"The US Food and Drug Administration (FDA) announced today that its review of two patients who died after receiving intramuscular injections of the schizophrenia drug olanzapine pamoate (Zyprexa Relprevv, Eli Lilly) is inconclusive, altho"...
Zyprexa Relprevv Side Effects Center
Medical Editor: William C. Shiel Jr., MD, FACP, FACR
Relprevv (olanzapine) is a drug prescribed for the treatment of schizophrenia and acute manic episodes associate with bipolar I disorder. Relprevv belongs to a drug class referred to as atypical antipsychotics. Common side effects of Relprevv include akathisia, constipation, dizziness, drowsiness, insomnia, dry mouth, orthostatic hypotension, tremor, and weight gain. More severe side effects include tardive dyskinesia, elevated blood sugar (hyperglycemia) in people with diabetes, coma, dementia in the elderly, abnormal menstruation, sexual dysfunction, and breast enlargement.
Dosing of Relprevv ranges from 10-20 mg daily for schizophrenia, and 10-15 mg daily for bipolar I disorder. The maximum dose is 20 mg daily for both schizophrenia and bipolar I disorder. There are several drugs that interact with Relprevv, so the patient should discuss all medications they are taking with the prescribing doctor. There are no adequate studies of Relprevv in pregnant women. Relprevv should only be prescribed to a pregnant woman if the benefits outweigh the unknown risks. Relprevv is excreted in breast milk; therefore it is recommended that nursing mothers not use Relprevv.
Our Relprevv Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
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.
What is Patient Information in Detail?
Easy-to-read and understand detailed drug information and pill images for the patient or caregiver from Cerner Multum.
Zyprexa Relprevv in Detail - Patient Information: Side Effects
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Tell your caregivers at once if you have a serious side effect such as:
- fast or slow heart rate;
- feeling like you might pass out;
- twitching or uncontrollable movements of your eyes, lips, tongue, face, arms, or legs; or
- being unable to sit still.
Less serious side effects may include:
- dizziness, drowsiness;
- tremors or shaking;
- nausea; or
- pain 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.
Read the entire detailed patient monograph for Zyprexa Relprevv (Olanzapine Extended Release Injectable Suspension)
What is Patient Information Overview?
A concise overview of the drug for the patient or caregiver from First DataBank.
Zyprexa Relprevv Overview - Patient Information: Side Effects
To reduce the risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.
Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.
Olanzapine extended-release injection is designed to release medication slowly over 2 to 4 weeks. If the medication releases too quickly, your drug levels may be too high. Seek immediate medical attention if any of these symptoms of high olanzapine levels occur: very drowsy/hard to wake up, severe dizziness, slowed breathing, new or worsening mental/mood changes (such as confusion, agitation, nervousness, aggression), restlessness, muscle stiffness/spasm, shaking (tremor), unusual weakness, difficulty walking or speaking, balance problems, seizure.
This drug may rarely make your blood sugar level rise, which can cause or worsen diabetes. Weight gain from this drug may increase the risk of this side effect. Tell your doctor immediately if you develop symptoms of high blood sugar such as increased thirst and urination, breath smells fruity, feel very hungry/weak/tired. If you already have diabetes, be sure to check your blood sugar level regularly.
This drug may cause significant weight gain and a rise in your blood cholesterol (or triglyceride) levels, especially in teenagers. These effects, along with diabetes, may increase your risk for developing heart disease. Discuss the risks and benefits of treatment with your doctor. (See also Notes section.)
Tell your doctor immediately if any of these unlikely but serious side effects occur: yellowing of the eyes/skin, severe abdominal pain, difficulty swallowing, signs of infection (such as fever, persistent sore throat), trouble urinating.
This medication may rarely cause a very serious condition called neuroleptic malignant syndrome (NMS). Get medical help right away if you have any of the following symptoms: fever, muscle stiffness/pain/tenderness/weakness, severe tiredness, severe confusion, sweating, fast/irregular heartbeat, dark urine, change in the amount of urine.
Olanzapine may rarely cause a condition known as tardive dyskinesia. In some cases, this condition may be permanent. Tell your doctor immediately if you develop any unusual/uncontrolled movements (especially of the face or tongue).
In rare cases, olanzapine may increase your level of a certain substance made by the body (prolactin). For females, this increase in prolactin may result in unwanted breast milk, missed/stopped periods, or difficulty becoming pregnant. For males, it may result in decreased sexual ability, inability to produce sperm, or enlarged breasts. If you develop any of these symptoms, tell your doctor immediately.
A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.
This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.
In the US -
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.
Read the entire patient information overview for Zyprexa Relprevv (Olanzapine Extended Release Injectable Suspension)
What is Prescribing information?
The FDA package insert formatted in easy-to-find categories for health professionals and clinicians.
Zyprexa Relprevv FDA Prescribing Information: Side Effects
Clinical Trials Experience
The information below for ZYPREXA RELPREVV is derived primarily from a clinical trial database consisting of 2058 patients with approximately 1948 patient years of exposure to ZYPREXA RELPREVV. This database includes safety data from 6 open-label studies and 2 double-blind comparator studies, conducted in patients with schizophrenia or schizoaffective disorder. Additionally, data obtained from patients treated with oral olanzapine are also presented below. Adverse reactions were assessed by the collection of adverse reactions, vital signs, weights, laboratory analytes, ECGs, and the results of physical and ophthalmologic examinations. In the tables and tabulations that follow for ZYPREXA RELPREVV, the MedDRA terminology has been used to classify reported adverse reactions. Data obtained from oral olanzapine studies was reported using the COSTART dictionary.
The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, a treatment- emergent adverse reaction of the type listed. A reaction was considered treatment emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation. Reactions listed elsewhere in labeling may not be repeated below. The entire label should be read to gain a complete understanding of the safety profile of ZYPREXA RELPREVV.
The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse reaction incidence in the population studied.
Adverse Reactions Associated with Discontinuation of Treatment in a Short-Term, Placebo-Controlled Trial
Overall, there was no difference in the incidence of discontinuation due to adverse reactions between ZYPREXA RELPREVV (4%; 13/306 patients) and placebo (5%; 5/98 patients) in an 8-week trial.
Commonly Observed Adverse Reactions in a Short-Term, Placebo-Controlled Trial
In an 8-week trial, treatment-emergent adverse reactions with an incidence of 5% or greater in at least one of the ZYPREXA RELPREVV treatment groups (210 mg/2 weeks, 405 mg/4 weeks, or 300 mg/2 weeks) and greater than placebo were: headache, sedation, weight gain, cough, diarrhea, back pain, nausea, somnolence, dry mouth, nasopharyngitis, increased appetite, and vomiting.
Adverse Reactions Occurring at an Incidence of 2% or More among ZYPREXA RELPREVV-Treated Patients in a Short-Term, Placebo-Controlled Trial
Table 9 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse reactions that occurred in 2% or more of patients treated with ZYPREXA RELPREVV and with incidence greater than placebo who participated in the 8-week, placebo-controlled trial.
Table 9: Treatment-Emergent Adverse Reactions: Incidence
in a Short-Term, Placebo-Controlled Clinical Trial with ZYPREXA RELPREVV
|Body System/Adverse Reaction||Placebo
|ZYPREXA RELPREVV 405 mg/4 wks
|ZYPREXA RELPREVV 210 mg/2 wks
|ZYPREXA RELPREVV 300 mg/2 wks
|Ear and Labyrinth Disorders|
|General Disorders and Administration Site Conditions|
|Injection site pain||0||2||3||2|
|Infections and Infestations|
|Upper respiratory tract infection||2||3||1||4|
|Injury, Poisoning and Procedural Complications|
|Electrocardiogram QT-corrected interval prolonged||1||0||0||2|
|Hepatic enzyme increasedc||1||4||1||3|
|Metabolism and Nutrition Disorders|
|Musculoskeletal and Connective Tissue Disorders|
|Nervous System Disorders|
|Reproductive System and Breast Disorders|
|Respiratory, Thoracic and Mediastinal Disorders|
|Skin and Subcutaneous Tissue Disorders|
|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.
Summary of Statistically Significant Changes by Dose
In a 24-week randomized, double-blind, fixed-dose study comparing 3 doses of ZYPREXA RELPREVV in patients with schizophrenia, statistically significant differences among dose groups were observed for the below safety outcomes (Table 10) [see WARNINGS AND PRECAUTIONS].
Table 10: Summary of Statistically Significant Changes by
Dose in a Double-Blind, Fixed-Dose Study for ZYPREXA RELPREVVa
|ZYPREXA RELPREVV Dose|
|150 mg/2 weeks||405 mg/4 weeks||300 mg/2 weeks|
|Weight: mean change in kg (N1)||0.67 (140)||0.89 (315)||1.70b(140)|
|Prolactin: mean change in μg/L (N1)||-5.61 (109)||-2.76 (259)||3.57b, c (115)|
|Fasting triglycerides: patients who met the criteriad for change from normal at baseline to high at anytime n/N2 (%)||4/62 (6.5)||13/133 (9.8)||13/53b, c (24.5)|
|a Abbreviations: N1=Number of patients who have
both baseline and post-baseline measurement; n=number of patients with an
abnormal post-baseline measurement at any time; N2=Number of patients with a
normal baseline and at least one post-baseline measurement.
b p < 0.05 versus 150 mg/2 weeks ZYPREXA RELPREVV; pairwise p-values.
c p < 0.05 versus 405 mg/4 weeks ZYPREXA RELPREVV; pairwise p-values.
d Triglycerides normal to high limits are < 150 mg/dL to 200 mg/dL ≤ X < 500 mg/dL.
Dose Dependency of Adverse Reactions in Short-Term, Placebo-Controlled Trials
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 11: Treatment-Emergent Extrapyramidal Symptoms
Assessed by Rating Scales Incidence in a Fixed Dosage Range, Placebo-Controlled
Clinical Trial of Oral Olanzapine in Schizophrenia - Acute Phase
|Percentage of Patients Reporting Event|
|Placebo||Olanzapine 5 ± 2.5 mg/day||Olanzapine 10 ± 2.5 mg/day||Olanzapine 15 ± 2.5 mg/day|
|a Percentage of patients with a Simpson-Angus Scale total score > 3.
b Percentage of patients with a Barnes Akathisia Scale global score ≥ 2.
The following table enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms as assessed by spontaneously reported adverse reactions during acute therapy in the same controlled clinical trial comparing olanzapine at 3 fixed doses with placebo in the treatment of schizophrenia in a 6-week trial.
Table 12: Treatment-Emergent Extrapyramidal Symptoms Assessed by Adverse Reactions Incidence in a Fixed Dosage Range, Placebo-Controlled Clinical Trial of Oral Olanzapine in Schizophrenia — Acute Phase
|Percentage of Patients Reporting Event|
|Olanzapine 5 ± 2.5 mg/day
|Olanzapine 10 ± 2.5 mg/day
|Olanzapine 15 ± 2.5 mg/day
|Any extrapyramidal event||16||15||25||32|
|a Patients with the following COSTART terms were
counted in this category: dystonia, generalized spasm, neck rigidity,
oculogyric crisis, opisthotonos, torticollis.
b Patients with the following COSTART terms were counted in this category: akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, masked facies, tremor.
c Patients with the following COSTART terms were counted in this category: akathisia, hyperkinesia.
d Patients with the following COSTART terms were counted in this category: buccoglossal syndrome, choreoathetosis, dyskinesia, tardive dyskinesia.
e Patients with the following COSTART terms were counted in this category: movement disorder, myoclonus, twitching.
Dystonia, Class Effect: Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue. While these symptoms can occur at low doses, the frequency and severity are greater with high potency and at higher doses of first generation antipsychotic drugs. In general, an elevated risk of acute dystonia may be observed in males and younger age groups receiving antipsychotics; however, events of dystonia have been reported infrequently ( < 1%) with olanzapine use.
Differences among Fixed-Dose Groups Observed in Oral Olanzapine Clinical Trials
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 patients with schizophrenia or schizoaffective disorder, differences among 3 dose groups were observed for the following safety outcomes: weight gain, prolactin elevation, fatigue and dizziness. Mean baseline to endpoint increase in weight (10 mg/day: 1.9 kg; 20 mg/day: 2.3 kg; 40 mg/day: 3 kg) was observed with significant differences between 10 vs 40 mg/day. Incidence of treatment-emergent prolactin elevation > 24.2 ng/mL (female) or > 18.77 ng/mL (male) at any time during the trial (10 mg/day: 31.2%; 20 mg/day: 42.7%; 40 mg/day: 61.1%) with significant differences between 10 vs 40 mg/day and 20 vs 40 mg/day; fatigue (10 mg/day: 1.5%; 20 mg/day: 2.1%; 40 mg/day: 6.6%) with significant differences between 10 vs 40 and 20 vs 40 mg/day; and dizziness (10 mg/day: 2.6%; 20 mg/day: 1.6%; 40 mg/day: 6.6%) with significant differences between 20 vs 40 mg, was observed.
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).
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.
Metabolic and Nutritional Disorders - Infrequent: alkaline phosphatase increased, bilirubinemia, hypoproteinemia.
Musculoskeletal System - Rare: osteoporosis.
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.
Vital Signs and Laboratory Studies
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-glutamyltranseferase (GGT) and sodium. 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.
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.
Rare postmarketing reports of hepatitis have been received for patients taking different formulations of olanzapine. Very rare cases of cholestatic or mixed liver injury have also been reported in the postmarketing period.
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], with an asymptomatic elevation of the eosinophil count in 0.3% of patients, and with an increase in CPK.
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].
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), diabetic coma, diabetic ketoacidosis, discontinuation reaction (diaphoresis, nausea, or vomiting), jaundice, neutropenia, pancreatitis, priapism, rash, 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.
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.
Read the entire FDA prescribing information for Zyprexa Relprevv (Olanzapine Extended Release Injectable Suspension)
Additional Zyprexa Relprevv Information
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