BYANNLI: Uses, Dosage & Side Effects

What Is BYANNLI and What Is It Used For?

BYANNLI contains the active substance paliperidone palmitate, which is the palmitate ester prodrug of paliperidone. Paliperidone (also known as 9-hydroxyrisperidone) is the major active metabolite of risperidone and belongs to the class of atypical (second-generation) antipsychotic medications. Atypical antipsychotics are distinguished from older, first-generation (typical) antipsychotics by their additional activity at serotonin receptors, which is believed to contribute to a more favorable side effect profile, particularly with regard to movement disorders (extrapyramidal symptoms).

Schizophrenia is a chronic and often severely debilitating mental health disorder that affects approximately 1% of the global population – around 24 million people worldwide according to the World Health Organization. It is characterized by a combination of positive symptoms (hallucinations, delusions, disorganized thinking), negative symptoms (social withdrawal, diminished emotional expression, reduced motivation), and cognitive impairment (difficulties with attention, memory, and executive function). Schizophrenia typically emerges in late adolescence or early adulthood and requires lifelong treatment to manage symptoms and prevent relapse.

One of the greatest challenges in the long-term management of schizophrenia is treatment adherence. Studies have consistently shown that up to 50–75% of patients with schizophrenia become partially or fully non-adherent to oral antipsychotic medication within the first two years of treatment. Non-adherence dramatically increases the risk of relapse, hospitalization, functional decline, and poorer long-term outcomes. Long-acting injectable (LAI) antipsychotics were developed specifically to address this challenge by providing sustained therapeutic drug levels over extended periods, eliminating the need for daily oral medication and ensuring continuous treatment delivery.

BYANNLI represents the latest advancement in LAI antipsychotic technology. It was developed using a nanosuspension formulation of paliperidone palmitate with a larger particle size and higher concentration compared to the 1-monthly and 3-monthly formulations. After intramuscular injection, the paliperidone palmitate particles dissolve very slowly at the injection site, are gradually hydrolyzed to release free paliperidone, and are then absorbed into the systemic circulation over a period of many months. This slow dissolution and absorption results in sustained therapeutic paliperidone plasma concentrations for up to 6 months from a single injection.

The efficacy of BYANNLI was established in the pivotal phase III TECH (Treatment with Extended-release injectable paliperidone palmitate – Continued Healthcare) study, a randomized, double-blind, non-inferiority trial comparing BYANNLI (administered every 6 months) to the 3-monthly formulation (TREVICTA/INVEGA TRINZA) in patients with schizophrenia who were already clinically stable. The primary endpoint was the relapse rate over 12 months of treatment. The study demonstrated that BYANNLI was non-inferior to the 3-monthly formulation, with similar relapse rates and sustained symptom control across the treatment period. The Positive and Negative Syndrome Scale (PANSS) total scores remained stable in both groups, confirming that switching from the 3-monthly to the 6-monthly formulation did not compromise efficacy.

BYANNLI was first approved by the European Medicines Agency (EMA) in June 2020 and subsequently by the U.S. Food and Drug Administration (FDA) in September 2021 (marketed as INVEGA HAFYERA in the United States). It is now available in multiple countries worldwide. BYANNLI is indicated for the maintenance treatment of schizophrenia in adult patients who are clinically stable on the 1-monthly or 3-monthly paliperidone palmitate injection formulations.

What Should You Know Before Taking BYANNLI?

Contraindications

BYANNLI must not be used if you have a known hypersensitivity (allergy) to paliperidone, risperidone, or any of the excipients in the formulation. Because paliperidone is the major active metabolite of risperidone, patients with a documented allergy to risperidone should also not receive BYANNLI. Hypersensitivity reactions to paliperidone products have included anaphylaxis, angioedema (swelling of the face, throat, or tongue), and severe skin reactions. If you experience any signs of an allergic reaction after receiving BYANNLI, seek immediate medical attention.

BYANNLI is contraindicated as a first-line treatment for schizophrenia. It should only be initiated in patients who have already demonstrated adequate tolerability and clinical stability on the 1-monthly or 3-monthly paliperidone palmitate formulations. The rationale for this requirement is the extremely long half-life of BYANNLI: once injected, paliperidone will remain in the body for many months, and if an adverse reaction occurs, it cannot be rapidly removed. Prior stabilization on shorter-acting formulations confirms that the patient tolerates paliperidone before committing to the 6-month dosing interval.

Warnings and Precautions

Before starting BYANNLI, discuss the following conditions and risk factors with your healthcare provider:

• Cardiovascular disease: Paliperidone can cause orthostatic hypotension (a drop in blood pressure upon standing), particularly during dose initiation. Patients with known cardiovascular disease, cerebrovascular disease, dehydration, or hypovolemia may be at increased risk. BYANNLI may also prolong the QT interval on an electrocardiogram (ECG), which can increase the risk of serious cardiac arrhythmias. Patients with a history of cardiac arrhythmias, congenital long QT syndrome, or those taking other QT-prolonging medications should be carefully evaluated.
• Metabolic effects: Atypical antipsychotics, including paliperidone, can cause metabolic changes such as weight gain, hyperglycemia (high blood sugar), dyslipidemia (abnormal cholesterol and triglyceride levels), and increased risk of developing type 2 diabetes mellitus. Regular monitoring of body weight, fasting glucose, and lipid profiles is recommended during treatment.
• Prolactin elevation: Paliperidone is a potent prolactin-elevating agent. Hyperprolactinemia can cause menstrual irregularities, galactorrhea (breast milk production), gynecomastia (breast enlargement in men), sexual dysfunction, and potentially contribute to decreased bone mineral density with long-term elevation. Patients should be informed of these potential effects.
• Tardive dyskinesia: Long-term use of antipsychotics carries a risk of tardive dyskinesia (TD), a potentially irreversible movement disorder characterized by involuntary, repetitive movements of the face, tongue, and extremities. The risk increases with duration of treatment and cumulative dose. If signs of TD develop, the benefits and risks of continuing treatment should be reassessed.
• Seizures: Paliperidone should be used with caution in patients with a history of seizures or conditions that lower the seizure threshold.
• Elderly patients with dementia: BYANNLI is not approved for the treatment of behavioral symptoms in elderly patients with dementia. Antipsychotic medications are associated with an increased risk of cerebrovascular events (stroke, transient ischemic attack) and death in this population.
• Venous thromboembolism (VTE): Cases of deep vein thrombosis and pulmonary embolism have been reported with antipsychotic use. Patients with risk factors for VTE should be identified and preventive measures taken.

Pregnancy and Breastfeeding

BYANNLI should not be used during pregnancy unless the potential benefit to the mother clearly outweighs the risk to the fetus. Neonates exposed to antipsychotics during the third trimester are at risk for extrapyramidal symptoms and withdrawal symptoms, which may include agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding difficulties. These symptoms are generally self-limiting but can be severe in some cases.

A critical consideration unique to BYANNLI is its extremely long half-life. Because paliperidone can remain in the body for many months after a single injection, women of childbearing potential must be counseled about the need for effective contraception during treatment and for at least 18 months after the last injection. If pregnancy occurs during treatment, the patient should contact her healthcare provider immediately to discuss the potential risks and management options.

Paliperidone is excreted in human breast milk. The effects of paliperidone on breastfed infants have not been adequately studied. The decision to breastfeed during treatment with BYANNLI should be made in consultation with the prescribing physician, weighing the benefit of breastfeeding against the potential risk to the infant. Given the prolonged exposure after BYANNLI injection, paliperidone will be present in breast milk for an extended period.

Driving and Operating Machinery

Paliperidone may cause somnolence (drowsiness), dizziness, and visual disturbances, all of which can impair the ability to drive or operate machinery. Patients should be advised not to drive, operate heavy machinery, or engage in activities requiring full mental alertness until they know how BYANNLI affects them. These effects may be particularly pronounced at the beginning of treatment or when the dose is changed.

How Does BYANNLI Interact with Other Drugs?

Understanding potential drug interactions is essential for safe use of BYANNLI. Paliperidone has a relatively favorable drug interaction profile compared to many other antipsychotics because it is not extensively metabolized by cytochrome P450 (CYP) enzymes. Approximately 59% of paliperidone is excreted unchanged in the urine, with limited hepatic metabolism. However, several clinically relevant interactions exist that healthcare providers and patients should be aware of.

Paliperidone is a substrate of P-glycoprotein (P-gp) and, to a limited extent, CYP3A4. Co-administration of strong inducers of both CYP3A4 and P-gp (such as carbamazepine, rifampicin, or St. John’s wort) may decrease paliperidone plasma concentrations, potentially reducing the efficacy of BYANNLI. However, due to the unique pharmacokinetic profile of the 6-month formulation – where absorption from the injection site is the rate-limiting step – the clinical significance of these interactions may be less pronounced compared to oral paliperidone or shorter-acting injectable formulations.

Paliperidone is not a clinically relevant inhibitor of CYP1A2, CYP2A6, CYP2C8/9/10, CYP2D6, CYP2E1, CYP3A4, or CYP3A5. Therefore, BYANNLI is not expected to affect the metabolism of other drugs that are substrates of these enzymes. Co-administration with paroxetine (a potent CYP2D6 inhibitor) increased paliperidone exposure by only 16% in a study with oral paliperidone, which is not considered clinically significant, and no dose adjustment is recommended.

It is important to note that due to the extremely long half-life of BYANNLI, any drug interaction will also have prolonged effects. If a strong CYP3A4/P-gp inducer is co-administered, the potential reduction in paliperidone levels will be sustained for the duration of inducer use. Conversely, when the inducer is discontinued, paliperidone levels may rise. Healthcare providers should monitor patients closely during any changes in concomitant medication.

What Is the Correct Dosage of BYANNLI?

BYANNLI is administered exclusively by healthcare professionals as an intramuscular injection. It is not suitable for self-administration. The medication is provided as a prolonged-release suspension for injection in a pre-filled syringe. Treatment with BYANNLI requires careful adherence to the recommended dosing schedule and transition pathway to ensure optimal therapeutic outcomes.

Adults

BYANNLI is available in a single strength of 700 mg paliperidone palmitate (equivalent to approximately 441 mg of paliperidone). The recommended dose is one injection every 6 months (approximately every 26 weeks), administered by intramuscular injection into either the deltoid muscle (upper arm) or the gluteal muscle (buttock).

The transition to BYANNLI should occur at the time of the next scheduled injection of the previous formulation. When transitioning from the 1-monthly formulation, patients must have been on a stable dose of 100 mg eq. or 150 mg eq. for at least 4 months. When transitioning from the 3-monthly formulation, patients must have received at least one injection at a dose of 350 mg eq. or 525 mg eq. The first BYANNLI injection is given in place of the next scheduled dose of the previous formulation.

BYANNLI should be injected using the provided needle (22-gauge, 1.5 inch [38 mm] for gluteal injection; 22-gauge, 1 inch [25 mm] for deltoid injection). The injection should be given slowly and steadily due to the high viscosity and volume of the suspension. The deltoid muscle is preferred for the first BYANNLI injection because it achieves higher initial plasma concentrations, helping to maintain therapeutic levels during the transition period.

Children and Adolescents

BYANNLI is not recommended for use in patients under 18 years of age. The safety and efficacy of BYANNLI have not been established in the pediatric population. Treatment of schizophrenia in adolescents should be managed with age-appropriate antipsychotic formulations under specialist psychiatric supervision.

Elderly Patients

No specific dose adjustment is required for elderly patients based solely on age. However, elderly patients may be more susceptible to the pharmacological effects of paliperidone, including orthostatic hypotension, sedation, and anticholinergic-like effects. Renal function should be assessed, as dose adjustments may be needed based on renal impairment. BYANNLI should not be used in elderly patients with dementia-related psychosis due to the increased risk of cerebrovascular events and mortality.

Missed Dose

Maintaining the regular 6-monthly injection schedule is important. If a dose is missed, the timing of the next injection depends on how long ago it was due:

• Up to 2 months late: Administer the missed BYANNLI injection as soon as possible, then resume the regular 6-monthly schedule from the date of that injection.
• 2 to 9 months late: Re-initiation with the 1-monthly formulation may be necessary, followed by a transition back to BYANNLI once the patient is restabilized. Your doctor will determine the appropriate re-initiation regimen.
• More than 9 months late: Full re-initiation of the paliperidone palmitate treatment sequence (starting with the 1-monthly formulation initiation regimen) is typically required.

Overdose

Due to the long-acting nature of BYANNLI, signs and symptoms of overdose may be delayed and prolonged. There is no specific antidote for paliperidone. Treatment should be supportive, including cardiovascular monitoring (ECG for QT prolongation and arrhythmias), respiratory monitoring, and management of symptoms such as severe extrapyramidal symptoms, hypotension, and excessive sedation. Close medical supervision and monitoring should continue for an extended period given the very long half-life of the formulation. Hemodialysis is not expected to be effective in removing paliperidone because it is highly protein-bound.

What Are the Side Effects of BYANNLI?

Like all antipsychotic medications, BYANNLI can cause side effects, although not everyone who receives it will experience them. The safety profile of BYANNLI is consistent with the well-established safety profile of paliperidone observed across the 1-monthly and 3-monthly formulations, with the addition of injection site reactions specific to the 6-month formulation. Clinical trial data from the pivotal TECH study and its open-label extensions provide the primary safety information for BYANNLI.

In the TECH study, the most commonly reported treatment-emergent adverse events in the BYANNLI group included injection site reactions, weight gain, nasopharyngitis, and headache. The overall incidence of adverse events was comparable between the BYANNLI and TREVICTA groups, with no new safety signals identified for the 6-monthly formulation. Injection site reactions were more common with BYANNLI than with the 3-monthly formulation, likely due to the larger injection volume and the physical characteristics of the nanosuspension.

Injection site reactions deserve special mention for BYANNLI. Because of the larger volume of injection (3.5 mL) and the formulation characteristics, patients may experience pain, induration (hardening), swelling, or palpable nodules at the injection site. In clinical trials, injection site reactions were reported in approximately 30–40% of patients receiving BYANNLI, with the majority being mild to moderate in intensity. Nodules at the injection site can persist for several weeks but typically resolve without intervention. Alternating between deltoid and gluteal injection sites between administrations may help reduce cumulative injection site reactions.

Weight gain is an important metabolic consideration with all atypical antipsychotics. In the TECH study, the mean weight change over 12 months of BYANNLI treatment was approximately +1.5 kg, which was comparable to the 3-monthly formulation group. Regular monitoring of body weight and metabolic parameters (fasting glucose, lipid profile) is recommended throughout treatment. Patients should be encouraged to maintain a healthy diet and regular physical activity to mitigate metabolic risks.

Prolactin elevation is a well-known class effect of paliperidone, which has higher prolactin-elevating properties compared to some other atypical antipsychotics. Elevated prolactin levels can lead to menstrual irregularities, galactorrhea, gynecomastia, sexual dysfunction, and potentially contribute to decreased bone mineral density over time. If clinically significant hyperprolactinemia develops, the benefits of continued treatment should be weighed against the potential long-term consequences, and treatment alternatives may need to be considered.

How Should You Store BYANNLI?

Proper storage is essential to maintain the integrity and efficacy of BYANNLI. As a nanosuspension formulation, the physical characteristics of the product can be affected by temperature extremes and improper handling.

• Refrigerated storage: Store BYANNLI in the refrigerator at 2–8 °C (36–46 °F). Keep the pre-filled syringe in the original carton to protect it from light. This is the primary storage condition.
• Do not freeze: Freezing can alter the suspension characteristics and compromise the drug product. If BYANNLI has been accidentally frozen, it must not be used.
• Temporary room temperature storage: BYANNLI may be removed from the refrigerator and stored at temperatures not exceeding 30 °C (86 °F) for a single period of up to 48 hours prior to administration. If not used within 48 hours at room temperature, the product must be discarded.
• Keep out of reach of children: Store in a location inaccessible to children.
• Check expiration date: Do not use BYANNLI after the expiration date printed on the carton and syringe label. The expiration date refers to the last day of that month.
• Shake vigorously before use: The syringe must be shaken vigorously for at least 15 seconds to ensure a homogeneous suspension before injection. This is a critical step in the preparation process.
• Single use only: Each pre-filled syringe is for single use and single patient use only. Discard any unused portion.

Healthcare facilities storing BYANNLI should ensure that refrigeration equipment is functioning properly and that temperature monitoring systems are in place. Any deviations from the recommended storage conditions should be reported to the pharmacy and the product should not be used if storage conditions have been compromised.

What Does BYANNLI Contain?

Understanding the composition of BYANNLI is important for identifying potential allergies or sensitivities. Below is a detailed breakdown of the active and inactive ingredients.

Active Ingredient

The active substance is paliperidone palmitate, a palmitate ester prodrug that is hydrolyzed in vivo to release paliperidone, the pharmacologically active compound. Paliperidone (9-hydroxyrisperidone) is an atypical antipsychotic that exerts its therapeutic effects primarily through combined dopamine D2 and serotonin 5-HT2A receptor antagonism. Each pre-filled syringe contains 700 mg of paliperidone palmitate in 3.5 mL of suspension, corresponding to a concentration of 200 mg/mL.

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

BYANNLI is supplied as a white to off-white prolonged-release suspension for intramuscular injection in a pre-filled syringe. Each carton contains one pre-filled syringe with 3.5 mL of suspension, two needles (one for deltoid injection and one for gluteal injection), and a plunger rod for assembly. The suspension must be shaken vigorously for at least 15 seconds immediately before use to ensure uniform distribution of the drug substance.

Marketing Authorization Holder and Manufacturer

BYANNLI is manufactured by Janssen Pharmaceutica NV (Beerse, Belgium) and marketed by Janssen-Cilag International NV. In the European Union, the marketing authorization holder is Janssen-Cilag International NV (Beerse, Belgium). In the United States, the product is marketed by Janssen Pharmaceuticals, Inc. under the brand name INVEGA HAFYERA. BYANNLI/INVEGA HAFYERA is available in multiple countries, though availability may vary by region.