Meclizine

Mechanism of Action

Meclizine is a first-generation antihistamine (non-selective H1 antagonist). It also has central anticholinergic actions.[5] The blocking actions on these receptors give meclizine its antiemetic and antivertigo properties. This blocking effect occurs in the vomiting center and chemoreceptor trigger zone (CTZ) located in the medulla.[6] 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. 

Absorption: Meclizine is absorbed post-oral administration. The drug reaches peak plasma levels roughly 3 hours after administration. 

Distribution: Meclizine's volume of distribution is unknown in humans because it has not had sufficient study.

Metabolism: The data on meclizine metabolism is limited, but according to in vitro metabolic studies, the dominant hepatic enzyme to metabolize meclizine was found to be CYP2D6.[7]

Excretion: The drug is excreted as a metabolite in the urine and is excreted unchanged in the feces.

Administration

Meclizine administration is chewable or non-chewable by oral tablets. Chewable tablets must be crushed or completely chewed before swallowing. The drug can be taken without regard to food.

Meclizine's half-life is about 6 hours, the onset of action is about 1 hour, and the duration of action is approximately 8 to 24 hours.[7][8]

Adult and Adolescent Dosing

Motion sickness – Orally, 25 to 50 mg one hour before embarkation for protection against motion sickness. Patients can take subsequent dosages once every 24 hours.

Vertigo – Orally, 25 to 100 mg daily, and subsequent dosages depend upon clinical response.

Radiation-induced nausea and vomiting – Orally, 50 mg two to twelve hours before radiotherapy treatment

Pediatric Dosing

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

Geriatric Dosing

Patients 65 years or older may be more sensitive to the effects of the usual adult dose due to the anticholinergic properties of meclizine. Caution is advisable when dosing for this population.

Pregnancy/Nursing Mothers

Meclizine is an FDA Pregnancy Category B drug. Studies conducted in child-bearing women have not shown an elevated risk of developing fetal abnormalities when taking meclizine.[9] Rat studies showed meclizine increases the risk of developing cleft palate when given increased doses 25 to 50 times more than the recommended human dose. It is unknown if meclizine passes through breast milk. There have not been any documented problems in nursing mothers. 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.[4] The anticholinergic actions of meclizine may also inhibit lactation.

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.

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

Due to meclizine's anticholinergic and CNS depressant properties, this drug has the potential to interact with a variety of medications. Especially those that have anticholinergic and sedative properties.[10] As well as drugs that are metabolized by the hepatic enzyme CYP2D6. Using meclizine with alcohol or CNS depression–producing medication may heighten the CNS depressant effects of either of these substances. Anticholinergic drugs or drugs with anticholinergic properties taken with meclizine may also increase anticholinergic effects.[3]

Adverse Effects

Common adverse effects of patients taking meclizine include drowsiness, urinary retention, dry mouth, headache, fatigue, and vomiting.[11] On rare occasions, there have been reports of blurred vision and anaphylactic reactions.[12]

Due to the potential to cause drowsiness, the prescriber should caution the patients against driving and using heavy machinery.

Patients should avoid alcoholic beverages, tranquilizers, and sedatives while taking meclizine due to an increased risk of central nervous system depression.

The potential anticholinergic actions of meclizine pose a risk to patients with asthma, glaucoma, or an enlarged prostate gland. Caution is necessary with the use of the drug in such patients.

Contraindications

Meclizine is contraindicated in individuals with a history of hypersensitivity to the drug or any of the inactive ingredients.

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, it has the potential to interact with a large variety of different drugs. 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/or exacerbating an already establish 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/or coma.  Hypotension can occur, but it is more likely to be seen in the elderly.  The anticholinergic effects and CNS stimulation of an overdose in children can present with hallucinations, seizures, and/or issues sleeping.[10]

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.[13]

Enhancing Healthcare Team Outcomes

Meclizine is a commonly prescribed drug by many healthcare professionals, including primary care providers, emergency medicine physicians, oncologists, internists, and PAs and nurse practitioners. When prescribing this medication, all healthcare providers should be aware of the most common adverse effects 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, health care providers should stress not to drink alcohol or take other drugs that can potentiate this effect. The elderly and patients with comorbidities such as asthma, glaucoma, and BPH should be aware of the anticholinergic properties of the drug to avoid further complications or be educated on what to do should they arrive.[10]

Other providers, such as pharmacists, should work in concert with prescribers to guarantee that the patient knows proper administration, dosing, and knowledge of potential drug interactions. Clinical nurses should be aware of the adverse effects of the medication. All healthcare professionals must be cognizant of possible adverse outcomes and work together to prevent, manage, and/or treat accordingly if such an event should occur. This form of interprofessional collaboration will lead to successful outcomes when prescribing meclizine. [Level 5]