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Rexulti: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Nov 23, 2020.

1. How it works

  • Rexulti is a brand (trade) name for brexpiprazole which is an atypical antipsychotic that may be used to treat adults with schizophrenia or depression.
  • Experts aren't sure exactly how Rexulti works to treat schizophrenia or depression but believe it is because of its partial agonist activity at serotonin 5-HT1A and dopamine D2 receptors, and antagonist activity at serotonin 5-HT2A receptors. This results in a re-balancing of levels of serotonin and dopamine in the brain. An imbalance in these two neurotransmitters is thought to be linked to several mental health conditions, including depression and schizophrenia.
  • Rexulti belongs to the class of medicines known as serotonin-dopamine activity modulators (SDAMs). It may also be called an atypical antipsychotic.

2. Upsides

  • May be used in combination with other medications to treat major depressive disorder (MDD) and either alone or in combination with other medications to treat schizophrenia.
  • Rexulti is an oral tablet that is taken once a day.
  • May be taken with or without food.
  • Available in 6 different strengths: 0.25 milligrams (mg), 0.5 mg, 1 mg, 2 mg, 3 mg, and 4 mg.
  • Rexulti is considered a second-generation version of aripiprazole (Abilify). The effectiveness of Rexulti and Abilify are similar, but Rexulti has slightly different activity at the serotonin and dopamine receptors which may reduce some extrapyramidal side effects such as restlessness.
  • Rexulti is not a controlled substance.
  • Animals given Rexulti did not self-administer the drug which suggests that it is unlikely to be addictive. There was also no evidence of withdrawal symptoms when Rexulti was discontinued in humans and animals administered it.

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Constipation, nasal congestion, weight increase, anxiety, dizziness, drowsiness, dyspepsia, fatigue, increased creatine phosphokinase in blood, tremor, increased appetite, akathisia (an inner restlessness), and headache are the most common side effects reported.
  • Rexulti, like most atypical antipsychotics, is associated with weight gain. This may be due to an increased appetite, less physical activity because of side effects like drowsiness or fatigue, or changes in metabolism.
  • A baseline weight should be taken on Rexulti initiation then a person's weight monitored regularly thereafter.
  • Rexulti may also cause other metabolic changes and increase the risk of high blood sugar levels, diabetes type 2, and high cholesterol.
  • Antipsychotic medicines like Rexulti can raise the risk of death in elderly patients who have lost touch with reality (psychosis) due to confusion and memory loss (dementia). Rexulti is not approved for the treatment of patients with dementia-related psychosis.
  • May increase the risk of suicidal thoughts and behaviors. If being used to treat depression, monitor for worsening depression, agitation, or mood changes, especially in young adults aged less than 24 years.
  • May cause a drop in blood pressure on standing, particularly during the initial dose-titration period; dosage may need reducing. May not be suitable for people with known cardiovascular disease (history of a heart attack, angina, heart failure, or arrhythmia), stroke, seizure disorders, and people at risk of dehydration.
  • Blood levels may need monitoring as Rexulti can cause numbers of white blood cells to decrease, resulting in leukopenia or neutropenia. Agranulocytosis (including fatal cases) has also been reported with other antipsychotics.
  • May increase blood sugar levels. People with a history of diabetes or at risk of diabetes should be monitored closely. May also cause undesirable changes in blood cholesterol and lipid levels.
  • Potentially irreversible tardive dyskinesia can develop, even with low dosages used short-term. Symptoms include facial grimacing, repetitive chewing, and tongue thrusting.
  • May require a dosage adjustment or may not be suitable for people with liver or kidney disease, CYP2D6 poor metabolizers, or with some other conditions. In people with liver or kidney disease, the maximum recommended dosage is 2 mg once daily for those with depression and 3 mg once daily for those with schizophrenia. Dosage adjustments are needed in people taking concomitant CYP3A4 inhibitors, CYP2D6 inhibitors, or strong CYP3A4 inducers, and the dosage of Rexulti will need adjusting again if these medications are discontinued.
  • Rarely, may cause Neuroleptic Malignant Syndrome; symptoms include high body temperature, muscle rigidity, and mental disturbances; discontinue immediately and seek urgent medical advice.
  • May interact with several drugs, including benzodiazepines, carbamazepine, fluoxetine, and itraconazole.
  • No generic version of Rexulti is currently available.

Note: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. View complete list of side effects

4. Bottom Line

Rexulti is an atypical antipsychotic that may be used to treat schizophrenia or in combination with other medications, to treat depression. Weight gain is a common side effect but it is less likely than Abilify to cause movement-related side effects such as restlessness.

5. Tips

  • The usual starting dose of Rexulti is 0.5mg or 1mg once daily. Dosage increases usually occur at weekly intervals until you reach a target dose of 2mg once daily. The maximum recommended daily dose is 3mg. Your doctor may prescribe more or less Rexulti depending on how well you tolerate or respond to it.
  • You may take Rexulti either with or without food. Try to take it at the same time each day (ie, with or before breakfast, or with or after dinner). If you miss a dose of Rexulti, take it as soon as you remember. However. if you are close to your next dose, just skip the missed dose and take your next dose at your regular time. Do not take 2 doses of Rexulti at the same time.
  • Be sure to tell your doctor or pharmacist about all of the medications you use, including prescription and over-the-counter (OTC) medicines, vitamins, and herbal products. Some of these can interact with Rexulti. Your doctor or pharmacist will review your medicines for drug interactions while you are taking Rexulti.
  • Rexulti may cause weight gain. You and your healthcare provider should check your weight regularly.
  • May cause sedation or impair judgment skills and affect your ability to drive or operate machinery. Avoid alcohol.
  • Some people taking Rexulti develop unusual urges such as gambling, binge eating, or eating that you cannot control (compulsive), compulsive shopping, and sexual urges. Talk to your healthcare provider if you or your family members notice that you are having unusual urges or behaviors.
  • Rexulti may disrupt your body's ability to reduce core body temperature. Strenuous exercise, exposure to extreme heat, dehydration, or some medications, such as anticholinergic medications may increase this risk. Avoid overheating and dehydration.
  • Be alert for worsening mood and suicide-related thoughts or behaviors. Seek medical advice if changes are apparent.
  • Seek urgent medical advice if you develop unusual body movements, confusion, high fever, lightheadedness, fainting, seizures, have problems controlling your body temperature, or difficulty swallowing.
  • Rexulti may make you feel dizzy when going from a sitting or lying down position to standing. This may increase your risk of falls. Stand up slowly and remove any fall hazards from your home (such as loose rugs).
  • Talk with your doctor if you develop any worrying side effects such as uncontrollable facial grimacing, restlessness, severe dizziness, or severe abdominal discomfort.
  • Tell your doctor if you are pregnant or intending to become pregnant. Rexulti is not recommended during pregnancy unless the benefits outweigh the risks and there is a pregnancy exposure registry for women exposed to Rexulti during pregnancy (the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388. Neonates whose mothers were exposed to antipsychotics, such as Rexulti, during the third trimester of pregnancy were more likely to experience movement-related or withdrawal symptoms. There is not enough data to determine if Rexulti is safe during breastfeeding.

6. Response and Effectiveness

  • Some improvements in the symptoms of depression or schizophrenia may be seen within 1 or 2 weeks of starting Rexulti, but it may take up to 6 weeks for the full effects to be seen.
  • In a 6-week long study in adults, adding Rexulti to ongoing antidepressant treatment led to a 62% greater reduction in symptoms of depression.
  • In two depression studies that investigated the effects of Rexulti plus an antidepressant (ADT), the response was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) (a common tool that looks at symptoms of depression such as sad feelings, attention, sleep patterns, and appetite). MADRS total scores dropped by: -1.3 points (with the 1 mg/day + ADT), -2 points (using the 3 mg/day + ADT), and -3.2 points (using the 2 mg/day + ADT). Compared to placebo, only the 2 mg/day dose was found to have a statistically significant effect on the MADRS score. For most patients with depression, the target dose of Rexulti is 2 mg once daily.
  • Rexulti has also been shown to be effective for adults with schizophrenia when compared to a placebo in two 6-week long studies. Researchers determine the effectiveness of Rexulti using the Positive and Negative Syndrome Scale (PANSS) total symptom severity score, a common scoring tool used in the study of schizophrenia. Overall, at the end of 6 weeks, the PANSS symptom score from baseline for patients taking Rexulti had declined significantly for both doses (2mg/day and 4mg/day). In one study, there was a significant decline in PANSS score of 20.7 points (2 mg/day) with Rexulti compared to a reduction of 8.7 points with placebo, 19.7 points (4 mg/day) with Rexulti compared to a reduction of 7.6 points with placebo. Statistical significance was not achieved for the primary endpoint with either the 1-mg/day dose or the 2-mg/day dose compared with placebo in one study. The recommended target dose for Rexulti is 2 mg to 4 mg once daily in patients with schizophrenia.
  • Rexulti has a long half-life (91 hours) and can stay in your system a long time. It usually takes 5 half-lives for a drug to be mostly eliminated from your body, so this equates to roughly 455 hours or 18 to 19 days for Rexulti. Drugs with long half-lives like Rexulti have an advantage as they can often be dosed once a day and blood levels remain more steady. But if you experience any side effects with Rexulti, and your doctor determines you should stop treatment, it may take longer for the side effect to subside. Do not stop treatment unless specifically directed by your doctor.

7. Interactions

Medicines that interact with Rexulti may either decrease its effect, affect how long it works for, increase side effects, or have less of an effect when taken with Rexulti. An interaction between two medications does not always mean that you must stop taking one of the medications; however, sometimes it does. Speak to your doctor about how drug interactions should be managed.

Common medications that may interact with Rexulti include:

  • abiraterone
  • anti-anxiety medications, including other benzodiazepines, such as diazepam and oxazepam
  • antibiotics, such as cotrimoxazole
  • anticonvulsants, such as carbamazepine, fosphenytoin, or phenytoin
  • antidepressants, such as amitriptyline, fluoxetine, imipramine, nortriptyline
  • antifungals, such as itraconazole or ketoconazole
  • antihistamines that cause sedation, such as diphenhydramine
  • antipsychotics, such as clozapine
  • aprepitant
  • bupropion
  • celecoxib
  • cimetidine
  • ciprofloxacin
  • diuretics, such as bendroflumethiazide
  • duloxetine
  • HIV medications such as amprenavir, cobicistat, indinavir, or ritonavir
  • HCV (hepatitis C medications) such as boceprevir
  • ginkgo
  • lithium
  • metoclopramide
  • opioid analgesics such as alfentanil, oxycodone and morphine
  • muscle relaxants such as cyclobenzaprine
  • quinidine
  • serotonin modulators, such as nefazodone and trazodone
  • sleeping pills, such as zolpidem
  • some anti-cancer treatments such as ceritinib or crizotinib
  • some heart medications, such as acebutolol, doxazosin, or prazosin
  • any medication that inhibits CYP2D6 (such as paroxetine, fluoxetine, or quinidine) or CYP3A4 (such as itraconazole, clarithromycin, or ketoconazole). Reduce the dosage of Rexulti
  • any medication that induces CYP3A4 (such as rifampin or St. John's wort). Increase the dosage of Rexulti

Alcohol may worsen the side effects of Rexulti such as drowsiness and dizziness.

Note that this list is not all-inclusive and includes only common medications that may interact with Rexulti. You should refer to the prescribing information for Rexulti for a complete list of interactions.

References

Further information

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use Rexulti only for the indication prescribed.

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