Pack Content Directory Botswana

Tuesday, 13 March 2012

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 levels^2,3 Elevated glucose levels⁴ Elevated triglyceride levels^2,5 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

Sunday, 11 March 2012

Cardioplen XL 2.5, 5, 10mg prolonged release tablets

Cardioplen XL 2.5 mg, 5 mg & 10 mg Prolonged Release Tablets

felodipine

Read all of this leaflet carefully before you start taking this medicine.

Keep this leaflet. You may need to read it again.

If you have any further questions, ask your doctor or pharmacist.

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What Cardioplen is and what it is used for
2. Before you take Cardioplen
3. How to take Cardioplen
4. Possible side effects
5. How to store Cardioplen
6. Further information

What Cardioplen is and what it is used for

Cardioplen XL Prolonged Release Tablets contain felodipine which belongs to a group of medicines called calcium-channel blockers that act on the cardiovascular system (the heart and blood vessels). Cardioplen has been prescribed by your doctor to treat your high blood pressure or to reduce the frequency of your anginal attacks. They are called prolonged release tablets because they are manufactured in a way that allows the felodipine to be released and slowly absorbed by your body over a period of several hours.

In high blood pressure, felodipine works by widening the blood vessels. This creates less resistance to the blood flow, and results in lower blood pressure, which in turn reduces the strain on your heart.

In angina, felodipine works by opening up the arteries supplying the heart muscle and this allows more blood and oxygen to reach the muscle, decreasing the chances of angina (chest pains) occurring when extra strain is placed upon the heart.

Before you take Cardioplen

Do not take Cardioplen:

if you are allergic to felodipine, other calcium-channel blockers (e.g. amlodipine, nisoldipine or nifedipine) or any of the other ingredients in Cardioplen

if you are pregnant, likely to become pregnant or are breast-feeding

if you have been told that you have a narrowing of the aortic valve in your heart

if you have experienced a collapse which was caused by a heart problem

if the severity or frequency of your angina has rapidly worsened over a matter of hours or days

if you have had a heart attack during the last month or have other severe heart problems.

Take special care with Cardioplen and always tell your doctor if:

you suffer from low blood pressure with abnormal rapid heartbeats

you have a poorly functioning left ventricle of your heart

you suffer from liver problems.

Taking other medicines

Before starting treatment, please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. If you have to go to a doctor, dentist or hospital for any reason, tell them that you are taking Cardioplen. This is especially important if you are likely to have an anaesthetic or an operation.

In particular, tell your doctor if you are taking:

cimetidine, to treat stomach ulcers

the antibiotic erythromycin, to treat bacterial infections

medicines to treat fungal infections, including itraconazole and ketoconazole

ritonavir, to treat HIV infection

tacrolimus, used after kidney or liver transplants

any other medicines to lower blood pressure

phenytoin, carbamazepine or phenobarbital, to treat seizures or epilepsy. If you are already taking any of these medicines, your doctor may prescribe higher than normal doses of Cardioplen for you to take.

Taking Cardioplen with food and drink

Do not drink grapefruit juice at the same time or soon after taking Cardioplen because grapefruit juice can increase the blood levels of felodipine and affect the way it works. It is best to take your tablets on an empty stomach or after a light meal.

Pregnancy and breast-feeding

Do not take Cardioplen if you are pregnant, trying to become pregnant or are breastfeeding.

Driving and using machines:

If you feel dizzy or extremely tired after taking Cardioplen, then do not drive or operate machinery.

Important information about some of the ingredients of Cardioplen

Cardioplen contains lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

How to take Cardioplen

Always take Cardioplen exactly as your doctor has told you to. You should check with your doctor or pharmacist if you are not sure.

The label on the carton will tell you how many tablets you should take and when. It is very important that you take your tablets regularly. Do not stop treatment even if you feel better unless told to do so by your doctor.

Cardioplen is formulated so that you only have to take your tablets once a day. It is important that you take your tablets at the same time each day, preferably in the morning on an empty stomach or after a light meal. Your tablets must be swallowed whole with a glass of water and not with grapefruit juice. Do not break or chew your tablets.

High blood pressure

Adults and the elderly: the usual dose is 5 mg once a day. Your doctor may decide to increase your dose to a maximum of 20 mg of Cardioplen once a day or prescribe another medicine to treat your high blood pressure for you to also take whilst you are taking Cardioplen.

If you are elderly, your doctor may prescribe a lower starting dose of 2.5 mg for you to take once a day.

Angina

Adults: the usual dose is 5 mg once a day. Your doctor may decide to increase your dose to a maximum of 10 mg of Cardioplen once a day.

Do not stop taking your medicine until your doctor tells you.

Children must not take this medicine.

If you take more Cardioplen than you should

If you accidentally take more Cardioplen than you should, contact your nearest casualty department or tell your doctor or pharmacist immediately. Remember to take the pack and any remaining tablets with you.

If you forget to take Cardioplen

Do not worry. Simply leave out that dose completely and then take your next dose at the right time. Do not take a double dose to make up for a missed dose.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Cardioplen can cause side effects, although not everyone gets them.

Allergic reactions, although serious, have been reported in isolated cases. If you experience any of the following, contact your doctor or casualty department immediately:

swelling of the face and throat

itchy red rash

If you experience chest pains when you first start taking Cardioplen, contact your doctor immediately.

The following side effects do not usually last long and are most likely to occur when you first start to take your medicine or if your dose has been increased. If they continue or if you are worried, contact your doctor or pharmacist immediately:

headache

palpitations

dizziness and tiredness

reddening of the skin

Also, some people experience:

swelling of the ankles

swollen gums

skin inflammation, rash or itching

skin sensitive to light

pain in joints and muscle aches

impotence

pins and needles in your toes and fingers

feeling sick

abnormal liver blood test

fainting

rapid heartbeat

swelling of the hands or feet caused by fluid build up under the skin

worsening of swollen gums. This can be prevented by careful dental hygiene.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store Cardioplen

Keep out of the reach and sight of children.

Do not store above 25°C. Store in the original packaging.

Do not use Cardioplen after the expiry date which is stated on the blister and carton. The expiry date refers to the last day of that month.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

Further Information

What Cardioplen contains:

The active substance in your tablets is felodipine. Each tablet contains 2.5 mg, 5 mg or 10 mg of felodipine.

The other ingredients are lactose monohydrate, cellulose microcrystalline, talc, hypromellose, povidone, propyl gallate, silica colloidal anhydrous, magnesium stearate, ferric oxide yellow (E172), ferric oxide red (E172), titanium dioxide (E171) and propylene glycol.

What Cardioplen looks like and the contents of the pack:

Cardioplen XL Tablets are round and biconvex in shape and are available in blister packs of 28 tablets. Each strength can be identified by its colour and marking.

2.5 mg tablets are yellow and marked with “2.5”

5 mg tablets are light pink and marked with “5”

10 mg tablets are reddish brown and marked with “10”

Marketing Authorisation Holder and Manufacturer:

The Marketing Authorisation holder and manufacturer is

Chiesi Limited

Cheadle Royal Business Park

Highfield

Cheadle

SK8 3GY

Is this leaflet hard to see or read? Phone 0161 488 5555 for help.

This leaflet was last approved in 07/2010

00271 V4/CP0025/3

Formoterol Solution

Pronunciation: for-MOE-ter-ol
Generic Name: Formoterol
Brand Name: Perforomist

Long-acting beta-agonists such as Formoterol Solution have been rarely associated with an increased risk of asthma-related death. Long-acting beta-agonists should not be used in asthma patients without another long-term asthma-control medicine (eg, inhaled corticosteroids). Formoterol Solution has not been approved to treat asthma. Safety and effectiveness of Formoterol Solution in patients with asthma have not been confirmed.

Formoterol Solution is used for:

Long-term treatment of chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It may also be used for other conditions as determined by your doctor.

Formoterol Solution is a long-acting beta-agonist bronchodilator. It works by widening the airways in the lungs, which helps you breathe more easily.

Do NOT use Formoterol Solution if:

you are allergic to any ingredient in Formoterol Solution

you are using another medicine that has a long-acting beta-agonist (eg, salmeterol) in it

you are having severe breathing problems (eg, sudden severe onset or worsening of COPD symptoms such as chest tightness, cough, shortness of breath, wheezing)

you have asthma and you are not currently using a long-term asthma-control medicine (eg, inhaled corticosteroids) or if you have asthma that is already controlled with the use of a long-term asthma-control medicine

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

Before using Formoterol Solution:

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

if you are pregnant, 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 other breathing problems (eg, asthma), diabetes, heart problems (eg, fast or irregular heartbeat, heart blood vessel problems), liver problems, high blood pressure, low blood potassium levels, seizures, or an overactive thyroid

if you have high blood or urine ketone or acid levels

if you have recently been to the emergency room for breathing problems, have a history of frequent hospitalizations for breathing problems, or have ever had a life-threatening breathing problem

if you have had an unusual reaction to a sympathomimetic medicine (eg, albuterol, pseudoephedrine), such as fast or irregular heartbeat, overexcitement, or severe trouble sleeping

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

Corticosteroids (eg, prednisone), diuretics (eg, furosemide, hydrochlorothiazide), or xanthines (eg, theophylline) because the risk of low blood potassium or irregular heartbeat may be increased

Catechol-O-methyltransferase (COMT) inhibitors (eg, entacapone), other long-acting beta-agonists (eg salmeterol), monoamine oxidase inhibitors (MAOIs) (eg, phenelzine), or tricyclic antidepressants (eg, amitriptyline) because they may increase the risk of Formoterol Solution's side effects

Beta-blockers (eg, propranolol) because they may decrease Formoterol Solution's effectiveness or worsen your condition

This may not be a complete list of all interactions that may occur. Ask your health care provider if Formoterol Solution 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 Formoterol Solution:

Use Formoterol Solution as directed by your doctor. Check the label on the medicine for exact dosing instructions.

Formoterol Solution comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Formoterol Solution refilled.

Be sure to use Formoterol Solution exactly as prescribed by your doctor. Space doses about 12 hours apart unless your doctor tells you otherwise. Do not use more than 2 vials in one day.

Formoterol Solution should only be inhaled using a nebulizer. Do not inject it or swallow it.

A health care provider will teach you how to use the nebulizer. Be sure you know what type of nebulizer to use with Formoterol Solution and how to use it. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.

Store Formoterol Solution in the original foil pouch in a dry place. Do not remove from the foil pouch or open the vial until right before use. Do not use medicine that has been stored in an open vial.

Do not use Formoterol Solution if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.

Do not mix Formoterol Solution with other medicines in your nebulizer machine.

To use Formoterol Solution, twist open the top of the vial and pour the entire contents into the nebulizer reservoir.

Connect the nebulizer reservoir to the mouthpiece or face mask. Connect the nebulizer to the compressor.

Sit in a comfortable, upright position. Place the mouthpiece in your mouth (or put on the face mask) and turn on the nebulizer.

Breathe as calmly, deeply, and evenly as possible until no more mist is formed in the nebulizer chamber (about 10 minutes).

Clean the nebulizer according to the instructions. Failure to properly clean the nebulizer could lead to bacteria entering the medicine. This may lead to an infection.

Continue to use Formoterol Solution even if you feel well. Do not miss any doses.

If you miss a dose of Formoterol Solution, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Formoterol Solution.

Important safety information:

Formoterol Solution may cause dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Formoterol Solution with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Formoterol Solution will not stop sudden symptoms of COPD once they have already started. Be sure to carry a short-acting bronchodilator inhaler (eg, albuterol) with you at all times to treat any breathing problems that may occur between doses of Formoterol Solution (eg, severe or sudden onset of wheezing or shortness of breath). If you have any questions about which medicines stop sudden symptoms, check with your doctor or pharmacist.

If you have been regularly using a short-acting bronchodilator inhaler, talk with your doctor about how to use it with Formoterol Solution. Short-acting bronchodilators are normally used with Formoterol Solution to treat breathing problems that may occur between doses.

The risk of serious heart problems (eg, irregular heartbeat) may be greater if you use Formoterol Solution in high doses. Do NOT use more than recommended dose or use more often than prescribed.

Tell your doctor at once if you notice that your short-acting bronchodilator inhaler does not work as well, if you need to use it often, or if your breathing problems get worse.

Contact your doctor or seek medical care right away if you have breathing problems that worsen quickly, or if you use your short-acting bronchodilator and do not get relief.

Talk with your doctor or pharmacist about all of your breathing medicines and how to use them. Do not start, stop, or change the dose of any breathing medicine unless your doctor tells you to.

The medicine may sometimes cause severe breathing problems right after you use a dose. If this happens, use your short-acting bronchodilator. Contact your doctor or seek other medical care at once.

Formoterol Solution may raise your blood sugar. High blood sugar may make you feel confused, drowsy, or thirsty. It can also make you flush, breathe faster, or have a fruit-like breath odor. If these symptoms occur, tell your doctor right away.

Lab tests, including lung function and blood potassium levels, may be performed while you use Formoterol Solution. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Formoterol Solution should not be used in CHILDREN; safety and effectiveness in children have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Formoterol Solution while you are pregnant. It is not known if Formoterol Solution is found in breast milk. If you are or will be breast-feeding while you use Formoterol Solution, check with your doctor. Discuss any possible risks to your baby.

Possible side effects of Formoterol Solution:

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:

Diarrhea; dizziness; dry mouth; headache; nausea; nervousness; sore throat; tiredness; tremor; trouble sleeping; vomiting.

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, tongue, or throat; unusual hoarseness); chest pain; fast or irregular heartbeat; new or worsening breathing problems (eg, increased chest tightness, coughing, shortness of breath, wheezing); severe or persistent headache, dizziness, tremor, or nervousness; severe or persistent muscle pain or cramps; symptoms of high blood sugar (eg, increased thirst, urination, or hunger; unusual weakness or drowsiness; confusion).

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: Formoterol 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; fast or irregular heartbeat; seizures; severe or persistent dizziness, dry mouth, fatigue, headache, muscle pain or cramps, nausea, nervousness, trouble sleeping, or tremors; severe or persistent symptoms of high blood sugar (eg, increased thirst, hunger, or urination; drowsiness; flushing of the skin; confusion; fruit-like breath odor).

Proper storage of Formoterol Solution:

Store Formoterol Solution in the refrigerator, between 36 and 46 degrees F (2 and 8 degrees C). Do not freeze. Unopened pouches may be stored at room temperature, between 68 and 77 degrees F (20 and 25 degrees C), for up to 3 months. If Formoterol Solution is stored at room temperature, throw it away after 3 months. Do not use Formoterol Solution if it is past the expiration date on the container. Store Formoterol Solution away from heat, moisture, and light. Keep Formoterol Solution out of the reach of children and away from pets.

General information:

If you have any questions about Formoterol Solution, please talk with your doctor, pharmacist, or other health care provider.

Formoterol Solution is 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 Formoterol Solution. 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

More Formoterol resources

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

Compare Formoterol with other medications

Asthma, Maintenance
Bronchospasm Prophylaxis
COPD, Maintenance

Saturday, 10 March 2012

treprostinil inhalation

Generic Name: treprostinil inhalation (tre PROS ti nil)

Brand Names: Tyvaso, Tyvaso Refill Kit, Tyvaso Starter Kit

What is treprostinil inhalation?

Treprostinil works by dilating (widening) blood vessels in your lungs and by keeps the platelets in your blood from coagulating (clotting) to prevent unwanted blood clots. These effects lower blood pressure in the pulmonary artery that leads from your heart to your lungs.

Treprostinil is used to treat pulmonary arterial hypertension (PAH). It improves your ability to exercise and prevents your condition from getting worse.

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

What is the most important information I should know about treprostinil inhalation?

Before using this medication, tell your doctor if you have a breathing disorder such as asthma or COPD (chronic obstructive pulmonary disease), an infection in your lungs (including pneumonia), low blood pressure, liver or kidney disease, or a bleeding or blood clotting disorder.

Treprostinil inhalation should be used only with a Tyvaso inhalation system. The inhalation system comes with patient instructions for safe and effective use. Do not use the medication at home if you do not fully understand how to use the inhalation system and properly clean it daily. Ask your doctor or pharmacist if you have any questions.

The effects of treprostinil inhalation will lessen over time between doses. Talk with your doctor if you need to time your dosing around any planned activities.

It is important to use treprostinil regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely. Make sure you have a backup inhalation system available so as not to interrupt your treatment if one system stops working.

Call your doctor if your symptoms do not improve or if they get worse.

What should I discuss with my healthcare provider before using treprostinil inhalation?

If you have certain conditions, you may need a dose adjustment or special tests to safely use this medication:

a breathing disorder such as asthma or COPD (chronic obstructive pulmonary disease);

an infection in your lungs, including pneumonia;

low blood pressure;

liver disease;

kidney disease; or

a bleeding or blood clotting disorder.

FDA pregnancy category B. It is not known whether this medication is harmful to an unborn baby. Use an effective form of birth control while you are using treprostinil inhalation. Tell your doctor if you become pregnant during treatment. It is not known whether treprostinil 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 is treprostinil inhalation given?

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

The inhalation form of treprostinil is usually given 4 times per day at evenly spaced intervals during waking hours. Each time you use the medication, you will inhale up to 9 breaths of the medication. Follow your doctor's instructions.

Your doctor may occasionally change your dose to make sure you get the best results from this medication. Most people start treatment with 1 to 3 breaths per treatment session, slowly increasing the number to 9 breaths per session.

Do not use more than 9 breaths per treatment session. Wash your hands before preparing your treprostinil doses in the inhalation system.

One ampule of treprostinil inhalation contains enough medicine for all 4 of a day's doses.

Before your first dose of each day, twist off the top of one ampule and squeeze out the entire contents into the medicine cup of the inhalation system. At the end of the day after the last dose has been given, empty and rinse out the medicine cup, even if there is still unused treprostinil left in it.

To keep the medicine in the cup from spilling, store the inhalation system upright and tightly capped with the plugs when not in use.

The effects of treprostinil inhalation will lessen over time between doses. Talk with your doctor if you need to time your dosing around any planned activities.

Call your doctor if your symptoms do not improve or if they get worse.

Store treprostinil ampules in their foil pouch at room temperature away from moisture, heat, and light. Once you have opened a foil pouch, the ampules in it should be used within 7 days.

Any treprostinil placed into the medicine cup of the inhalation system must be used within 24 hours. Throw away any unused medicine at the end of the day after your last dose.

What happens if I miss a dose?

Call your doctor for instructions.

What happens if I overdose?

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

Overdose symptoms may include flushing (warmth, redness or tingling), headache, nausea, vomiting, diarrhea, feeling light-headed, or fainting.

What should I avoid while using treprostinil inhalation?

Avoid getting treprostinil in your eyes or on your skin. If this does happen, rinse with water. Do not swallow treprostinil inhalation. The medication should be inhaled using only the Tyvaso inhalation system. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Treprostinil inhalation 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 at once if you have any of these serious side effects:

new or worsening PAH symptoms such as feeling short of breath (even with mild exertion), tiredness, chest pain, and pale skin;

feeling like you might pass out;

fever, chills, cough with yellow or green mucus, stabbing chest pain, wheezing;

unusual bleeding such as nosebleeds, bleeding gums, or any bleeding that will not stop;

pale skin, weakness, easy bruising;

unexpected vaginal bleeding;

blood in your urine or stools, black or tarry stools;

coughing up blood or vomit that looks like coffee grounds; or

swelling of your ankles or feet.

Less serious side effects may include:

cough, sore throat;

pain or irritation in your throat after use;

dizziness;

nausea, diarrhea;

headache or jaw pain; or

flushing (warmth, redness or tingling).

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.

Treprostinil inhalation Dosing Information

Usual Adult Dose for Pulmonary Hypertension:

Infusion:
Initial dose: 1.25 nanogram/kg per minute by continuous infusion. The subcutaneous route is preferred but the drug may be administered by a central intravenous line if the subcutaneous route is not tolerated. The rate may be decreased to 0.625 nanogram/kg/minute if the initial dose is not tolerated by the patient.
Maintenance dose: The infusion rate may be increased in increments of no more than 1.25 nanogram/kg/minute per week for the first 4 weeks, and thereafter by no more than 2.5 nanograms/kg/minute per week. Dosage adjustments should be titrated to a dose where PAH symptoms are improved and adverse effects are minimized (headache, nausea, emesis, restlessness, anxiety, and infusion site pain or reaction). Although doses of up to 100 nanograms/kg/minute have been reported, there is little experience with doses greater than 40 nanograms/kg/minute.

Inhalation:
Use only with the Tyvaso Inhalation System. Administer undiluted, as supplied. A single breath of Tyvaso delivers approximately 6 mcg of treprostinil
Initial dosage: 3 breaths [18 mcg] per treatment session. If 3 breaths are not tolerated, reduce to 1 or 2 breaths. Administer in 4 separate treatment sessions each day approximately four hours apart, during waking hours.
Maintenance dose: Dosage should be increased by an additional 3 breaths at approximately 1-2 week intervals, if tolerated. Titrate to target maintenance dosage of 9 breaths or 54 mcg per treatment session as tolerated.

Usual Pediatric Dose for Pulmonary Hypertension:

Inhalation:
Less than 16 years: Safety and efficacy have not been established.
16 to 18 years:
Initial dose: 1.25 nanogram/kg per minute by continuous infusion. The subcutaneous route is preferred but the drug may be administered by a central intravenous line if the subcutaneous route is not tolerated. The rate may be decreased to 0.625 nanogram/kg/minute if the initial dose is not tolerated by the patient.
Maintenance dose: The infusion rate may be increased in increments of no more than 1.25 nanogram/kg/minute per week for the first 4 weeks, and thereafter by no more than 2.5 nanograms/kg/minute per week. Dosage adjustments should be titrated to a dose where PAH symptoms are improved and adverse effects are minimized (headache, nausea, emesis, restlessness, anxiety, and infusion site pain or reaction). There is little experience with doses greater than 40 nanograms/kg/minute.

What other drugs will affect treprostinil inhalation?

Before using treprostinil, tell your doctor if you are using any of the following drugs:

gemfibrozil (Lopid);

delavirdine (Rescriptor);

nicardipine (Cardene);

pioglitazone (Actos, ActoPlus Met, Duetact);

tolbutamide (Orinase);

an antibiotic such as rifampin (Rifater, Rifadin, Rifamate) or rifapentine (Priftin);

antifungal medication such as fluconazole (Diflucan), or ketoconazole (Nizoral);

blood pressure medication;

a blood thinner such as warfarin (Coumadin).

a diuretic (water pill);

medication to treat congestive heart failure, such as hydralazine (Apresoline, BiDil), nesiritide (Natrecor), nitroglycerin, or nitroprusside (Nitropress);

an NSAID (non-steroidal anti-inflammatory drug) such as flurbiprofen (Ansaid), ibuprofen (Advil, Motrin), indomethacin (Indocin), mefenamic acid (Ponstel), or piroxicam (Feldene);

seizure medication such as carbamazepine (Carbatrol, Tegretol), phenytoin (Dilantin) fosphenytoin (Cerebyx), phenobarbital (Solfoton), primidone (Mysoline), or secobarbital (Seconal);or

sulfa drugs such as sulfisoxazole (Bactrim, Cotrim, Gantanol, Gantrisin, Septra), and others.

This list is not complete and there may be other drugs that can interact with treprostinil. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More treprostinil inhalation resources

Treprostinil inhalation Side Effects (in more detail)
Treprostinil inhalation Dosage
Treprostinil inhalation Use in Pregnancy & Breastfeeding
Treprostinil inhalation Drug Interactions
Treprostinil inhalation Support Group
4 Reviews for Treprostinil - Add your own review/rating

Compare treprostinil inhalation with other medications

Pulmonary Arterial Hypertension

Where can I get more information?

Your doctor or pharmacist can provide more information about treprostinil inhalation.

See also: treprostinil side effects (in more detail)

Saturday, 3 March 2012

Clinoril

Generic Name: Sulindac
Class: Other Nonsteroidal Anti-inflammatory Agents
CAS Number: 38194-50-2

Cardiovascular Risk

Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).¹⁰⁰ Risk may increase with duration of use.¹⁰⁰ Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.¹⁰⁰ (See Cardiovascular Effects under Cautions.)

Contraindicated for the treatment of pain in the setting of CABG surgery.¹⁰⁰

GI Risk

Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).¹⁰⁰ Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.¹⁰⁰ Geriatric individuals are at greater risk for serious GI events.¹⁰⁰ (See GI Effects under Cautions.)

Introduction

Prototypical NSAIA; indeneacetic acid derivative; structurally related to indomethacin.¹⁰⁰ ^a

Uses for Clinoril

Consider potential benefits and risks of sulindac therapy as well as alternative therapies before initiating therapy with the drug.¹⁰⁰ Use lowest effective dosage and shortest duration of therapy consistent with the patient's treatment goals.¹⁰⁰

Inflammatory Diseases

Symptomatic treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, acute painful shoulder (acute subacromial bursitis/supraspinatus tendinitis), and acute gouty arthritis.¹⁰⁰

Colorectal Polyps

Has been associated with a reduction of the number of adenomatous colorectal polyps in adults with familial adenomatous polyposis (FAP)†.¹⁵⁷ ¹⁵⁸ ¹⁵⁹ ¹⁶⁰

Clinoril Dosage and Administration

General

Consider potential benefits and risks of sulindac therapy as well as alternative therapies before initiating therapy with the drug.¹⁰⁰

Administration

Oral Administration

Administer orally twice daily with food.¹⁰⁰

Dosage

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient's treatment goals.¹⁰⁰ Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.¹⁰⁰

Adults

Inflammatory Diseases

Osteoarthritis, Rheumatoid Arthritis, or Ankylosing Spondylitis

Oral

Initially, 150 mg twice daily.¹⁰⁰ Adjust dosage based on response.¹⁰⁰

Acute Painful Shoulder

Oral

200 mg twice daily; reduce dosage based on response.¹⁰⁰ 7–14 days of therapy usually adequate.¹⁰⁰

Gout

Oral

200 mg twice daily; reduce dosage based on response.¹⁰⁰ 7 days of therapy usually adequate.¹⁰⁰

Colorectal Polyps†

Oral

150 mg twice daily.¹⁵⁸

Prescribing Limits

Adults

Inflammatory Diseases

Oral

Maximum 400 mg daily.¹⁰⁰

Special Populations

Hepatic Impairment

Dosage reduction may be required.¹⁰⁰

Renal Impairment

Dosage reduction may be required.¹⁰⁰

Cautions for Clinoril

Contraindications

Known hypersensitivity to sulindac or any ingredient in the formulation.¹⁰⁰

History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.¹⁰⁰

Treatment of perioperative pain in the setting of CABG surgery.¹⁰⁰

Warnings/Precautions

Warnings

Cardiovascular Effects

Selective COX-2 inhibitors have been associated with an increased risk of cardiovascular events in certain situations.¹⁷⁰ Several prototypical NSAIAs also have been associated with an increased risk of cardiovascular events.¹⁷³ ¹⁷⁴ ¹⁷⁵ Current data insufficient to assess risk associated with sulindac.¹⁷³ ¹⁷⁴ ¹⁷⁵

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dosage for the shortest duration necessary.¹⁰⁰

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).¹⁷⁰

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.¹⁰⁰ (See Specific Drugs under Interactions.)

Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.¹⁰⁰ Use with caution in patients with hypertension; monitor BP.¹⁰⁰ Impaired response to certain diuretics may occur.¹⁰⁰ (See Specific Drugs under Interactions.)

Fluid retention and edema reported.¹⁰⁰ Caution in patients with fluid retention or heart failure.¹⁰⁰

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.¹⁰⁰ ¹⁵⁴ ¹⁵⁶

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;¹¹² ¹²⁵ ¹⁵⁴ ¹⁵⁵ alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)¹¹² ¹²⁵ ¹⁵⁴ or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).¹¹²

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.¹⁰⁰ ¹⁶⁷

Potential for overt renal decompensation.¹⁰⁰ ¹⁰⁹ ¹¹⁰ ¹¹¹ Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.¹⁰⁰ ¹⁰⁹ ¹¹⁰ ¹¹¹ ¹⁷² (See Actions.)

Symptomatic renal calculi containing sulindac metabolites reported rarely.¹⁰⁰ ¹²¹ Factors predisposing to urinary crystal formation include increased urinary excretion of sulindac metabolites (related to size of single doses as well as total daily dosage), decreased urine flow, and relatively low urinary pH.¹²¹ Formation of crystals, and presumably renal calculi, appears unlikely when urine output >240 mL/hour or pH >5.8.¹²¹ (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported.¹⁰⁰ Hypersensitivity (e.g., severe dermatologic manifestations, hepatic abnormalities) reactions associated with fever reported.¹⁰⁰

Immediate medical intervention and discontinuance for anaphylaxis.¹⁰⁰ Discontinue if unexplained fever or other evidence of hypersensitivity occurs.¹⁰⁰

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.¹⁰⁰

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.¹⁰⁰ Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).¹⁰⁰

Major Toxicities

Pancreatitis

Pancreatitis reported.¹⁰⁰

If pancreatitis is suspected, discontinue the drug and appropriately evaluate, monitor, and treat the patient; do not reinstitute sulindac therapy.¹⁰⁰ Rule out other possible causes of pancreatitis or conditions that may mimic pancreatitis.¹⁰⁰

General Precautions

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs.¹⁰⁰ ^a

Elevations of serum ALT or AST reported.¹⁰⁰

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.¹⁰⁰ Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.¹⁰⁰

Hematologic Effects

Anemia reported rarely.¹⁰⁰ Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.¹⁰⁰

May inhibit platelet aggregation and prolong bleeding time.¹⁰⁰

Ocular Effects

Visual disturbances reported; if such effects occur, perform ophthalmic evaluation.¹⁰⁰

Aseptic Meningitis

Increased risk of aseptic meningitis in patients with systemic lupus erythematosus or mixed connective tissue disease.^b

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.¹⁰⁰

May mask certain signs of infection.¹⁰⁰

Obtain CBC and chemistry profile periodically during long-term use.¹⁰⁰

Specific Populations

Pregnancy

Category C.¹⁰⁰ Avoid use in third trimester because of possible premature closure of the ductus arteriosus.¹⁰⁰

Lactation

Distributed into milk in rats; not known whether distributed into milk in humans.¹⁰⁰ Discontinue nursing or the drug.¹⁰⁰

Pediatric Use

Safety and efficacy not established.¹⁰⁰

Geriatric Use

Caution advised.¹⁰⁰ Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.¹⁰⁰ Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.¹⁰⁰

Select dosage with caution because of age-related decreases in renal function.¹⁰⁰ May be useful to monitor renal function.¹⁰⁰

Hepatic Impairment

Monitor closely.¹⁰⁰ (See Hepatic Impairment under Dosage and Administration and see Special Populations under Pharmacokinetics.)

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.¹⁰⁰ (See Renal Impairment under Dosage and Administration.)

Sulindac and the sulfone metabolite eliminated principally via the kidney.¹⁰⁰ (See Special Populations under Pharmacokinetics.)

Use with caution in patients with a history of renal lithiasis; ensure proper hydration.¹⁰⁰ (See Renal Effects under Cautions.)

Common Adverse Effects

Dyspepsia, nausea, diarrhea, constipation, rash, dizziness, headache.¹⁰⁰

Interactions for Clinoril

Protein-bound Drugs

Potential for sulindac and its sulfide metabolite to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.^a Observe for adverse effects (especially in patients receiving higher than recommended dosages of sulindac and those with renal impairment or other metabolic dysfunction that might increase plasma concentrations of sulindac or its sulfide metabolite).^a

Specific Drugs

Drug	Interaction	Comments
ACE inhibitors	Reduced BP response to ACE inhibitor¹⁰⁰ Possible deterioration of renal function in individuals with renal impairment¹⁰⁰	Monitor BP¹⁰⁰
Acetaminophen	Pharmacokinetic interaction unlikely¹⁰⁰
Angiotensin II receptor antagonists	Reduced BP response to angiotensin II receptor antagonist¹⁰⁰ Possible deterioration of renal function in individuals with renal impairment¹⁰⁰	Monitor BP¹⁰⁰
Antacids (magnesium- or aluminum-containing)	Change in sulindac bioavailability unlikely¹⁰⁰
Anticoagulants, oral	Possibility of bleeding complications¹⁰⁰ Protein binding interaction unlikely¹⁰⁰	Caution advised; monitor PT; adjust anticoagulant dosage as needed¹⁰⁰
Cyclosporine	Possible increase in cyclosporine-induced toxicity¹⁰⁰	Use with caution; monitor renal function¹⁰⁰
Dimethylsulfoxide	Decreased plasma concentrations of sulfide metabolite of sulindac¹⁰⁰ Peripheral neuropathy reported¹⁰⁰	Avoid concomitant use¹⁰⁰
Diuretics (furosemide, thiazides)	Reduced natriuretic effects possible¹⁰⁰	Monitor for diuretic efficacy and renal failure¹⁰⁰
Hypoglycemic agents, oral	Protein binding interaction unlikely¹⁰⁰
Lithium	Pharmacokinetic interaction unlikely¹³⁵ ¹³⁶ ¹³⁷ ¹³⁸ ¹³⁹	Nevertheless, monitor for altered response to lithium when initiating or discontinuing sulindac¹³⁶
Methotrexate	Possible increased plasma methotrexate concentrations¹⁰⁰ ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³¹ ¹³²	Use with caution¹⁰⁰
NSAIAs	NSAIAs including aspirin: Increased risk of GI ulceration and other complications¹⁰⁰ Aspirin: Decreased plasma concentrations of sulfide metabolite of sulindac with aspirin 2.4 g daily¹⁰⁰ Aspirin: No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs¹⁰⁰ Diflunisal: Decreased plasma concentrations of the sulfide metabolite of sulindac with diflunisal¹⁰⁰	Concomitant use not recommended¹⁰⁰
Probenecid	Increased plasma concentrations of sulindac and its sulfone metabolite; minimal changes in plasma concentrations of the sulfide metabolite¹⁰⁰ Reduced uricosuric action of probenecid¹⁰⁰	Change in uricosuric action unlikely to be clinically important¹⁰⁰
Propoxyphene	Pharmacokinetic interaction unlikely¹⁰⁰
Thrombolytic agents	Possible bleeding complications^a

Clinoril Pharmacokinetics

Absorption

Bioavailability

Prodrug with little pharmacologic activity until reduced to active sulfide metabolite;¹⁰⁰ peak plasma concentrations of sulfide metabolite attained within about 5 hours.¹⁰⁰

Special Populations

Concentrations of the sulfide metabolite are higher in patients with alcoholic liver disease than in healthy individuals.^b

In patients with end-state renal disease requiring dialysis, concentrations of sulindac and the sulfone metabolite are similar to those in healthy individuals and concentrations of the sulfide metabolite are lower than those in healthy individuals.^b

Distribution

Extent

Widely distributed in animals.^a

Plasma Protein Binding

Sulindac: 93%.^b

Sulfide metabolite: 98%.^b

Elimination

Metabolism

Reduced to an active sulfide metabolite (reversible reaction) and oxidized to an inactive sulfone metabolite (irreversible reaction).¹⁰⁰ Sulindac and its sulfone metabolite undergo extensive enterohepatic circulation.¹⁰⁰

Elimination Route

Excreted in urine (50%) principally as sulindac and its conjugated sulfone metabolite and in feces (25%) as the sulfone and sulfide metabolites.¹⁰⁰

Sulindac and its metabolites not removed by hemodialysis.^b

Half-life

Sulindac: 7.8 hours.¹⁰⁰

Sulfide metabolite: 16.4 hours.¹⁰⁰

Stability

Storage

Oral

Tablets

15–30°C.^b

ActionsActions

Inhibits cyclooxygenase-1 (COX-1) and COX-2.¹⁴⁸ ¹⁴⁹ ¹⁵⁰ ¹⁵¹ ¹⁵² ¹⁵³

Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.¹⁰⁰ ^a

Conflicting data regarding effects on renal prostaglandin synthesis and renal function.¹⁰¹ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ¹⁰⁶ ¹⁰⁷ ¹⁰⁸ Some studies suggest no effect;¹⁰¹ ¹⁰² ¹⁰⁵ others suggest that sulindac inhibits renal prostaglandin synthesis and impairs renal function, but possibly to lesser degree than other NSAIAs (i.e., ibuprofen, indomethacin).¹⁰¹ ¹⁰³ ¹⁰⁴ ¹⁰⁶ ¹⁰⁷

Advice to Patients

Importance of reading the medication guide for NSAIAs that is provided each time the drug is dispensed.¹⁰⁰

Risk of serious cardiovascular events with long-term use.¹⁰⁰

Risk of GI bleeding and ulceration.¹⁰⁰

Risk of serious skin reactions.¹⁰⁰ Risk of anaphylactoid and other sensitivity reactions.¹⁰⁰

Risk of hepatotoxicity.¹⁰⁰

Importance of notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.¹⁰⁰

Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.¹⁰⁰

Importance of discontinuing sulindac and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.¹⁰⁰ Importance of seeking immediate medical attention if an anaphylactic reaction occurs.¹⁰⁰

Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.¹⁰⁰

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰⁰ Importance of avoiding sulindac in late pregnancy (third trimester).¹⁰⁰

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.¹⁰⁰

Importance of informing patients of other important precautionary information.¹⁰⁰ See Cautions.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Sulindac
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	150 mg*	Clinoril	Merck
			Sulindac Tablets
		200 mg*	Clinoril (scored)	Merck
			Sulindac Tablets

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Sulindac 150MG Tablets (MUTUAL PHARMACEUTICAL): 60/$18.99 or 180/$49.98

Sulindac 200MG Tablets (WATSON LABS): 100/$33.91 or 200/$67.83

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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b. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2007 Feb.

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Wednesday, 29 February 2012

Boots Cystitis Relief (Lemon Flavour)

1. Name Of The Medicinal Product

Cystitis Relief

Cystocalm

2. Qualitative And Quantitative Composition

Sodium Citrate Dihydrate BP 4.0g

3. Pharmaceutical Form

Granules to be reconstituted for oral adminstration.

4. Clinical Particulars

4.1 Therapeutic Indications

For the relief of the symptoms of cystitis in women.

4.2 Posology And Method Of Administration

For oral administration.

Adult women: The contents of one sachet dissolved in a glass of water, to be taken three times a day for 2 days.

Men and children: Not recommended.

4.3 Contraindications

Patients with diabetes, heart disease, hypertension, history of renal disease or those on a low salt diet.

During pregnancy and lactation.

4.4 Special Warnings And Precautions For Use

If symptoms persist after the 2 day course of treatment is completed, medical attention should be sought.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None stated.

4.6 Pregnancy And Lactation

Contraindicated during pregnancy and lactation.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

None stated.

4.9 Overdose

In the unlikely event of overdosage occurring with this product, treatment should be symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

The effect of Sodium Citrate is to render the urine less acidic.

5.2 Pharmacokinetic Properties

None relevant.

5.3 Preclinical Safety Data

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sucrose BP 1.5g, Colloidal Silicon Dioxide BP, Saccharin Sodium BP, Natural Lemon Flavour.

6.2 Incompatibilities

None stated.

6.3 Shelf Life

The granules have a two year shelf life.

The reconstituted solution should be used immediately.

6.4 Special Precautions For Storage

Store below 25°C in a dry place.

6.5 Nature And Contents Of Container

Foil laminate sachets (comprising of 44gsm clay coated kraft paper, 10 gsm polythene, 8 aluminium foil, 25gsm polythene) containing 5.535g of granule enclosed in a cardboard outer.

6.6 Special Precautions For Disposal And Other Handling

None stated.

7. Marketing Authorisation Holder

Galpharm Healthcare Limited

Hugh House,

Upper Cliffe Road

Dodworth Business Park

Dodworth

South Yorkshire

S75 3SP

8. Marketing Authorisation Number(S)

PL 16028/0017

9. Date Of First Authorisation/Renewal Of The Authorisation

22^nd September 1997

10. Date Of Revision Of The Text

April 1998