Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Serotonin
Syndrome
Additions and/or revisions underlined:
Serotonin-norepinephrine
reuptake inhibitors (SNRIs), including Effexor XR, 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, meperidine, methadone,
tryptophan, buspirone, amphetamines, and St. John’s Wort) and with drugs that
impair metabolism of serotonin, i.e., MAOIs [see
Contraindications (4), Drug Interactions (7.1)]. Serotonin syndrome can
also occur when these drugs are used alone.
5.4 Increased Risk of Bleeding
Additions and/or revisions underlined:
Drugs
that interfere with serotonin reuptake inhibition, including Effexor XR, may increase
the risk of bleeding events, ranging from ecchymoses, hematomas, epistaxis,
petechiae, and gastrointestinal hemorrhage to life-threatening hemorrhage.
Concomitant use of aspirin, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs),
warfarin, and other anti-coagulants or other drugs known to affect platelet
function 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. Based on data from the published observational
studies, exposure to SNRIs, particularly in the month before delivery, has been
associated with a less than 2-fold increase in the risk of postpartum
hemorrhage [see Use in Specific
Populations (8.1)].
Inform
patients about the increased risk of bleeding associated with the
concomitant use of Effexor XR and nonsteroidal anti-inflammatory drugs
(NSAIDs), aspirin, or other drugs that affect coagulation. For patients taking
warfarin, carefully monitor coagulation indices when initiating, titrating, or
discontinuing Effexor XR.
6
Adverse Reactions
6.2 Postmarketing
Experience
Additions and/or revisions underlined:
…
Respiratory,
Thoracic and Mediastinal Disorders – Anosmia,
dyspnea, hyposmia, interstitial lung disease, pulmonary eosinophilia [see Warnings and Precautions (5.12)]
…
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or revisions underlined:
…
Risk
Summary
Based
on data from published observational studies, exposure to SNRIs, particularly
in the month before delivery, has been associated with a less than 2-fold
increase in the risk of postpartum hemorrhage [see Warnings and Precautions (5.4) and Clinical Considerations].
…
Maternal Adverse
Reactions
Exposure
to Effexor XR in mid to late pregnancy may increase the risk for
preeclampsia, and exposure to Effexor XR in the month before delivery
may be associated with an increased risk of postpartum hemorrhage
[see Warnings and Precautions (5.4)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING
INFORMATION
Additions
and/or revisions underlined:
Serotonin
Syndrome
Caution
patients about the risk of serotonin syndrome, particularly with the
concomitant use of Effexor XR with other serotonergic drugs including triptans,
tricyclic antidepressants, opioids, lithium, tryptophan, buspirone,
amphetamines, St. John’s Wort, and with drugs that impair metabolism of
serotonin (in particular, MAOIs, both those intended to treat psychiatric
disorders and also others, such as linezolid). Instruct patients to contact
their healthcare provider or report to the emergency room if they experience
signs or symptoms of serotonin syndrome [see
Warnings and Precautions (5.2) and Drug Interactions (7.1)].
MEDICATION GUIDE
Additions
and/or revisions underlined:
Especially tell
your healthcare provider if you take:
…
- tramadol,
fentanyl, meperidine, methadone, or other opioids
…
Approved Drug Label (PDF)
Boxed Warning
PLR conversion; additions
and/or revisions underlined:
WARNING: SUICIDAL
THOUGHTS AND BEHAVIORS
Antidepressants increased the risk of suicidal thoughts
and behavior in pediatric and young adult patients in short-term studies. Closely
monitor all antidepressant-treated patients for clinical worsening, and emergence of suicidal thoughts
and behaviors [see Warnings
and Precautions (5.1]. Effexor
XR is not approved for use in pediatric patients [see Use in Specific Populations (8.4)].
4
Contraindications
PLR conversion; additions
and/or revisions underlined:
Effexor XR is contraindicated in patients:
with
known hypersensitivity to venlafaxine
hydrochloride, desvenlafaxine succinate or to any excipients in the formulation
taking, or within 14 days of
stopping, MAOIs (including the MAOIs linezolid and intravenous methylene blue) because of the risk of serotonin syndrome [see Dosage and
Administration (2.11), Warnings and Precautions (5.2), and Drug Interactions
(7.1)].
5
Warnings and Precautions
PLR conversion. Subsection titles
as below; please see label for complete information:
5.1 Suicidal Thoughts and
Behaviors in Adolescents and Young Adults
5.2 Serotonin Syndrome
5.3 Elevated Blood Pressure
5.4 Increased Risk of
Bleeding
5.5 Angle-Closure Glaucoma
5.6 Activation of Mania or
Hypomania
5.7 Discontinuation Syndrome
5.8 Seizures
5.9 Hyponatremia
5.10 Weight and Height
Changes in Pediatric Patients
5.11 Appetite Changes in
Pediatric Patients
5.12 Interstitial Lung Disease
and Eosinophilic Pneumonia
5.13 Sexual Dysfunction
6
Adverse Reactions
PLR conversion; additions
and/or revisions underlined:
The following adverse reactions are discussed in
more detail in other sections of the labeling:
Suicidal Thoughts and Behaviors
in Adolescents and Young Adults [see Warnings and Precautions (5.1)]
Elevated Blood Pressure [see Warnings and Precautions (5.3)
Increased Risk of Bleeding [see Warnings and Precautions (5.4)
Angle Closure Glaucoma [see Warnings and Precautions
(5.5)
Activation of Mania/Hypomania [see Warnings and
Precautions (5.6)
Discontinuation Syndrome [see Warnings and
Precautions (5.7)
Seizure [see Warnings and Precautions (5.8)]
Hyponatremia [see Warnings and Precautions (5.9)
Weight and Height changes in Pediatric Patients [see
Warnings and Precautions (5.10)]
Appetite Changes in Pediatric Patients [see Warnings
and Precautions (5.11)]
Interstitial Lung Disease and Eosinophilic Pneumonia
[see Warnings and Precautions (5.12)]
Sexual Dysfunction [see Warnings and Precautions
(5.13)]
6.1 Clinical Studies Experience
‘trials’ replaces ‘studies’
throughout first paragraph of section
Common Adverse Reactions in Placebo-controlled
Studies
Table 8: Patients Receiving
Effexor XR in Premarketing Clinical Studies Indication
Table 11: Sustained
Elevations in Effexor XR Premarketing Studies
a Maximum recommended dosage for Effexor XR is 225 mg
once daily.
7
Drug Interactions
PLR conversion; additions
and/or revisions underlined:
7.1 Drugs Having
Clinically Important Interactions with Effexor XR
Newly added table; please
refer to label for complete information.
Table 15: Clinically
Important Drug Interactions with Effexor XR
7.2 Other Drug
Interactions with Effexor XR
Central Nervous System (CNS)-Active Drugs
The risk of using venlafaxine concomitantly
with other CNS-active drugs (including alcohol) has not been systematically
evaluated. Consequently, caution is advised when Effexor XR is taken concomitantly
in combination with other CNS-active drugs.
Weight Loss Agents
Concomitant use of Effexor XR and weight loss
agents is not recommended.
The safety and efficacy of venlafaxine therapy in combination with weight loss
agents, including phentermine, have not been established. Effexor XR is not
indicated for weight loss alone or in combination with other products.
Laboratory Test Interference
False-positive urine immunoassay screening
tests for phencyclidine (PCP) and amphetamine have been reported in patients
taking venlafaxine due to lack of specificity of the screening tests. False
positive test results may be expected for several days following
discontinuation of venlafaxine therapy. Confirmatory tests, such as gas
chromatography/mass spectrometry, will distinguish venlafaxine from PCP and amphetamine.
8
Use in Specific Populations
8.1 Pregnancy
PLLR conversion. Extensive changes; please refer to label for
complete information.
8.2 Lactation
PLLR conversion. Extensive changes; please refer to label for
complete information.
8.4 Pediatric Use
Additions and/or revisions
underlined:
Safety and effectiveness of Effexor XR in
pediatric patients have not been established.
Two placebo-controlled trials in 766 pediatric
patients with MDD and two placebo-controlled trials in 793 pediatric patients
with GAD have been conducted with Effexor XR, and the data were not sufficient
to support a claim for use in pediatric patients.
In the studies conducted in pediatric patients
ages 6 to17 years, the occurrence of blood pressure and cholesterol increases
was considered to be clinically relevant in pediatric patients and was similar
to that observed in adult patients [see Warnings and Precautions (5.3), Adverse
Reactions (6.1)]. The following adverse reactions were also observed in
pediatric patients: abdominal pain, agitation, dyspepsia, ecchymosis,
epistaxis, and myalgia.
Although no studies have been designed to
primarily assess Effexor XR’s impact on the growth, development, and maturation
of children and adolescents, the studies that have been done suggest that
Effexor XR may adversely affect weight and height [see Warnings and Precautions
(5.10)].
Decreased appetite and weight loss were
observed in placebo-controlled studies of pediatric patients 6 to 17 years.
In pediatric clinical studies, the adverse
reaction, suicidal ideation, was observed. Antidepressants increased the risk
of suicidal thoughts and behaviors in pediatric patients [see Boxed Warning,
Warnings and Precautions (5.1)].
8.5 Geriatric Use
Additions and/or revisions
underlined:
The percentage of patients in clinical studies
for Effexor XR for MDD, GAD, SAD, and PD who were 65 years of age or older are
shown in Table 16.
Table 16: Percentage
(and Number of Patients Studied) of Patients 65 Years of Age and Older by
Indicationa
No overall differences in effectiveness or
safety were observed between geriatric patients and younger patients, and other
reported clinical experience generally has not identified differences in
response between the elderly and younger patients …
No dose adjustment is recommended for the elderly
on the basis of age alone, although other clinical circumstances, some of which
may be more common in the elderly, such as renal or hepatic impairment, may warrant
a dose reduction [see Dosage and Administration (2.8, 2.9)].
Newly added subsections:
8.6 Hepatic Impairment
Dosage adjustment is recommended in patients with
mild (Child-Pugh Class A), moderate (Child-Pugh Class B), or severe (Child-Pugh
Class C) hepatic impairment or hepatic cirrhosis [see Dosage and
Administration (2.8) and Clinical Pharmacology (12.3)].
8.7 Renal Impairment
Dosage adjustment is recommended in patients with
mild (CLcr= 60-89 mL/min), moderate (CLcr= 30- 59 mL/min), or severe (CLcr <
30 mL/min) renal impairment, and in patients undergoing hemodialysis [see
Dosage and Administration (2.9) and Clinical Pharmacology (12.3)].
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
PLR conversion. Extensive changes including formatting; please refer to label
for complete information.
PATIENT COUNSELING INFORMATION
PLR conversion. Extensive changes including formatting; please refer to label
for complete information.
Other
Approved Drug Label (PDF)
5
Warnings and Precautions
5.13 Sexual Dysfunction
(Newly added
subsection)
Use
of SNRIs, including Effexor XR, may cause symptoms of sexual dysfunction [see Adverse Reactions (6.1)]. In male
patients, SNRI use may result in ejaculatory delay or failure, decreased
libido, and erectile dysfunction. In female patients, SNRI use may result in
decreased libido and delayed or absent orgasm.
It
is important for prescribers to inquire about sexual function prior to
initiation of Effexor XR and to inquire specifically about changes in sexual
function during treatment, because sexual function may not be spontaneously
reported. When evaluating changes in sexual function, obtaining a detailed
history (including timing of symptom onset) is important because sexual
symptoms may have other causes, including the underlying psychiatric disorder.
Discuss potential management strategies to support patients in making informed
decisions about treatment.
6
Adverse Reactions
(Addition of the following
to the bulleted line listing)
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
MEDICATION GUIDE
(Additions and/or
revisions underlined)
…
3.
Changes in blood pressure. EFFEXOR XR may:
Symptoms in females may include:
Talk to your healthcare provider if you
develop any changes in your sexual function or if you have any questions or
concerns about sexual problems during treatment with EFFEXOR XR. There may be
treatments your healthcare provider can suggest.
…
14.
Sexual Problems (dysfunction). Taking serotonin and norepinephrine reuptake
inhibitors (SNRIs), including EFFEXOR XR, may cause sexual problems:
Symptoms in males may include:
Symptoms in females may include:
Talk to your healthcare provider if you
develop any changes in your sexual function or if you have any questions or
concerns about sexual problems during treatment with ??EFFEXOR XR. There may be
treatments your healthcare provider can suggest.
…
PATIENT COUNSELING INFORMATION
(Additions and/or
revisions underlined)
…
Sexual
Dysfunction
Advise
patients that use of Effexor XR may cause symptoms of sexual dysfunction in
both male and female patients. Inform patients that they should discuss any
changes in sexual function and potential management strategies with their healthcare
provider [see Warnings and Precautions
(5.13)].
…
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Serotonin Syndrome
(additions
underlined)
The development of a potentially life-threatening serotonin syndrome has been
reported with SNRIs and SSRIs, including Effexor XR alone, but particularly 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 in particular,
MAOIs, both those intended to treat psychiatric disorders and others, such as linezolid
or intravenous methylene blue).
…
If concomitant use of Effexor XR with other serotonergic drugs (e.g., triptans,
tricyclic antidepressants, mirtazapine, fentanyl, lithium, tramadol, buspirone,
amphetamines, tryptophan, or St. John's wort) is clinically warranted, careful
observation of the patient is advised, particularly during treatment initiation
and dose increases. Patients should be made aware of the potential risk of
serotonin syndrome. Treatment with Effexor XR and any concomitant serotonergic agents
should be discontinued immediately if the above events occur, and supportive symptomatic
treatment should be initiated.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(addition
underlined)
Patients should be cautioned about
the risk of serotonin syndrome, with the concomitant use of Effexor XR and triptans,
tramadol, amphetamines, tryptophan supplements, with antipsychotics or other
dopamine antagonists, or other serotonergic agents.
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