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Saturday, 15 September 2012

Quetiapine 150 mg Film-coated Tablets

1. Name Of The Medicinal Product

Quetiapine 150 mg Film-coated Tablets

2. Qualitative And Quantitative Composition

Each film-coated tablet contains 150 mg (as quetiapine hemifumarate).

Excipient (s):

Each 150 mg film-coated tablet contains 79.800 mg lactose monohydrate.

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Film-coated tablet

25mg tablets are pink coloured, round, biconvex, film-coated tablet, plain on both sides.

4. Clinical Particulars

4.1 Therapeutic Indications

Quetiapine tablet is indicated for the treatment of:

• Schizophrenia.

• Bipolar disorder, including:


	• moderate to severe manic episodes in bipolar disorder
	• major depressive episodes in bipolar disorder
	• prevention of recurrence in patients whose manic or depressive episode has responded to quetiapine treatment.

4.2 Posology And Method Of Administration

Quetiapine tablets can be administered, with or without food.

Adults

For the treatment of schizophrenia: Quetiapine tablets should be administered twice a daily. The total daily dose for the first 4 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 range 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 tablets should be administered twice a daily. 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 per day by Day 6 should be in increments of no greater than 200 mg per day.

The dose may be adjusted depending on clinical response and tolerability of the individual patient, within the range of 200 to 800 mg per day. The usual effective dose is in the range of 400 to 800 mg per day.

For the treatment of depressive episodes in bipolar disorder: Quetiapine tablets 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 (see section 5.1). 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 and mixed episodes 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 then 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 tablets should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration may need to be slower, and the daily therapeutic dose lower,than that used in younger patients, depending on the clinical response and tolerability of the individual patient. The mean plasma clearance of quetiapine was reduced by 30 - 50% in elderly subjects when compared to younger patients.

Efficacy and safety have not been evaluated in patients over 65 years with depressive episodes in the framework of bipolar disorder

Children and adolescents

Quetiapine tablets 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 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, Quetiapine 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 25 mg/day. The dosage should be increased daily with increments of 25 - 50 mg/day until an effective dosage, depending on the clinical response and tolerability of the individual patient.

4.3 Contraindications

Quetiapine tablet is contra-indicated in patients who are hypersensitive 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).

4.4 Special Warnings And Precautions For Use

Children and adolescents (10 to 17 years of age)

Quetiapine tablet 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. Clinical trials have shown that in addition to the known safety profile identified in adults (see section 4.8 Undesirable effects), certain adverse events occurred at a higher frequency in children and adolescents compared to adults (increased appetite, elevations in serum prolactin, and extrapyramidal symptoms) and one was identified that has not been previously seen in adult studies (increases in blood pressure). Changes in thyroid function tests have also been observed in children and adolescents.

Furthermore, the long-term safety implications of treatment on growth and maturation have not been studied beyond 26 weeks. Long-term implications for cognitive and behavioural development are not known.

In placebo-controlled clinical trials with children and adolescent patients, quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for schizophrenia and bipolar mania (see section 4.8 Undesirable effects).

Suicide/suicidal thoughts or clinical worsening

Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

In clinical studies of patients with major depressive episodes in bipolar disorder an increased risk of suicide-related events was observed in young adult patients less than 25 years of age who were treated with quetiapine as compared to those treated with placebo (3.0% vs. 0%, respectively).

In addition, physicians should consider the potential risk of suicide-related events after abrupt cessation of quetiapine treatment, due to the known risk factors for the disease being treated.

Somnolence

Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation (see Section 4.8 Undesirable effects). In clinical trials for treatment of patients with bipolar depression, onset was usually within the first 3 days of treatment and was predominantly of mild to moderate intensity. Bipolar depression 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.

Cardiovascular disease

Quetiapine tablets should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension.

Quetiapine may induce orthostatic hypotension, especially during the initial dose-titration period. Dose reduction or more gradual titration should be considered if this occurs.

Seizures

In controlled clinical trials there was no difference in the incidence of seizures in patients treated with quetiapine or placebo. As with other antipsychotics, caution is recommended when treating patients with a history of seizures (see section 4.8 Undesirable effects).

Extrapyramidal symptoms

In placebo controlled clinical trials of adult patients quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for major depressive episodes in bipolar disorder (see Section 4.8 Undesirable effects).

Tardive dyskinesia

Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic drugs including quetiapine. If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine tablets should be considered. The symptoms of tardive dyskinesia can worsen or even arise after discontinuation of treatment (see section 4.8 Undesirable effects).

Neuroleptic malignant syndrome

Neuroleptic malignant syndrome has been associated with antipsychotic treatment, including quetiapine (see Section 4.8 Undesirable effects). Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatine phosphokinase. In such an event, quetiapine should be discontinued and appropriate medical treatment given.

Severe neutropenia

Severe neutropenia (neutrophil count <0.5 X 10⁹/L) has been uncommonly reported in quetiapine tablets clinical trials. Most cases of severe neutropenia have occurred within a couple of months of starting therapy with quetiapine tablets. There is no apparent dose relationship. During post-marketing experience, resolution of leucopenia and/or neutropenia has followed cessation of therapy with quetiapine tablets. Possible risk factors for neutropenia include pre-existing low white cell count (WBC) and history of drug induced neutropenia. 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). (See Section 5.1 Pharmacodynamic properties).

Interactions

See also Section 4.5 Interactions with other medicinal products and other forms of interaction.

Concomitant use of quetiapine with a strong hepatic enzyme inducer such as carbamazepine or phenytoin substantially decreases quetiapine plasma concentrations, which could affect the efficacy of Quetiapine therapy. In patients receiving a hepatic enzyme inducer, 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).

Hyperglycaemia

Hyperglycaemia or exacerbation of pre-existing diabetes has been reported during treatment with quetiapine. Appropriate clinical monitoring is advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus (see also Section 4.8 Undesirable effects).

Lipids

Increases in triglycerides, LDL and total cholesterol, and decreases in HDL cholesterol have been observed in clinical trials with quetiapine (see Section 4.8 Undesirable effects). Lipid changes should be managed as clinically appropriate.

Metabolic Risk

Given the observed changes in weight, blood glucose (see hyperglycemia) and lipids seen in clinical studies, there may be possible worsening of the metabolic risk profile in individual patients, which should be managed as clinically appropriate (see also section 4.8).

QT Prolongation

In clinical trials and use in accordance with the SPC, quetiapine was not associated with a persistent increase in absolute QT intervals. In post-marketing, QT prolongation was reported with quetiapine at the therapeutic doses (see Section 4.8) and in overdose (see Section 4.9). 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 with medicines known to increase QTc interval, and concomitant neuroleptics, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia (see Section 4.5 Interaction with other medicinal products and other forms of interaction).

Acute Withdrawal reactions

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. (see section 4.8)

Elderly patients with dementia-related psychosis

Quetiapine is not approved for the treatment of patients with dementia-related psychosis.

An approximately 3-fold increased risk of cerebrovascular adverse events have been seen in randomised placebo controlled clinical trials in the dementia population with some atypical antipsychotics. The mechanism for this increased risk is not known. An increased risk cannot be excluded for other antipsychotics or other patient populations. Quetiapine should be used with caution in patients with risk factors for stroke.

In a meta-analysis of atypical antipsychotic drugs, it has been reported that elderly patients with dementia-related psychosis are at an increased risk of death compared to placebo. However in two 10-week placebo-controlled quetiapine studies in the same patient population (n=710); mean age: 83 years; range: 56-99 years) the incidence of mortality in quetiapine treated patients was 5.5% versus 3.2% in the placebo group. The patients in these trials died of a variety of causes that were consistent with expectations for this population. These data do not establish a causal relationship between quetiapine treatment and death in elderly patients with dementia.

Dysphagia

Dysphagia (see Section 4.8 Undesirable effects) has been reported with quetiapine. Quetiapine should be used with caution in patients at risk for aspiration pneumonia.

Venous thromboembolism

Cases of venous thromboembolism (VTE) have been reported with antipsychotic drugs. Since patients treated with antipsychotics often present with acquired risk factors for VTE, all possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures undertaken.

Lactose

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.

Additional information

Quetiapine data in combination with divalproex or lithium in acute moderate to severe manic episodes is limited; however, combination therapy was well tolerated (see section 4.8 Undesirable effects and 5.1 Pharmacodynamic properties). The data showed an additive effect at week 3

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Given the primary central nervous system effects of quetiapine, quetiapine should be used with caution in combination with other centrally acting drugs and alcohol.

Cytochrome P450 (CYP) 3A4 is the primary enzyme responsible for cytochrome P450 mediated metabolism of quetiapine. In an interaction study in healthy volunteers, concomitant administration of quetiapine (dosage of 25 mg) with ketoconazole, a CYP3A4 inhibitor, caused a 5- to 8-fold increase in the AUC of quetiapine. On the basis of this, concomitant use of quetiapine with CYP3A4 inhibitors is contraindicated. It is also not recommended to take quetiapine together with grapefruit juice.

In a multiple dose trial in patients to assess the pharmacokinetics of quetiapine given before and during treatment with carbamazepine (a known hepatic enzyme inducer), co-administration of carbamazepine significantly increased the clearance of quetiapine. This increase in clearance reduced systemic quetiapine exposure (as measured by AUC) to an average of 13% of the exposure during administration of quetiapine alone; although a greater effect was seen in some patients. As a consequence of this interaction, lower plasma concentrations can occur, which could affect the efficacy of quetiapine tablets therapy. Co-administration of quetiapine and phenytoin (another microsomal enzyme inducer) caused a greatly increased clearance of quetiapine by approx. 450%. In patients receiving a hepatic enzyme inducer, 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) (see also section 4.4 Special warnings and special precautions for use).

The pharmacokinetics of quetiapine were not significantly altered following co-administration with the antidepressants imipramine (a known CYP2D6 inhibitor) or fluoxetine (a known CYP3A4 and CYP2D6 inhibitor).

The pharmacokinetics of quetiapine were not significantly altered following co-administration with the antipsychotics risperidone or haloperidol. However co-administration of quetiapine tablets and thioridazine caused increases in the clearance of quetiapine by approx. 70%.

The pharmacokinetics of quetiapine were not altered following co-administration with cimetidine, a known P450 enzyme inhibitor.

The pharmacokinetics of lithium were not altered when co-administered with quetiapine tablets

The pharmacokinetics of sodium valproate and quetiapine were not altered to a clinically relevant extent when co-administered.

Formal interaction studies with commonly used cardiovascular drugs have not been performed.

Caution should be exercised when quetiapine is used concomitantly with drugs known to cause electrolyte imbalance or to increase QTc interval.

4.6 Pregnancy And Lactation

The safety and efficacy of quetiapine tablets during human pregnancy have not been established. Up to now there are no indications for harmfulness in animal tests, possible effects on the foetal eye have not been examined, though. Therefore, quetiapine tablets should only be used during pregnancy if the benefits justify the potential risks. Following pregnancies in which quetiapine was used, neonatal withdrawal symptoms were observed.

The degree to which quetiapine is excreted into human milk is unknown. Women who are breast-feeding should therefore be advised to avoid breast-feeding while taking quetiapine tablets.

4.7 Effects On Ability To Drive And Use Machines

Given its primary central nervous system effects, quetiapine may interfere with activities requiring mental alertness and may cause somnolence. Therefore, patients should be advised not to drive or operate machinery, until individual susceptibility to this is known.

4.8 Undesirable Effects

The most commonly reported Adverse Drug Reactions (ADRs) with quetiapine tablets are somnolence, dizziness, dry mouth, mild asthenia, constipation, tachycardia, orthostatic hypotension, and dyspepsia.

As with other antipsychotics, syncope, neuroleptic malignant syndrome, leucopenia, neutropenia and peripheral edema, have been associated with quetiapine tablets.

The incidences of ADRs associated with quetiapine tablets therapy, are tabulated below according to the format recommended by the Council for International Organizations of Medical Sciences (CIOMS III Working Group; 1995).

The frequencies of adverse events are ranked according to the following:

Very common (

Blood and lymphatic system disorders
Common:	Leucopenia ¹
Uncommon:	Eosinophilia, Thrombocytopenia
Unknown:	Neutropenia ¹
Immune system disorders
Uncommon:	Hypersensitivity
Very rare:	Anaphylactic reaction ⁶
Endocrine disorders
Common:	Hyperprolactinaemia¹⁶
Metabolism and nutritional disorders
Common:	Increased appetite
Very rare:	Diabetes Mellitus ^{1, 5, 6}
Psychiatric disorders
Common:	Abnormal dreams and nightmares
Nervous system disorders
Very Common:	Dizziness ^{4, 17}, somnolence ^2,¹⁷, headache
Common:	Syncope ^{4, 17}, Extrapyramidal symptoms ^{1, 13} Dysarthria,
Uncommon:	Seizure ¹, Restless leg syndrome, Tardive dyskinesia ¹
Cardiac disorders
Common:	Tachycardia ⁴
Eye disorders
Common:	Vision blurred
Vascular disorders
Common:	Orthostatic hypotension ^{4, 17}
Respiratory, thoracic and mediastinal disorders
Common:	Rhinitis
Gastrointestinal disorders
Very Common:	Dry mouth
Common:	Constipation, dyspepsia
Uncommon:	Dysphagia ⁸
Hepato-biliary disorders
Rare:	Jaundice ⁶
Very rare:	Hepatitis ⁶
Skin and subcutaneous tissue disorders
Very rare:	Angioedema ⁶, Stevens-Johnson syndrome ⁶
Reproductive system and breast disorders
Rare:	Priapism, galactorrhoea
General disorders and administration site conditions
Very Common:	Withdrawal (discontinuation) symptoms ^{1, 10}
Common:	Mild asthenia, peripheral oedema, irritability
Rare:	Neuroleptic malignant syndrome ¹
Investigations
Very Common:	Elevations in serum triglyceride levels ¹¹, elevations in total cholesterol (predominantly LDL cholesterol) ¹², decreases in HDL cholesterol ¹⁸, weight gain ⁹
Common:	Elevations in serum transaminases (ALT, AST) ³, decreased neutrophil count, blood glucose increased to hyperglycaemic levels ⁷
Uncommon:	Elevations in gamma-GT levels ³, platelet count decreased¹⁴ QT Prolongation ^{1, 13, 19}
Rare:	Elevations in blood creatine phosphokinase¹ Venous thromboembolism¹⁵

(1) See section 4.4

(2) Somnolence may occur, usually during the first two weeks of treatment and generally resolves with the continued administration of quetiapine .

(3) Asymptomatic elevations in serum transaminase (ALT, AST) or gamma-GT-levels have been observed in some patients administered quetiapine.

(4) As with other antipsychotics with alpha1 adrenergic blocking activity, quetiapine may commonly induce orthostatic hypotension, associated with dizziness, tachycardia and, in some patients, syncope, especially during the initial dose-titration period. (See section 4.4 Special warnings and special precautions for use).

(5) Exacerbation of pre-existing diabetes has been reported in very rare cases.

(6) Calculation of frequency for these ADRs have been taken from post-marketing data only.

(7) Fasting blood glucose

(8) An increase in the rate of dysphagia with quetiapine vs. placebo was only observed in the clinical trials in bipolar depression.

(9) Based on >7% increase in body weight from baseline. Occurs predominantly during the early weeks of treatment.

(10) The following withdrawal symptoms have been observed most frequently in acute placebo-controlled, monotherapy clinical trials, which evaluated discontinuation symptoms: insomnia, nausea, headache, diarrhoea, vomiting, dizziness, and irritability. The incidence of these reactions had decreased significantly after 1 week post-discontinuation.

(11) Triglycerides

(12) Cholesterol

(13) See text below.

(14) Platelets ⁹/L on at least one occasion.

(15) Based on clinical trial adverse event reports of blood creatine phosphokinase increase not associated with neuroleptic malignant syndrome.

(16) Prolactin levels (patients >18 years of age): >20μg/L (>869.56pmol/L) males;>30μg/L (>1304.34pmol/L) females at any time.

(17) May lead to falls.

(18) HDL cholesterol: <40 mg/dL (1.025mmol/L) males; <50 mg/dL (1.282mmol/L) females at any time.

(19) Incidence of patients who have a QTc shift from <450 msec to

Cases of QT prolongation, ventricular arrhythmia, sudden unexplained death, cardiac arrest and torsades de pointes have been reported with the use of neuroleptics and are considered class effects (see section 4.4).

In short-term, placebo-controlled clinical trials in bipolar depression the aggregated incidence of extrapyramidal symptoms was 8.9% for quetiapine compared to 3.8% for placebo, though the incidence of the individual adverse events (eg, akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, muscle contractions involuntary, psychomotor hyperactivity and muscle rigidity) were generally low and did not exceed 4% in any treatment group.

In short-term, placebo-controlled clinical trials in schizophrenia and bipolar mania the aggregated incidence of extrapyramidal symptoms was similar to placebo (schizophrenia: 7.8% for quetiapine and 8.0% for placebo; bipolar mania: 11.2% for quetiapine and 11.4% for placebo).

Quetiapine tablets treatment was associated with small dose-related decreases in thyroid hormone levels, particularly total T₄ and free T₄. The reduction in total and free T₄ was maximal within the first two to four weeks of quetiapine tablets treatment, with no further reduction during long-term treatment. In nearly all cases, cessation of quetiapine tablets treatment was associated with a reversal of the effects on total and free T₄, irrespective of the duration of treatment. Smaller decreases in total T₃ and reverse T₃ were seen only at higher doses. Levels of TBG were unchanged and in general, reciprocal increases in TSH were not observed, with no indication that quetiapine tablets causes clinically relevant hypothyroidism

Children and adolescents (10 to 17 years of age)

The same ADRs described above for adults should be considered for children and adolescents. The following table summarises ADRs that occur in a higher frequency category in children and adolescent patients (10-17 years of age) than in the adult population or ADRs that have not been identified in the adult population.

The frequencies of adverse events are ranked according to the following: Very common (
Metabolism and nutritional disorders
Very common:	Increased appetite
Investigations
Very common:	Elevations in prolactin ¹ , increases in blood pressure ²
Nervous system disorders
Very common:	Extrapyramidal symptoms ³
General disorders and administration site conditions
Common:	Irritability ⁴

(1) Prolactin levels (patients < 18 years of age):>20 μg/L (>869.56 pmol/L) males;>26 μg/L (>1130.428 pmol/L) females at any time. Less than 1% of patients had an increase to a prolactin level>100 μg/L.

(2) Based on shifts above clinically significant thresholds (adapted from the National Institute of Health criteria) or increases>20mmHg for systolic or>10 mmHg for diastolic blood pressure at any time in two acute (3-6 weeks) placebo-controlled trials in children and adolescents.

(3) See Section 5.1.

(4) Note: The frequency is consistent to that observed in adults, but irritability might be associated with different clinical implications in children and adolescents as compared to adults.

4.9 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 quetiapine tablets 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.

In general, reported signs and symptoms were those resulting from an exaggeration of the substance's known pharmacological effects, i.e., drowsiness and sedation, tachycardia and hypotension.

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 special precautions for use: Cardiovascular).

Management

There is no specific antidote to quetiapine. In cases of severe intoxication, 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 (after intubation, if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.

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

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: antipsychotics

ATC code: N05A HO4

Mechanism of action

Quetiapine is an atypical antipsychotic agent. Quetiapine and the active human plasma metabolite, norquetiapine interact with a broad range of neurotransmitter receptors. Quetiapine and norquetiapine exhibit affinity for brain serotonin (5HT2) and dopamine D1- and D2- receptors. It is this combination of receptor antagonism with a higher selectivity for 5HT2 relative to D2- receptors, which is believed to contribute to the clinical antipsychotic properties and low extrapyramidal side effect (EPS) liability of Quetiapine compared to typical antispychotics. Additionally, norquetiapine has high affinity for the norepinephrine ransporter (NET). Quetiapine and norquetiapine also have high affinity at histaminergic and adrenergic α₁ receptors, with a lower affinity at adrenergic α₂ and serotonin 5HT1A receptors. Quetiapine has no appreciable affinity at cholinergic muscarinic or benzodiazepine receptors.

Pharmacodynamic effect

Quetiapine is active in tests for antipsychotic activity, such as conditioned avoidance. It also blocks the action of dopamine agonists, measured either behaviourally or electrophysiologically, and elevates dopamine metabolite concentrations, a neurochemical index of D2-receptor blockade.

In pre-clinical tests predictive of EPS, quetiapine is unlike typical antipsychotics and has an atypical profile. Quetiapine does not produce dopamine D2-receptor supersensitivity after chronic administration. Quetiapine produces only weak catalepsy at effective dopamine D2-receptor blocking doses. Quetiapine demonstrates selectivity for the limbic system by producing depolarisation blockade of the mesolimbic but not the nigrostriatal dopamine-containing neurones following chronic administration. Quetiapine exhibits minimal dystonic liability in haloperidol-sensitised or drug-naive Cebus monkeys after acute and chronic administration. (See Section 4.8)

Clinical Efficacy

In three placebo-controlled clinical trials, in patients with schizophrenia, using variable doses of quetiapine, there were no differences between the quetiapine and placebo treatment groups in the incidence of EPS or concomitant use of anticholinergics. A placebo-controlled trial evaluating fixed doses of quetiapine across the range of 75 to 750 mg/day showed no evidence of an increase in EPS or the use of concomitant anticholinergics.

In four placebo-controlled clinical trials, evaluating doses of quetiapine up to 800 mg/day for the treatment of moderate to severe manic episodes, two each in monotherapy and as combination therapy to lithium or divalproex, there were no differences between the quetiapine and placebo treatment groups in the incidence of EPS or concomitant use of anticholinergics.

In placebo-controlled studies in elderly patients with dementia-related psychosis, the incidence of cerebrovascular adverse events per 100 patient years was not higher in quetiapine-treated patients than in placebo-treated patients.

In the treatment of moderate to severe manic episodes, quetiapine demonstrated superior efficacy to placebo in reduction of manic symptoms at 3 and 12 weeks, in two monotherapy trials. There are no data from long term studies to demonstrate quetiapine's effectiveness in preventing subsequent manic or depressive episodes. Quetiapine data in combination with divalproex or lithium in acute moderate to severe manic episodes at 3 and 6 weeks is limited; however, combination therapy was well tolerated. The data showed an additive effect at week 3. A second study did not demonstrate an additive effect at week 6.

The mean last week median dose of quetiapine in responders was approximately 600 mg/day and approximately 85% of the responders were in the dose range of 400 to 800 mg/day.

In 4 clinical trials with a duration of 8 weeks in patients with moderate to severe depressive episodes in bipolar I or bipolar II disorder, quetiapine IR 300 mg and 600 mg was significantly superior to placebo treated patients for the relevant outcome measures: mean improvement on the MADRS and for response defined as at least a 50% improvement in MADRS total score from baseline. There was no difference in magnitude of effect between the patients who received 300 mg Quetiapine IR and those who received 600 mg dose.

In the continuation phase in two of these studies, it was demonstrated that long-term treatment, of patients who responded on quetiapine IR 300 or 600 mg, was efficacious compared to placebo treatment with respect to depressive symptoms, but not with regard to manic symptoms.

In two recurrence prevention studies evaluating quetiapine in combination with mood stabilizers, in patients with manic, depressed or mixed mood episodes, the combination with Quetiapine was superior to mood stabilizers monotherapy in increasing the time to recurrence of any mood event (manic, mixed or depressed).

Quetiapine was administered twice-daily totalling 400 mg to 800 mg a day as combination therapy to lithium or valproate.

In one long-term study (up to 2 years treatment) evaluating recurrence prevention in patients with manic, depressed or mixed mood episodes quetiapine was superior to placebo in increasing the time to recurrence of any mood event (manic, mixed or depressed), in patients with bipolar I disorder. The number of patients with a mood event was 91 (22.5%) in the quetiapine group, 208 (51.5%) in the placebo group and 95 (26.1%) in the lithium treatment groups respectively. In patients who responded to quetiapine, when comparing continued treatment with quetiapine to switching to lithium, the results indicated that a switch to lithium treatment does not appear to be associated with an increased time to recurrence of a mood event.

Clinical trials have demonstrated that quetiapine is effective in schizophrenia and mania when given twice a day, although quetiapine h

Molipaxin Tablets 150mg

1. Name Of The Medicinal Product

Molipaxin 150mg Tablets

2. Qualitative And Quantitative Composition

Tablet containing 150mg of trazodone Hydrochloride.

For excipients, see 6.1

3. Pharmaceutical Form

Tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

Relief of symptoms in all types of depression including depression accompanied by anxiety.

4.2 Posology And Method Of Administration

Route of administration: Oral.

Depression:

a) Adults:

Initially 150mg/day in divided doses after food or as a single dose on retiring.

This may be increased up to 300mg/day in a single or divided doses. The major portion of a divided dose to be taken on retiring. The dose may be further increased to 600mg/day in divided doses in hospitalised patients.

b) Elderly:

For very elderly or frail patients the recommended initial starting dose is reduced to100mg/day given in divided doses or as a single night-time dose. This may be incrementally increased, under supervision, according to efficacy and tolerance. In general, single doses above 100 mg should be avoided in these patients. It is unlikely that 300mg/day will be exceeded.

Children:

Molipaxin is not recommended for use in children below the age of 18 years due to a lack of data on safety.

Depression accompanied by anxiety:

As for depression.

Anxiety:

75mg/day increasing to 300mg/day as necessary.

A decrease in side-effects (increase of the resorption and decrease of the peak plasma concentration) can be reached by taking Molipaxin after a meal..

Hepatic Impairment:

Molipaxin undergoes extensive hepatic metabolism, see section 5.2, and has also been associated with hepatotoxicity, see sections 4.4 and 4.8. Therefore caution should be exercised when prescribing for patients with hepatic impairment, particularly in cases of severe hepatic impairment. Periodic monitoring of liver function may be considered.

Renal Impairment:

No dosage adjustment is usually necessary, but caution should be exercised when prescribing for patients with severe renal impairment (see also section 4.4 and 5.2).

4.3 Contraindications

Known sensitivity to trazodone and any of the excipients.

Alcohol intoxication and intoxication with hypnotics.

Acute myocardial infarction.

4.4 Special Warnings And Precautions For Use

Use in children and adolescents under 18

Molipaxin should not be used in children and adolescents under 18 years old. Suicidal behaviour (suicidal attempt and suicidal planning) and hostility (essentially aggressiveness, opposing behavior and anger) has been observed in a clinical study on children and adolescents treated with antidepressant more frequently than with placebo. Moreover, long-term safety data on children and adolescents regarding growth, maturation and cognitive and behavioral development are not available.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Molipaxin is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.

Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

To minimise the potential risk of suicide attempts, particularly at therapy initiation, only restricted quantities of Molipaxin should be prescribed at each occasion.

It is recommended that careful dosing and regular monitoring is adopted in patients with the following conditions:

• Epilepsy, specifically abrupt increases or decreases of dosage should be avoided

• Patients with hepatic or renal impairment, particulary if severe

• Patients with cardiac disease, such as angina pectoris, conduction disorders or AV blocks of different degree, recent myocardial infarction

• Hyperthyroidism

• Micturition disorders, such as prostate hypertrophy, although problems would not be anticipated as the anticholinergic effect of Molipaxin is only minor

• Acute narrow angle glaucoma, raised intra-ocular pressure, although major changes would not be anticipated due to the minor anticholinergic effect of Molipaxin.

Should jaundice occur in a patient, Molipaxin therapy must be withdrawn.

Administration of antidepressants in patients with schizophrenia or other psychotic disorders may result in a possible worsening of psychotic symptoms. Paranoid thoughts may be intensified. During therapy with Molipaxin a depressive phase can change from a manic – depressive psychosis into a manic phase. In that case Molipaxin must be stopped.

Interactions in terms of serotonine syndrome/malignant neuroleptic syndrome have been described in case of concomitant use of other serotonergically acting substances like other antidepressants (e.g. tricyclic antidepressants, SSRI's, SNRI's and MAO-inhibitors) and neuroleptics. Malignant neuroleptic syndromes with fatal outcome have been reported in cases of coadministration with neuroleptics, for which this syndrome is a known possible adverse drug reaction. See Sections 4.5 and 4.8 for further information.

Since agranulocytosis may clinically reveal itself with influenza-like symptoms, sore throat, and fever, in these cases it is recommended to check haematology.

Hypotension, including orthostatic hypotension and syncope, has been reported to occur in patients receiving Molipaxin. Concomitant administration of antihypertensive therapy with Molipaxin may require a reduction in the dose of the antihypertensive drug

Elderly patients are often more sensitive to antidepressants, in particular to orthostatic hypotension and other anticholinergic effects.

Following therapy with Molipaxin, particularly for a prolonged period, an incremental dosage reduction to withdrawal is recommended, to minimise the occurrence of withdrawal syptoms, characterised by nausea, headache, and malaise.

There is no evidence that Molipaxin possesses any addictive properties.

As with other antidepressant drugs, cases of QT interval prolongation have been reported with Molipaxin very rarely. Caution is advised when prescribing Molipaxin with medicinal products known to prolong QT interval. Molipaxin should be used with caution in patients with known cardiovascular disease including those associated with prolongation of the QT interval.

Potent CYP3A4 inhibitors may lead to increases in trazodone serum levels. See section 4.5 for further information.

As with other drugs with alpha-adrenolytic activity, Molipaxin has very rarely been associated with priapism. This may be treated with an intracavernosum injection of an alpha-adrenergic agent such as adrenaline or metaraminol. However there are reports of Molipaxin-induced priapism which have required surgical intervention or led to permanent sexual dysfunction. Patients developing this suspected adverse reaction should cease Molipaxin immediately.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

General: The sedative effects of antipsychotics, hypnotics, sedatives, anxiolytics, and antihistaminic drugs may be intensified; dosage reduction is recommended in such instances.

The metabolism of antidepressants is accelerated due to hepatic effects by oral contraceptives, phenytoin, carbamazepine and barbiturates. The metabolism of antidepressants is inhibited by cimetidine and some other antipsychotics.

In vitro drug metabolism studies suggest that there is a potential for drug interactions when Molipaxin is given with potent CYP3A4 inhibitors such as erythromycin, ketoconazole, itraconazole, ritonavir, indinavir, and nefazodone. It is likely that potent CYP3A4 inhibitors may lead to substantial increases in trazodone plasma concentrations with the potential for adverse effects. Exposure to ritonavir during initiation or resumption of treatment in patients receiving Molipaxin will increase the potential for excessive sedation, cardiovascular, and gastrointestinal effects. It has been confirmed in in- vivo-studies in healthy volunteers, that a ritonavir dose of 200 mg BID increased the plasma levels of Molipaxin by greater than two-fold, leading to nausea, syncope and hypotension. If Molipaxin is used with a potent CYP3A4 inhibitor, a lower dose of Molipaxin should be considered. However, the co-administration of Molipaxin and potent CYP3A4 inhibitors should be avoided where possible.

Carbamazepine reduced plasma concentrations of trazodone when coadministered. Concomitant use of carbamazepine 400 mg daily led to a decrease of plasma concentrations of Molipaxin and its active metabolite m-chlorophenylpiperazine of 76 % and 60 %, respectively. Patients should be closely monitored to see if there is a need for an increased dose of Molipaxin when taken with carbamazepine.

Molipaxin may enhance the effects of muscle relaxants and volatile anaesthetics, and caution should be exercised in such instances. Similar considerations apply to combined administration with sedative and anti-depressant drugs, including alcohol. Molipaxin intensifies the sedative effects of alcohol. Alcohol should be avoided during Molipaxin therapy. Molipaxin has been well tolerated in depressed schizophrenic patients receiving standard phenothiazine therapy and also in depressed parkinsonian patients receiving therapy with levodopa. Antidepressants can accelerate the metabolism of levodopa.

Tricyclic antidepressants: Concurrent administration should be avoided due to the risk of interaction. Serotonine syndrome and cardiovascular side effects should be bewared.

Fluoxetine: Rare cases have been reported of elevated Molipaxin plasma levels and adverse effects when Molipaxin had been combined with fluoxetine, a CYP1A2/2D6 inhibitor. The mechanism underlying a pharmacokinetic interaction is not fully understood. A pharmacodynamic interaction (serotonine syndrome) could not be excluded.

Possible interactions with monoamine oxidase inhibitors have occasionally been reported. Although some clinicians do give both concurrently, use of Molipaxin with MAOIs, or within two weeks of stopping treatment with these compounds is not recommended. The giving of MAOIs within one week of stopping Molipaxin is also not recommended.

Phenothiazines: Severe orthostatic hypotension has been observed in case of concomitant use of phenothiazines, like e.g. chlorpromazine, fluphenazine, levomepromazine, perphenazine.

Other

Concomitant use of Molipaxin with drugs known to prolong the QT interval may increase the risk of ventricular arrhythmias, including torsade de pointes. Caution should be used when these drugs are coadministered with Molipaxin.

Since Molipaxin is only a very weak inhibitor of noradrenaline re-uptake and does not modify the blood pressure response to tyramine, interference with the hypotensive action of guanethidine-like compounds is unlikely. However, studies in laboratory animals suggest that Molipaxin may inhibit most of the acute actions of clonidine. In the case of other types of antihypertensive drug, although no clinical interactions have been reported, the possibility of potentiation should be considered.

Undesirable effects may be more frequent when Molipaxin is administered together with preparations containing Hypericum perforatum (St John's wort).

There have been reports of changes in prothrombin time in patients concomitantly receiving trazodone and warfarin.

Concurrent use with Molipaxin may result in elevated serum levels of digoxin or phenytoin. Monitoring of serum levels should be considered in these patients.

4.6 Pregnancy And Lactation

Pregnancy:

Data on a limited number (< 200) of exposed pregnancies indicate no adverse effects of Molipaxin on pregnancy or on the health of the foetus/newborn child. To date, no other relevant epidemiological data are available. The safety of Molipaxin in human pregnancy has not been established. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development at therapeutic doses. On basic principles, therefore, its use during the first trimester should be avoided.

Caution should be exercised when prescribing to pregnant women. When Molipaxin is used until delivery, newborns should be monitored for the occurrence of withdrawal symptoms.

Lactation:

Limited data indicate that excretion of Molipaxin in human breast milk is low, but levels of the active metabolite are not known. Due to the paucity of data, a decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with Molipaxin should be made taking into account the benefit of breast-feeding to the child and the benefit of Molipaxin therapy to the woman.

4.7 Effects On Ability To Drive And Use Machines

Molipaxin has minor or moderate influence on the ability to drive and use machines. As with all other drugs acting on the central nervous system, patients should be cautioned against the risks of driving or operating machinery until they are sure they are not affected by drowsiness, sedation, dizziness, confusional states, or blurred vision.

4.8 Undesirable Effects

Cases of suicidal ideation and suicidal behaviours have been reported during Molipaxin therapy or early after treatment discontinuation (see section 4.4).

Molipaxin has had no effect on arterial blood pCO₂ or pO₂ levels in patients with severe respiratory insufficiency due to chronic bronchial or pulmonary disease.

The following symptoms, some of which are commonly reported in cases of untreated depression, have also been recorded in patients receiving Molipaxin therapy.

MedDRA System Organ Class	Frequency not known (cannot be estimated from the available data)
Blood and the lymphatic system disorders	Blood dyscrasias (including agranulocytosis, thrombocytopenia, eosinophilia, leucopenia and anaemia)
Immune system disorders	Allergic reactions
Endocrine disorders	Syndrome of Inappropriate Antidiuretic Hormone Secretion
Metabolism and nutrition disorders	Hyponatraemia¹, weight loss, anorexia, increased appetite,
Psychiatric disorders	Suicidal ideation or suicidal behaviours², confusional state, insomnia, disorientation, mania, anxiety, nervousness, agitation (very occasionally exacerbating to delirium), delusion, aggressive reaction, hallucinations, nightmares, libido decreased, withdrawal syndrome
Nervous system disorders	Serotonin syndrome, convulsion, neuroleptic malignant syndrome, dizziness, vertigo, headache, drowsiness³, restlessness, decreased alertness, tremor, blurred vision, memory disturbance, myoclonus, expressive aphasia, paraesthesia, dystonia, taste altered
Cardiac disorders	Cardiac arrhythmias⁴ (including Torsade de Pointes, palpitations, premature ventricular contractions, ventricular couplets, ventricular tachycardia), bradycardia, tachycardia, ECG abnormalities (QT prolongation)²
Vascular disorders	Ortostatic hypotension, hypertension, syncope
Respiratory, thoracic and mediastinal disorders	Nasal congestion, dyspnoea
Gastrointestinal disorders	Nausea, vomiting, dry mouth, constipation, diarrhoea, dyspepsia, stomach pain, gastroenteritis, increased salivation, paralytic ileus
Hepato-biliary disorders	Hepatic function abnormalities (including jaundice and hepatocellular damage)⁵ , cholestasis intrahepatic
Skin and subcutaneous tissue disorders	Skin rash, pruritus, hyperhidrosis
Musculoskeletal and connective tissue disorders	Pain in limb, back pain, myalgia, arthralgia
Renal and urinary disorders	Micturition disorderd
Reproductive system and breast disorders	Priapism⁶
General disorders and administration site conditions	Weakness, oedema, influenza-like symptoms, fatigue, chest pain, fever
Investigations	Elevated liver enzymes

¹ Fluid and electrolyte status should be monitored in symptomatic patients.

² See also Section 4.4.

³ Trazodone is a sedative antidepressant and drowsiness, sometimes experienced during the first days of treatment, usually disappears on continued therapy.

⁴ Studies in animals have shown that trazodone is less cardiotoxic than the tricyclic antidepressants, and clinical studies suggest that the drug may be less likely to cause cardiac arrhythmias in man. Clinical studies in patients with pre-existing cardiac disease indicate that trazodone may be arrhythmogenic in some patients in that population.

⁵ Adverse effects on hepatic function, sometimes severe, have been rarely reported. Should such effects occur, trazodone should be immediately discontinued.

⁶ See also Section 4.4

4.9 Overdose

Features of toxicity

The most frequently reported reactions to overdose have included drowsiness, dizziness, nausea and vomiting. In more serious cases coma, tachycardia, hypotension, hyponatraemia, convulsions and respiratory failure have been reported. Cardiac features may include bradycardia, QT prolongation and torsade de pointes. Symptoms may appear 24 hours or more after overdose.

Overdoses of Molipaxin in combination with other antidepressants may cause serotonin syndrome.

Management

There is no specific antidote to trazodone. Activated charcoal should be considered in adults who have ingested more than 1 g trazodone, or in children who have ingested more than 150 mg trazodone within 1 hour of presentation. Alternatively, in adults, gastric lavage may be considered within 1 hour of ingestion of a potentially life-threatening overdose.

Observe for at least 6 hours after ingestion (or 12 hours if a sustained release preparation has been taken). Monitor BP, pulse and Glasgow Coma Scale (GCS). Monitor oxygen saturation if GCS is reduced. Cardiac monitoring is appropriate in symptomatic patients.

Single brief convulsions do not require treatment. Control frequent or prolonged convulsions with intravenous diazepam (0.1-0.3 mg/kg body weight) or lorazepam (4 mg in an adult and 0.05 mg/kg in a child). If these measures do not control the fits, an intravenous infusion of phenytoin may be useful. Give oxygen and correct acid base and metabolic disturbances as required.

Treatment should be symptomatic and supportive in the case of hypotension and excessive sedation. If severe hypotension persists consider use of inotropes, eg dopamine or dobutamine

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

ATC code: N06A X05. Other antidepressants.

Molipaxin is a potent antidepressant. It also has anxiety reducing activity. Molipaxin is a triazolopyridine derivative chemically unrelated to known tricyclic, tetracyclic and other antidepressant agents. It has negligible effect on noradrenaline re-uptake mechanisms. Whilst the mode of action of Molipaxin is not known precisely, its antidepressant activity may concern noradrenergic potentiation by mechanisms other than uptake blockade. A central antiserotonin effect may account for the drug's anxiety reducing properties.

5.2 Pharmacokinetic Properties

Trazodone is rapidly absorbed from the gastro-intestinal tract and extensively metabolised. Paths of metabolism of Trazodone include n-oxidation and hydroxylation. The metabolic m-chlorophenylpiperazine is active. Trazodone is excreted in the urine almost entirely in the form of its metabolites, either in free or in conjugated form. The elimination of Trazodone is biphasic, with a terminal elimination half-life of 5 to 13 hours. Trazodone is excreted in breast milk.

There was an approximate two-fold increase in terminal phase half-life and significantly higher plasma concentrations of Trazodone in 10 subjects aged 65 to 74 years compared with 12 subjects aged 23 to 30 years following a 100mg dose of Trazodone. It was suggested that there is an age-related reduction in the hepatic metabolism of Trazodone.

In vitro studies in human liver microsomes show that trazodone is metabolised by cytochrome P4503A4 (CYP3A4) to form m-chlorophenylpiperazine. Whilst significant, the role of this pathway in the total clearance of trazodone in vivo has not been fully determined.

5.3 Preclinical Safety Data

None stated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

The tablets also contain lactose, calcium hydrogen phosphate, microcrystalline cellulose, maize starch, sodium starch glycollate, povidone and magnesium stearate. The film coating contains hydroxypropyl methyl cellulose, propylene glycol, red iron oxide E172 and titanium dioxide.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Glass bottles: Store below 30 ºC.

Blister packs: Store in a dry place below 30ºC.

6.5 Nature And Contents Of Container

i) Amber glass bottles with jay-caps: pack sizes 28, 30 or 100

ii) Blister packs: pack size 28 or 100 tablets

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

8. Marketing Authorisation Number(S)

PL 04425/0606

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of First Authorisation: 30 January 2010

10. Date Of Revision Of The Text

27/09/2010

LEGAL CLASSIFICATION

POM

Thursday, 13 September 2012

Seconal

Generic Name: barbiturate (Oral route, Parenteral route, Rectal route)

Commonly used brand name(s)

In the U.S.

Butisol Sodium

Mebaral

Mysoline

Seconal

In Canada

Nova Rectal

Available Dosage Forms:

Elixir

Tablet

Suppository

Capsule

Enema

Suspension

Solution

Uses For Seconal

Barbiturates belong to the group of medicines called central nervous system (CNS) depressants (medicines that cause drowsiness). They act on the brain and CNS to produce effects that may be helpful or harmful. This depends on the individual patient's condition and response and the amount of medicine taken.

Some of the barbiturates may be used before surgery to relieve anxiety or tension. In addition, some of the barbiturates are used as anticonvulsants to help control seizures in certain disorders or diseases, such as epilepsy. Barbiturates may also be used for other conditions as determined by your doctor.

The barbiturates have been used to treat insomnia (trouble in sleeping); but if they are used regularly (for example, every day) for insomnia, they are usually not effective for longer than 2 weeks. The barbiturates have also been used to relieve nervousness or restlessness during the daytime. However, the barbiturates have generally been replaced by safer medicines for the treatment of insomnia and daytime nervousness or tension.

If too much of a barbiturate is used, it may become habit-forming.

Barbiturates should not be used for anxiety or tension caused by the stress of everyday life.

These medicines are available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, phenobarbital is used in certain patients with the following medical condition:

Hyperbilirubinemia (high amount of bile pigments in the blood that may lead to jaundice)

Before Using Seconal

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Unusual excitement may be more likely to occur in children, who are usually more sensitive than adults to the effects of barbiturates.

Geriatric

Confusion, mental depression, and unusual excitement may be more likely to occur in the elderly, who are usually more sensitive than younger adults to the effects of barbiturates.

Pregnancy

Barbiturates have been shown to increase the chance of birth defects in humans. However, this medicine may be needed in serious diseases or other situations that threaten the mother's life. Be sure you have discussed this and the following information with your doctor:

Taking barbiturates regularly during pregnancy may cause bleeding problems in the newborn infant. In addition, taking barbiturates regularly during the last 3 months of pregnancy may cause the baby to become dependent on the medicine. This may lead to withdrawal side effects in the baby after birth.

One study in humans has suggested that barbiturates taken during pregnancy may increase the chance of brain tumors in the baby.

Barbiturates taken for anesthesia during labor and delivery may reduce the force and frequency of contractions of the uterus; this may prolong labor and delay delivery.

Use of barbiturates during labor may cause breathing problems in the newborn infant.

Breast Feeding

Barbiturates pass into the breast milk and may cause drowsiness, slow heartbeat, shortness of breath, or troubled breathing in babies of nursing mothers taking this medicine.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking any of these medicines, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

Boceprevir

Nifedipine

Praziquantel

Ranolazine

Rilpivirine

Voriconazole

Using medicines in this class with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Abiraterone

Acenocoumarol

Adinazolam

Alfentanil

Alprazolam

Amobarbital

Anileridine

Anisindione

Aprobarbital

Bortezomib

Bromazepam

Brotizolam

Butabarbital

Butalbital

Cabazitaxel

Carisoprodol

Chloral Hydrate

Chlordiazepoxide

Chlorzoxazone

Clobazam

Clonazepam

Clorazepate

Codeine

Crizotinib

Dantrolene

Dasatinib

Delavirdine

Diazepam

Dicumarol

Dronedarone

Erlotinib

Estazolam

Ethchlorvynol

Etravirine

Everolimus

Fentanyl

Flunitrazepam

Flurazepam

Fospropofol

Halazepam

Hydrocodone

Hydromorphone

Imatinib

Irinotecan

Ixabepilone

Ketazolam

Ketorolac

Lapatinib

Levorphanol

Linagliptin

Lopinavir

Lorazepam

Lormetazepam

Maraviroc

Medazepam

Meperidine

Mephenesin

Mephobarbital

Meprobamate

Metaxalone

Methocarbamol

Methohexital

Methoxyflurane

Midazolam

Morphine

Morphine Sulfate Liposome

Naproxen

Nilotinib

Nitrazepam

Nordazepam

Oxazepam

Oxycodone

Oxymorphone

Pentobarbital

Phenindione

Phenobarbital

Phenprocoumon

Prazepam

Primidone

Propoxyphene

Quazepam

Quetiapine

Remifentanil

Rivaroxaban

Roflumilast

Romidepsin

Secobarbital

Sirolimus

Sodium Oxybate

Succinylcholine

Sufentanil

Sunitinib

Tacrolimus

Tapentadol

Temazepam

Temsirolimus

Teniposide

Thiopental

Ticagrelor

Tolvaptan

Triazolam

Valproic Acid

Vandetanib

Vemurafenib

Zolpidem

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Proper Use of barbiturate

This section provides information on the proper use of a number of products that contain barbiturate. It may not be specific to Seconal. Please read with care.

For patients taking the extended-release capsule or tablet form of this medicine:

These capsules or tablets are to be swallowed whole. Do not break, crush, or chew before swallowing.

For patients using the rectal suppository form of this medicine:

To insert the suppository: First remove the foil wrapper and moisten the suppository with cold water. Lie down on your side and use your finger to push the suppository well up into the rectum.

Wash your hands with soap and water.

Use this medicine only as directed by your doctor. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered. If too much is used, it may become habit-forming (causing mental or physical dependence).

If you think this medicine is not working properly after you have taken it for a few weeks, do not increase the dose. To do so may increase the chance of your becoming dependent on the medicine. Instead, check with your doctor.

If you are taking this medicine for epilepsy, it must be taken every day in regularly spaced doses as ordered by your doctor in order for it to control your seizures. This is necessary to keep a constant amount of medicine in the blood. To help keep the amount constant, do not miss any doses.

Dosing

The dose medicines in this class will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of these medicines. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For amobarbital

For oral dosage form (tablets or capsules):
- For trouble in sleeping:
  - Adults—65 to 200 milligrams (mg) at bedtime.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—50 to 300 mg, taken in smaller doses during the day.
  - Children—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 2 mg per kilogram (kg) (0.9 mg per pound) of body weight taken three times a day.
- For sedation before surgery:
  - Adults—200 mg taken one to two hours before surgery.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kg (0.9 to 2.7 mg per pound) of body weight, taken before surgery. However, the dose is usually not more than 100 mg.
- For sedation during labor:
  - Adults—200 to 400 mg every one to three hours if needed. However, the total dose is usually not more than 1000 mg.

For injection dosage form:
- For trouble in sleeping:
  - Adults—65 to 200 mg, injected into a muscle or vein.
  - Children up to 6 years of age—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 3 mg per kg (0.9 to 1.4 mg per pound) of body weight, injected into a muscle.
  - Children 6 years of age and over—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 3 mg per kg (0.9 to 1.4 mg per pound) of body weight, injected into a muscle, or 65 to 500 mg injected into a vein.
- For daytime sedation:
  - Adults—30 to 50 mg two or three times a day, injected into a muscle or vein
- For sedation before surgery:
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 3 to 5 mg per kg (1.4 to 2.3 mg per pound) of body weight or 65 to 500 mg per dose, injected into a vein.
- For control of seizures:
  - Adults and children 6 years of age and over—65 to 500 mg per dose, injected into a vein.
  - Children up to 6 years of age—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 3 to 5 mg per kg (1.4 to 2.3 mg per pound) of body weight, injected into a muscle or vein.

For aprobarbital

For oral dosage form (elixir):
- For trouble in sleeping:
  - Adults—40 to 160 milligrams (mg) at bedtime.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—40 mg three times a day.
  - Children—Dose must be determined by your doctor.

For butabarbital

For oral dosage forms (elixir or tablets):
- For trouble in sleeping:
  - Adults—50 to 100 milligrams (mg) at bedtime.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—15 to 30 mg three or four times a day.
  - Children—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 2 mg per kilogram (kg) (0.9 mg per pound) of body weight three times a day.
- For sedation before surgery:
  - Adults—50 to 100 mg sixty to ninety minutes before surgery.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kg (0.9 to 2.7 mg per pound) of body weight. However, the dose is usually not more than 100 mg.

For mephobarbital

For oral dosage form (tablets):
- For daytime sedation:
  - Adults—32 to 100 milligrams (mg) three or four times a day.
  - Children—16 to 32 mg three or four times a day.
- For control of seizures:
  - Adults—200 to 600 mg a day, taken in smaller doses during the day.
  - Children 5 years of age and over—32 to 64 mg three or four times a day.
  - Children up to 5 years of age—16 to 32 mg three or four times a day.

For metharbital

For oral dosage form (tablets):
- For control of seizures:
  - Adults—At first, 100 milligrams (mg) one to three times a day. Your doctor may increase your dose if needed. However, the dose is usually not more than 800 mg a day.
  - Children—50 mg one to three times a day.

For pentobarbital

For oral dosage forms (elixir or capsules):
- For trouble in sleeping:
  - Adults—100 milligrams (mg) at bedtime.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—20 mg three or four times a day.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kilogram (kg) (0.9 to 2.7 mg per pound) of body weight per day.
- For sedation before surgery:
  - Adults—100 mg before surgery.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kilogram (0.9 to 2.7 mg per pound) of body weight, taken before surgery. However, the dose is usually not more than 100 mg.

For injection dosage form:
- For trouble in sleeping:
  - Adults—150 to 200 mg, injected into a muscle. Or, 100 mg injected into a vein, with additional small doses given if needed. However, the dose is usually not more than 500 mg.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kg (0.9 to 2.7 mg per pound) of body weight, injected into a muscle. Or, 50 mg injected into a vein, with additional small doses given if needed.
- For sedation before surgery:
  - Adults—150 to 200 mg, injected into a muscle.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kg (0.9 to 2.7 mg per pound) of body weight, injected into a muscle. However, the dose is usually not more than 100 mg.
- For control of seizures:
  - Adults—At first, 100 mg injected into a vein. Additional small doses may be given if needed. However, the dose is usually not more than 500 mg.
  - Children—At first, 50 mg injected into a muscle or vein. Additional small doses may be given if needed.

For rectal dosage form (suppositories):
- For trouble in sleeping:
  - Adults—120 to 200 mg inserted into the rectum at bedtime.
  - Children 12 to 14 years of age—60 or 120 mg inserted into the rectum at bedtime.
  - Children 5 to 12 years of age—60 mg inserted into the rectum at bedtime.
  - Children 1 to 4 years of age—30 or 60 mg inserted into the rectum at bedtime.
  - Children 2 months to 1 year of age—30 mg inserted into the rectum at bedtime.
  - Children up to 2 months of age—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—30 mg inserted into the rectum two to four times a day.
  - Children—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 2 mg per kg (0.9 mg per pound) of body weight, inserted into the rectum three times a day.
- For sedation before surgery:
  - Children 12 to 14 years of age—60 or 120 mg inserted into the rectum.
  - Children 5 to 12 years of age—60 mg inserted into the rectum.
  - Children 1 to 4 years of age—30 or 60 mg inserted into the rectum.
  - Children 2 months to 1 year of age—30 mg inserted into the rectum.
  - Children up to 2 months of age—Dose must be determined by your doctor.

For phenobarbital

For oral dosage forms (elixir, capsules, or tablets):
- For trouble in sleeping:
  - Adults—100 to 320 milligrams (mg) at bedtime.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—30 to 120 mg a day, taken in smaller doses two or three times during the day.
  - Children—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 2 mg per kilogram (kg) (0.9 mg per pound) of body weight three times a day.
- For sedation before surgery:
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 1 to 3 mg per kg (0.45 to 1.4 mg per pound) of body weight.
- For control of seizures:
  - Adults—60 to 250 mg a day.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 1 to 6 mg per kg (0.45 to 2.7 mg per pound) of body weight a day.

For injection dosage form:
- For trouble in sleeping:
  - Adults—100 to 325 mg, injected into a muscle or vein, or under the skin.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—30 to 120 mg a day, injected into a muscle or a vein, or under the skin, in smaller doses two or three times during the day.
  - Children—Dose must be determined by your doctor.
- For sedation before surgery:
  - Adults—130 to 200 mg, injected into a muscle sixty to ninety minutes before surgery.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 1 to 3 mg per kg (0.45 to 1.4 mg per pound) of body weight, injected into a muscle or vein sixty to ninety minutes before surgery.
- For control of seizures:
  - Adults—100 to 320 mg injected into a vein. The dose may be repeated if needed, but is usually not more than 600 mg a day. However, higher doses may be needed for certain types of continuing seizures.
  - Children—Dose is based on body weight and must be determined by your doctor. At first, the usual dose is 10 to 20 mg per kg (4.5 to 9 mg per pound) of body weight, injected into a vein. Later, 1 to 6 mg per kg (0.45 to 2.7 mg per pound) of body weight a day, injected into a vein. Higher doses may be needed for certain types of continuing seizures.

For secobarbital

For oral dosage form (capsules):
- For trouble in sleeping:
  - Adults—100 milligrams (mg) at bedtime.
  - Children—Dose must be determined by your doctor.
- For daytime sedation:
  - Adults—30 to 50 mg three or four times a day.
  - Children—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 2 mg per kilogram (kg) (0.9 mg per pound) of body weight three times a day.
- For sedation before surgery:
  - Adults—200 to 300 mg one or two hours before surgery.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 2 to 6 mg per kg (0.9 to 2.7 mg per pound) of body weight one or two hours before surgery. However, the dose is usually not more than 100 mg.

For injection dosage form:
- For trouble in sleeping:
  - Adults—100 to 200 mg injected into a muscle, or 50 to 250 mg injected into a vein.
  - Children—Dose is based on body weight or size and must be determined by your doctor. The usual dose is 3 to 5 mg per kg (1.4 to 2.3 mg per pound) of body weight, injected into a muscle. However, the dose is usually not more than 100 mg.
- For sedation before dental procedures:
  - Adults—Dose is based on body weight and must be determined by your doctor. The usual dose is 1.1 to 2.2 mg per kg (0.5 to 1 mg per pound) of body weight, injected into a muscle ten to fifteen minutes before the procedure.
  - Children—Dose must be determined by your dentist.
- For sedation before a nerve block:
  - Adults—100 to 150 mg, injected into a vein.
- For sedation before surgery:
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 4 to 5 mg per kg (1.8 to 2.3 mg per pound) of body weight, injected into a muscle.
- For seizures from tetanus:
  - Adults—Dose is based on body weight and must be determined by your doctor. The usual dose is 5.5 mg per kg (2.5 mg per pound) of body weight, injected into a muscle or vein. Dose may be repeated every three to four hours if needed.
  - Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 3 to 5 mg per kg (1.4 to 2.3 mg per pound) of body weight, injected into a muscle or vein.

For secobarbital and amobarbital combination

For oral dosage form (capsules):
- For trouble in sleeping:
  - Adults—1 capsule at bedtime.
  - Children—Dose must be determined by your doctor.
- For sedation before surgery:
  - Adults—1 capsule taken one hour before surgery.
  - Children—Dose must be determined by your doctor.

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Keep out of the reach of children.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Do not keep outdated medicine or medicine no longer needed.

Store the suppository form of this medicine in the refrigerator.

Precautions While Using Seconal

If you will be using this medicine regularly for a long time:

Your doctor should check your progress at regular visits.

Do not stop using it without first checking with your doctor. Your doctor may want you to reduce gradually the amount you are using before stopping completely.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using this medicine .

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of the metyrapone test may be affected by this medicine.

If you have been using this medicine for a long time and you think that you may have become mentally or physically dependent on it, check with your doctor. Some signs of mental or physical dependence on barbiturates are:

a strong desire or need to continue taking the medicine.

a need to increase the dose to receive the effects of the medicine.

withdrawal side effects (for example, anxiety or restlessness, convulsions [seizures], feeling faint, nausea or vomiting, trembling of hands, trouble in sleeping) occurring after the medicine is stopped.

If you think you or someone else may have taken an overdose of this medicine, get emergency help at once. Taking an overdose of a barbiturate or taking alcohol or other CNS depressants with the barbiturate may lead to unconsciousness and possibly death. Some signs of an overdose are severe drowsiness, severe confusion, severe weakness, shortness of breath or slow or troubled breathing, slurred speech, staggering, and slow heartbeat.

This medicine may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert .

Oral contraceptives (birth control pills) containing estrogen may not work properly if you take them while you are taking barbiturates. Unplanned pregnancies may occur. You should use a different or additional means of birth control while you are taking barbiturates. If you have any questions about this, check with your health care professional.

Seconal Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

Rare

Bleeding sores on lips

chest pain

fever

muscle or joint pain

red, thickened, or scaly skin

skin rash or hives

sores, ulcers, or white spots in mouth (painful)

sore throat and/or fever

swelling of eyelids, face, or lips

wheezing or tightness in chest

Check with your doctor as soon as possible if any of the following side effects occur:

Less common

Confusion

mental depression

unusual excitement

Rare

Hallucinations (seeing, hearing, or feeling things that are not there)

unusual bleeding or bruising

unusual tiredness or weakness

With long-term or chronic use

Bone pain, tenderness, or aching

loss of appetite

muscle weakness

weight loss (unusual)

yellow eyes or skin

Symptoms of overdose

Confusion (severe)

decrease in or loss of reflexes

drowsiness (severe)

fever

irritability (continuing)

low body temperature

poor judgment

shortness of breath or slow or troubled breathing

slow heartbeat

slurred speech

staggering

trouble in sleeping

unusual movements of the eyes

weakness (severe)

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Clumsiness or unsteadiness

dizziness or lightheadedness

drowsiness

"hangover" effect

Less common

Anxiety or nervousness

constipation

feeling faint

headache

irritability

nausea or vomiting

nightmares or trouble in sleeping

Confusion, mental depression, and unusual excitement may be more likely to occur in very ill patients.

After you stop using this medicine, your body may need time to adjust. If you took this medicine in high doses or for a long time, this may take up to about 15 days. During this period of time check with your doctor if any of the following side effects occur (usually occur within 8 to 16 hours after medicine is stopped):

Anxiety or restlessness

convulsions (seizures)

dizziness or lightheadedness

feeling faint

hallucinations (seeing, hearing, or feeling things that are not there)

muscle twitching

nausea or vomiting

trembling of hands

trouble in sleeping, increased dreaming, or nightmares

vision problems

weakness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

Tuesday, 11 September 2012

Nitrozone Ointment

Dosage Form: FOR ANIMAL USE ONLY
NITROZONE SOLUBLE DRESSING

INDICATIONS:

For the prevention or treatment of surface bacterial infections of wounds, burns, and cutaneous ulcers.

ADMINISTRATION:

Apply directly on the lesion with a spatula, or first place on a piece of gauze. Application of a bandage is optional.

This preparation should be in contact with the lesion for at least 24 hours. The dressing may be changed several times daily or left on the lesion for a longer period.

PRECAUTION:

In case of deep or puncture wounds or serious burns, use only as recommended by a veterinarian. If redness, irritation, or swelling persists or increases, discontinue use, reconsult veterinarian. Avoid exposure to alkaline material and fluorescent lighting.

KEEP AWAY FROM EXCESSIVE HEAT OR DIRECT SUNLIGHT.

HUMAN WARNINGS:

CARCINOGENESIS: NITROFURAZONE, THE ACTIVE INGREDIENT OF NITROFURAZONE SOLUBLE DRESSING, HAS BEEN SHOWN TO PROOUCE MAMMARY TUMORS IN RATS AND OVARIAN TUMORS IN MICE.

SOME PEOPLE MAY BE HYPERSENSITIVE TO THIS PRODUCT. EITHER WEAR GLOVES WHEN APPLYING, OR WASH HANDS AFTERWARDS.

STORAGE:

Store at controlled room temperature between 15°-30°C (59°-86°F). Keep container tightly closed when not In use.

DISPLAY PANEL

For Use In Horses Only

An Antibacterial Preparation for Topical Application

CAUTION: FEDERAL LAW PROHIBITS THE USE OF THIS PRODUCT IN FOOD-PRODUCING ANIMALS.

FOR ANIMAL USE ONLY

KEEP OUT OF REACH OF CHILDREN

Manufactured For: First Companion Veterinary Proudcts, Westlake, TX 76262, U.S.A.

Iss. 09 - 09

NET CONTENTS:

1 lb (453.6 g)

IMAGE OF JAR LABEL

IMAGE OF CASE LABEL

NITROZONE SOLUBLE DRESSING
nitrofurazone ointment

Product Information
Product Type	OTC ANIMAL DRUG	NDC Product Code (Source)	64556-292
Route of Administration	TOPICAL	DEA Schedule

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
NITROFURAZONE (NITROFURAZONE)	NITROFURAZONE	0.2 g in 1 g

Inactive Ingredients
Ingredient Name	Strength
No Inactive Ingredients Found

Product Characteristics
Color	yellow (YELLOW)	Score
Shape		Size
Flavor		Imprint Code
Contains

Packaging
#	NDC	Package Description	Multilevel Packaging
1	64556-292-16	12 JAR In 1 CASE	contains a JAR
1		453.6 g In 1 JAR	This package is contained within the CASE (64556-292-16)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
ANADA	ANADA200425	09/01/2009

Labeler - FIRST COMPANION VETERINARY PRODUCTS (059580480)

Revised: 09/2009FIRST COMPANION VETERINARY PRODUCTS

Sunday, 9 September 2012

Breast Cancer, Palliative Medications

Drugs associated with Breast Cancer, Palliative

The following drugs and medications are in some way related to, or used in the treatment of Breast Cancer, Palliative. This service should be used as a supplement to, and NOT a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners.

Learn more about Breast Cancer, Palliative

Medical Encyclopedia:

Breast cancer
Cancer treatment information

Drug List:

First-Testosterone-Mc

Testosterone-Cypionate

Testosterone-Enanthate

Testred

Zoladex

Friday, 7 September 2012

Ethedent

Generic Name: fluoride topical (FLOR ide TOP i kal)

Brand Names: ACT Fluoride Rinse, ACT Kids Fluoride Rinse, ACT Restoring Mouthwash Cinnamon, ACT Restoring Mouthwash Mint, ACT Restoring Mouthwash Spearmint, ACT Restoring Mouthwash Vanilla Mint, Control Rx, Denta 5000 Plus, Dentagel, Ethedent, Fluoridex, Fluoridex Daily Defense, Fluoridex Daily Defense Enhanced Whitening, Fluorigard, Fluorinse, Gel-Kam, Gel-Kam Dental Therapy Pak, Gel-Kam Dentinbloc, Gel-Kam Sensitivity Therapy, NaFrinse Daily/Acidulated, NaFrinse Daily/Neutral, Nafrinse Solution, NaFrinse Weekly, Neutracare Gel, Neutragard, Neutragard Advanced, Neutral Sodium Fluoride Rinse, Omnii Gel, Omnii Gel Just For Kids, Oral B Anti-Cavity, Perfect Choice, Perio Med, Phos-Flur, Prevident, Prevident 500 Plus Boost, PreviDent 5000 Booster, Prevident 5000 Dry Mouth, Prevident 5000 Plus, Prevident 5000 Sensitive, Prevident Dental Rinse, SF, SF 5000 Plus, Stop, Thera-Flur-N

What is Ethedent (fluoride topical)?

Fluoride is a substance that strengthens tooth enamel. This helps to prevent dental cavities.

Fluoride topical is used as a medication to prevent tooth decay in patients that have a low level of fluoride topical in their drinking water. Fluoride topical is also used to prevent tooth decay in patients who undergo radiation of the head and/or neck, which may cause dryness of the mouth and an increased incidence of tooth decay.

Fluoride may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Ethedent (fluoride topical)?

Fluoride topical should not be used if the level of fluoride in the drinking water is greater than 0.7 parts per million (ppm).

Before using fluoride topical, tell your dentist and doctor if you are on a low salt or a salt free diet. You may not be able to use fluoride topical, or you may need special tests while you are using it.

Do not eat, drink, or rinse your mouth for 30 minutes after using a fluoride topical. Do not swallow fluoride topical. Spit it out after use. Do not allow a child to swallow fluoride topical or serious overdose symptoms could result.

Overdose symptoms may result if you swallow large amounts of fluoride while using it.

What should I discuss with my healthcare provider before using Ethedent (fluoride topical)?

Fluoride topical should not be used if the level of fluoride in the drinking water is greater than 0.7 parts per million (ppm).

If you have gum disease, some forms of fluoride topical may be irritating to your gums. Talk to your dentist or doctor if you have bothersome mouth irritation while using fluoride topical.

Talk to your doctor and dentist before using fluoride topical if you are pregnant. Talk to your doctor and dentist before using fluoride topical if you are breast-feeding. The use of fluoride is particularly important in children to protect against tooth decay. The American Dental Association's Council on Dental Therapeutics recommends the use of fluoride by children up to 13 years of age. The American Academy of Pediatrics recommends fluoride supplementation in children until the age of 16 years old. Do not allow a child to swallow fluoride topical or serious overdose symptoms could result.

How should I use Ethedent (fluoride topical)?

Use this medication exactly as directed on the label, or as it was prescribed by your dentist or doctor. Do not use it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Fluoride topical should be used immediately after brushing or flossing your teeth. For best results, use the medication just before bedtime, unless your doctor tells you otherwise.

Swish this medication in your mouth without swallowing. Then spit it out.

Do not eat, drink, or rinse your mouth for 30 minutes after using fluoride topical. Store fluoride topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Use the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to use the medicine and skip the missed dose. Do not use extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include nausea, vomiting, stomach pain, diarrhea, drooling, numbness or tingling, loss of feeling anywhere in your body, muscle stiffness, or seizure (convulsions).

Overdose symptoms may result if you swallow large amounts of fluoride while using it.

What should I avoid while using Ethedent (fluoride topical)?

Do not swallow fluoride topical. Spit it out after use.

Ethedent (fluoride topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor if you have any of the following side effects:

discolored teeth;

weakened tooth enamel; or

any changes in the appearance of your teeth.

Less serious side effects may include:

stomach upset;

headache; or

weakness.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Ethedent (fluoride topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied fluoride. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Ethedent resources

Ethedent Side Effects (in more detail)
Ethedent Use in Pregnancy & Breastfeeding
Ethedent Support Group
0 Reviews for Ethedent - Add your own review/rating

EtheDent Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)

EtheDent Advanced Consumer (Micromedex) - Includes Dosage Information

Gel-Kam Rinse MedFacts Consumer Leaflet (Wolters Kluwer)

Phos-Flur Cream MedFacts Consumer Leaflet (Wolters Kluwer)

PreviDent 5000 Sensitive MedFacts Consumer Leaflet (Wolters Kluwer)

Prevident 5000 Booster Prescribing Information (FDA)

Prevident 5000 Dry Mouth Prescribing Information (FDA)

Prevident 5000 Enamel Protect Prescribing Information (FDA)

Prevident 5000 Sensitive Prescribing Information (FDA)

Compare Ethedent with other medications

Prevention of Dental Caries

Where can I get more information?

Your pharmacist can provide more information about fluoride topical.

See also: Ethedent side effects (in more detail)

Saturday, 15 September 2012

Quetiapine 150 mg Film-coated Tablets

1. Name Of The Medicinal Product

2. Qualitative And Quantitative Composition

3. Pharmaceutical Form

4. Clinical Particulars

4.1 Therapeutic Indications

4.2 Posology And Method Of Administration

4.3 Contraindications

4.4 Special Warnings And Precautions For Use

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

4.6 Pregnancy And Lactation

4.7 Effects On Ability To Drive And Use Machines

4.8 Undesirable Effects

4.9 Overdose

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Molipaxin Tablets 150mg

1. Name Of The Medicinal Product

2. Qualitative And Quantitative Composition

3. Pharmaceutical Form

4. Clinical Particulars

4.1 Therapeutic Indications

4.2 Posology And Method Of Administration

4.3 Contraindications

4.4 Special Warnings And Precautions For Use

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

4.6 Pregnancy And Lactation

4.7 Effects On Ability To Drive And Use Machines

4.8 Undesirable Effects

4.9 Overdose

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

5.2 Pharmacokinetic Properties

5.3 Preclinical Safety Data

6. Pharmaceutical Particulars

6.1 List Of Excipients

6.2 Incompatibilities

6.3 Shelf Life

6.4 Special Precautions For Storage

6.5 Nature And Contents Of Container

6.6 Special Precautions For Disposal And Other Handling

7. Marketing Authorisation Holder

8. Marketing Authorisation Number(S)

9. Date Of First Authorisation/Renewal Of The Authorisation

10. Date Of Revision Of The Text

Thursday, 13 September 2012

Seconal

Commonly used brand name(s)

Uses For Seconal

Before Using Seconal

Allergies

Pediatric

Geriatric

Pregnancy

Breast Feeding

Interactions with Medicines

Interactions with Food/Tobacco/Alcohol

Other Medical Problems

Proper Use of barbiturate

Dosing

Missed Dose

Storage

Precautions While Using Seconal

Seconal Side Effects

Tuesday, 11 September 2012

Nitrozone Ointment

INDICATIONS:

ADMINISTRATION:

PRECAUTION:

CONTENTS:

HUMAN WARNINGS:

STORAGE:

DISPLAY PANEL

NET CONTENTS:

IMAGE OF JAR LABEL

IMAGE OF CASE LABEL

Sunday, 9 September 2012

Breast Cancer, Palliative Medications

Drugs associated with Breast Cancer, Palliative