雷美替胺(Ramelteon)的副作用如何缓解

Ramelteon may cause side effects during medication, and you need to inform your doctor in time for treatment.

Ramelteon (Ramelteon) side effects

1. Common adverse reactions (≥3%)

Drowsiness (3%), fatigue (3%), dizziness (4%), nausea (3%), aggravation of insomnia (3%), etc. Most of these reactions are mild to moderate and usually lessen as the medication time is extended.

2. Severe allergic reactions

Including angioedema (edema of tongue, throat, larynx), dyspnea, nausea and vomiting and other allergic-like reactions. Once it occurs, you need to seek medical attention immediately and must not use it again.

3. Complex sleep behaviors

Such as "sleep driving" (driving while not fully awake after taking medication), preparing and eating food, making phone calls, having sex, etc., which cannot be recalled afterwards. If such behavior occurs, medication should be discontinued immediately.

4. Neuropsychiatric symptoms

Including hallucinations, agitation, anxiety, worsening of depression, suicidal ideation, etc., especially among high-risk groups, which require close monitoring.

5. Endocrine effects

Long-term use can lead to a decrease in testosterone levels and an increase in prolactin levels. Clinical manifestations include female menstrual disorders, non-lactation lactation, loss of sexual desire, fertility problems, etc.

The pictures are from public channels (such as the official website of the FDA, the official website of the original drug manufacturer, etc.) and are for reference only.

Methods to alleviate side effects of Ramelteon

1. Dose adjustment

If the adverse reactions are intolerable, discontinuation of the drug should be considered.

2. Symptomatic support

(1) Dizziness, drowsiness: Avoid driving, operating machinery and other activities until symptoms subside.

(2) Nausea: Drink water in batches, avoid greasy food, and consult a doctor to use antiemetics if necessary.

3. Behavior monitoring

Patients and family members should closely observe whether complex sleep behaviors or mental symptoms occur, and seek medical treatment immediately if they occur.

4. Anaphylaxis

Stop medication immediately and seek emergency medical help.

5. Abnormal liver function

Patients with moderate to severe liver damage should avoid use, and patients with mild symptoms should be carefully monitored.

6. Drug interaction management

(1) Absolutely contraindicated combination: fluvoxamine (strong CYP1A2 inhibitor), as it can increase the plasma concentration of ramelteon by about 190 times.

(2). Use with caution:

Strong CYP inducers (such as rifampicin): may significantly reduce the efficacy.

Pharmacokinetics of Ramelteon

1. Absorption

It is rapidly absorbed after oral administration, with a peak time (Tmax) of approximately 0.75 hours (range 0.5-1.5 hours).

The absolute oral bioavailability is low (about 1.8%), due to significant first-pass effect.

2. Distribution

The protein binding rate is about 82%, mainly binding to albumin.

The apparent volume of distribution (Vd) is 73.6L, indicating widespread tissue distribution.

3. Metabolism

Mainly metabolized by the liver, hydroxyl and carbonyl derivatives are generated through oxidation (dominated by CYP1A2, minor participation by CYP2C and CYP3A4), and then glucuronic acid conjugates are formed.

The main active metabolite is M-II, its systemic exposure is 20-100 times that of the parent drug, and its affinity for MT₁/MT₂ receptors is 1/10 and 1/5 of the parent drug respectively.

4. Excretion

After oral administration, 84% is excreted in urine and 4% is excreted in feces.

The average elimination half-life of parent drug is 1-2.6 hours, and that of M-II is 2-5 hours.