SYNDROS (Page 2 of 6)

5.2 Hemodynamic Instability

Patients may experience occasional hypotension, possible hypertension, syncope, or tachycardia while taking SYNDROS [see Clinical Pharmacology (12.2)]. 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 SYNDROS.

5.3 Interaction with Disulfiram and Metronidazole

SYNDROS contains 50% (w/w) dehydrated alcohol and 5.5% (w/w) propylene glycol. Use of SYNDROS 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 SYNDROS and do not administer these products within 7 days of completing treatment with SYNDROS [see Contraindications (4), Drug Interactions (7.3)].

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 SYNDROS is unknown.

5.4 Seizures

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

Weigh this potential risk against the benefits before prescribing SYNDROS 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 SYNDROS therapy.

If a seizure occurs, advise patients to discontinue SYNDROS 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 SYNDROS as well. SYNDROS contains 50% (w/w) dehydrated alcohol.

Assess each patient’s risk for abuse or misuse prior to prescribing SYNDROS and monitor patients with a history of substance abuse during treatment with SYNDROS 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 SYNDROS. 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 or worsening of nausea, vomiting, or abdominal pain while being treated with SYNDROS. Consider dose reduction or discontinuing SYNDROS if a patient develops worsening nausea, vomiting, or abdominal pain while on treatment.

5.7 Toxicity in Preterm Neonates

SYNDROS 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 SYNDROS have not been established in pediatric patients. Avoid SYNDROS 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.

6 ADVERSE REACTIONS

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 [see Warnings and Precautions (5.1)]
  • Hemodynamic Instability [see Warnings and Precautions (5.2)]
  • Seizures [see Warnings and Precautions (5.4)]
  • Paradoxical Nausea, Vomiting, and Abdominal Pain [see Warnings and Precautions (5.6)]
  • Toxicity in Preterm Neonates [see Warnings and Precautions (5.7)]

The safety of SYNDROS has been established based on studies of dronabinol capsules. Studies of AIDS-related weight loss included 157 patients receiving dronabinol capsules and 67 receiving placebo. Studies of nausea and vomiting related to cancer chemotherapy included 317 patients receiving dronabinol capsules and 68 receiving placebo. In the tables below is a summary of the adverse reactions in 474 patients exposed to dronabinol 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 dronabinol 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 dronabinol 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 dronabinol 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 dronabinol capsules at an incidence less than or equal to 1%.

System Organ Class Adverse Reactions
General Chills, headache, malaise
Cardiovascular Hypotension, conjunctival injection [see Clinical Pharmacology (12.2)]
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

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