Side Effects of Marinol (dronabinol)

Marinol (dronabinol) is a man-made compound that contains cannabinoids found in the marijuana plant (Cannabis sativa L). 

Marinol contains tetrahydrocannabinol (THC) in standardized concentrations and does not contain other compounds found in street marijuana that is not approved by the FDA for medical use. 

The man-made compound is a drug prescribed to prevent nausea and vomiting associated with cancer chemotherapy in patients who have not responded to standard drugs to manage nausea and vomiting. It is also prescribed to improve the appetite in patients with AIDs who have problems maintaining weight.

Marinol activates cannabinoid receptors causing a wide range of effects in the brain, including short-term memory loss, euphoria, enhanced sensation, and increased appetite. It also prevents nausea and vomiting probably by inhibiting the vomiting center in the brain. 

Common side effects of Marinol include

• weakness,
• palpitations,
• rapid heartbeat,
• facial flushing,
• abdominal pain,
• nausea,
• vomiting,
• anxiety,
• nervousness,
• confusion,
• depersonalization,
• dizziness,
• euphoria,
• hallucinations,
• paranoid reaction, and
• abnormal thinking.

Less common side effects of Marinol include

• low blood pressure,
• eye problems,
• diarrhea,
• fecal incontinence,
• muscle pain,
• depression,
• nightmares,
• speech problems,
• ringing in the ears (tinnitus), and
• flushing.

Marinol is a controlled substance because it may be abused.

Although no drug-drug interactions were identified during clinical trials conducted by the manufacturer, Marinol should be used cautiously with other medications that are known to interact with cannabinoids.

People taking Marinol should not drink alcohol, smoke marijuana, take sedatives and hypnotics, or take other medicines that have an effect on the central nervous system such as

• diazepam,
• chlordiazepoxide,
• alprazolam,
• secobarbital,
• pentobarbital, and
• phenobarbital.  

There are no adequate and well-controlled studies evaluating the use of Marinol during pregnancy. Marinol should only be used during pregnancy if the potential benefit to the mother justifies the potential risk to the unborn baby. 

Marinol is not recommended for use during breastfeeding because it is excreted into breast milk and may have harmful effects on the nursing infant.

The most common side effects of dronabinol include

• weakness,
• palpitations,
• rapid heartbeat,
• facial flushing,
• abdominal pain,
• nausea,
• vomiting,
• anxiety,
• nervousness,
•  confusion,
• depersonalization,
• dizziness,
• euphoria,
• hallucinations,
• paranoid reaction, and
• abnormal thinking.

Less common side effects include

• low blood pressure,
• eye problems,
• diarrhea,
• fecal incontinence,
• muscle pain,
• depression,
• nightmares,
• speech problems,
• ringing in the ears (tinnitus), and
• flushing.

Dronabinol is a controlled substance because it may be abused.

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

Studies of AIDS-related weight loss included 157 patients receiving Marinol at a dose of 2.5 mg twice daily and 67 receiving placebo. Studies of nausea and vomiting related to cancer chemotherapy included 317 patients receiving Marinol and 68 receiving placebo. In the tables below is a summary of the adverse reactions in 474 patients exposed to Marinol in studies.

• Studies of different durations were combined by considering the first occurrence of events during the first 28 days.
• A cannabinoid dose-related “high” (easy laughing, elation and heightened awareness) has been reported by patients receiving Marinol 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 Marinol.
• 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 at an incidence greater than 1%.

Less Common Adverse Reactions

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

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of dronabinol capsules. 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

Additive CNS Effects

• Additive CNS effects (e.g., dizziness, confusion, sedation, somnolence) may occur when Marinol is taken concomitantly with drugs that have similar effects on the central nervous system such as CNS depressants.

Additive Cardiac Effects

• Additive cardiac effects (e.g., hypotension, hypertension, syncope, tachycardia) may occur when Marinol is taken concomitantly with drugs that have similar effects on the cardiovascular system.

Effect Of Other Drugs On Dronabinol

• Dronabinol is primarily metabolized by CYP2C9 and CYP3A4 enzymes based on published in vitro studies.
• Inhibitors of these enzymes may increase, while inducers may decrease, the systemic exposure of dronabinol and/or its active metabolite resulting in an increase in dronabinol-related adverse reactions or loss of efficacy of Marinol.
• Monitor for potentially increased dronabinol-related adverse reactions when Marinol is co-administered with inhibitors of CYP2C9 (e.g., amiodarone, fluconazole) and inhibitors of CYP3A4 enzymes (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, erythromycin, grapefruit juice).

Highly Protein-Bound Drugs

• Dronabinol 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 that are highly protein-bound (e.g., warfarin, cyclosporine, amphotericin B) when initiating treatment or increasing the dosage of Marinol.

Drug Abuse And Dependence

Controlled Substance

• Marinol contains dronabinol capsules, a Schedule III controlled substance.

Abuse

• Marinol contains dronabinol, the main psychoactive component in marijuana. Ingestion of high doses of dronabinol 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 an open-label study in patients with AIDS who received Marinol for up to five months, no abuse, diversion or systematic change in personality or social functioning were observed despite the inclusion of a substantial number of patients with a past history of drug abuse.
• Patients should be instructed to keep Marinol in a secure place out of reach of others for whom the medication has not been prescribed.

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 Marinol, and develops after chronic abuse of marijuana.
• A withdrawal syndrome was reported after the abrupt discontinuation of dronabinol 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 dronabinol.