Bula do remedy Serzone

the package insert of the medicine Serzone. Therapeutic class of the anti-Depressants. Active principles Hydrochloride Nefazodone.

what For?

Treatment of depression, including depression accompanied by anxiety or sleep disorders.

oral – adult Use

Contraindications

When should I not use?

Patients with known hypersensitivity to nefazodone, other antidepressants fenilpiperazínicos, or to any ingredient inactive product.

Dosage

How to use?

The recommended starting dose for Serzone is 200 mg/day (100 mg, 2 times a day).

In controlled clinical studies, the range of effective dose was 300 to 600 mg/day, administered in 2 doses over the day, therefore, the majority of patients, depending on tolerability and the need for a clinical effect more pronounced, you should have your dose increased to 100 mg/day (50 mg, 2 times a day), 200 mg/day (100 mg, 2 times a day), with intervals of approximately 1 week.

As noted with all antidepressants, it may take several weeks of treatment to obtain the full therapeutic effect.

elderly Patients and debilitated: the recommended initial dose for elderly patients or debilitated is 100 mg/day (50 mg, 2 times a day).

These patients have had, frequently, reduction of the clearance of nefazodone and increased sensitivity to adverse effects of drug action in the CNS.

it May be appropriate to modify the index of titration to the next dose and the final dose to be reached based on a careful assessment of the clinical response of the patient.

As the plasma levels stable are not modified with age, the average dose late in this group of patients, based on a careful assessment of the clinical response obtained, it can be similar to that of young healthy.

Patients transferred from or to therapy with monoamine oxidase inhibitors (MAOIS): you should be at least 14 days between discontinuation of a MAOI and initiation of therapy with nefazodone.

on the other hand, at least 7 days should elapse after stopping nefazodone before starting a MAOI.

renal Dysfunction: it was not observed a significant relationship between the pharmacokinetics and the degree of renal impairment.

however, with chronic administration may occur accumulation additional of nefazodone or its metabolites in patients with renal function severely compromised and it is recommended the use of the dose range of its lowest level.

the Therapy long-term: systematic evaluations of the effectiveness of nefazodone in controlled clinical studies with placebo, have demonstrated that the therapeutic benefit remains during continued treatment for periods of up to 1 year.

The response observed during an initial course of treatment can be kept securely with the same dose.

Side Effects

What are the evils that can cause me?

adverse effects most commonly observed, which occurred with an incidence significantly higher in patients treated with nefazodone than in patients treated with placebo were: dry mouth, nausea, drowsiness, dizziness, constipation, asthenia, feeling of empty head and blurred vision.

the Organism as a whole: asthenia, chills, fever; cardiovascular system: postural hypotension; digestive system: nausea, dry mouth, constipation; musculoskeletal system: arthralgia; nervous system: drowsiness, dizziness, feeling of empty head, paresthesia, vasodilation, confusion, abnormal dreams, memory impaired, incoordination, hiperestesia, ataxia; organs of the senses: blurred vision, eye disorders.

In controlled clinical studies with placebo, nefazodone has not been associated with the development of electrocardiographic abnormalities clinically important.

however, it was obsevada sinus bradycardia (< 50 bpm and a decrease of > 15 bpm) in some patients.

Adaptation to the adverse experiences are common: for a period of 6 weeks there was evidence of gradual adaptation with the continuation of the treatment in relation to the following adverse experiences: asthenia, blurred vision, constipation, dizziness, dry mouth, feeling of empty head, nausea, and drowsiness.

drug Abuse and dependence: physical and psychological dependence: the nefazodone showed no potential for abuse of the drug in the controlled study on this possibility in man.

Nefazodone has not been systematically studied in man with respect to their potential for tolerance, physical dependence or symptoms resulting from the withdrawal.

however, doctors should assess patients carefully with regard to the history of drug abuse and make rigorous follow-up of such patients by observing them for signs of misuse or abuse.

Warnings and Precautions

what should I know before using?

Based on experience with all antidepressants, including nefazodone, the following precautions should be observed: the potential for interaction with monoamine oxidase inhibitors: there were reports of serious reactions, sometimes fatal, in patients receiving antidepressants with pharmacological properties similar, but not identical to the nefazodone (p. ex., selective inhibitors of serotonin reuptake) in association with monoamine oxidase inhibitors (MAOIS).

These reactions have also been reported in patients who discontinued recently these drugs and started therapy with a MAOI.

once the nefazodone is an inhibitor of serotonin reuptake, it is recommended that nefazodone not be used in connection with a MAOI, or within a period of 14 days after discontinuation of treatment with MAOIS.

you Must leave a period of at least 1 week after discontinuation of nefazodone to start the treatment with a MAOI.

Potential interaction with terfenadine, astemizola and cisapride: the concomitant use of terfenadine, astemizola, or cisapride with nefazodone should be avoided.

The nefazodone demonstrated in vitro to be an inhibitor of the cytochrome P450 IIIa.

terfenadine, astemizola, and cisapride are all metabolized by the cytochrome IIIa and it has been demonstrated that ketoconazole, erythromycin, and other inhibitors of IIIa can block the metabolism of these drugs resulting in increased plasma concentration of the same.

plasma Concentrations increased terfenadine, astemizola and cisapride are associated with QT interval prolongation and with rare cases of adverse events serious cardiovascular, including death, due principally to ventricular tachycardia type torsade de pointes.

postural Hypotension: it has occurred to postural hypotension associated with the use of nefazodone.

The rates of adverse events characterized as postural hypotension in clinical studies of nefazodone have been the following: nefazodone, tricyclic antidepressants, selective inhibitors of the reuptake of serotonin and placebo; therefore, the nefazodone should be used with caution in patients with cardiovascular diseases, or cerebrovascular well-known, which may be exacerbated by hypotension (history of myocardial infarction, angina and ischemia), and conditions that predispose patients to hypotension (dehydration, hypovolemia and treatment with medication anti-hypertensive).

a History of mania/hypomania: as with other agents, antidepressants, activation of mania/hypomania is a known risk in a small proportion of patients with the disorder affective greater treated with antidepressants, have occurred also during clinical studies with nefazodone.

The nefazodone should be used with caution in patients with a history of mania.

Suicide: the possibility of a suicide attempt in patients with severe depression is inherent in the illness and may persist even during an improvement apparent symptoms.

close supervision of high-risk patients should accompany the initial therapy with the drug.

The prescriptions for Serzone should be made with the smallest quantity of tablets in order to reduce the risk of overdose.

Seizures: as with other antidepressants, nefazodone should be used with caution in patients with a history of seizures.

During the studies of pre-trade, were not observed convulsions of the grand mal type or focal length.

Priapism: although the priapism has not occurred with nefazodone during the experiences of pre-marketing, this adverse reaction has been reported with a drug structurally related to nefazodone, trazodone.

If they have erections prolonged or inappropriate, patients should discontinue therapy immediately and consult your doctor.

electroconvulsive Therapy (TEC): there were no clinical studies involving the combined use of electroconvulsive therapy and nefazodone.

Use in patients with concomitant diseases: caution is advised when use of nefazodone in patients with diseases or conditions, such as dysfunction of the liver or kidney, which can affect the metabolism and elimination of the drug.

The values of AUC of nefazodone and hidroxinefazodona in patients with cirrhosis of the liver are increased by approximately 25%.

it Can occur a accumulation additional of nefazodone and its metabolites in patients with renal function severely compromised when the chronic administration, recommending the use of a lower dose or less frequent.

there was observed no specific relationship between the pharmacokinetics parameters and the degree of renal impairment.

Patients with a recent history of myocardial infarction or heart disease unstable have been excluids of the clinical studies.

The assessment of electrocardiograms (ECG) of patients who received nefazodone in placebo-controlled studies did not indicate that nefazodone is associated with the development of abnormalities electrocardiographic clinically important.

Patients with a recent history of myocardial infarction or heart disease unstable should be treated with caution.

Serzone in pregnancy: there are no controlled studies with nefazodone in human pregnancy.

in view of that animal reproduction studies are not always predizentes of human response, this drug should be used during pregnancy only if the potential benefits exceed the potential risk.

Labor: the effect of Serzone on labor is not known.

Use in lactation: it is not known if nefazodone and its metabolites are excreted in human milk.

however, it should be use cautiously when administration of Serzone to a mother in lactation.

paediatric Use: have not been established safety and effectiveness in children below the age of 18.

Use geriatric: no phenomenon adverse clinical not the usual age-related has been identified in the safety assessment in more than 500 elderly subjects (> 65 years) treated with nefazodone.

Due to the increasing exposure systemic to nefazodone observadado in studies of single-dose in elderly patients, treatment with nefazodone should be initiated with half the usual dose, with titration of increasing according to the need to achieve the therapeutic response with tolerability ideal.

The precautions usual should be observed in elderly patients who have diseases or are receiving drugs concomitantly with treatment with Serzone.

Effects on ability to drive or operate machinery: any psychoactive drug may impair judgment, thinking, or motor skills, and patients should be cautioned with respect to the operation of machinery complex, including automobiles, until they are really certain that the drug does not affect them adversely as to the ability to perform such activities.

Drug interactions

Triazolobenzodiazepínicos: triazolam: concomitant use of nefazodone and triazolam should be avoided, because the peak concentration, the half-life and the AUC of triazolam in a state of equilibrium, increasing by 1.7, 3, and 4 times, respectively, when administered concomitantly with nefazodone.

The co-administration of nefazodone potentiates the adverse effects of triazolam on tests of psychomotor performance.

The plasma concentrations of nefazodone are not affected by the triazolam.

Alprazolam is recommended if reduction of dosage of alprazolam, in the case of concomitant administration of nefazodone.

there is no need for adjustment of dosage for nefazodone.

When the nefazodone and alprazolam are administered concomitantly, the values of peak concentration, AUC and half-life for alprazolam increase approximately two times in a state of equilibrium.

The plasma concentrations of nefazodone are not affected by alprazolam.

Lorazepam: will not occur change of any parameter pharmacokinetic to lorazepam and nefazodone when both are administered concomitantly.

monoamine oxidase Inhibitors (MAOIS): see warnings and precautions.

Lithium: the concomitant administration of nefazodone and lithium does not cause any interaction adverse.

Haloperidol: when a single oral dose of 5 mg of haloperidol was administered concomitantly with the nefazodone in a state of equilibrium, the AUC of haloperidol increased by 35%, without significant increase in Cmáx and Tmax.

there were No changes in the pharmacokinetics parameters of nefazodone.

These changes are not considered clinically significant and dose adjustment is not usually necessary for both the drugs.

Fluoxetina: the pre-treatment or co-administration of fluoxetine with nefazodone significantly increases the values of AUC of the metabolite of nefazodone, the m-chlorophenyl piperazine (m-cpp) in approximately 3 to 6 times.

Patients who are removed and transferred immediately from fluoxetine to nefazodone may suffer some adverse event transient (for example, nausea, lightheadedness, headache).

These adverse events can be minimized, establishing a period without medication before initiation of therapy with nefazodone and by the reduction of the initial dose of nefazodone.

In view of the long half-life of fluoxetine and its metabolites, this period without medication can vary from one to several weeks, depending on the dose of fluoxetine and other individual variables of the patient.

The nefazodone does not affect the pharmacokinetics of fluoxetine or norfluoxetina.

Anti-hypertensive drugs: there was reports of postural hypotension in patients treated with nefazodone.

concomitant Administration of antihypertensive therapy and nefazodone may require a reduction in dose of the drug anti-hypertensive.

Digoxin: due to the restricted therapeutic index of digoxin, you should use caution when concomitant administration of nefazodone and digoxin; it is recommended to monitor the plasma levels of digoxin.

Propranolol: kinetics of nefazodone, hidroxinefazodona and triazoladiona were not affected by co-administration of propranolol.

there is No need to change the initial dose of the drug and dose adjustments should be made based on clinical response.

Alcohol: it is prudent to avoid the concomitant use of alcohol and nefazodone.

Anaesthetics, general: the potential for interaction between nefazodone and anesthetics general is little known; therefore, before you opt for surgery, nefazodone should be discontinued as soon as clinically possible.

Cimetidine: no interactions were observed for clinical or pharmacokinetic significant between nefazodone and cimetidine.

caution is advised in the associated use of nefazodone with any drugs known to be metabolized by the isoenzyme IIIa4 (p. ex., antagonists of calcium channels, ciclosporinas, clarithromycin, erythromycin, ketoconazole, intraconazol, midazolam, vimblastina), in particular terfenadine, astemizola, or cisapride.

General: the nefazodone binds widely to plasma proteins in man (> 99%).

The effect of nefazodone on the links to the plasma proteins of drugs with the potential to be co-administered should be considered.

conversely, adverse effects may result from displacement of nefazodone by other drugs with high binding rate to plasma proteins.

Other drugs: during the interaction studies, no interactions were observed pharmacokinetic or pharmacodynamic significant when the nefazodone was co-administered with theophylline, and warfarin.

Carcinogenesis, mutagênese: there is no evidence of carcinogenicity, mutagenicity or genotoxic effects with Serzone.