Suicidal risk. With depression, there is a likelihood of suicidal attempts, which can persist until the onset of persistent remission. As with other drugs of similar pharmacological action (antidepressants), separate cases of suicidal thoughts and suicidal behavior were described against fluoxetine therapy or shortly after its termination.
In other disorders, in which the
fluoxetine, may also increase the risk of suicidal behavior. In addition, these disorders can accompany a major depressive disorder. Therefore, in the treatment of these disorders should be the same caution as in the treatment of major depressive disorder. Despite the fact that the effect of fluoxetine on the occurrence of such cases has not been established, data from the combined studies of the use of antidepressants in mentaldisorders showed an increased risk of suicidal thoughts and / or suicidal behavior in children and young patients (younger than 25 years) as compared to placebo.
It is necessary to carefully monitor patients, in particular with a high risk of developing suicidal behavior, especially in the early stages of treatment and after changing the dosage. Patients, carers and caring for patients should be alerted about the need to monitor any deterioration of clinical status, suicidal behavior or thoughts and unusual changes in behavior and should immediately contact your doctor if any of these symptoms.
In studies on adult patients with major depressive disorder in both groups taking placebo and
fluoxetine, the following risk factors for suicide were identified.
Before treatment:
- more severe course of depression,
- the presence of thoughts of death.
During treatment:
- weighting depression,
- development of insomnia.
During the treatment with fluoxetine, a risk factor was also the development of severe psychomotor activity (eg, agitation, akathisia, panic).
The presence or occurrence of these conditions before or during therapy is the basis for strengthening clinical control or adjusting the treatment. Cardiovascular effects. When fluoxetine is taken, the QT interval may be prolonged, and ventricular arrhythmia or ventricular pirouette tachycardia, reported during the post-marketing fluoxetine study, may also occur.
Fluoxetine should be used with caution in patients with congenital QT interval prolongation syndrome, acquired QT interval prolongation syndrome (eg, while taking fluoxetine with QT prolonging medications), if there is an anamnesis indicating prolongation of the QT interval in the patient's relatives, in other clinical conditions , predisposing to the development of arrhythmia (eg, hypokalemia or hypomagnesemia, bradycardia, acute myocardial infarction or decompensated heart failure) or with increased exposure to fluoxetine (eg, with reduced liver function). Patients with stable heart disease, fluoxetine, like any antidepressant, should be discontinued if the patient is manic.
Akathisia / psychomotor anxiety.
It is necessary to conduct an ECG study before starting fluoxetine therapy. When developing signs of arrhythmia during therapy, fluoxetine should be discontinued and an ECG study performed. Skin rash. It is reported on the occurrence of skin rash, anaphylactic reactions and progressive systemic disorders, sometimes serious involving the pathological process of the skin, kidneys, liver and lungs in patients taking
fluoxetine. If skin rashes or other possible allergic reactions occur, the etiology of which can not be determined, fluoxetine should be withdrawn.
Epileptic seizures. As with other antidepressants,
fluoxetine should be administered with caution to patients who have previously had epileptic seizures. Fluoxetine therapy should be discontinued when epileptic seizures develop in any patient. Also, fluoxetine therapy should not be given to patients with unstable epilepsy, patients with controlled epilepsy should be closely monitored.
Mania. Antidepressants should be used with caution in patients with history of mania / hypomania.The intake of fluoxetine, like any antidepressant, must be discontinued if the patient is in a manic state.
Akathisia / psychomotor anxiety. The use of fluoxetine leads to the development of akathisia, which is manifested subjectively unpleasant sensations or restlessness, the need for constant movement, often without the possibility of sitting or standing still. Most often, such phenomena are observed during the first few weeks of treatment. In patients with these symptoms, increasing the dose of fluoxetine can have negative consequences.
Symptoms of withdrawal. Often, with discontinuation of fluoxetine therapy, especially with a sharp abolition, withdrawal symptoms were noted. In clinical studies, approximately 60% of patients developed various side effects when treatment was withdrawn, both in the fluoxetine group and in the placebo group. In the fluoxetine group, 17% of these events were severe, in the placebo group, 12%.
The risk of developing withdrawal symptoms depends on several factors, including the duration of therapy, the dose and the rate of dose reduction. The most frequently reported dizziness, sensory disturbances (including paresthesia),sleep disturbances (including insomnia and deep sleep), asthenia, anxiety or arousal, nausea and / or vomiting, tremor and headache. Usually, these episodes were mild and moderate, but some patients could have a more pronounced character. In most cases, these phenomena are resolved on their own within two weeks, but sometimes may be longer (2-3 months or more). In this regard, the abolition of fluoxetine therapy should be carried out gradually, within one or two weeks, depending on the needs of the patient.
Tamoxysien.
Fluoxetine. as a potent inhibitor of the isoenzyme CYP2D6, can lead to a decrease in the concentration of endoxifene, one of the most important active metabolites of tamoxifen. Therefore, when using tamoxifen, fluoxetine should be avoided. Loss of body weight. When fluoxetine is used, patients may have a loss of body weight, however, it is usually proportional to the initial mean body weight.
Hyponotremia. There were cases of hyponatremia (in some cases, the level of sodium in the blood serum was less than 110 mmol / l). In most cases, such cases were observed in elderly patients, in patients receiving diuretics and in patients with a decrease in the volume of circulating blood.
Glycemic control.In patients with diabetes during treatment with fluoxetine, hypoglycemia was noted, and after the drug was discontinued, hyperglycemia developed. At the beginning or after the end of treatment with fluoxetine, you may need to adjust the doses of insulin and / or hypoglycemic drugs for ingestion.
Hepatic / Renal Failure
Fluoxetine is subjected to intensive metabolism in the liver and is excreted by the kidneys. Patients with severe impairment of liver function are recommended to prescribe lower doses of fluoxetine, or prescribe the drug every other day. When fluoxetine was taken at a dose of 20 mg / day for two months, patients with severe renal dysfunction (CC <10 ml / min) in need of hemodialysis did not show differences in fluoxetine and norfluoxetine concentrations in plasma from healthy individuals with normal function kidney.
Meadois. Mydriasis associated with fluoxetine was reported. Caution should be exercised when administering fluoxetine to patients with increased intraocular pressure or patients at risk of developing acute angle-closure glaucoma.
Increased bleeding.When applying SSRIs, it was reported about ecchymosis, purpura and other similar disorders associated with increased bleeding. About ecchymosis was reported infrequently, other hemorrhagic phenomena (gynecological bleeding, gastrointestinal bleeding, etc.) were rare. Caution should be exercised in fluoxetine therapy, particularly in patients with concomitant therapy with oral anticoagulants and other agents that affect platelet function (eg with atypical antipsychotics such as
clozapine, with phenothiazines, with most tricyclic antidepressants, acetylsalicylic acid, non-steroidal anti-inflammatory drugs), and with concomitant therapy with drugs that can increase the tendency to bleeding and patients with bleeding history. Electroconvulsive therapy. In patients receiving electroconvulsive therapy, with the use of fluoxetine in rare cases, there were prolonged convulsive seizures. It is advisable to be careful with fluoxetine therapy in such patients.
Facilities. containing St. John's Wort.With the joint use of SSRIs (including fluoxetine) with products containing St. John's Wort, it is possible to increase serotonergic effects, such as serotonin syndrome.
In rare cases, it has been reported that associated with the administration of fluoxetine, the development of serotonin syndrome or malignant neuroleptic syndrome, especially when combined with other serotonergic agents (including those containing L-tryptophan) and / or antipsychotics. Since these syndromes can lead to a life-threatening condition, fluoxetine therapy should be discontinued in case of a combination of symptoms: hyperthermia, rigidity, myoclonus, autonomic nervous system disorder with the development of fluctuations in vital signs, changes in mental state, including confusion, irritability, extreme excitement possible development of delirium and coma) and prescribe the necessary symptomatic therapy.
All patients taking antidepressants for any indication should be under appropriate supervision, careful monitoring of the appearance of signs of clinical deterioration,suicidal intentions and unusual behavioral changes, especially during the first months of therapy or during dosage changes (increase or decrease).