Fluoxetine Contraindications and Precautions
- abrupt discontinuation
- anorexia nervosa
- bipolar disorder
- bleeding
- breast-feeding
- cardiac disease
- children
- dehydration
- diabetes mellitus
- driving or operating machinery
- elderly
- electroconvulsive therapy (ECT)
- hepatic disease
- hyponatremia
- infants
- mania
- neonates
- pregnancy
- renal failure
- renal impairment
- seizure disorder
- suicidal ideation
Fluoxetine Contraindications and Precautions
Fluoxetine is contraindicated in those patients with a hypersensitivity to the drug or any of the formulation components.
Avoid abrupt discontinuation of any SSRI if possible. Gradual tapering is recommended during discontinuation of any SSRI to decrease or prevent the occurrence of potential withdrawal symptoms. However, fluoxetine is a long-acting SSRI, and withdrawal symptoms are uncommon due to the long half-life of the drug’s active metabolite. Withdrawal symptoms have been reported with abrupt or rapid discontinuation of short-acting SSRIs (e.g., sertraline). However, the manufacturer has reported that abrupt withdrawal of fluoxetine (Sarafem®) has also been associated with adverse CNS effects, including but not limited to dysphoric mood, irritability, agitation, dizziness, paresthesias, and headache. The difference in the incidence of withdrawal symptoms among SSRIs is most likely due to differences in the half-lives of the active moieties.
Fluoxetine should be used with caution in patients with a seizure disorder. Seizures have been reported rarely in patients taking fluoxetine; however, they have occurred primarily in cases of fluoxetine overdose. Fluoxetine’s effects during electroconvulsive therapy (ECT) have not been evaluated in clinical studies to date. Some clinicians have reported that in rare instances ECT-induced seizures were prolonged in patients taking fluoxetine. A possible mechanism of seizure prolongation may be a lowering of the seizure threshold caused by high concentrations of fluoxetine or its active metabolite norfluoxetine.
All effective antidepressants can transform depression into mania or hypomania in predisposed individuals. If a patient develops manic symptoms, fluoxetine should be withheld, and appropriate therapy initiated to treat the manic symptoms. Additionally, depression may be the presenting symptom of a mixed/manic episode of bipolar disorder. Patients should be adequately screened for bipolar disorder prior to initiating an antidepressant.
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. Patients with a history of suicidal ideation and who are at high risk for suicide attempt should be closely supervised during initial drug therapy with fluoxetine. In addition, fluoxetine 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, 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 fluoxetine is not approved for use in treating bipolar depression.
Fluoxetine is contraindicated for concomitant use in patients receiving MAO inhibitor therapy.
In patients with cirrhosis, the elimination half-life of fluoxetine and norfluoxetine is significantly prolonged. Thus, fluoxetine should be used with caution in patients with hepatic disease. If fluoxetine is administered to a patient with hepatic impairment, a lower dose or less frequent dosing interval should be used.
Studies in depressed patients on dialysis did not reveal excessive accumulation of fluoxetine or norfluoxetine in plasma. Although patients with renal dysfunction do not usually require a reduced dose of fluoxetine, the drug should probably be used with caution in those with severe renal impairment or renal failure.
Although clinical trial data indicate that fluoxetine is not associated with the development of clinically significant ECG abnormalities, the use of fluoxetine has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable cardiac disease.
Fluoxetine can cause a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) that presents as hypoosmolarity of serum and urine, and hyponatremia. Elderly patients and those receiving diuretics (i.e., dehydration) appear to be at greatest risk for hyponatremia.
Fluoxetine should be used with caution in patients with diabetes mellitus since fluoxetine can dysregulate glucose control. Dose adjustments of hypoglycemics may be necessary.
Because fluoxetine can cause weight loss, it should be used with caution in patients with anorexia nervosa or in other patients where weight loss is undesirable.
Fluoxetine is classified as FDA pregnancy risk category C. Animal teratology studies with fluoxetine have failed to show an increased risk of fetal malformations. However, animal studies have shown that SSRIs downregulate serotonin receptors in the fetal cortex and that these changes can be present for a period of time after birth. The applicability of these animal findings to human gestation is unknown; some human epidemiologic studies have suggested that the cognitive and behavioral development of infants prenatally exposed to fluoxetine does not differ from controls. In one prospective study, 228 women taking fluoxetine during pregnancy were evaluated against a control group of women exposed to nonteratogens. The rates of spontaneous abortion were similar in both groups. Rates of major structural anomalies in the neonates prenatally exposed to fluoxetine were also not significantly different from controls. However, the fluoxetine group reported the presence of 3 or more minor anomalies more frequently. In an analysis based on use during a specific trimester, neonates exposed to fluoxetine during the last trimester had higher rate of neonatal prematurity, low-birth weight in term infants, and poor neonatal adaptation. A prospective, human cohort study was conducted to evaluate the outcome of neonates born to 267 women who took an SSRI during pregnancy. Compared with a neonatal control group, SSRI-exposed neonates had similar rates of major malformation, spontaneous and elective abortion, and stillbirth. In addition, mean birth weight and gestational age were similar among the two groups of neonates. Of the SSRIs, there is clearly more data available for fluoxetine at this time. Additionally, neonates exposed to SSRIs or SNRIs, late in the third trimester have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding upon delivery. Symptoms have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome. When treating a pregnant woman with an SSRI or SNRI during the third trimester, the physician should carefully consider the potential risks and benefits of treatment. If clinically feasible, and taking the half-life into consideration, tapering of the serotonergic agent prior to delivery may be considered.
Fluoxetine should be used with caution in breast-feeding mothers because of the excretion of the drug into breast milk. SSRI concentrations in breast milk are typically similar to those of maternal serum. Patients should advise their physician of their intention to breast-feed. Fluoxetine has been observed to cause increased irritability, colic, vomiting, and decreased sleep in infants. The FDA has recommended against fluoxetine use during lactation, but some authors have not concurred. The American Academy of Pediatrics has suggested that SSRI use during breast-feeding may be of concern. Because fluoxetine and its active metabolite are eliminated slowly, consideration should be given to the possible presence of the drug in breast milk for a prolonged period after discontinuation of therapy. If breast-feeding is continued, the infant should be observed for evidence of adverse effects, and breast-feeding should be avoided at times of peak serum concentrations.
Fluoxetine is approved for the treatment of depression in children >= 8 years of age, and for the treatment of obsessive-compulsive disorder (OCD) in children >= 7 years of age. The safety and effectiveness of fluoxetine in children < 8 years of age (for depression) and < 7 years of age (for OCD) have not been established. 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. 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, akathesia, irritability, suicidality, loss of sleep and other unusual changes in behavior. Patients should be observed 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.
Because any psychoactive drug may impair judgement, thinking, or motor skills, patients should use caution when driving or operating machinery, until they are reasonably certain that fluoxetine does not affect them. The US olympic committee has only banned the use of the SSRI-type antidepressants in sporting events that involve rifelry.
Bleeding has rarely been reported during fluoxetine therapy. While a causal relationship to fluoxetine has not been established, impaired platelet aggregation may result from platelet serotonin depletion and may contribute to abnormal bleeding.
[ Last revised: 4/18/2005 11:20:00 AM ]
Related entries
Syndicate
|
