ATC Class:A04AD

AHFS Class:

• Antihistamines 56:22.08

Generic Name(s):

• dimenhyDRINATE

Dimenhydrinate, an ethanolamine-derivative antihistamine containing a diphenhydramine moiety, is an antiemetic.

Motion Sickness

Dimenhydrinate is used principally in the prevention and treatment of nausea, vomiting, and/or vertigo associated with motion sickness, although scopolamine, promethazine, or meclizine may be more effective. Dimenhydrinate is most effective against motion sickness when given prophylactically, although susceptibility to motion sickness may vary with the patient's age, previous exposure to motion, and the type, severity, and duration of motion.

Other Uses

Dimenhydrinate has been used for symptomatic treatment of Ménière's disease† and other vestibular disturbances†. Like other antihistamines, dimenhydrinate may be less effective than the phenothiazines in controlling nausea and vomiting not related to vestibular stimulation.

Although dimenhydrinate is a histamine antagonist, its use in allergic states has not been evaluated.

Administration

Dimenhydrinate may be administered orally or by IM or IV injection. For IV injection, each 50 mg of dimenhydrinate must be diluted with 10 mL of 0.9% sodium chloride injection and administered slowly over a period of 2 minutes.

Dosage

For the prevention of motion sickness, dimenhydrinate should be taken orally 30 minutes before exposure to motion. For the prevention and treatment of nausea, vomiting, and/or vertigo associated with motion sickness, the usual oral dosage of dimenhydrinate for self-medication in adults and children 12 years of age or older is 50-100 mg every 4-6 hours, not to exceed 400 mg in 24 hours, or as directed by a clinician.100,101,102 The same dosage can be given parenterally in adults to treat motion sickness. Children 6 to younger than 12 years of age may receive 25-50 mg orally every 6-8 hours, not to exceed 150 mg in 24 hours, or as directed by a clinician.100,101,102 Children 2 to younger than 6 years of age may receive 12.5-25 mg orally every 6-8 hours, not to exceed 75 mg in 24 hours, or as directed by a clinician.100,101,102 Alternatively, children may be given 1.25 mg/kg or 37.5 mg/m², orally or IM 4 times daily, up to a maximum of 300 mg daily. Children younger than 2 years of age should receive oral dimenhydrinate only under the direction of a clinician.100,101 IV dosage has not been established for children.

For symptomatic relief of Ménière's disease, 25-50 mg of dimenhydrinate has been given orally 3 times daily for maintenance, or 50 mg has been given IM for acute attacks.

Adverse Effects

Drowsiness commonly occurs after administration of dimenhydrinate. Paradoxical CNS stimulation may occur in children and occasionally in adults.

Other adverse effects include headache, blurred vision, tinnitus, dryness of the mouth and respiratory passages, incoordination, palpitation, dizziness, and hypotension. Anorexia, constipation or diarrhea, urinary frequency, and dysuria are less common. Pain may occur at the site of IM injection. Because dimenhydrinate contains diphenhydramine, the possibility of other diphenhydramine-related adverse effects should also be considered. (See the Antihistamines General Statement 4:00 and Diphenhydramine Hydrochloride 4:04.)

Precautions and Contraindications

Patients should be warned that dimenhydrinate may impair their ability to perform hazardous activities requiring mental alertness or physical coordination (e.g., operating machinery or driving a motor vehicle). Sedation may be enhanced by other CNS depressants. (See Drug Interactions: CNS Depressants.)

Dramamine^® chewable tablets contain the dye tartrazine (FD&C yellow No. 5), which may cause allergic reactions including bronchial asthma in certain susceptible individuals. Although the incidence of tartrazine sensitivity is low, it frequently occurs in individuals who are sensitive to aspirin.

Dimenhydrinate should be used with caution in patients with seizure disorders. The anticholinergic effects of the drug should be considered when administering dimenhydrinate to patients with conditions that might be aggravated by anticholinergic therapy (e.g., angle-closure glaucoma, enlargement of the prostate gland). The drug may mask symptoms of ototoxicity and therefore should be administered with caution to patients receiving known ototoxic drugs. These patients should be closely monitored during therapy with dimenhydrinate.

Pregnancy, Fertility, and Lactation

Pregnancy

Reproduction studies in rats and rabbits using dimenhydrinate doses up to 20 and 25 times the human dose (on a mg/kg basis), respectively, have not revealed evidence of harm to the fetus. There are no adequate and well-controlled studies using dimenhydrinate in pregnant women. Clinical studies to date in pregnant women receiving the drug have not indicated an increased risk of abnormalities when administered during any trimester. Although the possibility of harm to the fetus appears remote, dimenhydrinate should be used during pregnancy only when clearly needed.

Fertility

Reproduction studies in rats and rabbits using dimenhydrinate doses up to 20 and 25 times the human dose (on a mg/kg basis), respectively, have not revealed evidence of impaired fertility.

Lactation

Small amounts of dimenhydrinate are distributed into milk. Because of the potential for adverse reactions to dimenhydrinate in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

CNS Depressants

Dimenhydrinate may enhance the effects of other CNS depressants such as alcohol and barbiturates. If dimenhydrinate is used concomitantly with other CNS depressants, caution should be used to avoid overdosage.

Drugs with Anticholinergic Effects

Because dimenhydrinate also has anticholinergic activity, it may potentiate the effects of other drugs with anticholinergic activity including tricyclic antidepressants.

Ototoxic Drugs

When given concurrently with aminoglycoside antibiotics or other ototoxic drugs, dimenhydrinate may mask the early symptoms of ototoxicity. (See Cautions: Precautions and Contraindications.)

Other Drugs

Although dimenhydrinate has been reported to induce hepatic microsomal enzymes in animals, there is no clinical evidence that dimenhydrinate influences the metabolism of other drugs in humans.

Acute Toxicity

Manifestations

Accidental antihistamine overdose occurs frequently in infants and children. Symptoms of dimenhydrinate toxicity in children may resemble atropine overdosage and include dilated pupils, flushed face, excitation, hallucinations, confusion, ataxia, intermittent clonic convulsions, coma, cardiorespiratory collapse, and death. Symptoms may be delayed for up to 2 hours after ingestion; death may occur within 18 hours.

In adults, 500 mg or more of dimenhydrinate may cause extreme difficulty in speech and swallowing, and produces a psychosis indistinguishable from that of atropine poisoning. CNS excitation may be preceded by sedation, leading to a cycle of CNS excitation, seizures, and postictal depression.

Treatment

Treatment of dimenhydrinate toxicity is symptomatic and supportive. Emetics are usually ineffective, but in the absence of seizures, early gastric lavage (with an endotracheal tube with cuff inflated in place to prevent aspiration of gastric contents) may be beneficial. Patients should be kept quiet to minimize CNS stimulation; seizures may be treated with diazepam in adults and phenobarbital in children. Mechanical respiratory assistance may be required.

Pharmacology

The pharmacologic effects of dimenhydrinate are believed to result principally from its diphenhydramine moiety. Like diphenhydramine, dimenhydrinate has CNS depressant, anticholinergic, antiemetic, antihistaminic, and local anesthetic effects. Although its exact mechanism of antiemetic action is unknown, dimenhydrinate has been shown to inhibit vestibular stimulation, acting first on the otolith system, and in larger doses on the semicircular canals. Dimenhydrinate inhibits acetylcholine; some investigators believe this is its primary mechanism of action, since cholinergic stimulation in the vestibular and reticular systems may be responsible for the nausea and vomiting of motion sickness. Tolerance to CNS depressant effects usually occurs after a few days of treatment, and some decrease in antiemetic effectiveness may be noted after prolonged use.

Pharmacokinetics

Absorption

Dimenhydrinate is well absorbed after oral or parenteral administration. Antiemetic effects occur almost immediately after IV administration, within 15-30 minutes after oral administration, and 20-30 minutes after IM administration. The duration of action is 3-6 hours.

Distribution and Elimination

Little information is available on the distribution and metabolic fate of dimenhydrinate. Like other antihistamines, the drug probably is widely distributed into body tissues, crosses the placenta, is metabolized by the liver, and is excreted in urine. Small amounts of dimenhydrinate are distributed into milk.

Chemistry and Stability

Chemistry

Dimenhydrinate is an ethanolamine-derivative antihistamine that is used as an antiemetic. The drug contains 53-55.5% diphenhydramine and 44-47% 8-chlorotheophylline. Dimenhydrinate occurs as a white, odorless, crystalline powder with a bitter, numbing taste, and is slightly soluble in water and freely soluble in alcohol and in propylene glycol. Dimenhydrinate injection is a sterile solution of the drug in a mixture of propylene glycol and water and has a pH of 6.4-7.2.

Stability

Dimenhydrinate preparations should be stored at room temperature; freezing of the oral solution and injection should be avoided. Dimenhydrinate tablets should be stored in well-closed containers and the oral solution in tight containers.

Dimenhydrinate injection has been reported to be incompatible with many drugs, but the compatibility depends on several factors (e.g., concentrations of the drugs, specific diluents used, resulting pH, temperature). Specialized references should be consulted for specific compatibility information.

100. Food and Drug Administration. Antiemetic drug products for over-the-counter human use; final monograph. Fed Regist . 1987; 52:15886-93.

101. Richardson-Vicks Inc. Dramamine^® Liquid, Dramamine^® tablets, and Dramamine^® Chewable tablets prescribing information. In: Huff BB, ed. Physicians' desk reference. 42nd ed. Oradell, NJ: Medical Economics Company Inc; 1988(Suppl A):A30-1.

102. Food and Drug Administration. Over-the-counter drug products; final monographs for antiemetic, antitussive, bronchodilator, and antihelmintic drug products; updating and technical changes Fed Regist . 1988; 53:35808-10. (21 CFR Parts 336, 341, and 357 [Docket No. 88N-0070])