ZYPREXA Relprevv

ZYPREXA Relprevv is an FDA-registered drug product whose active ingredient is OLANZAPINE PAMOATE. It is labelled by H2-Pharma LLC taken by intramuscular and marketed as a human prescription drug product. Identifiers on file: NDC 61269-660, application NDA022173, label effective 20260519. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing OLANZAPINE PAMOATE are most often described in connection with: zyprexa relprevv, trial adults, treatment schizophrenia, established two, clinical trials, one week, available only, through restricted. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE ZYPREXA RELPREVV is available only through a restricted distribution program [see Warnings and Precautions ( 5.2 )] . ZYPREXA RELPREVV must not be dispensed directly to a patient. For a patient to receive treatment, the prescriber, healthcare setting, patient, and pharmacy must all be enrolled in the ZYPREXA RELPREVV REMS. To enroll, call 1-877-772-9390. ZYPREXA ® RELPREVV™ is a long-acting atypical antipsychotic for intramuscular injection indicated for the treatment of schizophrenia. ( 1.1 ) Efficacy was established in two clinical trials in patients with schizophrenia: one 8-week trial in adults and one maintenance trial in adults. ( 14.1 ) 1.1 Schizophrenia ZYPREXA RELPREVV is indicated for the treatment of schizophrenia. Efficacy was established in two clinical trials in patients with schizophrenia: one 8-week trial in adults and one maintenance trial in adults [see Clinical Studies ( 14.1 )] .

2 DOSAGE AND ADMINISTRATION 150 mg/2 wks, 300 mg/4 wks, 210 mg/2 wks, 405 mg/4 wks, or 300 mg/2 wks. See Table 1 for dosing recommendations. ( 2.1 ) ZYPREXA RELPREVV is intended for deep intramuscular gluteal injection only. Do not administer intravenously or subcutaneously. ( 2.1 ) Be aware that there are two ZYPREXA intramuscular formulations with different dosing schedules. ZYPREXA IntraMuscular (10 mg/vial) is a short-acting formulation and should not be confused with ZYPREXA RELPREVV. ( 2.1 ) Establish tolerability with oral olanzapine prior to initiating treatment. ( 2.1 ) ZYPREXA RELPREVV doses above 405 mg every 4 weeks or 300 mg every 2 weeks have not been evaluated in clinical trials. ( 2.1 ) Use in specific populations (including renal and hepatic impaired, and pediatric population) has not been studied. ( 2.1 ) Must be suspended using only the diluent for ZYPREXA RELPREVV provided in the convenience kit. ( 2.2 ) 2.1 Dosage ZYPREXA RELPREVV is intended for deep intramuscular gluteal injection only and should not be administered intravenously or subcutaneously. Be aware that there are two ZYPREXA intramuscular formulations with different dosing schedules. ZYPREXA IntraMuscular (10 mg/vial) is a short-acting formulation and should not be confused with ZYPREXA RELPREVV. Refer to the package insert for ZYPREXA IntraMuscular for more information about that product. Establish tolerability with oral olanzapine prior to initiating treatment. ZYPREXA RELPREVV should be administered by a healthcare professional every 2 to 4 weeks by deep intramuscular gluteal injection using a 19-gauge, 1.5-inch needle. Following insertion of the needle into the muscle, aspiration should be maintained for several seconds to ensure that no blood is drawn into the syringe. If any blood is aspirated into the syringe, it should be discarded and fresh drug should be prepared using a new convenience kit. The injection should be performed at a steady, continuous pressure. Do not massage the injection site. Dose Selection — The efficacy of ZYPREXA RELPREVV has been demonstrated within the range of 150 mg to 300 mg administered every 2 weeks and with 405 mg administered every 4 weeks. Dose recommendations considering oral ZYPREXA and ZYPREXA RELPREVV are shown in Table 1 . Table 1: Recommended Dosing for ZYPREXA RELPREVV Based on Correspondence to Oral ZYPREXA Doses Target Oral ZYPREXA Dose Dosing of ZYPREXA RELPREVV During the First 8 Weeks Maintenance Dose After 8 Weeks of ZYPREXA RELPREVV Treatment 10 mg/day 210 mg/2 weeks or 150 mg/2 weeks or 405 mg/4 weeks 300 mg/4 weeks 15 mg/day 300 mg/2 weeks 210 mg/2 weeks or 405 mg/4 weeks 20 mg/day 300 mg/2 weeks 300 mg/2 weeks ZYPREXA RELPREVV doses greater than 405 mg every 4 weeks or 300 mg every 2 weeks have not been evaluated in clinical trials. Post-Injection Delirium/Sedation Syndrome — During premarketing clinical studies, adverse events 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 Boxed Warning , Warnings and Precautions ( 5.1 ), and Overdosage ( 10.1 )] . Patients should be informed of this risk and how to recognize related symptoms [see Patient Counseling Information ( 17 )] . ZYPREXA RELPREVV must be administered in a certified healthcare setting with ready access to emergency response services. After each ZYPREXA RELPREVV injection, a healthcare professional must continuously observe the patient at the healthcare setting for at least 3 hours for symptoms consistent with olanzapine overdose, including sedation (ranging from mild in severity to coma) and/or delirium (including confusion, disorientation, agitation, anxiety, and other cognitive impairment). Other symptoms noted include extrapyramidal symptoms, dysarthria, ataxia, aggression, dizziness, weakness, hypertension, and convulsion. The potential for onset of an event is greatest within the first hour. The majority of cases have occurred within the first 3 hours after injection; however, the event has occurred after 3 hours. Following the 3-hour observation period, healthcare professionals must confirm that the patient is alert, oriented, and absent of any signs and symptoms of post-injection delirium/sedation syndrome prior to being released. All patients must be accompanied to their destination upon leaving the facility. For the remainder of the day of each injection, patients should not drive or operate heavy machinery, and should be advised to be vigilant for symptoms of post-injection delirium/sedation syndrome and be able to obtain medical assistance if needed. If post-injection delirium/sedation syndrome is suspected, close medical supervision and monitoring should be instituted in a facility capable of resuscitation [see Overdosage ( 10 )] . Dosing in Specific Populations — Tolerance of oral ZYPREXA should be established prior to initiating treatment with ZYPREXA RELPREVV. The recommended starting dose is ZYPREXA RELPREVV 150 mg/4 wks in patients who are debilitated, who have a predisposition to hypotensive reactions, who otherwise exhibit a combination of factors that may result in slower metabolism of olanzapine (e.g., nonsmoking female patients ≥65 years of age), or who may be more pharmacodynamically sensitive to olanzapine. When indicated, dose escalation should be undertaken with caution in these patients [see Warnings and Precautions ( 5.18 ), Drug Interactions ( 7 ), and Clinical Pharmacology ( 12.3 )] . ZYPREXA RELPREVV has not been studied in subjects under 18 years of age [see Warnings and Precautions ( 5.7 )] . Maintenance Treatment — Although no controlled studies have been conducted to determine how long patients should be treated with ZYPREXA RELPREVV, efficacy has been demonstrated over a period of 24 weeks in patients with stabilized schizophrenia. Additionally, oral ZYPREXA has been shown to be effective in maintenance of treatment response in schizophrenia in longer-term use. Patients should be periodically reassessed to determine the need for continued treatment. Switching from Other Antipsychotics — There are no systematically collected data to specifically address how to switch patients with schizophrenia from other antipsychotics to ZYPREXA RELPREVV. 2.2 Instructions to Reconstitute and Administer ZYPREXA RELPREVV For deep intramuscular gluteal injection only. Not to be injected intravenously or subcutaneously. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Step 1: Preparing Materials Convenience kit includes: Single-dose 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. See additional insert entitled "Instructions to Reconstitute and Administer ZYPREXA RELPREVV" (included) for more information regarding the safe and effective use of the Hypodermic Needle-Pro syringe and needle. Step 2: Determining Reconstitution Volume Refer to the table below 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. Dose Vial Strength Diluent to Add 150 mg 210 mg 1.3 mL 210 mg 210 mg 1.3 mL 300 mg 300 mg 1.8 mL 405 mg 405 mg 2.3 mL 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. Loosen the powder by lightly tapping the vial. Open the prepackaged Hypodermic Needle-Pro syringe and needle with needle protection device. Withdraw the pre-determined diluent volume ( Step 2 ) into the syringe. Inject the diluent into the powder vial. Withdraw air to equalize the pressure in the vial by pulling back slightly on the plunger in the syringe. Remove the needle from the vial, holding the vial upright to prevent any loss of material. Engage the needle safety device (refer to complete Hypodermic Needle-Pro Instructions for Use). Pad a hard surface to cushion impact ( see Figure 1 ). Tap the vial firmly and repeatedly on the surface until no powder is visible. Figure 1: Tap firmly to mix. 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 2 ). Figure 2: Check for unsuspended powder and repeat tapping if needed. 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 3 ). Figure 3: Vigorously shake vial. 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 at room temperature for up to 24 hours in the vial. Step 4: Injecting ZYPREXA RELPREVV 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 below to determine the final volume to inject. Suspension concentration is 150 mg/mL ZYPREXA RELPREVV. Dose Final Volume to Inject 150 mg 1 mL 210 mg 1.4 mL 300 mg 2 mL 405 mg 2.7 mL Attach a new safety needle to the syringe. Slowly withdraw the desired amount into the syringe. Some excess product will remain in the vial. Engage the needle safety device and remove the needle from syringe. 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. 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. Select and prepare a site for injection in the gluteal area. 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. Engage the needle safety device. Dispose of the vials, needles, and syringe appropriately after injection. The vial is for single-dose only. Figure 1 Figure 2 Figure 3

4 CONTRAINDICATIONS None. None.

6 ADVERSE REACTIONS Most common adverse reactions (≥5% in at least one of the treatment groups and greater than placebo) associated with ZYPREXA RELPREVV treatment: headache, sedation, weight gain, cough, diarrhea, back pain, nausea, somnolence, dry mouth, nasopharyngitis, increased appetite, and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact the Safety Call Center at 1-866-770-9010 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect or predict the rates observed in practice. 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 healthcare provider 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 ZYPREXA RELPREVV ZYPREXA RELPREVV ZYPREXA RELPREVV Placebo 405 mg/4 wks 210 mg/2 wks 300 mg/2 wks Body System/Adverse Reaction (N=98) (N=100) (N=106) (N=100) Ear and Labyrinth Disorders Ear pain 2 1 1 4 Gastrointestinal Disorders Abdominal pain a 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 infection b 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 increased c 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 Headache d 8 13 15 18 Sedation e 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 congestion f 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 Olanzapine Olanzapine Olanzapine Placebo 5 ± 2.5 mg/day 10 ± 2.5 mg/day 15 ± 2.5 mg/day Parkinsonism a 15 14 12 14 Akathisia b 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 Olanzapine Olanzapine Olanzapine Placebo 5 ± 2.5 mg/day 10 ± 2.5 mg/day 15 ± 2.5 mg/day (N=68) (N=65) (N=64) (N=69) Dystonic events a 1 3 2 3 Parkinsonism events b 10 8 14 20 Akathisia events c 1 5 11 10 Dyskinetic events d 4 0 2 1 Residual events e 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 attempt 1 ; Rare: chills and fever, hangover effect, sudden death 1 . 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: amenorrhea 2 , breast pain, decreased menstruation, impotence 2 , increased menstruation 2 , menorrhagia 2 , metrorrhagia 2 , polyuria 2 , 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 )] . 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of ZYPREXA and ZYPREXA RELPREVV. Because these reactions are reported voluntarily from a population of uncertain size, it is difficult to reliably estimate their frequency or evaluate a causal relationship to drug exposure. 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, salivary hypersecretion, stuttering 1 , venous thromboembolic events (including pulmonary embolism and deep venous thrombosis), fecal incontinence, somnambulism, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). 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. 1 Stuttering was only studied in oral and long acting injection (LAI) formulations.

What is ZYPREXA Relprevv used for?
1 INDICATIONS AND USAGE ZYPREXA RELPREVV is available only through a restricted distribution program [see Warnings and Precautions ( 5.2 )] . ZYPREXA RELPREVV must not be dispensed directly to a patient. For a patient to receive treatment, the prescriber, healthcare setting, patient, and pharmacy must all be enrolled in the ZYPREXA RELPREVV REMS. To enroll, call 1-877-772-9390. ZYPREXA ® …

Who makes ZYPREXA Relprevv?
H2-Pharma LLC is the labeler of record for ZYPREXA Relprevv.

What form does ZYPREXA Relprevv come in?
administered by intramuscular. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is ZYPREXA Relprevv prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Has ZYPREXA Relprevv been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.