Dimenhydrinate

By | 2011-08-17

Chemistry

An ethanolamine derivative antihistamine, dimenhydrinate contains approximately 54% diphenhydramine and 46% 8-chlorotheophylline. It occurs as an odorless, bitter and numbing-tasting, white crystalline powder with a melting range of 102°-107°C. Dimenhydrinate is slightly soluble in water and is freely soluble in propylene glycol or alcohol. The pH of the commercially available injection ranges from 6.4 to 7.2.

Storage – Stability – Compatibility

Dimenhydrinate products should be stored at room temperature; avoid freezing the oral solution and injectable products. The oral solution should be stored in tight containers and tablets stored in well-closed containers.

Dimenhydrinate injection is reportedly compatible with all commonly used intravenous replenishment solutions and the following drugs: amikacin sulfate, atropine sulfate, calcium gluconate, chloramphenicol sodium succinate, corticotropin, ditrizoate meglumine and sodium, diphenhydramine HCl, droperidol, fentanyl citrate, heparin sodium, iothalamate meglumine and sodium, meperidine HCl, methicillin sodium, metoclopramide, morphine sulfate, norepinephrine bitartrate, oxytetracycline HCl, penicillin G potassium, pentazocine lactate, perphenazine, phenobarbital sodium, potassium chloride, scopolamine HBr, vancomycin HCl and vitamin B-complex w/ vitamin C.

The following drugs are either incompatible or compatible only in certain concentrations with dimenhydrinate: aminophylline, ammonium chloride, amobarbital sodium, butorphanol tartrate, glycopyrrolate, hydrocortisone sodium succinate, hydroxyzine, iodipamide meglumine, pentobarbital sodium, prochlorperazine edisylate, promazine HCl, promethazine HCl, tetracycline HCl, and thiopental sodium. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluents used and it is suggested to consult specialized references for more specific information.

Dimenhydrinate: Pharmacology

Dimenhydrinate has antihistaminic, antiemetic, anticholinergic, CNS depressant and local anesthetic effects. These principle pharmacologic actions are thought to be a result of only the diphenhydramine moiety. Used most commonly for its antiemetic/motion sickness effects, dimenhydrinate’s exact mechanism of action for this indication is unknown, but the drug does inhibit vestibular stimulation. The anticholinergic actions of dimenhydrinate may play a role in blocking acetylcholine stimulation of the vestibular and reticular systems. Tolerance to the CNS depressant effects can ensue after a few days of therapy and antiemetic effectiveness also may diminish with prolonged use.

Dimenhydrinate: Uses – Indications

In veterinary medicine, dimenhydrinate is used primarily for its antiemetic effects in the prophylactic treatment of motion sickness in dogs and cats.

Pharmacokinetics

The pharmacokinetics of this agent have apparently not been studied in veterinary species. In humans, the drug is well absorbed after oral administration with antiemetic effects occurring within 30 minutes of administration. Antiemetic effects occur almost immediately after IV injection. The duration of effect is usually 3-6 hours.

Diphenhydramine is metabolized in the liver, and the majority of the drug is excreted as metabolites into the urine. The terminal elimination half-life in adult humans ranges from 2.4 – 9.3 hours.

Contraindications/Precautions

Dimenhydrinate is contraindicated in patients who are hypersensitive to it or to other antihistamines in its class. Because of their anticholinergic activity, an-tihistamines should be used with caution in patients with angle closure glaucoma, prostatic hypertrophy, pyloroduodenal or bladder neck obstruction, and COPD if mucosal secretions are a problem. Additionally, they should be used with caution in patients with hyperthyroidism, seizure disorders, cardiovascular disease or hypertension. It may mask the symptoms of ototoxicity and should therefore be used with this knowledge when concomitantly administering with ototoxic drugs.

Dimenhydrinate: Adverse Effects – Warnings

Most common adverse reactions seen are CNS depression (lethargy, somnolence) and anticholinergic effects (dry mouth, urinary retention). GI effects (diarrhea, vomiting, anorexia) are less common, but have been noted.

The sedative effects of antihistamines, may adversely affect the performance of working dogs. The sedative effects of antihistamines may diminish with time.

Dimenhydrinate: Overdosage

Overdosage may cause CNS stimulation (excitement to seizures) or depression (lethargy to coma), anticholinergic effects, respiratory depression and death. Treatment consists of emptying the gut if the ingestion was oral. Induce emesis if the patient is alert and CNS status is stable. Administration of a saline cathartic and/or activated charcoal may be given after emesis or gastric lavage. Treatment of other symptoms should be performed using symptomatic and supportive therapies. Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdose in humans; use of barbiturates and diazepam are avoided.

Dimenhydrinate: Drug Interactions

Increased sedation can occur if dimenhydrinate (diphenhydramine) is combined with other CNS depressant drugs. Antihistamines may partially counteract the anticoagulation effects of heparin or warfarin. Diphenhydramine may enhance the effects of epinephrine. Dimenhydrinate may potentiate the anticholinergic effects of other anticholinergic drugs. Dimenhydrinate has been demonstrated to induce hepatic microsomal enzymes in animals (species not specified); the clinical implications of this effect are unclear.

Laboratory Interactions – Antihistamines can decrease the wheal and flare response to antigen skin testing. In humans, it is suggested that antihistamines be discontinued at least 4 days before testing.

Dimenhydrinate: Doses

Doses for dogs:

For prevention and treatment of motion sickness:

a) 8 mg/kg PO q8h

b) 25 – 50 mg PO once to 3 times a day

c) 4 – 8 mg/kg PO q8h

Doses for cats:

For prevention and treatment of motion sickness:

a) 12.5 mg (total dose) PO q8h

b) 12.5 mg PO once to 3 times a day

c) 8 mg/kg PO q8h

d) 4 – 8 mg/kg PO q8h

Monitoring Parameters

1) Clinical efficacy and adverse effects (sedation, anticholinergic signs, etc.)

Dosage Forms – Preparations – FDA Approval Status – Withholding Times

Veterinary-Approved Products:

None

Human-Approved Products:

Dimenhydrinate Tablets or capsules 50 mg; Commonly known as Dramamine® (Upjohn) (OTC); Many other OTC products also available

Dimenhydrinate Oral Liquid 12.5 mg/4 ml, 12.5 mg/5 ml and 15.62 mg/5 ml; in pints and gallons and in 90 ml, 120 ml and 480 ml bottles Children’s Dramamine® (Upjohn) (OTC); generic (OTC)

Dimenhydrinate Injection 50 mg/ml; in 1 ml amps and vials, 5 & 10 ml vials; Dramamine® (Upjohn); Generic; (Rx)