Lurasidone HCl - Dosage, Administration, Indications, Contraindications, Side Effects, Warnings and Precautions

Overview:

Lurasidone is a medicine belonging to the antipsychotic drug group. This drug is commonly used to treat schizophrenia. Lurasidone has also been found to help improve the mood of people dealing with bipolar depression. Lurasidone blocks certain communication pathways in the brain involving chemicals. It attaches to receptors for dopamine and serotonin. Lurasidone got approval from the Food and Drug Administration (FDA) for treating schizophrenia in adults in October 2010. About three years later, in July 2012, it was approved for treating depressive episodes linked to bipolar I disorder.

Drug Group:

Lurasidone HCl is a medication used to treat schizophrenia, which is an antipsychotic drug. It belongs to a chemical group called benzisothiazole derivatives. It is a white powder that does not dissolve well in water. It helps with schizophrenia by affecting dopamine D2 brain receptors present in the brain.

Dosage Forms:

• 20 mg(milligrams) tablets are round and white or off-white with "L20" on one side.

• 40 mg tablets are round and white or off-white with "L40" on one side.

• 60 mg tablets are oblong (stretched oval), white, or off-white with "L60" on one side.

• 80 mg tablets are pale green and shaped like ovals with "L80" on one side.

• 120 mg tablets are oval, white, or off-white with "L120" on one side.

Available Doses:

Lurasidone should always be taken with a meal (at least 350 calories) for better absorption.

For Adults:

• Lurasidone is started by taking 40 mg once a day.

• It is well between the dosages of 40 mg and 160 mg per day.

• 160 mg per day is the maximum dose that an individual can take.

For Adolescents:

• If the person is a teenager, they should start the dosing schedule with 40 mg once a day. There is no need to change the dose initially.

• The effective range for adolescents is between 40 mg and 80 mg per day.

• The maximum dose for teens is 80 mg per day.

Dosage for Dealing With Bipolar I Disorder and Depression (In Adults):

• Adults should start with 20 mg a day, either on its own or with Lithium or Valproate.

• A person does not need to increase the dose to get results.

• It is effective in the dosage of 20 mg to 120 mg per day, either alone or with other medicines.

• The maximum recommended dosing in a day is 120 mg. As per studies, taking more than 80 mg to 120 mg did not show extra benefits compared to taking 20 to 60 mg per day.

For Patients

What Is Atypical Psychotics?

Atypical psychotics is a major mental disorder, either due to a physical issue or emotional factors, where a person's ability to think, feel, remember, communicate, understand reality, and act properly is seriously affected. This makes it very hard for them to handle everyday life.

How Does Lurasidone HCL Work?

Lurasidone, the active ingredient, is a medication used to treat conditions like schizophrenia. It works in the brain by affecting certain receptors that are like switches for chemicals (neurotransmitters) that help brain cells communicate. Lurasidone mainly blocks receptors for three important neurotransmitters, which are dopamine, serotonin (5-hydroxytryptamine), and noradrenaline. By doing this, it helps bring balance to brain activity, which in turn reduces the symptoms of schizophrenia.

Dosage of Lurasidone

It is recommended to take Lurasidone after a meal (at least 350 calories) to improve absorption.

Schizophrenia Treatment:

• Lurasidone is started with 40 mg per day.

• The dose can be adjusted based on the response and tolerance.

• The effective range is usually between 40 and 160 mg per day.

• It should not exceed 160 mg per day.

Bipolar I Disorder (Depressive Episodes):

• Lurasidone is started with 20 mg per day.

• This can be used alone or with Lithium or Valproate.

• The doctor may adjust the dose as needed.

• 20 mg to 120 mg per day has proven to be effective.

• The maximum amount is 120 mg per day.

Adjusting for Kidney Disease:

• If a person has moderate kidney disease (creatinine clearance 30 to <50 ml/min), they should start with 20 mg per day.

• It should not be taken beyond 80 mg per day.

Adjusting for Liver Disease:

• For moderate liver disease (Child-Pugh Score seven to nine), a person should start with 20 mg daily.

• The dose should not exceed 80 mg per day.

• For severe liver disease (Child-Pugh Score 10 to 15), the starting dose is also 20 mg per day.

• The maximum dose for severe liver disease is 40 mg per day.

What Are the Things to Inform the Doctor Before Taking Lurasidone?

Inform the doctor about the following conditions:

• Symptoms that are troubling the most.

• If an individual attempts to hurt themselves.

• Any medicines an individual tried before, and if that helped or caused problems.

• Had issues like muscle stiffness, shaking, or unusual reactions to drugs.

• Side effects from the current medicines should be discussed with their provider. Some might go away over time, but others may need a medication change.

• Mental or medical problems like heart issues, diabetes (high blood sugar), or seizures (uncontrolled electrical activity in the brain cells).

• Family history of diabetes or heart disease.

• List all the medications, even over-the-counter, herbal, or dietary supplements, and any allergies to medicines.

• Mention other treatments like therapy or help for substance abuse, and let the provider explain how they work with the medication.

• Pregnant, or planning to get pregnant, or breastfeeding.

• Smoke, drink alcohol, or use illegal drugs.

• Seizures, abnormal thyroid tests, high prolactin levels.

How Is Lurasidone Administered?

• For Schizophrenia: Lurasidone is started with a 40 mg dose once a day. There is no need to change the dose at the beginning. The doctor increases the dose if they feel the need for the same. The maximum dose that the doctor can recommend is 160 mg per day.

• For Depressive Episodes Related to Bipolar I Disorder: If the person is dealing with depressive episodes related to bipolar I disorder, they should start with a 20 mg dose once a day, either on its own or with Lithium or Valproate. They should not change the dose at first. It can be effective in the range of 20 mg to 120 mg a day, whether alone or with other medicines. Taking more than 120 mg a day usually does not give extra benefits.

Administration of Lurasidone: Always take Lurasidone with food that has at least 350 calories. It helps the body absorb the medicine better.

Changing the Dose for Special Cases:

• Kidney Disorders: If a person has kidney problems, especially moderate or severe ones, they should start with a dose of 20 mg a day. The dose should not exceed 80 mg a day.

• Liver Disorders: For people with liver issues, especially moderate or severe cases, should start with a dose of 20 mg a day. If it is moderate, they should not take more than 80 mg a day, and if it is severe, not more than 40 mg a day.

What Are the Side Effects of Lurasidone?

• This medication may raise the risk of death in elderly patients.

• People should be cautious about thinking of hurting themselves.

• Cerebrovascular issues can include strokes in elderly patients with dementia-related psychosis.

• Neuroleptic malignant syndrome (caused by the use of antipsychotic agents, characterized by mental health change, fever, rigidity, fever, and dysautonomia) is a rare but severe reaction.

• Tardive dyskinesia (movement disorder characterized by repetitive, uncontrollable, abnormal movement of the face or any other body parts) can cause potential movement disorders in a person.

• Metabolic changes lead to issues like high blood sugar, diabetes, abnormal cholesterol levels, and weight gain.

• High prolactin levels in an individual may cause hormone imbalance.

• Watch for signs like infections, as this medication might affect the blood cells.

• Dizziness when standing up can happen, leading to fainting.

• Seizures are rare.

• Cognitive and motor Impairment, which includes thinking and movement, may be affected.

• Be cautious about regulating the body temperature.

• Mania or hypomania can trigger these conditions in some cases.

• Some people might have trouble swallowing while taking this medication.

• People with neurological issues with Parkinson's or Lewy body dementia have to be aware of potential neurological side effects.

Dietary Considerations:

• Grapefruit and grapefruit juice may not interact well with this medication, so it is safer to skip them.

• Avoid alcohol, as it can have harmful effects.

• Be cautious when driving and using heavy machinery until the person understands how the medication affects them.

• Take care when getting up quickly to prevent dizziness, which could lead to accidents or falls.

Missed Dose:

If a person forgets to take a dose of Lurasidone, they should take it when they remember, but not if their next dose is soon. Talk to the healthcare provider about it. Do not take extra to make up for the missed one. Stick to the prescribed amount.

Overdose:

If a person ingests more than the recommended amount of Lurasidone, it leads to an overdose. Overdose can lead to drowsiness, dizziness, seizure, trouble breathing, passing out, or abnormal head and neck movements. In case of these situations, report to the doctor.

Overdose Management:

• If someone overdoses on Lurasidone, contact a Poison Control Center for assistance.

• There is no specific medicine to counteract Lurasidone’s effects, so treatment focuses on supportive care and close monitoring.

• Overdose cases may involve other substances, so it is crucial to take this into account.

• Doctors will closely watch the person's heart for irregular rhythms. Caution is needed when using certain heart medications (Disopyramide, Procainamide, Quinidine) alongside Lurasidone overdose.

• If low blood pressure is a concern, doctors will take appropriate measures. They should avoid using drugs like Epinephrine and Dopamine that can worsen low blood pressure when combined with Lurasidone overdose.

• In cases of severe muscle control problems, anticholinergic medication may be administered to address symptoms like muscle stiffness or trembling.

Storage:

Keep Lurasidone tablets at a temperature around 77°F (degree Fahrenheit) or 25°C (degree Celsius), but it is okay if it goes between 59°F to 86°F (15°C to 30°C) occasionally.

For Doctors

Indication:

Lurasidone is used for:

• Schizophrenia: Treating schizophrenia in both adults and adolescents aged 13 to 17. For schizophrenia, its effectiveness has been shown for up to six weeks, but its long-term use beyond this has not been firmly established.

• Bipolar Depression: Managing major depressive episodes linked to bipolar I disorder (bipolar depression) in adults, either as a standalone treatment or in combination with Lithium or Valproate. For bipolar depression, it has been proven to work for six weeks, both when used alone and when combined with Lithium or Valproate. The effectiveness of Lurasidone beyond six weeks has not been proven. Lurasidone has not been proven effective for treating mania associated with bipolar disorder.

Dosage and Administration:

1. Schizophrenia:

• Recommended Starting Dose: Begin with 40 mg of Lurasidone HCl once daily.

• Dosage Range: The effective range is between 40 mg to 160 mg per day.

2. Bipolar I Disorder with Depressive Episodes:

• Monotherapy: Start with 20 mg of Lurasidone once daily.

• Adjunctive Therapy with Lithium or Valproate: Initiate treatment with 20 mg per day.

• Dosage Range: Suitable effective dosage ranges from 20 mg to 120 mg daily.

Administration:

Take Lurasidone with food (at least 350 calories) as it significantly improves its absorption. This enhances drug exposure by about two-fold and peak levels by about three-fold.

Dose Adjustments for Special Populations:

1. Renal Impairment:

• Moderate: If the creatinine clearance is between 30 and <50 (milliliter/minute) mL/min, start with 20 mg per day.

• Severe: For creatinine clearance <30 mL/min, the initial dose should be 20 mg per day, and it should not exceed 80 mg per day.

2. Hepatic Impairment:

• Moderate: Start with 20 mg per day if the Child-Pugh Score is seven to nine. The maximum dose for moderate hepatic impairment is 80 mg per day.

• Severe: For a Child-Pugh Score of 10 to 15, the initial dose should be 20 mg per day, and it should not exceed 40 mg per day.

Dose Modifications Due to Drug Interactions:

1. Strong CYP3A4 Inhibitors: Avoid using strong CYP3A4 inhibitors (for example, Ketoconazole, Clarithromycin, etc.) with Lurasidone.

2. Moderate CYP3A4 Inhibitors: If a moderate CYP3A4 inhibitor is added to the treatment while a person is taking Lurasidone, the Lurasidone dose should be reduced to half of the original dose level. The recommended starting dose is 20 mg per day, and the maximum is 80 mg per day.

3. Avoid Grapefruit: Do not consume grapefruit or its juice when using Lurasidone.

4. Strong CYP3A4 Inducers: Avoid taking strong CYP3A4 inducers (for example, Rifampin, St. John's wort, etc.) with Lurasidone. If a person is on a moderate CYP3A4 inducer, they may need to increase their Lurasidone dose after seven or more days of treatment with the inducer.

Dosage Forms and Strengths:

Lurasidone tablets are available in the following strengths:

• 20 mg (white to off-white, round, marked L20).

• 40 mg (white to off-white, round, marked L40).

• 80 mg (pale green, oval, marked L80).

• 120 mg (white to off-white, oval, marked L120).

What Are the Pharmacological Aspects of Lurasidone?

Pharmacodynamics:

Lurasidone acts as an antagonist, binding strongly to specific brain receptors, including dopamine D2, serotonin 5-HT2A, and 5-HT7 receptors. It also moderately binds to α2C (alpha)adrenergic receptors, partially activates serotonin 5-HT1A receptors, and acts as an antagonist at α2A adrenergic receptors. However, it has minimal affinity for histamine H1 and muscarinic M1 receptors. Regarding heart activity, a study showed that Lurasidone can cause a slight increase in the QTc interval on ECG, with a maximum increase of 7.5 milliseconds at a 120 mg dose and 4.6 milliseconds at a 600 mg dose. This increase occurred a few hours after taking the medication, but there was no clear relationship between the dose and this effect. In short-term studies for schizophrenia and bipolar depression, Lurasidone did not significantly prolong QT intervals beyond 500 milliseconds, indicating it is generally well-tolerated regarding its impact on heart activity.

Mechanism of Action:

While the precise way Lurasidone works to treat schizophrenia and bipolar depression remains unclear, it is believed that its effectiveness in managing these conditions may result from its ability to block specific receptors in the brain, including dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptors.

Pharmacokinetics:

Lurasidone primarily works through the parent drug. Its behavior in the body is directly proportional to the dose, with steady levels achieved in about a week. After taking 40 mg of Lurasidone, around 50 percent is removed from the body in roughly 18 hours. The drug is absorbed within one to three hours, with nine to19 percent of the dose being absorbed. It strongly binds to blood proteins, particularly when taken with food. Lurasidone is primarily processed by the CYP3A4 enzyme, producing active and inactive metabolites. It does not interact significantly with various other enzymes, and smoking does not affect its processing. Following Lurasidone intake, about 89 percent is eliminated through urine and feces, 80 percent through feces, and nine percent through urine. The apparent clearance from the body after taking 40 mg of Lurasidone is approximately 3902 mL/min.

Toxicity:

• Cancer Risk: In animal studies, Lurasidone was linked to an increased risk of breast tumors and pituitary gland growths in female mice and breast cancer in female rats when given at high doses. These effects were not observed in male mice or rats.

• Genetic Effects: Lurasidone did not cause genetic mutations or chromosomal abnormalities in various tests, indicating it is not likely to cause DNA damage.

• Fertility Impact: In female rats, Lurasidone disrupted their productive cycle at high doses, affecting their ability to get pregnant. This effect was reversible when the drug was stopped. In male rats, Lurasidone did not affect fertility, even at high doses.

Clinical Studies:

Schizophrenia:

• Lurasidone’s effectiveness was evaluated in five short-term (six-week) studies involving adult patients meeting the criteria for schizophrenia.

• These studies used various assessment tools to measure psychiatric symptoms, such as the PANSS (positive and negative syndrome scale), BPRSd (brief psychiatric rating scale), and CGI-S (clinical global impression - severity scale).

• The results showed that Lurasidone, at doses of 40 to 160 mg per day, was more effective than placebos in improving these symptoms, as indicated by changes from baseline scores. Some studies also included active-control arms.

• Subgroup analyses based on age, gender, and race did not reveal significant differences in responsiveness to Lurasidone.

Depressive Episodes Associated With Bipolar I Disorder:

• In one study, Lurasidone was compared to a placebo in adult patients with major depressive episodes linked to bipolar I disorder.

• The primary assessment tool used was the MADRS (Montgomery-Rosberg depression rating scale), which measures depressive symptoms.

• Lurasidone, at doses of 20 to 60 mg per day or 80 to 120 mg per day, demonstrated superior effectiveness compared to the placebo in reducing MADRS and CGI-BP-S scores after six weeks.

• The high dose range did not offer additional efficacy compared to the low dose range.

• In another study, Lurasidone was tested as an adjunctive therapy with lithium or Valproate in patients who remained symptomatic after initial treatment. Lurasidone showed superior effectiveness when used along with Lithium or Valproate.

What Are the Contraindications of Lurasidone?

• Avoid using this medication if there is a known hypersensitivity (allergic reaction) to Lurasidone HCl or any of the components in the formulation.

• Be aware that angioedema, a severe allergic reaction involving rapid skin swelling, has been associated with Lurasidone.

• Exercise caution when taking this medication with strong CYP3A4 inhibitors, such as Ketoconazole, Clarithromycin, Ritonavir, Voriconazole, and Mibefradil, as they may affect its metabolism.

• Similarly, exercise caution with strong CYP3A4 inducers like Rifampin, Avasimibe, St. John's wort, Phenytoin, and Carbamazepine, as they can impact the metabolism of this drug.

Warnings and Precautions:

• Increased Risk of Death in Elderly Patients with Dementia-Related Psychosis: Elderly patients with dementia-related psychosis treated with antipsychotic drugs, especially atypical ones, may have a higher risk of death. The main causes of death appear to be related to heart problems or infections.

• Suicidal Thoughts and Behaviors in Adolescents and Young Adults: Antidepressant drugs can sometimes lead to an increased risk of suicidal thoughts and behaviors in young people with major depressive disorder. This risk is generally higher in adolescents and young adults.

• Cerebrovascular Adverse Reactions, Including Stroke in Elderly Patients with Dementia-Related Psychosis: Antipsychotic drugs like Risperidone, Aripiprazole, and Olanzapine may lead to a higher incidence of stroke and related events in elderly patients with dementia. This is a concern, especially for this age group.

• Neuroleptic Malignant Syndrome: This is a potentially fatal condition associated with antipsychotic drug use. It can cause symptoms like high fever, muscle rigidity, and altered mental state. It requires immediate medical attention.

• Tardive Dyskinesia: This syndrome involves involuntary, potentially irreversible movements and can develop in patients treated with antipsychotic drugs, particularly with long-term use.

• Metabolic Changes: Antipsychotic drugs can lead to metabolic changes, including increased risk factors for cardiovascular disease like high blood sugar and cholesterol levels. This risk may vary depending on the specific drug.

• Hyperprolactinemia: Antipsychotic drugs can elevate prolactin levels, which may cause issues like breast changes, menstrual irregularities, and impotence.

• Leukopenia, Neutropenia, and Agranulocytosis: Some patients may experience a decrease in white blood cell count, which can weaken the immune system. This is more common in patients with a history of such issues.

• Orthostatic Hypotension and Syncope: These drugs can cause a drop in blood pressure when standing up, which may lead to dizziness or fainting.

• Seizures: Antipsychotic drugs should be used cautiously in patients with a history of seizures or conditions that lower the seizure threshold.

• Potential for Cognitive and Motor Impairment: These drugs can impair judgment, thinking, or motor skills, so patients should be cautious when operating machinery or vehicles.

• Body Temperature Dysregulation: Antipsychotic drugs can affect the body's ability to regulate temperature, so care is needed in extreme conditions.

• Suicidal Risk: Patients with psychiatric disorders may have an increased risk of suicidal thoughts or behaviors, and this should be closely monitored during treatment.

• Activation of Mania or Hypomania: Antidepressant treatment, in particular, can increase the risk of manic or hypomanic episodes in patients with bipolar disorder.

• Dysphagia: Antipsychotic drug use has been associated with swallowing difficulties, which can lead to aspiration pneumonia in some cases.

• Neurological Adverse Reactions in Patients with Parkinson’s Disease or Dementia with Lewy Bodies: Patients with these conditions can be more sensitive to antipsychotic medications, which can lead to various neurological symptoms.

What Are the Drug Interactions of Lurasidone?

• CYP3A4 Inhibitors and Inducers: Lurasidone is mainly processed by the CYP3A4 enzyme. Avoid using Lurasidone with strong CYP3A4 inhibitors (for example, Ketoconazole, Ritonavir) or strong CYP3A4 inducers (for example, Rifampin, Phenytoin). When using Lurasidone with moderate CYP3A4 inhibitors, reduce the Lurasidone dose. If combined with a moderate CYP3A4 inducer, consider increasing the Lurasidone dose.

• Lithium: No dose adjustment is required when combining Lurasidone with Lithium.

• Valproate: No dose adjustment is needed when Lurasidone is used alongside Valproate. Interaction studies have shown that Valproate levels are unaffected by Lurasidone, and its concentrations remain unchanged with Valproate use.

• Grapefruit: Patients taking Lurasidone should avoid consuming grapefruit or grapefruit juice.

Special Considerations:

• Pregnancy: Lurasidone is classified as Pregnancy Category B. Neonates exposed to antipsychotic drugs in the third trimester are at risk for withdrawal symptoms. Symptoms in neonates include agitation, muscle tone changes, tremors, drowsiness, respiratory issues, and feeding problems. Lurasidone should only be used during pregnancy if the potential benefits outweigh the potential risks to the fetus.

• Nursing Mothers: Lurasidone has been detected in the milk of lactating rats, but its presence in human milk is unknown. Due to the potential for serious adverse effects in nursing infants, a decision should be made to discontinue nursing or Lurasidone, considering the risks to the mother.

• Pediatric Use: The safety and effectiveness of Lurasidone have not been established in pediatric patients.

• Geriatric Use: Lurasidone concentrations were similar between elderly and young subjects. Elderly patients with dementia-related psychosis using Lurasidone face an increased risk of death compared to placebo.

• Other Patient Factors: The impact of inherent patient characteristics on Lurasidone’s pharmacokinetics is provided. These considerations are crucial when prescribing Lurasidone, taking into account the specific patient population and potential risks and benefits.