Meclizine

Mechanism of Action

Meclizine is a first-generation antihistamine (non-selective H1 antagonist). The drug also has central anticholinergic actions. The blocking actions on these receptors give meclizine its antiemetic and antivertigo properties. This blocking effect occurs in the medulla's vomiting center and chemoreceptor trigger zone (CTZ).[10] These effects result in the inhibition of signals through histamine neurotransmission from the nucleus of the solitary tract and the vestibular nuclei to the chemoreceptor trigger zone and vomiting center located in the medulla. This effect also reduces vestibular incitation and labyrinth excitability. 

The results of clinical trials demonstrate that meclizine exerts an inhibitory influence on eye movement reflexes related explicitly to low accelerations during visual-vestibular (VIS+VES) tasks. This finding suggests that meclizine's mechanism of action may not primarily involve sensory-specific pathways but rather operates at a more central level. Meclizine addresses motion sickness induced by routine activities; its use may not be effective in vertigo caused by high acceleration.[11]

Pharmacokinetics

Absorption: Meclizine is absorbed post-oral administration. The drug reaches peak plasma levels roughly 3 hours after administration. The onset of action is about 1 hour after oral administration.

Distribution: The results of a pharmacokinetic study revealed that meclizine has a volume of distribution of approximately 6.78 ± 3.52 L.[12] Meclizine can cross the blood-brain barrier.[13]

Metabolism: The data on meclizine metabolism are limited, but according to in vitro metabolic studies, the dominant hepatic enzyme that metabolizes meclizine was found to be CYP2D6.

Elimination: The drug is excreted as a metabolite in the urine and is excreted unchanged in the feces. Meclizine's half-life is about 6 hours, and the duration of action is approximately 8 to 24 hours.[14]

Administration

Available Dosage Forms

Meclizine administration is administered as chewable or non-chewable oral tablets. The dose for oral tablets is 25 to 50 mg. Chewable tablets are available as 25 mg. Chewable tablets must be crushed or completely chewed before swallowing. The drug can be taken without regard to food.

Adult Dosing

Motion sickness: The recommended dosages for controlling motion sickness are 25 to 50 mg orally, taken 1 hour before embarking to protect against motion sickness. Additional doses can be repeated once every 24 hours as necessary.

Vertigo: The recommended daily oral dosages for controlling vertigo in vestibular diseases range from 25 to 100 mg. Subsequent dosages should be adjusted based on the individual's clinical response.[1]

Mèniére disease: The recommended dose of meclizine is 12.5 to 25 mg every 8 hours.[3]

Radiation-induced nausea and vomiting: 50 mg orally 2 to 12 hours before radiotherapy treatment.

Specific Patient Population

Hepatic impairment: There is limited data on how hepatic impairment affects the pharmacokinetics of meclizine. Hepatic impairment could increase systemic exposure to the drug because the liver metabolizes meclizine. Caution is necessary when administering meclizine in patients with hepatic impairment.

Renal impairment: There is limited data on how renal impairment affects the pharmacokinetics of meclizine. Because the drug is renally excreted, there is a potential for the drug/metabolite to accumulate. In such cases, meclizine administration requires caution in patients with reduced renal function.

Pregnancy considerations: Preclinical studies showed meclizine increases the risk of developing cleft palate when given increased doses 25 to 50 times more than the recommended human dose.[15] Meclizine is a former FDA Pregnancy Category B drug. Meclizine is safe to use to treat nausea and vomiting during pregnancy and is not thought to harm an unborn baby.

Breastfeeding considerations: There have not been any documented problems in nursing mothers. Periodic administration of meclizine is likely acceptable while breastfeeding. Extended use and hefty doses of meclizine may cause effects in breastfeeding or decrease the milk supply, especially in combination with sympathomimetic drugs such as pseudoephedrine.[16]

Pediatric patients: The drug is not approved for children younger than 12 because safety and efficacy have not been established. For children 12 and older, dosing is similar to that of adults and adolescents.

Older patients: According to the American Geriatrics Society (AGS Beers Criteria 2023), the long-term use of anticholinergic medications such as meclizine is associated with an elevated risk of delirium, falls, delirium, and dementia among older adults. Evaluate the overall anticholinergic burden when conducting routine annual check-ups.[17] Meclizine may cause urinary retention and amnesia in older adults. Clinicians should prescribe meclizine at the lowest dosage for older patients.

Adverse Effects

Common adverse effects of patients taking meclizine include drowsiness, urinary retention, dry mouth, headache, fatigue, and vomiting.[18] On rare occasions, there have been reports of blurred vision and anaphylactic reactions when taking meclizine.[19]

Drug-Drug Interactions

Due to meclizine's anticholinergic and CNS depressant properties, the drug has the potential to interact with a variety of medications, especially those with anticholinergic and sedative properties. Patients should avoid alcoholic beverages, tranquilizers, and sedatives while taking meclizine due to an increased risk of central nervous system depression.[20]

Due to meclizine's metabolism by CYP2D6, meclizine has the potential for drug interactions with CYP2D6 inhibitors. Consequently, clinicians must closely monitor for adverse reactions and assess the clinical effects when meclizine is co-administered with CYP2D6 inhibitors. Anticholinergic drugs or drugs with anticholinergic properties taken with meclizine may also increase anticholinergic effects.[5]

Contraindications

Meclizine is contraindicated in individuals with a history of hypersensitivity to the drug or excipients like tartrazine. Tartrazine-containing formulations can be associated with allergic reactions.[21]

Warning and Precautions

Drowsiness: Patients should be warned of the possibility of sedation due to meclizine and advised against operating hazardous machinery or driving a car.

Ileus: The anticholinergic effects of meclizine can reduce GI tone and motility. This can aggravate ileus and worsen pyloro-duodenal GI obstruction.

Comorbidities: The potential anticholinergic actions of meclizine pose a risk to patients with asthma, glaucoma, or benign prostatic hyperplasia (BPH). Antihistamines like meclizine can induce acute angle closure glaucoma due to anticholinergic properties.[22] Caution is necessary with the use of the drug in such patients. Patients with bladder obstruction or BPH are at risk for urinary retention due to anticholinergic adverse effects of meclizine.

Genetic polymorphism: The genetic variability in the CYP2D6 enzyme results in different phenotypes, including poor, intermediate, extensive, and ultrarapid metabolizers. These phenotypic variations have a significant impact on the metabolism of meclizine. Prescribers should monitor for potential adverse reactions and evaluate the clinical effectiveness when prescribing meclizine to patients with CYP2D6 polymorphisms.[12]

Phenylketonuria: Some meclizine products contain phenylalanine. Use with caution in patients with phenylketonuria.[23]

Monitoring

Meclizine has not been shown to require serum testing for monitoring. There is no established therapeutic level for meclizine. Just like any drug, patients require clinical monitoring for any adverse reactions.

Due to meclizine's anticholinergic effects, its ability to cause CNS depression, and its metabolism by CYP enzymes, the drug has the potential to interact with a large variety of different medications.[17] Before prescribing, the healthcare provider should carefully review a patient's current medication list and past medical history to avoid interactions, systemic drug accumulation, and exacerbating an already established ailment.

Toxicity

There are no specific antidotes available for meclizine overdose. Treatment is primarily supportive and focused on symptoms. Symptoms of an overdose may include signs of CNS depression such as drowsiness, seizures, and coma. Hypotension can occur, but it is more likely to be seen in older people. The anticholinergic effects and CNS stimulation of an overdose in children can present with hallucinations, seizures, and insomnia.[20] With recent ingestion, induce emesis or perform gastric lavage to prevent further drug absorption. Activated charcoal is also an option. There is no known antidote for meclizine, but physostigmine can help to counter the systemic anticholinergic effects of meclizine.[24]

Enhancing Healthcare Team Outcomes

Meclizine is a commonly prescribed drug by many healthcare professionals, including primary care providers, emergency medicine physicians, oncologists, internists, and advanced practice practitioners. When prescribing this medication, all healthcare practitioners should be aware of the common adverse reactions of the drug and the most susceptible population. The successful use of the drug also depends on the patient's adherence to and knowledge of the potential effects of the drug.

Patients should be aware of the drowsiness and fatigue that the drug can cause so they can avoid driving or operating dangerous machinery when taken. Due to the CNS depression effects of meclizine, healthcare providers should emphasize not drinking alcohol or taking other drugs that can potentiate this effect. Older patients and patients with comorbidities such as asthma, glaucoma, and BPH should be aware of the drug's anticholinergic properties to avoid further complications or be educated on what to do should they arrive.[20]

Other interprofessional healthcare team members, such as pharmacists, should collaborate with prescribers to guarantee that the patient understands proper administration, dosing, and knowledge of potential drug interactions. Clinical nurses should be aware of the adverse effects of the medication and monitor patients. All healthcare professionals must be aware of possible negative outcomes and work together to prevent, manage, and treat accordingly if such an event should occur. Interprofessional collaboration with open communication and shared decision-making will lead to successful outcomes when prescribing meclizine.