openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
Warnings sections page 1 of 2 · 7 matching rows.
warnings and cautions
5 WARNINGS AND PRECAUTIONS • Ÿ Serotonin Syndrome : Increased risk when co-administered with other serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also when taken alone. If it occurs, discontinue Effexor XR and initiate supportive treatment ( 4 , 5.2 , 7.1 ). • Ÿ Elevated Blood Pressure : Control hypertension before initiating treatment. Monitor blood pressure regularly during treatment ( 5.3 ). • Increased Risk of Bleeding : Concomitant use of aspirin, NSAIDs, other antiplatelet drugs, warfarin, and other anticoagulants may increase risk ( 5.4 ). • Angle-Closure Glaucoma : Angle-closure glaucoma has occurred in patients with untreated anatomically narrow angles, treated with antidepressants ( 5.5 ). • Activation of Mania or Hypomania : Screen patients for bipolar disorder ( 5.6 ). • Ÿ Discontinuation Syndrome : Taper dose and monitor for discontinuation symptoms ( 5.7 ). • Ÿ Seizures : Can occur. Use cautiously in patients with seizure disorder ( 5.8 ). • Ÿ Hyponatremia : Can occur in association with SIADH ( 5.9 ). • Interstitial Lung Disease and Eosinophilic Pneumonia : Can occur ( 5.12 ). • Sexual Dysfunction : Effexor XR may cause symptoms of sexual dysfunction ( 5.13 ). 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 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 patients with MDD. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric Effexor XR is not approved in pediatric patients. and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts and Behaviors per 1,000 Patients Treated Increases Compared to Placebo <18 years old 14 additional patients 18–24 years old 5 additional patients Decreases Compared to Placebo 25–64 years old 1 fewer patient ≥65 years old 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 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 Effexor XR, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome 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, 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. Serotonin syndrome signs and symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, 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 Effexor XR with MAOIs is contraindicated. In addition, do not initiate Effexor XR in a patient 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 Effexor XR, discontinue Effexor XR before initiating treatment with the MAOI [see Contraindications (4) , Drug Interactions (7.1) ] . Monitor all patients taking Effexor XR for the emergence of serotonin syndrome. Discontinue treatment with Effexor XR and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Effexor XR with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Elevated Blood Pressure In controlled trials, there were dose-related increases in systolic and diastolic blood pressure, as well as cases of sustained hypertension [see Adverse Reactions (6.1) ]. Monitor blood pressure before initiating treatment with Effexor XR and regularly during treatment. Control pre-existing hypertension before initiating treatment with Effexor XR. Use caution in treating patients with pre-existing hypertension or cardiovascular or cerebrovascular conditions that might be compromised by increases in blood pressure. Sustained blood pressure elevation can lead to adverse outcomes. Cases of elevated blood pressure requiring immediate treatment have been reported with Effexor XR. Consider dose reduction or discontinuation of treatment for patients who experience a sustained increase in blood pressure. Across all clinical studies with Effexor, 1.4% of patients in the Effexor XR treated groups experienced a ≥15 mm Hg increase in supine diastolic blood pressure (SDBP) ≥105 mm Hg, compared to 0.9% of patients in the placebo groups. Similarly, 1% of patients in the Effexor XR treated groups experienced a ≥20 mm Hg increase in supine systolic blood pressure (SSBP) with blood pressure ≥180 mm Hg, compared to 0.3% of patients in the placebo groups [see Adverse Reactions (6.1) ] . Treatment with Effexor XR was associated with sustained hypertension defined as SDBP ≥90 mm Hg and ≥10 mm Hg above baseline for three consecutive on-therapy visits [see Adverse Reactions (6.1) ] . An insufficient number of patients received mean doses of Effexor XR over 300 mg per day in clinical studies to fully evaluate the incidence of sustained increases in blood pressure at these higher doses. 5.4 Increased Risk of Bleeding 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. Inform patients about the 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. 5.5 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including Effexor XR 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 Effexor XR, in patients with untreated anatomically narrow angles. 5.6 Activation of Mania or Hypomania In patients with bipolar disorder, treating a depressive episode with Effexor XR or another antidepressant may precipitate a mixed/manic episode. Mania or hypomania was reported in Effexor XR treated patients in the premarketing studies in MDD, SAD, and PD (see Table 2 ). Prior to initiating treatment with Effexor XR, screen for any personal or family history of bipolar disorder, mania, or hypomania. Table 2: Incidence (%) of Mania or Hypomania Reported in Effexor XR Treated Patients in the Premarketing Studies Indication Effexor XR Placebo MDD 0.3 0.0 GAD 0.0 0.2 SAD 0.2 0.0 PD 0.1 0.0 5.7 Discontinuation Syndrome Discontinuation symptoms have been systematically evaluated in patients taking venlafaxine, including prospective analyses of clinical studies in GAD and retrospective surveys of studies in MDD and SAD. Abrupt discontinuation or dose reduction of venlafaxine at various doses has been found to be associated with the appearance of new symptoms, the frequency of which increased with increased dose level and with longer duration of treatment. Reported symptoms include agitation, anorexia, anxiety, confusion, impaired coordination and balance, diarrhea, dizziness, dry mouth, dysphoric mood, fasciculation, fatigue, flu-like symptoms, headaches, hypomania, insomnia, nausea, nervousness, nightmares, sensory disturbances (including shock-like electrical sensations), somnolence, sweating, tremor, vertigo, and vomiting. There have been postmarketing reports of serious discontinuation symptoms which can be protracted and severe. Completed suicide, suicidal thoughts, aggression and violent behavior have been observed in patients during reduction in Effexor XR dosage, including during discontinuation. Other postmarketing reports describe visual changes (such as blurred vision or trouble focusing) and increased blood pressure after stopping or reducing the dose of Effexor XR. During marketing of Effexor XR, other SNRIs, and SSRIs, there have been reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: irritability, lethargy, emotional lability, tinnitus, and seizures. Patients should be monitored for these symptoms when discontinuing treatment with Effexor XR. A gradual reduction in the dose, rather than abrupt cessation, is recommended. 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 healthcare provider may continue decreasing the dose, but at a more gradual rate. In some patients, discontinuation may need to occur over a period of several months [see Dosage and Administration (2.10) ] . 5.8 Seizures Cases of seizure have been reported with venlafaxine therapy. Effexor XR has not been systematically evaluated in patients with seizure disorder. Effexor XR should be prescribed with caution in patients with a seizure disorder. 5.9 Hyponatremia Hyponatremia can occur as a result of treatment with SNRIs, including Effexor XR. In many cases, the hyponatremia appears to be the result of the Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion. Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SNRIs. Also, patients taking diuretics, or those who are otherwise volume-depleted, may be at greater risk [see Use in Specific Populations (8.5) and Clinical Pharmacology (12.3) ] . Consider discontinuation of Effexor XR in patients with symptomatic hyponatremia, and institute appropriate medical intervention. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death. 5.10 Weight and Height Changes in Pediatric Patients Weight Changes The average change in body weight and incidence of weight loss (percentage of patients who lost 3.5% or more) in the placebo-controlled pediatric studies in MDD, GAD, and SAD are shown in Tables 3 and 4. Table 3: Average Change in Body Weight (kg) From Beginning of Treatment in Pediatric Patients Effexor XR is not approved for use in pediatric patients. in Double-blind, Placebo-controlled Studies of Effexor XR Indication (Duration) Effexor XR Placebo MDD and GAD (4 pooled studies, 8 weeks) -0.45 (n = 333) +0.77 (n = 333) SAD (16 weeks) -0.75 (n = 137) +0.76 (n = 148) Table 4: Incidence (%) of Pediatric Patients Effexor XR is not approved for use in pediatric patients. Experiencing Weight Loss (3.5% or more) in Double-blind, Placebo-controlled Studies of Effexor XR Indication (Duration) Effexor XR Placebo MDD and GAD (4 pooled studies, 8 weeks) 18 p <0.001 versus placebo (n = 333) 3.6 (n = 333) SAD (16 weeks) 47 (n = 137) 14 (n = 148) Weight loss was not limited to patients with anorexia [see Warnings and Precautions (5.11) ] . The risks associated with longer term Effexor XR use were assessed in an open-label MDD study of children and adolescents who received Effexor XR for up to six months. The children and adolescents in the study had increases in weight that were less than expected, based on data from age- and sex-matched peers. The difference between observed weight gain and expected weight gain was larger for children (<12 years old) than for adolescents (≥12 years old). Effexor XR is not approved for use in pediatric patients [Use in Specific Populations (8.4)] . Height Changes Table 5 shows the average height increase in pediatric patients in the short-term, placebo-controlled MDD, GAD, and SAD studies. The differences in height increases in GAD and MDD studies were most notable in patients younger than 12 years old. Table 5: Average Height Increases (cm) in Pediatric Patients Effexor XR is not approved for use in pediatric patients. in Placebo-controlled Studies of Effexor XR Indication (Duration) Effexor XR Placebo MDD (8 weeks) 0.8 (n = 146) 0.7 (n = 147) GAD (8 weeks) 0.3 p = 0.041 (n = 122) 1.0 (n = 132) SAD (16 weeks) 1.0 (n = 109) 1.0 (n = 112) In the six-month, open-label MDD study, children and adolescents had height increases that were less than expected, based on data from age- and sex-matched peers. The difference between observed and expected growth rates was larger for children (<12 years old) than for adolescents (≥12 years old) [see Use in Specific Populations (8.4) ] . 5.11 Appetite Changes in Pediatric Patients Decreased appetite (reported as anorexia) was more commonly observed in Effexor XR treated patients versus placebo-treated patients in the premarketing evaluation of Effexor XR for MDD, GAD, and SAD (see Table 6 ). Effexor XR is not approved for use in pediatric patients [see Use in Specific Populations (8.4) ] . Table 6: Incidence (%) of Decreased Appetite and Associated Discontinuation Rates The discontinuation rates for weight loss were 0.7% for patients receiving either Effexor XR or placebo. (%) in Pediatric Patients Effexor XR is not approved for use in pediatric patients. in Placebo-controlled Studies of Effexor XR Indication (Duration) Effexor XR Incidence Discontinuation Placebo Incidence Discontinuation MDD and GAD (pooled, 8 weeks) 10 0.0 3 – SAD (16 weeks) 22 0.7 3 0.0 5.12 Interstitial Lung Disease and Eosinophilic Pneumonia Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy have been rarely reported. The possibility of these events should be considered in Effexor XR-treated patients who present with progressive dyspnea, cough or chest discomfort. Such patients should undergo a prompt medical evaluation, and discontinuation of Effexor XR should be considered. 5.13 Sexual Dysfunction 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.