Observed Quetiapine Concentrations and Pharmacokinetics. In our case report the measured serum concentrations of quetiapine were lower than the expected quetiapine concentrations due to the absorption rate constant, time -1 and displayed a reduced absorption of quetiapine after ingestion Figure 1. These findings are consistent with previously findings [ 11 , 12 ]. Lower than expected peak concentrations may be explained by potential anticholinergic effects of quetiapine reducing absorption.
With regard to a delayed absorption the expected time to maximum quetiapine concentration is supposed to be prolonged in these cases. In contrast to the findings of Hunfeld et al. We assume that the impacts of side effects after ingestion of a very high amount of quetiapine may have contributed a decreased absorption with no influence on terminal elimination half-life.
A comprehensive drug screen via immunoassay was positive for tricyclic antidepressants and benzodiazepines in particular. Though an additional spectrophotometric UV -HPLC-method performed by the institute of forensic medicine did not confirm the concomitant intake of lorazepam. A comprehensive drug screening of tricyclic antidepressants could not be confirmed in additional analyses with UV-HPLC.
Recommendations for Management of Therapy after Quetiapine Intoxication. The treatment of quetiapine intoxications in case of an unknown ingested amount in particular consists in a supportive therapy and the patients should be monitored in an intensive care unit.
Forced Diuresis with Furosemide and Saline. In case of a hypotensive patient the administration of diuretic drugs e. Gastric Lavage after 27 Hours. It should be noted that the risk of death following atypical antipsychotic overdose is very low [ 13 ] and gastric lavage is not routinely recommended after the 60 minutes time range [ 13 , 29 ]. Monitoring of cardiac and respiratory function, intravenous access, and a lead ECG is required [ 7 , 13 , 14 ]. Serum potassium should be maintained in the high-normal range 4.
Monitoring of thyroid function in quetiapine treated patients with a history of or a vulnerability to thyroid disease is strongly recommended [ 31 ]. Symptoms associated with intoxication were coma without arterial hypotension, persistent tachycardia, hyperglycemia, transient hypothyroidism, and a moderately extended -interval.
Management of overdose consisted in primarily supportive therapy on an intensive care unit. In addition the present case may help us to understand the different side effects of an atypical antipsychotic drug with regard to receptor-pharmacological mechanisms.
Therapeutic drug monitoring and pharmacokinetic analysis of quetiapine after intoxication displayed a moderately increased elimination and a reduced absorption of quetiapine. Despite the extreme overdose of quetiapine the patient exhibited a rapid clinical improvement and recovered without residual symptoms. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Reuter, 2 and C. Academic Editor: Rade B. Received 17 Oct Accepted 23 Nov Published 03 Jan Abstract Quetiapine is an atypical antipsychotic approved for the treatment of patients with psychotic disorders.
Introduction Quetiapine is indicated and approved for the treatment of psychotic disorders in adults by the U. Table 1. Figure 1. Solid-line: fitted line based on a two-compartment model assuming a reduced resorption. Dotted line: fitted line expected by population pharmacokinetic parameters and normal resorption. References C. DeVane and C. View at: Google Scholar J. Goren and G. View at: Google Scholar L. Fabre Jr. Arvanitis, J. Pultz, V. Jones, J. Malick, and V. View at: Google Scholar B.
View at: Google Scholar T. Healthcare, Intranet database, version 5. Saller and A. View at: Google Scholar C. Balit, G. Isbister, L.
Hackett, and I. Hunfeld, E. High blood sugar can occur in people with or without diabetes. Symptoms can include feeling very thirsty or hungry, needing to urinate more than usual, feeling weak or tired, or having fruity-smelling breath. Your doctor will monitor you for these metabolic changes.
Quetiapine can cause tardive dyskinesia. Tardive dyskinesia may not go away even if you stop taking quetiapine. It may also start after you stop taking this drug.
Taking quetiapine with other anticholinergic drugs may increase your risks of anticholinergic effects that may cause serious injuries.
Symptoms may include severe constipation or stomach pain, inability to empty your bladder urinary retention , blurred vision, drowsiness, delirium, confusion, and falls. Your risks may be increased if you are over 65 and have a history of these side effects. If you experience any of these symptoms, call your doctor right away. Taking it again could be fatal cause death. Quetiapine can cause drowsiness. The use of drinks that contain alcohol raises your risk of this side effect. If you drink alcohol, talk to your doctor about whether this drug is safe for you.
For people with diabetes or high blood sugar: Quetiapine may increase your blood sugar levels, which can worsen your condition. Extremely high blood sugar may lead to coma or death. If you have diabetes or risk factors of diabetes, talk with your doctor. They should check your blood sugar before and during treatment with quetiapine. For people with hyperlipidemia high fat levels in the blood : Quetiapine may further increase the levels of fat cholesterol and triglycerides in your blood.
High fat levels raise your risk of heart attack and stroke. Therefore, your doctor may check your blood cholesterol and triglycerides during treatment with quetiapine. For people with low or high blood pressure : Quetiapine may worsen your high or low blood pressure.
It may also increase blood pressure in children and teenagers. Your doctor should monitor your blood pressure while you take quetiapine. For people with a low white blood cell count: Quetiapine may lower your low white blood cell count even more. Your doctor should monitor your white blood cell count often during your first few months of treatment.
This can help make sure that quetiapine is not decreasing your white blood cell count. For people with cataracts : Quetiapine may worsen your cataracts. Your doctor will monitor you for changes in your cataracts. They will examine your eyes when you start treatment and every 6 months during treatment. For people with seizures: Seizures have occurred in patients with or without epilepsy while taking quetiapine.
Quetiapine may make it harder to control seizures in people with epilepsy. Your doctor should monitor you for an increase in seizures while taking this drug.
For people with hypothyroidism low thyroid level : Quetiapine may lower thyroid hormone levels and worsen your existing condition. Your doctor should monitor your blood thyroid hormone levels before and during treatment with this drug. For people with heart problems: Ask your doctor if this drug is safe for you. This drug increases the risk of abnormal heart rhythms.
For people with liver problems: Quetiapine is mainly broken down in the body by the liver. As a result, people with liver problems may have increased blood levels of this drug. This raises the risk of side effects from this drug. For people with severe constipation : Quetiapine can cause constipation and increase your risk of gastrointestinal problems including bowel block. This has been deadly in people taking this drug with other drugs that slow movement through your gastrointestinal tract.
If you have questions, talk with your doctor. Using quetiapine with anticholinergic drugs may increase the risk of gastrointestinal problems. For pregnant women: Quetiapine is a category C pregnancy drug. That means two things:. This drug should only be used if the potential benefit justifies the potential risk.
For women who are breastfeeding: Quetiapine may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication. For seniors: The kidneys and livers of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, a higher amount of a drug stays in your body for a longer time.
This raises your risk of side effects. All possible dosages and drug forms may not be included here. Your dosage, drug form, and how often you take the drug will depend on:. Your doctor may start you on a lowered dosage or a different dosing schedule. This can help keep levels of this drug from building up too much in your body. By day 2 of hospitalization in the ICU about 48 h after ingestion , sedation was discontinued and the patient regained consciousness and became alert and able to follow simple commands.
A weaning protocol was started, and the patient was extubated shortly thereafter. By ICU day 3 about 72 h after the ingestion , the patient became agitated, and consequently needed sedation. On day 4 of hospitalization, the patient was moved to a medical ward. At this time, ECG showed sinus rhythm with a heart rate of 90 beats per minute and a QTc of ms, incomplete right bundle branch block, but no further signs of left branch hemiblock; he was conscious, sometimes agitated, and partially cooperative; diuresis was valid; the nasogastric tube was removed, and oral feeding was possible.
On day 5 after ingestion, the patient had a body temperature of A blood sample was positive for Staphylococcus aureus and Staphylococcus lugdunensis. The case was referred to an infectivology consultant, who diagnosed a probable infection starting from the CVC. Following his suggestions to exclude other possible causes or complications, an echocardiogram was performed, which excluded the presence of myocarditis or endocarditis.
Cardiac function was as follows: left ventricle of normal size and global and segmental kinetics; mild symmetrical hypertrophy. Ejection fraction EF A chest X-ray was also performed, with no evidence of either parenchymal focal lesion or pleural effusion. Antibiotic therapy with amoxicillin clavulanate was started, with progressive improvement of symptoms and laboratory indexes in about 14 days.
The CVC and bladder catheter were then removed. At day 6 from ingestion, the patient was voluntarily transferred to an acute psychiatric care unit for further observation and treatment.
Upon the arrival in the acute psychiatric ward APW the patient was alert, lucid, oriented, and cooperative; psychomotricity was normal. Mood was only slightly depressed, but the patient reported a strong feeling of intense anxiety and distress. He had insight into the dangerousness of the suicide attempt, and he was aware that it followed a period of emotional stress and depression. Neither abnormal thinking nor alterations of perception were visible.
ECG was normal, with a heart rate of about 90 beats per minute. On day 12 of hospitalization in the APW day 18 from ingestion , the patient experienced a second episode of PSVT, which was again treated with intravenous adenosine triphosphate 6 mg with benefit.
In the APW, a specific therapy was gradually set, consisting of aripiprazole 30 mg, valproate 1, mg, sertraline mg, and trazodone mg per day. During the remaining period in the APW, there were no other physical problems and an outpatient psychiatric follow-up was decided. The patient was discharged to home on the 36th day after the suicide attempt. Here we report a case of coma with severe respiratory failure, hypotension, and tachycardia induced by the intentional ingestion of quetiapine fumarate XR 20 g in a year-old man with bipolar disorder.
Further, on day 10 and 18 after voluntary overdose, the patient developed two episodes of PSVT. To our knowledge, our report is among few clinical cases involving patients older than 70 years [ 9 , 28 ].
The toxicity reported for quetiapine seems to vary widely, with fatalities reported with therapeutic doses [ 29 ] as well as with massive ingestions: coma and death have been reported after an acute overdose of Ongoing chronic treatment with the 3A4 inhibitors ketoconazole, fluvoxamine, protease inhibitors, and erythromycin may increase quetiapine toxicity, leading to increased plasma concentration [ 17 , 30 , 31 ].
Additional risk factors include medical comorbidities such as hepatic and cardiac dysfunctions, age, and previous electrolyte imbalances [ 3 , 32 ]. Among psychiatric medications, the two most commonly suggested mechanisms in cardiac dysrhythmias are sodium channel antagonism producing prolonged QRS interval duration and ventricular dysrhythmias and potassium channel antagonism producing QTc interval prolongation and torsade de pointes.
The affinity of quetiapine for cardiac sodium channels is not well described, but a number of quetiapine overdose reports describe QRS interval prolongation similar to the type 1A anti-dysrhythmics [ 33 ]. Comparing the potency of potassium channel inhibition with the therapeutic plasma levels of the drugs, the difference between the inhibitory potency and the therapeutic dose is highest in the case of quetiapine along with olanzapine and risperidone , with thioridazine showing the smallest difference.
Some additional cellular effects of particular factors diseases, electrolytes disturbances, genetic damage, drug interactions could make the individual vulnerable to arrhythmia [ 34 ].
Despite the presence of several risk factors, such as age and hypertension, our patient recovered completely from a high oral overdose of quetiapine, without residual symptoms. Unfortunately, we have neither data on quetiapine plasma levels before day 4 nor measurements of other drugs that the patient was taking at the time of overdose.
Further, in our case, there was no evidence of co-ingestion of other drugs or alcohol; drug screening was positive for TCAs, likely due to the cross-reactivity of TCAs with quetiapine [ 10 ]. The management of quetiapine intoxication includes supportive care and continuous cardiac monitoring.
Activated charcoal can be given for initial decontamination [ 38 ]. Gastric lavage is not routinely recommended after 60 min [ 39 , 40 ]; in our case, the latency from ingestion to presentation was uncertain, and a gastric lavage was performed as suggested by the Pavia poison control center. The use of multi-dose activated charcoal could also be considered, despite that its use is not recommended in quetiapine overdoses [ 41 ].
Monitoring of cardiac and respiratory function, intravenous access, and a lead ECG is required [ 12 , 40 ]. In patients with QTc prolongation, serum potassium and magnesium should be maintained in the high—normal range, and concomitant drugs interfering with quetiapine metabolism should be discontinued [ 42 , 43 ].
We presented a case of overdose with quetiapine 20 g in a year-old man, leading to deep coma, respiratory depression, hypotension, and tachycardia. Further, on day 10 and 18 after overdose, the patient developed two episodes of PSVT, a causal relation of which with intoxication is quite unlikely.
The patient fully recovered without residual symptoms after intense supportive care and close monitoring. Given the widespread use of quetiapine in psychiatric practice, the present case report helps to better define the safety and risk—benefit profile of this drug.
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