Detoxicol

Detoxicol may be available in the countries listed below.

Ingredient matches for Detoxicol

Lactulose

Lactulose is reported as an ingredient of Detoxicol in the following countries:

• Sri Lanka

International Drug Name Search

Zyprexa 2.5mg, 5mg, 7.5mg, 10mg, 15mg, and 20mg coated tablets. Zyprexa Velotab 5mg, 10mg, 15mg, and 20mg orodispersible tablets

1. Name Of The Medicinal Product

ZYPREXA* 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, and 20 mg coated tablets.

ZYPREXA VELOTAB* 5 mg, 10 mg, 15 mg, and 20 mg orodispersible tablets.

2. Qualitative And Quantitative Composition

Each coated tablet contains 2.5 mg olanzapine.

Excipient: 102 mg lactose monohydrate.

Each coated tablet contains 5 mg olanzapine.

Excipient: 156 mg lactose monohydrate.

Each coated tablet contains 7.5 mg olanzapine.

Excipient: 234 mg lactose monohydrate.

Each coated tablet contains 10 mg olanzapine.

Excipient: 312 mg lactose monohydrate.

Each coated tablet contains 15 mg olanzapine.

Excipient: 178 mg lactose monohydrate.

Each coated tablet contains 20 mg olanzapine.

Excipient: 238 mg lactose monohydrate.

Each orodispersible tablet contains 5 mg olanzapine.

Excipients: Each orodispersible tablet contains

0.60 mg aspartame

0.1125 mg sodium methyl parahydroxybenzoate

0.0375 mg sodium propyl parahydroxybenzoate

Each orodispersible tablet contains 10 mg olanzapine.

Excipients: Each orodispersible tablet contains

0.80 mg aspartame

0.15 mg sodium methyl parahydroxybenzoate

0.05 mg sodium propyl parahydroxybenzoate

Each orodispersible tablet contains 15 mg olanzapine.

Excipients: Each orodispersible tablet contains

1.20 mg aspartame

0.225 mg sodium methyl parahydroxybenzoate

0.075 mg sodium propyl parahydroxybenzoate

Each orodispersible tablet contains 20 mg olanzapine.

Excipients: Each orodispersible tablet contains

1.60 mg aspartame

0.30 mg sodium methyl parahydroxybenzoate

0.10 mg sodium propyl parahydroxybenzoate

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Coated Tablets

ZYPREXA 2.5 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4112'.

ZYPREXA 5 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4115'.

ZYPREXA 7.5 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4116'.

ZYPREXA 10 mg tablets: Round, white, coated tablets imprinted with 'LILLY' and a numeric identicode '4117'.

ZYPREXA 15 mg tablets: Elliptical, blue, coated tablets debossed with 'LILLY' and a numeric identicode '4415'.

ZYPREXA 20 mg tablets: Pink, elliptical, coated tablets debossed with 'LILLY' and a numeric identicode '4420'.

Orodispersible Tablets

ZYPREXA VELOTAB 5 mg, 10 mg, 15 mg, and 20 mg orodispersible tablet is a yellow, round, freeze-dried, rapid-dispersing preparation to be placed in the mouth or alternatively to be dispersed in water or other suitable beverage for administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Adults

Olanzapine is indicated for the treatment of schizophrenia.

Olanzapine is effective in maintaining the clinical improvement during continuation therapy in patients who have shown an initial treatment response.

Olanzapine is indicated for the treatment of moderate to severe manic episode.

In patients whose manic episode has responded to olanzapine treatment, olanzapine is indicated for the prevention of recurrence in patients with bipolar disorder (see section 5.1).

4.2 Posology And Method Of Administration

Adults

Schizophrenia: The recommended starting dose for olanzapine is 10 mg/day.

Manic episode: The starting dose is 15 mg as a single daily dose in monotherapy or 10 mg daily in combination therapy (see section 5.1).

Preventing recurrence in bipolar disorder: The recommended starting dose is 10 mg/day. For patients who have been receiving olanzapine for treatment of manic episode, continue therapy for preventing recurrence at the same dose. If a new manic, mixed, or depressive episode occurs, olanzapine treatment should be continued (with dose optimisation as needed), with supplementary therapy to treat mood symptoms, as clinically indicated.

During treatment for schizophrenia, manic episode, and recurrence prevention in bipolar disorder, daily dosage may subsequently be adjusted on the basis of individual clinical status within the range 5-20 mg/day. An increase to a dose greater than the recommended starting dose is advised only after appropriate clinical reassessment and should generally occur at intervals of not less than 24 hours.

Olanzapine can be given without regard for meals, as absorption is not affected by food. Gradual tapering of the dose should be considered when discontinuing olanzapine.

ZYPREXA VELOTAB orodispersible tablet should be placed in the mouth, where it will rapidly disperse in saliva, so it can be easily swallowed. Removal of the intact orodispersible tablet from the mouth is difficult. Since the orodispersible tablet is fragile, it should be taken immediately on opening the blister. Alternatively, it may be dispersed in a full glass of water or other suitable beverage (orange juice, apple juice, milk, or coffee) immediately before administration.

Olanzapine orodispersible tablet is bioequivalent to olanzapine coated tablets, with a similar rate and extent of absorption. It has the same dosage and frequency of administration as olanzapine coated tablets. Olanzapine orodispersible tablets may be used as an alternative to olanzapine coated tablets.

Paediatric population

Olanzapine is not recommended for use in children and adolescents below 18 years of age due to a lack of data on safety and efficacy. A greater magnitude of weight gain, lipid and prolactin alterations has been reported in short-term studies of adolescent patients than in studies of adult patients (see sections 4.4, 4.8, 5.1 and 5.2).

Elderly

A lower starting dose (5 mg/day) is not routinely indicated but should be considered for those 65 and over when clinical factors warrant (see section 4.4).

Renal and/or hepatic impairment

A lower starting dose (5 mg) should be considered for such patients. In cases of moderate hepatic insufficiency (cirrhosis, Child-Pugh class A or B), the starting dose should be 5 mg and only increased with caution.

Gender

The starting dose and dose range need not be routinely altered for female patients relative to male patients.

Smokers

The starting dose and dose range need not be routinely altered for non-smokers relative to smokers.

When more than one factor is present which might result in slower metabolism (female gender, geriatric age, non-smoking status), consideration should be given to decreasing the starting dose. Dose escalation, when indicated, should be conservative in such patients.

In cases where dose increments of 2.5 mg are considered necessary, ZYPREXA coated tablets should be used.

(See sections 4.5 and 5.2.)

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients. Patients with known risk of narrow-angle glaucoma.

4.4 Special Warnings And Precautions For Use

During antipsychotic treatment, improvement in the patient's clinical condition may take several days to some weeks. Patients should be closely monitored during this period.

Dementia-related psychosis and/or behavioural disturbances

Olanzapine is not approved for the treatment of dementia-related psychosis and/or behavioural disturbances and is not recommended for use in this particular group of patients because of an increase in mortality and the risk of cerebrovascular accident. In placebo-controlled clinical trials (6-12 weeks duration) of elderly patients (mean age 78 years) with dementia-related psychosis and/or disturbed behaviours, there was a 2-fold increase in the incidence of death in olanzapine-treated patients compared to patients treated with placebo (3.5% vs. 1.5%, respectively). The higher incidence of death was not associated with olanzapine dose (mean daily dose 4.4 mg) or duration of treatment. Risk factors that may predispose this patient population to increased mortality include age > 65 years, dysphagia, sedation, malnutrition and dehydration, pulmonary conditions (e.g., pneumonia, with or without aspiration), or concomitant use of benzodiazepines. However, the incidence of death was higher in olanzapine-treated than in placebo-treated patients independent of these risk factors.

In the same clinical trials, cerebrovascular adverse events (CVAE e.g., stroke, transient ischaemic attack), including fatalities, were reported. There was a 3-fold increase in CVAE in patients treated with olanzapine compared to patients treated with placebo (1.3% vs. 0.4%, respectively). All olanzapine- and placebo-treated patients who experienced a cerebrovascular event had pre-existing risk factors. Age > 75 years and vascular/mixed type dementia were identified as risk factors for CVAE in association with olanzapine treatment. The efficacy of olanzapine was not established in these trials.

Parkinson's disease

The use of olanzapine in the treatment of dopamine agonist associated psychosis in patients with Parkinson's disease is not recommended. In clinical trials, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo (see section 4.8), and olanzapine was not more effective than placebo in the treatment of psychotic symptoms. In these trials, patients were initially required to be stable on the lowest effective dose of anti-Parkinsonian medicinal products (dopamine agonist) and to remain on the same anti-Parkinsonian medicinal products and dosages throughout the study. Olanzapine was started at 2.5 mg/day and titrated to a maximum of 15 mg/day based on investigator judgement.

Neuroleptic Malignant Syndrome (NMS)

NMS is a potentially life-threatening condition associated with antipsychotic medicinal product. Rare cases reported as NMS have also been received in association with olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure. If a patient develops signs and symptoms indicative of NMS, or presents with unexplained high fever without additional clinical manifestations of NMS, all antipsychotic medicines, including olanzapine must be discontinued.

Hyperglycaemia and diabetes

Hyperglycaemia and/or development or exacerbation of diabetes, occasionally associated with ketoacidosis or coma, has been reported rarely, including some fatal cases (see section 4.8). In some cases, a prior increase in body weight has been reported, which may be a predisposing factor. Appropriate clinical monitoring is advisable in accordance with utilised antipsychotic guidelines, e.g., measuring of blood glucose at baseline, 12 weeks after starting olanzapine treatment and annually thereafter. Patients treated with any antipsychotic agents, including ZYPREXA/ZYPREXA VELOTAB, should be observed for signs and symptoms of hyperglycaemia (such as polydipsia, polyuria, polyphagia, and weakness) and patients with diabetes mellitus or with risk factors for diabetes mellitus should be monitored regularly for worsening of glucose control. Weight should be monitored regularly, e.g., at baseline, 4, 8 and 12 weeks after starting olanzapine treatment and quarterly thereafter.

Lipid alterations

Undesirable alterations in lipids have been observed in olanzapine-treated patients in placebo-controlled clinical trials (see section 4.8). Lipid alterations should be managed as clinically appropriate, particularly in dyslipidemic patients and in patients with risk factors for the development of lipids disorders. Patients treated with any antipsychotic agents, including ZYPREXA/ZYPREXA VELOTAB, should be monitored regularly for lipids in accordance with utilised antipsychotic guidelines, e.g., at baseline, 12 weeks after starting olanzapine treatment and every 5 years thereafter.

Anticholinergic activity

While olanzapine demonstrated anticholinergic activity in vitro, experience during the clinical trials revealed a low incidence of related events. However, as clinical experience with olanzapine in patients with concomitant illness is limited, caution is advised when prescribing for patients with prostatic hypertrophy, or paralytic ileus and related conditions.

Hepatic function

Transient, asymptomatic elevations of hepatic aminotransferases, alanine transferase (ALT), aspartate transferase (AST) have been seen commonly, especially in early treatment. Caution should be exercised and follow-up organised in patients with elevated ALT and/or AST, in patients with signs and symptoms of hepatic impairment, in patients with pre-existing conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic medicines. In cases where hepatitis (including hepatocellular, cholestatic or mixed liver injury) has been diagnosed, olanzapine treatment should be discontinued.

Neutropenia

Caution should be exercised in patients with low leucocyte and/or neutrophil counts for any reason, in patients receiving medicines known to cause neutropenia, in patients with a history of drug-induced bone marrow depression/toxicity, in patients with bone marrow depression caused by concomitant illness, radiation therapy or chemotherapy and in patients with hypereosinophilic conditions or with myeloproliferative disease. Neutropenia has been reported commonly when olanzapine and valproate are used concomitantly (see section 4.8).

Discontinuation of treatment

Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea, or vomiting have been reported very rarely (<0.01%) when olanzapine is stopped abruptly.

QT interval

In clinical trials, clinically meaningful QTc prolongations (Fridericia QT correction [QTcF]

Thromboembolism

Temporal association of olanzapine treatment and venous thromboembolism has been reported uncommonly (

General CNS activity

Given the primary CNS effects of olanzapine, caution should be used when it is taken in combination with other centrally acting medicines and alcohol. As it exhibits in vitro dopamine antagonism, olanzapine may antagonise the effects of direct and indirect dopamine agonists.

Seizures

Olanzapine should be used cautiously in patients who have a history of seizures or are subject to factors which may lower the seizure threshold. Seizures have been reported to occur rarely in patients when treated with olanzapine. In most of these cases, a history of seizures or risk factors for seizures were reported.

Tardive dyskinesia

In comparator studies of one year or less duration, olanzapine was associated with a statistically significant lower incidence of treatment-emergent dyskinesia. However, the risk of tardive dyskinesia increases with long-term exposure, and therefore if signs or symptoms of tardive dyskinesia appear in a patient on olanzapine, a dose reduction or discontinuation should be considered. These symptoms can temporally deteriorate or even arise after discontinuation of treatment.

Postural hypotension

Postural hypotension was infrequently observed in the elderly in olanzapine clinical trials. As with other antipsychotics, it is recommended that blood pressure is measured periodically in patients over 65 years.

Sudden cardiac death

In postmarketing reports with olanzapine, the event of sudden cardiac death has been reported in patients with olanzapine. In a retrospective observational cohort study, the risk of presumed sudden cardiac death in patients treated with olanzapine was approximately twice the risk in patients not using antipsychotics. In the study, the risk of olanzapine was comparable to the risk of atypical antipsychotics included in a pooled analysis.

Paediatric population

Olanzapine is not indicated for use in the treatment of children and adolescents. Studies in patients aged 13-17 years showed various adverse reactions, including weight gain, changes in metabolic parameters and increases in prolactin levels. Long-term outcomes associated with these events have not been studied and remain unknown (see sections 4.8 and 5.1).

Phenylalanine

ZYPREXA VELOTAB orodispersible tablet contains aspartame, which is a source of phenylalanine. May be harmful for people with phenylketonuria.

Mannitol

ZYPREXA VELOTAB orodispersible tablet contains mannitol.

Sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate

Olanzapine orodispersible tablet contains sodium methyl parahydroxybenzoate and sodium propyl parahydroxybenzoate. These preservatives are known to cause urticaria. Generally, delayed type reactions such as contact dermatitis may occur, but rarely, immediate reactions with bronchospasm may occur.

Lactose

ZYPREXA tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Paediatric population

Interaction studies have only been performed in adults.

Potential Interactions Affecting Olanzapine

Since olanzapine is metabolised by CYP1A2, substances that can specifically induce or inhibit this isoenzyme may affect the pharmacokinetics of olanzapine.

Induction of CYP1A2

The metabolism of olanzapine may be induced by smoking and carbamazepine, which may lead to reduced olanzapine concentrations. Only slight to moderate increase in olanzapine clearance has been observed. The clinical consequences are likely to be limited, but clinical monitoring is recommended and an increase of olanzapine dose may be considered if necessary (see section 4.2).

Inhibition of CYP1A2

Fluvoxamine, a specific CYP1A2 inhibitor, has been shown to significantly inhibit the metabolism of olanzapine. The mean increase in olanzapine C_max following fluvoxamine was 54% in female non-smokers and 77% in male smokers. The mean increase in olanzapine AUC was 52% and 108%, respectively. A lower starting dose of olanzapine should be considered in patients who are using fluvoxamine or any other CYP1A2 inhibitors, such as ciprofloxacin. A decrease in the dose of olanzapine should be considered if treatment with an inhibitor of CYP1A2 is initiated.

Decreased bioavailability

Activated charcoal reduces the bioavailability of oral olanzapine by 50 to 60% and should be taken at least 2 hours before or after olanzapine.

Fluoxetine (a CYP2D6 inhibitor), single doses of antacid (aluminium, magnesium) or cimetidine have not been found to significantly affect the pharmacokinetics of olanzapine.

Potential for Olanzapine to Affect Other Medicinal Products

Olanzapine may antagonise the effects of direct and indirect dopamine agonists.

Olanzapine does not inhibit the main CYP450 isoenzymes in vitro (e.g., 1A2, 2D6, 2C9, 2C19, 3A4). Thus, no particular interaction is expected, as verified through in vivo studies, where no inhibition of metabolism of the following active substances was found: tricyclic antidepressant (representing mostly CYP2D6 pathway), warfarin (CYP2C9), theophylline (CYP1A2), or diazepam (CYP3A4 and 2C19).

Olanzapine showed no interaction when co-administered with lithium or biperiden.

Therapeutic monitoring of valproate plasma levels did not indicate that valproate dosage adjustment is required after the introduction of concomitant olanzapine.

General CNS activity

Caution should be exercised in patients who consume alcohol or receive medicinal products that can cause central nervous system depression.

The concomitant use of olanzapine with anti-Parkinsonian medicinal products in patients with Parkinson's disease and dementia is not recommended (see section 4.4).

QTc interval

Caution should be used if olanzapine is being administered concomitantly with medicinal products known to increase QTc interval (see section 4.4).

4.6 Pregnancy And Lactation

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with olanzapine. Nevertheless, because human experience is limited, olanzapine should be used in pregnancy only if the potential benefit justifies the potential risk to the foetus.

Neonates exposed to antipsychotics (including olanzapine) during the third trimester of pregnancy are at risk of adverse reactions including extrapyramidal and/or withdrawal symptoms that may vary in severity and duration following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, or feeding disorder. Consequently, newborns should be monitored carefully.

Breast feeding

In a study in breast feeding, healthy women, olanzapine was excreted in breast milk. Mean infant exposure (mg/kg) at steady-state was estimated to be 1.8% of the maternal olanzapine dose (mg/kg). Patients should be advised not to breast feed an infant if they are taking olanzapine.

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed. Because olanzapine may cause somnolence and dizziness, patients should be cautioned about operating machinery, including motor vehicles.

4.8 Undesirable Effects

Adults

The most frequently (seen in

The following table lists the adverse reactions and laboratory investigations observed from spontaneous reporting and in clinical trials. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very common (

Very common	Common	Uncommon	Not known
Blood and the lymphatic system disorders
	Eosinophilia	Leucopenia Neutropenia	Thrombocytopenia
Immune system disorders
			Allergic reaction
Metabolism and nutrition disorders
Weight gain1	Elevated cholesterol levels2,3 Elevated glucose levels4 Elevated triglyceride levels2,5 Glucosuria Increased appetite		Development or exacerbation of diabetes occasionally associated with ketoacidosis or coma, including some fatal cases (see section 4.4) Hypothermia
Nervous system disorders
Somnolence	Dizziness Akathisia6 Parkinsonism6 Dyskinesia6		Seizures where in most cases a history of seizures or risk factors for seizures were reported Neuroleptic malignant syndrome (see section 4.4) Dystonia (including oculogyration) Tardive dyskinesia Discontinuation symptoms7
Cardiac disorders
		Bradycardia QTc prolongation (see section 4.4)	Ventricular tachycardia/fibrillation, sudden death (see section 4.4)
Vascular disorders
	Orthostatic hypotension		Thromboembolism (including pulmonary embolism and deep vein thrombosis) (see section 4.4)
Gastrointestinal disorders
	Mild, transient anticholinergic effects including constipation and dry mouth		Pancreatitis
Hepato-biliary disorders
	Transient, asymptomatic elevations of hepatic aminotransferases (ALT, AST), especially in early treatment (see section 4.4)		Hepatitis (including hepatocellular, cholestatic or mixed liver injury)
Skin and subcutaneous tissue disorders
	Rash	Photosensitivity reaction Alopecia
Musculoskeletal and connective tissue disorders
			Rhabdomyolysis
Renal and urinary disorders
		Urinary incontinence	Urinary hesitation
Pregnancy, puerperium and perinatal conditions
			Drug withdrawal syndrome neonatal (see section 4.6)
Reproductive system and breast disorders
			Priapism
General disorders and administration site conditions
	Asthenia Fatigue Oedema
Investigations
Elevated plasma prolactin levels8		High creatine phosphokinase Increased total bilirubin	Increased alkaline phosphatase

¹Clinically significant weight gain was observed across all baseline Body Mass Index (BMI) categories. Following short-term treatment (median duration 47 days), weight gain

²Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline.

³Observed for fasting normal levels at baseline (< 5.17 mmol/l) which increased to high (

⁴Observed for fasting normal levels at baseline (< 5.56 mmol/l) which increased to high (

⁵Observed for fasting normal levels at baseline (< 1.69 mmol/l) which increased to high (

⁶In clinical trials, the incidence of Parkinsonism and dystonia in olanzapine-treated patients was numerically higher, but not statistically significantly different from placebo. Olanzapine-treated patients had a lower incidence of Parkinsonism, akathisia and dystonia compared with titrated doses of haloperidol. In the absence of detailed information on the pre-existing history of individual acute and tardive extrapyramidal movement disorders, it can not be concluded at present that olanzapine produces less tardive dyskinesia and/or other tardive extrapyramidal syndromes.

⁷Acute symptoms such as sweating, insomnia, tremor, anxiety, nausea and vomiting have been reported when olanzapine is stopped abruptly.

⁸ In clinical trials of up to 12 weeks, plasma prolactin concentrations exceeded the upper limit of normal range in approximately 30% of olanzapine-treated patients with normal baseline prolactin value. In the majority of these patients the elevations were generally mild, and remained below two times the upper limit of normal range. Generally in olanzapine-treated patients potentially associated breast- and menstrual-related clinical manifestations (e.g., amenorrhoea, breast enlargement, galactorrhea in females, and gynaecomastia/breast enlargement in males) were uncommon. Potentially associated sexual function-related adverse reactions (e.g., erectile dysfunction in males and decreased libido in both genders) were commonly observed.

Long-term exposure (at least 48 weeks)

The proportion of patients who had adverse, clinically significant changes in weight gain, glucose, total/LDL/HDL cholesterol or triglycerides increased over time. In adult patients who completed 9-12 months of therapy, the rate of increase in mean blood glucose slowed after approximately 6 months.

Additional information on special populations

In clinical trials in elderly patients with dementia, olanzapine treatment was associated with a higher incidence of death and cerebrovascular adverse reactions compared to placebo (see also section 4.4). Very common adverse reactions associated with the use of olanzapine in this patient group were abnormal gait and falls. Pneumonia, increased body temperature, lethargy, erythema, visual hallucinations and urinary incontinence were observed commonly.

In clinical trials in patients with drug-induced (dopamine agonist) psychosis associated with Parkinson's disease, worsening of Parkinsonian symptomatology and hallucinations were reported very commonly and more frequently than with placebo.

In one clinical trial in patients with bipolar mania, valproate combination therapy with olanzapine resulted in an incidence of neutropenia of 4.1%; a potential contributing factor could be high plasma valproate levels. Olanzapine administered with lithium or valproate resulted in increased levels (

Paediatric population

Olanzapine is not indicated for the treatment of children and adolescent patients below 18 years. Although no clinical studies designed to compare adolescents to adults have been conducted, data from the adolescent trials were compared to those of the adult trials.

The following table summarises the adverse reactions reported with a greater frequency in adolescent patients (aged 13-17 years) than in adult patients or adverse reactions only identified during short-term clinical trials in adolescent patients. Clinically significant weight gain (

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The frequency terms listed are defined as follows: Very common (

Metabolism and nutrition disorders Very common: Weight gain9, elevated triglyceride levels10, increased appetite. Common: Elevated cholesterol levels11.

Nervous system disorders Very common: Sedation (including: hypersomnia, lethargy, somnolence).

Gastrointestinal disorders Common: Dry mouth.

Hepato-biliary disorders Very common: Elevations of hepatic aminotransferases (ALT/AST; see section 4.4).

Investigations Very common: Decreased total bilirubin, increased GGT, elevated plasma prolactin levels12.

⁹Following short-term treatment (median duration 22 days), weight gain

¹⁰Observed for fasting normal levels at baseline (< 1.016 mmol/l) which increased to high (

¹¹Changes in total fasting cholesterol levels from normal at baseline (< 4.39 mmol/l) to high (

¹²Elevated plasma prolactin levels were reported in 47.4% of adolescent patients.

4.9 Overdose

Signs and Symptoms

Very common symptoms in overdose (>10% incidence) include tachycardia, agitation/aggressiveness, dysarthria, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma.

Other medically significant sequelae of overdose include delirium, convulsion, coma, possible neuroleptic malignant syndrome, respiratory depression, aspiration, hypertension or hypotension, cardiac arrhythmias (<2% of overdose cases), and cardiopulmonary arrest. Fatal outcomes have been reported for acute overdoses as low as 450 mg, but survival has also been reported following acute overdose of approximately 2 g of oral olanzapine.

Management of Overdose

There is no specific antidote for olanzapine. Induction of emesis is not recommended. Standard procedures for management of overdose may be indicated (i.e., gastric lavage, administration of activated charcoal). The concomitant administration of activated charcoal was shown to reduce the oral bioavailability of olanzapine by 50 to 60%.

Symptomatic treatment and monitoring of vital organ function should be instituted according to clinical presentation, including treatment of hypotension and circulatory collapse and support of respiratory function. Do not use epinephrine, dopamine, or other sympathomimetic agents with beta-agonist activity, since beta stimulation may worsen hypotension. Cardiovascular monitoring is necessary to detect possible arrhythmias. Close medical supervision and monitoring should continue until the patient recovers.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Diazepines, oxazepines and thiazepines. ATC code: N05A H03.

Olanzapine is an antipsychotic, antimanic, and mood stabilising agent that demonstrates a broad pharmacologic profile across a number of receptor systems.

In preclinical studies, olanzapine exhibited a range of receptor affinities (K_i <100nM) for serotonin 5HT_2A/2C, 5HT₃, 5HT₆; dopamine D₁, D₂, D₃, D₄, D₅; cholinergic muscarinic receptors M₁-M₅; α₁ adrenergic; and histamine H₁ receptors. Animal behavioural studies with olanzapine indicated 5HT, dopamine, and cholinergic antagonism, consistent with the receptor-binding profile. Olanzapine demonstrated a greater in vitro affinity for serotonin 5HT₂ than dopamine D₂ receptors and greater 5HT₂ than D₂ activity in in vivo models. Electrophysiological studies demonstrated that olanzapine selectively reduced the firing of mesolimbic (A10) dopaminergic neurons, while having little effect on the striatal (A9) pathways involved in motor function. Olanzapine reduced a conditioned avoidance response, a test indicative of antipsychotic activity, at doses below those producing catalepsy, an effect indicative of motor side-effects. Unlike some other antipsychotic agents, olanzapine increases responding in an 'anxiolytic' test.

In a single oral dose (10 mg) Positron Emission Tomography (PET) study in healthy volunteers, olanzapine produced a higher 5HT_2A than dopamine D₂ receptor occupancy. In addition, a Single Photon Emission Computed Tomography (SPECT) imaging study in schizophrenic patients revealed that olanzapine-responsive patients had lower striatal D₂ occupancy than some other antipsychotic- and risperidone-responsive patients, while being comparable to clozapine-responsive patients.

In two of two placebo- and two of three comparator-controlled trials with over 2,900 schizophrenic patients presenting with both positive and negative symptoms, olanzapine was associated with statistically significantly greater improvements in negative as well as positive symptoms.

In a multinational, double-blind, comparative study of schizophrenia, schizoaffective and related disorders, which included 1,481 patients with varying degrees of associated depressive symptoms (baseline mean of 16.6 on the Montgomery-Asberg Depression Rating Scale), a prospective secondary analysis of baseline to endpoint mood score change demonstrated a statistically significant improvement (P = 0.001) favouring olanzapine (-6.0) versus haloperidol (-3.1).

In patients with a manic or mixed episode of bipolar disorder, olanzapine demonstrated superior efficacy to placebo and valproate semisodium (divalproex) in reduction of manic symptoms over 3 weeks. Olanzapine also demonstrated comparable efficacy results to haloperidol in terms of the proportion of patients in symptomatic remission from mania and depression at 6 and 12 weeks. In a co-therapy study of patients treated with lithium or valproate for a minimum of 2 weeks, the addition of olanzapine 10 mg (co-therapy with lithium or valproate) resulted in a greater reduction in symptoms of mania than lithium or valproate monotherapy after 6 weeks.

In a 12-month recurrence prevention study in manic episode patients who achieved remission on olanzapine and were then randomised to olanzapine or placebo, olanzapine demonstrated statistically significant superiority over placebo on the primary endpoint of bipolar recurrence. Olanzapine also showed a statistically significant advantage over placebo in terms of preventing either recurrence into mania or recurrence into depression.

In a second 12-month recurrence prevention study in manic episode patients who achieved remission with a combination of olanzapine and lithium and were then randomised to olanzapine or lithium alone, olanzapine was statisti

Dexavetaderm

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• Slovenia

Gestodene

Gestodene is reported as an ingredient of Logest in the following countries:

• Croatia (Hrvatska)


• Czech Republic


• Estonia


• Latvia


• Lithuania


• Slovakia


• Slovenia

International Drug Name Search

Canibioprim

Canibioprim may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for Canibioprim

Sulfamethoxazole

Sulfamethoxazole is reported as an ingredient of Canibioprim in the following countries:

• France

Trimethoprim

Trimethoprim is reported as an ingredient of Canibioprim in the following countries:

• France

International Drug Name Search

Cytra-2

Generic Name: citric acid and sodium citrate (SIT rik AS id and SOE dee um SIT rayt)

Brand Names: Bicitra, Cytra-2, Liqui-Dual Citra, Oracit

What is Cytra-2 (citric acid and sodium citrate)?

Citric acid and sodium citrate are both alkalinizing agents that make the urine less acidic.

The combination of citric acid and sodium citrate is used to prevent gout or kidney stones, or metabolic acidosis in people with kidney problems.

Citric acid and sodium citrate may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Cytra-2 (citric acid and sodium citrate)?

You should not use this medication if you have kidney failure, severe heart damage (such as from a prior heart attack), Addison's disease (an adrenal gland disorder), high levels of potassium in your blood (hyperkalemia), or if you are severely dehydrated or have heat cramps.

Before you take citric acid and sodium citrate, tell your doctor about all your medical conditions, especially kidney disease, heart disease, high blood pressure, a history of heart attack, urinary problems, swelling (edema), or chronic diarrhea (such as ulcerative colitis, Crohn's disease).

Also tell your doctor about all other medications you use, including over-the-counter medications and household remedies.

Citric acid and sodium citrate should be taken after meals to help prevent stomach or intestinal side effects.

The liquid medicine should be mixed with water or juice. Drink plenty of liquids while you are taking citric acid and sodium citrate. Your treatment may include a special diet. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

Avoid using antacids without your doctor's advice, including household baking soda (sodium bicarbonate). Antacids that contain aluminum or sodium can interact with citric acid and sodium citrate, causing a serious electrolyte imbalance or aluminum toxicity.

Avoid eating foods that are high in salt, or using extra table salt on your meals.

To be sure citric acid and sodium citrate is helping your condition, your blood and urine may need to be tested often. Follow your doctor's instructions carefully and do not miss any scheduled appointments.

Serious side effects of citric acid and sodium citrate include muscle twitching or cramps, swelling or weight gain, weakness, mood changes, rapid and shallow breathing, fast heart rate, restless feeling, black or bloody stools, severe diarrhea, or seizure (convulsions).

What should I discuss with my healthcare provider before taking Cytra-2 (citric acid and sodium citrate)?

You should not use this medication if you are allergic to it, or if you have:

• 
  

  kidney failure;

  
  


• 
  

  severe heart damage (such as from a prior heart attack);

  
  


• 
  

  Addison's disease (an adrenal gland disorder);

  
  


• 
  

  high levels of potassium in your blood (hyperkalemia); or

  
  


• 
  

  if you are severely dehydrated or have heat cramps.

  
  

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before you take citric acid and sodium citrate, tell your doctor if you have:

• kidney disease;


• 
  

  congestive heart failure, enlarged heart, or history of heart attack;

  
  


• 
  

  other heart disease or high blood pressure;

  
  


• 
  

  low levels of calcium in your blood (hypocalcemia);

  
  


• 
  

  a urinary tract infection;

  
  


• 
  

  toxemia of pregnancy;

  
  


• 
  

  urination problems (or if you are unable to urinate);

  
  


• 
  

  swelling of your hands or feet, or in your lungs (pulmonary edema); or

  
  


• 
  

  chronic diarrhea (such as ulcerative colitis, Crohn's disease).

  
  

It is not known whether this medication is harmful to an unborn baby. Before taking citric acid and sodium citrate, Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether citric acid and sodium citrate passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take Cytra-2 (citric acid and sodium citrate)?

Take this medication exactly as prescribed by your doctor. Do not take it in larger amounts or for longer than recommended. Follow the directions on your prescription label.

Citric acid and sodium citrate should be taken after meals to help prevent stomach or intestinal side effects. You may also need to take the medicine at bedtime. Follow your doctor's instructions.

Shake the oral solution (liquid) well just before you measure a dose. To be sure you get the correct dose, measure the liquid with a marked measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. The liquid medicine should be mixed with at lease 4 ounces of water or juice. Drink this mixture slowly and then add a little more water to the same glass, swirl gently and drink right away. You may chill the mixed medicine to make it taste better, but do not allow it to freeze.

Drink plenty of liquids while you are taking citric acid and sodium citrate.

Your treatment may include a special diet. It is very important to follow the diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

To be sure citric acid and sodium citrate is helping your condition, your blood and urine may need to be tested often. Follow your doctor's instructions carefully and do not miss any scheduled appointments.

Store citric acid and sodium citrate at room temperature away from moisture, heat, or freezing. Keep the medication in a closed container.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If you are more than 2 hours late in taking your medicine, wait until your next regularly scheduled time to take the medicine and skip the missed dose. Do not take 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 muscle spasms or seizure (convulsions).

What should I avoid while taking Cytra-2 (citric acid and sodium citrate)?

Avoid using antacids without your doctor's advice, including household baking soda (sodium bicarbonate). Antacids that contain aluminum or sodium can interact with citric acid and sodium citrate, causing a serious electrolyte imbalance or aluminum toxicity.

Avoid eating foods that are high in salt, or using extra table salt on your meals.

It is very important to follow any diet plan created for you by your doctor or nutrition counselor. You should become very familiar with the list of foods you should eat or avoid to help control your condition.

Cytra-2 (citric acid and sodium citrate) 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. Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  swelling, tingling, or numbness in your hands or feet;

  
  


• 
  

  muscle twitching or pain, leg pain or cramps;

  
  


• 
  

  unusual weakness, rapid and shallow breathing, fast or slow heart rate, dizziness, confusion, or mood changes;

  
  


• 
  

  feeling restless, nervous, or irritable;

  
  


• 
  

  black, bloody, or tarry stools;

  
  


• 
  

  severe or ongoing diarrhea; or

  
  


• 
  

  seizure (convulsions).

  
  

Less serious side effects may include:

• 
  

  nausea, or vomiting, stomach pain;

  
  


• 
  

  mild or occasional diarrhea; or

  
  


• 
  

  mild stomach pain.

  
  

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 Cytra-2 (citric acid and sodium citrate)?

The following drugs can interact with citric acid and sodium citrate. Tell your doctor if you are using any of these:

• 
  

  lithium (Eskalith, LithoBid);

  
  


• 
  

  methenamine (Hiprex, Mandelamine, Urex),

  
  


• 
  

  quinidine (Quinaglute, Quinidex, Quin-Release);

  
  


• 
  

  cold or allergy medicine (decongestants), diet pills, ADHD medication;

  
  


• 
  

  a vitamin, mineral supplement, or medication that contains calcium;

  
  


• 
  

  salicylates such as aspirin, Backache Relief Extra Strength, Novasal, Nuprin Backache Caplet, Doan's Pills Extra Strength, Tricosal, and others; or

  
  


• 
  

  an antacid that contains aluminum or sodium, including Alka-Seltzer, Maalox, Mylanta, Di-Gel, Gelusil, Alamag Plus, Rulox Plus, Tempo, and others.

  
  

This list is not complete and there may be other drugs that can interact with citric acid and sodium citrate. 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 Cytra-2 resources

• Cytra-2 Side Effects (in more detail)
• Cytra-2 Use in Pregnancy & Breastfeeding
• Cytra-2 Drug Interactions
• Cytra-2 Support Group
• 0 Reviews for Cytra-2 - Add your own review/rating

• Cytra-2 MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Cytra-2 with other medications

• Urinary Alkalinization
• Urinary Tract Stones

Where can I get more information?

• Your pharmacist can provide more information about citric acid and sodium citrate.

See also: Cytra-2 side effects (in more detail)

DolipraneOro

DolipraneOro may be available in the countries listed below.

Ingredient matches for DolipraneOro

Paracetamol

Paracetamol is reported as an ingredient of DolipraneOro in the following countries:

• France

International Drug Name Search

Doan's

Ingredient matches for Doan's

Salicylic Acid

Salicylic Acid magnesium (a derivative of Salicylic Acid) is reported as an ingredient of Doan's in the following countries:

• United States

International Drug Name Search

Monovit D3

Monovit D3 may be available in the countries listed below.

Ingredient matches for Monovit D3

Colecalciferol

Colecalciferol is reported as an ingredient of Monovit D3 in the following countries:

• Turkey

International Drug Name Search

Paracetamol Sopharma

Paracetamol Sopharma may be available in the countries listed below.

Ingredient matches for Paracetamol Sopharma

Paracetamol

Paracetamol is reported as an ingredient of Paracetamol Sopharma in the following countries:

• Lithuania

International Drug Name Search

Daewoong Lanfra

Daewoong Lanfra may be available in the countries listed below.

Ingredient matches for Daewoong Lanfra

Lansoprazole

Lansoprazole is reported as an ingredient of Daewoong Lanfra in the following countries:

• Vietnam

International Drug Name Search

Doloctaprin

Doloctaprin may be available in the countries listed below.

Ingredient matches for Doloctaprin

Orphenadrine

Orphenadrine is reported as an ingredient of Doloctaprin in the following countries:

• Peru

International Drug Name Search

Pentothal

In some countries, this medicine may only be approved for veterinary use.

In the US, Pentothal (thiopental systemic) is a member of the drug class general anesthetics and is used to treat Anesthesia, Anesthetic Adjunct, Coma Induction, Psychosis and Seizures.

US matches:

• Pentothal

Ingredient matches for Pentothal

Thiopental

Thiopental Sodium is reported as an ingredient of Pentothal in the following countries:

• Australia


• Belgium


• Canada


• Denmark


• Indonesia


• Israel


• Italy


• Luxembourg


• Norway


• Switzerland


• Taiwan


• Thailand


• United States

International Drug Name Search

Divascan

Divascan may be available in the countries listed below.

Ingredient matches for Divascan

Iprazochrome

Iprazochrome is reported as an ingredient of Divascan in the following countries:

• Hungary


• Poland

International Drug Name Search

Dolofenac

Dolofenac may be available in the countries listed below.

Ingredient matches for Dolofenac

Diclofenac

Diclofenac is reported as an ingredient of Dolofenac in the following countries:

• Peru

International Drug Name Search

Caffeine/Ergotamine Suppositories

Pronunciation: ka-FEEN/er-GOT-a-meen
Generic Name: Caffeine/Ergotamine
Brand Name: Examples include Cafergot and Migergot

Serious and sometimes life-threatening decreases in the blood supply to the extremities (eg, hands, feet) or brain may occur if Caffeine/Ergotamine Suppositories are taken with certain other medicines, including HIV protease inhibitors (eg, ritonavir) and macrolide antibiotics (eg, erythromycin). Do not use Caffeine/Ergotamine Suppositories if you are also taking these other medicines. Inform your doctor of all the medicines that you are taking.

Caffeine/Ergotamine Suppositories are used for:

Preventing and treating certain kinds of headaches (eg, migraines, migraine variants, "histaminic cephalalgia"). It may also be used for other conditions as determined by your doctor.

Caffeine/Ergotamine Suppositories are a combination of 2 vasoconstrictors. It works by constricting blood vessels in the lining of the brain, which helps to decrease the pain from migraine headaches.

Do NOT use Caffeine/Ergotamine Suppositories if:

• you are allergic to any ingredient in Caffeine/Ergotamine Suppositories


• you are pregnant or may become pregnant


• you are in labor


• you have blood vessel problems (eg, peripheral vascular disease), coronary heart disease, high blood pressure, liver or kidney problems, or severe infection (eg, sepsis)


• you are taking an azole antifungal (eg, itraconazole, ketoconazole, voriconazole), delavirdine, HIV protease inhibitors (eg, delavirdine, indinavir, nelfinavir, ritonavir), efavirenz, a ketolide antibiotic (eg, telithromycin), a macrolide antibiotic (eg, clarithromycin, erythromycin), or selective 5-HT agonists (eg, sumatriptan, eletriptan)

Contact your doctor or health care provider right away if any of these apply to you.

Before using Caffeine/Ergotamine Suppositories:

Some medical conditions may interact with Caffeine/Ergotamine Suppositories. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are planning to become pregnant or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have a history of blood problems (eg, porphyria), stroke, anxiety, trouble sleeping, or heart problems


• if you smoke

Some MEDICINES MAY INTERACT with Caffeine/Ergotamine Suppositories. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Clotrimazole, fluconazole, fluoxetine, fluvoxamine, metronidazole, nefazodone, saquinavir, or zileuton because side effects of Caffeine/Ergotamine Suppositories may be increased


• Azole antifungals (eg, itraconazole, ketoconazole, voriconazole), beta-blockers (eg, propranolol), delavirdine, HIV protease inhibitors (eg, delavirdine, indinavir, nelfinavir, ritonavir), efavirenz, ketolide antibiotics (eg, telithromycin), macrolide antibiotics (eg, erythromycin, clarithromycin), or selective 5-HT agonists (eg, sumatriptan, eletriptan) because the risk of severe side effects, including irregular heartbeat or decreased oxygen to the extremities (eg, hands, feet) or brain, may be increased


• Pressor agents (eg, norepinephrine) or sympathomimetics (eg, pseudoephedrine, albuterol) because risk of side effects, including severe high blood pressure, may be increased


• Quinolones (eg, levofloxacin) because risk of side effects, such as nervousness, sleeplessness, and fast heartbeat, may be increased


• Theophylline because actions and side effects may be increased by Caffeine/Ergotamine Suppositories

This may not be a complete list of all interactions that may occur. Ask your health care provider if Caffeine/Ergotamine Suppositories may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Caffeine/Ergotamine Suppositories:

Use Caffeine/Ergotamine Suppositories as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Caffeine/Ergotamine Suppositories may be taken with or without food.


• Eating grapefruit or drinking grapefruit juice may affect the amount of Caffeine/Ergotamine Suppositories in your blood. Talk with your doctor before including grapefruit or grapefruit juice in your diet.


• Caffeine/Ergotamine Suppositories are only to be used as needed for a migraine attack.


• Use Caffeine/Ergotamine Suppositories at the first sign of a headache. Remove the wrapper and moisten the suppository with cool water. Lie down on your side. Insert the pointed end of the suppository into the rectum, then use your finger to push it in completely. Wash your hands thoroughly after using Caffeine/Ergotamine Suppositories.


• If the suppository has softened because of a period of unavoidable exposure to heat, place in the refrigerator for about 15 minutes or chill in ice cold water before removing the wrapper.


• If the initial dose does not relieve your headache, an additional dose may be needed according to your doctor's instructions. Do not use a dose of Caffeine/Ergotamine Suppositories within 1 hour of your last dose.


• Do not use more than 2 suppositories for a single migraine headache or more than 5 suppositories during any 7-day period without first checking with your doctor.


• If you miss a dose of Caffeine/Ergotamine Suppositories and you still have a headache, use it as soon as you remember. Do not use a dose of Caffeine/Ergotamine Suppositories within 1 hour of your last dose. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Caffeine/Ergotamine Suppositories.

Important safety information:

• Do NOT exceed the recommended dose or use Caffeine/Ergotamine Suppositories for longer than prescribed without checking with your doctor. Caffeine/Ergotamine Suppositories are not for long-term daily use.


• Do not use Caffeine/Ergotamine Suppositories for any other kind of headaches. Caffeine/Ergotamine Suppositories are not effective in treating other types of headaches.


• Use of nicotine may increase the risk of severe side effects with Caffeine/Ergotamine Suppositories. Talk to you doctor before using Caffeine/Ergotamine Suppositories if you smoke or use any other kind of nicotine.


• Use Caffeine/Ergotamine Suppositories with extreme caution in CHILDREN. Safety and effectiveness have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Do not use Caffeine/Ergotamine Suppositories if you are pregnant. If you suspect that you could be pregnant, contact your doctor immediately. Caffeine/Ergotamine Suppositories should not be used during labor and delivery. Caffeine/Ergotamine Suppositories are excreted in breast milk. If you are or will be breast-feeding while you are using Caffeine/Ergotamine Suppositories, check with your doctor or pharmacist to discuss the risks to your baby.

When used for long periods of time or at high doses, some people develop a need to continue taking Caffeine/Ergotamine Suppositories. This is known as DEPENDENCE or addiction. It is important that you take Caffeine/Ergotamine Suppositories as instructed by your doctor. Caffeine/Ergotamine Suppositories are not for long-term daily use.

Possible side effects of Caffeine/Ergotamine Suppositories:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Nausea.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blue color of the fingers or toes; chest pain or tightness; cold or pale fingers or toes; diarrhea; dizziness; hallucinations; headache; irregular heartbeat; leg cramps or weakness; mental or mood changes; muscle pain; numbness or tingling of the hands, feet, or skin; rectal sores; ringing in the ears; seizure; severe or persistent nausea or vomiting; shortness of breath; swelling; temporary fast or slow heartbeat; vomiting; weak pulse.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Caffeine/Ergotamine side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include chest pain; coma; diarrhea; difficulty breathing; drowsiness; numbness, coldness, pain, tingling, or blue color of the extremities; seizures; severe headache or dizziness; shock; vomiting; weak pulse.

Proper storage of Caffeine/Ergotamine Suppositories:

Store Caffeine/Ergotamine Suppositories in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Caffeine/Ergotamine Suppositories out of the reach of children and away from pets.

General information:

• If you have any questions about Caffeine/Ergotamine Suppositories, please talk with your doctor, pharmacist, or other health care provider.


• Caffeine/Ergotamine Suppositories are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Caffeine/Ergotamine Suppositories. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Caffeine/Ergotamine resources

• Caffeine/Ergotamine Side Effects (in more detail)
• Caffeine/Ergotamine Use in Pregnancy & Breastfeeding
• Drug Images
• Caffeine/Ergotamine Drug Interactions
• Caffeine/Ergotamine Support Group
• 12 Reviews for Caffeine/Ergotamine - Add your own review/rating

Compare Caffeine/Ergotamine with other medications

• Cluster Headaches
• Migraine

Cefteram Pivoxil

Cefteram Pivoxil may be available in the countries listed below.

Ingredient matches for Cefteram Pivoxil

Cefteram

Cefteram Pivoxil (JAN) is also known as Cefteram (Rec.INN)

International Drug Name Search

Glossary

JAN	Japanese Accepted Name
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)

Click for further information on drug naming conventions and International Nonproprietary Names.

Diéthylstilbestrol

Diéthylstilbestrol may be available in the countries listed below.

Ingredient matches for Diéthylstilbestrol

Diethylstilbestrol

Diéthylstilbestrol (DCF) is known as Diethylstilbestrol in the US.

International Drug Name Search

Glossary

DCF	Dénomination Commune Française

Click for further information on drug naming conventions and International Nonproprietary Names.

Danilon Topico

Danilon Topico may be available in the countries listed below.

Ingredient matches for Danilon Topico

Suxibuzone

Suxibuzone is reported as an ingredient of Danilon Topico in the following countries:

• Spain

International Drug Name Search

Nicotrol NS

Generic Name: nicotine (Nasal route)

NIK-oh-teen

Commonly used brand name(s)

In the U.S.

• Nicotrol NS

Available Dosage Forms:

• Spray

Therapeutic Class: Smoking Cessation Agent

Pharmacologic Class: Cholinergic

Uses For Nicotrol NS

Nicotine in a nasal spray is used to help you stop smoking. It is used for up to 6 months as part of a stop-smoking program. This program may include counseling, education, or psychological support.

With the nasal spray, nicotine is inhaled through your nose and passes into your blood stream. This nicotine takes the place of the nicotine you would otherwise get from smoking. In this way, the withdrawal effects of not smoking are less severe. Then, as your body adjusts to not smoking, the use of nicotine nasal spray is decreased gradually over several weeks. Finally, use is stopped altogether.

Children, pregnant women, and nonsmokers should not use nicotine nasal spray because of harmful effects.

This medicine is available only with your doctor's prescription.

Before Using Nicotrol NS

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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

Because of nicotine nasal spray's toxicity, use in children is not recommended.

Geriatric

Although appropriate studies on the relationship of age to the effects of nicotine nasal spray have not been performed in the geriatric population, no geriatric-specific problems have been documented to date. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving nicotine nasal spray.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	D	Studies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding

Studies in women breastfeeding have demonstrated harmful infant effects. An alternative to this medication should be prescribed or you should stop breastfeeding while using 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 this medicine, 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 this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Clozapine

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.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergies or


• Common cold or


• Nose polyps or


• Rhinitis or


• Sinusitis—Nicotine nasal spray may not work properly.

• Asthma or other breathing problems or


• Heart attack, history of or


• Heart or blood vessel disease or


• Heart rhythm problems or


• Hypertension (high blood pressure) or


• Overactive thyroid or


• Pheochromocytoma (an adrenal problem) or


• Stomach ulcer or


• Type 1 diabetes (sugar diabetes)—Use with caution. Nicotine may make these conditions worse.

• Drug abuse or


• Drug dependence—Dependence may be more likely to develop.

• Kidney disease or


• Liver disease—Use with caution. Effects may be increased because of slower removal of the medicine from the body.

Proper Use of Nicotrol NS

Nicotine nasal spray usually comes with patient directions. Read the directions carefully before using this medicine. Ask your doctor if you have any questions.

You should stop smoking completely before you start using this medicine. If you continue to smoke during treatment, you may have an increased risk of nicotine overdose.

Use this medicine exactly as directed by your doctor. Remember that it is also important to participate in a stop-smoking program during treatment. This may make it easier for you to stop smoking.

To use the nasal spray:

• Tilt your head back slightly as you spray this medicine to your nose. Be careful not to sniff, swallow, or inhale this medicine.

Use of nicotine nasal spray may be gradually reduced by using only one half of a dose at a time or skipping doses by not using the spray every hour. You may also keep track of the number of doses and use fewer each day, or set a date to stop using nicotine nasal spray.

Dosing

The dose of this medicine 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 this medicine. 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 the nasal spray dosage form:
  
  • To help you stop smoking:
    
    • Adults—At first, 1 or 2 sprays (0.5 to 1 milligram [mg]) into each nostril every hour. The dose should then be adjusted based on the number of cigarettes you smoked each day before beginning treatment with the nasal spray and the side effects the nasal spray causes. Your doctor may increase your dose as needed. However, the total dose is usually not more than 80 sprays (40 mg).
    
    
    • Children—Use and 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

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

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Nicotrol NS

Nicotine nasal spray should not be used by people who do not smoke because they can become addicted to nicotine.

Nicotine should not be used in pregnancy. If there is a possibility you might become pregnant, you may want to use some type of birth control. If you think you may have become pregnant, stop using this medicine immediately and check with your doctor.

During the first week of use, you may have a hot, peppery feeling in the back of your throat or nose; coughing; runny nose; sneezing; or watery eyes. Do not stop using this medicine. If you continue to use nicotine nasal spray regularly, you should adjust to these effects. If these effects do not lessen after 1 week, check with your doctor.

Avoid contact with the skin, mouth, eyes, and ears . If even a small amount of nicotine nasal spray comes into contact with the skin, mouth, eyes, or ears, the affected area should be immediately rinsed with water only.

Do not use nicotine nasal spray for longer than 6 months. This may result in physical dependence on the nicotine.

Nicotine products must be kept out of the reach of children and pets. Even very small amounts of nicotine may cause poisoning in children. If a child uses nicotine nasal spray, contact your doctor or poison control center at once.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Nicotrol NS 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:

More common

• Feelings of dependence


• joint pain


• shortness of breath


• swelling of the gums, mouth, or tongue


• tightness in the chest


• tingling in the arms, legs, hands, or feet

Less common

• Burning, tingling, or prickly sensations in the nose, mouth, or head


• confusion


• difficulty with swallowing


• dryness or pain in the throat


• fast or irregular heartbeat


• muscle pain


• nasal blister or sore


• numbness of the nose or mouth

Rare

• Blood-containing blisters on the skin


• difficulty with speaking


• loss of memory


• migraine headache


• skin rash


• swelling of the feet or lower legs


• wheezing

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Cold sweat


• convulsions (seizures)


• disturbed hearing and vision


• dizziness


• drooling


• pale skin


• slow heartbeat


• tremors


• unusual tiredness or weakness


• vomiting

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

• Back pain


• constipation


• cough


• headache


• hot, peppery feeling in the back of the throat or nose


• indigestion


• nausea


• runny nose


• sneezing


• watery eyes

Less common

• Abdominal or stomach pain


• acne


• change in sense of smell or taste


• dryness, burning, itching, or irritation of the eyes


• earache


• flushing of the face


• hoarseness


• itching


• menstrual problems


• nosebleed


• passing of gas


• sinus problems


• soreness of the teeth and gums


• stuffy nose

Rare

• Changes in vision


• diarrhea


• dryness of the mouth


• hiccups


• increased amount of sputum

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.

See also: Nicotrol NS side effects (in more detail)

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