Effexor Contraindications and Precautions
- abrupt discontinuation
- anorexia nervosa
- bipolar disorder
- breast-feeding
- cardiac disease
- children
- closed-angle glaucoma
- CNS depression
- driving or operating machinery
- elderly
- glaucoma
- heart failure
- hepatic disease
- hypertension
- hyperthyroidism
- mania
- myocardial infarction
- neonates
- pregnancy
- renal failure
- renal impairment
- seizure disorder
- seizures
- suicidal ideation
- tardive dyskinesia
Effexor XR (Venlafaxine) Contraindications and Precautions
Venlafaxine should not be given to any patient with a known or suspected hypersensitivity reaction to venlafaxine or any other ingredient in the formulation.
The manufacturer warns that venlafaxine should not be used in patients receiving MAOIs (see Drug Interactions).
Avoid abrupt discontinuation of venlafaxine. When discontinuing venlafaxine after more than 1 week of therapy, it is generally recommended that the dose be tapered to minimize the risk of discontinuation symptoms. Patients who have received venlafaxine for more than 6 weeks or more should have their dose tapered gradually over at least a 2-week period. In clinical trials in patients taking the extended-release product (i.e., Effexor XR® ), tapering was achieved by reducing the daily dose by 75 mg at one week intervals. Individualization of tapering may be necessary. 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 physician may continue decreasing the dose but at a more gradual rate.
Venlafaxine is classified as FDA pregnancy risk category C. Animal teratology studies with venlafaxine have failed to show an increased risk of fetal malformations. However, an increase in stillbirths, low birth-weight, and pup deaths postnatally has been noted when venlafaxine was given throughout gestation and continued during lactation. The applicability of any of these findings to humans is unknown. There are no available reports on the use of venlafaxine during human pregnancy. Venlafaxine should be used in pregnancy only where the benefit to the mother clearly outweighs any potential risk to the fetus. Alternative agents should be considered. If the clinician and patient decide to continue venlafaxine during pregnancy, discontinuation symptoms should be considered in the newborn at birth. Neonates exposed to serotonergic antidepressants late in the third trimester have developed complications (see Adverse Reactions) requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Features are consistent with either a direct toxic effect of serotonergic agents or, possibly, a neonatal abstinence syndrome (see Adverse Reactions). It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. When treating a pregnant woman with an SNRI or other serotonergic agent during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, gradual tapering of the medication (in the mother) prior to delivery may be considered.
Venlafaxine and its active metabolite, O-desmethylvenlafaxine are both excreted in breast milk during lactation. Preliminary data show that the total dose of these agents ingested by breast-feeding infants can be roughly 9 - 10% of the maternal intake. Measurable concentrations of venlafaxine in infant plasma have also been observed. The decision to continue breast-feeding should take into account the benefit of the medication to the mother and the possible effects of venlafaxine on the breast-feeding infant. Exposed infants should be closely observed for adverse effects.
Venlafaxine should be used with caution in patients with renal impairment or renal failure because clearance is reduced. Patients with hepatic impairment have an increase in plasma concentrations of venlafaxine compared to patients without hepatic disease. Thus, this drug should be used with caution in patients with hepatic impairment. Reduced dosages of venlafaxine may be necessary in these patient populations (see Dosage).
Venlafaxine has not been extensively studied in patients with a recent history of significant cardiac disease. Because venlafaxine is associated with dose-related sustained increases in supine diastolic blood pressure, it should be used with caution in patients with preexisting hypertension, as well as patients with hyperthyroidism, recent myocardial infarction, or heart failure, particularly with doses > 200 mg/day. Blood pressure should be routinely monitored during therapy with venlafaxine. For patients who experience increased blood pressure while on venlafaxine, either dose reduction or discontinuation should be considered. Statistically significant and dose-dependent increases in heart rate have been observed on ECGs during venlafaxine therapy. Doses ranging 200 to 375 mg/day resulted in a mean increase of 4 beats per minute, while mean doses > 300 mg/day resulted in a heart rate increase of roughly 8 beats per minute.
All effective antidepressants can transform depression into mania in predisposed individuals. Based on reports during use of venlafaxine, this drug may activate mania or hypomania. Venlafaxine should be used cautiously in patients with a history of mania.
Venlafaxine is not FDA-approved for the treatment of depression in pediatric patients. The possibility of a suicide attempt is inherent in patients with depressive symptoms, whether these occur in primary depression or in association with another primary disorder such as OCD. Patients with suicidal ideation, including both adult and pediatric patients, should be closely supervised, whether or not they are taking an antidepressant. In addition, all antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients. The risk of suicidality for these drugs was identified in a pooled analysis of 24 placebo-controlled trials (n=4400) lasting up to 16 weeks in pediatric patients with major depressive disorder (MDD), obsessive compulsive disorder (OCD), or other psychiatric disorders. The analysis showed a greater risk of suicidality during the first few months of treatment in those receiving antidepressants (SSRIs and others). The average risk of such events on drug was 4% and 2% for placebo; however, no suicides occurred in these trials. Based on these data, FDA has determined that the following points are appropriate for inclusion in the boxed warning: antidepressants increase the risk of suicidal thinking and behavior (suicidality) in pediatric patients with MDD and other psychiatric disorders (OCD, social anxiety disorder); anyone considering the use of an antidepressant in a pediatric patient for any clinical use must balance the risk of increased suicidality with the clinical need; patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior, particularly within the first few months of starting therapy or at the time of dose increases or decreases; such observation would generally include at least weekly face-to-face contact with patients, family members or caregivers during the first 4 weeks of treatment, then every other week visits for the next 4 weeks, then at 12 weeks, and as clinically indicated beyond 12 weeks; additional contact by telephone may be appropriate between face-to-face visits; adults with MDD or co-morbid depression in the setting of other psychiatric illness being treated with antidepressants should be observed similarly for clinical worsening and suicidality, especially during the initial few months of a course of drug therapy, or at times of dose changes; families and caregivers should be advised to closely observe the patient (adult or child) on a daily basis for the emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality, and to communicate immediately with the prescriber. It is unknown if the suicidality risk in pediatric patients extends to longer-term therapy (i.e., beyond several months) or to adult patients. In patients who exhibit changes in symptoms (see Adverse Events), worsening of depression or emergent suicidality, a decision should be made to change or discontinue treatment. If discontinuing, medication should be tapered as rapidly as possible, but with recognition that abrupt discontinuation can also cause adverse symptoms. A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described represent such a conversion is unknown. Patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder prior to initiating treatment. Such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that venlafaxine is not approved for use in treating bipolar depression.
In October, 2004, the FDA directed manufacturers of all antidepressants to include a Black Box warning detailing the risk of suicide in pediatric patients. A causal role for antidepressants in inducing suicidality has been established in pediatric patients (see Contraindications, suicidal ideation). Pediatric patients should be monitored closely for the risk of suicide with any antidepressant medication. Among the antidepressants, only fluoxetine is approved for use in treating depression in pediatric patients. Fluoxetine, sertraline, fluvoxamine, and clomipramine are approved for OCD in pediatric patients. None of the drugs is approved for other psychiatric indications in children. Pediatric patients being treated with antidepressants for any indication should be observed daily by caregivers for clinical worsening, as well as agitation, irritability, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases. If concerns arise, contact with health care providers should be made immediately. Antidepressants should be prescribed in the smallest quantity consistent with good patient management in order to reduce the risk of overdose. A patient Medication Guide about using antidepressants in children and adolescents is available. Health care providers should instruct patients and caregivers to read the guide and discuss any questions with them. Venlafaxine has also been shown to lead to dose-dependent weight loss in children ages 6 - 17 (see Adverse Reactions).
In pre-marketing studies, venlafaxine was associated with a low incidence of seizures (0.26%). This agent should be used with caution in patients with a history of seizures or seizure disorder. If seizures develop during therapy, use of venlafaxine should be terminated. The addition of venlafaxine to established clozapine therapy may produce seizure activity (see Drug Interactions).
Venlafaxine produces a dose-dependent weight loss (see Adverse Reactions). Cautious use of venlafaxine in underweight depressed patients is recommended, especially those known to have anorexia nervosa. Patients who are debilitated, elderly, or who have body weights < 45 kg may need more careful dosage titration of venlafaxine. Venlafaxine is not approved for use in pediatric patients. Studies have been done that suggest venlafaxine may adversely affect weight and height in pediatric patients. 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. Venlafaxine is not indicated as a therapeutic agent for weight loss alone or in combination with other products.
Mydriasis has been reported in association with venlafaxine; patients with raised intra-ocular pressure or acute closed-angle glaucoma should be monitored.
Venlafaxine should be used cautiously in patients at greater risk for CNS depression as drowsiness and dizziness are common side effects. Patients should use caution when driving or operating machinery until the full effects of the drug are known.
In spontaneous adverse reaction reports, venlafaxine has been associated with tardive dyskinesia, although the causality is unknown.
[ Last revised: 12/19/2005 9:24:00 PM ]
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