Generic Seroquel (Quetiapine Fumarate): Drug Class,  Uses and Dosage, Seroquel and Dementia, Metabolism and Half-Life, Side Effects and Overdose, Alternatives, Seroquel and Pregnancy, Food And Drug Interactions

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Seroquel

Seroquel Drug Class

Seroquel or Quetiapine (generic name) is an atypical antipsychotic drug for treatment of chronic or reactive schizophrenia either with positive or deficit symptoms; of major depressive disorder (in combination with antidepressants) and several other mental illnesses. Antipsychotic activity of this drug is similar to haloperidol.

Seroquel Drug Class

Seroquel Uses

Seroquel is indicative to the patients suffering from the following disorders:

  • Schizophrenia;
  • Maniac and depressive episodes in the setting of bipolar affective disorder (I and II type);
  • Major depressive disorder;
  • Organic psychotic disorders.

Seroquel takes antagonistic effects on a large number of receptors for the neurotransmitters in brain. It is congenerous with serotonin, dopamine, and adrenergic receptors; it is also a stronger inhibitor of cerebrum serotonin receptors in comparison with the dopamine ones. Moreover, Seroquel is similar to histaminergic and alpha-adrenergic receptors. Antipsychotic and rare extrapyramidal substances are supposedly connected with a special combination of antagonistic impact on receptors.

Drowsiness occurring after Seroquel intake is explained by its high congeniality with histaminic receptors. Likewise, the cases of postural hypotension after the intake of high dosage of the drug may be explained by its high congeniality with alpha-adrenergic receptors.

Animal studies for exposure of possible extrapyramidal symptoms have discovered a very weak catalepsy after the Seroquel impact in the dosage effectively blocking dopamine receptors. The drug takes a selective action on mesolimbic system. It demonstrates its capacity to decrease the frequency of mesolimbic neurons discharge in comparison with nigrostriatal neurons (participating in motor function).  Seroquel had a minimal ability to cause dystonia among monkeys sensitized by neuroleptic agents.

Three placebo controlled trials including research study with application of a wide range of Seroquel dose (from 75 up to 750mg per day) haven’t shown any differences between the groups of Seroquel and placebo according to the frequency of extrapyramidal symptoms. Seroquel doesn’t cause constant increase of prolactin level. The clinical trials with many-times intake of fixed doses haven’t discover any prolactin level differences upon finishing of research in groups taking Seroquel in recommended range of doses and placebo.

Seroquel activity is demonstrated by tests of antipsychotic action (by conditioned avoidance test). Combined with mood stabilizing agents, Seroquel prevents from repeated bout of maniac and depressive episodes in the setting of bipolar affective disorder (I type); the risk of depression episode is considerably decreased.

Seroquel and Dementia

Treatment of dementia technique depends on diagnostics during which it would be possible to discover the cause of the disease. Among various types of this disease there are those in which the cognitive function disorder may be reversible. In these cases, the efforts are focused on elimination of cause of the disease. An important part of dementia therapy is correction of behavioral problems. Usually patients have psychomotor agitation the causes of which may be either depression or psychosis. Anyway, the restlessness may be caused by pain or infection. Seroquel is an atypical antipsychotic drug for dementia treatment. Among its indications there are mood disorders, depression, insomnia, aggression, etc.

Seroquel Dosage

Seroquel DosagePresentation form: coated tablets.

  • Seroquel 25mg. Active substance is Quetiapine Fumarate in quantity of 28,78mg equivalent to 25mg of freebase of quetiapine.
  • Seroquel 100mg. Active substance is Quetiapine Fumarate in quantity of 115,13mg equivalent to 100mg of freebase of quetiapine.
  • Seroquel 200mg. Active substance is Quetiapine Fumarate in quantity of 230,26mg equivalent to 200mg of freebase of quetiapine.

Auxiliary agents: povidone, calcium hydrophosphate, cryptocrystalline cellulose, sodium carboxymethyl starch, lactose monohydrate, magnesium stearate.

Tablet coating contains iron oxide red (25mg tablets), iron oxide yellow (25mg and 100mg tablets), titania, hypromellose, macrogol.

Seroquel should be taken twice a day regardless of food acceptance. For adults treating acute or chronic psychosis including schizophrenia, the daily dosage for four therapeutic days is as follows: 1st day – 50mg, 2nd day – 100mg, 3rd day – 200mg, 4th day – 300mg. In accordance with clinical effect and individual tolerance of a patient, a dose may vary within a scope of 150mg and 750mg per day. Maximum daily dosage is 750mg.

For treatment of maniac episodes in the setting of bipolar affective disorder, Seroquel is applied in the capacity of monotherapy or adjuvant therapy for mood stabilization. Recommended daily intake for the first four days of therapy: 1st day – 100mg, 2nd day – 200mg, 3rd day – 300mg, 4th day – 400mg. In the following, the dose may be enlarged by the 6th day up to 800mg.

For treatment of depressive episodes in the setting of bipolar affective disorder, Seroquel is administered once per day. The recommended dose is 300mg. The daily dosage for four therapeutic days is as follows: 1st day – 50mg, 2nd day – 100mg, 3rd day – 200mg, 4th day – 300mg. Maximum daily dosage makes 600mg. No clinical improvement was registered in case of increase of 600mg dose.

Aged patients should start taking Seroquel in dose of 25mg. It should be increased by 25-50mg until the dose is effective enough. But still it will be less than the one for young patients.

Patients suffering from renal of hepatic disorder are recommended to start Seroquel treatment with 25mg per day. They need to enlarge the dosage gradually by 25-50mg until the desired effect is achieved.

Seroquel Metabolism and Half-Life

Clinical trials have demonstrated that the medicine is effective if taken twice a day. This is proved by the fact that according to positron emission tomography, Seroquel impact on serotonin and dopamine receptors lasts up to 12 hours. If taken perorally, Seroquel is well absorbed. Food acceptance doesn’t affect bioaccessibility of the drug. Maximal concentration in blood plasma is registered in 1,5 h.

Seroquel gets connected with serum proteins approximately by 83%. The apparent volume of Seroquel distribution is 10±4 l/kg. Seroquel is metabolized mainly in liver; the principle ways of biotransformation are sufoxidation and acidification. The main enzyme of metabolism is CYP3 A4 of cytochrome system P450. The main produced metabolites do not have a pronounced pharmacological activity. Seroquel and its metabolites are weak inhibitors of cytochrome P450 isoenzymes in a man only in concentrations surpassing it by 10-50 times. They are observed right after the intake of traditional effective doses. Based on these trials it may be assumed that Seroquel combined intake along with other medications may cause clinically significant medicinal inhibition of another drug by means of cytochrome P450.

Seroquel half-life is about seven hours. After the intake of a sole dose of C-marked Seroquel, around 5% of cleared substance is in unchanged condition. Around 73% of metabolites is cleared with urine and 21% – with feces. Pharmacokinetics of Seroquel is linear in therapeutic margins of safety and doesn’t have any significant sexual or race differences. Medium clearance of Seroquel among aged patients is as 30-50% less than among patients between 18 and 65 years of age.

Average plasmatic clearance of Seroquel was decreased by 25% among patients suffering from severe renal disorders and among patients with hepatic failure (alcoholic cirrhosis at the stage of compensation), but individually the clearance level was to the extent corresponding to healthy people.

Seroquel and Seroquel XR: What Is the Difference?

Main difference between Seroquel and Seroquel XR lies in their dosage. Seroquel contains 25mg, 100mg and 200mg of active substance, quetiapine. On one side of the tablet is marked by a print showing the quantity of chemical compound, such as Seroquel 25, Seroquel WO, Seroquel 200. Seroquel XR is issued in tableted form as well. According to the composition, a tablet may be marked in accordance of quetiapine dosage contained in it, for instance XR50, XR150, XR200, XR300 and XR400.

Seroquel Alternatives

Being perfect for treatment of mania and psychosis and having fewer undesired effects than many other antibiotics, Seroquel (quetiapine) has alternative medications.

  • Abilify containing aripiprazole as an active substance;
  • Risperdal containing risperidobne as an active substance

Seroquel and Weight Gain

Seroquel has much less risk of clinically significant weight gain in comparison with clozapine and olanzapine (medicines falling into group of atypical antipsychotics), which is much higher in comparison with such atypical antipsychotics as ziprasidone and aripiprazole. After a year of therapy, the average gain weight is around 2,2kg. Increase of weight due to neuroleptic agents’ intake is tightly connected with hyperglycemia, insulin resistance and diabetes development. Along with clozapine and olanzapine, Seroquel causes diabetes more often than other antipsychotics. Besides diabetes, the consequences of obesity caused by neuroleptic agents include increased risk of atherosclerotic cardiovascular disease, arterial hypertension, oncological diseases, osteoarthrosis, sleep apnea, acute myocardial infarction and apoplectic attack.

Seroquel Interaction with Other Drugs

Quetiapine doesn’t affect lithium pharmacokinetics. It doesn’t influence antipyrine metabolism either. Simultaneous prescription of quetiapine and phenytoin (inductor of hepatic microsomal enzymes) causes increase of Seroquel clearance. Thus, the combined intake of Seroquel and phenytoin (or other inductors of hepatic microsomal enzymes, such as carbamazepine, barbiturate, rifampicine) may require Seroquel dosage increase.

The dosage reduction of this drug may be required in case of phenytoin intake cessation and its substitution with non-inductive microsomal enzymes, such as NaVPA. Quetiapine pharmacokinetics will not change considerably due to its combination with risperidone and haloperidol. Nevertheless, simultaneous usage of Seroquel along with thioridazine causes Seroquel clearance.

Simultaneous administration of quetiapine and antidepressants, such as lmipramine (known as CYP2 D6 inhibitor) or fluoxetine (known as CYP3 A4 and CYP2 D6 inhibitor) didn’t have a significant effect on pharmacokinetics of Seroquel. CYP3 A4 is a key enzyme in quetiapine metabolism. It is recommended to take due care while using Seroquel along with potential CYP3

A4 inhibitors, such as ketoconazole and erythromycin.

Patients taking quetiapine reported false-positive results of screening tests for exposure of methadone and tricyclic antidepressants by means of enzyme-linked immunosorbent assay. In order to confirm screening results, it is recommended to conduct a chromatographic study. Seroquel should be taken with care along with other medications affecting CNS and with alcohol as well. A patient should refuse grapefruit juice during therapy course with Seroquel.

Seroquel and Ativan

The one-time intake of Ativan along with Seroquel in dosage of 250mg twice a day decreases clearance by 20%.

Seroquel and Zoloft

Quetiapine along with Zoloft (sertraline) may cause a heartbeat disorder that is quite serious and may be dangerous for patient’s life. A patient may have an underlying risk of this condition if he has other heart disorders, congenital long QT syndrome, electrolyte disturbance or conduction anomaly. First you should consult your physician in case you are not sure of your health state in order to avoid life-threatening conditions.

Seroquel and Trazadone

These drugs taken simultaneously increase the possibility of struggle against insomnia. So, the effect of drowsiness is enhanced significantly.

Seroquel and Xanax

Co-administered with Xanax, Seroquel may cause aggravated side-effects including vertigo, concentration difficulty, drowsiness. Aged people may also feel decreased motor coordination, thinking and judgment impairment.

Seroquel and Prozac

The combination of quetiapine (Seroquel) and fluoxetine (Prozac) may lead to higher risk of arrhythmia. This condition may be life-threatening. Nevertheless this undesired effect takes place quire rarely. A patient may have an underlying risk of arrhythmia in case he arrhythmia has other heart disorders, congenital long QT syndrome, conduction abnormality, disturbance of electrolyte, such as long-term diarrhea, potassium or magnesium loss or vomit. In case you experience sudden syncope or fainting, short breath, heartbeats during therapy course of co-administered Prozac and Seroquel, seek immediate medical attendance.

Seroquel and Ambien

Along with Ambien Seroquel may cause aggravated unadvisable effect, such as vertigo, drowsiness, or concentration difficulty. Elderly people may also experience decreased motor coordination, thinking and judgment impairment.

Seroquel and Lexapro

Co-administration of quetiapine (Seroquel) with escitalopram (Lexapro) may cause a life-threatening arrhythmia. This side-effect is a rare condition, but patients suffering from some of heart disorders, electrolyte disturbances, conduction abnormalities, or congenital long QT syndrome, should refuse the intake of such drug combination.

Seroquel and Alcohol

The reviews from Seroquel users and a lot of clinical trials have demonstrated that Seroquel and alcohol are incompatible. Within the therapy course, a patient must refuse alcoholic beverages.

Seroquel Black Box Warning

Seroquel is counter-indicative in the following cases:

  • Hypersensitivity to any drug components;
  • Simultaneous intake along with cytochrome P450 inhibitors, such as HIV-protease inhibitors, antifungal agents, erythromycin, clarithromycin, nefazodone;
  • In case of pregnancy, Seroquel may be used only if potential benefit to the mother outweighs any potential risk to the fetus;
  • Lactation;
  • In case of planned pregnancy.

Seroquel and Pregnancy

Seroquel and PregnancyIn case of pregnancy, Seroquel may be used only if potential benefit to the mother outweighs any potential risk to the fetus. The clearance level of quetiapine with breast milk is not studied. Women must refuse Seroquel intake during lactation.

Generic Seroquel Side-Effects

According to some estimates, quetiapine is one of the most favorable medicines among atypical antipsychotics from security parameters point of view. The most frequently-met side-effects are sedation, drowsiness, postural hypotension, vertigo, dyspepsia in comparatively mild manifestation. They may be blocked by reduction of Seroquel dosage.

First off, the below-mentioned list of side-effects is dedicated for physicians. By no means will this medicine cause these side-effects, but if they occur, they may be caused by Seroquel administration.

In this case, a psychiatrist may take decision of reduction of dosage, cessation of Seroquel therapy or its substitution.

  • From the part of overall organism: headache, asthenia, abdominal pain, backache, weight gain, fever, chest pain.
  • From the part of CNS: drowsiness, vertigo, anxiety, extrapyramidal disorders.
  • From the part of cardio-vascular system: postural hypotension, tachycardia, arterial hypertension.
  • From the part of gastro-intestinal system: uncleared bowels, dryness in mouth, dyspepsia, diarrhea, increase of hepatic transaminases.
  • From the part of blood-making organs: symptom-free leucocytopenia and/or neutropenia, eosinophilia.
  • From the part of musculoskeletal system: myodynia.
  • From the part of respiratory system: rhinitis.
  • From the part of skin covering: rash, dryness of skin.
  • From the part of acoustic apparatus: ear pain.
  • From the part of urogenital system: sexual disorders, urinary tract infections.

Seroquel Overdose

There is little information about Seroquel abuse. During clinical trials with quetiapine, its dosage surpassed 10g, and lethal cases were not registered. All patients restored without any consequences. In whole, overdose symptoms are the result of enhancement of new pharmacological effects of the drug, such as drowsiness, sedative effect, tachycardia, and hypotension. Specific antidote to Seroquel is unknown. The constant control and maintenance of vital functions (breathing and respiration) as well as symptomatic therapy are required until all symptoms disappear.