Afaxor 75/Afaxor 150 Special Precautions

Discontinuation of Treatment with Venlafaxine: Discontinuation symptoms have been systematically evaluated in patients taking venlafaxine, to include prospective analysis of clinical trials in Generalized Anxiety disorder and retrospective surveys of trials in major depressive disorder, and Social Anxiety Disorder. Abrupt discontinuation or dose reduction of venlafaxine at various doses have 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.
During marketing of Venlafaxine, other SNRIs (Serotonin and Norepinephrine Reuptake inhibitors), and SSRIs (Selective Serotonin Reuptake Inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: Dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g. paresthesias such as electric shock sensation), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored for these symptoms when discontinuing treatment with Venlafaxine. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. If intolerable symptoms occur following a decrease in the dose or upon discontinuation or treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose but at a more gradual rate.
Insomnia and Nervousness: Treatment-emergent insomnia and nervousness were commonly reported for patients treated with Venlafaxine capsules.
Insomnia and nervousness each led to drug discontinuation in 0.9% of the patients treated with Venlafaxine in major depressive disorder studies.
In GAD trials, insomnia and nervousness led to drug discontinuation in 0.9% of the patients treated with Venlafaxine in major depressive disorder studies.
Venlafaxine in major depressive disorder studies.
In GAD trials, insomnia and nervousness led to drug discontinuation in 3% and 2% respectively of the patient treated with Venlafaxine up to 8 weeks and 2% and 0.7%, respectively, of the patients treated with the Effexor XR up to 6 months.
In panic disorder trials, insomnia and nervousness led to drug discontinuation in 1% and 0.1%, respectively, of the patients treated with Venlafaxine up to 12 weeks.
Changes in Weight: Adult Patients: A loss of 5% or more of body weight occurred in 7% Venlafaxine -treated and 2% of placebo-treated patients in the short-term placebo-controlled major depressive disorder trials, The discontinuation rate for weight loss associated with Venlafaxine was 0.1 % in major depressive disorder studies, In placebo-controlled GAD studies, a loss of 7% or more of body weight occurred in 3% of Venlafaxine patients and 1% of placebo patients who received treatment for up to 6 months, The discontinuation rate for weight loss was 0,3% for patients receiving Venlafaxine in GAD studies for up to eight weeks, In placebo-controlled Social Anxiety Disorder trials, 4% of the Venlafaxine-treated and 1% of the placebo-treated patients sustained a loss of 7% or more of body weight during up to 6 months of treatment. None of the patients receiving Venlafaxine in Social Anxiety Disorder studies discontinued for weight loss, In placebo-controlled panic disorder trials, 3% of the Venlafaxine-treated and 2% of the placebo-treated patients sustained a loss of 7% or more of body weight during up to 12 weeks of treatment None of the patients receiving Venlafaxine in panic disorder studies discontinued for weight loss.
The safety and efficacy of venlafaxine therapy in combination with weight loss agents, including phentermine, have not been established, Co-administration of Venlafaxine and weight loss agents is not recommended. Venlafaxine is not indicated for weight loss alone or in combination with other products.
Pediatric Patients: The risks associated with longer-term Venlafaxine use were assessed in an open-label MDD study of children and adolescents who received Venlafaxine 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).
Activation of Mania/Hypomania: Mania/hypomania has also been reported in a small proportion of patients with mood disorders who were treated with other marketed drugs to treat major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, Venlafaxine should be used cautiously in patients with a history of mania.
Hyponatremia: Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including Venlafaxine, In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also patients taking diuretics or who are otherwise volume depleted may be at greater risk. Discontinuation of Venlafaxine should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.
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.
Abnormal Bleeding: SSRIs and SNRIs, including Venlafaxine, 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, warfarin, and other anticoagulants or other drugs known to affect platelet function may add to this risk. Patients should be cautioned about the risk of bleeding associated with the concomitant use of Venlafaxine and NSAIDs, aspirin, or other drugs that affect coagulation.
Interstitial Lung Disease and Eosinophilic Pneumonia: Interstitial lung disease and eosinophilic pneumonia associated with venlafaxine therapy have been rarely reported. The possibility of these adverse events should be considered in venlafaxine-treated patients who present with progressive dyspnea, cough or chest discomfort. Such patients should undergo a prompt medical evaluation, and discontinuation of venlafaxine therapy should be considered.
Use in Patients with Concomitant Illness: Venlafaxine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease.
As increases in heart rate were observed, caution should be exercised in patients whose underlying medical conditions might be compromised by increases in heart rate (e.g., patient with hyperthyroidism, heart failure, or recent myocardial infarction).
In patients with renal impairment (GFR = 10 to 70 mL/min) or cirrhosis of the liver, the clearances of venlafaxine and its active metabolites were decreased, thus prolonging the elimination half-lives of these substances. A lower dose may be necessary. Venlafaxine, like all drugs effective in the treatment of major depressive disorder, should be used with caution in such patients.
Use in Children: Safety and effectiveness in the pediatric population have not been established. Anyone considering the use of Venlafaxine in a child or adolescent must balance the potential risks with the clinical need. Although no studies have been designed to primarily assess Venlafaxine impact on the growth, development, and maturation of children and adolescents, the studies that have been done suggest that Venlafaxine may adversely affect weight and height. Should the decision be made to treat a pediatric patient with Venlafaxine, regular monitoring of weight and height is recommended during treatment, particularly if it is to be continued long term. The safety of Venlafaxine treatment for pediatric patients has not been systematically assessed for chronic treatment longer than six months in duration.
Use in the Elderly: 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. However, greater sensitivity of some older individuals cannot be ruled out SSRIs and SNRIs, including Venlafaxine have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event. The pharmacokinetics of venlafaxine and ODV are not substantially altered in the elderly. 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.