Olanzapine Extended Release Injectable Suspension

Name: Olanzapine Extended Release Injectable Suspension

Side effects

Clinical Trials Experience

The information below for ZYPREXA RELPREVV is derived primarily from a clinical trial database consisting of 2058 patients with approximately 1948 patient years of exposure to ZYPREXA RELPREVV. This database includes safety data from 6 open-label studies and 2 double-blind comparator studies, conducted in patients with schizophrenia or schizoaffective disorder. Additionally, data obtained from patients treated with oral olanzapine are also presented below. Adverse reactions were assessed by the collection of adverse reactions, vital signs, weights, laboratory analytes, ECGs, and the results of physical and ophthalmologic examinations. In the tables and tabulations that follow for ZYPREXA RELPREVV, the MedDRA terminology has been used to classify reported adverse reactions. Data obtained from oral olanzapine studies was reported using the COSTART and MedDRA dictionaries.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Reactions listed elsewhere in labeling may not be repeated below. The entire label should be read to gain a complete understanding of the safety profile of ZYPREXA RELPREVV.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reaction incidence in the population studied.

Adverse Reactions Associated With Discontinuation Of Treatment In A Short-Term, Placebo-Controlled Trial

Overall, there was no difference in the incidence of discontinuation due to adverse reactions between ZYPREXA RELPREVV (4%; 13/306 patients) and placebo (5%; 5/98 patients) in an 8-week trial.

Commonly Observed Adverse Reactions In A Short-Term, Placebo-Controlled Trial

In an 8-week trial, treatment-emergent adverse reactions with an incidence of 5% or greater in at least one of the ZYPREXA RELPREVV treatment groups (210 mg/2 weeks, 405 mg/4 weeks, or 300 mg/2 weeks) and greater than placebo were: headache, sedation, weight gain, cough, diarrhea, back pain, nausea, somnolence, dry mouth, nasopharyngitis, increased appetite, and vomiting.

Adverse Reactions Occurring At An Incidence Of 2% Or More Among ZYPREXA RELPREVV-Treated Patients In A Short-Term, Placebo-Controlled Trial

Table 9 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with ZYPREXA RELPREVV and with incidence greater than placebo who participated in the 8-week, placebo-controlled trial.

Table 9: Treatment-Emergent Adverse Reactions: Incidence in a Short-Term, Placebo-Controlled Clinical Trial with ZYPREXA RELPREVV

Body System/
Adverse Reaction
Percentage of Patients Reporting Adverse Event
Placebo
(N=98)
ZYPREXA RELPREVV
405 mg/4 wks
(N=100)
ZYPREXA RELPREVV
210 mg/2 wks
(N=106)
ZYPREXA RELPREVV
300 mg/2 wks
(N=100)
Ear and Labyrinth Disorders
Ear pain 2 1 1 4
Gastrointestinal Disorders
Abdominal paina 2 3 3 3
Diarrhea 4 2 7 5
Dry mouth 1 2 6 4
Flatulence 0 2 2 1
Nausea 2 5 5 4
Toothache 0 3 4 3
Vomiting 2 6 1 2
General Disorders and Administration Site Conditions
Fatigue 2 4 2 3
Injection site pain 0 2 3 2
Pain 0 0 2 3
Pyrexia 0 2 0 0
Infections and Infestations
Nasopharyngitis 2 3 6 1
Tooth infectionb 0 4 0 0
Upper respiratory tract infection 2 3 1 4
Viral infection 0 0 0 2
Injury, Poisoning and Procedural Complications
Procedural pain 0 2 0 0
Investigations        
Electrocardiogram QT-corrected interval prolonged 1 0 0 2
Hepatic enzyme increasedc 1 4 1 3
Weight increased 5 5 6 7
Metabolism and Nutrition Disorders
Increased appetite 0 1 4 6
Musculoskeletal and Connective Tissue Disorders
Arthralgia 0 3 3 3
Back pain 4 4 3 5
Muscle spasms 0 3 1 2
Musculoskeletal stiffness 1 1 4 4
Nervous System Disorders
Dizziness 2 4 4 1
Dysarthria 0 0 1 2
Headached 8 13 15 18
Sedatione 7 13 8 13
Tremor 1 3 0 1
Psychiatric Disorders        
Abnormal dreams 0 0 0 2
Hallucination, auditory 2 3 1 0
Restlessness 2 2 3 1
Sleep disorder 1 0 0 2
Thinking abnormal 1 3 0 0
Reproductive System and Breast Disorders
Vaginal discharge 0 0 4 4
Respiratory, Thoracic and Mediastinal Disorders        
Cough 5 3 5 9
Nasal congestionf 3 2 1 7
Pharyngolaryngeal pain 2 2 3 3
Sneezing 0 0 0 2
Skin and Subcutaneous Tissue Disorders
Acne 0 2 0 2
Vascular Disorders        
Hypertension 0 3 2 0
a The term abdominal pain upper was combined under abdominal pain.
b The term tooth abscess was combined under tooth infection.
c The terms alanine aminotransferase increased, aspartate aminotransferase increased, and gamma-glutamyltransferase increased were combined under hepatic enzyme increased.
d The term tension headache was combined under headache.
e The term somnolence was combined under sedation.
f The term sinus congestion was combined under nasal congestion.

Dose Dependency Of Adverse Reactions

Dose group differences have been observed for weight, fasting triglycerides and prolactin elevation for ZYPREXA RELPREVV [see WARNINGS AND PRECAUTIONS].

A dose group difference for oral olanzapine has been observed for fatigue, dizziness, weight gain and prolactin elevation. In a single 8-week randomized, double-blind, fixed-dose study comparing 10 (N=199), 20 (N=200) and 40 (N=200) mg/day of oral olanzapine in adult patients with schizophrenia or schizoaffective disorder, incidence of fatigue (10 mg/day: 1.5%; 20 mg/day: 2.1%; 40 mg/day: 6.6%) was observed with significant differences between 10 vs 40 and 20 vs 40 mg/day. The incidence of dizziness (10 mg/day: 2.6%; 20 mg/day: 1.6%; 40 mg/day: 6.6%) was observed with significant differences between 20 vs 40 mg. Dose group differences were also noted for weight gain and prolactin elevation [see WARNINGS AND PRECAUTIONS].

Extrapyramidal Symptoms

The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by categorical analyses of formal rating scales during acute therapy in a controlled clinical trial comparing oral olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.

Table 10: Treatment-Emergent Extrapyramidal Symptoms Assessed by Rating Scales Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia . Acute Phase

  Percentage of Patients Reporting Event
Placebo Olanzapine
5 ± 2.5 mg/day
Olanzapine
10 ± 2.5 mg/day
Olanzapine
15 ± 2.5 mg/day
Parkinsonisma 15 14 12 14
Akathisiab 23 16 19 27
a Percentage of patients with a Simpson-Angus Scale total score >3.
b Percentage of patients with a Barnes Akathisia Scale global score ≥2.

The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy in the same controlled clinical trial comparing olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.

Table 11: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia . Acute Phase

  Percentage of Patients Reporting Event
Placebo
(N=68)
Olanzapine
5 ± 2.5 mg/day
(N=65)
Olanzapine
10 ± 2.5 mg/day
(N=64)
Olanzapine
15 ± 2.5 mg/day
(N=69)
Dystonic eventsa 1 3 2 3
Parkinsonism eventsb 10 8 14 20
Akathisia eventsc 1 5 11 10
Dyskinetic eventsd 4 0 2 1
Residual eventse 1 2 5 1
Any extrapyramidal event 16 15 25 32
a Patients with the following COSTART terms were counted in this category: dystonia, generalized spasm, neck rigidity, oculogyric crisis, opisthotonos, torticollis.
b Patients with the following COSTART terms were counted in this category: akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, tremor.
c Patients with the following COSTART terms were counted in this category: akathisia, hyperkinesia.
d Patients with the following COSTART terms were counted in this category: buccoglossal syndrome, choreoathetosis, dyskinesia, tardive dyskinesia.
e Patients with the following COSTART terms were counted in this category: movement disorder, myoclonus, twitching.

Dystonia, Class Effect:

Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, the frequency and severity are greater with high potency and at higher doses of first generation antipsychotic drugs. In general, an elevated risk of acute dystonia may be observed in males and younger age groups receiving antipsychotics; however, events of dystonia have been reported infrequently (<1%) with olanzapine use.

Other Adverse Reactions

Local Injection Site Reactions

Eleven ZYPREXA RELPREVV-treated patients (3.6%) and 0 placebo-treated patients experienced treatment-emergent injection-related adverse reactions (injection site pain, buttock pain, injection site mass, induration, injection site induration) in the placebo-controlled database. The most frequently occurring treatment-emergent adverse reaction was injection site pain (2.3% ZYPREXA RELPREVV-treated; 0% placebo-treated).

Other Adverse Reactions Observed During The Clinical Trial Evaluation Of Olanzapine For Extended-Release Injectable Suspension

Injection site abscess has been reported in clinical trials with ZYPREXA RELPREVV therapy. Isolated cases required surgical intervention.

Commonly Observed Adverse Reactions During The Clinical Trial Evaluation Of Oral Olanzapine

In clinical trials of oral olanzapine monotherapy for the treatment of schizophrenia in adult patients, treatment-emergent adverse reactions with an incidence of 5% or greater in the olanzapine treatment arm and at least twice that of placebo were: postural hypotension, constipation, weight gain, dizziness, personality disorder, and akathisia.

Other Adverse Reactions Observed During The Clinical Trial Evaluation Of Oral Olanzapine

Following is a list of treatment-emergent adverse reactions reported by patients treated with oral olanzapine (at multiple doses ≥1 mg/day) in clinical trials. This listing is not intended to include reactions (1) already listed in previous tables or elsewhere in labeling, (2) for which a drug cause was remote, (3) which were so general as to be uninformative,(4) which were not considered to have significant clinical implications, or (5) which occurred at a rate equal to or less than placebo. Reactions are classified by body system using the following definitions: frequent adverse reactions are those occurring in at least 1/100 patients; infrequent adverse reactions are those occurring in 1/100 to 1/1000 patients; rare adverse reactions are those occurring in fewer than 1/1000 patients.

Body as a WholeInfrequent: chills, face edema, photosensitivity reaction, suicide attempt1;Rare: chills and fever, hangover effect, sudden death1 .

Cardiovascular SystemInfrequent: cerebrovascular accident, vasodilatation.

Digestive SystemInfrequent: abdominal distension, nausea and vomiting, tongue edema; Rare: ileus, intestinal obstruction, liver fatty deposit.

Hemic and Lymphatic SystemInfrequent: thrombocytopenia. Metabolic and Nutritional Disorders . Frequent: alkaline phosphatase increased; Infrequent: bilirubinemia, hypoproteinemia.

Musculoskeletal SystemRare: osteoporosis.

Nervous System Infrequent: ataxia, dysarthria, libido decreased, stupor; Rare: coma.

Respiratory SystemInfrequent: epistaxis; Rare: lung edema.

Skin and AppendagesInfrequent: alopecia.

Special SensesInfrequent: abnormality of accommodation, dry eyes; Rare: mydriasis.

Urogenital System Infrequent: amenorrhea2, breast pain, decreased menstruation, impotence2, increased menstruation2, menorrhagia2, metrorrhagia2, polyuria2, urinary frequency, urinary retention, urinary urgency, urination impaired.

1These terms represent serious adverse events but do not meet the definition for adverse drug reactions. They are included here because of their seriousness.
2 Adjusted for gender.

Vital Signs And Laboratory Studies

Laboratory Changes

ZYPREXA RELPREVV in Adults: Statistically significant within group mean changes for ZYPREXA RELPREVV, which were also significantly different from placebo, were observed for the following: eosinophils, monocytes, cholesterol, low-density lipoprotein (LDL), triglycerides, and direct bilirubin. There were no statistically significant differences between ZYPREXA RELPREVV and placebo in the incidence of potentially clinically significant changes in any of the laboratory values studied.

Statistically significant within group mean changes for ZYPREXA RELPREVV, which were also significantly different from oral olanzapine (in a 24-week double-blind study), were observed for the following: gammaglutamyltransferase (GGT) and sodium.

From an analysis of the laboratory data in an integrated database of 41 completed clinical studies in adult patients treated with oral olanzapine, high GGT levels were recorded in ≥1% (88/5245) of patients.

Statistically significant differences were observed between ZYPREXA RELPREVV and oral olanzapine for the incidence of treatment-emergent low platelet count (0% ZYPREXA RELPREVV vs 1% oral olanzapine); and low total bilirubin (2.8% ZYPREXA RELPREVV vs 0.7% for oral olanzapine). There was a statistically significant difference between ZYPREXA RELPREVV and oral olanzapine in potentially clinically significant changes for high leukocyte count (0% ZYPREXA RELPREVV vs 1% oral olanzapine).

Changes in aminotransferases observed with ZYPREXA RELPREVV treatment were similar to those reported with ZYPREXA treatment. In placebo-controlled ZYPREXA RELPREVV studies, clinically significant ALT elevations (≥3 times the upper limit of the normal range) were observed in 2.7% (8/291) of patients exposed to olanzapine compared to 3.2% (3/94) of the placebo patients. None of these patients experienced jaundice. In 3 of these patients, liver enzymes reverted to the normal range despite continued treatment, and in 5 cases enzymes values decreased, but were still above the normal range at the end of therapy.

Within the larger premarketing ZYPREXA RELPREVV database of 1886 patients with baseline ALT ≤90 IU/L, the incidence of ALT elevation to >200 IU/L was 0.8%. None of these patients experienced jaundice or other symptoms attributable to liver impairment and most had transient changes that tended to normalize while ZYPREXA RELPREVV treatment was continued.

From an analysis of the laboratory data in an integrated database of 41 completed clinical studies in adult patients treated with oral olanzapine, elevated uric acid was recorded in ≥3% (171/4641) of patients.

Olanzapine Monotherapy in Adults

An assessment of the premarketing experience for oral olanzapine revealed an association with asymptomatic increases in ALT, AST, and GGT. Within the original premarketing database of about 2400 adult patients with baseline ALT ≤90 IU/L, the incidence of ALT elevations to >200 IU/L was 2% (50/2381). None of these patients experienced jaundice or other symptoms attributable to liver impairment and most had transient changes that tended to normalize while olanzapine treatment was continued.

In placebo-controlled oral olanzapine monotherapy studies in adults, clinically significant ALT elevations (change from <3 times the upper limit of normal [ULN] at baseline to ≥3 times ULN) were observed in 5% (77/1426) of patients exposed to olanzapine compared to 1% (10/1187) of patients exposed to placebo. ALT elevations ≥5 times ULN were observed in 2% (29/1438) of olanzapine-treated patients, compared to 0.3% (4/1196) of placebo-treated patients. ALT values returned to normal, or were decreasing, at last follow-up in the majority of patients who either continued treatment with olanzapine or discontinued olanzapine. No patient with elevated ALT values experienced jaundice, liver failure, or met the criteria for Hy’s Rule.

Caution should be exercised in patients with signs and symptoms of hepatic impairment, in patients with preexisting conditions associated with limited hepatic functional reserve, and in patients who are being treated with potentially hepatotoxic drugs.

Oral olanzapine administration was also associated with increases in serum prolactin [see WARNINGS AND PRECAUTIONS], with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK.

ECG Changes

Comparison of ZYPREXA RELPREVV and oral olanzapine, in a 24 week study, revealed no significant differences on ECG changes. Between-group comparisons for pooled placebo-controlled trials revealed no significant oral olanzapine/placebo differences in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc, and PR intervals. Oral olanzapine use was associated with a mean increase in heart rate of 2.4 beats per minute compared to no change among placebo patients. This slight tendency to tachycardia may be related to olanzapine’s potential for inducing orthostatic changes [see WARNINGS AND PRECAUTIONS].

Postmarketing Experience

Adverse reactions reported since market introduction that were temporally (but not necessarily causally) related to ZYPREXA therapy include the following: allergic reaction (e.g., anaphylactoid reaction, angioedema, pruritus or urticaria), cholestatic or mixed liver injury, diabetic coma, diabetic ketoacidosis, discontinuation reaction (diaphoresis, nausea, or vomiting), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), hepatitis, jaundice, neutropenia, pancreatitis, priapism, rash, restless legs syndrome, rhabdomyolysis, and venous thromboembolic events (including pulmonary embolism and deep venous thrombosis). Random cholesterol levels of ≥240 mg/dL and random triglyceride levels of .1000 mg/dL have been reported. Additionally, injection site abscess has been reported in postmarketing reports with ZYPREXA RELPREVV therapy. Isolated cases required surgical intervention.

Overdose

Human Experience

During premarketing clinical studies of ZYPREXA RELPREVV, adverse reactions that presented with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, were reported in patients following an injection of ZYPREXA RELPREVV [see BOX WARNING and DOSAGE AND ADMINISTRATION]. These reactions occurred in <0.1% of injections and in approximately 2% of patients who received injections for up to 46 months. These reactions were correlated with an unintentional rapid increase in serum olanzapine concentrations to supra-therapeutic ranges in some cases. While a rapid and greater than expected increase in serum olanzapine concentration has been observed in some patients with these reactions, the exact mechanism by which the drug was unintentionally introduced into the blood stream is not known. Clinical signs and symptoms included dizziness, confusion, disorientation, slurred speech, altered gait, difficulty ambulating, weakness, agitation, extrapyramidal symptoms, hypertension, convulsion, and reduced level of consciousness ranging from mild sedation to coma. Time after injection to event ranged from soon after injection to greater than 3 hours after injection. The majority of patients were hospitalized and some required supportive care, including intubation, in several cases. All patients had largely recovered by 72 hours. The risk of an event is the same at each injection, so the risk per patient is cumulative (i.e., increases with the number of injections) [see WARNINGS AND PRECAUTIONS].

In postmarketing reports of overdose with oral olanzapine alone, symptoms have been reported in the majority of cases. In symptomatic patients, symptoms with ≥10% incidence included agitation/aggressiveness, dysarthria, tachycardia, various extrapyramidal symptoms, and reduced level of consciousness ranging from sedation to coma. Among less commonly reported symptoms were the following potentially medically serious reactions: aspiration, cardiopulmonary arrest, cardiac arrhythmias (such as supraventricular tachycardia and 1 patient experiencing sinus pause with spontaneous resumption of normal rhythm), delirium, possible neuroleptic malignant syndrome, respiratory depression/arrest, convulsion, hypertension, and hypotension. Eli Lilly and Company has received reports of fatality in association with overdose of oral olanzapine alone. In 1 case of death, the amount of acutely ingested oral olanzapine was reported to be possibly as low as 450 mg of oral olanzapine; however, in another case, a patient was reported to survive an acute olanzapine ingestion of approximately 2 g of oral olanzapine.

Management Of Overdose

Post-injection delirium/sedation syndrome may occur with each injection of ZYPREXA RELPREVV. Signs and symptoms consistent with olanzapine overdose have been observed, and access to emergency response services must be readily available for safe use [see BOX WARNING and WARNINGS AND PRECAUTIONS].

There is no specific antidote to olanzapine. Therefore, appropriate supportive measures should be initiated. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids and/or sympathomimetic agents. (Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of olanzapine-induced alpha blockade.) Respiratory support, including ventilation, may be required. Close medical supervision and monitoring should continue until the patient recovers.

The possibility of multiple drug involvement should be considered. In case of acute overdosage, establish and maintain an airway and ensure adequate oxygenation and ventilation, which may include intubation. The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis. Cardiovascular monitoring should commence immediately and should include continuous electrocardiographic monitoring to detect possible arrhythmias.

Patient information

ZYPREXAR RELPREVV.
(zy-PREX-a REL-prev)
(olanzapine) for Extended Release Injectable Suspension

Read the Medication Guide that comes with ZYPREXA RELPREVV before you start taking it andeach time before you get an injection. There may be new information. This Medication Guide doesnot take the place of talking to your doctor about your medical condition or treatment. Talk with yourdoctor if there is something you do not understand or you want to learn more about ZYPREXARELPREVV.

What is the most important information I should know about ZYPREXA RELPREVV?

Before you receive ZYPREXA RELPREVV treatment you must:

  • understand the risks and benefits of ZYPREXA RELPREVV treatment. Your doctor will talk to you about the risks and benefits of ZYPREXA RELPREVV treatment.
  • register in the ZYPREXA RELPREVV Patient Care Program. You must agree to the rulesof the ZYPREXA RELPREVV Patient Care Program before you register.

ZYPREXA RELPREVV may cause serious side effects, including:

  1. Post-injection Delirium Sedation Syndrome (PDSS).
  2. Increased risk of death in elderly people who are confused, have memory loss and havelost touch with reality (dementia-related psychosis).
  3. High blood sugar (hyperglycemia).
  4. High fat levels in your blood (increased cholesterol and triglycerides), especially in teenagers age 13 to 17.
  5. Weight gain, especially in teenagers age 13 to 17.

These serious side effects are described below.

  1. Post-injection Delirium Sedation Syndrome (PDSS). PDSS is a serious problem that canhappen after you get a ZYPREXA RELPREVV injection if the medicine gets in your blood too fast.This problem usually happens within 3 hours after you receive ZYPREXA RELPREVV. If the medicine gets in your blood too fast, you may have some of the following symptoms:
    • feel more sleepy than usual
    • feel dizzy
    • feel confused or disoriented
    • trouble talking or walking
    • muscles feel stiff or shaking
    • feel weak
    • feel grouchy or angry
    • feel nervous or anxious
    • higher blood pressure
    • seizures (convulsions)
    • pass out (become unconscious or coma)

    You will need to stay at the clinic where you receive the injection for at least 3 hours so yourdoctor can make sure you do not have symptoms of PDSS. When you leave the clinicsomeone must be with you. If you have symptoms of PDSS after you leave the clinic, getmedical help or go to an emergency room right away.

  2. Increased risk of death in elderly people who are confused, have memory loss and havelost touch with reality (dementia-related psychosis). ZYPREXA RELPREVV is not approved for treating psychosis in elderly people with dementia.
  3. High blood sugar (hyperglycemia). High blood sugar can happen if you have diabetes alreadyor if you have never had diabetes. High blood sugar could lead to:
    • a build up of acid in your blood due to ketones (ketoacidosis)
    • coma
    • death

    Your doctor should do tests to check your blood sugar before you start taking ZYPREXA RELPREVVand during treatment. In people who do not have diabetes, sometimes high blood sugar goes awaywhen ZYPREXA RELPREVV is stopped. People with diabetes and some people who did not have diabetes before taking ZYPREXA RELPREVV need to take medicine for high blood sugar even afterthey stop taking ZYPREXA RELPREVV.

    If you have diabetes, follow your doctor’s instructions about how often to check your blood sugarwhile taking ZYPREXA RELPREVV.

    Call your doctor if you have any of these symptoms of high blood sugar (hyperglycemia) whiletaking ZYPREXA RELPREVV:

    • feel very thirsty
    • need to urinate more than usual
    • feel very hungry
    • feel weak or tired
    • feel sick to your stomach
    • feel confused or your breath smells fruity
  4. High fat levels in your blood (cholesterol and triglycerides). High fat levels may happen in people treated with ZYPREXA RELPREVV, especially in teenagers (13 to 17 years old). ZYPREXARELPREVV is not approved in patients less than 18 years old. You may not have any symptoms, soyour doctor should do blood tests to check your cholesterol and triglyceride levels before you starttaking ZYPREXA RELPREVV and during treatment.
  5. Weight gain. Weight gain is very common in people who take ZYPREXA RELPREVV.Teenagers (13 to 17 years old) are more likely to gain weight and to gain more weight than adults.ZYPREXA RELPREVV is not approved in patients less than 18 years old. Some people may gain a lot of weight while taking ZYPREXA RELPREVV, so you and your doctor should check your weightregularly. Talk to your doctor about ways to control weight gain, such as eating a healthy, balanced diet, and exercising.

What is ZYPREXA RELPREVV?

ZYPREXA RELPREVV is a long-acting prescription medicine given by injection and used to treatschizophrenia in adults. The symptoms of schizophrenia include:

  • hearing voices
  • seeing things that are not there
  • having beliefs that are not true
  • being suspicious or withdrawn

Some of your symptoms of schizophrenia may improve with treatment with ZYPREXA RELPREVV. Ifyou do not think you are getting better, call your doctor.

It is not known if ZYPREXA RELPREVV is safe and effective in children under 18 years of age.

What should I tell my doctor before taking ZYPREXA RELPREVV?

ZYPREXA RELPREVV may not be right for you. Before starting ZYPREXA RELPREVV, tell yourdoctor if you have or had:

  • heart problems
  • seizures
  • diabetes or high blood sugar levels (hyperglycemia)
  • high cholesterol or triglyceride levels in your blood
  • liver problems
  • low or high blood pressure
  • strokes or “mini-strokes” also called transient ischemic attacks (TIAs)
  • Alzheimer’s disease
  • narrow-angle glaucoma
  • enlarged prostate in men
  • bowel obstruction
  • breast cancer
  • thoughts of suicide or hurting yourself
  • any other medical condition
  • are pregnant or plan to become pregnant. It is not known if ZYPREXA RELPREVV will harmyour unborn baby.
  • are breast-feeding or plan to breast-feed. ZYPREXA RELPREVV can pass into your breastmilk and may harm your baby. You should not breast-feed while taking ZYPREXARELPREVV. Talk to your doctor about the best way to feed your baby if you take ZYPREXARELPREVV.

Tell your doctor if you exercise a lot or are in hot places often.

The symptoms of schizophrenia may include thoughts of suicide or of hurting yourself or others. If you have these thoughts at any time, tell your doctor or go to an emergency room right away.

Tell your doctor about all the medicines that you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. ZYPREXA RELPREVV and some medicines mayinteract with each other and may not work as well, or cause possible serious side effects. Your doctorcan tell you if it is safe to take ZYPREXA RELPREVV with your other medicines. Do not start or stop any medicine while taking ZYPREXA RELPREVV without talking to your doctor first.

How should I receive ZYPREXA RELPREVV?

  • ZYPREXA RELPREVV will be injected into the muscle in your buttock (gluteus) by your doctoror nurse at the clinic.
  • After receiving ZYPREXA RELPREVV, you will need to stay at the clinic for at least 3 hours.
  • When you leave the clinic, someone must be with you.
  • Call your doctor if you do not think you are getting better or have any concerns about yourcondition while taking ZYPREXA RELPREVV.

What should I avoid while receiving ZYPREXA RELPREVV?

  • ZYPREXA RELPREVV can cause sleepiness and may affect your ability to make decisions,think clearly, or react quickly. Do not drive, operate heavy machinery, or do other dangerousactivities until you know how ZYPREXA RELPREVV affects you. You should not drive oroperate heavy machinery for the rest of the day after each injection.
  • Avoid drinking alcohol while taking ZYPREXA RELPREVV. Drinking alcohol while you take ZYPREXA RELPREVV may make you sleepier than if you take ZYPREXA RELPREVV alone.

What are the possible side effects of ZYPREXA RELPREVV?

Serious side effects may happen when you take ZYPREXA RELPREVV, including:

  • See “What is the most important information I should know about ZYPREXARELPREVV?”, which describes the risk of post-injection delirium sedation syndrome(PDSS), increased risk of death in elderly people with dementia-related psychosis andthe risks of high blood sugar, high cholesterol and triglyceride levels, and weight gain.
  • Increased incidence of stroke or “mini-strokes” called transient ischemic attacks (TIAs)in elderly people with dementia-related psychosis (elderly people who have lost touch with reality due to confusion and memory loss). ZYPREXA RELPREVV is not approved for these patients.
  • Neuroleptic Malignant Syndrome (NMS): NMS is a rare but very serious condition that can happen in people who take antipsychotic medicines, including ZYPREXA RELPREVV. NMScan cause death and must be treated in a hospital. Call your doctor right away if you become severely ill and have any of these symptoms:
    • high fever
    • excessive sweating
    • rigid muscles
    • confusion
    • changes in your breathing, heartbeat, and blood pressure
  • Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): DRESS can occur with ZYPREXA RELPREVV. Features of DRESS may include rash, fever, swollen glands and other internal organ involvement such as liver, kidney, lung and heart. DRESS is sometimesfatal; therefore, tell your doctor immediately if you experience any of these signs.
  • Tardive Dyskinesia: This condition causes body movements that keep happening and thatyou can not control. These movements usually affect the face and tongue. Tardive dyskinesia may not go away, even if you stop taking ZYPREXA RELPREVV. It may also start after you stop taking ZYPREXA RELPREVV. Tell your doctor if you get any body movements that you can not control.
  • Decreased blood pressure when you change positions, with symptoms of dizziness,fast or slow heartbeat, or fainting.
  • Difficulty swallowing, that can cause food or liquid to get into your lungs.
  • Seizures: Tell your doctor if you have a seizure during treatment with ZYPREXA RELPREVV.
  • Problems with control of body temperature: You could become very hot, for instance when you exercise a lot or stay in an area that is very hot. It is important for you to drink water toavoid dehydration. Call your doctor right away if you become severely ill and have any of these symptoms of dehydration:
    • sweating too much or not at all
    • dry mouth
    • feeling very hot
    • feeling thirsty
    • not able to produce urine

Common side effects of ZYPREXA RELPREVV include: headache, sleepiness or drowsiness,weight gain, dry mouth, diarrhea, nausea, common cold, eating more (increased appetite), vomiting,cough, back pain, or pain at the injection site.

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

These are not all the possible side effects with ZYPREXA RELPREVV. For more information, askyour doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at1-800-FDA-1088.

General information about ZYPREXA RELPREVV

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide.

This Medication Guide summarizes the most important information about ZYPREXA RELPREVV. Ifyou would like more information, talk with your doctor. You can ask your doctor or pharmacist forinformation about ZYPREXA RELPREVV that was written for healthcare professionals. For moreinformation about ZYPREXA RELPREVV call 1-800-Lilly-Rx (1-800-545-5979) or visitwww.zyprexarelprevv.com.

What are the ingredients in ZYPREXA RELPREVV?

Active ingredient: olanzapine

Inactive ingredients: carboxymethylcellulose sodium, mannitol, polysorbate 80, sodium hydroxide and/or hydrochloric acid for pH adjustment, and water for injection

This Medication Guide has been approved by the U.S. Food and Drug Administration.

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