Quetiazic

 1. Name of ther medicinal product:

Quetiazic 50 mg, 150 mg, 300 mg , 400 mg Extended release film coated tablets.

 

2. Qualitative and quantitative composition

Each 50 mg tablet contains 50 mg quetiapine (as quetiapine fumarate)

Each 150 mg tablet contains 150 mg quetiapine (as quetiapine fumarate)

Each 300 mg tablet contains 300 mg quetiapine (as quetiapine fumarate)

Each 400 mg tablet contains 400 mg quetiapine (as quetiapine fumarate)

For a full list of excipients, see section 6.1.

 

3. Pharmaceutical form

Extended release film coated tablets.

 

4. Clinical particulars

4.1 Therapeutic indications

 

Quetiazic is indicated for:

- Treatment of schizophrenia including:

preventing relapse in stable schizophrenic patients who have been maintained on Quetiazic (see

section 5.1 Pharmacodynamic properties).

- Treatment of bipolar disorder including:

manic episodes associated with bipolar disorder

major depressive episodes in bipolar disorder

preventing recurrence in bipolar disorder in patients whose manic, mixed or depressive

episode has responded to quetiapine treatment.

- Add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD)

who have had sub-optimal response to antidepressant monotherapy (see section 5.1

Pharmacodynamic properties). Prior to initiating treatment, clinicians should consider the safety

profile of Quetiazic (see section 4.4 Special warnings and precautions for use).

4.2 Posology and method of administration

Different dosing schedules exist for each indication. It must therefore be ensured that patients receive

clear information on the appropriate dosage for their condition.

Quetiazic should be administered once daily, without food (at least one hour before a meal). The

tablets should be swallowed whole and not split, chewed or crushed.

Adults:

For the treatment of schizophrenia

The daily dose at the start of therapy is 300 mg on Day 1 and 600 mg on Day 2. The recommended

daily dose is 600 mg. Enhanced efficacy at doses higher than 600 mg has not been demonstrated,

although individual patients may benefit from a dose up to 800 mg daily. Doses greater than 600 mg

should be initiated by a specialist. The dose should be adjusted within the effective dose range of 400

mg to 800 mg per day, depending on the clinical response and tolerability of the patient. For

maintenance therapy in schizophrenia no dosage adjustment is necessary.

For the treatment of manic episodes associated with bipolar disorder

The daily dose at the start of therapy is 300 mg on Day 1, 600 mg on Day 2 and up to 800 mg after

Day 2. The dose should be adjusted within the effective dose range of 400 mg to 800 mg per day,

depending on the clinical response and tolerability of the patient.

For the treatment of depressive episodes associated with bipolar disorder

Quetiazic 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. 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. When treating depressive episodes in bipolar disorder, treatment should be

initiated by physicians experienced in treating bipolar disorder.

For preventing recurrence in bipolar disorder

For prevention of recurrence of manic, depressive or mixed episodes in bipolar disorder, patients who

have responded to Quetiazic for acute treatment of bipolar disorder should continue on Quetiazic at

the same dose administered at bedtime. The dose may be adjusted depending on clinical response

and tolerability of the individual patient within the dose range of 300 mg to 800 mg/day. It is important

that the lowest effective dose is used for maintenance therapy.

For add-on treatment of major depressive episodes in MDD:

Quetiazic should be administered prior to bedtime. The daily dose at the start of therapy is 50 mg on

Day 1 and 2, and 150 mg on Day 3 and 4. Antidepressant effect was seen at 150 and 300 mg/day in

short-term trials as add-on therapy (with amitriptyline, bupropion, citalopram, duloxetine,

escitalopram, fluoxetine, paroxetine, sertraline and venlafaxine - see section 5.1 Pharmacodynamic

properties) and at 50 mg/day in short-term monotherapy trials. There is an increased risk of adverse

events at higher doses. Clinicians should therefore ensure that the lowest effective dose, starting with

50 mg/day, is used for treatment. The need to increase the dose from 150 to 300 mg/day should be

based on individual patient evaluation.

Switching from Quetiazic immediate-release tablets:

For more convenient dosing, patients who are currently being treated with divided doses of

immediate-release Quetiazic tablets (Quetiazic IR, tradename Quetiazic ) may be switched to

Quetiazic at the equivalent total daily dose taken once daily. To ensure the maintenance of clinical

response, a period of dose titration may be required.

Elderly:

As with other antipsychotics and antidepressants, Quetiazic should be used with caution in the

elderly, especially during the initial dosing period. The rate of dose titration of Quetiazic may need to

be slower, and the daily therapeutic dose lower, than that used in younger patients. The mean

plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to

younger patients. Elderly patients should be started on 50 mg/day. The dose can be increased in

increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of

the individual patient.

In elderly patients with major depressive episodes in MDD, dosing should begin with 50 mg/day on

Days 1-3, increasing to 100 mg/day on Day 4 and 150 mg/day on Day 8. The lowest effective dose,

starting from 50 mg/day should be used. Based on individual patient evaluation, if dose increase to

300 mg/day is required this should not be prior to Day 22 of treatment.

Efficacy and safety have not been evaluated in patients over 65 years with depressive episodes in

the framework of bipolar disorder.

Children and Adolescents:

Quetiazic 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. The available evidence from placebo-controlled clinical

trials with Quetiazic is presented in sections 4.4, 4.8, 5.1 and 5.2.

Renal impairment:

Dosage adjustment is not necessary in patients with renal impairment.

Hepatic impairment:

Quetiapine is extensively metabolised by the liver. Therefore, Quetiazic should be used with caution

in patients with known hepatic impairment, especially during the initial dosing period. Patients with

known hepatic impairment should be started with 50 mg/day. The dose can be increased in

increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of

the individual patient.

4.3 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. (See also

section 4.5 Interaction with other medicinal products and other forms of interaction).

As Quetiazic is indicated for the treatment of schizophrenia, bipolar disorder .

4.4 Overdose

Fatal outcome has been reported in clinical trials following an acute overdose at 13.6 grams, and in

post-marketing on doses as low as 6 grams of Quetiazic alone. However, survival has also been

reported following acute overdoses of up to 30 grams. In post marketing experience, there have been

very rare reports of overdose of quetiapine alone resulting in death or coma or QT-prolongation.

Patients with pre-existing severe cardiovascular disease may be at an increased risk of the effects of

overdose. (See section 4.4 Special warnings and precautions for use: Cardiovascular).

In general, reported signs and symptoms were those resulting from an exaggeration of the drug's

known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension.

Management of overdose

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, including

establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and

monitoring and support of the cardiovascular system. Whilst the prevention of absorption in overdose

has not been investigated, gastric lavage can be indicated in severe poisonings and if possible to

perform within one hour of ingestion. The administration of activated charcoal should be considered.

In cases of quetiapine overdose refractory hypotension should be treated with appropriate measures

such as intravenous fluids and/or sympathomimetic agents (epinephrine and dopamine should be

avoided, since beta stimulation may worsen hypotension in the setting of quetiapine-induced alpha

blockade).

Close medical supervision and monitoring should be continued until the patient recovers.

5. Pharmaceutical particulars

5.1 List of excipients

Quetiazic 50 mg contain: hypromellose, tri-sodium citrate,lactose monohydrate microcrystalline

cellulose, magnesium stearate , Sepifilm

Quetiazic 150 mg, 300, and 400 mg tablets contains: hypromellose, tri-sodium citrate,lactose

monohydrate microcrystalline cellulose, magnesium stearate , Opadry

5.2 Shelf life

2 years

5.3 Special precautions for storage

Store at temperature not exceeding 30°C. in a dry place.

5.4 Nature and contents of container

Carton box containing 1, 2 or 3 (Al/ Transparent PVC) blisters, each of 10 extended release film

coated tablets and inner leaflet.