Arlevert: Uses, Dosage & Side Effects

What Is Arlevert and What Is It Used For?

Arlevert contains two well-established active substances that have been used individually in the treatment of vertigo and vestibular disorders for decades. By combining cinnarizine and dimenhydrinate in a single fixed-dose tablet, Arlevert provides a dual-action approach to vertigo treatment that has been shown in clinical studies to be more effective than either component administered alone. This synergistic combination allows for lower doses of each individual ingredient compared to their standard monotherapy doses, which contributes to a more favorable side effect profile while maintaining or enhancing therapeutic efficacy.

Vertigo is a specific type of dizziness characterized by a false sensation of movement, most commonly a spinning sensation, that occurs when there is a mismatch between the information received by the brain from the vestibular system (inner ear), the visual system, and proprioceptive inputs (body position sensors). It can be caused by disorders affecting the peripheral vestibular apparatus (the inner ear and vestibular nerve), the central vestibular pathways (brainstem and cerebellum), or a combination of both. Common conditions that cause vertigo include benign paroxysmal positional vertigo (BPPV), Ménière's disease, vestibular neuritis, labyrinthitis, and central vestibular syndromes. Vertigo can be severely debilitating, affecting daily activities, work, and quality of life, and is often accompanied by nausea, vomiting, unsteadiness, and anxiety.

The first active ingredient in Arlevert, cinnarizine, is a piperazine derivative that acts as a selective calcium channel blocker with antihistaminic (H1) properties. In the context of vestibular function, cinnarizine exerts its primary therapeutic effect by blocking voltage-gated calcium channels in the vestibular labyrinth. When vestibular hair cells and associated neurons are depolarized (as occurs during abnormal vestibular stimulation in vertigo), calcium ions flow into these cells through voltage-gated channels, amplifying the abnormal vestibular signal. Cinnarizine reduces this calcium influx, thereby dampening the excessive vestibular stimulation that generates the sensation of vertigo. Additionally, cinnarizine has a mild vasodilatory effect on cerebral and labyrinthine blood vessels, which may contribute to improved blood flow to the inner ear and vestibular structures. Its antihistaminic properties further contribute to suppression of vestibular activity, as histamine H1 receptors are involved in vestibular signal transmission.

The second active ingredient, dimenhydrinate, is an ethanolamine antihistamine that consists of a combination of diphenhydramine and 8-chlorotheophylline in equimolar proportions. Dimenhydrinate exerts its antivertigo effects through two primary mechanisms. First, as an H1-antihistamine, it blocks histamine receptors in the vestibular nuclei of the brainstem, where histaminergic neurons play a key role in processing vestibular information and mediating the vestibulo-ocular reflex and vestibulospinal responses. By reducing histaminergic transmission in these nuclei, dimenhydrinate suppresses the central processing of abnormal vestibular signals. Second, dimenhydrinate has significant anticholinergic (antimuscarinic) properties, blocking muscarinic acetylcholine receptors that are abundantly expressed in the vestibular nuclei, the vomiting center, and the chemoreceptor trigger zone. This anticholinergic action is particularly important for controlling the nausea and vomiting that frequently accompany vertigo.

The rationale for combining cinnarizine and dimenhydrinate in Arlevert is based on the principle that vertigo involves multiple neurotransmitter systems and anatomical levels of the vestibular pathway. Cinnarizine acts primarily at the peripheral level (vestibular labyrinth) by blocking calcium channels, while dimenhydrinate acts primarily at the central level (vestibular nuclei in the brainstem) through antihistaminic and anticholinergic mechanisms. This complementary, dual-level approach results in a more comprehensive suppression of vertigo than can be achieved by targeting only one level or one neurotransmitter system. Clinical evidence supports this concept: in randomized controlled trials, the fixed-dose combination of cinnarizine 20 mg and dimenhydrinate 40 mg has been shown to produce significantly greater reductions in vertigo severity, frequency, and duration compared with cinnarizine 20 mg alone, dimenhydrinate 40 mg alone, or placebo.

A landmark randomized, double-blind, controlled trial by Schremmer et al. compared the fixed-dose combination (cinnarizine 20 mg / dimenhydrinate 40 mg) with cinnarizine 20 mg alone, dimenhydrinate 40 mg alone, and placebo in patients with vertigo of peripheral, central, or mixed origin. The primary endpoint was the mean vertigo score (MVS), a composite measure of vertigo frequency, intensity, and duration. After 4 weeks of treatment, the combination group showed a significantly greater reduction in MVS compared with all other groups, confirming the synergistic effect of the two components. Additional studies have demonstrated that the combination is at least as effective as higher-dose betahistine (a commonly used antivertigo drug) in reducing vertigo symptoms, with comparable or superior tolerability.

What Should You Know Before Taking Arlevert?

Contraindications

Arlevert must not be taken in the following situations, as the risks significantly outweigh any potential therapeutic benefit:

• Hypersensitivity: Do not use Arlevert if you are allergic to cinnarizine, dimenhydrinate, diphenhydramine, 8-chlorotheophylline, or any of the other inactive ingredients in the tablet. Allergic reactions can range from skin rash and itching to more severe reactions including angioedema and anaphylaxis.
• Porphyria: Arlevert is contraindicated in patients with any form of porphyria (a group of metabolic disorders affecting heme synthesis). Dimenhydrinate may trigger or exacerbate acute porphyric attacks, which can be life-threatening.
• Prostatic hypertrophy with residual urine: The anticholinergic properties of dimenhydrinate can worsen urinary retention in men with benign prostatic hyperplasia who already have difficulty emptying the bladder completely. This can lead to acute urinary retention, a medical emergency.
• Narrow-angle glaucoma: The anticholinergic effects of dimenhydrinate can increase intraocular pressure by causing pupil dilation (mydriasis) and impeding aqueous humor drainage, which can precipitate an acute angle-closure glaucoma attack.
• Epilepsy: Dimenhydrinate may lower the seizure threshold, potentially increasing the risk and frequency of seizures in patients with epilepsy or a history of seizures.
• Concurrent MAO inhibitor use: Monoamine oxidase (MAO) inhibitors can intensify and prolong the anticholinergic and central nervous system depressant effects of dimenhydrinate, potentially leading to dangerous interactions including severe hypotension, excessive sedation, and serotonergic effects.

Warnings and Precautions

Before starting Arlevert, discuss the following conditions with your healthcare provider, as special precautions or dose adjustments may be necessary:

• Liver disease: Both cinnarizine and dimenhydrinate are metabolized in the liver. Patients with significant hepatic impairment may experience slower drug clearance and increased drug exposure, potentially leading to enhanced side effects. Dose reduction or more careful monitoring may be required.
• Kidney disease: While renal impairment is less likely to significantly affect the clearance of these medications (as they are primarily hepatically metabolized), patients with severe kidney disease should be monitored, as metabolites may accumulate.
• Cardiovascular disease: Cinnarizine has mild calcium channel-blocking and vasodilatory effects that could theoretically affect blood pressure or cardiac conduction in susceptible individuals. Patients with significant cardiovascular conditions should be monitored during treatment.
• Parkinson's disease or extrapyramidal disorders: Cinnarizine has been associated with rare cases of drug-induced parkinsonism, particularly with prolonged use and in elderly patients. If you have Parkinson's disease or are at risk for extrapyramidal symptoms, Arlevert should be used with caution and under close medical supervision.
• Depression: Cinnarizine has been rarely reported to cause or worsen depressive symptoms, particularly during long-term use. Inform your doctor if you have a history of depression.
• Asthma or chronic respiratory conditions: The anticholinergic properties of dimenhydrinate can potentially thicken bronchial secretions. Patients with asthma or chronic obstructive pulmonary disease (COPD) should use Arlevert with caution.
• Gastrointestinal obstruction or stenosis: The anticholinergic effects of dimenhydrinate can reduce gastrointestinal motility, which may be problematic in patients with existing gastrointestinal obstructive conditions.

Pregnancy and Breastfeeding

Arlevert is not recommended for use during pregnancy. There are insufficient clinical data on the safety of the cinnarizine/dimenhydrinate combination in pregnant women. Although individual animal studies with cinnarizine and dimenhydrinate have not demonstrated clear teratogenic effects, the absence of adequate human safety data means that Arlevert should be avoided during pregnancy unless the expected benefit to the mother clearly outweighs the potential risk to the fetus. Women of childbearing potential should discuss contraception with their doctor if long-term treatment with Arlevert is planned.

It is not established whether cinnarizine or dimenhydrinate (and its active component diphenhydramine) are excreted in human breast milk. Given the pharmacological properties of both components (sedation, anticholinergic effects), there is a theoretical risk of adverse effects in breastfed infants, including sedation, irritability, and feeding difficulties. Therefore, Arlevert should not be used during breastfeeding. If treatment with Arlevert is necessary, breastfeeding should be discontinued for the duration of treatment and for an appropriate washout period thereafter. Consult your doctor for advice.

How Does Arlevert Interact with Other Drugs?

Because Arlevert contains two pharmacologically active compounds with antihistaminic, anticholinergic, and calcium channel-blocking properties, it has the potential to interact with various other medications. Understanding these interactions is essential for safe and effective use of the medication. The most clinically significant interactions are described below.

Major Interactions

MAO inhibitors: The concurrent use of Arlevert with monoamine oxidase inhibitors (such as phenelzine, tranylcypromine, moclobemide, or selegiline) is strictly contraindicated. MAO inhibitors can intensify and prolong the anticholinergic and sedative effects of dimenhydrinate to a dangerous degree, potentially leading to severe hypotension, excessive sedation, and neurotoxicity. A washout period of at least 14 days after discontinuing an irreversible MAO inhibitor should be observed before starting Arlevert.

CNS depressants: Any medication that depresses central nervous system function can have additive effects with Arlevert. This includes benzodiazepines (e.g., diazepam, lorazepam), opioid analgesics (e.g., codeine, morphine, tramadol), barbiturates, antipsychotics, sedating antidepressants (e.g., amitriptyline, mirtazapine), and sedating antihistamines. The combined use may lead to excessive drowsiness, impaired psychomotor function, falls (especially in elderly patients), and in severe cases, respiratory depression. If co-administration is unavoidable, dose reductions and close monitoring are necessary.

Aminoglycoside antibiotics: Aminoglycosides (such as gentamicin, tobramycin, and amikacin) are known to have ototoxic potential, meaning they can damage the inner ear and cause hearing loss or vestibular damage. Because Arlevert suppresses vestibular symptoms, it can mask the early signs of aminoglycoside-induced ototoxicity (such as dizziness and tinnitus), potentially allowing irreversible hearing damage to progress undetected. If you require aminoglycoside treatment while taking Arlevert, your hearing function should be closely monitored through audiometric testing.

Minor Interactions

Anticholinergic drugs: Medications with anticholinergic properties, such as certain antidepressants (tricyclics), antiparkinson drugs (trihexyphenidyl, benztropine), antispasmodics (hyoscine, atropine), and some antihistamines, can have additive anticholinergic effects when combined with Arlevert. This may increase the risk of dry mouth, blurred vision, constipation, urinary retention, tachycardia, and cognitive impairment, particularly in elderly patients. While not absolutely contraindicated, the combination should be used with caution.

Antihypertensive drugs: Cinnarizine has mild vasodilatory properties due to its calcium channel-blocking activity. When combined with antihypertensive medications (such as ACE inhibitors, angiotensin receptor blockers, calcium channel blockers, or beta-blockers), there is a theoretical risk of enhanced blood pressure lowering. Patients should be monitored for symptoms of hypotension, such as dizziness upon standing, lightheadedness, or fainting.

What Is the Correct Dosage of Arlevert?

Always take Arlevert exactly as your doctor has instructed. Do not change the dose or duration of treatment without consulting your healthcare provider. The tablets should be swallowed whole with a sufficient amount of water, preferably with or after meals to reduce the risk of gastrointestinal discomfort.

Adults

Treatment should be initiated at the full dose (one tablet three times daily) from the start. Unlike some medications that require gradual dose escalation, Arlevert can be started at its full therapeutic dose immediately. The duration of treatment should be guided by the clinical response and the underlying condition. For acute vertigo episodes, treatment may last from a few days to several weeks. For chronic or recurrent vertigo, longer treatment courses may be appropriate, but the need for continued treatment should be reassessed regularly by your doctor.

Elderly

Elderly patients can generally use the standard adult dose of one tablet three times daily. However, elderly patients are more susceptible to the sedative and anticholinergic effects of Arlevert, and may also be at increased risk of falls due to drowsiness or dizziness. Your doctor may recommend a reduced dose (for example, one tablet twice daily) if side effects are problematic. Additionally, elderly patients should be monitored for extrapyramidal symptoms (such as tremor, rigidity, or slowness of movement) during prolonged use, as cinnarizine has been rarely associated with drug-induced parkinsonism, particularly in older individuals.

Children

Arlevert is not recommended for use in children and adolescents under 18 years of age. The safety and efficacy of the cinnarizine/dimenhydrinate combination have not been established in pediatric patients. Vertigo in children may have different causes than in adults and often requires specialized diagnostic evaluation and treatment approaches. If your child experiences vertigo, consult a pediatrician or pediatric ENT specialist for appropriate management.

Missed Dose

If you miss a dose of Arlevert, take it as soon as you remember, unless it is almost time for your next scheduled dose. In that case, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten one, as this may increase the risk of side effects, particularly drowsiness. If you frequently forget to take your medication, consider setting reminders or using a pill organizer to help maintain a consistent dosing schedule.

Overdose

If you suspect an overdose of Arlevert, seek emergency medical attention immediately. Symptoms of overdose may reflect the combined effects of both active ingredients and can include severe drowsiness or loss of consciousness, dry mouth, flushed skin, dilated pupils, difficulty urinating, tachycardia (rapid heart rate), gastrointestinal disturbances (nausea, vomiting), and in severe cases, convulsions, respiratory depression, and cardiovascular collapse. There is no specific antidote for cinnarizine or dimenhydrinate overdose. Treatment is supportive and symptomatic, which may include gastric lavage (if ingestion was recent), administration of activated charcoal, monitoring of vital signs, and supportive care for specific symptoms. Due to the anticholinergic properties of dimenhydrinate, physostigmine may be considered in severe cases under specialist guidance.

What Are the Side Effects of Arlevert?

Like all medicines, Arlevert can cause side effects, although not everyone who takes it will experience them. The side effects listed below are based on clinical trial data, post-marketing surveillance, and the known pharmacological profiles of cinnarizine and dimenhydrinate. The overall tolerability of the fixed-dose combination is generally considered favorable, as the lower individual doses used in the combination (compared to standard monotherapy doses) contribute to a reduced incidence of dose-dependent side effects.

In clinical trials comparing the fixed-dose combination with each component alone, the combination showed a similar or lower overall incidence of adverse events compared with monotherapy at standard doses. The most commonly reported side effect was drowsiness, which typically occurred at the beginning of treatment and often diminished with continued use as tolerance developed. Gastrointestinal side effects were generally mild and transient.

Drowsiness is the most frequently observed side effect and is an expected pharmacological consequence of the antihistaminic properties of both cinnarizine and dimenhydrinate. It is most pronounced during the initial days of treatment and typically becomes less noticeable as treatment continues. Taking the evening dose at bedtime can help manage daytime drowsiness. If excessive drowsiness persists and significantly impairs daily functioning, consult your doctor about possible dose adjustment.

Extrapyramidal symptoms (EPS) deserve special attention. Cinnarizine has been identified as a cause of drug-induced parkinsonism, particularly when used at higher doses or for prolonged periods. This occurs because cinnarizine, in addition to its calcium channel-blocking effects, has some dopamine receptor-blocking activity. The risk of EPS is higher in elderly patients and those with a family history of Parkinson's disease. Symptoms may include tremor (especially of the hands), muscle rigidity, slowness of movement (bradykinesia), and gait disturbance. These symptoms are generally reversible upon discontinuation of the drug, but recovery may take weeks to months. If you notice any of these symptoms during Arlevert treatment, inform your doctor immediately.

The anticholinergic effects of dimenhydrinate can cause a constellation of symptoms including dry mouth, blurred vision, constipation, and difficulty urinating. These effects are usually mild at the doses used in Arlevert but may be more pronounced in elderly patients or when Arlevert is taken together with other anticholinergic medications. Adequate fluid intake can help mitigate dry mouth, and a diet rich in fiber can help prevent constipation.

How Should You Store Arlevert?

Proper storage of Arlevert is important to maintain the quality, safety, and effectiveness of the medication throughout its shelf life. Follow these storage guidelines:

• Temperature: Store Arlevert below 25°C (77°F). Do not expose the tablets to excessive heat or direct sunlight, as this may degrade the active ingredients and reduce the medication's effectiveness.
• Moisture protection: Keep the tablets in the original packaging (blister pack or container) to protect them from moisture. Do not transfer them to a different container that may not provide adequate moisture protection. High humidity can cause tablet deterioration.
• Keep out of reach of children: Store Arlevert in a secure location where children cannot see or reach it. Accidental ingestion by children can cause serious adverse effects due to the anticholinergic and sedative properties of the medication.
• Expiration date: Do not use Arlevert after the expiration date stated on the packaging (after "EXP"). The expiration date refers to the last day of the indicated month. Expired medications may have reduced potency and should be disposed of properly.
• Disposal: Do not dispose of unused or expired Arlevert tablets via household waste or wastewater (down the toilet or sink). Ask your pharmacist about local medication take-back programs or proper disposal methods. Correct disposal helps protect the environment.

When traveling with Arlevert, keep the tablets in their original packaging and carry them in your hand luggage to avoid exposure to extreme temperatures that may occur in checked baggage. If you are crossing time zones and take Arlevert three times daily, adjust your dosing schedule gradually to match the local time at your destination.

What Does Arlevert Contain?

Understanding the full composition of Arlevert is important, particularly if you have known allergies or intolerances to specific pharmaceutical ingredients. Below is a detailed breakdown of the active and inactive ingredients.

Active Ingredients

Each Arlevert tablet contains two active pharmaceutical ingredients that work synergistically to treat vertigo:

• Cinnarizine 20 mg: A piperazine derivative that functions as a selective calcium channel blocker on the vestibular labyrinth and also possesses antihistaminic (H1) properties. It acts primarily on the peripheral vestibular system by reducing excessive calcium influx into depolarized vestibular hair cells and neurons.
• Dimenhydrinate 40 mg: An ethanolamine antihistamine composed of equimolar amounts of diphenhydramine and 8-chlorotheophylline. It acts primarily on the central vestibular pathways through H1-antihistaminic and anticholinergic (antimuscarinic) mechanisms, suppressing vestibular nuclei activity and reducing nausea and vomiting associated with vertigo.

Inactive Ingredients (Excipients)

Lactose Content

Arlevert tablets contain lactose monohydrate as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medication. If you have a known lactose intolerance, discuss with your doctor whether the amount of lactose in Arlevert is likely to cause problems for you, as the quantity per tablet is typically small.

Appearance and Pack Sizes

Arlevert tablets are round, white to off-white, flat tablets. They are supplied in blister packs. Common pack sizes include 20, 50, and 100 tablets. Not all pack sizes may be available in every country. Arlevert is manufactured by Hennig Arzneimittel GmbH & Co. KG, Florsheim am Main, Germany.