Dimenhydrinate

Dimenhydrinate is a Histamine H₁ Antagonist belonging to Antiemetic agent.

Dimenhydrinate is a medication used to prevent and treat nausea, vomiting, vertigo, and motion sickness.

Dimenhydrinate is well absorbed and it’s time to peak plasma concentration is approximately 1-2 hours. The volume of distribution of Dimenhydrinate is 3-4 L/kg and is 70-85% protein bound in plasma. Dimenhydrinate extensively metabolized in the liver to metabolites (diphenyl-methoxy-ethylamine, diphenyl-methoxy-acetic, diphenyl-methoxy-N-methylamine). Dimenhydrinate is excreted in urine, as metabolites. The elimination half-life is about 5-8 hours.

Dimenhydrinate shows side effects like Drowsiness, excitement, or hyperactivity (especially in children), headache, new or worsening dizziness, blurred vision, ringing in the ears, dry mouth, nose, or throat, problems with coordination, fainting, dizziness, nausea.

Dimenhydrinate is available in the form of Oral Tablet and Injectable solution.

Dimenhydrinate is available in India, US, Spain, Canada, Germany, Japan, Australia, France, Russia, China, UK, Malaysia, and Italy.

Dimenhydrinate belongs to the Antiemetic agent acts as a Histamine H₁ Antagonist.

Dimenhydrinate is a theoclate salt that separates into diphenhydramine and 8-chlorotheophylline. While the exact mechanism of action is unknown, diphenhydramine is theorized to reduce disturbances to equilibrium through antimuscarinic effects or histamine H1 antagonism. 8-chlorotheophylline may produce excitation through blocking adenosine receptors, reducing the drowsiness produced by diphenhydramine.

The Onset of action of Dimenhydrinate is about 15-30 minutes.

The Duration of action of Dimenhydrinate is about 4-6 hours.

The Tmax of Dimenhydrinate is approximately 1-2 hour.

Dimenhydrinate is available in the form of Oral Tablet and Injectable solution.

Dimenhydrinate tablet is taken orally, and injectable solution is given via intravenous or intramuscular route.

Dimenhydrinate is an antihistamine used to prevent nausea and vomiting caused by motion sickness. It is also used in the treatment of vertigo. Dimenhydrinate is not recommended for use in patients less than 2 years of age.

Dimenhydrinate is a Histamine H₁ Antagonist belonging to Antiemetic agent.

Dimenhydrinate competes with histamine for H₁-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity.

Dimenhydrinate is approved for use in the following clinical indications

• Motion sickness; motion sickness-associated nausea/vomiting
• Nausea and vomiting, pregnancy associated, severe or refractory
• Postoperative nausea/vomiting
• Radiation sickness
• Vertigo, acute episodes

• Motion sickness; motion sickness-associated nausea/vomiting

Adult Dose

Oral:

Immediate release: 50 to 100 mg every 4 to 6 hours (maximum: 400 mg/day).

Immediate-release/sustained-release combination: 100 mg every 8 to 12 hours (maximum: 300 mg/day).

IM, IV: 50 mg every 4 hours; maximum: 100 mg every 4 hours.

Pediatric Dose

Oral Dose

Fixed dose: Administer initial dose 30 to 60 minutes before travel/activity

Children ≥2 to <6 years: Oral: 12.5 to 25 mg every 6 to 8 hours; maximum daily dose: 75 mg/24 hours

Children ≥6 years to <12 years: Oral: 25 to 50 mg every 6 to 8 hours; maximum daily dose: 150 mg/24 hours

Children ≥12 years and Adolescents: Oral: 50 to 100 mg every 4 to 6 hours; maximum daily dose: 400 mg/24 hours

Weight-based dosing: Children 2 to 12 years: Oral: Limited data available: 1 to 1.5 mg/kg/dose every 6 hours; maximum dose: 25 mg/dose. First dose should be administered 60 minutes prior to travel.

Parenteral Dose:

Weight-based dosing: Infants, Children, and Adolescents: IM: 1.25 mg/kg/dose 4 times daily; maximum daily dose: 300 mg/day

BSA-based dosing: Infants, Children, and Adolescents: IM: 37.5 mg/m²/dose 4 times daily; maximum daily dose: 300 mg/day

• Nausea and vomiting, pregnancy associated, severe or refractory

Oral: 25 to 50 mg every 4 to 6 hours as needed; maximum: 300 mg per day.

IV: 50 mg administered over 20 minutes every 4 to 6 hours as needed; maximum: 300 mg per day.

• Postoperative nausea/vomiting

Adult Dose

Oral: 50 to 100 mg prior to procedure then 50 to 100 mg post-procedure; repeat as necessary (maximum: 400 mg/day).

IM, IV: 50 mg prior to treatment than 50 mg post-procedure; repeat as necessary (maximum: 400 mg/day).

Pediatric Dose

Weight-directed: Infants, Children, and Adolescents: IV: 0.5 mg/kg/dose; maximum dose: 25 mg/dose; for treatment of PONV, use only if prophylaxis fails and dimenhydrinate is from a different pharmacologic class than prophylactic drug.

Fixed dose: Children 6 to 7 years: IM, IV: 15 to 25 mg two or three times daily

Children 8 to 12 years: IM, IV: 25 to 50 mg two or three times daily

Children ≥12 years and Adolescents: IM, IV: 50 mg two or three times daily

• Radiation sickness

IM, IV: 50 to 100 mg 30 to 60 minutes prior to treatment; 50 mg 1.5 and 3 hours after treatment. Repeat dose as necessary (maximum: 400 mg/day).

• Vertigo, acute episodes

Oral:

Immediate release: 50 mg every 4 to 6 hours.

Immediate-release/sustained-release combination: 100 mg every 8 to 12 hours (maximum: 300 mg/day).

IM, IV: 50 mg every 4 to 6 hours.

Dimenhydrinate is available in various strengths as 50 mg/mL; 50 mg; 12.5 mg/5 mL; 12.5 mg/4 mL; 25 mg.

Dimenhydrinate is available in the form of Oral Tablet and Injectable solution.

Dimenhydrinate is contraindicated in patients with

• Hypersensitivity to dimenhydrinate or any component of the formulation; neonates (injection contains benzyl alcohol).

• CNS depression

May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving). Other CNS effects which may be observed, particularly at higher dosages include euphoria, hallucinations, confusion, temporary amnesia, and paranoia.

• Dermatologic reactions

Rare cases of serious skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) have been reported; discontinue use if skin rash develops and consult health care provider.

• Cardiovascular disease

Use with caution in patients with cardiovascular disease (including arrhythmias, hypertension, and ischemic heart disease).

• Hepatic impairment

Use with caution in patients with hepatic impairment.

• Increased intraocular pressure/glaucoma

Use with caution in patients with increased intraocular pressure or angle-closure glaucoma.

• Prostatic hyperplasia/urinary obstruction

Use with caution in patients with prostatic hyperplasia and/or GU obstruction.

• Pyloroduodenal obstruction

Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer).

• Respiratory disease

Use with caution in patients with a history of asthma or lower respiratory tract symptoms.

• Seizures

Use with caution in patients with seizure disorders.

• Thyroid dysfunction

Use with caution in patients with thyroid dysfunction.

• Antibiotics

Use caution if used in conjunction with antibiotics that have the potential to cause ototoxicity. Dimenhydrinate may mask symptoms of ototoxicity.

Consumption of alcohol is not recommended during treatment with this medicine due to the increased risk of side effects such as drowsiness and dizziness.

Dimenhydrinate is not recommended for use in breastfeeding women unless necessary. All the risks and benefits should be discussed with the doctor before taking Dimenhydrinate.

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

Common

Tachycardia, Dizziness, drowsiness, excitement, headache, insomnia, lassitude, nervousness, restlessness, Skin rash, Anorexia, epigastric distress, nausea, xerostomia, Dysuria, Blurred vision, Thickening of bronchial secretions.

• Topiramate

Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate.

• Zolpidem

CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol.

• Acetylcholinesterase Inhibitors

May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors.

• Aclidinium

May enhance the anticholinergic effect of Anticholinergic Agents.

• Alcohol (Ethyl)

CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl).

• Alizapride

May enhance the CNS depressant effect of CNS Depressants.

• Amantadine

May enhance the anticholinergic effect of Anticholinergic Agents.

• Amezinium

Antihistamines may enhance the stimulatory effect of Amezinium.

• Anticholinergic Agents

May enhance the adverse/toxic effect of other Anticholinergic Agents

• Azelastine (Nasal)

May enhance the CNS depressant effect of CNS Depressants

• Benzylpenicilloyl Polylysine

Antihistamines may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management

Suspend systemic H1 antagonists for benzylpenicilloyl-polylysine skin testing and delay testing until systemic antihistaminic effects have dissipated. A histamine skin test may be used to assess persistent antihistaminic effects.

• Betahistine

May diminish the therapeutic effect of Antihistamines. Antihistamines may diminish the therapeutic effect of Betahistine

• Blonanserin

CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin.

• Botulinum Toxin-Containing Products

May enhance the anticholinergic effect of Anticholinergic Agents.

• Brexanolone

Brexanolone CNS Depressants may enhance the CNS depressant effect of Brexanolone

• Brimonidine (Topical)

Brimonidine may enhance the effect of CNS Depressants.

• Bromopride

Bromopride may enhance the effect of CNS Depressants.

• Bromperidol

Bromperidol may enhance the effect of CNS Depressants

• Buprenorphine

CNS Depressants may enhance the CNS depressant effect of Buprenorphine.

Management: Consider reduced doses of other CNS depressants and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants.

The common side effects of Dimenhydrinate include the following

• Common side effects

Drowsiness, excitement, or hyperactivity (especially in children), headache, new or worsening dizziness, blurred vision, ringing in the ears, dry mouth, nose, or throat, problems with coordination, fainting, dizziness, nausea.

• Rare side effects

Constipation, Difficulty in falling asleep, Vision disturbances.

• Pregnancy

Pregnancy Category B

Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.

• Nursing Mothers

Dimenhydrinate is not recommended for use in breastfeeding women unless necessary. All the risks and benefits should be discussed with the doctor before taking Dimenhydrinate.

• Pediatric Use

Dimenhydrinate is not recommended for use in patients less than 2 years of age since the safety and efficacy of use are not clinically established.

• Geriatric Use

Use with caution in older adults; may be more sensitive to adverse effects.

Symptoms: Dilated pupils, flushed face, excitation, hallucinations, confusion, ataxia, intermittent clonic convulsions, coma, cardiorespiratory collapse (children); extreme difficulty in speech and swallowing, cycle of CNS excitation, seizures, and postictal depression (adult).

Management: Symptomatic and supportive treatment. In the absence of seizures, performing early gastric lavage (with an endotracheal tube with cuff inflated in place to prevent aspiration of gastric contents) is beneficial. In case of seizures, may give diazepam (in adults) or phenobarbital (in children). Mechanical respiratory assistance may be necessary.

Pharmacodynamic

Dimenhydrinate is indicated for the prevention and treatment of nausea, vomiting, or vertigo of motion sickness. It has a short duration of action of 4-8 hours.

Pharmacokinetics

• Absorption

Dimenhydrinate is well absorbed and it’s time to peak plasma concentration is approximately 1-2 hours.

• Distribution

The volume of distribution of Dimenhydrinate is 3-4 L/kg and is 70-85% protein bound in plasma.

• Metabolism and Excretion

Dimenhydrinate extensively metabolized in the liver to metabolites (diphenyl-methoxy-ethylamine, diphenyl-methoxy-acetic, diphenyl-methoxy-N-methylamine). Dimenhydrinate is excreted in urine, as metabolites. The elimination half-life is about 5-8 hours.

• https://medlineplus.gov/druginfo/meds/a607046.html#:~:text=Dimenhydrinate is used to prevent,preventing problems with body balance.
• https://reference.medscape.com/drug/dramamine-dimenhydrinate-342045
• https://www.rxlist.com/consumer__dramamine/drugs-condition.htm
• https://www.uptodate.com/contents/dimenhydrinate-drug-information?search=dimenhydrinate&source=panel_search_result&selectedTitle=1~31&usage_type=panel&kp_tab=drug_general&display_rank=1
• https://www.drugs.com/pregnancy/dimenhydrinate.html
• https://go.drugbank.com/drugs/DB00985
• https://www.mims.com/india/drug/info/dimenhydrinate?type=full&mtype=generic#pregnancy-category
• https://www.practo.com/medicine-info/dimenhydrinate-1423-api#:~:text=Dimenhydrinate is an antihistamine used,than 2 years of age.