Aplenzin

Name: Aplenzin

Is bupropion available as a generic drug?

GENERIC AVAILABLE: Yes

Side effects

See also Warning section.Dry mouth, sore throat, dizziness, nausea, vomiting, ringing in the ears, headache, decreased appetite, weight loss, constipation, trouble sleeping, increased sweating, or shaking (tremor) may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.An empty tablet shell may appear in your stool. This effect is harmless because your body has already absorbed the medication.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Tell your doctor right away if you have any serious side effects, including: fast/pounding/irregular heartbeat, mental/mood changes (such as anxiety, agitation, confusion, unusual behavior/thinking, memory loss), unusual weight loss or gain.Stop taking bupropion and get medical help right away if you have any very serious side effects, including: seizure.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), painful sores in the mouth/around the eyes, severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Aplenzin Overview

Aplenzin is a prescription medication used to treat depression and prevents seasonal depression.

Aplenzin belongs to a group of drugs called antidepressants, which work by affecting certain natural chemicals in the brain.

This medication comes in extended-release tablets and is typically taken once daily

Common side effects of Aplenzin include nervousness, constipation, trouble sleeping, headache, and nausea.

Aplenzin Usage

Take Aplenzin exactly as prescribed by your doctor.

  • Take Aplenzin at the same time each day.
    • If you are taking Aplenzin for the prevention of seasonal major depressive episodes associated with seasonal affective disorder, it is important to keep taking Aplenzin through the autumn-winter season, or as directed by your healthcare provider.
  • Take Aplenzin once a day, with or without food.
    • Do not chew, crush, or break Aplenzin tablets. Swallow tablets whole. 
  • If you miss a dose, do not take an extra tablet to make up for the dose you missed. Wait and take your next tablet at the regular time. This is very important. Too much Aplenzin can increase your chance of having a seizure. 
  • Do not take any other medicines while using Aplenzin unless your doctor has told you it is okay.
  • For treating depression, it may take several weeks for you to feel that Aplenzin is working. Once you feel better, it is important to keep taking Aplenzin exactly as directed by your doctor. Call your doctor if you do not feel Aplenzin is working for you.
  • Do not change your dose or stop taking bupropion without talking with your doctor first.

Aplenzin FDA Warning

WARNING: SUICIDAL THOUGHTS AND BEHAVIORS and NEUROPSYCHIATRIC REACTIONS

  • Increased risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants.
  • Monitor for worsening and emergence of suicidal thoughts and behaviors.
  • Serious neuropsychiatric events have been reported in patients taking bupropion for smoking cessation. 

How should I take bupropion?

Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended. Too much of this medicine can increase your risk of a seizure.

You may take bupropion with or without food.

Do not crush, chew, or break an extended-release tablet. Swallow it whole.

You should not change your dose or stop using bupropion suddenly, unless you have a seizure while taking this medicine. Stopping suddenly can cause unpleasant withdrawal symptoms. Ask your doctor how to safely stop using bupropion.

If you take Zyban to help you stop smoking, you may continue to smoke for about 1 week after you start the medicine. Set a date to quit smoking during the second week of treatment. Talk to your doctor if you have trouble quitting after taking Zyban for 7 weeks.

Your doctor may prescribe nicotine patches or gum to help you stop smoking. Do not smoke at any time if you are using a nicotine product along with Zyban. Too much nicotine can cause serious side effects.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

You may have nicotine withdrawal symptoms when you stop smoking, including: increased appetite, weight gain, trouble sleeping, trouble concentrating, slower heart rate, having the urge to smoke, and feeling anxious, restless, depressed, angry, frustrated, or irritated. These symptoms may occur with or without using medication such as Zyban.

Smoking cessation may also cause new or worsening mental health problems, such as depression.

Bupropion can cause you to have a false positive drug screening test. If you provide a urine sample for drug screening, tell the laboratory staff that you are taking bupropion.

Store at room temperature away from moisture, heat, and light.

How do I store and/or throw out Aplenzin?

  • Store at room temperature.
  • Protect from light.
  • Store in a dry place. Do not store in a bathroom.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Aplenzin - Clinical Pharmacology

Mechanism of Action

The mechanism of action of bupropion is unknown, as is the case with other antidepressants. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine and does not inhibit monoamine oxidase or the reuptake of serotonin.

Pharmacokinetics

Bupropion is a racemic mixture. The pharmacologic activity and pharmacokinetics of the individual enantiomers have not been studied.

Following chronic dosing of Aplenzin 348 mg once-daily tablets, the mean peak steady-state plasma concentration and area under the curve of bupropion were 134.3 (±38.2) ng/mL and 1409 (±346) ng•hr/mL, respectively. Steady-state plasma concentrations of bupropion were reached within 8 days. The elimination half-life (±SD) of bupropion after a single dose is 21.3 (±6.7) hours.

In a study comparing 10-day dosing with Aplenzin 348 mg once-daily and bupropion HCl extended-release 300 mg once-daily, (following a 3-day titration with bupropion HCl extended-release 150 mg once-daily), Aplenzin peak plasma concentration and area under the curve for bupropion and the 3 metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) were equivalent to bupropion HCl extended-release 300 mg, with the average being 8 to 14% lower.

In a single dose study, two Aplenzin tablets 174 mg once-daily and one Aplenzin tablet 348 mg once-daily were evaluated. Equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the 3 metabolites.

A multiple dose study compared 14-day dosing with Aplenzin tablets 522 mg once-daily to dosing with three Aplenzin tablets 174 mg once-daily, following a 3-day titration with one Aplenzin tablet 174 mg once-daily, and a succeeding 5-day titration with two Aplenzin tablets 174 mg once-daily. Equivalence was demonstrated for peak plasma concentration and area under the curve for bupropion and the 3 metabolites.

These findings demonstrate that Aplenzin tablets 174 mg, 348 mg, and 522 mg are dose proportional.

Absorption

Following single oral administration of Aplenzin tablets to healthy volunteers, the median time to peak plasma concentrations for bupropion was approximately 5 hours. The presence of food did not affect the peak concentration and time to peak plasma concentration of bupropion; the area under the curve was increased by 19%.

Distribution

In vitro tests demonstrated that bupropion is 84% bound to human plasma proteins at concentrations up to 200 mcg/mL. The extent of protein binding of the hydroxybupropion metabolite is similar to that for bupropion, whereas the extent of protein binding of the threohydrobupropion metabolite is about half that of bupropion.

Metabolism

Bupropion is extensively metabolized in humans. Three metabolites are active: hydroxybupropion, which is formed via hydroxylation of the tert-butyl group of bupropion, and the amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, which are formed via reduction of the carbonyl group. In vitro findings suggest that CYP2B6 is the principal isoenzyme involved in the formation of hydroxybupropion, while cytochrome P450 enzymes are not involved in the formation of threohydrobupropion. Oxidation of the bupropion side chain results in the formation of a glycine conjugate of meta-chlorobenzoic acid, which is then excreted as the major urinary metabolite. The potency and toxicity of the metabolites relative to bupropion have not been fully characterized. However, it has been demonstrated in an antidepressant screening test in mice that hydroxybupropion is one half as potent as bupropion, while threohydrobupropion and erythrohydrobupropion are 5-fold less potent than bupropion. This may be of clinical importance, because the plasma concentrations of the metabolites are as high or higher than those of bupropion.

Following chronic administration in healthy volunteers, peak plasma concentration of hydroxybupropion occurred approximately 6 hours after administration of Aplenzin. The peak plasma concentrations of hydroxybupropion were approximately 9 times the peak level of the parent drug at steady state. The elimination half-life of hydroxybupropion is approximately 24.3 (±4.9) hours, and its AUC at steady state is about 15.6 times that of bupropion. The times to peak concentrations for the erythrohydrobupropion and threohydrobupropion metabolites are similar to that of hydroxybupropion. However, the elimination half-lives of erythrohydrobupropion and threohydrobupropion are longer, approximately 31.1(±7.8) and 50.8 (±8.5) hours, respectively, and steady-state AUCs were 1.5 and 6.8 times that of bupropion, respectively.

Bupropion and its metabolites exhibit linear kinetics following chronic administration of 300 mg to 450 mg/day of bupropion hydrochloride (equivalent to 348 mg and 522 mg of Aplenzin, respectively).

Elimination

Following oral administration of 200 mg of 14C-bupropion in humans, 87% and 10% of the radioactive dose were recovered in the urine and feces, respectively. Only 0.5% of the oral dose was excreted as unchanged bupropion.

Population Subgroups

Factors or conditions altering metabolic capacity (e.g., liver disease, congestive heart failure [CHF], age, concomitant medications, etc.) or elimination may be expected to influence the degree and extent of accumulation of the active metabolites of bupropion. The elimination of the major metabolites of bupropion may be affected by reduced renal or hepatic function, because they are moderately polar compounds and are likely to undergo further metabolism or conjugation in the liver prior to urinary excretion.

Renal Impairment

There is limited information on the pharmacokinetics of bupropion in patients with renal impairment. An inter-trial comparison between normal subjects and subjects with end-stage renal failure demonstrated that the parent drug Cmax and AUC values were comparable in the 2 groups, whereas the hydroxybupropion and threohydrobupropion metabolites had a 2.3- and 2.8-fold increase, respectively, in AUC for subjects with end-stage renal failure. A second study, comparing normal subjects and subjects with moderate-to-severe renal impairment (GFR 30.9 ± 10.8 mL/min) showed that after a single 150 mg dose of sustained-release bupropion, exposure to bupropion was approximately 2-fold higher in subjects with impaired renal function, while levels of the hydroxybupropion and threo/erythrohydrobupropion (combined) metabolites were similar in the 2 groups. Bupropion is extensively metabolized in the liver to active metabolites, which are further metabolized and subsequently excreted by the kidneys. The elimination of the major metabolites of bupropion may be reduced by impaired renal function. Aplenzin should be used with caution in patients with renal impairment, and a reduced frequency and/or dose should be considered [see Dosage and Administration (2.7) and Use in Specific Populations (8.6)].

Hepatic Impairment

The effect of hepatic impairment on the pharmacokinetics of bupropion was characterized in 2 single-dose trials, one in subjects with alcoholic liver disease and one in subjects with mild to severe cirrhosis. The first trial demonstrated that the half-life of hydroxybupropion was significantly longer in 8 subjects with alcoholic liver disease than in 8 healthy volunteers (32±14 hours versus 21±5 hours, respectively). Although not statistically significant, the AUCs for bupropion and hydroxybupropion were more variable and tended to be greater (by 53% to 57%) in patients with alcoholic liver disease. The differences in half-life for bupropion and the other metabolites in the 2 groups were minimal.

The second trial demonstrated no statistically significant differences in the pharmacokinetics of bupropion and its active metabolites in 9 subjects with mild to moderate hepatic cirrhosis compared to 8 healthy volunteers. However, more variability was observed in some of the pharmacokinetic parameters for bupropion (AUC, Cmax, and Tmax) and its active metabolites (t½) in subjects with mild to moderate hepatic cirrhosis. In addition, in patients with severe hepatic cirrhosis, the bupropion Cmax and AUC were substantially increased (mean difference: by approximately 70% and 3-fold, respectively) and more variable when compared to values in healthy volunteers; the mean bupropion half-life was also longer (29 hours in subjects with severe hepatic cirrhosis vs. 19 hours in healthy subjects). For the metabolite hydroxybupropion, the mean Cmax was approximately 69% lower. For the combined amino-alcohol isomers threohydrobupropion and erythrohydrobupropion, the mean Cmax was approximately 31% lower. The mean AUC increased by about 1½-fold for hydroxybupropion and about 2½-fold for threo/erythrohydrobupropion. The median Tmax was observed 19 hours later for hydroxybupropion and 31 hours later for threo/erythrohydrobupropion. The mean half-lives for hydroxybupropion and threo/erythrohydrobupropion were increased 5- and 2-fold, respectively, in patients with severe hepatic cirrhosis compared to healthy volunteers [see Dosage and Administration (2.6) and Use in Specific Populations (8.7)].

Left Ventricular Dysfunction

During a chronic dosing study with bupropion in 14 depressed patients with left ventricular dysfunction (history of CHF or an enlarged heart on x-ray), there was no apparent effect on the pharmacokinetics of bupropion or its metabolites, compared to healthy volunteers.

Age

The effects of age on the pharmacokinetics of bupropion and its metabolites have not been fully characterized, but an exploration of steady-state bupropion concentrations from several depression efficacy studies involving patients dosed in a range of 300 to 750 mg/day, on a 3 times daily schedule, revealed no relationship between age (18 to 83 years) and plasma concentration of bupropion. A single-dose pharmacokinetic study demonstrated that the disposition of bupropion and its metabolites in elderly subjects was similar to that in younger subjects. These data suggest that there is no prominent effect of age on bupropion concentration; however, another single- and multiple-dose pharmacokinetic study suggested that the elderly are at increased risk for accumulation of bupropion and its metabolites [see Use in Specific Populations (8.5)].

Gender

A single-dose study involving 12 healthy male and 12 healthy female volunteers revealed no sex-related differences in the pharmacokinetic parameters of bupropion. In addition, pooled analysis of bupropion pharmacokinetic data from 90 healthy male and 90 healthy female volunteers revealed no sex-related differences in the peak plasma concentrations of bupropion. The mean systemic exposure (AUC) was approximately 13% higher in male volunteers compared to female volunteers.

Smokers

The effects of cigarette smoking on the pharmacokinetics of bupropion hydrochloride were studied in 34 healthy male and female volunteers; 17 were chronic cigarette smokers and 17 were nonsmokers. Following oral administration of a single 150 mg dose of bupropion, there was no statistically significant difference in Cmax, half-life, Tmax, AUC, or clearance of bupropion or its active metabolites between smokers and nonsmokers.

Drug Interactions

Potential for Other Drugs to Affect Aplenzin

In vitro studies indicate that bupropion is primarily metabolized to hydroxybupropion by CYP2B6. Therefore, the potential exists for drug interactions between Aplenzin and drugs that are inhibitors or inducers of CYP2B6. In addition, in vitro studies suggest that paroxetine, sertraline, norfluoxetine, fluvoxamine, and nelfinavir inhibit the hydroxylation of bupropion.

Inhibitors of CYP2B6

Ticlopidine, Clopidogrel: In a study in healthy male volunteers, clopidogrel 75 mg once daily or ticlopidine 250 mg twice daily increased exposures (Cmax and AUC) of bupropion by 40% and 60% for clopidogrel, by 38% and 85% for ticlopidine, respectively. The exposures of hydroxybupropion were decreased.

Prasugrel: In healthy subjects, prasugrel increased bupropion Cmax and AUC values by 14% and 18%, respectively, and decreased Cmax and AUC values of hydroxybupropion by 32% and 24%, respectively.

Cimetidine: Following oral administration of bupropion 300 mg with and without cimetidine 800 mg in 24 healthy young male volunteers, the pharmacokinetics of bupropion and hydroxybupropion were unaffected. However, there were 16% and 32% increases in the AUC and Cmax, respectively, of the combined moieties of threohydrobupropion and erythrohydrobupropion.

Citalopram: Citalopram did not affect the pharmacokinetics of bupropion and its three metabolites.

Inducers of CYP2B6

Ritonavir and Lopinavir: In a healthy volunteer study, ritonavir 100 mg twice daily reduced the AUC and Cmax of bupropion by 22% and 21%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 23%, the threohydrobupropion decreased by 38%, and the erythrohydrobupropion decreased by 48%. In a second healthy volunteer study, ritonavir 600 mg twice daily decreased the AUC and Cmax of bupropion by 66% and 62%, respectively. The exposure of the hydroxybupropion metabolite was decreased by 78%, the threohydrobupropion decreased by 50%, and the erythrohydrobupropion decreased by 68%.

In another healthy volunteer study, lopinavir 400 mg/ritonavir 100 mg twice daily decreased bupropion AUC and Cmax by 57%. The AUC and Cmax of hydroxybupropion metabolite were decreased by 50% and 31%, respectively.

Efavirenz: In a study of healthy volunteers, efavirenz 600 mg once daily for 2 weeks reduced the AUC and Cmax of bupropion by approximately 55% and 34%, respectively. The AUC of hydroxybupropion was unchanged, whereas Cmax of hydroxybupropion was increased by 50%.

Carbamazepine, Phenobarbital, Phenytoin: While not systematically studied, these drugs may induce the metabolism of bupropion.

Potential for Aplenzin to Affect Other Drugs

Animal data indicated that bupropion may be an inducer of drug-metabolizing enzymes in humans. In a study of 8 healthy male volunteers, following a 14-day administration of bupropion 100 mg three times per day, there was no evidence of induction of its own metabolism. Nevertheless, there may be the potential for clinically important alterations of blood levels of coadministered drugs.

Drugs Metabolized by CYP2D6

In vitro, bupropion and hydroxybupropion are CYP2D6 inhibitors. In a clinical study of 15 male subjects (ages 19 to 35 years) who were extensive metabolizers of CYP2D6, bupropion given as 150 mg twice daily followed by a single dose of 50 mg desipramine increased the Cmax, AUC, and T1/2 of desipramine by an average of approximately 2-, 5-, and 2-fold, respectively. The effect was present for at least 7 days after the last dose of bupropion. Concomitant use of bupropion with other drugs metabolized by CYP2D6 has not been formally studied.

Citalopram: Although citalopram is not primarily metabolized by CYP2D6, in one study bupropion increased the Cmax and AUC of citalopram by 30% and 40%, respectively.

Lamotrigine: Multiple oral doses of bupropion had no statistically significant effects on the single-dose pharmacokinetics of lamotrigine in 12 healthy volunteers.

Where can i get more information?

Your pharmacist can provide more information about bupropion.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of bupropion can be fatal. Overdose symptoms may include muscle stiffness, hallucinations, fast or uneven heartbeat, shallow breathing, or fainting.

What should I avoid while taking Aplenzin?

Drinking alcohol with bupropion may increase your risk of seizures. If you drink alcohol regularly, talk with your doctor before changing the amount you drink. Aplenzin can also cause seizures in people who drink a lot of alcohol and then suddenly quit drinking when they start using the medication.

Aplenzin may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Aplenzin side effects

Get emergency medical help if you have any of these signs of an allergic reaction to Aplenzin: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, depression, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

  • a seizure (convulsions);

  • unusual changes in mood or behavior;

  • a manic episode - racing thoughts, increased energy, reckless behavior, feeling extremely happy or irritable, talking more than usual, severe problems with sleep;

  • blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;

  • fast heartbeats; or

  • severe skin reaction, fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Common Aplenzin side effects may include:

  • dry mouth, stuffy nose;

  • nausea, constipation;

  • sleep problems (insomnia);

  • feeling anxious;

  • dizziness; or

  • joint pain.

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

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