Liver test abnormalities may occur in up to 30% of patients on long term therapy with Risnia, usually arising within the first 8 weeks of treatment. The ALT elevations are usually mild, transient and may resolve even with continuation of medication. Instances of more marked ALT and alkaline phosphatase elevations, with or without symptoms and with or without jaundice, have also been reported. The onset of injury typically occurs within a few days of starting Risnia and resolves rapidly with stopping. Instances of acute liver injury with jaundice arising several months and even years after starting Risnia have also been reported. The pattern of serum enzyme elevations is typically cholestatic, but cases with hepatocellular and mixed patterns have also been described. Immunoallergic manifestations (rash, fever, eosinophilia) are rare; a case of autoimmune hepatitis apparently triggered by Risnia therapy was been published, but most cases do not have autoimmune features.
Likelihood score: C (probable rare cause of clinically apparent liver injury).
Risper > Risnia is a benzisoxazole derivative approved by the FDA for treatment of schizophrenia in 1994, for short-term treatment of the mixed and manic states of bipolar disorder in 2003, and for treatment of irritability in children with autism in 2006. In 2007 it was approved as a treatment for schizophrenia and bipolar disorder in children. Its pharmacology is characterized by binding affinity for 5-HT 2A receptors that is 20 times that for D2 dopamine receptors. D2 receptor affinity is approximately 50 times, and 5-HT2A receptor affinity approximately 20 times, that of clozapine. Risnia also has strong affinity for α1/α2-adrenergic and H1 histamine receptors. Affinity for D1 receptors is low, and it has no affinity at muscarinic receptors. Protein binding is 90%, and it is metabolized by CYP 2D6. D2 receptor occupancy at therapeutic doses is 63% to 89%, which would be expected to be associated with a significant incidence of EPS. 97 The addition of strong serotonergic antagonism, with a 5-HT2 receptor occupancy of 95%, is thought to confer protection against D2 antagonist effects on the nigrostriatal pathway, and the incidence of EPS is low. Nonetheless, unlike other SGAs with relatively lower affinities for D2 receptors that permit dynamic responses to surges in dopamine, Risnia is tightly bound and does cause significant hyperprolactinemia. 98 It can also cause orthostatic hypotension during early treatment. Risnia does not cause prolongation of the QTc and is less arrhythmogenic than other antipsychotics. It carries a boxed warning for increased risk of death in older patients receiving antipsychotics for dementia-related psychosis.
Outcome and Management
The serum aminotransferase elevations that occur on Risnia therapy are usually self-limited and often do not require dose modification or discontinuation of therapy. No instances of acute liver failure or vanishing bile duct syndrome have been attributed to Risnia. A single case of autoimmune hepatitis due to Risnia has been published. There may be some cross reactivity to liver injury between Risnia and quetiapine, but usually not with clozapine and olanzapine.
Interactions that can make your drugs less effective
When Risnia is used with certain drugs, it may not work as well to treat your condition. This is because the amount of Risnia in your body may be decreased. Examples of these drugs include:
- Phenytoin. Your doctor may increase your Risnia dose.
- Carbamazepine. Your doctor may increase your Risnia dose.
- Rifampin. Your doctor may increase your Risnia dose.
- Phenobarbital. Your doctor may increase your Risnia dose.
Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.
What Are the Most Common and Serious Side Effects of Risnia?
Common side effects of Risnia (Risperdal) include:
- Nausea or vomiting
- Dry mouth
- Increased saliva
- Increased appetite
- Weight gain
- Stomach pain
- More frequent dreaming
- Trouble sleeping
- Low sex drive or sexual problems
- Unusual breast milk production
- Vision problems
- Muscle or joint pain
- Dry or discolored skin
- Trouble urinating
Serious side effects can also occur while taking Risnia. If you have any of these side effects, call your doctor immediately:
- Muscle stiffness
- Fast or irregular pulse
- Abnormal movements of your face or body that you cannot control
- Slow movements or shuffling walk
- Trouble breathing or swallowing
- Painful erection that lasts for hours
Risper > Risnia is a benzisoxazole derivative approved by the FDA for treatment of schizophrenia in 1994, for short-term treatment of the mixed and manic states of bipolar disorder in 2003, and for treatment of irritability in children with autism in 2006. In 2007 it was approved as a treatment for schizophrenia and bipolar disorder in children. Its pharmacology is characterized by binding affinity for 5-HT 2A receptors that is 20 times that for D2-dopamine receptors. D2-receptor affinity is approximately 50 times, and 5-HT2A receptor affinity approximately 20 times that of clozapine. Risnia also has strong affinity for α1-/α2-adrenergic and H1-histamine receptors. Affinity for D1 receptors is low, and it has no affinity at muscarinic receptors. Protein binding is 90%, and it is metabolized by CYP 2D6. D2-receptor occupancy at therapeutic doses is 63% to 89%, which would be expected to be associated with a significant incidence of EPS. 110 The addition of strong serotonergic antagonism, with a 5-HT2 receptor occupancy of 95%, is thought to confer protection against D2 antagonist effects on the nigrostriatal pathway, and the incidence of EPS is low. Nonetheless, unlike other SGAs with relatively lower affinities for D2 receptors that permit dynamic responses to surges in dopamine, Risnia is tightly bound and does cause significant hyperprolactinemia. 111,112 It can also cause orthostatic hypotension during early treatment. Risnia does not cause prolongation of the QTc and is less arrhythmogenic than other antipsychotics. It carries a boxed warning for increased risk of death in older patients receiving antipsychotics for dementia-related psychosis.
The dose of RISPERDAL® should be adjusted when used in combination with CYP2D6 enzyme inhibitors (e.g., fluoxetine, and paroxetine) and enzyme inducers (e.g., carbamazepine) . Dose adjustment is not recommended for RISPERDAL® when co-administered with ranitidine, cimetidine, amitriptyline, or erythromycin .
Table 18 : Summary of Effect of Coadministered Drugs on Exposure to Active Moiety (Risnia + 9-Hydroxy-Risnia) in Healthy Subjects or Patients with Schizophrenia
While the pharmacokinetics of Risnia in subjects with liver disease were comparable to those in young healthy subjects, the mean free fraction of Risnia in plasma was increased by about 35% because of the diminished concentration of both albumin and α1-acid glycoprotein. RISPERDAL® doses should be reduced in patients with liver disease .
Some side effects can be serious. If you experience any of the following symptoms or those listed in the IMPORTANT WARNING section or the SPECIAL PRECAUTIONS section, call your doctor immediately:
- muscle stiffness
- fast or irregular pulse
- unusual movements of your face or body that you cannot control
- slow movements or shuffling walk
- difficulty breathing or swallowing
- painful erection of the penis that lasts for hours
Risnia may cause children to gain more weight than expected and for boys and male teenagers to have an increase in the size of their breasts. Talk to your doctor about the risks of giving this medication to your child.
Risnia may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).
Before taking Risnia, tell your doctor or pharmacist if you are allergic to it; or to paliperidone; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.
Risnia may cause a condition that affects the heart rhythm (QT prolongation). QT prolongation can rarely cause serious (rarely fatal) fast/irregular heartbeat and other symptoms (such as severe dizziness, fainting) that need medical attention right away.
The risk of QT prolongation may be increased if you have certain medical conditions or are taking other drugs that may cause QT prolongation. Before using Risnia, tell your doctor or pharmacist of all the drugs you take and if you have any of the following conditions: certain heart problems (heart failure, slow heartbeat, QT prolongation in the EKG), family history of certain heart problems (QT prolongation in the EKG, sudden cardiac death).
Low levels of potassium or magnesium in the blood may also increase your risk of QT prolongation. This risk may increase if you use certain drugs (such as diuretics/"water pills") or if you have conditions such as severe sweating, diarrhea, or vomiting. Talk to your doctor about using Risnia safely.
This drug may make you dizzy or drowsy. Alcohol or marijuana (cannabis) can make you more dizzy or drowsy. Do not drive, use machinery, or do anything that needs alertness until you can do it safely. Avoid alcoholic beverages. Talk to your doctor if you are using marijuana (cannabis).
Before having surgery (including cataract/glaucoma eye surgery), tell your doctor or dentist if you are taking or have ever taken this medication, and about all the other products you use (including prescription drugs, nonprescription drugs, and herbal products).
This medication may make you sweat less, making you more likely to get heat stroke. Avoid doing things that may cause you to overheat, such as hard work or exercise in hot weather, or using hot tubs. When the weather is hot, drink a lot of fluids and dress lightly. If you overheat, quickly look for a place to cool down and rest. Get medical help right away if you have a fever that does not go away, mental/mood changes, headache, or dizziness.
Older adults may be more sensitive to the side effects of this drug, especially drowsiness, dizziness, lightheadedness, and QT prolongation (see above). Drowsiness, dizziness, and lightheadedness can increase the risk of falling.
During pregnancy, this medication should be used only when clearly needed. Babies born to mothers who have used this drug during the last 3 months of pregnancy may rarely develop symptoms including muscle stiffness or shakiness, drowsiness, feeding/breathing difficulties, or constant crying. If you notice any of these symptoms in your newborn especially during their first month, tell the doctor right away.
Since untreated mental/mood problems (such as schizophrenia, bipolar disorder, depression) can be a serious condition, do not stop taking this medication unless directed by your doctor. If you are planning pregnancy, become pregnant, or think you may be pregnant, immediately discuss with your doctor the benefits and risks of using this medication during pregnancy.
This medication passes into breast milk and may have undesirable effects on a nursing infant. Tell the doctor right away if your baby develops symptoms such as muscle stiffness or shakiness, unusual sleepiness, or difficulty feeding. Consult your doctor before breast-feeding.
References updated: 04 June 2018
15 months; only 1 had ALT elevation , degree of surveillance unclear; abstract only).
1 month after discontinuation).
4 years; ultrasound suggested fatty liver).
3300 patients]; average monthly weight gain in pounds was +0.1 with placebo, +0.8 olanzapine, 0.6 Risnia, -0.3 ziprasidone; a 5% increase in weight occurred after one year in 13% of placebo, 39% haloperidol, 20% ziprasidone, 45% Risnia and 60% olanzapine treated subjects).
Given the primary CNS effects of Risnia, caution should be used when RISPERDAL® is taken in combination with other centrally-acting drugs and alcohol.