Seroquel (Quetiapine). Dosage, Side Effects, Interactions
Seroquel (Quetiapine) is an atypical neuroleptic or antipsychotic drug that mainly blocks dopamine D2 receptors and serotonin 5HT-2 receptors. Quetiapine is used for conditions such as schizophrenia and manic and depressive episodes.
- moderate to severe manic episodes in bipolar disorder
- major depressive episodes in bipolar disorder
- Prevention of recurrence of manic or depressive episodes in patients with bipolar disorder who have previously responded to quetiapine treatment
Quetiapine is available on the market as an oral suspension, as film-coated tablets and as prolonged-release tablets.
How Seroquel (Quetiapine) works
Quetiapine is an atypically acting antipsychotic ( neuroleptic ). The drug and its active metabolite N-desalkylquetiapine interact with a wide range of neurotransmitter receptors.
These include cerebral serotonergic (5HT2) and dopaminergic D1 and D2 receptors. This combination of receptor antagonism with higher selectivity for 5HT2 versus D2 receptors is believed to contribute to the clinical antipsychotic properties and the low extrapyramidal side-effects (EPS) profile of quetiapine compared to typical antipsychotics.
Inhibition of the norepinephrine transporter and partial agonist activity at 5HT1A receptors by N-desalkylquetiapine may contribute to the antidepressant activity of quetiapine.
- Quetiapine is well absorbed after oral administration and extensively metabolised.
- Quetiapine is approximately 83% plasma protein bound.
- Quetiapine is extensively metabolised in the liver.
- CYP3A4 is primarily responsible for the metabolism of quetiapine.
- N-desalkylquetiapine is primarily formed and cleared by CYP3A4.
- Approximately 73% of the active substance is excreted in the urine and 21% in the faeces.
- The elimination half-lives for quetiapine and N-desalkylquetiapine are approximately 7 and 12 hours, respectively.
Dosage of Seroquel (Quetiapine)
Treatment of schizophrenia in adults
Film- coated tablets: For the treatment of schizophrenia, quetiapine film-coated tablets should be taken twice daily. On the first day of treatment, 25 mg twice a day, on the second day 50 mg twice, on the third day 100 mg twice and on the fourth day 150 mg twice a day. Thereafter, the dose should be adjusted up to the usual effective dose of 300 to 450 mg per day. In general, the dose can range from 150 to 750 mg of quetiapine per day.
Prolonged- release tablets Quetiapine prolonged-release tablets should be taken once daily at least one hour before a meal. On the first day of treatment, the daily dose is 300 mg, and on the second day 600 mg. The recommended daily dose is 600 mg and should be adjusted between 400 mg and 800 mg per day depending on patient response and tolerability.
Treatment of moderate to severe manic episodes in adult bipolar disorder
Film-coated tablets: On the first day of treatment, 50 mg twice a day, on the second day 100 mg twice, on the third day 150 mg twice and on the fourth day 200 mg twice a day. Further dose adjustments up to quetiapine 400 mg twice daily on Day 6 should be made. The usual effective dose is between 400 and 800 mg per day, but can be reduced to 200 mg per day depending on patient tolerance and response.
Prolonged- release tablets: Quetiapine prolonged-release tablets should be taken once a day at least one hour before a meal. On the first day of treatment, the daily dose is 300 mg, and on the second day 600 mg. The recommended daily dose is 600 mg and should be adjusted between 400 mg and 800 mg per day depending on patient response and tolerability.
Treatment of major depressive episodes in adult bipolar disorder
Both the film-coated tablets and the prolonged-release tablets should be taken once a day at bedtime. On the first day of treatment 50 mg once a day, on the second day 100 mg once a day, on the third day 200 mg once a day and on the fourth day 300 mg once a day. The recommended daily dose is 300 mg.
Relapse prevention in adult bipolar disorder
Patients who have responded to quetiapine for the treatment of bipolar disorder should continue treatment at the same dose. The recommended maintenance dose is between 300 and 800 mg per day and the lowest effective dose should be used. The film-coated tablets should be taken twice a day and the prolonged-release tablets should be taken once a day.
Adjunctive therapy for depressive disorders in adults
Quetiapine prolonged-release tablets should be taken at bedtime, although the film-coated tablets are not approved for adjunctive therapy in depressive disorders. The daily dose is 50 mg on the first and second day and 150 mg on the third and fourth day and can be increased up to 300 mg depending on the patient’s response and tolerability.
Caution is advised, especially in the initial treatment phase, and it may be necessary to adjust the dose more slowly and to select a lower therapeutic daily dose than in younger patients. In clinical studies, the mean plasma clearance of quetiapine was 30-50% lower in elderly patients compared to younger patients. Efficacy and safety in elderly patients with depressive episodes in the context of bipolar disorder have also not been studied.
children and young people
The use of quetiapine in children and adolescents below 18 years of age is not recommended due to the lack of data.
Impaired kidney function
Dose adjustment is not required in patients with renal impairment.
Impaired liver function
Quetiapine should be used with caution in patients with known hepatic impairment, particularly during the initial treatment period, since quetiapine is primarily metabolised in the liver. The starting dose of the film-coated tablets should be 25 mg per day and the prolonged-release tablets should be 50 mg per day. Depending on the patient’s individual response and tolerability, the daily dose of the film-coated tablets should be increased stepwise by 25-50 mg per day and the prolonged-release tablets by 50 mg per day until the effective dose is reached.
type of application
Quetiapine prolonged-release tablets should be taken once daily, not with a meal, at least one hour before a meal. The prolonged-release tablets should be swallowed whole and not divided, chewed or crushed. Quetiapine film-coated tablets can be taken with or without food.
Switching from quetiapine film-coated tablets to prolonged-release tablets
For ease of dosing, patients treated with multiple doses of immediate-release quetiapine film-coated tablets may be switched to quetiapine prolonged-release tablets. The total daily dose is equivalent and is taken once a day. Individual dose adjustments may be necessary.
Side effects of Seroquel (Quetiapine)
The most commonly reported adverse reactions to quetiapine (≥10%) are:
- dry mouth
- Discontinuation symptoms when stopping treatment
- Increase in serum triglyceride levels
- Increase in total cholesterol (mainly LDL cholesterol)
- Decrease in HDL cholesterol
- weight gain
- decreased hemoglobin level
- extrapyramidal symptoms
- Carbamazepine or phenytoin ► Quetiapine plasma concentrations are significantly reduced
- Combination with other centrally acting drugs and alcohol
- Quetiapine is metabolised via CYP3A4 ► Concomitant use of quetiapine and CYP3A4 inhibitors is contraindicated
- grapefruit juice
- Thioridazine ► increase in quetiapine clearance
- Lithium ► Increased incidence of extrapyramidal-associated events (especially tremor), somnolence and weight gain
- Sodium Valproate ► Increased incidence of leucopenia and neutropenia
- Drugs that disrupt electrolyte balance or prolong the QT interval
The drug is contraindicated in:
- Hypersensitivity to the active substance
- concomitant use of cytochrome P450 3A4 inhibitors such as HIV protease inhibitors, azole-type antifungal drugs, erythromycin , clarithromycin and nefazodone
Neonates exposed to antipsychotics (including quetiapine) during the third trimester of pregnancy are at risk of adverse reactions, including extrapyramidal and/or withdrawal symptoms , which may vary in severity and duration after delivery. There have been reports of agitation, increased or decreased muscle tone, tremor, somnolence, dyspnoea or feeding disorders. Accordingly, newborns should be carefully monitored
In the absence of conclusive data, a decision must be made whether to discontinue breast-feeding or discontinue quetiapine treatment.
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