Active matter: Bupropion hydrochloride 150 mg

Auxiliary matters: cellulose microcrystalline, hypromellose, cysteine hydrochloride monohydrate, magnesium stearate, concentrate of white белого dye (Opadry OY-7300 White or Opadry YS-1-18202-A White), wax carnauba, black alimentary paint.

Tablets are covered by the tunic. The pills possess by the prolonged action.

The main physical-chemical properties are convexo-convex tablets of white color, covered by the film tunic, with white core, with marking by the black color «GX CH7» from one side and without any marking from other side of a pill.

Psychoactivators (or psychoactive substances). Other antidepressants. Code АТХ N06A X12.

Pharmacological:

Bupropion is a selective inhibitor of the neuronal capture of the catecholamines (noradrenaline and dopamine) with minimal influence on the indolamine (serotonin) seizure and full absence of the MAO oppression.

Pharmacokinetics:

absorption

After the applying of these medicines by the healthy volunteers the maximal concentration in blood plasma is reached over 3 hours.

By the data of three clinical researches it can be supposed that the level of Bupropion can be heightened if it will be used together with some food. Under the application together with eating the maximal concentration of Bupropion in blood plasma (Cmax) is increased on 11%, 16% and 35%, but the general level (AUC) is enlarged on 17%, 17% and 19% in three researches.

Bupropion and its metabolites have the linear kinetics under the prolonged application in dosages from 150mg till 300mg in a day.

distribution

Bupropion is subject to the wide distribution. Its dimensions of breakdown are about 2000 liters. This substance and its metabolite as hydroxibupropion are moderately tied together with proteins of blood plasma (84% and 77% appropriately). The connecting degree with proteins of threohydrobupropion metabolite is approximately a half of such that is observed for Bupropion.

metabolism

Bupropion is intensively metabolized in the human organism. In blood plasma it is identified three pharmacologically active metabolites as hydroxibupropion and its amino alcohol isomers – threohydrobupropion and erythrohydrobupropion.

Withdrawal:

About 87% of Bupropion is usually taken away with urine (less than 10% are in view of active metabolites), till 10% – with feces. With intact view it is taken off only 0,5% of Bupropion. On the average the clearance after the applying of the substance’s prescribing is about 200 l/h and the medium period of Bupropion partial ejection – approximately 20 hours.

Patients with renal insufficiency

Bupropion and its main metabolites excretion can be damaged under the lowering function of the kidneys. The sick persons with terminal stage of the renal insufficiency or with moderate and expressed lesions of the kidneys have the heightening influence of Bupropion and its active metabolites.

Patients with hepatic inefficiency

The pharmacokinetics of Bupropion and its active metabolites by patients with light and moderate degree of cirrhosis is little differed for such one by the healthy people. By the patients with heavy hepatic cirrhosis the maximal concentration of Bupropion and the area under the curve «concentration – time» are considerably heightened, the period of partial ejection is also prolonged one as compared with healthy persons.

Aged patients

Pharmacokinetic researches of the aged people give ambiguous results. The clinical experiment isn’t settled any difference in portability by aged patients and young individuals but the presence of larger apprehensibility to the main active substance by the aged persons is impossible to exclude.

Treatment of the large depressed conditions

Wellbutrin SR is contra-indicated by the patients with hypersensitivity to Bupropion hydrochloride or to each other components entered into the structure of this medical preparation.

The drug is also contraindicated for patients with convulsions or for sick persons who have suddenly stopped the applying of alcohol or some sedative medications in presence time.

These tablets consist of such matter as Bupropion hydrochloride so they cannot be allocated for ill individuals used other medical preparations with this main active matter in their structure because the frequency of the convulsions development is dosage depended one.

Wellbutrin SR isn’t taken by the patients with existed in present time or in anamnesis the nervous bulimia or anorexia because it is usually observed the large frequency of the convulsions development under the applying of Bupropion form of the quick disengagement.

The simultaneous applying of this medicant together with MAO inhibitors is contra-indicated. It is needed fourteen days between the beginning of treatment by antidepressants and withdrawal of the irreversible inhibitors MAO.

Bupropion is metabolized in its main active metabolite – hydroxibupropion mainly with helping of cytochrome Р450 (CYP2B6). That’s why it is necessary to prescribe Wellbutrin SR with prudence together with some medical preparations which influence on the isoenzyme CYP2B6 (for example, orphenadrine, cyclophosphamide, iphosphamide, tyclopidine, clopidogrel).

Though Bupropion isn’t metabolized by the isoenzyme CYP2B6 the researches in vitro 450 by some people had shown that the substance Bupropion and the matter hydroxibupropion are the inhibitors of the metabolic way of CYP2D6. In pharmacokinetic researches on the people the applications of Bupropion is heightened the level of desipramine in blood plasma. This action is observed during not less than seven days after last dosage of Bupropion.

The synchronous applying of this substance together with medications which are metabolized mostly by this ferment (such as separate b-blockers, antiarrhythmic drugs, selective inhibitors of serotonin’s reversible capture, tricyclic antidepressants, antipsychotic remedies) is followed to begin from minimal dosages of accompanied preparation. If Wellbutrin is included into the treating scheme of sick individual which have already given this medical agent metabolized by CYP2D6 it is followed to estimate the necessity of dose diminishing of this medication especially for the medical remedies with wide therapeutical index.

The officinal remedies needed the metabolic activation with taking part of CYP2D6 (fro example, tamoxiphen) for effective work can diminish their effectiveness under the synchronous applying together with CYP2D6 inhibitors such as Bupropion.

Citalopram isn’t primary metabolized by CYP2D6 but Bupropion increases С max (maximal concentration) and AUC (area under the curve «concentration-time») of Citalopram on 30% and 40% appropriately.

As far as Bupropion is intensively metabolized the synchronous prescribing of medical preparations strengthened the metabolism (for example, Carbamazepine, Phenobarbital, Phenitoin, Ritonavir, Ephavirense) or suppressed metabolism can change its clinical activity.

By the data of clinical researches the medications as Ritonavir (100 mg twice per day or 600 mg 2 twice per day) or Ritonavir 100 mg and Lopinavir 400 mg twice a day had dose-dependently diminished the concentration of Bupropion and its main metabolites approximately on 20-80%. In such case the medication as Ephavirense 600 mg once a day during two weeks diminishes the concentration of Bupropion approximately on 55%. This effect of Ritonavir / Lopinavir and Ephavirense is tied together with induction of Bupropion metabolism. The patients who are treated by each of these medical preparations together with medicaments contained the matter as Bupropion in their structure can be needed the dosage increasing but it is impossibly to heightened the maximal recommended doses.

It wasn’t exposed any pharmacological interaction between Wellbutrin and alcohol by the data of clinical researches but there are some separate reports about different side effects from the side of central nervous system (CNS) or diminishing tolerance to the alcohol by patients who use alcohol under the treatment by Wellbutrin or other antidepressants. Alcohol using is needed to minimize or fully avoid if you have treatment by Wellbutrin or its analogs.

It is reported about heightening of toxic influence in the CNS under the synchronous applying of Bupropion with Levodopa and amantadine. The prescribing of Wellbutrin for sick persons given such preparations as Levodopa and amantadine is followed to take with some prudence.

The synchronous application of Wellbutrin and nicotinic transdermal system (NTS) can call the heightening of the arterial pressure level.

By the data researches it can be supposed that level of Bupropion is increased under its applying together with some food.

Interaction with involvement of labor tests

It is reported that Wellbutrin can interact with some tests. It is applied for quick definition of the officinal remedies’ presence in the urine. As a result it can be given the false-positive results especially under the definition of amphetamines. For confirmation of positive result it is followed to apply the alternative chemical method.

Families and persons looked after the patients which have the treatment by the antidepressants must be know beforehand about the necessity of the fixed controlling for every worsening of their condition (including the appearance of new symptoms, agitation, irritability, unusual behavior) and / or appearance of suicidal ideas / behavior or some intentions to harm theirselves. In cases of such symptoms appearances it is followed to appeal immediately for the medical help. The doctor must set a diagnosis and prescribe the right treating scheme with applying of necessary antidepressants.

Convulsions

The recommended dosage of Wellbutrin isn’t followed to increase because the dose-depended development of convulsions is typical for Bupropion. In doses which aren’t heightened maximally recommended daily norm (till 300 mg of Wellbutrin per day) the frequency of the convulsion development is about 0,1% (1/1000).

The risk of convulsions development tied together with Wellbutrin applying intimately correlates with presence of the risk’s factors. So this medical preparation is prescribed with some prudence for patients who have one or several such factors promoted to some lowering of the convulsive readiness’s threshold. These factors are

– head trauma in anamnesis;

– neoplasms of the central nervous system;

– convulsions in anamnesis;

– synchronous prescribing of other medications brought down the convulsive threshold.

Besides it is followed to be careful in some clinical cases tied together with vessels’ heightening risk. They include the alcohol abuse, some stimulators of the central nervous system or different sedative medications, diabetes mellitus, for curing of which it is applied the sugar-lowering preparations and insulin, arterial-venous malformations, infections of the central nervous system, metabolic discomposing (hypoxemia), heavy stroke, applying of opiates, stimulators or anorexants. It is followed to abolish the drug of Wellbutrin and it isn’t followed to applying this medication secondary for the patients who is observed the convulsive attacks during the treatment.

Glaucoma

The mydriatic pupils that is usually happened after some using of different antidepressants including Wellbutrin SR can bring the crisis of narrow-angle glaucoma by sick individuals with anatomically narrow angle.

Reactions of hypersensibility

It is followed to stop the application of Wellbutrin if it was appeared some symptoms of hypersensibility by the patient during the medical cure by this drug.

Hepatic insufficiency

Bupropion is intensively metabolized in liver with some formation of active metabolites which are subject to following metabolism. It isn’t observed any statically reliable difference in pharmacokinetics of Bupropion by patients with light and moderate degree of hepatocirrhosis as compared with healthy persons but on the level of the substance in blood plasma of separate patients they were very variable. So Wellbutrin is needed to apply with prudence by some patients with liver’s pathology diminished the dosing frequency by sick persons with light and moderate degree of hepatocirrhosis.

Wellbutrin is prescribed extremely carefully for ill people with heavy hepatocirrhosis. It is followed to decrease the dosing frequency for such category of patients because the highest concentrations of Bupropion in them are considerably increased and the preparation accumulation is happened in considerably big degree.

It is followed to observe all patients with liver’s pathology on the subject of possible side phenomena (for example, insomnia, dryness in mouth, convulsions) which can indicate on high levels of this preparation or its metabolites.

Patients with renal insufficiency and aged patients

Bupropion and its metabolites are taken away mainly by the kidneys. That’s why the treatment of the patients with kidneys’ lesions is needed to start with diminished dosages or frequency of application because the matter of Bupropion and its metabolites are accumulated in beg level than usual one by such category of sick individuals. It is followed the careful observation for all patients from the risk of possible side effects’ development (for example, insomnia, dryness in mouth, convulsions) which can indicate on high levels of this preparation or its metabolites.

The clinical test of Bupropion applying didn’t reveal any difficulties bin portability by the aged patients as compared with other adults. But it is impossible to exclude the presence of bigger apprehensibility by some aged sick persons that’s why it is followed to decrease the application frequency or preparation dosing.

Children and teenagers

The treatment by antidepressants is usually associated with heightened risk of suicidal ideas and behavior by children and teenager with bigger depressed damages and other psychical disorders.

It can be worsened the symptomatology of depressed condition and / or capability to some perception and formation of suicidal ideas and behavior independently from applying of different antidepressants by sick persons with depression. The risk of this fact stays during all time till remission beginning. As far as some improvement of condition cannot begin during the first weeks (or more) of the medical cure the patient must by under the observation with a goal of the reasons exposure of condition’s clinical worsening (including the appearance of the new symptoms) or suicidal ideas and behavior especially in the beginning if the treating course or under the dosages exchanging as increasing as diminishing ones. Taking into account the general clinical test it is considered that under all antidepressants using there is some risk of suicides increasing on the early stages of recovery.

The sick persons with suicidal behavior or expectancies in anamnesis and the young patients manifest in larger degree the capability to the formation and perception of suicidal ideas till the medical cure beginning. They are the group of big risk for suicidal ideas and suicidal attempts that’s why they must be under the careful controlling during the treatment.

The patients must be anticipated about the necessity of the careful control for every worsening of their condition (including the new symptoms appearance) and / or appearance of suicidal ideas / behavior or intentions to harm theirselves. In cases of such symptoms appearance it is followed to appeal for the medical helping immediately. It is followed to take into account that appearance of neuropsychic symptoms can be tied together such with main sickness as with preparation applying.

The sick persons with worsening of condition (including the development of new symptoms) and / or appearance of suicidal ideas / behavior (especially if these symptoms have the heavy form) arise suddenly or not the part of the present symptoms needed in the substitute pf treatment’s therapeutic regime taken into account the medical cure stopping.

Neuropsychic symptoms including mania and bipolar disorder

There are some information about neuropsychic symptoms appearance. Particularly by the patients with some psychical sicknesses it is observed the psychotic and maniacal symptomatology. Additionally the large depressed episode can be the beginning manifestation of the bipolar disorder. There is a generally accepted opinion (it isn’t corroborated by any clinical researches) that the treatment of such episodes by different antidepressants independently can increase the possibility of mixed / maniacal episodes strengthening by sick people with some risks of the bipolar disorders’ development. The limited clinical data about Bupropion using in combination with mood stabilizers by patients with bipolar upset in anamnesis allow supposing the lowest degree of mania appearance. The sick persons must take an adequate inspection with a goal of risk identification of bipolar disorders appearance till the beginning of the medical cure by antidepressants. Such inspection includes the collection of detailed psychiatric anamnesis including anamnesis by the members of a family about the presence of suicides, bipolar disorders and depressions.

The treatment by antidepressants is tied together with heightened risk of suicidal ideas manifestations and appearance of the inadequate behavior by the children and teenagers which are sick in depressing and other psychical disorders.

Cardio-vascular sicknesses

Clinical experiment of Bupropion using for treatment of depression by the ill persons with some cardio-vascular sicknesses is limited that’s why it is followed to apply this medical preparation with some prudence. But in clinical researches with Bupropion application for smoking dishabituation by sick individuals with cardiovascular diseases this medication is passed well.

Arterial pressure

In clinical research with taking part of some sick persons which aren’t ill on depression (including such patients who smoke as people who don’t smoke) and have not treated stage of arterial hypertension the applying of Bupropion didn’t bring to statically meaningful influence on the arterial pressure. But it is also observed the spontaneous reports about heightening of arterial pressure sometimes in view of side effects or overdosing. The synchronous usage of Bupropion and nicotinic transdermal system can bring to the arterial pressure heightening.

Insufficient ways of introduction

Bupropion is indicated for applying per orally only. There are some reports about inhalation of crushed pills or injection of Bupropion dissolution which can bring to the quickest deblocking, accelerated absorption and potential overdosing. There are also some information about epileptic attacks and / or lethal cases (patients’ death) when Bupropion was brought intranasal pr by the way of parenteral injection.

Fertility:

The influence of Bupropion on the human fertility isn’t established. The researches of the reproductive function by the rats didn’t reveal any influencing on the fertility.

Pregnancy:

After some epidemiological researches of influencing on the gestation it was reported about associated risk of the development of cardio-vascular system’s intrauterine pathology by fetus under Bupropion application of pregnant woman in the first term. These data were identical ones in different researches.

Physician must consider the possibility of the alternative treatment of the pregnant person or woman planned the gestation and he has to prescribe Wellbutrin SR only in cases when the waited benefit from the medical cure heightened the potential risk.

According to the data of pregnancy international register the indicators of the inherent cardiac defects under Bupropion application in the first term are 9/675 (1,3%).

Breast-feeding:

As far as Bupropion hydrochloride and its metabolites are egested in the breast milk the women, who apply Wellbutrin SR or other drugs from this category, must stop breast-feeding.

As other medical agents influenced on the person’s central nervous system the substance as Bupropion hydrochloride can influence on the capability to implement some tasks needed the heightened attention and movement coordination. That’s why the patients must observe some care under car driving and some other mechanisms controlling to make sure that Wellbutrin doesn’t disturb their functions.

The preparation begins to operate not earlier than over 14 days after the therapy starting. As under the application of other antidepressants the full effect of this medication is observed over several weeks of the treatment.

Wellbutrin tablets is followed to swallow filly, not divided, not crushed and not masticated because as consequence it can be enlarged the risk of side effects appearance including convulsions.

By the researching data it can be supposed that level of Bupropion can be heightened if the patient would apply this drug with food.

adults

The maximal single dose mustn’t heighten 150 mg. The tablets Wellbutrin t can be used in two applications a day with interval not less than eight hours. The wide-spread side effect under the applying of this medication is insomnia which often has a transient character. You can diminish the frequency of this phenomen appearance if you begin to abstain from application of this drug before sleeping (under the condition of 8-hour interval between dosing observation) or decrease the medicant’s dosage if it is clinically grounded.

The beginning dose is 150 mg once per day.

Bupropion action starting is registered over fourteen days after the treatment beginning. The full anti-depressed effect of Wellbutrin (as other antidepressants) can be manifested not earlier than over several weeks after the medical cure beginning.

Sick persons who is not enough the dosage as 150 mg per day can feel some improvement under the dose increasing till maximal one as 300 mg a day (150 mg two times per day).

The acutest episodes of depression are needed some treating courses by antidepressants during the period not less than six months. It is settled that Wellbutrin in dose as 300 mg a day is effectively used during the prolonged (till one year) period of medical cure.

aged patients

As far as it is impossible to exclude the heightened apprehensibility to this medical preparation by some aged patients it can be needed some diminishing of the applying frequency or medication dosing.

patients with damages of kidneys’ function

It is followed to start the treatment with decreased dosages and / or with less frequency of applying because Bupropion and its metabolites in such sick persons are accumulated in more degree than it is usually happened.

patients with damages of liver’s function

The sick persons with pathology of liver must apply this medical agent with some prudence. Taking into account the heightened variability of this medication’s pharmacokinetics it is necessary to prescribe this medicament in recommended dosage as 150 mg once per day.

The patients with heavy degree of the hepatocirrhosis it is followed to take Wellbutrin vary carefully. The dosages cannot be more than 150 mg a day by such ill persons.

children

The medical preparation is intended for treatment of some children and teenagers. Effectiveness and safety of Wellbutrin applying for this age group isn’t settles.

Besides consequences described in the category of «Side effects» the overdosing call some symptoms which are manifested by sleepiness, loss of consciousness and such exchanges on ECG as damages of conductivity (including the lengthening of QRS interval) or arrhythmia. It was also reported about some fatal outcome under Wellbutrin SR overdosages.

Treatment:

In case of overdosing it is recommended the hospitalization with ECG controlling and some indicators of vital functions. It is necessary to make sure in adequate patency of airways, oxygenation and ventilation. It is recommended the applying of activated carbon. It isn’t recommended the vomiting calling. The specifical antidote for Bupropion isn’t known. The following treatment depends on the clinical condition of patient or some recommendations of the special institution by the curing of poisoning under presence.

By the results of clinical applying the side effects are systematized by the organs and systems and frequency of appearance. By the frequency of appearance all collateral results are divided into very often (≥ 1 on 10), often (≥ 1 on 100 and <1 on 10), not often (≥ 1 on 1000 and <1 on 100), seldom (≥ 1 on 10000 and <1 on 1000), very seldom <(1 on 10000), unknown (by having data the frequency is impossible to define).

The patients applied Wellbutrin SR can have some exchanges of psychical conditions, mania or hypomania.

From the side of immune system*

Often: the reaction of hypersensibility such as nettle rush.

Very seldom: more heavy reaction of hypersensibility including the angioneurotic edema, breathlessness / bronchial spasm or anaphylactic shock.

Arthralgia, myalgia and fever are also appeared in connection with some precipitation and other symptoms of hypersensibility with moderated type. These symptoms can remind the serum sickness.

From the side of metabolism and disorders of digestion*

Often: anorexia.

Not often: body weight decreasing. If the body weight decreasing is the largest symptom of patient’s depression it is followed to take into account such potentials of Wellbutrin SR as anorexia and / or body weight decreasing.

Very seldom: discomposing of the glucose level on blood.

From the side of psychics*

Very often: insomnia.

Unknown: sleeping damages, euphoria, mania, hypomania, some exchanges of the psychical condition.

Often: excitation, stimulation, anxiety.

Not often: depression, dysphoria, random orientation.

Very seldom: aggression, hostility, irritability, uneasiness, hallucinations, unusual dreams, depersonalization, delirium, paranoid thoughts.

Frequency is unknown: suicidal ideas and suicidal behavior, psychosis.

From the side of the central nervous system*

Very often: headaches.

Often: tremor, dizziness, taste discomposing, memory damages, nervousness, agitation, anxiety, myoclonus, dystonia, migraine.

Not often: disorders of the attention concentration, vertigo, acathisia, dysarthria.

Seldom: convulsions, damages of ECG.

Very seldom: dystonia, ataxia, parkinsonism, disorders of the movements’ coordination, memory discomposing, paresthesia, fainting fit.

Unknown: coma, delirium, damages of the apprehensibility, dyskinesia.

From the side of visual organs*

Often: visual disorders.

Seldom: diplopia.

Not often: mydriasis.

Unknown: heightening of eyes pressure.

From the side of hearing organs*

Often: ringing in the ears.

From the side of heart*

Not often: tachycardia, damages of the cardiac rhythm, some changes of ECG.

Seldom: myocardial infarction.

Unknown: heightening of the arterial pressure, edemas.

Very seldom: the strongest palpitation.

From the side of vessels*

Often: heightening of the arterial pressure (in some case it can be considerable one), reddening.

Very seldom: vasodilation, orthostatic hypotension.

From the side of gastrointestinal tract*

Very often: dryness in mouth, gastrointestinal disorders including nausea and vomiting.

Often: some pains in stomach, constipation, dyspepsia.

Not often: toothaches, gums irritation.

Unknown: perforation of the bowels.

Very seldom: heightening of the hepatic ferments’ level, jaundice, hepatitis.

From the side of skin and hypodermic tissue*

Often: precipitation, itching, hyperhidrosis.

Very often: polymorphous erythema, Stevens-Johnson syndrome, psoriasis sharpening.

Unknown: alopecia.

From the side of respiratory system*

Seldom: pulmonary embolism.

Unknown: bronchitis.

From the side of locomotive apparatus and connecting tissues*

Very seldom: vellication or muscle convulsions.

Unknown: arthritis, arthrosis.

From the side of kidneys and urogenital system*

Often: infections of the urogenital system.

Not often: libido lowering.

Very seldom: increasing of the urination frequency and / or its delay.

Unknown: erectile dysfunction, damages of the menstrual cycle, gynecomastia, testicles edema, glycosuria, nocturia.

General disorders*

Often: fever, some pains in breast, asthenia.

From the side of blood*

Unknown: leukocytosis, leukocytopenia, thrombocytopenia.

Two years

It is followed to keep these medicines under the temperature not higher than 25°С in original package. Keep this drug in place too difficult for children.

By 10 pills in blister from polyamide / aluminic foil / polyvinylchloride from one side and aluminic foil covered by the laminated paper for protection from the opening by the children from other side, by 6 blisters in the box.

Wellbutrin, Bupropion, Zyban, Bupron SR, Bupropion hydrochloride