Taking Control of Tardive Dyskinesia Symptoms with Ingrezza

1. Taking Control of Tardive Dyskinesia Symptoms with Ingrezza Tardive dyskinesia (TD) is a neurological condition that leads to involuntary and repetitive movements, typically involving the face, mouth, tongue, or limbs.1,2 These movements might look like rapid eye blinking, lip-smacking, frowning, or jerky arm and leg motions.2 TD usually occurs as a side effect of long-term treatment with medications that block dopamine receptors in the brain including antipsychotics and antiemetics.1 Why is tardive dyskinesia a concern? For many psychiatric patients, developing TD can be deeply distressing. Involuntary movements are often visible to others, leading to stigma, embarrassment, and social isolation.1 People with TD may also face difficulty in speaking, eating, or performing daily activities.2 TD in patients with schizophrenia is linked with cognitive decline, poor treatment outcomes, higher relapse rates, longer hospital stays, and even increased mortality.1 In short, TD not only affects the body—it affects mental well-being of the patient.2 How does dopamine imbalance lead to TD? Dopamine plays a key role in controlling movement. When these medications reduce dopamine activity for extended periods, the brain tries to adjust by becoming overly responsive to dopamine. This change in sensitivity can lead to abnormal motor signals, causing the uncontrolled movements seen in tardive dyskinesia.1 Vesicular monoamine transporters and their role To understand modern treatment approaches for TD, it's helpful to know about vesicular monoamine transporters (VMATs). These are proteins inside nerve cells that critical role in the packaging, storage and release of dopamine.1 Inhibiting VMAT2 reduces the packaging and release of dopamine from nerve cells. As a result, more dopamine is broken down inside the cell, decreasing its availability to overstimulate hypersensitive receptors. This process helps control the abnormal movements associated with tardive dyskinesia.1 Medications that inhibit VMAT2 have shown encouraging results in managing hyperkinetic movement disorders. One such treatment, Ingrezza is specifically approved for treating tardive dyskinesia.1 Treating TD with Ingrezza Ingrezza, also known by its generic name valbenazine, is the first medication approved specifically for the treatment of tardive dyskinesia.3 It works by selectively inhibiting VMAT2, reducing the amount of dopamine released into the synapse. This action helps normalize the dopamine signaling in motor pathways and reduce the abnormal movements associated with TD.3,4 Dosage Recommendations for Ingrezza

2. Valbenazine is available in capsule form. In most cases, treatment begins with a dose of 40 mg once daily, taken with or without food. After one week, the dose may be increased to 80 mg once daily, based on the patient’s response and tolerance.4 Here are key dosage considerations4: • Elderly patients usually do not require dose adjustments. • Patients with moderate or severe liver impairment should stick to 40 mg once daily. • Patients with severe renal impairment should not use Ingrezza. • No dose changes are typically needed for mild-to-moderate renal impairment. • When used with strong CYP3A4 inhibitors, the dose should be reduced. • Do not use CYP3A4 inducers with Ingrezza. • Patients who are poor CYP2D6 metabolizers or take strong CYP2D6 inhibitors may also need dose adjustments. Safety Profile and side effects Ingrezza has been shown to be generally safe and well-tolerated. The most commonly reported side effect is mild drowsiness. Other side effects that may occur include fatigue, dry mouth, nausea, sedation, headache, decreased appetite, vomiting and back pain.4 Importantly, Ingrezza does not appear to worsen psychiatric symptoms. There is no strong evidence linking it to increased suicidal thoughts, new-onset depression, or a return of psychosis. The psychiatric status of patients remained stable in clinical studies.4 Precautions and drug interactions Before starting Ingrezza, patients should inform their doctor about all medications they are taking. Key precautions include4: • Avoid combining with monoamine oxidase inhibitors, as this could increase the risk of serotonin syndrome or reduce Ingrezza's effect. • Ingrezza can raise digoxin levels, combining the two requires careful monitoring. • Patients with liver or kidney impairment may require special dosing. • Discuss any history of heart conditions, especially if taking medications that prolong the QT interval. Comparing Ingrezza with other available therapies Tardive dyskinesia can significantly impact a patient's quality of life, leading to challenges such as treatment nonadherence and an increased risk of morbidity and mortality. One of the earlier treatments used for managing TD is tetrabenazine.5 While tetrabenazine can effectively reduce involuntary movements, it has notable limitations. The drug has a short half-life and displays variable pharmacokinetics, meaning it behaves differently across individuals, making consistent symptom control more difficult. In addition, its use is often constrained by side effects, including drowsiness, restlessness, depressive symptoms, and signs of parkinsonism.5

3. To address these challenges, Ingrezza was derived from the active metabolite of tetrabenazine but engineered to offer a longer half-life and a more predictable pharmacological profile. This results in the potential for once-daily dosing and fewer side effects.4,5 Accessing Ingrezza in India Through the Named Patient Program (NPP) As of now, Ingrezza is not commercially available in India. However, patients may still be able to access it under a special program known as the Named Patient Program (NPP).6 Through the NPP, doctors can apply for access to Ingrezza on behalf of patients with a clear medical need. The process usually involves: 1.Obtaining a valid prescription and case justification from a licensed doctor. 2.Partnering with a licensed importer like Rx4U to streamline the process of importation, manage documentation, and provide legal compliance. 3.Regulatory clearance from Indian health authorities for personal import. This route allows patients in India to receive life-changing therapies like Ingrezza. Key Takeaways • Tardive dyskinesia is a serious caused by long-term dopamine receptor blockade. • Ingrezza (valbenazine) is a VMAT2 inhibitor that reduces dopamine release and helps control abnormal movements. • It has a favourable safety profile, is taken once daily, and does not worsen mental health symptoms. • Patients in India can access Ingrezza through the Named Patient Program with a doctor’s guidance. Frequently Asked Questions (FAQs) Q. What exactly is Ingrezza used for? Ingrezza is a medication used to treat involuntary movements caused by tardive dyskinesia (TD). It helps reduce abnormal facial, tongue, or limb movements that may develop after long-term use of certain psychiatric medications.3,4 Q. Will Ingrezza affect my mental health or worsen my psychiatric condition? No. Ingrezza is not known to worsen psychiatric symptoms such as depression, anxiety, or psychosis.4 Q. What are the most common side effects of Ingrezza? The most common side effect is drowsiness. Some people may also experience fatigue, dry mouth, headache, or nausea. Most side effects are mild and temporary.4 Q. Can Ingrezza be taken by elderly patients? Yes. Ingrezza can be safely used by older adults, although dosing may need to be adjusted in some cases, especially if there are liver or kidney issues.4 Note:

4. The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment. Disclaimer: Rx4U procures prescribed medicines directly from manufacturers or authorized distributors. It does not claim ownership of any trademarks and complies with the provisions of the Trademark Act, 1999, particularly Sections 30 and 30(1) concerning ‘Fair Use’. It solely facilitates access to new launches through named patient import. References: 1.Caroff SN, Aggarwal S, Yonan C. Treatment of tardive dyskinesia with tetrabenazine or valbenazine: a systematic review. J. Comp.Eff.Res. 2018;7(2):135-48. 2.Tardive Dyskinesia. Cleveland Clinic. Updated on October 7, 2024. Accessed July 7, 2025. https://my.clevelandclinic.org/health/diseases/6125-tardive-dyskinesia 3.Uhlyar S, Rey JA. Valbenazine (Ingrezza): The first FDA-approved treatment for tardive dyskinesia. P&T. 2018;43(6):328. 4.Müller T. Valbenazine for the treatment of tardive dyskinesia. Expert Rev. Neurother. 2017;17(12):1135-44. 5.Seeberger LC, Hauser RA. Valbenazine for the treatment of tardive dyskinesia. Expert Opin.Pharmacother. 2017;18(12):1279-87. 6.Patil S. Early access programs: Benefits, challenges, and key considerations for successful implementation.Perspect Clin Res. 2016;7(1):4-8. doi:10.4103/2229- 3485.173779