Aripiprazole Lauroxil

Serious side effects have been reported with aripiprazole lauroxil. See the “Aripiprazole lauroxil Precautions” section.

The most common side effect of aripiprazole lauroxil is the feeling like you need to move to stop unpleasant feelings in your legs (restless leg syndrome or akathisia).

This is not a complete list of aripiprazole lauroxil side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that block a protein in the body (CYP3A4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone
• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin (Rifadin), St John's wort, and nimodipine (Nimotop)
• medications that block a protein in the body (CYP2D6) such as quinidine (Qualaquin), fluoxetine (Prozac, Sarafem), amitriptyline (Elavil), and paroxetine (Paxil)
• medications to treat high blood pressure
• benzodiazepines such as lorazepam (Ativan)

This is not a complete list of drug interactions. Ask your doctor or pharmacist for more information.

Serious side effects have been reported with aripiprazole lauroxil including the following:

• Stroke in elderly people (cardiovascular problems) that can lead to death.
• Neuroleptic malignant syndrome (NMS): Tell your healthcare provider right away if you have some or all of the following symptoms: high fever, stiff muscles, confusion, sweating, changes in pulse, heart rate, and blood pressure. These may be symptoms of a rare and serious condition that can lead to death. Call your healthcare provider right away if you have any of these symptoms.
• Uncontrolled body movements (tardive dyskinesia): Aripiprazole lauroxil may cause movements that you cannot control in your face, tongue, or other body parts. Tardive dyskinesia may not go away, even if you stop receiving aripiprazole lauroxil. Tardive dyskinesia may also start after you stop receiving aripiprazole lauroxil.
• Problems with your metabolism such as:
  • High blood sugar (hyperglycemia): Increases in blood sugar can happen in some people who take aripiprazole lauroxil. Extremely high blood sugar can lead to coma or death. If you have diabetes or risk factors for diabetes (such as being overweight or a family history of diabetes), your healthcare provider should check your blood sugar before you start receiving aripiprazole lauroxil and during your treatment. Call your healthcare provider if you have symptoms of high blood sugar while receiving aripiprazole lauroxil such as feeling very thirsty, the need to urinate more than usual, feeling very hungry, feeling weak or tired, feeling sick to your stomach, confusion, and/or fruity breath
  • Increased fat levels (cholesterol and triglycerides) in your blood.
  • Weight gain. You and your healthcare provider should check your weight regularly.
• Decreased blood pressure (orthostatic hypotension). You may feel lightheaded or faint when you rise too quickly from a sitting or lying position.
• Low white blood cell count
• Seizures (convulsions)
• Problems controlling your body temperature so that you feel too warm.
• Difficulty swallowing 
• Gambling urges and other uncontrollable (compulsive) behaviors such as an increased sex drive, spending money (compulsive shopping), binge eating or eating that you cannot control. If you or your family members notice any of these behaviors, speak with your health care provider. 

This medication may make you feel tired or have trouble with balance. This may lead to the risk of falls. 

Aripiprazole lauroxil may make you feel drowsy. Do not drive a car, operate machinery, or do other dangerous activities until you know how aripiprazole lauroxil affects you.

Do not drink alcohol while you receive aripiprazole lauroxil.

Do not become too hot or dehydrated while you receive aripiprazole lauroxil.

• Do not exercise too much.
• In hot weather, stay inside in a cool place if possible.
• Stay out of the sun.
• Do not wear too much clothing or heavy clothing.
• Drink plenty of water

Do not take this medication if you are allergic to aripiprazole lauroxil or to any of its ingredients.

Tell your doctor if you are pregnant or plan to become pregnant.

Aripiprazole lauroxil use during pregnancy can cause extrapyramidal and/or withdrawal symptoms in neonates in women exposed during the third trimester of pregnancy.

If you become pregnant while taking aripiprazole lauroxil, talk to your healthcare provider about registering with the National Pregnancy Registry for Atypical Antipsychotics. This registry monitors pregnancy outcomes in women exposed to aripiprazole lauroxil during pregnancy. For more information, contact the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388.

Do not miss a dose of aripiprazole lauroxil. If you miss a dose for some reason, call your healthcare provider right away to discuss what you should do next.

• Second Generation (Atypical) Antipsychotic

Schizophrenia: IM: Establish tolerability with oral aripiprazole prior to initiating treatment with aripiprazole lauroxil (may take up to 2 weeks). Base the initial aripiprazole lauroxil dose on the current oral aripiprazole dose and administer in conjunction with oral aripiprazole for 21 consecutive days. Adjust dose as needed; if a dose is required earlier than the recommended interval(s), do not administer <14 days after the previous injection.

Oral aripiprazole 10 mg/day: Initial intramuscular aripiprazole lauroxil dose: 441 mg per month

Oral aripiprazole 15 mg/day: Initial intramuscular aripiprazole lauroxil dose: 662 mg per month OR 882 mg every 6 weeks OR 1064 mg every 2 months

Oral aripiprazole ≥20 mg/day: Initial intramuscular aripiprazole lauroxil dose: 882 mg every month

Missed dose: Administer as soon as possible. Supplementation with oral aripiprazole may be required. In patients who require oral supplementation, administer the same dose of oral aripiprazole that the patient was receiving prior to initiation of aripiprazole lauroxil:

Current dose of aripiprazole lauroxil: 441 mg per month:

Last injection occurred ≤6 weeks ago: Administer aripiprazole lauroxil immediately; no oral aripiprazole supplementation required.

Last injection occurred >6 and ≤7 weeks ago: Administer aripiprazole lauroxil immediately in conjunction with oral aripiprazole supplementation for 7 days.

Last injection occurred >7 weeks ago: Administer aripiprazole lauroxil immediately in conjunction with oral aripiprazole supplementation for 21 days.

Current dose of aripiprazole lauroxil: 662 to 882 mg per month or 882 mg every 6 weeks:

Last injection occurred ≤8 weeks ago: Administer aripiprazole lauroxil immediately; no oral aripiprazole supplement.

Last injection occurred >8 and ≤12 weeks ago: Administer aripiprazole lauroxil immediately in conjunction with oral aripiprazole supplementation for 7 days.

Last injection occurred >12 weeks ago: Administer aripiprazole lauroxil immediately in conjunction with oral aripiprazole supplementation for 21 days.

Current dose of aripiprazole lauroxil: 1064 mg every 2 months:

Last injection occurred ≤10 weeks ago: Administer aripiprazole lauroxil immediately; no oral aripiprazole supplement.

Last injection occurred >10 and ≤12 weeks ago: Administer aripiprazole lauroxil immediately in conjunction with oral aripiprazole supplementation for 7 days.

Last injection occurred >12 weeks ago: Administer aripiprazole lauroxil immediately in conjunction with oral aripiprazole supplementation for 21 days.

Dosage adjustment for concomitant therapy (patients stabilized on aripiprazole lauroxil):

CYP450 modulators added for <2 weeks: No dosage adjustment necessary.

Initiation of a strong CYP3A4 inhibitor for ≥2 weeks: Reduce the dose of aripiprazole lauroxil to the next lower strength; in patients receiving 882 mg every 6 weeks or 1064 mg every 2 months, the next lower dose should be 441 mg every month. If the patient is a known poor metabolizer of CYP2D6, reduce the aripiprazole lauroxil dose to 441 mg regardless of the current dose. In patients receiving aripiprazole lauroxil 441 mg, no dosage adjustment necessary, if tolerated.

Initiation of a strong CYP2D6 inhibitor for ≥2 weeks: Reduce the dose of aripiprazole lauroxil to the next lower strength; in patients receiving 882 mg every 6 weeks or 1064 mg every 2 months, the next lower dose should be 441 mg every month. If the patient is a known poor metabolizer of CYP2D6 or if the patient is receiving aripiprazole lauroxil 441 mg, no dosage adjustment necessary, if tolerated.

Initiation of both a strong CYP3A4 and a strong CYP2D6 inhibitor for ≥2 weeks: Avoid use in patients receiving aripiprazole lauroxil 662 mg, 882 mg, or 1064 mg. In patients receiving aripiprazole lauroxil 441 mg, no dosage adjustment necessary, if tolerated.

Initiation of CYP3A4 inducer for ≥2 weeks: In patients receiving aripiprazole lauroxil 441 mg, increase the dose to 662 mg. In patients receiving aripiprazole lauroxil 662 mg, 882 mg, or 1064 mg, no dosage adjustment necessary.

Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

>10%: Central nervous system: Akathisia (11%)

1% to 10%:

Central nervous system: Headache (5%), parkinsonian-like syndrome (4%), insomnia (3% to 4%), restlessness (3%), dystonia (2%)

Endocrine & metabolic: Weight gain (2%; ≥7% increase: 9% to 10%)

Local: Pain at injection site (3% to 4%)

Neuromuscular & skeletal: Increased creatine phosphokinase (1% to 2%)

Frequency not defined:

Cardiovascular: Angina pectoris, palpitations, tachycardia

Central nervous system: Anxiety, dizziness, myasthenia

Gastrointestinal: Constipation, xerostomia

Neuromuscular & skeletal: Weakness

<1% (Limited to important or life-threatening): Impulse control disorder (including pathologic gambling, binge eating, and hypersexuality) (FDA Safety Alert May 3, 2016), orthostatic hypotension

Aripiprazole crosses the placenta; aripiprazole and dehydro-aripiprazole can be detected in the cord blood at delivery (Nguyen 2011; Watanabe 2011).

Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.

Data collection to monitor pregnancy and infant outcomes following exposure to aripiprazole lauroxil is ongoing. Healthcare providers are encouraged to enroll women exposed to aripiprazole lauroxil during pregnancy in the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry.