Dosage Form: injection
FULL PRESCRIBING INFORMATION
Post-Injection Delirium/Sedation Syndrome — Adverse events with signs and symptoms consistent with olanzapine overdose, in particular, sedation (including coma) and/or delirium, have been reported following injections of Zyprexa Relprevv. Zyprexa Relprevv must be administered in a registered healthcare facility with ready access to emergency response services. After each injection, patients must be observed at the healthcare facility by a healthcare professional for at least 3 hours. 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 [see Dosage and Administration (2.1), Warnings and Precautions (5.1, 5.2), Overdosage (10.2), and Patient Counseling Information (17.2)].
Increased Mortality in Elderly Patients with Dementia-Related Psychosis — Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Analyses of seventeen placebo-controlled trials (modal duration of 10 weeks), largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g., heart failure, sudden death) or infectious (e.g., pneumonia) in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies may be attributed to the antipsychotic drug as opposed to some characteristic(s) of the patients is not clear. Zyprexa Relprevv is not approved for the treatment of patients with dementia-related psychosis [see Warnings and Precautions (5.3, 5.16) and Patient Counseling Information (17.3)].
Indications and Usage for Zyprexa Relprevv
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 facility, patient, and pharmacy must all be enrolled in the Zyprexa Relprevv Patient Care Program. To enroll, call 1-877-772-9390.
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)].
Zyprexa Relprevv Dosage and Administration
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.
| 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 405 mg/4 weeks | 150 mg/2 weeks or 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 (17.1, 17.2)]. Zyprexa Relprevv must be administered in a registered healthcare facility with ready access to emergency response services. After each Zyprexa Relprevv injection, a healthcare professional must continuously observe the patient at the healthcare facility 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 (5.4), 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 (5.6, 5.7, and 5.8)].
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.
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:
- 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.
- 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).
- 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).
- 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
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 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-use only.
Dosage Forms and Strengths
Zyprexa Relprevv is a powder for suspension for intramuscular use only. Zyprexa Relprevv is present as a yellow solid in a glass vial equivalent to 210, 300, or 405 mg olanzapine per vial. The diluent is a clear, colorless to slightly yellow solution in a glass vial [see Description (11) and How Supplied/Storage and Handling (16)]. The reconstituted suspension will be yellow and opaque [see Dosage and Administration (2.2)].
Contraindications
None.
Warnings and Precautions
Post-Injection Delirium/Sedation Syndrome
During premarketing clinical studies of Zyprexa Relprevv, 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 and Dosage and Administration (2.1)]. These events occurred in <0.1% of injections and in approximately 2% of patients who received injections for up to 46 months. These events were correlated with an unintentional rapid increase in serum olanzapine concentrations to supra-therapeutic ranges in some cases. While a rapid and greater than expected increase in serum olanzapine concentration has been observed in some patients with these events, the exact mechanism by which the drug was unintentionally introduced into the blood stream is not known. Clinical signs and symptoms included dizziness, confusion, disorientation, slurred speech, altered gait, difficulty ambulating, weakness, agitation, extrapyramidal symptoms, hypertension, convulsion, and reduced level of consciousness ranging from mild sedation to coma. Time after injection to event ranged from soon after injection to greater than 3 hours after injection. The majority of patients were hospitalized and some required supportive care, including intubation, in several cases. All patients had largely recovered by 72 hours. The risk of an event is the same at each injection, so the risk per patient is cumulative (i.e., increases with the number of injections) [see Overdosage (10.1)].
Healthcare professionals are advised to discuss this potential risk with patients each time they prescribe and administer Zyprexa Relprevv [see Patient Counseling Information (17.1, 17.2)].
Prescribing and Distribution Program for Zyprexa Relprevv
Zyprexa Relprevv is available only through a restricted distribution program [see Boxed Warning, Indications and Usage (1), and Patient Counseling Information (17.2)]. Zyprexa Relprevv must not be dispensed directly to a patient. For a patient to receive treatment, the prescriber, healthcare facility, patient, and pharmacy must all be enrolled in the Zyprexa Relprevv Patient Care Program. To enroll, call 1-877-772-9390.
Zyprexa Relprevv must be administered in a registered healthcare facility (such as a hospital, clinic, residential treatment center, or community healthcare center) with ready access to emergency response services. After each Zyprexa Relprevv injection, a healthcare professional must continuously observe the patient at the healthcare facility for at least 3 hours and 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)]. If parenteral benzodiazepines are required for patient management during an event of post-injection delirium/sedation syndrome, careful evaluation of clinical status for excessive sedation and cardiorespiratory depression is recommended.
Elderly Patients with Dementia-Related Psychosis
Increased Mortality
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 [see Boxed Warning, Warnings and Precautions (5.16), and Patient Counseling Information (17.3)].
In placebo-controlled oral olanzapine clinical trials of elderly patients with dementia-related psychosis, the incidence of death in olanzapine-treated patients was significantly greater than placebo-treated patients (3.5% vs 1.5%, respectively).
Cerebrovascular Adverse Events (CVAE), Including Stroke
Cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatalities, were reported in patients in trials of oral olanzapine in elderly patients with dementia-related psychosis. In placebo-controlled trials, there was a significantly higher incidence of cerebrovascular adverse events in patients treated with oral olanzapine compared to patients treated with placebo. Zyprexa Relprevv is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning and Patient Counseling Information (17.3)].
Suicide
The possibility of a suicide attempt is inherent in schizophrenia, and close supervision of high-risk patients should accompany drug therapy.
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including olanzapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac dysrhythmia). Additional signs may include elevated creatinine phosphokinase, myoglobinuria (rhabdomyolysis), and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever, and primary central nervous system pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered and tolerability with oral olanzapine should be established prior to initiating treatment with Zyprexa Relprevv [see Dosage and Administration (2.1)]. The patient should be carefully monitored, since recurrences of NMS have been reported [see Patient Counseling Information (17.4)].
Hyperglycemia
Physicians should consider the risks and benefits when prescribing olanzapine to patients with an established diagnosis of diabetes mellitus, or having borderline increased blood glucose level (fasting 100-126 mg/dL, nonfasting 140-200 mg/dL). Patients taking olanzapine should be monitored regularly for worsening of glucose control. Patients starting treatment with olanzapine should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug [see Patient Counseling Information (17.5)].
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics including olanzapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. While relative risk estimates are inconsistent, the association between atypical antipsychotics and increases in glucose levels appears to fall on a continuum and olanzapine appears to have a greater association than some other atypical antipsychotics.
Mean increases in blood glucose have been observed in patients treated (median exposure of 9.2 months) with olanzapine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). The mean increase of serum glucose (fasting and nonfasting samples) from baseline to the average of the 2 highest serum concentrations was 15.0 mg/dL.
In a study of healthy volunteers, subjects who received olanzapine (N=22) for 3 weeks had a mean increase compared to baseline in fasting blood glucose of 2.3 mg/dL. Placebo-treated subjects (N=19) had a mean increase in fasting blood glucose compared to baseline of 0.34 mg/dL.
Olanzapine Monotherapy in Adults — In an analysis of 5 placebo-controlled adult olanzapine monotherapy studies with a median treatment duration of approximately 3 weeks, olanzapine was associated with a greater mean change in fasting glucose levels compared to placebo (2.76 mg/dL versus 0.17 mg/dL). The difference in mean changes between olanzapine and placebo was greater in patients with evidence of glucose dysregulation at baseline (patients diagnosed with diabetes mellitus or related adverse reactions, patients treated with anti-diabetic agents, patients with a baseline random glucose level ≥200 mg/dL, and/or a baseline fasting glucose level ≥126 mg/dL).
Olanzapine-treated patients had a greater mean HbA1c increase from baseline of 0.04% (median exposure 21 days), compared to a mean HbA1c decrease of 0.06% in placebo-treated subjects (median exposure 17 days).
In an analysis of 8 placebo-controlled studies (median treatment exposure 4-5 weeks), 6.1% of olanzapine-treated subjects (N=855) had treatment-emergent glycosuria compared to 2.8% of placebo-treated subjects (N=599). Table 2 shows short-term and long-term changes in fasting glucose levels from adult olanzapine monotherapy studies.
a Not Applicable. | ||||||
| Up to 12 weeks exposure | At least 48 weeks exposure | |||||
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients | N | Patients |
| Fasting Glucose | Normal to High (<100 mg/dL to ≥126 mg/dL) | Olanzapine | 543 | 2.2% | 345 | 12.8% |
| Placebo | 293 | 3.4% | NAa | NAa | ||
| Borderline to High (≥100 mg/dL and <126 mg/dL to ≥126 mg/dL) | Olanzapine | 178 | 17.4% | 127 | 26.0% | |
| Placebo | 96 | 11.5% | NAa | NAa | ||
The mean change in fasting glucose for patients exposed at least 48 weeks was 4.2 mg/dL (N=487). In analyses of patients who completed 9-12 months of olanzapine therapy, mean change in fasting and nonfasting glucose levels continued to increase over time.
Olanzapine Monotherapy in Adolescents — The safety and efficacy of Zyprexa Relprevv have not been established in patients under the age of 18 years.
In an analysis of 3 placebo-controlled oral olanzapine monotherapy studies of adolescent patients (13-17 years), including those with schizophrenia (6 weeks) or bipolar I disorder (manic or mixed episodes) (3 weeks), olanzapine was associated with a greater mean change from baseline in fasting glucose levels compared to placebo (2.68 mg/dL versus -2.59 mg/dL). The mean change in fasting glucose for adolescents exposed at least 24 weeks was 3.1 mg/dL (N=121). Table 3 shows short-term and long-term changes in fasting blood glucose from adolescent oral olanzapine monotherapy studies.
a Not Applicable. | ||||||
| Up to 12 weeks exposure | At least 24 weeks exposure | |||||
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients | N | Patients |
| Fasting Glucose | Normal to High (<100 mg/dL to ≥126 mg/dL) | Olanzapine | 124 | 0% | 108 | 0.9% |
| Placebo | 53 | 1.9% | NAa | NAa | ||
| Borderline to High (≥100 mg/dL and <126 mg/dL to ≥126 mg/dL) | Olanzapine | 14 | 14.3% | 13 | 23.1% | |
| Placebo | 13 | 0% | NAa | NAa | ||
Hyperlipidemia
Undesirable alterations in lipids have been observed with olanzapine use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using olanzapine, is recommended [see Patient Counseling Information (17.6)].
Clinically significant, and sometimes very high (>500 mg/dL), elevations in triglyceride levels have been observed with olanzapine use. Modest mean increases in total cholesterol have also been seen with olanzapine use.
Olanzapine Monotherapy in Adults — In an analysis of 5 placebo-controlled olanzapine monotherapy studies with treatment duration up to 12 weeks, olanzapine-treated patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.3 mg/dL, 3.0 mg/dL, and 20.8 mg/dL respectively compared to decreases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 6.1 mg/dL, 4.3 mg/dL, and 10.7 mg/dL for placebo-treated patients. For fasting HDL cholesterol, no clinically meaningful differences were observed between olanzapine-treated patients and placebo-treated patients. Mean increases in fasting lipid values (total cholesterol, LDL cholesterol, and triglycerides) were greater in patients without evidence of lipid dysregulation at baseline, where lipid dysregulation was defined as patients diagnosed with dyslipidemia or related adverse reactions, patients treated with lipid lowering agents, or patients with high baseline lipid levels.
In long-term studies (at least 48 weeks), patients had increases from baseline in mean fasting total cholesterol, LDL cholesterol, and triglycerides of 5.6 mg/dL, 2.5 mg/dL, and 18.7 mg/dL, respectively, and a mean decrease in fasting HDL cholesterol of 0.16 mg/dL. In an analysis of patients who completed 12 months of therapy, the mean nonfasting total cholesterol did not increase further after approximately 4-6 months.
The proportion of patients who had changes (at least once) in total cholesterol, LDL cholesterol or triglycerides from normal or borderline to high, or changes in HDL cholesterol from normal or borderline to low, was greater in long-term studies (at least 48 weeks) as compared with short-term studies. Table 4 shows categorical changes in fasting lipids values.
a Not Applicable. | ||||||
| Up to 12 weeks exposure | At least 48 weeks exposure | |||||
| Laboratory Analyte | Category Change (at least once) from Baseline | Treatment Arm | N | Patients | N | Patients |
| Fasting Triglycerides | Increase by ≥50 mg/dL | Olanzapine | 745 | 39.6% | 487 | 61.4% |
| Placebo | 402 | 26.1% | NAa | NAa | ||
| Normal to High (<150 mg/dL to ≥200 mg/dL) | Olanzapine | 457 | 9.2% | 293 | 32.4% | |
| Placebo | 251 | 4.4% | NAa | NAa | ||
| Borderline to High (≥150 mg/dL and <200 mg/dL to ≥200 mg/dL) | Olanzapine | 135 | 39.3% | 75 | 70.7% | |
| Placebo | 65 | 20.0% | NAa | NAa | ||
| Fasting Total Cholesterol | Increase by ≥40 mg/dL | Olanzapine | 745 | 21.6% | 489 | 32.9% |
| Placebo | 402 | 9.5% | NAa | NAa | ||
| Normal to High (<200 mg/dL to ≥240 mg/dL) | Olanzapine | 392 | 2.8% | 283 | 14.8% | |
| Placebo | 207 | 2.4% | NAa | NAa | ||
| Borderline to High (≥200 mg/dL and <240 mg/dL to ≥240 mg/dL) | Olanzapine | 222 | 23.0% | 125 | 55.2% | |
| Placebo | 112 | 12.5% | NAa | NAa | ||
| Fasting LDL Cholesterol | Increase by ≥30 mg/dL | Olanzapine | 536 | 23.7% | 483 | 39.8% |
| Placebo | 304 | 14.1% | NAa | NAa | ||
| Normal to High (<100 mg/dL to ≥160 mg/dL) | Olanzapine | 154 | 0% | 123 | 7.3% | |
| Placebo | 82 | 1.2% | NAa | NAa | ||
| Borderline to High (≥100 mg/dL and <160 mg/dL to ≥160 mg/dL) | Olanzapine | 302 | 10.6% | 284 | 31.0% | |
| Placebo | 1 | |||||
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