Opipza

Indications and Usage for Opipza

OPIPZA is prescribed for the:

• management of schizophrenia in individuals 13 years and older
• supplementary treatment of major depressive disorder (MDD) in adults
• relief of irritability linked to autistic disorder in children 6 years and older
• control of Tourette’s disorder in children 6 years and older

Opipza Dosage and Administration

Schizophrenia in Patients 13 Years and Older

Adults

The suggested initial and maintenance dose of OPIPZA for treating schizophrenia in adults is 10 mg or 15 mg taken once daily. Research has thoroughly assessed aripiprazole, proving its efficacy within a dosage span of 10 mg to 30 mg daily; however, amounts exceeding 10 mg or 15 mg daily did not outperform the lower doses. Dose escalation should typically wait at least 2 weeks, the duration required to reach steady-state.

Pediatric Patients Ages 13 Years and Older

The advised starting dose of OPIPZA for addressing schizophrenia in youths 13 years and older is 2 mg once daily. The preferred maintenance dose is 10 mg once daily. Studies explored aripiprazole in adolescents aged 13 to 17 with schizophrenia using daily doses of 10 mg and 30 mg. Treatment began at 2 mg daily, increased to 5 mg after 2 days, and reached the goal of 10 mg after 2 more days. Further dose hikes should proceed in 5 mg steps. The 30 mg daily dose did not prove superior to the 10 mg daily dose.

Adjunctive Treatment of Major Depressive Disorder in Adults

The advised initial dose for OPIPZA as a supplemental treatment for MDD in adults on antidepressants is 2 mg to 5 mg once daily. The suggested dose range spans 2 mg to 15 mg daily. Adjustments up to 5 mg daily should be gradual, spaced at least one week apart. Regular reevaluation is necessary to confirm the ongoing need for sustained therapy.

Irritability Linked to Autism Spectrum Disorder in Children Aged 6 and Up

The recommended dose range for treating irritability tied to autistic disorder in children aged 6 to 17 is 5 mg to 15 mg once daily.

Therapy should begin at 2 mg once daily. This should rise to 5 mg daily, with further increases to 10 mg or 15 mg daily if required. Adjustments up to 5 mg daily should occur slowly, with at least one-week gaps. Periodic reassessment is essential to verify the need for continued treatment.

Tourette’s Disorder in Pediatric Patients 6 Years and Older

The suggested dose range for managing Tourette’s disorder in children 6 years and older is 5 mg to 20 mg once daily.

For patients under 50 kg, treatment should start at 2 mg once daily, aiming for 5 mg daily after 2 days. The dose may increase to 10 mg daily if tic control remains inadequate. Adjustments should be gradual, with at least one-week intervals.

For patients 50 kg or heavier, dosing begins at 2 mg daily for 2 days, rises to 5 mg daily for 5 days, and targets 10 mg daily by Day 8. The dose may climb to 20 mg daily if tics aren’t fully managed. Adjustments should proceed in 5 mg daily increments, spaced at least one week apart.

Regular reevaluation is needed to assess the ongoing necessity of treatment.

Important Administration Information of OPIPZA

1. Guide patients and/or caregivers to thoroughly review the “Instruction for Use” for precise steps on measuring and delivering OPIPZA.
2. Give OPIPZA by mouth, with or without meals.
3. Place OPIPZA atop the tongue, where it melts in saliva and can be swallowed naturally without requiring water or other fluids.
4. Advise the patient not to chew the film or ingest it undissolved. Avoid slicing or dividing OPIPZA.
5. Use only one oral film per dose. If another film is needed to fulfill the dose, apply it after the prior one has fully dissolved.

Dosage Forms and Strengths

OPIPZA is a white rectangular film available in doses of 2 mg (1 cm by 1.2 cm), 5 mg (2 cm by 1.5 cm), and 10 mg (2 cm by 3 cm), marked with A2, A5, and A10, respectively.

Contraindications

OPIPZA must not be used in individuals with a past allergic reaction to aripiprazole. Allergic responses, varying from itching/hives to severe anaphylaxis, have occurred in patients taking aripiprazole.

Warnings and Precautions

Increased Risk of Mortality in Elderly Patients

Older adults with psychosis linked to dementia face a heightened risk of death when treated with antipsychotic medications. Reviews of 17 placebo-controlled studies (typically lasting 10 weeks), mostly involving atypical antipsychotics, showed a mortality risk in treated patients 1.6 to 1.7 times higher than in those receiving placebo. During a standard 10-week trial, the death rate among treated patients was approximately 4.5%, versus about 2.6% in the placebo group.

While causes of death differed, most were tied to cardiovascular issues (e.g., heart failure, sudden death) or infections (e.g., pneumonia). Observational research indicates that, like atypical antipsychotics, traditional antipsychotics may also elevate mortality. It remains uncertain how much these findings reflect the medication versus patient-specific factors.

OPIPZA is not authorized for treating dementia-related psychosis in patients.

Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis

In placebo-controlled trials (two with flexible dosing, one with fixed dosing) for dementia-related psychosis, aripiprazole-treated patients (average age: 84 years; range: 78 to 88 years) showed a higher rate of cerebrovascular events (e.g., stroke, transient ischemic attack), some fatal. The fixed-dose study revealed a clear dose-related increase in these events among aripiprazole recipients. OPIPZA is not approved for managing dementia-related psychosis.

Suicidal Thoughts and Behaviors in Adolescents and Young Adults

Combined analyses of placebo-controlled antidepressant trials (SSRIs and other classes), covering around 77,000 adults and 4,500 children, found a greater occurrence of suicidal thoughts and actions in treated patients aged 24 and younger compared to placebo recipients. Risk levels varied across drugs, yet most showed elevated danger in younger patients. Absolute risk differed by condition, with major depressive disorder (MDD) showing the highest rates.

Whether this risk persists with extended use (beyond four months) in children, teens, and young adults is unclear. Still, robust evidence from adult MDD maintenance trials shows antidepressants reduce depression recurrence, a known trigger for suicidal tendencies.

Track all patients on antidepressants for worsening symptoms or emerging suicidal thoughts and behaviors, particularly in the first few months of treatment or during dose adjustments. Advise families or caregivers to watch for behavioral shifts and notify the doctor. If depression worsens consistently or suicidal tendencies arise, consider altering treatment, potentially stopping OPIPZA. Note that OPIPZA lacks approval for pediatric depression treatment.

Neuroleptic Malignant Syndrome (NMS)

Neuroleptic Malignant Syndrome (NMS), a rare but life-threatening condition, has been linked to antipsychotics, including aripiprazole. Isolated NMS cases have surfaced in aripiprazole’s worldwide clinical records.

NMS symptoms include high fever, stiff muscles, confusion, and autonomic dysfunction (e.g., erratic pulse or blood pressure, rapid heartbeat, sweating, and heart rhythm issues). Other signs might involve raised creatine phosphokinase, muscle breakdown (myoglobinuria), and sudden kidney failure.

If NMS is suspected, stop OPIPZA immediately and begin supportive care and observation.

Tardive Dyskinesia

Tardive dyskinesia, a condition marked by persistent, uncontrollable movements, may occur in antipsychotic-treated patients. Though more common in older adults, particularly women, predicting who will develop it is challenging. It’s unknown if antipsychotics vary in their likelihood of causing this condition.

The chance of tardive dyskinesia, and its permanence, seems to rise with longer treatment and higher total doses. Yet, it can emerge after short-term use at low doses or even post-treatment cessation.

Symptoms may lessen or resolve fully if antipsychotics are stopped. However, ongoing treatment might hide or reduce symptoms, potentially obscuring the condition’s root cause. The impact of this masking on its long-term progression remains uncertain.

Thus, prescribe OPIPZA to minimize tardive dyskinesia risk. Limit long-term antipsychotic use to patients with chronic conditions (1) responsive to such drugs and (2) lacking safer, equally effective options. For those needing prolonged therapy, aim for the lowest dose and shortest duration yielding positive results, with periodic reassessment of necessity.

If tardive dyskinesia signs appear in an OPIPZA patient, weigh discontinuation. Some may still need OPIPZA despite the condition’s presence.

OPIPZA interaction with other drugs

OPIPZA (aripiprazole) interacts with drugs affecting its metabolism, mainly through CYP2D6 and CYP3A4 enzymes.
It can increase side effects when taken with certain inhibitors and lose effectiveness with inducers.
Common interacting drugs include antidepressants, antifungals, and anticonvulsants.

What Drugs Does OPIPZA Interact With?

OPIPZA, containing aripiprazole, can interact with many medications, especially those that affect how your body processes it. Here’s a simple breakdown:

Drugs That Increase OPIPZA Levels

Some drugs slow down how OPIPZA is broken down, leading to higher levels in your body, which can cause more side effects like drowsiness or movement issues. For example:

• Antifungals like ketoconazole and itraconazole.
• Antibiotics like clarithromycin and erythromycin.
• Antidepressants like fluoxetine and paroxetine, which are also used for depression or anxiety.

If you’re on these, your doctor might lower your OPIPZA dose to avoid problems.

Drugs That Decrease OPIPZA Levels

Other drugs speed up OPIPZA breakdown, reducing its effectiveness, meaning it might not help as much with conditions like schizophrenia or depression. Examples include:

• Anticonvulsants like carbamazepine and phenytoin, used for seizures.
• Herbs like St. John’s wort, often taken for mood.
• Your doctor might need to increase your dose if you’re on these.

Other Interactions to Watch For

OPIPZA can also interact in other ways:

• Sedatives like benzodiazepines or alcohol can make you feel more sleepy or dizzy when combined with OPIPZA.
• Diabetes medications might need adjusting because OPIPZA can raise blood sugar.
• Parkinson’s drugs like levodopa might not work as well due to OPIPZA’s effects on dopamine.

Surprising Detail: Herbal Risks

It’s surprising that something as common as St. John’s wort, often seen as a natural remedy, can reduce OPIPZA’s effectiveness by speeding up its breakdown.

Detailed Analysis of OPIPZA Drug Interactions

This detailed examination explores the drug interactions associated with OPIPZA (aripiprazole), an antipsychotic medication primarily metabolized by cytochrome P450 enzymes CYP2D6 and CYP3A4. Understanding these interactions is crucial for ensuring safe and effective treatment, particularly for conditions like schizophrenia, major depressive disorder (MDD), and irritability associated with autistic disorder.

Metabolic Interactions: CYP Enzyme Modulation

Aripiprazole’s metabolism is significantly influenced by drugs that inhibit or induce CYP2D6 and CYP3A4, affecting its plasma levels and therapeutic efficacy. The following categories detail specific interactions:

1. Strong CYP3A4 Inhibitors

These drugs can increase aripiprazole levels by inhibiting its metabolism, potentially leading to enhanced side effects such as sedation, akathisia, or QT prolongation. The prescribing information recommends reducing the aripiprazole dose to half when coadministered with strong CYP3A4 inhibitors. Examples include:

• Antifungal agents include ketoconazole, itraconazole, voriconazole, and posaconazole.
• Antibiotics: clarithromycin, erythromycin, telithromycin.
• Antidepressants: nefazodone.
• Antiretrovirals: indinavir, nelfinavir, ritonavir, saquinavir.
• Calcium Channel Blockers: diltiazem, verapamil.
• Histamine H2 Receptor Antagonists: cimetidine.

For instance, ketoconazole can increase aripiprazole levels by approximately 200%, necessitating careful dose adjustment.

2. Moderate CYP3A4 Inhibitors

Moderate inhibitors may also elevate aripiprazole levels, requiring monitoring and potential dosage adjustments based on clinical response. Examples include:

• Antidepressants: fluoxetine, fluvoxamine.
• Natural Products: grapefruit juice, which can inhibit CYP3A4 in the gut.

Fluoxetine, notably, is also a strong CYP2D6 inhibitor, compounding its effect on aripiprazole metabolism.

3. CYP2D6 Inhibitors

CYP2D6 inhibitors affect the conversion of aripiprazole to its active metabolite, dehydroaripiprazole, which has similar activity. Generally, no dosage adjustment is required, but patients, especially those who are poor CYP2D6 metabolizers, should be monitored for side effects. Examples include:

• Antidepressants: fluoxetine, paroxetine, duloxetine, bupropion.
• Antiarrhythmics: quinidine.
• Others: haloperidol, terbinafine.

For example, paroxetine can increase aripiprazole levels by about 30% for the parent drug, potentially leading to increased side effects.

4. Strong CYP3A4 Inducers

These drugs accelerate aripiprazole metabolism, reducing its plasma levels and potentially diminishing efficacy. Dosage increases may be necessary, and patients should be monitored for therapeutic response. Examples include:

• Anticonvulsants: carbamazepine, phenytoin, phenobarbital.
• Antibiotics: rifampin, rifabutin, rifapentine.
• Herbs: St. John’s wort.

Carbamazepine, for instance, can decrease aripiprazole levels significantly, requiring dose doubling in some cases.

Pharmacodynamic Interactions: Additive and Antagonistic Effects

Beyond metabolic interactions, aripiprazole can interact pharmacodynamically with other drugs, affecting shared physiological systems:

1. CNS Depressants

Aripiprazole can have additive effects with other central nervous system (CNS) depressants, leading to increased sedation, motor impairment, and risk of falls. This is particularly relevant for:

• Benzodiazepines: e.g., lorazepam, diazepam.
• Alcohol: can exacerbate sedation and impair coordination.
• Opioids: e.g., morphine, oxycodone.
• Antihistamines: e.g., diphenhydramine, which can enhance drowsiness.

Patients should be cautioned against alcohol consumption and monitored for excessive sedation when combining these agents.

2. QT-Prolonging Drugs

Although aripiprazole has a low risk for QT prolongation, combining it with other QT-prolonging drugs may increase the risk of arrhythmias, particularly in patients with predisposing factors. Examples include:

• Antipsychotics: ziprasidone, haloperidol.
• Antibiotics: erythromycin, moxifloxacin.
• Antiarrhythmics: quinidine, amiodarone.

Monitoring for ECG changes may be warranted in such cases.

3. Antidiabetic Agents

Aripiprazole can cause hyperglycemia, potentially affecting blood sugar control in patients taking antidiabetic medications. Examples include:

• Insulin: may require dose adjustments.
• Oral Hypoglycemics: e.g., metformin, sulfonylureas.

Regular monitoring of blood glucose levels is recommended to manage potential interactions.

4. Levodopa and Dopamine Agonists

As a partial dopamine agonist, aripiprazole may interfere with the efficacy of levodopa and other dopamine agonists used in Parkinson’s disease, potentially worsening motor symptoms. Examples include:

• Levodopa: used for Parkinson’s, may have reduced effectiveness.
• Pramipexole: a dopamine agonist, may be affected similarly.

Patients should be monitored for changes in parkinsonian symptoms, and alternative treatments may be considered.

Drugs with No Significant Interactions

Aripiprazole does not significantly inhibit or induce cytochrome P450 enzymes, minimizing its impact on the metabolism of other drugs. Studies have shown no significant interactions with:

• Lithium: commonly used in bipolar disorder.
• Valproate: an anticonvulsant and mood stabilizer.
• Lorazepam: a benzodiazepine for anxiety.

This lack of interaction simplifies coadministration with these agents in clinical practice.

Clinical Management and Dosage Adjustments

The prescribing information for aripiprazole provides specific guidance for managing interactions, particularly for cytochrome P450 considerations. For example:

• When coadministered with strong CYP3A4 inhibitors, reduce the aripiprazole dose to half.
• For strong CYP3A4 inducers, consider doubling the dose, with monitoring for efficacy.
• For patients taking a combination of strong, moderate, and weak inhibitors of CYP3A4 and CYP2D6 (e.g., a strong CYP3A4 inhibitor with a moderate CYP2D6 inhibitor), the dose may be reduced to one-quarter (25%) of the recommended dose initially, then adjusted to achieve clinical response.

Regular monitoring for efficacy and side effects is essential, especially in complex polypharmacy scenarios.

Conclusion

OPIPZA’s drug interactions are primarily driven by its metabolism via CYP2D6 and CYP3A4, with significant implications for dosage adjustments when coadministered with inhibitors or inducers. Pharmacodynamic interactions, such as additive CNS depression and effects on blood sugar, also require careful management. Healthcare providers should review patients’ medication lists, adjust doses as recommended, and monitor for efficacy and side effects to ensure safe use.

Sources and publications:

1. https://pmc.ncbi.nlm.nih.gov/articles/PMC6373521/
2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216655s000lbl.pdf
3. https://www.webmd.com/drugs/2/drug-189785/opipza-oral/details
4. https://www.webmd.com/drugs/2/drug-64439/abilify-oral/details
5. https://go.drugbank.com/drugs/DB00334
6. https://www.medcentral.com/drugs/monograph/64437-302040/aripiprazole-oral