Fluoxetine precautions

List of precautions
Abnormal Bleeding Anxiety and insomnia Altered appetite and weight Activation of mania/hypomania Hyponatremia Seizures Use in patients with concomitant illness Interference with cognitive and motor performance Discontinuation of Treatment with Fluoxetine

Abnormal Bleeding
Published case reports have documented the occurrence of bleeding episodes in patients treated with psychotropic drugs that interfere with serotonin reuptake. Subsequent epidemiological studies, both of the case-control and cohort design, have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. In two studies, concurrent use of a nonsteroidal anti-inflammatory drug (NSAID) or aspirin potentiated the risk of bleeding. Although these studies focused on upper gastrointestinal bleeding, there is reason to believe that bleeding at other sites may be similarly potentiated. Patients should be cautioned regarding the risk of bleeding associated with the concomitant use of Fluoxetine with NSAIDs, aspirin, or other drugs that affect coagulation. Return to top

Anxiety and insomnia
In US placebo-controlled clinical trials for major depressive disorder, 12% to 16% of patients treated with Fluoxetine and 7% to 9% of patients treated with placebo reported anxiety, nervousness, or insomnia. In US placebo-controlled clinical trials for OCD, insomnia was reported in 28% of patients treated with Fluoxetine and in 22% of patients treated with placebo. Anxiety was reported in 14% of patients treated with Fluoxetine and in 7% of patients treated with placebo. In US placebo-controlled clinical trials for bulimia nervosa, insomnia was reported in 33% of patients treated with Fluoxetine 60 mg, and 13% of patients treated with placebo. Anxiety and nervousness were reported, respectively, in 15% and 11% of patients treated with Fluoxetine 60 mg and in 9% and 5% of patients treated with placebo. Among the most common adverse events associated with discontinuation (incidence at least twice that for placebo and at least 1% for Fluoxetine in clinical trials collecting only a primary event associated with discontinuation) in US placebo-controlled fluoxetine clinical trials were anxiety (2% in OCD), insomnia (1% in combined indications and 2% in bulimia), and nervousness (1% in major depressive disorder). Return to top

Altered appetite and weight
Significant weight loss, especially in underweight depressed or bulimic patients may be an undesirable result of treatment with Fluoxetine. In US placebo-controlled clinical trials for major depressive disorder, 11% of patients treated with Fluoxetine and 2% of patients treated with placebo reported anorexia (decreased appetite). Weight loss was reported in 1.4% of patients treated with Fluoxetine and in 0.5% of patients treated with placebo. However, only rarely have patients discontinued treatment with Fluoxetine because of anorexia or weight loss. In US placebo-controlled clinical trials for OCD, 17% of patients treated with Fluoxetine and 10% of patients treated with placebo reported anorexia (decreased appetite). One patient discontinued treatment with Fluoxetine because of anorexia. In US placebo-controlled clinical trials for bulimia nervosa, 8% of patients treated with Fluoxetine 60 mg and 4% of patients treated with placebo reported anorexia (decreased appetite). Patients treated with Fluoxetine 60 mg on average lost 0.45 kg compared with a gain of 0.16 kg by patients treated with placebo in the 16-week double-blind trial.Weight change should be monitored during therapy. Return to top

Activation of mania/hypomania
In US placebo-controlled clinical trials for major depressive disorder, mania/hypomania was reported in 0.1% of patients treated with Fluoxetine and 0.1% of patients treated with placebo. Activation of mania/hypomania has also been reported in a small proportion of patients with Major Affective Disorder treated with other marketed drugs effective in the treatment of major depressive disorder. In US placebo-controlled clinical trials for OCD, mania/hypomania was reported in 0.8% of patients treated with Fluoxetine and no patients treated with placebo. No patients reported mania/hypomania in US placebo-controlled clinical trials for bulimia. In all US Fluoxetine clinical trials as of May 8, 1995, 0.7% of 10,782 patients reported mania/hypomania. Return to top

Hyponatremia
Cases of hyponatremia (some with serum sodium lower than 110 mmol/L) have been reported. The hyponatremia appeared to be reversible when Fluoxetine was discontinued. Although these cases were complex with varying possible etiologies, some were possibly due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The majority of these occurrences have been in older patients and in patients taking diuretics or who were otherwise volume depleted. In two 6-week controlled studies in patients ≥60 years of age, 10 of 323 fluoxetine patients and 6 of 327 placebo recipients had a lowering of serum sodium below the reference range; this difference was not statistically significant. The lowest observed concentration was 129 mmol/L. The observed decreases were not clinically significant. Return to top

Seizures
In US placebo-controlled clinical trials for major depressive disorder, convulsions (or events described as possibly having been seizures) were reported in 0.1% of patients treated with Fluoxetine and 0.2% of patients treated with placebo. No patients reported convulsions in US placebo-controlled clinical trials for either OCD or bulimia. In all US Fluoxetine clinical trials as of May 8, 1995, 0.2% of 10,782 patients reported convulsions. The percentage appears to be similar to that associated with other marketed drugs effective in the treatment of major depressive disorder. Fluoxetine should be introduced with care in patients with a history of seizures. The long elimination half-lives of fluoxetine and its metabolites — Because of the long elimination half-lives of the parent drug and its major active metabolite, changes in dose will not be fully reflected in plasma for several weeks, affecting both strategies for titration to final dose and withdrawal from treatment. Return to top

Use in patients with concomitant illness
Clinical experience with Fluoxetine in patients with concomitant systemic illness is limited. Caution is advisable in using Fluoxetine in patients with diseases or conditions that could affect metabolism or hemodynamic responses. Fluoxetine has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were systematically excluded from clinical studies during the product’s premarket testing. However, the electrocardiograms of 312 patients who received Fluoxetine in double-blind trials were retrospectively evaluated; no conduction abnormalities that resulted in heart block were observed. The mean heart rate was reduced by approximately 3 beats/min. In subjects with cirrhosis of the liver, the clearances of fluoxetine and its active metabolite, norfluoxetine, were decreased, thus increasing the elimination half-lives of these substances. A lower or less frequent dose should be used in patients with cirrhosis. Studies in depressed patients on dialysis did not reveal excessive accumulation of fluoxetine or norfluoxetine in plasma. Use of a lower or less frequent dose for renally impaired patients is not routinely necessary. In patients with diabetes, Fluoxetine may alter glycemic control. Hypoglycemia has occurred during therapy with Fluoxetine, and hyperglycemia has developed following discontinuation of the drug. As is true with many other types of medication when taken concurrently by patients with diabetes, insulin and/or oral hypoglycemic dosage may need to be adjusted when therapy with Fluoxetine is instituted or discontinued. Return to top

Interference with cognitive and motor performance
Any psychoactive drug may impair judgment, thinking, or motor skills, and patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that the drug treatment does not affect them adversely. Return to top

Discontinuation of Treatment with Fluoxetine
During marketing of Fluoxetine and other SSRIs and SNRIs (serotonin and norepinephrine 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 sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. 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 Fluoxetine. 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 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. Plasma fluoxetine and norfluoxetine concentration decrease gradually at the conclusion of therapy, which may minimize the risk of discontinuation symptoms with this drug. Return to top