Meladura (Melatonin 2 mg Prolonged-Release)

What Is Meladura and What Is It Used For?

Meladura is a prolonged-release melatonin tablet (2 mg) used to treat primary insomnia in adults aged 55 years and older. It works by supplementing the body's naturally declining melatonin levels, helping regulate the circadian rhythm and improving sleep quality without the risks associated with traditional hypnotic medications.

Melatonin is a hormone produced by the pineal gland in the brain. Its production is triggered by darkness and suppressed by light, creating a natural internal clock that signals to the body when it is time to sleep. In healthy young adults, melatonin levels begin to rise in the evening, peak during the middle of the night, and fall to very low levels during the day. This rhythmic pattern is essential for maintaining a healthy sleep-wake cycle.

As people age, the pineal gland produces progressively less melatonin. By the age of 55, many individuals produce significantly less melatonin than they did in their younger years. This decline in melatonin production is considered one of the key factors contributing to the increased prevalence of insomnia among older adults. Studies have shown that reduced melatonin secretion correlates with poorer sleep quality, longer sleep onset latency, and more frequent nighttime awakenings.

Meladura addresses this age-related decline by providing exogenous melatonin in a prolonged-release formulation. Unlike immediate-release melatonin supplements, the prolonged-release design of Meladura gradually releases melatonin over several hours, mimicking the natural physiological profile of endogenous melatonin secretion. This sustained release helps not only with falling asleep but also with maintaining sleep throughout the night.

The European Medicines Agency (EMA) has approved prolonged-release melatonin 2 mg as monotherapy for the short-term treatment of primary insomnia characterized by poor quality of sleep in patients aged 55 years and over. Primary insomnia means that the sleep difficulties are not caused by another medical condition, medication, or substance. It is important to distinguish primary insomnia from secondary insomnia, which results from conditions such as depression, chronic pain, sleep apnea, or medication side effects.

How does Meladura work in the body?

Meladura works by binding to melatonin receptors, specifically the MT1 and MT2 receptors located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN is often called the body's "master clock" because it coordinates circadian rhythms throughout the body. When melatonin binds to MT1 receptors, it promotes sleepiness and reduces alertness. When it binds to MT2 receptors, it helps shift the timing of the circadian clock, reinforcing the natural sleep-wake pattern.

The prolonged-release formulation ensures that melatonin is released gradually over approximately 8 to 10 hours after ingestion. This mimics the natural nocturnal melatonin curve and helps maintain sleep throughout the night. Clinical trials have demonstrated that prolonged-release melatonin 2 mg significantly improves sleep quality, reduces sleep onset latency, and improves morning alertness compared to placebo, without impairing psychomotor function or causing next-day hangover effects.

What conditions does Meladura treat?

Meladura is specifically indicated for primary insomnia in adults aged 55 and over. However, melatonin-based treatments have also been studied in the context of several other conditions, including circadian rhythm sleep disorders, jet lag, shift work sleep disorder, and insomnia associated with neurodevelopmental conditions in children (though different formulations and doses are used for paediatric patients). The 2 mg prolonged-release formulation of Meladura is approved only for adult primary insomnia and should not be used for other indications without medical supervision.

What Should You Know Before Taking Meladura?

Before taking Meladura, inform your doctor about all existing medical conditions, particularly liver disease, autoimmune disorders, or if you are pregnant or breastfeeding. Meladura is not recommended for individuals under 55 years of age, and several drug interactions should be considered.

While melatonin is generally regarded as a well-tolerated medication with a favourable safety profile, there are important considerations that patients and healthcare providers should be aware of before initiating treatment with Meladura. A thorough medical history and review of current medications is essential to ensure safe and effective use.

Contraindications

Meladura should not be taken by individuals who have a known hypersensitivity (allergy) to melatonin or any of the excipients in the tablet formulation. While true allergic reactions to melatonin are rare, they can occur and may manifest as skin rash, itching, or in very rare cases, anaphylactic reactions. If you have previously experienced an allergic reaction to any melatonin product, you should not take Meladura.

Meladura is not recommended for use in children and adolescents under 18 years of age. Although melatonin is sometimes prescribed off-label for sleep disturbances in children, particularly those with autism spectrum disorder or attention deficit hyperactivity disorder (ADHD), different formulations and dosing regimens are used in these populations. The 2 mg prolonged-release tablet is specifically designed for adults aged 55 and over.

Warnings and Precautions

Patients with hepatic (liver) impairment should use Meladura with caution. Melatonin is extensively metabolised in the liver, primarily through the cytochrome P450 enzyme CYP1A2. Patients with liver disease may have significantly elevated melatonin plasma levels due to reduced hepatic clearance, which could lead to excessive sedation or other adverse effects. Meladura is not recommended for patients with severe hepatic impairment.

Individuals with autoimmune disorders should consult their doctor before taking Meladura. Melatonin has immunomodulatory properties and may theoretically stimulate immune function. While clinical evidence of harmful effects in autoimmune conditions is limited, caution is advised in patients with conditions such as rheumatoid arthritis, systemic lupus erythematosus, or multiple sclerosis.

Meladura may cause drowsiness. Patients should avoid driving or operating heavy machinery if they feel drowsy after taking the medication. The drowsiness is typically most pronounced in the first few hours after ingestion and generally subsides by morning. However, individual sensitivity varies, and patients should assess their own response before engaging in activities requiring full alertness.

Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take Meladura, as the tablet formulation contains lactose.

Pregnancy and Breastfeeding

Meladura is not recommended during pregnancy. There is insufficient data on the use of melatonin in pregnant women, and as melatonin is a hormone that crosses the placenta, potential effects on foetal development cannot be excluded. Women of childbearing age should use effective contraception while taking Meladura.

Melatonin is naturally present in breast milk, and exogenous melatonin from Meladura may increase melatonin levels in breast milk. The effects of elevated melatonin exposure on nursing infants are not well established. Therefore, breastfeeding is not recommended during treatment with Meladura. If treatment is essential, the physician and patient should weigh the benefits of treatment against the potential risks to the infant.

How Does Meladura Interact with Other Drugs?

Meladura interacts primarily with CYP1A2 inhibitors (such as fluvoxamine and ciprofloxacin), which can dramatically increase melatonin blood levels. CYP1A2 inducers (such as carbamazepine and rifampicin) reduce its effectiveness. Concurrent use with other sedatives may enhance drowsiness.

Drug interactions with Meladura are primarily related to the metabolism of melatonin through the CYP1A2 enzyme system in the liver. Understanding these interactions is critical because some can lead to dramatically increased melatonin levels (causing excessive sedation) while others can render the treatment ineffective by accelerating melatonin breakdown.

Melatonin is metabolised primarily by CYP1A2, with minor contributions from CYP2C19. Any substance that inhibits or induces CYP1A2 can significantly alter the pharmacokinetics of melatonin. Additionally, melatonin has mild sedative properties that can be additive with other central nervous system (CNS) depressants.

Major Interactions

Fluvoxamine is the most clinically significant interaction with Meladura. Fluvoxamine is a potent CYP1A2 inhibitor and a selective serotonin reuptake inhibitor (SSRI) used to treat obsessive-compulsive disorder and depression. Co-administration with Meladura can increase melatonin plasma levels by up to 17-fold, leading to excessive sedation, dizziness, and impaired cognitive function. This combination should be avoided.

Ciprofloxacin, a widely used fluoroquinolone antibiotic, is a moderate CYP1A2 inhibitor. Taking ciprofloxacin with Meladura can significantly increase melatonin levels. If concomitant use is unavoidable, patients should be monitored for signs of excessive sedation and the melatonin dose may need to be reduced or temporarily discontinued during the antibiotic course.

Minor Interactions

Smoking (tobacco) is an important factor to consider. Cigarette smoking induces CYP1A2 activity, which can accelerate the metabolism of melatonin and reduce its plasma levels. Patients who smoke may experience reduced effectiveness of Meladura. Conversely, patients who stop smoking during treatment may notice increased melatonin effects as CYP1A2 activity normalises.

Caffeine is also metabolised by CYP1A2 and may compete with melatonin for metabolism. While the clinical significance of this interaction is generally minor, consuming large amounts of caffeine in the evening may both directly interfere with sleep and modestly alter melatonin metabolism. Patients taking Meladura should limit caffeine intake, particularly in the afternoon and evening.

Oestrogen-containing medicines, such as oral contraceptives or hormone replacement therapy, can inhibit CYP1A2 and increase melatonin plasma levels. While this interaction is usually modest, patients on oestrogen therapy should be aware of the potential for increased sedation when starting Meladura.

What Is the Correct Dosage of Meladura?

The recommended dose of Meladura is one 2 mg tablet taken once daily, 1 to 2 hours before bedtime, after food. The tablet must be swallowed whole. The recommended treatment duration is up to 13 weeks, with the possibility of extension under medical supervision.

Correct dosing of Meladura is essential for achieving optimal therapeutic benefit. The prolonged-release formulation has specific administration requirements that must be followed to ensure the medication works as intended. The timing, relationship to food intake, and method of administration all play important roles in the drug's efficacy.

Adults (55 years and over)

The importance of taking Meladura after food cannot be overstated. Food intake affects the pharmacokinetic profile of the medication by slowing gastric emptying and extending the absorption phase. This results in a more gradual release of melatonin into the bloodstream, which more closely mimics the natural endogenous melatonin profile. Taking Meladura on an empty stomach may lead to faster absorption and a less sustained effect.

Similarly, the prolonged-release mechanism of the tablet is critical to its therapeutic effect. If the tablet is crushed or chewed, the entire 2 mg dose of melatonin will be released immediately rather than gradually over several hours. This can result in a brief spike in melatonin levels followed by a rapid decline, which does not provide the sustained sleep-promoting effect intended by the formulation.

Children

Meladura 2 mg prolonged-release tablets are not indicated for use in children and adolescents under 18 years of age. The safety and efficacy of this formulation have not been established in paediatric populations. For children with sleep disorders, particularly those associated with autism spectrum disorder or ADHD, different melatonin formulations at different doses may be considered by a specialist, but this is outside the scope of Meladura's approved indication.

Elderly (over 75 years)

No dose adjustment is generally required for elderly patients over 75 years. However, as hepatic function may decline with advancing age, plasma levels of melatonin may be higher than expected. Physicians should monitor elderly patients for signs of excessive sedation and consider the overall medication burden, as older patients are more likely to be taking multiple medications that could interact with Meladura.

Renal and Hepatic Impairment

There is limited data on the use of Meladura in patients with renal impairment, but dose adjustment is generally not considered necessary because melatonin is primarily metabolised in the liver. However, in patients with hepatic impairment, melatonin clearance is significantly reduced. Meladura is not recommended for patients with severe hepatic impairment. For patients with mild to moderate hepatic impairment, caution should be exercised and the patient should be monitored for adverse effects.

Missed Dose

If you forget to take Meladura at the usual time, skip the missed dose and take the next dose at the regular time the following evening. Do not take a double dose to make up for the forgotten dose. Taking melatonin too late in the night or early in the morning can disrupt the circadian rhythm and cause daytime drowsiness, so it is important to only take the tablet within the recommended 1 to 2 hours before bedtime window.

Overdose

Melatonin has a wide safety margin, and serious adverse effects from overdose are unlikely. In clinical studies and post-marketing surveillance, doses of up to 300 mg of melatonin have been administered without causing significant life-threatening effects. However, excessive doses may cause pronounced drowsiness, headache, dizziness, nausea, and hypothermia. If an overdose is suspected, supportive care should be provided. There is no specific antidote for melatonin overdose. Contact your local poison control centre or emergency department if you have taken significantly more than the prescribed dose.

What Are the Side Effects of Meladura?

Meladura is generally well tolerated. The most commonly reported side effects include headache, nasopharyngitis (cold symptoms), back pain, and arthralgia (joint pain). Serious side effects are rare. Unlike benzodiazepines, Meladura does not cause dependence, tolerance, or significant rebound insomnia.

The safety profile of prolonged-release melatonin 2 mg has been well-characterised through multiple clinical trials and extensive post-marketing surveillance. Overall, the adverse event profile is favourable, with most side effects being mild and transient. The following frequency classifications are based on data from randomised controlled trials and post-marketing reports.

In clinical trials comparing prolonged-release melatonin 2 mg with placebo, the overall incidence of adverse events was similar between the treatment and placebo groups, suggesting that many of the reported side effects may not be directly caused by the medication. Nevertheless, patients should be aware of the potential side effects and report any concerning symptoms to their healthcare provider.

Long-term safety

One of the most important advantages of Meladura over traditional hypnotic medications is its favourable long-term safety profile. Clinical studies lasting up to 6 months and post-marketing data covering several years of use have not revealed any evidence of tolerance (needing higher doses to achieve the same effect), physical dependence, or withdrawal symptoms upon discontinuation.

In contrast, benzodiazepine and Z-drug hypnotics (such as zolpidem and zopiclone) are associated with tolerance, dependence, rebound insomnia, cognitive impairment, and an increased risk of falls in elderly patients. The European Sleep Research Society and the British Association for Psychopharmacology have both highlighted prolonged-release melatonin as a preferred first-line option for insomnia in older adults, particularly given the risks associated with benzodiazepine and Z-drug use in this population.

Rebound insomnia, a worsening of sleep difficulties that occurs when a sleeping medication is suddenly stopped, has not been observed with Meladura in clinical trials. This is a significant clinical advantage, as rebound insomnia is a common problem with conventional hypnotics and often leads patients to continue taking these medications longer than recommended.

How Should You Store Meladura?

Store Meladura at room temperature below 25°C (77°F), in its original packaging to protect from light. Keep out of the sight and reach of children. Do not use after the expiry date printed on the package.

Proper storage of Meladura is essential to maintain the quality and effectiveness of the medication throughout its shelf life. Melatonin can degrade when exposed to excessive heat, moisture, or light, which may reduce the potency of the active ingredient and compromise the prolonged-release mechanism of the tablet.

The recommended storage conditions are as follows:

• Temperature: Store below 25°C (77°F). Do not refrigerate or freeze.
• Light: Keep the tablets in their original blister packaging until use to protect from light exposure.
• Moisture: Store in a dry place. Do not store in the bathroom or other humid environments.
• Children: Keep out of the sight and reach of children.
• Expiry: Do not use Meladura after the expiry date stated on the carton and blister. The expiry date refers to the last day of that month.

Do not throw away medications via wastewater or household waste. Ask your pharmacist how to dispose of medications you no longer use. These measures help to protect the environment and prevent accidental ingestion by children or pets.

What Does Meladura Contain?

Each Meladura prolonged-release tablet contains 2 mg of melatonin as the active substance. The tablets also contain excipients including ammonio methacrylate copolymer, calcium hydrogen phosphate dihydrate, lactose monohydrate, silica, talc, and magnesium stearate.

Understanding the composition of Meladura is important for patients who may have allergies or intolerances to specific excipients. The following is a breakdown of the active and inactive ingredients in the formulation.

Active ingredient

Each prolonged-release tablet contains 2 mg of melatonin. Melatonin (chemical name: N-acetyl-5-methoxytryptamine) is a synthetic form of the naturally occurring hormone produced by the pineal gland. The synthetic melatonin used in Meladura is chemically identical to endogenous human melatonin.

Inactive ingredients (excipients)

The excipients in Meladura serve various functions in the tablet formulation, including controlling the rate of drug release, providing structural integrity, and ensuring consistent manufacturing quality. Common excipients include:

• Ammonio methacrylate copolymer (Type B): A polymer used to control the prolonged-release mechanism of the tablet
• Calcium hydrogen phosphate dihydrate: A filler that provides bulk to the tablet
• Lactose monohydrate: A sugar used as a filler (patients with lactose intolerance should be aware of this ingredient)
• Colloidal anhydrous silica: A flow agent that ensures uniform mixing of ingredients
• Talc: A lubricant used in the manufacturing process
• Magnesium stearate: A lubricant that prevents the tablet from sticking to manufacturing equipment

Frequently Asked Questions about Meladura