ZyPREXA Relprevv

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:

• diazepam (Valium)
• alcohol
• carbamazepine (Tegretol)
• fluvoxamine (Luvox)
• fluoxetine (Prozac, Symbax)
• levodopa
• lorazepam
• antidepressants
• antihistamines
• medicines for anxiety
• medicines for high blood pressure

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

Tell your doctor if you are breastfeeding or plan to breastfeed. Zyprexa (olanzapine) may be excreted in human breast milk. It is recommended women receiving Zyprexa Relprevv should not breastfeed.

• Take Zyprexa Relprevv exactly as prescribed. Your doctor may need to change (adjust) the dose of Zyprexa Relprevv until it is right for you.

• Zyprexa Relprevv is available as a long acting injection and is to be given directly into the muscle every 2 or 4 weeks depending on the dose given. 
• It is not to be injected intravenously (vein) or subcutaneously (under the skin).

Call your doctor if you do not think you are getting better or have any concerns about your condition while receiving Zyprexa Relprevv.

Patients are at risk for severe sedation (including coma) and/or delirium after each injection and must be observed for at least 3 hours in a registered facility with ready access to emergency response services. Because of this risk, ZYPREXA RELPREVV is available only through a restricted distribution program called Zyprexa Relprevv Patient Care Program and requires prescriber, healthcare facility, patient, and pharmacy enrollment.

 Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Zyprexa Relprevv is not approved for the treatment of patients with dementia-related psychosis. 

In the U.S.

• ZyPREXA IntraMuscular
• ZyPREXA Relprevv

Available Dosage Forms:

• Powder for Solution
• Powder for Suspension, Extended Release

Therapeutic Class: Antipsychotic

Chemical Class: Thienobenzodiazepine

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Drink lots of noncaffeine liquids unless told to drink less liquid by your doctor.
• Be careful in hot weather or while being active. Drink lots of fluids to stop fluid loss.
• Check your blood sugar as you have been told by your doctor.
• It is given as a shot into a muscle.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• If you need to store Zyprexa Relprevv at home, talk with your doctor, nurse, or pharmacist about how to store it.

None.

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

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.
	Percentage of Patients Reporting Adverse Event
Body System/Adverse Reaction	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

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 (5.7, 5.17)].

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 (5.7, 5.17)].

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

a Percentage of patients with a Simpson-Angus Scale total score >3.
b Percentage of patients with a Barnes Akathisia Scale global score ≥2.
	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

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

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.
	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

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 Whole Infrequent: chills, face edema, photosensitivity reaction, suicide attempt1; Rare: chills and fever, hangover effect, sudden death1.   Cardiovascular System Infrequent: cerebrovascular accident, vasodilatation.   Digestive System Infrequent: abdominal distension, nausea and vomiting, tongue edema; Rare: ileus, intestinal obstruction, liver fatty deposit.   Hemic and Lymphatic System Infrequent: thrombocytopenia.   Metabolic and Nutritional Disorders Frequent: alkaline phosphatase increased; Infrequent: bilirubinemia, hypoproteinemia.   Musculoskeletal System Rare: osteoporosis.   Nervous System Infrequent: ataxia, dysarthria, libido decreased, stupor; Rare: coma.   Respiratory System Infrequent: epistaxis; Rare: lung edema.   Skin and Appendages Infrequent: alopecia.   Special Senses Infrequent: 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.

1 These 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: gamma-glutamyltransferase (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 pre-existing 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 (5.17)], 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 (5.11)].

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.

Schizophrenia

The short-term effectiveness of Zyprexa Relprevv was established in an 8-week, placebo-controlled trial in adult patients (n=404) who were experiencing psychotic symptoms and met DSM-IV or DSM-IV-TR criteria for schizophrenia. Patients were randomized to receive injections of Zyprexa Relprevv 210 mg every 2 weeks, Zyprexa Relprevv 405 mg every 4 weeks, Zyprexa Relprevv 300 mg every 2 weeks, or placebo every 2 weeks. Patients were discontinued from their previous antipsychotics and underwent a 2-7 day washout period. No oral antipsychotic supplementation was allowed throughout the trial. The primary efficacy measure was change from baseline to endpoint in total Positive and Negative Syndrome Scale (PANSS) score (mean baseline total PANSS score 101). Total PANSS scores showed statistically significant improvement from baseline to endpoint with each dose of Zyprexa Relprevv (210 mg every 2 weeks, 405 mg every 4 weeks, and 300 mg every 2 weeks) as compared to placebo. The effectiveness of Zyprexa Relprevv in the treatment of schizophrenia is further supported by the established effectiveness of the oral formulation of olanzapine.

A longer-term trial enrolled patients with schizophrenia (n=1065) who had remained stable for 4 to 8 weeks on open-label treatment with oral olanzapine (mean baseline total PANSS score 56) and were then randomized to continue their current oral olanzapine dose (10, 15, or 20 mg/day); or to Zyprexa Relprevv 150 mg every 2 weeks (405 mg every 4 weeks, 300 mg every 2 weeks, or 45 mg every 4 weeks). No oral antipsychotic supplementation was allowed throughout the trial. The primary efficacy measure was time to exacerbation of symptoms of schizophrenia defined in terms of increases in Brief Psychiatric Rating Scale (BPRS) positive symptoms or hospitalization. Zyprexa Relprevv doses of 150 mg every 2 weeks, 405 mg every 4 weeks, and 300 mg every 2 weeks were each statistically significantly superior to low dose Zyprexa Relprevv (45 mg every 4 weeks).

How Supplied

Zyprexa Relprevv convenience kit is supplied in single-use cartons. Each carton includes one vial of olanzapine pamoate monohydrate in dosage strengths that are equivalent to 210 mg olanzapine (483 mg olanzapine pamoate monohydrate), 300 mg olanzapine (690 mg olanzapine pamoate monohydrate), and 405 mg olanzapine (931 mg olanzapine pamoate monohydrate) per vial; one vial of approximately 3 mL of diluent for Zyprexa Relprevv used to suspend the drug product; one 3-mL syringe with pre-attached 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needle with needle protection device; and two 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needles with needle protection device.

Needle-Pro® is a registered trademark of Smiths Medical.

  NDC 0002-7635-11 single-use convenience kit: 210 mg vial (VL7635) with rust flip-off cap and 3-mL vial of sterile diluent (VL7622) with gray flip-off cap   NDC 0002-7636-11 single-use convenience kit: 300 mg vial (VL7636) with olive flip-off cap and 3-mL vial of sterile diluent (VL7622) with gray flip-off cap   NDC 0002-7637-11 single-use convenience kit: 405 mg vial (VL7637) with steel blue flip-off cap and 3-mL vial of sterile diluent (VL7622) with gray flip-off cap

Storage and Handling

Zyprexa Relprevv should be stored at room temperature not to exceed 30°C (86°F).

When the drug product is suspended in the solution for Zyprexa Relprevv, it may be held at room temperature for 24 hours. The vial should be agitated immediately prior to product withdrawal. Once the suspension is withdrawn into the syringe, it should be used immediately [see Dosage and Administration (2.2)].

See FDA-approved Medication Guide.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking Zyprexa Relprevv. Patients should be advised to call their doctor if they do not think they are getting better or have concerns about their condition.

Information on Medication Guide

Prescribers or other health professionals should inform patients, their families, and their caregivers about the potential benefits and potential risks associated with treatment with Zyprexa Relprevv, and should counsel them in its appropriate use. A patient Medication Guide is available for Zyprexa Relprevv. Prescribers or other health professionals should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have.

Post-Injection Delirium/Sedation Syndrome

During premarketing clinical studies, reactions that presented with signs and symptoms consistent with olanzapine overdose have been reported in patients following an injection of Zyprexa Relprevv. It is mandatory that patients be enrolled in the Zyprexa Relprevv Patient Care Program to receive Zyprexa Relprevv treatment. Patients should be advised of the risk of post-injection delirium/sedation syndrome each time they receive an injection [see Warnings and Precautions (5.1, 5.2)]. Patient and caregivers should be advised that after each Zyprexa Relprevv injection, patients must be observed at the healthcare facility for at least 3 hours and must be accompanied to their destination upon leaving the facility. The Medication Guide should be distributed each time patients receive an injection.

Elderly Patients with Dementia-Related Psychosis: Increased Mortality and Cerebrovascular Adverse Events (CVAE), Including Stroke

Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Patients and caregivers should be advised that elderly patients with dementia-related psychosis treated with ZYPREXA had a significantly higher incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack) compared with placebo.

Zyprexa Relprevv is not approved for elderly patients with dementia-related psychosis [see Boxed Warning and Warnings and Precautions (5.3)].

Neuroleptic Malignant Syndrome (NMS)

Patients and caregivers should be counseled that a potentially fatal symptom complex sometimes referred to as NMS has been reported in association with administration of antipsychotic drugs, including ZYPREXA. Signs and symptoms of NMS include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia) [see Warnings and Precautions (5.5)].

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)

Patients should be advised to report to their health care provider at the earliest onset of any signs or symptoms that may be associated with Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) [see Warnings and Precautions (5.6)].

Hyperglycemia and Diabetes Mellitus

Patients should be advised of the potential risk of hyperglycemia-related adverse reactions related to Zyprexa Relprevv. Patients should be monitored regularly for worsening of glucose control. Patients who have diabetes should follow their doctor's instructions about how often to check their blood sugar while taking Zyprexa Relprevv [see Warnings and Precautions (5.7)].

Dyslipidemia

Patients should be counseled that dyslipidemia has occurred during treatment with Zyprexa Relprevv. Patients should have their lipid profile monitored regularly [see Warnings and Precautions (5.7)].

Weight Gain

Patients should be counseled that weight gain has occurred during treatment with Zyprexa Relprevv. Patients should have their weight monitored regularly [see Warnings and Precautions (5.7)].

Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension, and in association with the use of concomitant drugs that may potentiate the orthostatic effect of Zyprexa Relprevv, e.g., diazepam or alcohol [see Warnings and Precautions (5.9) and Drug Interactions (7)]. Patients should be advised to change positions carefully to help prevent orthostatic hypotension, and to lie down if they feel dizzy or faint, until they feel better. Patients should be advised to call their doctor if they experience any of the following signs and symptoms associated with orthostatic hypotension: dizziness, fast or slow heartbeat, or fainting.

Potential for Cognitive and Motor Impairment

Because Zyprexa Relprevv has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that Zyprexa Relprevv therapy does not affect them adversely. Additionally, due to the risk of post-injection delirium/sedation syndrome, patients should not drive or operate heavy machinery for the remainder of the day of each injection [see Dosage and Administration (2.1) and Warnings and Precautions (5.1, 5.14)].

Body Temperature Regulation

Patients should be advised regarding appropriate care in avoiding overheating and dehydration. Patients should be advised to call their doctor right away if they become severely ill and have some or all of these symptoms of dehydration: sweating too much or not at all, dry mouth, feeling very hot, feeling thirsty, not able to produce urine [see Warnings and Precautions (5.15)].

Concomitant Medication

Patients should be advised to inform their physicians if they are taking, or plan to take, ZYPREXA or Symbyax® (olanzapine/fluoxetine combination). Patients should also be advised to inform their physicians if they are taking, plan to take, or have stopped taking any prescription or over-the-counter drugs, including herbal supplements, since there is a potential for interactions [see Drug Interactions (7)].

Alcohol

Patients should be advised to avoid alcohol while taking Zyprexa Relprevv [see Drug Interactions (7.1)].

Use in Specific Populations

Pregnancy Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy with Zyprexa Relprevv [see Use in Specific Populations (8.1)].

Nursing Mothers Patients should be advised not to breast-feed an infant if they are taking Zyprexa Relprevv [see Use in Specific Populations (8.3)].

Pediatric Use Safety and effectiveness of Zyprexa Relprevv in patients under 18 years have not been established [see Use in Specific Populations (8.4)].

Literature revised January 23, 2017

Marketed by: Lilly USA, LLC, Indianapolis, IN 46285, USA

Copyright © 2009, 2017, Eli Lilly and Company. All rights reserved.

ZYPR-0006-USPI-20170123

Medication Guide

ZYPREXA® 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 and each time before you get an injection. There may be new information. This Medication Guide does not take the place of talking to your doctor about your medical condition or treatment. Talk with your doctor if there is something you do not understand or you want to learn more about Zyprexa Relprevv.

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 rules of 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 have lost 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 can happen 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 your doctor can make sure you do not have symptoms of PDSS. When you leave the clinic someone must be with you. If you have symptoms of PDSS after you leave the clinic, get medical help or go to an emergency room right away.

2. Increased risk of death in elderly people who are confused, have memory loss and have lost 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 already or 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 Relprevv and during treatment. In people who do not have diabetes, sometimes high blood sugar goes away when 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 after they stop taking Zyprexa Relprevv.

   If you have diabetes, follow your doctor's instructions about how often to check your blood sugar while taking Zyprexa Relprevv.

   Call your doctor if you have any of these symptoms of high blood sugar (hyperglycemia) while taking 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). Zyprexa Relprevv is not approved in patients less than 18 years old. You may not have any symptoms, so your doctor should do blood tests to check your cholesterol and triglyceride levels before you start taking 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 weight regularly. 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 treat schizophrenia 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. If you 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 your doctor 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 harm your unborn baby.
• are breast-feeding or plan to breast-feed. Zyprexa Relprevv can pass into your breast milk and may harm your baby. You should not breast-feed while taking Zyprexa Relprevv. Talk to your doctor about the best way to feed your baby if you take Zyprexa Relprevv.

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 may interact with each other and may not work as well, or cause possible serious side effects. Your doctor can 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 doctor or 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 your condition 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 dangerous activities until you know how Zyprexa Relprevv affects you. You should not drive or operate 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 Zyprexa Relprevv?”, which describes the risk of post-injection delirium sedation syndrome (PDSS), increased risk of death in elderly people with dementia-related psychosis and the 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. NMS can 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 sometimes fatal; therefore, tell your doctor immediately if you experience any of these signs.
• Tardive Dyskinesia: This condition causes body movements that keep happening and that you 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 to avoid 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, ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-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. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Zyprexa Relprevv that was written for healthcare professionals. For more information about Zyprexa Relprevv call 1-800-Lilly-Rx (1-800-545-5979) or visit www.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.

Medication Guide revised October 6, 2016

Marketed by: Lilly USA, LLC

Indianapolis, IN 46285, USA

www.zyprexarelprevv.com

Copyright © 2009, 2016, Eli Lilly and Company. All rights reserved.

ZYPR-0001-MG-20161006

Instructions to Reconstitute and Administer Zyprexa® Relprevv™
FOR DEEP INTRAMUSCULAR GLUTEAL INJECTION ONLY.
NOT TO BE INJECTED INTRAVENOUSLY OR SUBCUTANEOUSLY.
STEP 1
PREPARING MATERIALS
Convenience kit includes:
(see Figure 1 on right)
Vial of Zyprexa Relprevv powder 3-mL vial of diluent One 3-mL syringe with pre-attached 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro® needle with needle protection device Two 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needles with needle protection device
For obese patients, a 2-inch (50 mm), 19-gauge or larger needle (not included in convenience kit) may be used for administration.
Zyprexa Relprevv must be suspended using only the diluent supplied in the convenience kit.
It is recommended that gloves are used when reconstituting, as Zyprexa Relprevv may be irritating to the skin. Flush with water if contact is made with skin.
STEP 2
DETERMINING RECONSTITUTION VOLUME
Refer to the table at right to determine the amount of diluent to be added to powder for reconstitution of each vial strength.
It is important to note that there is more diluent in the vial than is needed to reconstitute.
STEP 3
RECONSTITUTING Zyprexa Relprevv
Please read the Hypodermic Needle-Pro Instructions for Use before proceeding with Step 3. Failure to follow these instructions may result in a needlestick injury.
3.1	Loosen the powder by lightly tapping the vial.
3.2	Open the prepackaged Hypodermic Needle-Pro syringe and needle with needle protection device.
3.3	Withdraw the pre-determined diluent volume (Step 2) into the syringe.
3.4	Inject the diluent into the powder vial.
3.5	Withdraw air to equalize the pressure in the vial by pulling back slightly on the plunger in the syringe.
3.6	Remove the needle from the vial, holding the vial upright to prevent any loss of material.
3.7	Engage the needle safety device (refer to complete Hypodermic Needle-Pro Instructions for Use).
3.8	Pad a hard surface to cushion impact (see Figure 2). Tap the vial firmly and repeatedly on the surface until no powder is visible.
3.9	Visually check the vial for clumps. Unsuspended powder appears as yellow, dry clumps clinging to the vial. Additional tapping may be required if large clumps remain (see Figure 3).
3.10	Shake the vial vigorously until the suspension appears smooth and is consistent in color and texture. The suspended product will be yellow and opaque (see Figure 4).
If foam forms, let vial stand to allow foam to dissipate.
If the product is not used right away, it should be shaken vigorously to re-suspend. Reconstituted Zyprexa Relprevv remains stable for up to 24 hours in the vial.
STEP 4
INJECTING Zyprexa Relprevv
	IMPORTANT
Before administering the injection, confirm there will be someone to accompany the patient after the 3-hour observation period. If this cannot be confirmed, do not give the injection.
Refer to the table at right to determine the final volume to inject. Suspension concentration is 150 mg/mL Zyprexa Relprevv.
4.1	Attach a new safety needle to the syringe.
4.2	Slowly withdraw the desired amount into the syringe.
	SOME EXCESS PRODUCT WILL REMAIN IN THE VIAL.
4.3	Engage the needle safety device and remove needle from syringe.
4.4	For administration, select the 19-gauge, 1.5-inch (38 mm) Hypodermic Needle-Pro needle with needle protection device. For obese patients, a 2-inch (50 mm), 19-gauge or larger needle (not included in convenience kit) may be used. To help prevent clogging, a 19-gauge or larger needle must be used.
4.5	Attach the new safety needle to the syringe prior to injection. Once the suspension has been removed from the vial, it should be injected immediately.
	FOR DEEP INTRAMUSCULAR GLUTEAL INJECTION ONLY.
	DO NOT INJECT INTRAVENOUSLY OR SUBCUTANEOUSLY.
4.6	Select and prepare a site for injection in the gluteal area.
4.7	After insertion of the needle into the muscle, aspirate for several seconds to ensure that no blood appears. If any blood is drawn into the syringe, discard the syringe and the dose and begin with a new convenience kit. The injection should be performed with steady, continuous pressure.
	DO NOT MASSAGE THE INJECTION SITE.
4.8	Engage the needle safety device.
4.9	Dispose of the vials, needles, and syringe appropriately after injection. The vial is for single-use only.
JELCO®
Hypodermic Needle-Pro® Needle
With Needle Protection Device
1.	DESCRIPTION:
	The Jelco® Hypodermic Needle-Pro® device is a sterile, single use device. It includes a needle and needle safety sheath. The Needle-Pro® device can be used with a Luer slip or Luer lock syringe.
2.	INDICATIONS FOR USE:
	This device is intended for injection or aspiration of fluids. The needle protection device covers the needle after use to help prevent needle sticks.
3.	CONTRAINDICATIONS:
	None known.
4.	WARNINGS:
4.1	A needle stick with a contaminated needle may cause infectious diseases.
4.2	Intentional disengagement of the Needle-Pro® device may result in a needle stick with a contaminated needle.
4.3	Bent or damaged needles can result in breakage or damage to the tissue or accidental needle puncture. If the needle is bent or damaged, no attempt should be made to straighten the needle or engage the Needle-Pro® device. The Needle-Pro® device may not properly contain a bent needle and/or the needle could puncture the needle protection device which may result in a needle stick with a contaminated needle.
4.4	Mishandling of the needle protection device may cause needles, especially short or small gauge needles, to bend whereby they protrude from the needle protector sheath which may result in a contaminated needle stick.
4.5	Do not use with Paraldehyde.
5.	CAUTION:
5.1	Do Not Reuse: Medical devices require specific material characteristics to perform as intended. These characteristics have been verified for single use only. Any attempt to re-process the device for subsequent re-use may adversely affect the integrity of the device or lead to deterioration in performance.
5.2	Follow standard infection control procedures as specified by the Centers for Disease Control and Prevention (USA) or local equivalent.
6.	INSTRUCTIONS FOR USE:
6.1	Peel blister pouch and remove device.
6.2	Attach a syringe (if not already attached) to the Luer connection of the Needle-Pro® device with an easy twisting motion. Seat the needle firmly on the Needle-Pro® device with a push and a clockwise twist, then pull the needle cap straight away from the needle.
6.3	After procedure is completed, press the needle into the sheath using a one-handed technique. Perform a one-handed technique by gently pressing the sheath against a flat surface. As The Sheath Is Pressed (Fig. 1), The Needle Is Firmly Engaged Into The Sheath (Fig. 2).
6.4	Visually confirm that the needle is fully engaged into the needle protection sheath.
6.5	Only remove the Needle-Pro® device with engaged needle from the syringe when required by a specific medical procedure. Remove by grasping the Luer hub of the needle protection device with thumb and forefinger, keeping the free fingers clear of the end of the device containing the needle point. (See Fig. 3)
6.6	After use, place sharps in a suitable sharps container. Dispose of contaminated product in a safe manner according to Centers for Disease Control and Prevention, USA and Federal/State/Local regulations (EPA, OSHA) and health care facility guidelines or local equivalent.
	NOTE: Additional dead space added by Needle-Pro® device averages 0.036ml.
Caution • Do Not Reuse • Not made with natural rubber latex • Do not use if package is damaged • Sterilized using ethylene oxide • Non-pyrogenic fluid path • Caution: Federal (USA) law restricts this device to sale by or on the order of a physician • Catalogue Number • Batch Code • Date of Manufacture • Use by • Quantity
The Smiths Medical and Jelco design marks; Needle-Pro; and the color orange applied to the needle protection device are trademarks of Smiths Medical. The symbol ® indicates the trademark is registered in the U.S. Patent and Trademark Office and certain other countries.
© 2013 Smiths Medical. All rights reserved.
Manufacturer:
Smiths Medical ASD, Inc.
10 Bowman Drive, Keene, NH 03431 USA
Tel: 1 800 258 5361 (US/CA)
Tel: +1 614 210 7300
www.smiths-medical.com
CE
0473
Zyprexa® Relprevv™ is a registered trademark of Eli Lilly and Company.
Copyright © 2009, 2014, Eli Lilly and Company. All rights reserved.
Literature revised: October 30, 2014
ZYPR-0001-IFU-20141030

PACKAGE LABEL - Zyprexa Relprevv 210 mg

NDC 0002-7635-11

Medication Guide is to be dispensed to patients.

VL7635/VL7622

ZYPREXA® Relprevv™

(olanzapine)

For Extended Release Injectable Suspension

210 mg/vial Convenience kit

Convenience kit includes:

One vial of Zyprexa® Relprevv™ 210 mg/vial

One 3-mL vial of diluent

One 3-mL syringe with pre-attached 19-gauge, 1.5-inch Hypodermic Needle-Pro® needle with needle protection device

Two 19-gauge, 1.5-inch Hypodermic Needle-Pro needles with needle protection device

Hypodermic Needle-Pro is a registered trademark of Smiths Medical.

Reconstitute each vial with 1.3 mL of enclosed diluent. The resultant solution will contain 150 mg/mL.

Rx only

FOR DEEP INTRAMUSCULAR GLUTEAL INJECTION ONLY.

Dosing Frequency: Once every two weeks

www.zyprexarelprevv.com

Lilly

PACKAGE LABEL - Zyprexa Relprevv 300 mg

NDC 0002-7636-11

Medication Guide is to be dispensed to patients.

VL7636/VL7622

ZYPREXA® Relprevv™

(olanzapine)

For Extended Release Injectable Suspension

300 mg/vial Convenience kit

Convenience kit includes:

One vial of Zyprexa® Relprevv™ 300 mg/vial

One 3-mL vial of diluent

One 3-mL syringe with pre-attached 19-gauge, 1.5-inch Hypodermic Needle-Pro® needle with needle protection device

Two 19-gauge, 1.5-inch Hypodermic Needle-Pro needles with needle protection device

Hypodermic Needle-Pro is a registered trademark of Smiths Medical.

Reconstitute each vial with 1.8 mL of enclosed diluent. The resultant solution will contain 150 mg/mL.

Rx only

FOR DEEP INTRAMUSCULAR GLUTEAL INJECTION ONLY.

Dosing Frequency: Once every two or four weeks

www.zyprexarelprevv.com

Lilly

PACKAGE LABEL - Zyprexa Relprevv 405 mg

NDC 0002-7637-11

Medication Guide is to be dispensed to patients.

VL7637/VL7622

ZYPREXA® Relprevv™

(olanzapine)

For Extended Release Injectable Suspension

405 mg/vial Convenience kit

Convenience kit includes:

One vial of Zyprexa® Relprevv™ 405 mg/vial

One 3-mL vial of diluent

One 3-mL syringe with pre-attached 19-gauge, 1.5-inch Hypodermic Needle-Pro® needle with needle protection device

Two 19-gauge, 1.5-inch Hypodermic Needle-Pro needles with needle protection device

Hypodermic Needle-Pro is a registered trademark of Smiths Medical.

Reconstitute each vial with 2.3 mL of enclosed diluent. The resultant solution will contain 150 mg/mL.

Rx only

FOR DEEP INTRAMUSCULAR GLUTEAL INJECTION ONLY.

Dosing Frequency: Once every four weeks

www.zyprexarelprevv.com

Lilly

ZYPREXA  RELPREVV olanzapine pamoate kit

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0002-7635

Packaging # Item Code Package Description 1 NDC:0002-7635-11 1 KIT in 1 CARTON

Quantity of Parts Part # Package Quantity Total Product Quantity Part 1 1 VIAL 1.4 mL Part 2 1 VIAL 3 mL

Part 1 of 2 ZYPREXA  RELPREVV olanzapine pamoate injection, powder, for suspension, extended release

Product Information Item Code (Source) NDC:0002-7658 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Olanzapine pamoate (Olanzapine) Olanzapine 210 mg  in 1.4 mL

Packaging # Item Code Package Description 1 NDC:0002-7658-01 1.4 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Part 2 of 2 DILUENT  FOR Zyprexa Relprevv diluent injection, solution

Product Information Item Code (Source) NDC:0002-7622 Route of Administration INTRAMUSCULAR DEA Schedule

Inactive Ingredients Ingredient Name Strength Carboxymethylcellulose sodium 7.5 mg  in 1 mL Mannitol 50 mg  in 1 mL Polysorbate 80 1.0 mg  in 1 mL Hydrochloric acid   Sodium hydroxide   Water

Packaging # Item Code Package Description 1 NDC:0002-7622-01 3 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

ZYPREXA  RELPREVV olanzapine pamoate kit

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0002-7636

Packaging # Item Code Package Description 1 NDC:0002-7636-11 1 KIT in 1 CARTON

Quantity of Parts Part # Package Quantity Total Product Quantity Part 1 1 VIAL 2.0 mL Part 2 1 VIAL 3 mL

Part 1 of 2 ZYPREXA  RELPREVV olanzapine pamoate injection, powder, for suspension, extended release

Product Information Item Code (Source) NDC:0002-7659 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Olanzapine pamoate (Olanzapine) Olanzapine 300 mg  in 2.0 mL

Packaging # Item Code Package Description 1 NDC:0002-7659-01 2.0 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Part 2 of 2 DILUENT  FOR Zyprexa Relprevv diluent injection, solution

Product Information Item Code (Source) NDC:0002-7622 Route of Administration INTRAMUSCULAR DEA Schedule

Inactive Ingredients Ingredient Name Strength Carboxymethylcellulose sodium 7.5 mg  in 1 mL Mannitol 50 mg  in 1 mL Polysorbate 80 1 mg  in 1 mL Hydrochloric acid   Sodium hydroxide   Water

Packaging # Item Code Package Description 1 NDC:0002-7622-01 3 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

ZYPREXA  RELPREVV olanzapine pamoate kit

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0002-7637

Packaging # Item Code Package Description 1 NDC:0002-7637-11 1 KIT in 1 CARTON

Quantity of Parts Part # Package Quantity Total Product Quantity Part 1 1 VIAL 2.7 mL Part 2 1 VIAL 3 mL

Part 1 of 2 ZYPREXA  RELPREVV olanzapine pamoate injection, powder, for suspension, extended release

Product Information Item Code (Source) NDC:0002-7660 Route of Administration INTRAMUSCULAR DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Olanzapine pamoate (Olanzapine) Olanzapine 405 mg  in 2.7 mL

Packaging # Item Code Package Description 1 NDC:0002-7660-01 2.7 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Part 2 of 2 DILUENT  FOR Zyprexa Relprevv diluent injection, solution

Product Information Item Code (Source) NDC:0002-7622 Route of Administration INTRAMUSCULAR DEA Schedule

Inactive Ingredients Ingredient Name Strength Carboxymethylcellulose sodium 7.5 mg  in 1 mL Mannitol 50 mg  in 1 mL Polysorbate 80 1.0 mg  in 1 mL Hydrochloric acid   Sodium hydroxide   Water

Packaging # Item Code Package Description 1 NDC:0002-7622-01 3 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA022173 12/11/2009

Labeler - Eli Lilly and Company (006421325)

Revised: 07/2017   Eli Lilly and Company

Get emergency medical help if you have signs of an allergic reaction to Zyprexa Relprevv: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Zyprexa Relprevv can cause serious symptoms if the medicine gets into your bloodstream too fast. During the first 3 hours after your injection you will be watched for the following signs:

• severe dizziness, drowsiness, or weakness;

• confusion, anxiety, feeling angry or hostile;

• feeling nervous or shaky;

• trouble walking or talking;

• seizure (convulsions); or

• a light-headed feeling, like you might pass out.

In rare cases, olanzapine may cause a severe skin reaction that can be fatal if it spreads to other parts of the body. Seek medical treatment if you have a new or worsening skin rash with fever, swollen glands, or swelling in your face.

Call your doctor at once if you have:

• twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs;

• trouble swallowing;

• signs of dehydration--if you feel very thirsty or hot, are unable to urinate, and have heavy sweating or hot and dry skin;

• weak immune system--sudden weakness or ill feeling, fever, chills, swollen gums, painful mouth sores, sore throat, trouble swallowing, skin sores, cold or flu symptoms, cough, trouble breathing;

• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss; or

• severe nervous system reaction--very stiff (rigid) muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors.

Common Zyprexa Relprevv side effects may include:

• headache, back pain;

• weight gain, increased appetite;

• mild drowsiness;

• dry mouth, nausea, vomiting, diarrhea;

• sinus pain, runny or stuffy nose, cough; or

• pain, bruising, swelling, or other irritation where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Taking other drugs that make you sleepy can worsen this effect. Ask your doctor before taking a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Other drugs may interact with Zyprexa Relprevv injection, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.