Elevat

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Elevat uses



Elevat is indicated in adults for the treatment of:

  • anorexia associated with weight loss in patients with Acquired Immune Deficiency Syndrome (AIDS).
  • nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.

Elevat is a cannabinoid indicated in adults for the treatment of:

  • anorexia associated with weight loss in patients with AIDS. (1)
  • nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments. (1)

2 DOSAGE AND ADMINISTRATION

Administration :

  • Always use the enclosed calibrated oral dosing syringe.
  • The calibrated oral syringe measures a maximum Elevat dose of 5 mg. If the prescribed dose is greater than 5 mg, the total dose will need to be divided and drawn up in two or more portions using the oral syringe.
  • Take Elevat with a full glass of water (6 to 8 ounces).

Anorexia Associated with Weight Loss in Adult Patients with AIDS ( 2.2 ):

  • The recommended starting dosage is 2.1 mg orally twice daily, one hour before lunch and dinner.
  • See the full prescribing information for dosage titration to manage adverse reactions and to achieve desired therapeutic effect

Nausea and Vomiting Associated with Chemotherapy in Adult Patients Who Failed Conventional Antiemetics (2.3):

  • The recommended starting dosage is 4.2 mg/m2, administered 1 to 3 hours prior to chemotherapy, then every 2 to 4 hours after chemotherapy for a total of 4 to 6 doses per day. Administer the first dose on an empty stomach at least 30 minutes prior to eating; subsequent doses can be taken without regard to meals.
  • See the full prescribing information for dosage titration to manage adverse reactions and to achieve desired therapeutic effect.

2.1 Important Administration Instructions

  • Always use the enclosed calibrated oral dosing syringe when administering Elevat to ensure the dose is measured and administered accurately.
  • The calibrated oral syringe measures a maximum Elevat dose of 5 mg. If the prescribed dose is greater than 5 mg, the total dose will need to be divided and drawn up in two or more portions using the oral syringe.
  • Take each dose of Elevat with a full glass of water (6 to 8 ounces).
  • For information on dosing Elevat with regard to meals, see Dosage and Administration 2.2 and 2.3 .

2.2 Anorexia Associated with Weight Loss in Adult Patients with AIDS

Starting Dosage

The recommended adult starting dosage of Elevat is 2.1 mg orally twice daily, one hour before lunch and one hour before dinner.

In elderly patients, or patients unable to tolerate 2.1 mg twice daily, consider initiating Elevat at 2.1 mg once daily one hour before dinner or at bedtime to reduce the risk of central nervous system symptoms [see Use in Specific Populations (8.5)].

Dosing later in the day may reduce the frequency of Central Nervous System (CNS) adverse reactions. CNS adverse reactions are dose-related ; therefore monitor patients and reduce the dosage as needed. If CNS adverse reactions of feeling high, dizziness, confusion, and somnolence occur, they usually resolve in 1 to 3 days and usually do not require dosage reduction. If CNS adverse reactions are severe or persistent, reduce the dosage to 2.1 mg once daily one hour before dinner or in the evening at bedtime.

Dosage Titration

  • If tolerated and further therapeutic effect is desired, the dosage may be increased gradually to 2.1 mg one hour before lunch and 4.2 mg one hour before dinner. Increase the dose of Elevat gradually in order to reduce the frequency of dose-related adverse reactions .
  • Most patients respond to 2.1 mg twice daily, but the dose may be further increased to 4.2 mg one hour before lunch and 4.2 mg one hour before dinner, as tolerated to achieve a therapeutic effect.
  • Maximum

    Dosage: 8.4 mg twice daily.

2.3 Nausea and Vomiting Associated with Cancer Chemotherapy in Adult Patients Who Failed Conventional Antiemetics

Starting Dosage

The recommended starting dosage of Elevat is 4.2 mg/m2 orally administered 1 to 3 hours prior to chemotherapy and then every 2 to 4 hours after chemotherapy for a total of 4 to 6 doses per day.

  • Calculate the starting dose by following the steps below:
    • Starting dose (mg) = Patient body surface area (BSA) in m2 multiplied by 4.2 mg/m2
    • Round dose to the nearest 0.1 mg increment
    • To correspond with the calibrated oral dosing syringe, the dose may need to be rounded to the nearest 0.1 mL increment

In elderly patients, consider initiating Elevat at 2.1 mg/m2 once daily 1 to 3 hours prior to chemotherapy to reduce the risk of CNS symptoms .

Because food delays the absorption of Elevat, administer the first dose on an empty stomach at least 30 minutes before eating. Subsequent doses can be taken without regard to meals.

Because food can substantially change the systemic exposure to Elevat and its active metabolite, the timing of dosing in relation to meal times should be kept consistent for each chemotherapy cycle, once the dosage has been determined from the titration process.

Dosage Titration

  • The dosage can be titrated to clinical response during a chemotherapy cycle or subsequent cycles, based upon initial effect, as tolerated to achieve a clinical effect, in increments of 2.1 mg/m2.
  • Maximum

    Dosage: 12.6 mg/m2 per dose for 4 to 6 doses per day.

  • Adverse reactions are dose-related and psychiatric symptoms increase significantly at the maximum dosage .

Monitor patients for adverse reactions and consider decreasing the dose to 2.1 mg once daily 1 to 3 hours prior to chemotherapy to reduce the risk of CNS adverse reactions.

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3 DOSAGE FORMS AND STRENGTHS

Oral Solution: 5 mg/mL, a clear, pale yellow to brown solution.

Oral Solution: 5 mg/ mL (3)

4 CONTRAINDICATIONS

Elevat is contraindicated in patients:

  • with a history of a hypersensitivity reaction to Elevat. Reported hypersensitivity reactions to Elevat include lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, throat tightness .
  • with a history of a hypersensitivity reaction to alcohol.
  • who are receiving, or have recently received, disulfiram- or metronidazole-containing products within 14 days . Elevat contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol.

Patients:

  • with a sensitivity to Elevat or alcohol.(4)
  • with a history of hypersensitivity reaction to alcohol.(4)
  • who are receiving, or have received, disulfiram- or metronidazole-containing products within the past 14 days. (4, 5.3, 7.1)

5 WARNINGS AND PRECAUTIONS

  • Neuropsychiatric Adverse Reactions: May cause psychiatric and cognitive effects and impair mental and/or physical abilities. Avoid use in patients with a psychiatric history. Monitor for symptoms and avoid concomitant use of drugs with similar effects. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that Elevat does not affect them adversely.
  • Hemodynamic Instability: Patients with cardiac disorders may experience hypotension, hypertension, syncope or tachycardia. Avoid concomitant use of drugs with similar effects and monitor for hemodynamic changes after initiating or increasing the dosage of Elevat. (5.2)
  • Interaction with Disulfiram and Metronidazole: May cause disulfiram-like reaction. Discontinue products containing disulfiram or metronidazole at least 14 days before and do not administer 7 days after treatment with Elevat. (4, 5.3, 7.1)
  • Seizures and Seizure-like Activity: Weigh the potential risk versus benefits before prescribing Elevat to patients with a history of seizures, including those requiring anti-epileptic medication or with other factors that lower the seizure threshold. Monitor patients and discontinue if seizures occur. (5.4)
  • Multiple Substance Abuse: Assess risk for abuse or misuse in patients with a history of substance abuse or dependence, prior to prescribing Elevat and monitor for the development of associated behaviors or conditions (5.5)
  • Paradoxical Nausea, Vomiting, or Abdominal Pain: Consider dose reduction or discontinuation, if worsening of symptoms while on treatment. (5.6)
  • Toxicities Related to Propylene Glycol in Preterm Neonates: The safety and effectiveness of Elevat have not been established in pediatric patients. Avoid use in preterm neonates in the immediate postnatal period. (5.7)

5.1 Neuropsychiatric Adverse Reactions

Psychiatric Adverse Reactions

Elevat has been reported to exacerbate mania, depression, or schizophrenia. Prior to initiating treatment with Elevat, screen patients for a history of these illnesses. Avoid use in patients with a psychiatric history or, if the drug cannot be avoided, monitor patients for new or worsening psychiatric symptoms during treatment. Also, avoid concomitant use with other drugs that are associated with similar psychiatric effects.

Cognitive Adverse Reactions

Use of Elevat has been associated with cognitive impairment and altered mental state. Reduce the dose of Elevat or discontinue use of Elevat if signs or symptoms of cognitive impairment develop. Elderly and pediatric patients may be more sensitive to the neurological and psychoactive effects of Elevat .

Hazardous Activities

Elevat can cause and may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle or operating machinery. Concomitant use of other drugs that cause dizziness, confusion, sedation, or somnolence such as CNS depressants may increase this effect (e.g., barbiturates, benzodiazepines, lithium, opioids, buspirone, scopolamine, antihistamines, tricyclic antidepressants, other anticholinergic agents,and muscle relaxants). Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that Elevat does not affect them adversely.

5.2 Hemodynamic Instability

Patients may experience occasional hypotension, possible hypertension, syncope, or tachycardia while taking Elevat . Patients with cardiac disorders may be at higher risk. Avoid concomitant use of other drugs that are also associated with similar cardiac effects (e.g., amphetamines, other sympathomimetic agents, atropine, amoxapine, scopolamine, antihistamines, other anticholinergic agents, amitriptyline, desipramine, other tricyclic antidepressants). Monitor patients for changes in blood pressure, heart rate, and syncope after initiating or increasing the dosage of Elevat.

5.3 Interaction with Disulfiram and Metronidazole

Elevat contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol. Use of Elevat may cause a disulfiram-like reaction, characterized by abdominal cramps, nausea, vomiting, headaches, and flushing, in patients receiving disulfiram or other drugs that produce this reaction (e.g., metronidazole). Discontinue products containing disulfiram or metronidazole at least 14 days before starting treatment with Elevat and do not administer these products within 7 days of completing treatment with Elevat .

When administered concomitantly with propylene glycol, ethanol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations of propylene glycol. However, the contribution of propylene glycol, if any, to the interaction between disulfiram and Elevat is unknown.

5.4 Seizures

Seizures and seizure-like activity have been reported in patients receiving Elevat.

Weigh this potential risk against the benefits before prescribing Elevat to patients with a history of seizures, including those receiving anti-epileptic medication or with other factors that can lower the seizure threshold. Monitor patients with a history of seizure disorders for worsened seizure control during Elevat therapy.

If a seizure occurs, advise patients to discontinue Elevat and contact a healthcare provider immediately.

5.5 Multiple Substance Abuse

Patients with a history of substance abuse or dependence, including marijuana or alcohol, may be more likely to abuse Elevat as well. Elevat contains 50% dehydrated alcohol.

Assess each patient’s risk for abuse or misuse prior to prescribing Elevat and monitor patients with a history of substance abuse during treatment with Elevat for the development of these behaviors or conditions.

5.6 Paradoxical Nausea, Vomiting, or Abdominal Pain

New or worsening nausea, vomiting, or abdominal pain can occur during treatment with synthetic delta-9 tetrahydrocannabinol (delta-9-THC), the active ingredient in Elevat. In some cases, these adverse reactions were severe (e.g., dehydration, electrolyte abnormalities) and required dose reduction or drug discontinuation. Symptoms are similar to cannabinoid hyperemesis syndrome (CHS), which is described as cyclical events of abdominal pain, nausea, and vomiting in chronic, long-term users of delta-9-THC products.

Because patients may not recognize these symptoms as abnormal, it is important to specifically ask patients or their caregivers about the development of worsening of nausea, vomiting, or abdominal pain while being treated with Elevat. Consider dose reduction or discontinuing Elevat if a patient develops worsening nausea, vomiting, or abdominal pain while on treatment.

5.7 Toxicity in Preterm Neonates

Elevat contains the excipients dehydrated alcohol (50%, w/w) and propylene glycol (5.5%, w/w). When administered concomitantly with propylene glycol, ethanol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations of propylene glycol. Preterm neonates may be at increased risk of propylene glycol-associated adverse reactions due to a diminished ability to metabolize propylene glycol, thereby, leading to accumulation.

The safety and effectiveness of Elevat have not been established in pediatric patients. Avoid Elevat in preterm neonates in the immediate postnatal period because of possible propylene glycol-associated toxicities including: hyperosmolarity, with or without lactic acidosis, renal toxicity, CNS depression (including stupor, coma, and apnea), seizures, hypotonia, cardiac arrhythmias, electrocardiogram (ECG) changes, and hemolysis.

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6 ADVERSE REACTIONS

Most common adverse reactions are: abdominal pain, dizziness, euphoria, nausea, paranoid reaction, somnolence, thinking abnormal, and vomiting. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Insys Therapeutics, Inc. at 1-855-978-2797 or FDA at MedWatch phone number 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 the rates observed in practice.

The following serious adverse reactions are described below and elsewhere in the labeling.

  • Neuropsychiatric Adverse Reactions
  • Hemodynamic Instability
  • Seizures
  • Paradoxical Nausea, Vomiting, and Abdominal Pain
  • Toxicity in Preterm Neonates

The safety of Elevat has been established based on studies of Elevat capsules. Studies of AIDS-related weight loss included 157 patients receiving Elevat capsules and 67 receiving placebo. Studies of nausea and vomiting related to cancer chemotherapy included 317 patients receiving Elevat capsules and 68 receiving placebo. In the tables below is a summary of the adverse reactions in 474 patients exposed to Elevat capsules in studies.

Studies of different durations were combined by considering the first occurrence of adverse reactions during the first 28 days.

A cannabinoid dose-related “high” (easy laughing, elation and heightened awareness) has been reported by patients receiving Elevat capsules in both the antiemetic (24%) and the lower dose appetite stimulant clinical trials (8%). The most frequently reported adverse experiences in patients with AIDS during placebo-controlled clinical trials involved the CNS and were reported by 33% of patients receiving Elevat capsules. About 25% of patients reported a CNS adverse reaction during the first 2 weeks and about 4% reported such a reaction each week for the next 6 weeks thereafter.

Common Adverse Reactions

The following adverse reactions were reported in clinical trials of Elevat capsules at an incidence greater than 1%.

*Actual Incidence 3% to 10%
System Organ Class Adverse Reactions
General Asthenia
Cardiovascular Palpitations, tachycardia, vasodilation/facial flush
Gastrointestinal Abdominal pain*, nausea*, vomiting*
Central Nervous System Dizziness*, euphoria*, paranoid reaction*, somnolence*, thinking abnormal*, amnesia, anxiety/nervousness, ataxia, confusion, depersonalization, hallucination

Less Common Adverse Reactions

The following adverse reactions were reported in clinical trials of Elevat capsules at an incidence less than or equal to 1%.

System Organ Class Adverse Reactions
General Chills, headache, malaise
Cardiovascular Hypotension, conjunctival injection
Gastrointestinal Diarrhea, fecal incontinence, anorexia, hepatic enzyme elevation
Musculoskeletal Myalgias
Central Nervous System Depression, nightmares, speech difficulties, tinnitus
Respiratory Cough, rhinitis, sinusitis
Skin Flushing, sweating
Sensory Vision difficulties

6.2 Postmarketing Experience

The following adverse reactions have been identified during post-approval use of another oral formulation of Elevat. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

General disorders and administration site conditions: fatigue.

Hypersensitivity reactions: lip swelling, hives, disseminated rash, oral lesions, skin burning, flushing, throat tightness .

Injury, poisoning and procedural complications: fall .

Nervous system disorders: seizures , disorientation, movement disorder, loss of consciousness.

Psychiatric disorders: delirium, insomnia, panic attack.

Vascular disorders: syncope .

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7 DRUG INTERACTIONS

  • Inhibitors and Inducers of CYP2C9 and CYP3A4: May alter Elevat systemic exposure; monitor for dronabinol-related adverse reactions or loss of efficacy.
  • Highly Protein-Bound Drugs: Potential for displacement of other drugs from plasma proteins; monitor for adverse reactions to concomitant narrow therapeutic index drugs (e.g., warfarin, cyclosporine, or amphotericin B) when initiating or increasing the dosage of Elevat. (7.3)

7.1 Disulfiram and Metronidazole

Elevat contains 50% (w/w) dehydrated alcohol 5.5% (w/w) propylene glycol, which can produce disulfiram-like reactions when co-administered with disulfiram or other drugs that produce this reaction (e.g., metronidazole). Discontinue products containing disulfiram or metronidazole at least 14 days before starting treatment with Elevat and do not administer these products within 7 days of completing treatment with Elevat .

When administered concomitantly with propylene glycol, ethanol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations of propylene glycol. However, the contribution of propylene glycol, if any, to the interaction between disulfiram and Elevat is unknown.

7.2 Effect of Other Drugs on Elevat

Elevat is primarily metabolized by CYP2C9 and CYP3A4 enzymes. Inhibitors of these enzymes may increase, while inducers may decrease, the systemic exposure of Elevat and/or its active metabolite resulting in an increase in dronabinol-related adverse reactions or loss of efficacy of Elevat.

Monitor for increased dronabinol-related adverse reactions when Elevat is co-administered with inhibitors of CYP2C9 and inhibitors of CYP3A4 enzymes (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice).

7.3 Highly Protein-Bound Drugs

Elevat is highly bound to plasma proteins, and therefore, might displace and increase the free fraction of other concomitantly administered protein-bound drugs. Although this displacement has not been confirmed in vivo, monitor patients for increased adverse reactions to narrow therapeutic index drugs (e.g., warfarin, cyclosporine, amphotericin B) when initiating treatment or increasing the dosage of Elevat.

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8 USE IN SPECIFIC POPULATIONS

  • Pregnancy: May cause fetal harm.
  • Lactation: Advise HIV infected women not to breastfeed and women with nausea and vomiting associated with cancer chemotherapy not to breastfeed during treatment with Elevat and for 9 days after the last dose.(8.2)
  • Geriatric Use: Elderly patients may be more sensitive to the neuropsychiatric and postural hypotensive effects. Consider a lower starting dose in elderly patients. (2.2, 2.3, 5.1, 5.2, 8.5)

8.1 Pregnancy

Risk Summary

Elevat, a synthetic cannabinoid containing alcohol, may cause fetal harm. Avoid use of Elevat in pregnant women. Although there is little published data on the use of synthetic cannabinoids during pregnancy, use of cannabis (e.g., marijuana) and use of alcohol during pregnancy have been associated with adverse fetal/neonatal outcomes . Cannabinoids have been found in the umbilical cord blood from pregnant women who smoke cannabis. In animal reproduction studies, no teratogenicity was reported in mice administered Elevat at up to 30 times the MRHD (maximum recommended human doses) and up to 5 times the MRHD for patients with AIDS and cancer, respectively. Similar findings were reported in pregnant rats administered Elevat at up to 5 to 20 times the MRHD and 3 times the MRHD for patients with AIDS and cancer, respectively. Decreased maternal weight gain and number of viable pups and increased fetal mortality and early resorptions were observed in both species at doses which induced maternal toxicity. In published studies, offspring of pregnant rats administered delta-9-THC during and after organogenesis have been reported to exhibit neurotoxicity with adverse effects on brain development, including abnormal neuronal connectivity and impairments in cognitive and motor function .

The estimated background risk of major birth defects and miscarriage for the indicated populations are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Fetal/Neonatal Adverse Reactions

Published studies suggest that during pregnancy, the use of cannabis, which includes THC, whether for recreational or medicinal purposes, may increase the risk of adverse fetal/neonatal outcomes including fetal growth restriction, low birth weight, preterm birth, small-for-gestational age, admission to the NICU, and stillbirth. Therefore, use of cannabis during pregnancy should be avoided.

Elevat contains alcohol. Published studies have demonstrated that alcohol is associated with fetal harm including central nervous system abnormalities, behavioral disorders, and impaired intellectual development. Avoid use of Elevat in pregnant women.

Data

Human Data

Delta-9-THC has been measured in the cord blood of some infants whose mothers reported prenatal use of cannabis, suggesting that Elevat may cross the placenta to the fetus during pregnancy. The effects of delta-9-THC on the fetus are not known.

Animal Data

The recommended dose ranges for Elevat in AIDS and cancer patients are designed to achieve the same systemic exposure ranges as with the recommended dose ranges for Elevat capsules. Therefore, animal to human dose multiples, as shown below, are based on the MRHDs (maximum recommended human doses) for Elevat capsules, instead of the MRHDs for Elevat, which are 15% lower. This approach for dose comparison between animals and humans is supported by the demonstrated difference in Elevat bioavailability between Elevat and Elevat capsules.

Reproduction studies with Elevat have been performed in mice at 15 to 450 mg/m2, equivalent to 1 to 30 times the MRHD of 15 mg/m2/day (dronabinol capsules) in AIDS patients or 0.2 to 5 times the MRHD of 90 mg/m2/day (dronabinol capsules) in cancer patients, and in rats at 74 to 295 mg/m2 (equivalent to 5 to 20 times the MRHD of 15 mg/m2/day in AIDS patients or 0.8 to 3 times the MRHD of 90 mg/m2/day in cancer patients). These studies have revealed no evidence of teratogenicity due to Elevat. At these dosages in mice and rats, Elevat decreased maternal weight gain and number of viable pups and increased fetal mortality and early resorptions. Such effects were dose dependent and less apparent at lower doses that produced less maternal toxicity.

Review of published literature indicates that the endocannabinoid system plays a role in neurodevelopmental processes such as neurogenesis, migration, and synaptogenesis. Exposure of pregnant rats to delta-9-THC (during and after organogenesis) may modulate these processes to result in abnormal patterns of neuronal connectivity and subsequent cognitive impairments in the offspring. Nonclinical toxicity studies in pregnant rats and newborn pups have shown prenatal exposure to THC that resulted in impairment of motor function, alteration in synaptic activity, and interference in cortical projection of neuron development in the offspring. Prenatal exposure has shown effects on cognitive function such as learning, short- and long-term memory, attention, decreased ability to remember task, and ability to discriminate between novel and same objects. Overall, prenatal exposure to THC has resulted in significant and long-term changes in brain development, cognition, and behavior in rat offspring.

8.2 Lactation

Risk Summary

For mothers infected with the Human Immunodeficiency Virus, the Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV. Because of the potential for HIV transmission (in HIV-negative infants) and serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving Elevat.

For mothers with nausea and vomiting associated with cancer chemotherapy, there are limited data on the presence of Elevat in human milk, the effects on the breastfed infant, or the effects on milk production. The reported effects of inhaled cannabis transferred to the breastfeeding infant have been inconsistent and insufficient to establish causality. Because of the possible adverse effects from Elevat on the breastfeeding infant, advise women with nausea and vomiting associated with cancer chemotherapy not to breastfeed during treatment with Elevat and for 9 days after the last dose.

8.4 Pediatric Use

The safety and effectiveness of Elevat have not been established in pediatric patients.

Pediatric patients may be more sensitive to neurological and psychoactive effects of Elevat . Elevat contains the excipients 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol. Ethanol competitively inhibits the metabolism of propylene glycol, which may lead to elevated concentrations of propylene glycol. Preterm neonates may be at increased risk of propylene glycol-associated adverse events due to diminished ability to metabolize propylene glycol, thereby, leading to accumulation .

8.5 Geriatric Use

Clinical studies of Elevat capsules in AIDS and cancer patients did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.

Elderly patients may be more sensitive to the neuropsychiatric and postural hypotensive effects of Elevat .

Elderly patients with dementia are at increased risk for falls as a result of their underlying disease state, which may be exacerbated by the CNS effects of somnolence and dizziness associated with Elevat . These patients should be monitored closely and placed on fall precautions prior to initiating Elevat therapy. In antiemetic studies, no difference in efficacy was apparent in patients greater than 55 years of age compared to younger patients.

In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of falls, decreased hepatic, renal, or cardiac function, increased sensitivity to psychoactive effects, and of concomitant disease or other drug therapy .

8.6 Effect of CYP2C9 Polymorphism

Published data suggest that systemic clearance of Elevat may be reduced and concentrations may be increased in presence of CYP2C9 genetic polymorphism. Monitoring for increased adverse reactions is recommended in patients known to carry genetic variants associated with diminished CYP2C9 function .

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Elevat contains Elevat oral solution, a Schedule II controlled substance.

9.2 Abuse

Elevat contains Elevat, the main psychoactive component in marijuana. Ingestion of high doses of Elevat increases the risk of psychiatric adverse reactions if abused or misused, while continued administration can lead to addiction. Psychiatric adverse reactions may include psychosis, hallucinations, depersonalization, mood alteration, and paranoia.

In vitro studies demonstrate that Elevat can be easily and effectively abused without manipulation. Elevat contains 50% dehydrated alcohol .

In a randomized, single-dose, double-blind, placebo- and active-controlled crossover pharmacodynamic study of 43 experienced marijuana smokers, “drug liking” responses and safety of Elevat were compared with placebo and Elevat in sesame oil oral capsules. Treatment arms were 10 mg and 30 mg Elevat capsules, 10 mg and 30 mg Elevat from Elevat, and placebo oral solution and capsules. Greater “drug liking” scores were reported with the 30 mg dose, compared with the 10 mg dose, for both Elevat and dronabinol-containing capsules. Overall, the pharmacodynamic results from this study demonstrated no statistically significant differences in various measures of drug liking for the doses taken, though the Elevat results were consistently greater than those of Elevat capsules. Similarly, observed adverse reactions were greater for Elevat. The pharmacodynamic and safety effects of Elevat following multiple doses have not been evaluated.

Patients should be instructed to keep Elevat in a secure place out of reach of others for whom the medication has not been prescribed.

9.3 Dependence

Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use. Physical dependence manifests by drug class-specific withdrawal symptoms after abrupt discontinuation or a significant dose reduction of a drug. The appearance of a withdrawal syndrome when administration of the drug is terminated is the only actual evidence of physical dependence. Physical dependence can develop during chronic therapy with Elevat, and develops after chronic abuse of marijuana.

A withdrawal syndrome was reported after the abrupt discontinuation of Elevat capsules in subjects receiving dosages of 210 mg per day for 12 to 16 consecutive days. Within 12 hours after discontinuation, subjects manifested symptoms such as irritability, insomnia, and restlessness. By approximately 24 hours post-dronabinol discontinuation, withdrawal symptoms intensified to include “hot flashes”, sweating, rhinorrhea, loose stools, hiccoughs, and anorexia. These withdrawal symptoms gradually dissipated over the next 48 hours.

Electroencephalographic changes consistent with the effects of drug withdrawal (hyperexcitation) were recorded in patients after abrupt dechallenge. Patients also complained of disturbed sleep for several weeks after discontinuing therapy with high dosages of Elevat.

10 OVERDOSAGE

Elevat contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol. Ingestion of the product over the recommended dose could result in significant toxicity.

Elevat

Signs and symptoms of Elevat overdose include drowsiness, euphoria, heightened sensory awareness, altered time perception, reddened conjunctiva, dry mouth, tachycardia, memory impairment, depersonalization, mood alteration, urinary retention, reduced bowel motility, decreased motor coordination, lethargy, slurred speech, and postural hypotension. Patients may also experience panic reactions if they have a prior history of nervousness or anxiety and seizures may occur in patients with existing seizure disorders.

It is not known if Elevat can be removed by dialysis in cases of overdose.

Alcohol

Signs and symptoms of alcohol overdose include changes in mood or behavior, impaired judgment or social functioning and one or more physical signs such as slurred speech, unsteadiness, lack of coordination, increased or irregular heart rate, respiratory depression, impaired attention or loss of consciousness.

Propylene Glycol

Signs and symptoms of acute poisoning occur only in rare circumstances where patients ingest large amounts of propylene glycol over several days. These include hypoglycemia, severe metabolic acidosis (caused by the metabolism into lactic acid), and CNS depression including coma and seizures.

Management of Overdosage

If over-exposure of Elevat occurs, call your Poison Control Center at 1-800-222-1222 for current information on the management of poisoning or overdosage.

11 DESCRIPTION

Elevat is a cannabinoid designated chemically as (6aR,10aR)-6a,7,8,10a-Tetrahydro-6,6,9-trimethyl-3-pentyl-6H-dibenzo[b,d]-pyran-1-ol. Elevat has the following empirical and structural formulas:

C21H30O2 (molecular weight=314.46)

Elevat is a clear colorless to amber oil. Elevat is insoluble in water. It has a pKa of 10.6 and an octanol-water partition coefficient: 6,000:1 at pH 7.

Elevat (dronabinol) oral solution, 5 mg/mL is a clear, pale yellow to brown solution. Each mL of SYNDROS contains 5 mg of Elevat as an active ingredient and the following inactive ingredients: 50 % (w/w) dehydrated alcohol, polyethylene glycol 400, propylene glycol, sucralose, methyl paraben, propyl paraben, butylated hydroxyanisole, and water.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Elevat is an orally active cannabinoid which has complex effects on the CNS, including central sympathomimetic activity. Cannabinoid receptors have been discovered in neural tissues. These receptors may play a role in mediating the effects of Elevat.

12.2 Pharmacodynamics

Effects on the Cardiovascular System

Dronabinol-induced sympathomimetic activity may result in tachycardia and/or conjunctival injection. Its effects on blood pressure are inconsistent, but subjects have experienced orthostatic hypotension and/or syncope upon abrupt standing .

Effects on the Central Nervous System

Elevat also demonstrates reversible effects on appetite, mood, cognition, memory, and perception. These phenomena appear to be dose-related, increasing in frequency with higher dosages, and subject to great inter-patient variability. After oral administration, Elevat capsules have an onset of action of approximately 0.5 to 1 hours and peak effect at 2 to 4 hours. Duration of action for psychoactive effects is 4 to 6 hours, but the appetite stimulant effect of Elevat may continue for 24 hours or longer after administration.

Tachyphylaxis and tolerance develop to some of the cardiovascular and CNS pharmacologic effects of dronabinol with chronic use, suggesting an indirect effect on sympathetic neurons. In a study of the pharmacodynamics of chronic Elevat exposure, healthy male subjects (N = 12) received 12 times the maximum dose for anorexia associated with weight loss in patients with AIDS of Elevat capsules in divided doses for 16 days. An initial tachycardia induced by Elevat was replaced successively by normal sinus rhythm and then bradycardia. A decrease in supine blood pressure, made worse by standing, was also observed initially. These subjects developed tolerance to the cardiovascular and subjective adverse CNS effects of dronabinol within 12 days of treatment initiation.

Tachyphylaxis and tolerance do not appear to develop to the appetite stimulant effect of Elevat. In clinical studies of Elevat capsules in AIDS patients, at the recommended dosage, the appetite stimulant effect was sustained for up to five months.

12.3 Pharmacokinetics

Absorption

Elevat (delta-9-THC) is almost completely absorbed (90 to 95%) after single oral doses. Due to the combined effects of first pass hepatic metabolism and high lipid solubility, only 10 to 20% of the administered dose reaches the systemic circulation. Relative bioavailability data from healthy male and female subjects suggest that a dose of 4.2 mg of Elevat provides comparable systemic exposure (Cmax and AUC) to a 5 mg Elevat capsule, under fasted conditions . The concentrations of both Elevat and its major active metabolite (11-hydroxy-delta-9-THC) peak at approximately 0.5 to 4 hours after oral dosing with Elevat and decline over several days. The mean inter- and intra-subject variability in Elevat pharmacokinetics (Cmax and AUCinf) was approximately 66% and 47% and 67% and 14%, respectively, following administration of Elevat to healthy subjects.

*Arithmetic mean ± standard deviation except Tmax for which the median [range] is reported
Parameter* Elevat
Cmax (ng/mL) 1.9 ± 1.3
Tmax (h) 1.0 [0.5 to 4.0]
AUC(inf) (ng.h/mL) 3.8 ± 1.8
t½ (h) 5.6 ± 2.7

Food Effect: The effect of food on the pharmacokinetics of Elevat was studied by concomitant dosing of Elevat with a high-fat (59 grams of fat, approximately 50% of total caloric content of the meal), high calorie meal (approximately 950 calories). An appreciable food effect was observed: food resulted in approximately a 2.5-fold increase in total exposure (AUCinf) and approximately a 5 hour delay in median Tmax. Food also decreased Cmax by approximately 20% ).

Distribution:

Elevat has an apparent volume of distribution of approximately 10 L/kg, because of its lipid solubility. The plasma protein binding of Elevat and its metabolites is approximately 97% .

Elimination

The pharmacokinetics of Elevat can be described using a two compartment model with an initial (alpha) half-life of about 5 hours and a terminal (beta) half-life of 25 to 36 hours. Values for clearance average about 0.2 L/kg-hr; but are highly variable due to the complexity of cannabinoid distribution.

Metabolism

Elevat undergoes extensive first-pass hepatic metabolism, primarily by hydroxylation, yielding both active and inactive metabolites. The major metabolite (11-hydroxy-delta-9-THC) is pharmacologically active. Published in vitro data indicates that CYP2C9 and CYP3A4 are the primary enzymes in the metabolism of Elevat. CYP2C9 appears to be the enzyme responsible for the formation of the primary active metabolite .

Excretion

Elevat and its biotransformation products are excreted in both feces and urine. Biliary excretion is the major route of excretion with about half of a radio-labeled oral dose being recovered from the feces within 72 hours as contrasted with 10 to 15% recovered from urine. Less than 5% of an oral dose is recovered unchanged in the feces.

Due to its re-distribution, Elevat and its metabolites may be excreted for prolonged periods of time. Following single dose administration, Elevat metabolites have been detected for more than 5 weeks in the urine and feces.

In a study of Elevat capsules involving AIDS patients, urinary cannabinoid/creatinine concentration ratios were studied bi-weekly over a six week period. The urinary cannabinoid/creatinine ratio was closely correlated with dose. No increase in the cannabinoid/creatinine ratio was observed after the first two weeks of treatment, indicating that steady-state cannabinoid levels had been reached. This conclusion is consistent with predictions based on the observed terminal half-life of Elevat.

Drug Interaction Studies

Formal drug-drug interaction studies have not been conducted with Elevat.

The enzyme inhibition and induction potential of Elevat and its active metabolite are not completely understood.

Published data showed an increase in the elimination half-life of pentobarbital by 4 hours when concomitantly dosed with Elevat .

12.5 Pharmacogenomics

Published data indicate a 2- to 3-fold higher Elevat exposure in individuals carrying genetic variants associated with diminished CYP2C9 function.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

The recommended dose ranges for Elevat in AIDS and cancer patients are designed to achieve the same systemic exposure ranges as with the recommended dose ranges for Elevat capsules.

Therefore, the animal to human dose multiples for carcinogenicity studies, as shown below, are based on the MRHD (maximum recommended human dose) for Elevat capsules in AIDS patients, instead of the MRHD for Elevat which is 15% lower. This approach for dose comparison between animals and humans is supported by the demonstrated difference in Elevat bioavailability between Elevat and Elevat capsules. The animal to human dose multiples for the fertility study in rats, as shown below, are based on the MRHD for Elevat capsules in AIDS or cancer patients.

In 2-year carcinogenicity studies, there was no evidence of carcinogenicity in rats at doses up to 50 mg/kg/day Elevat (approximately 20 times the MRHD for Elevat capsules in AIDS patients on a body surface area basis) or in mice at doses up to 500 mg/kg/day (approximately 100 times the MRHD for Elevat capsules in AIDS patients on a body surface area basis).

Elevat was not genotoxic in the Ames tests, the in vitro chromosomal aberration test in Chinese hamster ovary cells, and the in vivo mouse micronucleus test. However, Elevat produced a weak positive response in a sister chromatid exchange test in Chinese hamster ovary cells.

In a long-term study (77 days) in rats, oral administration of Elevat at doses of 30 to 150 mg/m2, equivalent to 2 to 10 times the MRHD of 15 mg/m2/day (dronabinol capsules) in AIDS patients or 0.3 to 1.5 times the MRHD of 90 mg/m2/day (dronabinol capsules) in cancer patients, reduced ventral prostate, seminal vesicle and epididymal weights and caused a decrease in seminal fluid volume. Decreases in spermatogenesis, number of developing germ cells, and number of Leydig cells in the testis were also observed. However, sperm count, mating success and testosterone levels were not affected. The significance of these animal findings in humans is not known.

14 CLINICAL STUDIES

The effectiveness of Elevat has been established based on studies of Elevat capsules for the treatment of anorexia associated with weight loss in patients with AIDS and nausea and vomiting associated with cancer chemotherapy in patients who have failed to respond adequately to conventional antiemetic treatments.

16 HOW SUPPLIED/STORAGE AND HANDLING

  • Elevat (dronabinol) oral solution, 5 mg/mL is a clear, pale yellow to brown solution. Elevat is supplied in a multi-dose, clear, amber-colored 30 mL glass bottle. It is closed with a 20 mm child-resistant, white polypropylene screw cap with a Teflon coated liner. The bottle is wrapped with a polyvinyl chloride body band to provide tamper evidence and packaged in a carton with an oral syringe, and a push-in bottle adapter.

    NDC 20482-335-30 (30 mL multi-dose bottle, an oral syringe and a push-in bottle adapter)

  • Store in a refrigerator between 2°C and 8°C (36°F and 46°F); excursions permitted to 15°C and 25°C (59°F and 77°F). The opened bottle can be stored at 25°C (77°F). Discard unused portion 28 days after first opening.
  • Keep Elevat oral solution and the oral syringe in the supplied carton.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Accidental Ingestion

Inform patients that accidental ingestion of Elevat, which contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol, may result in toxicity . Instruct patients to seek immediate medical attention in case of accidental injection. Also, instruct patients to store Elevat securely.

Administration Instructions

  • Counsel patients on proper dosing and administration techniques. Advise patients to read the Instructions for Use.
  • Instruct patients to take each Elevat dose with a full glass of water (6 to 8 ounces).

Neuropsychiatric Adverse Reactions

  • Advise patients that psychiatric adverse reactions may occur, especially in patients with a past psychiatric history or in those receiving other drugs also associated with psychiatric effects, and to report to their healthcare provider any new or worsening psychiatric symptoms.
  • Advise patients, especially elderly patients, that cognitive impairment or an altered mental state may also occur during treatment with SYDNROS and to report to their healthcare provider if they develop signs or symptoms of cognitive impairment.
  • Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that Elevat does not affect them adversely.

Hemodynamic Instability

Advise patients, especially those with cardiac disorders, to report to their healthcare provider if they experience any signs or symptoms of hemodynamic instability, including hypotension, hypertension, syncope or tachycardia, especially after initiating or increasing the dosage of Elevat .

Interaction with Disulfiram and Metronidazole

Inform patients that taking Elevat with products containing disulfiram or metronidazole may cause a disulfiram-like reaction due to the alcohol content of Elevat. Advise patients not to take products containing disulfiram or metronidazole during treatment with Elevat and for up to 7 days of completing treatment with Elevat .

Seizures

Advise patients to discontinue Elevat and contact a healthcare provider immediately if they experience a seizure .

Multiple Substance Abuse

Inform patients with a history of substance abuse or dependence, including marijuana or alcohol, that they may be more likely to abuse Elevat. Advise patients to report to their healthcare provider if they develop abuse behaviors or conditions .

Paradoxical Nausea, Vomiting, or Abdominal Pain

Advise patients to report worsening nausea, vomiting, or abdominal pain to their healthcare provider.

Pregnancy

  • Advise a pregnant woman of the potential risk to a fetus and to avoid use of Elevat during pregnancy.

Lactation

  • Advise HIV infected women with anorexia associated with weight loss, not to breastfeed.
  • Advise women with nausea and vomiting associated with cancer chemotherapy not to breastfeed during treatment with Elevat and for 9 days after the last dose.

Manufactured for:

Insys Therapeutics, Inc.

Chandler, AZ 85286

By:

Renaissance Lakewood LLC

Lakewood, NJ 08701


PATIENT INFORMATION

Elevat (sin dros)

(dronabinol)

oral solution, CII

What is the most important information I should know about Elevat?

Elevat can cause serious side effects, including:

  • Worsening mental (psychiatric) symptoms. Psychiatric symptoms can worsen in people who have mania, depression, or schizophrenia and who take Elevat. Elevat taken with medicines that cause psychiatric symptoms can worsen psychiatric symptoms. Elderly people who take Elevat may have a greater risk of having psychiatric symptoms. Tell your doctor if you have new or worsening mood symptoms, including symptoms of mania, depression, or schizophrenia.
  • Problems thinking clearly. Tell your doctor if you have trouble remembering things, concentrating, have increased sleepiness, or confusion. Elderly people may have a greater risk of having problems thinking clearly.
  • Changes in your blood pressure. Elevat may increase or decrease your blood pressure, especially when you start taking Elevat or when your dose is changed. Tell your doctor if you have signs or symptoms of changes in your blood pressure including: headaches, vision problems, dizziness, feeling lightheaded, fainting, or a fast heartbeat. Elderly people, especially those with dementia, and people with heart problems may have an increased risk of changes in blood pressure and an increased risk of falls.
  • Interactions with disulfiram or metronidazole. Elevat contains alcohol, which can cause you to have a reaction to medicines that contain disulfiram or metronidazole. You should not use any medicine that contains disulfiram (Antabuse) or metronidazole (Pylera, Flagyl, Flagyl ER, Nuvessa, Vandazole) if you take Elevat. You should not use a medicine that contains disulfiram or metronidazole for at least 14 days before you start taking Elevat and within 7 days after your last dose of Elevat. Tell your doctor if you have signs or symptoms of a reaction to disulfiram or metronidazole including: stomach-area (abdominal) cramping, nausea, vomiting, headache, and flushing.

What is Elevat?

Elevat is a prescription medicine used in adults to treat:

  • loss of appetite (anorexia) in people with AIDS (Acquired Immune Deficiency Syndrome) who have lost weight.
  • nausea and vomiting caused by anti-cancer medicine (chemotherapy) in people whose nausea and vomiting have not improved with usual anti-nausea medicines.

Elevat is a controlled substance (CII) because it contains Elevat which can be a target for people who abuse prescription medicines or street drugs. Keep your Elevat in a safe place to protect it from theft. Never give your Elevat to anyone else because it may cause death or harm them. Selling or giving away this medicine is against the law.

It is not known if Elevat is safe and effective in children.


Do not take Elevat if you:

  • had an allergic reaction to Elevat. Signs and symptoms of an allergic reaction to Elevat include: swelling of the lips, hives, a rash over your whole body, mouth sores, skin burning, flushing, and throat tightness.
  • had an allergic reaction to alcohol.
  • are using a medicine that contains disulfiram (Antabuse) or metronidazole (Pylera, Flagyl, Flagyl ER, Nuvessa, Vandazole) or have taken or received a medicine that contains disulfiram or metronidazole in the last 14 days.

Before taking Elevat, tell your doctor about all of your medical conditions, including if you:

  • have or had heart problems.
  • have or had problems with drug abuse or dependence.
  • have or had problems with alcohol abuse or dependence.
  • have or had mental health problems including mania, depression or schizophrenia.
  • have had a seizure or have a medical condition that may increase your risk of having a seizure.
  • are pregnant or plan to become pregnant. Elevat may harm your unborn baby. Avoid the use of Elevat if you are pregnant.
  • are breastfeeding or plan to breastfeed. The Centers for Disease Control and Prevention recommends that mothers with HIV not breastfeed because they can pass the HIV through their breast milk to the baby. It is not known if Elevat passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take Elevat. Do not breastfeed while taking Elevat and for 9 days after your last dose of Elevat if you are being treated for nausea and vomiting caused by anti-cancer medicine.

Tell your doctor about all the medicines you take or have taken in the last 14 days, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Elevat and certain other medicines can affect each other, causing serious side effects.


How should I take Elevat?

  • See the “Instructions for Use” at the end of the Patient Information for detailed instructions about the right way to take Elevat.
  • Always use the oral syringe that comes with your Elevat oral solution to measure your prescribed dose. Ask your doctor or pharmacist to show you how to measure your prescribed dose.
  • Take Elevat exactly as your doctor tells you to. Your doctor may change your dose after seeing how it affects you. Do not change your dose unless your doctor tells you to change it.
  • Drink a full glass of water (6 to 8 ounces) right after you take your prescribed dose of Elevat oral solution.
  • If you are an adult with AIDS with loss of appetite and weight loss:
    • Elevat is usually taken 2 times each day, 1 hour before lunch and 1 hour before dinner. If you are elderly, or unable to tolerate this dose of Elevat, your doctor may prescribe Elevat to be taken 1 time each day, 1 hour before dinner or bedtime.
  • If you are an adult with nausea and vomiting caused by anti-cancer medicine:
    • Elevat is usually taken 1 to 3 hours before your chemotherapy treatment and then every 2 to 4 hours after chemotherapy for up to 4 to 6 doses each day. If you are elderly, your doctor may prescribe Elevat to be taken 1 to 3 hours before your chemotherapy, 1 time each day.
    • Take your first dose of Elevat on an empty stomach at least 30 minutes before eating. After your first dose of Elevat, you can take Elevat with or without food.
    • After your doctor has decided the dose of Elevat that is right for you, take Elevat exactly at the same time before or after meals during future chemotherapy treatment.
  • If you take too much Elevat, call your Poison Control Center at 1-800-222-1222 right away or go to the nearest emergency room.

What should I avoid while taking Elevat?

  • Do not drive, operate machinery, or do other dangerous activities until you know how Elevat affects you. Elevat taken with medicines that cause dizziness, confusion, and sleepiness may make these symptoms worse.

What are the possible side effects of Elevat?

Elevat may cause serious side effects, including:

  • See “What is the most important information I should know about Elevat?”
  • Seizures. Elevat may increase your risk of seizures. Stop taking Elevat and call your doctor and get medical care right away if you have a seizure during treatment with Elevat.
  • Drug and alcohol abuse. You may have an increased risk of abusing Elevat if you have a history of drug or alcohol abuse or dependence, including marijuana. Tell your doctor if you develop abuse behaviors such as increased irritability, nervousness, restlessness or want more or higher doses of Elevat during your treatment.
  • Nausea, vomiting, or stomach-area (abdominal) pain. Tell your doctor if you have nausea, vomiting, or abdominal pain or if your nausea, vomiting, or abdominal pain gets worse during treatment with Elevat.

The most common side effects of Elevat include:

- stomach-area (abdominal) pain - sleepiness
- dizziness - abnormal thoughts
- feeling extremely happy (euphoria) - vomiting
- nausea
- overly suspicious or feeling people want to harm you (paranoid reaction)

These are not all the possible side effects of Elevat. Tell your doctor if you have any side effect that bothers you or does not go away. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


General information about the safe and effective use of Elevat

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Elevat for a condition for which it was not prescribed. Do not give Elevat to other people, even if they have the same symptoms that you have. It may harm them. You can ask your doctor or pharmacist for information about Elevat that is written for health professionals.


What are the ingredients in Elevat?

Active ingredient: Elevat

Inactive ingredients: dehydrated alcohol, polyethylene glycol 400, propylene glycol, sucralose, methyl paraben, propyl paraben, butylated hydroxyanisole, and water


INSTRUCTIONS FOR USE

Elevat (sin dros)

(dronabinol)

oral solution, CII

Read this Instructions for Use before you start taking Elevat oral solution and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

Important information about measuring Elevat oral solution:
  • Always use the oral syringe that comes with your Elevat oral solution to measure your prescribed dose. Ask your doctor or pharmacist to show you how to measure your prescribed dose.
  • Each Elevat carton contains :
    • 1 bottle of Elevat oral solution
    • 1 oral syringe
    • 1 adapter (You will need to insert the adapter into the bottle before using the bottle for the first time.)

    The contents in the Elevat carton are wrapped in plastic. Do not use the contents if they are not wrapped in plastic when you receive them.

Call Insys Therapeutics at 1-855-978-2797 or www.syndros.com if:
  • you do not receive an oral syringe or adapter with your Elevat
  • you lose the oral syringe that comes with Elevat
  • the contents in the Elevat carton are not wrapped in plastic when you receive them

How to prepare a bottle of Elevat oral solution before using for the first time:

Step 1: Remove the plastic wrap from the bottle and throw it away.

Step 2: Open the bottle by pushing down firmly on the child-resistant cap and turning it counter-clockwise. Do not throw away the child-resistant cap.


Step 3: Remove the adapter from the plastic wrap. You may need to use a pair of scissors.

Step 4: Place the open bottle upright on a flat surface. Firmly push down on the adapter until the ribbed end of the adapter fits into the neck of the bottle as far as it will go and is firmly in place. The top edge of the adapter should be in full contact with the top rim of the bottle. Do not remove the adapter from the bottle after it is inserted.

Step 5: Follow the instructions in “How to prepare a dose of Elevat oral solution after the adapter is inserted.”



How to prepare a dose of Elevat oral solution after the adapter is inserted:

Step 1: Open the bottle by pushing down firmly on the child-resistant cap and turning it counter-clockwise. Do not throw away the child-resistant cap.

Step 2: If you are using the oral syringe for the first time, remove the oral syringe from the plastic wrap. You may need to use a pair of scissors.

Step 3: Hold the oral syringe in one hand. With your other hand, fully push down (depress) the plunger.


Step 4: Keeping the bottle in an upright position, insert the syringe tip firmly into the adapter.


Step 5: Carefully turn the bottle upside down with the syringe tip firmly inserted into the adapter.


Step 6: Slowly pull back on the plunger until the measuring ring is at the line marking for the dose prescribed by your doctor. The measuring ring is the widest part of the plunger at the bottom of the tip of plunger. and H(b)). Figure H(a) shows a dose of 0.4 mL as an example.

If you see air bubbles in the oral syringe, fully push in the plunger so that the oral solution flows back into the bottle. Then, withdraw your prescribed dose of oral solution.

If your prescribed dose is more than 1 mL, you will need to draw up two or more doses.

For example, if your dose is 1.2 mL, you will need to draw up a 1 mL dose followed by a 0.2 mL dose.


Step 7: Leave the oral syringe in the adapter and turn the bottle to an upright position. Place the bottle onto a flat surface. Remove the oral syringe from the bottle adapter by gently pulling straight up on the oral syringe.

Step 8: Check that the correct dose of Elevat oral solution was drawn up into the oral syringe. If the dose is not correct, insert the syringe tip firmly into the bottle adapter. Fully push in the plunger so that the oral solution flows back into the bottle.

Repeat Steps 5-8.



Step 9: Open your mouth. Place the oral syringe tip in the back of your mouth on top of your tongue. Tilt your head back slightly and close your lips around the barrel of the oral syringe. Slowly push down the plunger until the oral syringe is empty.

Swallow the oral solution.

If your prescribed dose is more than 1 mL, repeat Steps 4-8 to draw up the remaining dose until the prescribed dose is given. For example, if your prescribed dose is 1.6 mL, take a 1 mL dose first, then an additional dose of 0.6 mL.

Take your Elevat oral solution right away after it is drawn up into the oral syringe.


Step 10: Drink a full glass of water (6 to 8 ounces) right after you take your prescribed dose of Elevat oral solution.

Step 11: Leave the adapter in the bottle. Put the child-resistant cap back on the bottle.

Step 12: Remove the plunger from the oral syringe barrel. Rinse the oral syringe barrel and plunger with warm water after each use and let them air dry. When the oral syringe barrel and plunger are dry, put the plunger back into the oral syringe barrel for the next use. Keep Elevat oral solution and the oral syringe in the carton that it comes in. Do not throw away the oral syringe.

How should I store Elevat?

  • Store Elevat in the refrigerator between 36°F to 46°F (2°C to 8°C).
  • After the bottle is opened, Elevat can be stored at room temperature, between 68°F to 77°F (20°C to 25°C), for up to 28 days.
  • Do not use Elevat that has been stored in the refrigerator or at room temperature 28 days after opening the bottle. Write the date that you open the bottle of Elevat on the bottle and carton it comes in. See “How should I dispose of unused Elevat?”

Keep Elevat and all medicines out of the reach of children.

How should I dispose of unused Elevat?

  • Dispose of unused Elevat as soon as you no longer need it or 28 days after opening the bottle.

Talk to your doctor or pharmacist if you have questions about how to use Elevat oral solution.

For more information, go to www.syndros.com or call 1-855-978-2797.

This Patient Information and Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Renaissance Lakewood, LLC, Lakewood, NJ 08701

Manufactured for:

Insys Therapeutics, Inc., Chandler, AZ 85286

Revised: May 2017

PRINCIPAL DISPLAY PANEL - NDC: 20482-335-30 - 30 mL Bottle Carton Label

PRINCIPAL DISPLAY PANEL - NDC: 20482-335-30 - 30 mL Bottle Container Label

Elevat pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Elevat available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Elevat destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Elevat Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Elevat pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."SYNDROS (DRONABINOL) SOLUTION [INSYS THERAPEUTICS, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."DRONABINOL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "Dronabinol". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Elevat?

Depending on the reaction of the Elevat after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Elevat not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Elevat addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Elevat, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Elevat consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

One visitor reported time for results

What is the time duration Elevat drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed 1 day to notice the result from using Elevat drug. The time needed to show improvement in health condition after using the medicine Elevat need not be same for all the users. It varies based on other factors.
Visitors%
1 day1
100.0%

Visitor reported administration

No survey data has been collected yet

Visitor reported age

No survey data has been collected yet

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The information was verified by Dr. Arunabha Ray, MD Pharmacology

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