Orthostatic hypotension
Caution should be exercised in appointing quetiapine to patients with cardiovascular and cerebrovascular diseases or other conditions predisposing to hypotension. The use of quetiapine can cause orthostatic hypotension, especially in the initial period of dose selection (in elderly patients it is observed more often than in young patients). If orthostatic hypotension occurs, a dose reduction or slower titration may be required. Drowsiness and dizziness Quetiapine treatment may cause drowsiness and related symptoms, for example, sedation.With the development of severe drowsiness, patients with depression in the structure of bipolar disorder may need more frequent visits to the doctor within 2 weeks of the onset of drowsiness or to a decrease in the severity of symptoms. In some cases quetiapine therapy may be discontinued.
The withdrawal syndrome
With a sharp cancellation of high doses of antipsychotics, withdrawal can occur with the following acute symptoms: nausea, vomiting, insomnia, headache, dizziness, diarrhea.
It is recommended that Quetiapine be gradually withdrawn for a minimum of 1-2 weeks.
Wrong application and dependence
Incidents of erroneous use of quetiapine and the development of drug dependence have been reported. Care should be taken when assigning quetiapine patients with alcohol or drug dependence in history.
Sleep apnea syndrome
In patients receiving quetiapine, reported the development of the syndrome of nocturnal sleep apnea. Koumental should be used with caution in patients who are simultaneously receiving drugs that depress the central nervous system, or have a history of cases or risk factors for the development of the syndrome of nocturnal sleep apnea, such as overweight / obesity, male sex.
Suicide / suicidal thoughts and clinical deterioration
Depression is associated with an increased risk of suicidal thoughts, self-injury and suicide in children, adolescents and young people (under 25). This risk remains until the onset of severe remission. In view of the fact that before the improvement of the patient's condition from the beginning of treatment, several weeks or more may pass, patients should be under close medical supervision before the onset of improvement. Also, the doctor should assess the potential risk of suicide after quitting quetiapine. According to clinical experience, the risk of suicide may increase in the early stages of the onset of remission.
Other mental disorders for which treatment is prescribed quetiapineare also associated with an increased risk of suicidal events. In addition, such conditions can be comorbid with a depressive episode. Therefore, the precautions used in the treatment of patients with a depressive episode should be taken and treated in patients with other psychiatric disorders.
Patients with a history of suicidal events that clearly express suicidal thoughts before starting therapy, as well as patients younger than 25 with episodes of depression in bipolar disorder, are at increased risk of suicidal intentions and suicidal attempts and should be carefully observed during treatment.
Extrapyramidal symptoms
In adult patients treated for major depressive episodes in bipolar disorder, the use of quetiapine may be associated with an increased risk of developing extrapyramidal symptoms compared with placebo. The use of quetiapine was associated with the development of akathisia, characterized by subjectively unpleasant or irritating anxiety and the need to move, often accompanied by an inability to stand or sit still. The probability of this is greatest in the first few weeks of treatment. Increasing the dose in patients who develop these symptoms can cause harm.
Liver failure
Quetiapine is extensively metabolized in the liver. Therefore, caution should be exercised when using quetiapine in patients with hepatic insufficiency, especially at the onset of therapy.
Late dyskinesia
When signs of late dyskinesia should be reduced dose of quetiapine or to cancel the drug. Symptoms of tardive dyskinesia can worsen, and also occur even after discontinuation of treatment.
Malignant neuroleptic syndrome
The occurrence of malignant neuroleptic syndrome can be associated with ongoing antipsychotic treatment.
Clinical manifestation of the syndrome includes hyperthermia, changes in mental state, muscle rigidity, instability of the autonomic nervous system, increased activity of creatine phosphokinase. In such cases, quetiapine should be discontinued and treated accordingly.
Severe neutropenia and agranulocytosis
In clinical studies of quetiapine, severe neutropenia (<0.5 x 109 / L) was rarely observed. Most cases of severe neutropenia developed within 2 months after initiation of quetiapine treatment. Clear communication with the dose of the drug is not revealed. According to the experience of post-registration application after quetiapine withdrawal, resolution of leukopenia and / or neutropenia was observed. Possible risk factors for neutropenia include previous leukopenia and data on drug-induced neutropenia in history.Quetiapine treatment should be discontinued in patients with a reduction in the number of neutrophils <1.0 x 109/ l. Patients should be monitored for signs and symptoms of infection, as well as neutrophil levels (until this figure exceeds 1.5 x 109/ l).
It should be assumed neutropenia in patients with infection and fever, especially in the absence of obvious predisposing factors, and conduct appropriate treatment. Patients should be advised immediately to report the appearance of signs / symptoms associated with agranulocytosis or infection (such as fever, weakness, drowsiness, sore throat) at any time during treatment with quetiapine. In such patients, the number of leukocytes and the absolute number of neutrophils should be urgently assessed.
Weight gain and hyperglycemia
Patients taking any antipsychotics, including quetiapine, cases of weight gain have been described, therefore, the body weight of the patients should be monitored and symptomatic therapy should be administered in accordance with the guidelines for the use of antipsychotics.
In rare cases, hyperglycemia and / or the development or exacerbation of diabetes mellitus, sometimes associated with ketoacidosis or coma, have been described, including several lethal cases. In some cases, the previous increase in body weight was described, which could serve as a predisposing factor. It is recommended that appropriate clinical monitoring is performed in accordance with the current recommendations for treatment with neuroleptics. Patients receiving any antipsychotics, including quetiapine, should be monitored for signs and symptoms of hyperglycemia (such as polydipsia, polyuria, polyphagia, and weakness); patients with diabetes mellitus or with risk factors for developing diabetes should be monitored regularly for impaired glucose control. Regular monitoring of body weight is necessary.
Lipid profile
With the use of quetiapine, there was an increase in the concentration of triglycerides, LDL and total cholesterol, as well as a decrease in HDL in the serum, therefore, if necessary, control changes in the lipid profile.
Elderly patients with psychoses associated with dementia
Quetiapine is not indicated for the treatment of psychoses associated with dementia. Some atypical antipsychotics may increase the risk of developing cerebrovascular complications in patients with dementia. The mechanism of this increase in risk has not been studied. A similar risk of an increased incidence of cerebrovascular complications can not be ruled out
for other antipsychotic drugs or other groups of patients. Quetiapine should be used with caution in patients at risk of stroke.
A meta-analysis of the use of atypical antipsychotics for the treatment of psychoses associated with dementia in elderly patients revealed an increase in the mortality rate in the group of patients receiving drugs of this group, compared with the placebo group. There was no causal relationship between the treatment of quetiapine and the risk of increased mortality in elderly patients with dementia.
Convulsions
There were no differences in the incidence of seizures in patients taking quetiapine or placebo. However, as with other antipsychotics, caution should be exercised in the treatment of patients with a history of seizures.
Thyroid hormones
Quetiapine therapy may be accompanied by a slight dose-dependent decrease in the concentration of thyroid hormones, in particular, total and free thyroxin (T4). The maximum decrease was recorded at the second and fourth weeks of quetiapine therapy without further reduction in the concentration of hormones during long-term treatment. In practically all cases, the concentration of the total and free T4 returned to the baseline after quitting Quetiapine treatment regardless of the duration of treatment. A slight decrease in total and reverse triiodothyronine (T3) was noted only when high doses were used. There were no signs of clinically significant changes in TSH concentration, nor is there evidence of quetiapine's influence on the development of clinically significant hypothyroidism. The concentration of thyroxin-binding globulin remained unchanged.
QT interval extension
There was no correlation between the use of quetiapine and the prolongation of the QT interval. However, when prescribing quetiapine concurrently with drugs that extend the QT interval or neuroleptics, care must be taken, especially in the elderly,patients with the syndrome of congenital prolongation of the QT interval, chronic heart failure, myocardial hypertrophy, hypokalemia, or hypomagnesemia. In the postmarketing period, cases of prolongation of the QT interval with quetiapine were reported in both recommended doses and overdose. As with the use of other antipsychotics, caution should be exercised in patients with cardiovascular disease or with a family history of prolonging the QT interval.
Cardiomyopathy and myocarditis
Cardiomyopathy and myocarditis have been described in clinical studies and during post-marketing use, but the cause-and-effect relationship with the use of quetiapine has not been established. When suspicion of cardiomyopathy or myocarditis should be reviewed the issue of the need for treatment with quetiapine.
Dysphagia
Dysphagia was reported in patients taking quetiapine. Caution should be exercised when using quetiapine in patients at risk of aspiration pneumonia. Constipation and Intestinal Obstruction Constipation is a risk factor for intestinal obstruction.The cases of constipation and intestinal obstruction were reported with the use of quetiapine. They included fatal outcomes in patients with an increased risk of developing bowel obstruction, including those who received several drugs at the same time that reduce intestinal motility and / or could not report symptoms of constipation. Patients with intestinal obstruction / ileus should be under close supervision and in the context of emergency care.
Venous thromboembolism
When taking antipsychotic drugs, cases of venous thromboembolism were recorded. Because patients taking antipsychotics are often at high risk for venous thromboembolism, all possible risk factors for venous thromboembolism should be identified and administered before and during treatment with quetiapine.
Pancreatitis
Cases of pancreatitis have been reported in clinical trials and during post-marketing surveillance. Although not all cases in post-marketing reports were associated with risk factors, many patients had factors associated with pancreatitis,such as increased serum triglyceride concentrations, gallstones, alcohol consumption.
Anticholinergic (muscarinic) effects
Norquetiapine (an active metabolite of quetiapine) weakens pronounced affinity for several subtypes of muscarinic receptors. This contributes to the development of unwanted reactions associated with anticholinergic effects, with the use of quetiapine in the recommended doses together with other drugs with anticholinergic activity and against an overdose. Quetiapine should be used with caution in patients who are simultaneously receiving other drugs with anticholinergic action or who have quetiapine or a history of urinary retention, clinically significant prostatic hypertrophy, intestinal obstruction (or similar conditions), increased intraocular pressure, or a closed angle glaucoma. Interactions (see section "Interaction with other drugs")
With the concomitant use of quetiapine and strong inducers of hepatic enzymes, such as carbamazepine and phenytoin, the plasma concentration of quetiapine is significantly reduced, which can affect the effectiveness of treatment. When assigning quetiapine to a patient receiving hepatic enzyme inducers, the physician should carefully evaluate the benefit-risk relationship. It is important to take into account the gradual change in the dose of inducers of liver enzymes and, if necessary, they can be replaced with other drugs, for example, sodium valproate.
Data from studies of quetiapine in combination with divalproex (a complex compound of valproic acid and sodium valproate) or lithium preparations in acute moderate or severe episodes of mania are limited, but the combination therapy was well tolerated.
Quetiapine mainly affects the central nervous system, so caution should be exercised when combined with other drugs that have a depressant effect on the central nervous system. Use with alcohol is undesirable.