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Invega Sustenna: 7 things you should know

Medically reviewed by Carmen Fookes, BPharm. Last updated on Dec 30, 2022.

1. How it works

  • Invega Sustenna is a brand (trade) name for paliperidone palmitate, which may be used to treat schizophrenia or schizoaffective disorder in adults.
  • Although experts aren't exactly sure how Invega Sustenna (paliperidone palmitate) works, they know that it is hydrolyzed in the body to paliperidone, which is the major active metabolite of risperidone. Some suggest paliperidone works in schizophrenia by blocking central dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptors.
  • Invega Sustenna belongs to the class of medicines known as atypical antipsychotics.

2. Upsides

  • May be used to treat schizophrenia in adults.
  • May also be used to treat schizoaffective disorder in adults as the sole treatment or in combination with mood stabilizers or antidepressants.
  • Works like a depot preparation but needs to be given by a healthcare professional into a large muscle such as the deltoid muscle of the arm or the gluteal muscle of the buttocks (intramuscularly).
  • The effects of Invega Sustenna last for 1 month.
  • Using a long-acting injectable medicine like Invega Sustenna can help people to remain on treatment without the burden of having to remember to take a daily pill.
  • Recommended to be used before transitioning a person to either Invega Trinza (lasts for 3 months) or Invega Hayfera (lasts for 6 months). Before transitioning to Invega Hayfera, patients must be adequately treated with Invega Sustenna for at least 4 months and tolerated it well.
  • Usually started with a dose of 234mg given IM, followed by 156mg IM one week later. Thereafter, monthly injections of 39mg to 234mg IM are given, depending on the condition being treated, individual dosage requirements, and how well the person tolerates Invega Sustenna.
  • Not a controlled substance but has not been studied for its potential for abuse, tolerance, or physical dependence.

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:

  • Drowsiness that may affect your ability to drive or operate machinery. Avoid alcohol.
  • Other common side effects include headache, agitation, anxiety, abdominal discomfort, diarrhea, dry mouth, nausea, toothache, vomiting, fatigue, infections, or pain. Uncommonly, a reduction in the number of white blood cells, swallowing difficulty, priapism (sustained erections), dysphagia, disruption of body temperature regulation, and seizures may occur.
  • A drop in blood pressure on standing, particularly during the initial dose-titration period. May not be suitable for people with known cardiovascular disease (history of a heart attack, angina, heart failure, or arrhythmia), stroke, and people at risk of dehydration. This may increase the risk of falls.
  • Extrapyramidal symptoms (such as restlessness, tremor, uncontrolled muscle contractions, and tardive dyskinesia) have been reported in people treated with antipsychotic drugs, such as Invega Sustenna.
  • An increase in 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 and weight gain (ranging from an increase of 0.4 to 1.4 kg [0.9 to 3 pounds] from baseline).
  • An increase in prolactin levels (risk is higher than with most other antipsychotics), which can lead to side effects such as impaired fertility, an absence of menstruation, unwanted lactation, breast enlargement in men, impotence, and decreased bone density. May not be suitable for people with a history of prolactin-dependent breast cancer.
  • Do not give to patients with a known hypersensitivity to either paliperidone, risperidone, or any of the excipients in Invega Sustenna. Anaphylaxis and angioedema have been reported.
  • Must be administered by a healthcare professional.
  • Only needles supplied with the Invega Sustenna kit should be used. It should only be administered into a muscle, not by any other route. The entire dose should be administered slowly, as a single injection, not as divided injections.
  • There is little data about the use of Invega Sustenna in kidney disease. For people with mild renal impairment (CLCR >/50 mL/min to < 80 mL/min) initiate Invega Sustenna with a dose of 156mg on day 1 and 117mg one week later. Administer both doses in the deltoid muscle. Thereafter follow up with monthly injections of 78mg in either the deltoid or gluteal muscle.
  • Has not been studied in liver disease but no dosage adjustment is recommended in mild to moderate liver disease.
  • Establish tolerability with oral paliperidone or oral or injectable risperidone in patients who have never taken these medications before initiating Invega Sustenna.
  • Rarely, may cause Neuroleptic Malignant Syndrome (NMS); symptoms include high body temperature, muscle rigidity, and mental disturbances; discontinue immediately and seek urgent medical advice.
  • Antipsychotics, such as Invega Sustenna should not be used for the treatment of dementia-related psychosis in elderly people because they have been associated with a higher risk of death and cerebrovascular events. Patients with Parkinson's disease or Lewy body dementia are at higher risk of side effects such as confusion, falling, extrapyramidal symptoms, and NMS.
  • May cause a modest increase in the corrected QT (QTc) interval. Avoid in combination with drugs known to prolong the QT interval.
  • Not for use in children under the age of 18 years.
  • There are no controlled studies investigating the use of Invega Sustenna in pregnant women. Neonates exposed to antipsychotic agents, such as Invega Sustenna, paliperidone, or risperidone, in the third trimester are at risk for extrapyramidal or withdrawal symptoms following delivery. Only use in pregnancy if the potential benefits justify the risk. Paliperidone (the active ingredient of Invega Sustenna) is present in breast milk, and breastfeeding is not recommended. May reduce fertility in females.

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

Invega Sustenna is a long-acting form of paliperidone that is injected into the deltoid or gluteal muscle once a month after an initial loading dose. It is similar in its pharmacology and action to risperidone, and tolerance to either risperidone or paliperidone should be established before initiating Invega Sustenna. The main side effects are headache, anxiety, agitation, and drowsiness, and it may be used to transition to longer-acting antipsychotic medications used for schizophrenia or schizoaffective disorder such as Invega Trinza or Invega Hayfera.

5. Tips

  • Invega Sustenna is a long-acting medicine given by injection once a month after a loading dose of two injections given one week apart. Your doctor will give you these injections.
  • It’s important to stay on schedule with your Invega Sustenna injections. Go to all of your appointments so you can get your medication on time and discuss your progress with your doctor. If you must miss an appointment, contact your doctor to reschedule as soon as possible.
  • Invega Sustenna, or other Invega products (such as Invega Trinza or Invega Hayfera) are usually taken for a long time. Your symptoms may not completely disappear, but should improve over time.
  • Do not drink alcohol while being treated with Invega Sustenna because it can increase side effects such as dizziness, drowsiness, and trouble concentrating. This may also affect your ability to make decisions, think clearly, or react quickly. Drinking alcohol can also lead to dehydration.
  • Avoid becoming dehydrated while taking Invega Sustenna. Drink 6 to 8 glasses of water per day.
  • Do not drive, operate heavy machinery, or do other dangerous activities until you know how Invega Sustenna affects you.
  • Invega Sustenna 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.
  • You should always tell your doctor and other healthcare providers about any medicines you use, including prescription and over-the-counter (OTC) drugs, herbal supplements, and vitamins. Your healthcare provider can check for any drug, food, or disease interactions with your medicines.
  • Tell your doctor if you are intending to become pregnant and you are taking Invega Sustenna because your doctor may wish to change you to a different medication before you fall pregnant. Invega Sustenna is incompatible with breastfeeding.

6. Response and effectiveness

  • Studies have reported an improvement in PANSS scores in people given Invega Sustenna compared to those given a placebo. The placebo-subtracted change in baseline ranged from -3.5 to -14 depending on the study.
  • At 120 days, only 15% of patients with schizophrenia had relapsed who were taking Invega Sustenna, compared with over 40% who had been taking a placebo.
  • For patients with schizoaffective disorder, only 10% had relapsed at day 120 compared to 15% with a placebo. On day 330, 15% relapsed with Invega Sustenna compared to over 35% with placebo.
  • Switching from Invega Sustenna to Invega Hayfera. For a seamless transition, it is recommended that the last two doses of Invega Sustenna are the same dosage strength. Start Invega Hayfera up to 7 days before, on, or 7 days after the day the next 1-month Invega Sustenna dose was due. Before transitioning to Invega Hayfera, a person must have been administered Invega Sustenna for at least 4 months or Invega Trinza for at least one three-month cycle and tolerated either of them well.
  • Invega Sustenna, Invega Trinza, and Invega Hayfera all utilize Alkermes' nano-particle technology. Invega Trinza has a greater concentration (312 vs 156 mg/mL of paliperidone palmitate) and a larger particle size than Invega Sustenna. Invega Hayfera has the same concentration (312 vs 312 mg/mL of paliperidone palmitate) as Invega Trinza but has been formulated to release its active ingredient over 6 months.

7. Interactions

Medicines that interact with Invega Sustenna may either decrease its effect, affect how long it works, increase side effects, or have less of an effect when taken with Invega Sustenna. 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.

Over 590 different medications interact with Invega Sustenna. Most of these interactions are considered major or moderate. Common medications that may interact with Invega Sustenna include:

  • antidepressants such as citalopram, escitalopram, or fluoxetine
  • antipsychotics such as aripiprazole, clozapine, or haloperidol
  • azelastine
  • bupropion
  • clozapine
  • cisapride
  • CYP2D6 inhibitors or inducers, such as fluoxetine
  • CYP3A4 inducers, such as carbamazepine, oxcarbazepine, phenytoin, rifampin, St. John's Wort (avoid coadministration if possible. Consider using oral paliperidone extended-release tablets instead)
  • CYP3A4 inhibitors, such as clarithromycin, cyclosporine, fluconazole, ketoconazole, nefazodone, ritonavir, tamoxifen, or verapamil
  • diuretics, such as furosemide or hydrochlorothiazide
  • droperidol
  • heart medications, such as amlodipine, betaxolol, candesartan, or carisprodol
  • HIV medications, such as saquinavir
  • insulin
  • glucagon
  • kava kava
  • lithium
  • magnesium sulfate
  • medications used to treat Parkinson's Disease, such as cabergoline and levodopa (can antagonize the effects of Invega Sustenna)
  • nitroglycerin
  • opioids, such as alfentanil, fentanyl, buprenorphine, methadone, or oxycodone
  • pimozide
  • QT-prolonging medications, such as amiodarone, clarithromycin, domperidone, flupentixol, sotalol, or voriconazole
  • tramadol
  • valproate
  • zolpidem.

Any medication that can cause drowsiness, dizziness, confusion, or orthostatic hypotension can add to the side effects of Invega Sustena. Alcohol use with Invega Sustenna can worsen dizziness, drowsiness, confusion, and other central nervous symptoms. Do not drink alcohol while using Invega Sustenna.

Because the active ingredient of Invega Sustenna, paliperidone, is the major active metabolite of risperidone, be cautious when administering Invega Sustena and risperidone or oral paliperidone for extended periods. Safety data investigating the use of Invega Sustenna with other antipsychotics is limited.

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

Always discuss the potential for drug interactions with your doctor and pharmacist with each new prescription or non-prescription (OTC) medicine or supplement you use.


Further information

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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

Copyright 1996-2023 Revision date: December 29, 2022.