Domiquel

Domiquel

Composition:
Each film coated tablet contains 100 , 200 or 300 mg quetiapine

Mechanism of action:
Quetiapine is an atypical antipsychotic agent. Quetiapine and its active human plasma metabolite, norquetiapine exhibit affinity for brain serotonin (5HT2) and dopamine D1- and D2- receptors. It is this combination of receptor antagonism, which is believed to contribute to the clinical antipsychotic properties and low extrapyramidal side effect (EPS) liability of quetiapine compared to typical antipsychotics.

Pharmacokinetics :
Quetiapine is well absorbed and extensively metabolized following oral administration. Quetiapine is approximately 83% bound to plasma proteins

Indications:
Quetiapine is indicated for:
-Treatment of Schizophrenia.
-Treatment of bipolar disorder:
-For the treatment of moderate to severe manic episodes in bipolar disorder
-For the treatment of major depressive episodes in bipolar disorder
-For the prevention of recurrence of manic or depressed episodes in patients with bipolar disorder who previously responded to quetiapine treatment.

Dosage:
Quetiapine can be administered with or without food.
Adults:
For the treatment of schizophrenia:
Quetiapine should be administered twice a day. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4) From Day 4 onwards, the dose should be titrated to the usual effective dose of 300 to 450 mg/day. Depending on the clinical response and tolerability of the individual patient, the dose may be adjusted within the range 150 to 750 mg/day.
For the treatment of moderate to severe manic episodes in bipolar disorder:
Quetiapine should be administered twice a day. The total daily dose for the first four days of therapy is 100 mg (Day 1), 200 mg (Day 2), 300 mg (Day 3) and 400 mg (Day 4). Further dosage adjustments up to 800 mg/day by Day 6 should be in increments of no greater than 200 mg/day.
The dose may be adjusted depending on clinical response and tolerability of the individual patient, within the range of 200 to 800 mg/day. The usual effective dose is in the range of 400 to 800 mg/day.
For the treatment of major depressive episodes in bipolar disorder:
Quetiapine should be administered once daily at bedtime. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). The recommended daily dose is 300 mg. In clinical trials, no additional benefit was seen in the 600 mg group compared to the 300 mg group. Individual patients may benefit from a 600 mg dose. Doses greater than 300 mg should be initiated by physicians experienced in treating bipolar disorder. In individual patients, in the event of tolerance concerns, clinical trials have indicated that dose reduction to a minimum of 200 mg could be considered.
For preventing recurrence in bipolar disorder:
Patients who have responded to quetiapine for acute treatment of bipolar disorder should continue therapy at the same dose. The dose may be adjusted depending on clinical response and tolerability of the individual patient, within the range of 300 to 800 mg/day administered twice daily. It is important that the lowest effective dose is used for maintenance therapy.
Elderly:
As with other antipsychotics, Quetiapine should be used with caution in the elderly, especially during the initial dosing period. 
Pediatric Population:
Quetiapine is not recommended for use in children and adolescents below 18 years of age.
Renal Impairment:
Dosage adjustment is not necessary in patients with renal impairment.
Hepatic Impairment:
Quetiapine is extensively metabolized by the liver. Therefore, Quetiapine should be used with caution in patients with known hepatic impairment, especially during the initial dosing period.

Overdose:

Reported signs and symptoms were those resulting from an exaggeration of the active substance's known pharmacological effects.
There is no specific antidote to quetiapine. In cases of severe signs, the possibility of multiple drug involvement should be considered, and intensive care procedures are recommended.
Close medical supervision and monitoring should be continued until the patient recovers.

Side effects:
The most commonly reported Adverse Drug Reactions with quetiapine are somnolence, dizziness, headache, dry mouth, withdrawal (discontinuation) symptoms, elevations in serum triglyceride levels, elevations in total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain, decreased haemoglobin and extrapyramidal symptoms.
Common side effects: leucopenia, decreased neutrophil count, eosinophils increased, hyperprolactinaemia,  decreases in total T4, free T4, total T3, increases in TSH, increased appetite, blood glucose increased, dysarthria, tachycardia, Palpitations, vision blurred, orthostatic hypotension, dyspnoea, constipation, dyspepsia, vomiting,  elevations in serum alanine aminotransferase (ALT),  mild asthenia, peripheral oedema, irritability, pyrexia.
Uncommon side effects :
Neutropenia, Thrombocytopenia, Anemia, platelet count decreased, Hypersensitivity (including allergic skin reactions), Decreases in free T324, Hypothyroidism , Hyponatraemia ,Diabetes Mellitus, Exacerbation of pre-existing diabetes, Seizure, Restless ,legs syndrome, Tardive dyskinesia ,Syncope , QT prolongation, Bradycardia, Rhinitis , Dysphagia, Elevations in serum aspartate aminotransferase (AST)3, Urinary retention, Sexual dysfunction.

Contraindications:
Hypersensitivity to the active substance or to any of the excipients of this product.
Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone, is contraindicated.

Drug and food interactions:
-Quetiapine should be used with caution in combination with other centrally acting medicinal products and alcohol.
-Concomitant use of quetiapine with CYP3A4 inhibitors is contraindicated. It is also not recommended to consume grapefruit juice while on quetiapine therapy.
-In patients receiving a hepatic enzyme inducer (such as carbamazepine and phenytoin), initiation of quetiapine treatment should only occur if the physician considers that the benefits of quetiapine outweigh the risks of removing the hepatic enzyme inducer. It is important that any change in the inducer is gradual, and if required, replaced with a non-inducer (e.g. sodium valproate).
-The pharmacokinetics of quetiapine were not significantly altered by co-administration of the antidepressants imipramine (a known CYP 2D6 inhibitor) or fluoxetine (a known CYP 3A4 and CYP 2D6 inhibitor).
-The pharmacokinetics of quetiapine were not significantly altered by co-administration of the antipsychotics risperidone or haloperidol nor by cimetidine.
-Concomitant use of quetiapine and thioridazine caused an increased clearance of quetiapine.
-The pharmacokinetics of lithium were not altered when co-administered with quetiapine.
-The pharmacokinetics of sodium valproate and quetiapine were not altered to a clinically relevant extent when co-administered.
-Caution should be exercised when quetiapine is used concomitantly with medicinal products known to cause electrolyte imbalance or to increase QT interval,

Precautions:
-Quetiapine is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group and certain adverse events occurred at a higher frequency.
-Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm and suicide. Patients should be closely monitored until such improvement occurs. 
-Physicians should consider the potential risk of suicide-related events after abrupt cessation of quetiapine treatment.
-Patients' metabolic parameters should be assessed at the time of treatment initiation and changes in these parameters should be regularly controlled for during the course of treatment.
-In patients who develop akathisia, characterised by an inability to sit or stand still, increasing the dose may be detrimental.
-If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered.
-Patients experiencing somnolence of severe intensity may require more frequent contact for a minimum of 2 weeks from onset of somnolence, or until symptoms improve and treatment discontinuation may need to be considered.
-Quetiapine treatment has been associated with orthostatic hypotension and related dizziness. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects.
-Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension.
-As with other antipsychotics, caution is recommended when treating patients with a history of seizures.
-Neuroleptic malignant syndrome has been associated with antipsychotic treatment, including quetiapine.. In such an event, quetiapine should be discontinued and appropriate medical treatment given.
-Severe neutropenia has been reported in quetiapine clinical trials. Quetiapine should be discontinued in patients with a neutrophil count <1.0 X 109/L. Patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1.5 X 109/L).
-Patients should be advised to immediately report the appearance of signs/symptoms consistent with agranulocytosis or infection at any time during Quetiapine therapy. Such patients should have a WBC count and an absolute neutrophil count (ANC) performed promptly .
-Patients treated with any antipsychotic agent including quetiapine, should be observed for signs and symptoms of hyperglycaemia and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly.
-Lipid changes (↑TG, LDL and total cholesterol, ↓HDL) should be managed as clinically appropriate.
-As with other antipsychotics, caution should be exercised when quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also, caution should be exercised when quetiapine is prescribed either with medicines known to increase QT interval or with concomitant neuroleptics, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia.
-Treatment with quetiapine should be reassessed in patients with suspected cardiomyopathy or myocarditis.
-Acute withdrawal symptoms such as insomnia, nausea, headache, diarrhoea, vomiting, dizziness and irritability have been described after abrupt cessation of quetiapine. Gradual withdrawal over a period of at least one to two weeks is advisable.
-Quetiapine is not approved for the treatment of dementia-related psychosis.
-Quetiapine should be used with caution in patients at risk for aspiration pneumonia (dysphagia).
-Patients with intestinal obstruction/ileus should be managed with close monitoring and urgent care.
-All possible risk factors for venous thromboembolism (VTE) should be identified before and during treatment with quetiapine and preventive measures undertaken.
-Quetiapine tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

Use in pregnancy or lactation:
Quetiapine should only be used during pregnancy if the benefits justify the potential risks.
The decision must be made whether to discontinue breast-feeding or to discontinue Quetiapine therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.


Address

Domina Pharmaceuticals
P.O. Box : 9622
Damascus - Syria

Contacts

Email: info@dominapharm.com
Phone: +963 (11) 33 192 32
Phone: +963 (11) 33 201 04
Mobile: +963 (932) 993 304 159
Mobile: +963 (932) 993 366 254