment of mental and motor skills caused by 326

alcohol, use of duloxetine concomitantly with heavy alcohol

intake may be associated with for patients with 328

substantial alcohol use. 329

 

Patients should be advised to notify their physician if

they become pregnant or intend to become 330 pregnant

during therapy. 331

 

Patients should be advised to notify their physician if

they are breast-feeding. 332

 

While patients may notice improvement with duloxetine

therapy in 1 to 4 weeks, they should be 333 advised to

continue therapy as directed. 334PREGNANCY (page 9) Pregnancy-Nonteratogenic Effects 408

Neonates exposed to SSRIs or serotonin and norepinephrine

reuptake inhibitors (SNRIs), late in 409 the third trimester

have developed complications requiring prolonged hospitalization,

respiratory 410 support, and tube feeding. Such complications

can arise immediately upon delivery. Reported 411 clinicalfindings have included respiratory distress, cyanosis, apnea,

seizures, temperature 412 instability, feeding difficulty,

vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia,

413 tremor, jitteriness, irritability, and constant crying.

These features are consistent with either a 414 direct toxic

effect of SSRIs and SNRIs or, possibly, a drug discontinuationsyndrome. It should be 415 noted that, in some cases, the

clinical picture is consistent with serotonin syndrome

(see 416 WARNINGS, Monoamine Oxidase Inhibitors).

When treating a pregnant woman with Cymbalta 417 during

the third trimester, the physician should carefully consider

the potential risks and benefits of 418 treatment

(see DOSAGE AND ADMINISTRATION). 419SEE ENTIRE LABEL HERE:http://www.fda.gov/cder/foi/label/2004/21427lbl.pdf

 

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