Side Effects of Rozerem (ramelteon)

Rozerem is a hypnotic sedative that treats insomnia by stimulating melatonin receptors in the brain.

Melatonin and its receptors control the body’s circadian rhythm, which regulates the sleep/wake cycle. Unlike other insomnia medications, Rozerem is non-addictive and not a controlled substance. It also does not cause withdrawal or rebound insomnia upon discontinuation.

Common side effects of Rozerem include:

Serious side effects of Rozerem include:

• Abnormal thinking
• Behavior changes
• Depression
• Suicidal thoughts
• Manic episodes
• Sleep-driving
• Rare severe allergic reactions involving tongue swelling and throat closure

Rozerem may interact with doxepin, donepezil, fluvoxamine, ketoconazole, and fluconazole, which can increase side effects. Rifampin may decrease Rozerem’s effectiveness.

Alcohol can enhance the sedative effects of Rozerem.

Rozerem has not been evaluated in pregnant or nursing women. Consult your doctor if you are pregnant or breastfeeding.

Important Side Effects of Rozerem (ramelteon)

Side effects of ramelteon include:

Rare cases of severe allergic reactions involving tongue swelling and throat closure have been reported.

Other important side effects include:

• Abnormal thinking
• Behavior changes
• Depression
• Suicidal thoughts
• Manic episodes
• Sleep driving

Rozerem (ramelteon) Side Effects for Healthcare Professionals

The following serious adverse reactions are discussed in detail in other sections:

• Severe anaphylactic and anaphylactoid reactions
• Abnormal thinking, behavior changes, and complex behaviors
• CNS effects

Clinical Trials Experience

Adverse Reactions Resulting in Discontinuation of Treatment

Data from 5373 subjects, including 722 exposed for six months or longer, and 448 subjects for one year, showed that 6% of those exposed to Rozerem discontinued treatment due to adverse events, compared to 2% in the placebo group. The most common reasons for discontinuation were somnolence, dizziness, nausea, fatigue, headache, and insomnia, each occurring in 1% or less of patients.

Most Commonly Observed Adverse Events with Rozerem

Table 1 shows the incidence of adverse events reported by 2861 chronic insomnia patients in placebo-controlled trials of Rozerem. It is important to note that rates observed in clinical trials may not directly reflect rates in practice.

Table 1. Incidence (% of subjects) of Treatment-Emergent Adverse Events

Drug Interactions with Rozerem (ramelteon)

Effects of Other Drugs on Rozerem

Fluvoxamine (Strong CYP1A2 Inhibitor)

When administered with fluvoxamine, Rozerem’s AUC0-inf increased approximately 190-fold, and the Cmax increased approximately 70-fold. Therefore, Rozerem should not be combined with fluvoxamine. Caution is advised when using Rozerem with weaker CYP1A2 inhibitors.

Rifampin (Strong CYP Enzyme Inducer)

Multiple doses of rifampin resulted in an approximately 80% decrease in total exposure to ramelteon and its metabolite M-II. Efficacy may be reduced when Rozerem is used with strong CYP enzyme inducers like rifampin.

Ketoconazole (Strong CYP3A4 Inhibitor)

Coadministration of ketoconazole with Rozerem increased AUC0-inf by approximately 84% and Cmax by approximately 36%. Caution is advised when using Rozerem with strong CYP3A4 inhibitors such as ketoconazole.

Fluconazole (Strong CYP2C9 Inhibitor)

Ramelteon’s AUC0-inf and Cmax increased by approximately 150% when coadministered with fluconazole. Caution is advised when using Rozerem with strong CYP2C9 inhibitors like fluconazole.

Donepezil

When coadministered with donepezil, ramelteon’s AUC0-inf and Cmax increased by approximately 100% and 87%, respectively. Close monitoring is recommended when using Rozerem with donepezil.

Doxepin

When coadministered with doxepin, ramelteon’s AUC0-inf and Cmax increased by approximately 66% and 69%, respectively. Close monitoring is recommended when using Rozerem with doxepin.

Effect of Alcohol on Rozerem

Alcohol impairs performance and causes sleepiness. Since Rozerem’s intended effect is to promote sleep, patients should avoid consuming alcohol while using Rozerem. Combining the two may amplify their effects.

Drug/Laboratory Test Interactions

Rozerem is not known to interfere with commonly used clinical laboratory tests. In addition, in vitro data shows that ramelteon does not cause false-positive results in urine drug screening tests for benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines.

Does Rozerem (ramelteon) cause addiction or withdrawal symptoms?

Drug Abuse and Dependence

Rozerem is not a controlled substance and does not produce physical dependence. Discontinuation of ramelteon in animal and human studies did not result in withdrawal signs. Laboratory studies on abuse potential also showed no rewarding effects.

Human Data

A laboratory study on abuse potential found no signals indicating rewarding effects of Rozerem.

Animal Data

Animal behavioral studies in monkeys and rats did not demonstrate self-administration or conditioned place preference for ramelteon. Ramelteon did not impair motor function or potentiate the effects of diazepam on motor performance.

Summary

Rozerem is a hypnotic sedative that treats insomnia by stimulating melatonin receptors in the brain. Common side effects include headache, drowsiness, fatigue, dizziness, nausea, worsening of insomnia, and diarrhea. Rozerem should not be used in pregnant women unless necessary, and its use has not been evaluated in nursing mothers. Consult your doctor if you are pregnant or breastfeeding.