• Oltha PLUS indications
• Uses of Oltha PLUS in details
• Oltha PLUS dosage
• Oltha PLUS interactions
• Oltha PLUS side effects
• Oltha PLUS contraindications

What is Oltha PLUS?

Fluoxetine (Oltha PLUS) is an antidepressant in a group of drugs called selective serotonin reuptake inhibitors (SSRIs).

Olanzapine (Oltha PLUS) is an antipsychotic medication. These drugs affect chemicals in the brain.

Oltha PLUS is a combination medicine used to treat depression caused by bipolar disorder (manic depression). Oltha PLUS is also used to treat depression after at least 2 other medications have been tried without successful treatment of symptoms.

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

Oltha PLUS indications

Depressive Episodes Associated with Bipolar I Disorder

Oltha PLUS® is indicated for the acute treatment of depressive episodes associated with Bipolar I Disorder.

Treatment Resistant Depression

Oltha PLUS is indicated for the acute treatment of treatment resistant depression (Major Depressive Disorder in adults who do not respond to 2 separate trials of different antidepressants of adequate dose and duration in the current episode).

How should I use Oltha PLUS?

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

• Oltha PLUS comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Oltha PLUS refilled.
• Take Oltha PLUS by mouth on an empty stomach or with food.
• Take Oltha PLUS in the evening, unless your doctor tells you otherwise.
• Continue to take Oltha PLUS even if you feel well. Do not miss any doses.
• Do not suddenly stop taking Oltha PLUS without checking with your doctor. Side effects may occur. They may include mental or mood changes, agitation, anxiety, irritability, numbness or tingling of the skin, dizziness, confusion, headache, trouble sleeping, or unusual tiredness. You will be closely monitored when you start Oltha PLUS and whenever a change in dose is made.
• If you miss a dose of Oltha PLUS, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Oltha PLUS.

Uses of Oltha PLUS in details

Use: Labeled Indications

Depression, acute (associated with bipolar I disorder): Treatment of acute depressive episodes associated with bipolar I disorder

Depression, treatment-resistant: Treatment of treatment-resistant depression (eg, unresponsive to 2 trials of different antidepressants in the current episode)

Oltha PLUS dosage

Oltha PLUS Dosage

Generic name: Olanzapine (Oltha PLUS) 6mg, Fluoxetine (Oltha PLUS) hydrochloride 25mg

Dosage form: capsule

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

Depressive Episodes Associated with Bipolar I Disorder

Adults — Administer Oltha PLUS once daily in the evening, generally beginning with the 6 mg/25 mg (mg Olanzapine (Oltha PLUS)/mg equivalent Fluoxetine (Oltha PLUS)) capsule. While food has no appreciable effect on the absorption of Olanzapine (Oltha PLUS) and Fluoxetine (Oltha PLUS) given individually, the effect of food on the absorption of Oltha PLUS has not been studied. Make dosage adjustments, if indicated, according to efficacy and tolerability. Antidepressant efficacy was demonstrated with Oltha PLUS in a dose range of Olanzapine (Oltha PLUS) 6 mg to 12 mg and Fluoxetine (Oltha PLUS) 25 mg to 50 mg. The safety of doses above 18 mg of Olanzapine (Oltha PLUS) and 75 mg of Fluoxetine (Oltha PLUS) has not been evaluated in adult clinical studies. Periodically reexamine the need for continued pharmacotherapy.

Children and Adolescents (10 to 17 years of age) — Administer Oltha PLUS once daily in the evening, generally beginning with the 3 mg/25 mg capsule, without regard to meals, with a recommended target dose within the approved dosing range (6/25; 6/50; 12/25; 12/50 mg). The safety of doses above 12 mg of Olanzapine (Oltha PLUS) and 50 mg of Fluoxetine (Oltha PLUS) has not been evaluated in pediatric clinical studies. Periodically reexamine the need for continued pharmacotherapy.

Treatment Resistant Depression

Administer Oltha PLUS once daily in the evening, generally beginning with the 6 mg/25 mg capsule. While food has no appreciable effect on the absorption of Olanzapine (Oltha PLUS) and Fluoxetine (Oltha PLUS) given individually, the effect of food on the absorption of Oltha PLUS has not been studied. Adjust dosage, if indicated, according to efficacy and tolerability. Antidepressant efficacy was demonstrated with Oltha PLUS in a dose range of Olanzapine (Oltha PLUS) 6 mg to 18 mg and Fluoxetine (Oltha PLUS) 25 mg to 50 mg. The safety of doses above 18 mg/75 mg has not been evaluated in clinical studies. Periodically reexamine the need for continued pharmacotherapy.

Specific Populations

Start Oltha PLUS at 3 mg/25 mg or 6 mg/25 mg in patients with a predisposition to hypotensive reactions, patients with hepatic impairment, or patients who exhibit a combination of factors that may slow the metabolism of Oltha PLUS (female gender, geriatric age, nonsmoking status) or those patients who may be pharmacodynamically sensitive to Olanzapine (Oltha PLUS). Titrate slowly and adjust dosage as needed in patients who exhibit a combination of factors that may slow metabolism. Oltha PLUS has not been systematically studied in patients >65 years of age or in patients <10 years of age.

Treatment of Pregnant Women — When treating pregnant women with Fluoxetine (Oltha PLUS), a component of Oltha PLUS, the physician should carefully consider the potential risks and potential benefits of treatment. Neonates exposed to SSRIs or SNRIs late in the third trimester have developed complications requiring prolonged hospitalizations, respiratory support, and tube feeding..

Switching a Patient To or From a Monoamine Oxidase Inhibitor (MAOI) Intended to Treat Psychiatric Disorders

At least 14 days should elapse between discontinuation of an MAOI intended to treat psychiatric disorders and initiation of therapy with Oltha PLUS. Conversely, at least 5 weeks should be allowed after stopping Oltha PLUS before starting an MAOI intended to treat psychiatric disorders.

Use of Oltha PLUS with Other MAOIs such as Linezolid or Methylene Blue

Do not start Oltha PLUS in a patient who is being treated with linezolid or intravenous methylene blue because there is an increased risk of serotonin syndrome. In a patient who requires more urgent treatment of a psychiatric condition, other interventions, including hospitalization, should be considered.

In some cases, a patient already receiving Oltha PLUS therapy may require urgent treatment with linezolid or intravenous methylene blue. If acceptable alternatives to linezolid or intravenous methylene blue treatment are not available and the potential benefits of linezolid or intravenous methylene blue are judged to outweigh the risks of serotonin syndrome in a particular patient, Oltha PLUS should be stopped promptly, and linezolid or intravenous methylene blue can be administered. The patient should be monitored for symptoms of serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid or intravenous methylene blue, whichever comes first. Therapy with Oltha PLUS may be resumed 24 hours after the last dose of linezolid or intravenous methylene blue.

The risk of administering methylene blue by non-intravenous routes (such as oral tablets or by local injection) or in intravenous doses much lower than 1 mg/kg with Oltha PLUS is unclear. The clinician should, nevertheless, be aware of the possibility of emergent symptoms of serotonin syndrome with such use.

Discontinuation of Treatment with Oltha PLUS

Symptoms associated with discontinuation of Fluoxetine (Oltha PLUS), a component of Oltha PLUS, SNRIs, and SSRIs, have been reported.

More about Oltha PLUS (Fluoxetine (Oltha PLUS) / Olanzapine (Oltha PLUS))

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• During Pregnancy
• Dosage Information
• Drug Images
• Drug Interactions
• Support Group
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• En Espanol
• 46 Reviews - Add your own review/rating
• Generic Availability

Consumer resources

• Oltha PLUS
• Oltha PLUS (Advanced Reading)

Professional resources

• Oltha PLUS (FDA)

Related treatment guides

• Depression
• Major Depressive Disorder
• Bipolar Disorder

Oltha PLUS interactions

See also:
What other drugs will affect Oltha PLUS?

The risks of using Oltha PLUS in combination with other drugs have not been extensively evaluated in systematic studies. The drug-drug interactions sections of Oltha PLUS are applicable to Oltha PLUS. As with all drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic drug inhibition or enhancement, etc.) is a possibility. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status.

Monoamine Oxidase Inhibitors (MAOIs)

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CNS Acting Drugs

Caution is advised if the concomitant administration of Oltha PLUS and other CNS-active drugs is required. In evaluating individual cases, consideration should be given to using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status.

Serotonergic Drugs

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Drugs that Interfere with Hemostasis (e.g., NSAIDs, Aspirin, Warfarin)

Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies of the case-control and cohort design that have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding have also shown that concurrent use of an NSAID or aspirin may potentiate this risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SNRIs or SSRIs are coadministered with warfarin. Warfarin (20 mg single dose) did not affect Olanzapine (Oltha PLUS) pharmacokinetics. Single doses of Olanzapine (Oltha PLUS) did not affect the pharmacokinetics of warfarin. Patients receiving warfarin therapy should be carefully monitored when Oltha PLUS is initiated or discontinued.

Electroconvulsive Therapy (ECT)

There are no clinical studies establishing the benefit of the combined use of ECT and Fluoxetine (Oltha PLUS). There have been rare reports of prolonged seizures in patients on Fluoxetine (Oltha PLUS) receiving ECT treatment.

Potential for Other Drugs to Affect Oltha PLUS

Benzodiazepines — Co-administration of diazepam with Olanzapine (Oltha PLUS) potentiated the orthostatic hypotension observed with Olanzapine (Oltha PLUS).

Inducers of 1A2 — Carbamazepine therapy (200 mg BID) causes an approximate 50% increase in the clearance of Olanzapine (Oltha PLUS). This increase is likely due to the fact that carbamazepine is a potent inducer of CYP1A2 activity. Higher daily doses of carbamazepine may cause an even greater increase in Olanzapine (Oltha PLUS) clearance.

Alcohol — Ethanol (45 mg/70 kg single dose) did not have an effect on Olanzapine (Oltha PLUS) pharmacokinetics.

Inhibitors of CYP1A2 — Fluvoxamine decreases the clearance of Olanzapine (Oltha PLUS). This results in a mean increase in Olanzapine (Oltha PLUS) Cmax following fluvoxamine administration of 54% in female nonsmokers and 77% in male smokers. The mean increase in Olanzapine (Oltha PLUS) AUC is 52% and 108%, respectively. Lower doses of the Olanzapine (Oltha PLUS) component of Oltha PLUS should be considered in patients receiving concomitant treatment with fluvoxamine.

The Effect of Other Drugs on Olanzapine (Oltha PLUS) — Fluoxetine (Oltha PLUS), an inhibitor of CYP2D6, decreases Olanzapine (Oltha PLUS) clearance a small amount. Agents that induce CYP1A2 or glucuronyl transferase enzymes, such as omeprazole and rifampin, may cause an increase in Olanzapine (Oltha PLUS) clearance. The effect of CYP1A2 inhibitors, such as fluvoxamine and some fluoroquinolone antibiotics, on Oltha PLUS has not been evaluated. Although Olanzapine (Oltha PLUS) is metabolized by multiple enzyme systems, induction or inhibition of a single enzyme may appreciably alter Olanzapine (Oltha PLUS) clearance. Therefore, a dosage increase (for induction) or a dosage decrease (for inhibition) may need to be considered with specific drugs.

Potential for Oltha PLUS to Affect Other Drugs

Pimozide — Concomitant use of Oltha PLUS and pimozide is contraindicated. Pimozide can prolong the QT interval. Oltha PLUS can increase the level of pimozide through inhibition of CYP2D6. Oltha PLUS can also prolong the QT interval. Clinical studies of pimozide with other antidepressants demonstrate an increase in drug interaction or QTc prolongation. While a specific study with pimozide and Oltha PLUS has not been conducted, the potential for drug interactions or QTc prolongation warrants restricting the concurrent use of pimozide and Oltha PLUS.

Carbamazepine — Patients on stable doses of carbamazepine have developed elevated plasma anticonvulsant concentrations and clinical anticonvulsant toxicity following initiation of concomitant Fluoxetine (Oltha PLUS) treatment.

Alcohol — The coadministration of ethanol with Oltha PLUS may potentiate sedation and orthostatic hypotension.

Thioridazine — Thioridazine should not be administered with Oltha PLUS or administered within a minimum of 5 weeks after discontinuation of Oltha PLUS, because of the risk of QT prolongation.

In a study of 19 healthy male subjects, which included 6 slow and 13 rapid hydroxylators of debrisoquin, a single 25 mg oral dose of thioridazine produced a 2.4-fold higher Cmax and a 4.5-fold higher AUC for thioridazine in the slow hydroxylators compared with the rapid hydroxylators. The rate of debrisoquin hydroxylation is felt to depend on the level of CYP2D6 isozyme activity. Thus, this study suggests that drugs that inhibit CYP2D6, such as certain SSRIs, including Fluoxetine (Oltha PLUS), will produce elevated plasma levels of thioridazine.

Thioridazine administration produces a dose-related prolongation of the QTc interval, which is associated with serious ventricular arrhythmias, such as torsades de pointes-type arrhythmias and sudden death. This risk is expected to increase with Fluoxetine (Oltha PLUS)-induced inhibition of thioridazine metabolism.

Due to the risk of serious ventricular arrhythmias and sudden death potentially associated with elevated thioridazine plasma levels, thioridazine should not be administered with Fluoxetine (Oltha PLUS) or within a minimum of 5 weeks after Fluoxetine (Oltha PLUS) has been discontinued.

Tricyclic Antidepressants (TCAs) — Single doses of Olanzapine (Oltha PLUS) did not affect the pharmacokinetics of imipramine or its active metabolite desipramine.

In 2 Fluoxetine (Oltha PLUS) studies, previously stable plasma levels of imipramine and desipramine have increased > 2- to 10fold when Fluoxetine (Oltha PLUS) has been administered in combination. This influence may persist for 3 weeks or longer after Fluoxetine (Oltha PLUS) is discontinued. Thus, the dose of TCA may need to be reduced and plasma TCA concentrations may need to be monitored temporarily when Oltha PLUS is coadministered or has been recently discontinued.

Antihypertensive Agents — Because of the potential for Olanzapine (Oltha PLUS) to induce hypotension, Oltha PLUS may enhance the effects of certain antihypertensive agents.

Levodopa and Dopamine Agonists — The Olanzapine (Oltha PLUS) component of Oltha PLUS may antagonize the effects of levodopa and dopamine agonists.

Benzodiazepines — Multiple doses of Olanzapine (Oltha PLUS) did not influence the pharmacokinetics of diazepam and its active metabolite N-desmethyldiazepam.

When concurrently administered with Fluoxetine (Oltha PLUS), the half-life of diazepam may be prolonged in some patients. Coadministration of alprazolam and Fluoxetine (Oltha PLUS) has resulted in increased alprazolam plasma concentrations and in further psychomotor performance decrement due to increased alprazolam levels.

Clozapine — Elevation of blood levels of clozapine has been observed in patients receiving concomitant Fluoxetine (Oltha PLUS).

Haloperidol — Elevation of blood levels of haloperidol has been observed in patients receiving concomitant Fluoxetine (Oltha PLUS).

Phenytoin — Patients on stable doses of phenytoin have developed elevated plasma levels of phenytoin with clinical phenytoin toxicity following initiation of concomitant Fluoxetine (Oltha PLUS).

Drugs Metabolized by CYP2D6 — In vitro studies utilizing human liver microsomes suggest that Olanzapine (Oltha PLUS) has little potential to inhibit CYP2D6. Thus, Olanzapine (Oltha PLUS) is unlikely to cause clinically important drug interactions mediated by this enzyme.

Fluoxetine (Oltha PLUS) inhibits the activity of CYP2D6 and may make individuals with normal CYP2D6 metabolic activity resemble a poor metabolizer. Coadministration of Fluoxetine (Oltha PLUS) with other drugs that are metabolized by CYP2D6, including certain antidepressants (e.g., TCAs), antipsychotics (e.g., phenothiazines and most atypicals), and antiarrhythmics (e.g., propafenone, flecainide, and others) should be approached with caution. Therapy with medications that are predominantly metabolized by the CYP2D6 system and that have a relatively narrow therapeutic index should be initiated at the low end of the dose range if a patient is receiving Fluoxetine (Oltha PLUS) concurrently or has taken it in the previous 5 weeks. If Fluoxetine (Oltha PLUS) is added to the treatment regimen of a patient already receiving a drug metabolized by CYP2D6, the need for a decreased dose of the original medication should be considered. Drugs with a narrow therapeutic index represent the greatest concern (including but not limited to, flecainide, propafenone, vinblastine, and TCAs).

Drugs Metabolized by CYP3A — In vitro studies utilizing human liver microsomes suggest that Olanzapine (Oltha PLUS) has little potential to inhibit CYP3A. Thus, Olanzapine (Oltha PLUS) is unlikely to cause clinically important drug interactions mediated by these enzymes.

In an in vivo interaction study involving the coadministration of Fluoxetine (Oltha PLUS) with single doses of terfenadine (a CYP3A substrate), no increase in plasma terfenadine concentrations occurred with concomitant Fluoxetine (Oltha PLUS). In addition, in vitro studies have shown ketoconazole, a potent inhibitor of CYP3A activity, to be at least 100 times more potent than Fluoxetine (Oltha PLUS) or norfluoxetine as an inhibitor of the metabolism of several substrates for this enzyme, including astemizole, cisapride, and midazolam. These data indicate that Fluoxetine (Oltha PLUS)'s extent of inhibition of CYP3A activity is not likely to be of clinical significance.

Effect of Olanzapine (Oltha PLUS) on Drugs Metabolized by Other CYP Enzymes — In vitro studies utilizing human liver microsomes suggest that Olanzapine (Oltha PLUS) has little potential to inhibit CYP1A2, CYP2C9, and CYP2C19. Thus, Olanzapine (Oltha PLUS) is unlikely to cause clinically important drug interactions mediated by these enzymes.

Lithium — Multiple doses of Olanzapine (Oltha PLUS) did not influence the pharmacokinetics of lithium.

There have been reports of both increased and decreased lithium levels when lithium was used concomitantly with Fluoxetine (Oltha PLUS). Cases of lithium toxicity and increased serotonergic effects have been reported. Lithium levels should be monitored in patients taking Oltha PLUS concomitantly with lithium.

Drugs Tightly Bound to Plasma Proteins — The in vitro binding of Oltha PLUS to human plasma proteins is similar to the individual components. The interaction between Oltha PLUS and other highly protein-bound drugs has not been fully evaluated. Because Fluoxetine (Oltha PLUS) is tightly bound to plasma protein, the administration of Fluoxetine (Oltha PLUS) to a patient taking another drug that is tightly bound to protein (e.g., Coumadin, digitoxin) may cause a shift in plasma concentrations potentially resulting in an adverse effect. Conversely, adverse effects may result from displacement of protein-bound Fluoxetine (Oltha PLUS) by other tightly bound drugs.

Valproate — In vitro studies using human liver microsomes determined that Olanzapine (Oltha PLUS) has little potential to inhibit the major metabolic pathway, glucuronidation, of valproate. Further, valproate has little effect on the metabolism of Olanzapine (Oltha PLUS) in vitro. Thus, a clinically significant pharmacokinetic interaction between Olanzapine (Oltha PLUS) and valproate is unlikely.

Biperiden — Multiple doses of Olanzapine (Oltha PLUS) did not influence the pharmacokinetics of biperiden.

Theophylline — Multiple doses of Olanzapine (Oltha PLUS) did not affect the pharmacokinetics of theophylline or its metabolites.

Drugs that Prolong the QT Interval

Do not use Oltha PLUS in combination with thioridazine or pimozide. Use Oltha PLUS with caution in combination with other drugs that cause QT prolongation. These include: specific antipsychotics (e.g., ziprasidone, iloperidone, chlorpromazine, mesoridazine, droperidol); specific antibiotics (e.g., erythromycin, gatifloxacin, moxifloxacin, sparfloxacin); Class 1A antiarrhythmic medications (e.g., quinidine, procainamide); Class III antiarrhythmics (e.g., amiodarone, sotalol); and others (e.g., pentamidine, levomethadyl acetate, methadone, halofantrine, mefloquine, dolasetron mesylate, probucol or tacrolimus). Fluoxetine (Oltha PLUS) is primarily metabolized by CYP2D6. Concomitant treatment with CYP2D6 inhibitors can increase the concentration of Fluoxetine (Oltha PLUS). Concomitant use of other highly protein-bound drugs can increase the concentration of Fluoxetine (Oltha PLUS).

Drug Abuse And Dependence

Dependence

Oltha PLUS, as with Oltha PLUS, has not been systematically studied in humans for its potential for abuse, tolerance, or physical dependence. While the clinical studies did not reveal any tendency for any drug-seeking behavior, these observations were not systematic, and it is not possible to predict on the basis of this limited experience the extent to which a CNS-active drug will be misused, diverted, and/or abused once marketed. Consequently, physicians should carefully evaluate patients for history of drug abuse and follow such patients closely, observing them for signs of misuse or abuse of Oltha PLUS (e.g., development of tolerance, incrementation of dose, drug-seeking behavior).

In studies in rats and rhesus monkeys designed to assess abuse and dependence potential, Olanzapine (Oltha PLUS) alone was shown to have acute depressive CNS effects but little or no potential of abuse or physical dependence at oral doses up to 15 (rat) and 8 (monkey) times the MRHD (20 mg) on a mg/m² basis.

Oltha PLUS side effects

See also:
What are the possible side effects of Oltha PLUS?

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice.

Clinical Trials Experience

Adverse reactions were recorded by clinical investigators using descriptive terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse reactions without first grouping similar types of reactions into a limited (i.e., reduced) number of standardized reaction categories.

In the tables and tabulations that follow, MedDRA or COSTART Dictionary terminology has been used to classify reported adverse reactions. The data in the tables represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. It is possible that reactions reported during therapy were not necessarily related to drug exposure.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing clinician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence rate in the population studied.

Adults

The information below is derived from a clinical study database for Oltha PLUS consisting of 2547 patients with treatment resistant depression, depressive episodes associated with Bipolar I Disorder, Major Depressive Disorder with psychosis, or sexual dysfunction with approximately 1085 patient-years of exposure. The conditions and duration of treatment with Oltha PLUS varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, fixed-dose and dose-titration studies, and short-term or long-term exposure.

Adverse Reactions Associated with Discontinuation of Treatment in Short-Term, Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression

Overall, 11.3% of the 771 patients in the Oltha PLUS group discontinued due to adverse reactions compared with 4.4% of the 477 patients for placebo. Adverse reactions leading to discontinuation associated with the use of Oltha PLUS (incidence of at least 1% for Oltha PLUS and greater than that for placebo) using MedDRA Dictionary coding were weight increased (2%) and sedation (1%) versus placebo patients which had 0% incidence of weight increased and sedation.

Commonly Observed Adverse Reactions in Short-Term, Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression

The most commonly observed adverse reactions associated with the use of Oltha PLUS (incidence ≥ 5% and at least twice that for placebo in the Oltha PLUS-controlled database) using MedDRA Dictionary coding were: disturbance in attention, dry mouth, fatigue, hypersomnia, increased appetite, peripheral edema, sedation, somnolence, tremor, vision blurred, and weight increased. Adverse reactions reported in clinical trials of Olanzapine (Oltha PLUS) and Fluoxetine (Oltha PLUS) in combination are generally consistent with treatment-emergent adverse reactions during Olanzapine (Oltha PLUS) or Fluoxetine (Oltha PLUS) monotherapy.

Adverse Reactions Occurring at an Incidence of 2% or More in Short-Term Controlled Studies Including Depressive Episodes Associated with Bipolar I Disorder and Treatment Resistant Depression

Table 13 enumerates the treatment-emergent adverse reactions associated with the use of Oltha PLUS (incidence of at least 2% for Oltha PLUS and twice or more than for placebo). The Oltha PLUS-controlled column includes patients with various diagnoses while the placebo column includes only patients with bipolar depression and major depression with psychotic features.

Table 13: Treatment-Emergent Adverse Reactions: Incidence in the Adult Controlled Clinical Studies