Version May 2024
Motion sickness; motion sickness-associated nausea/vomiting:
Oral:
Immediate release: 50 to 100 mg every 4 to 6 hours (maximum: 400 mg/day).
Immediate-release/sustained-release combination [Canadian product]: 100 mg every 8 to 12 hours (maximum: 300 mg/day).
Rectal [Canadian product]: 50 to 100 mg every 6 to 8 hours as necessary.
IM, IV: 50 mg every 4 hours; may increase to 100 mg every 4 hours if needed.
Nausea and vomiting, pregnancy-associated, severe or refractory (alternative agent) (off-label use): Note: May be considered as a component of combination therapy when symptoms persist following initial pharmacologic therapy (ACOG 2018). Combined use with doxylamine (or other H1 antagonist) may increase adverse reactions (Campbell 2016); some experts recommend discontinuation of doxylamine when initiating dimenhydrinate (Smith 2022).
Oral: 25 to 50 mg every 4 to 6 hours as needed; maximum: 300 mg per day. Note: Maximum of 200 mg per day if patient is also taking doxylamine (ACOG 2018, Campbell 2016; Smith 2022, manufacturer's labeling).
IV: 50 mg administered over 20 minutes every 4 to 6 hours as needed; maximum: 300 mg per day. Note: Maximum: 200 mg per day if patient is also taking doxylamine (ACOG 2018, Campbell 2016; Smith 2022).
Rectal [Canadian product]: 50 mg every 4 to 6 hours as needed; maximum: 300 mg per day. Note: Maximum: 200 mg per day if patient is also taking doxylamine (Campbell 2016; Smith 2022).
Postoperative nausea and vomiting:
Oral [Canadian labeled indication]: 50 to 100 mg prior to procedure, then 50 to 100 mg post-procedure; repeat as necessary (maximum: 400 mg/day).
IM, IV [Canadian product]: 50 mg prior to treatment, then 50 mg post-procedure; repeat as necessary (maximum: 400 mg/day).
Radiation sickness:
IM, IV [Canadian labeled indication]: 50 to 100 mg 30 to 60 minutes prior to treatment, then 50 mg at 90 minutes after treatment, followed by 50 mg at 3 hours after treatment. Repeat dose as necessary (maximum: 400 mg/day).
Rectal [Canadian product]: 50 to 100 mg 30 to 60 minutes prior to treatment; repeat as necessary (maximum: 400 mg/day).
Vertigo, acute episodes:
Note: Reserve use for symptomatic relief of episodes lasting several hours to days (maximum duration: 3 days); chronic use may impede adaptation and recovery (Furman 2022).
Oral:
Immediate release: 50 mg every 4 to 6 hours (Zajonc 2006). The manufacturer's labeling recommends a maximum of 400 mg/day; however, some experts do not recommend doses greater than 300 mg/day (Hain 2003; Zajonc 2006; manufacturer's labeling).
Immediate-release/sustained-release combination [Canadian product]: 100 mg every 8 to 12 hours (maximum: 300 mg/day).
Rectal [Canadian product]: 50 to 100 mg every 6 to 8 hours.
IM, IV: 50 mg every 4 to 6 hours (Ercin 2021; Zajonc 2006).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
Avoid use (Ref).
(For additional information see "Dimenhydrinate: Pediatric drug information")
Motion sickness, nausea/vomiting, or vertigo, prophylaxis:
Oral products:
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 (CDC 2017).
Parenteral products: IM:
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
Canadian labeling: Rectal suppository [Canadian product]:
Children 2 to ≤5 years: Rectal: 12.5 mg to 25 mg once; if more doses needed, contact health care provider
Children 6 to 7 years: Rectal: 12.5 to 25 mg every 8 to 12 hours as needed
Children 8 to 11 years: Rectal: 25 to 50 mg every 8 to 12 hours as needed
Children ≥12 years and Adolescents: Rectal: 50 mg every 8 to 12 hours as needed
Postoperative nausea and vomiting (PONV): Limited data available:
Prevention: Infants, Children, and Adolescents: IV: 0.5 mg/kg/dose; maximum dose: 25 mg/dose (Gan 2014)
Treatment:
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 (Gan 2014)
Fixed dose (Gravol prescribing information [Canada] 2016):
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
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.
Cardiovascular: Tachycardia
Central nervous system: Dizziness, drowsiness, excitement, headache, insomnia, lassitude, nervousness, restlessness
Dermatologic: Skin rash
Gastrointestinal: Anorexia, epigastric distress, nausea, xerostomia
Genitourinary: Dysuria
Ophthalmic: Blurred vision
Respiratory: Thickening of bronchial secretions
Hypersensitivity to dimenhydrinate or any component of the formulation; neonates (injection contains benzyl alcohol)
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to dimenhydrinate, its components (diphenhydramine or 8-chlorotheophylline) or any component of the formulation; concurrent use of or use within 14 days following therapy with a monoamine oxidase inhibitor; narrow angle glaucoma; chronic pulmonary disease; prostatic hypertrophy; patients <2 years of age
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• 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.
Disease-related concerns:
• 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.
Concurrent drug therapy issues:
• Antibiotics: Use caution if used in conjunction with antibiotics that have the potential to cause ototoxicity. Dimenhydrinate may mask symptoms of ototoxicity.
Special populations:
• Older adult: Use with caution in older adults; may be more sensitive to adverse effects.
• Pediatric: Antihistamines may cause excitation in young children. Not for OTC use in children <2 years of age.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
• Parenteral formulations: Do not inject intra-arterially.
• Phenylalanine: Some products may contain phenylalanine.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Abuse/withdrawal: Has abuse potential due to its hallucinogenic and euphoric effects; discontinuation after chronic abuse may lead to withdrawal symptoms (eg, lethargy, agitation, hostility, hallucinations, confusion, aggression, nausea/vomiting).
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, Injection:
Generic: 50 mg/mL (1 mL)
Tablet, Oral:
Dramamine: 50 mg
Driminate: 50 mg
Driminate: 50 mg [scored]
GoodSense Motion Sickness: 50 mg [DSC] [scored]
Tablet Chewable, Oral:
Dramamine: 50 mg
May be product dependent
Solution (dimenhyDRINATE Injection)
50 mg/mL (per mL): $13.84
Tablets (Driminate Oral)
50 mg (per each): $0.08
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Gravol: 50 mg/mL (1 mL, 5 mL)
Generic: 10 mg/mL (5 mL); 50 mg/mL (1 mL, 5 mL)
Suppository, Rectal:
Gravol Comfort Shaped Suppository: 100 mg
Gravol Kids Comfort Shaped Suppository: 25 mg
Oral: To prevent motion sickness, administer 30 to 60 minutes prior to exposure.
Solution for injection:
IM: Administer undiluted
IV: Dilute and inject over 2 minutes. When using for pregnancy-associated nausea and vomiting, administer dose (diluted in 50 mL of normal saline) over 20 minutes (ACOG 2018; SOGC [Campbell 2016]).
Rectal suppository [Canadian product]: To prevent motion sickness, nausea/vomiting, or vertigo, administer 30 minutes prior to event.
Oral: Motion sickness: Administer 30 to 60 minutes before travel/activity that causes motion sickness
Parenteral:
IM: Administer undiluted
IV: Although not recommended (per manufacturer), may further dilute and administer IV over 2 minutes; do not inject intra-arterially (Gravol Canadian labeling 2016)
Rectal: Rectal suppository [Canadian product]: Children ≥2 years and Adolescents: Remove outer wrapper and smooth any edges (for comfort); may need to cut suppository to achieve appropriate dose. To prevent motion sickness, nausea/vomiting, or vertigo, administer 30 minutes prior to event.
US labeling: Motion sickness: Treatment and prevention of nausea, vertigo, and vomiting associated with motion sickness.
Canadian labeling: Nausea, vomiting and/or vertigo: Treatment and prevention of nausea, vomiting and/or vertigo associated with motion sickness, radiation sickness, postoperative recovery, use of other drugs, Ménière disease and other labyrinthine disturbances.
Nausea and vomiting, pregnancy-associated, severe or refractory; Vertigo, acute episodes
DimenhyDRINATE may be confused with diphenhydrAMINE
Dramamine (dimenhydrinate) may be confused with Dramamine (ginger root), Dramamine (meclizine)
Beers Criteria: Dimenhydrinate, a first-generation antihistamine, is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older (independent of diagnosis or condition) due to its potent anticholinergic properties resulting in increased risk of confusion, dry mouth, constipation, and other anticholinergic effects or toxicity; use should also be avoided due to reduced clearance with advanced age and tolerance associated with use as a hypnotic. Exposure to concurrent anticholinergic drugs also increases risk of falls, delirium, and dementia; consider total anticholinergic burden when conducting medication reviews (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Amezinium: Antihistamines may enhance the stimulatory effect of Amezinium. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Betahistine may diminish the therapeutic effect of Antihistamines. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pitolisant: Antihistamines may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Dimenhydrinate crosses the placenta. The risk of fetal abnormalities was not increased following maternal use of dimenhydrinate during any trimester of pregnancy.
Dimenhydrinate may be used for the adjunctive treatment of pregnancy-associated nausea and vomiting (ACOG 2018; SOGC [Campbell 2016]). Dimenhydrinate may have an oxytocic effect if used during labor.
Dimenhydrinate is present in breast milk.
Drowsiness and irritability have been reported in breastfed infants exposed to antihistamines; of these effects, irritability was reported in one infant exposed to dimenhydrinate (Ito 1993). The manufacturer recommends that the decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother. In general, if a breastfed infant is exposed to a first generation antihistamine via breast milk, they should be monitored for irritability or drowsiness (Butler 2014).
Antihistamines may decrease maternal serum prolactin concentrations when administered prior to the establishment of lactation (Messinis 1985).
Tablets may be taken with food or water. Some products may contain phenylalanine.
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
Note: Dimenhydrinate is a salt of two drugs: Diphenhydramine (53% to 55.5%) and 8-chlorotheophylline (44% to 47%). Refer to DiphenhydrAMINE (Systemic) monograph.
Onset of action: Antiemetic: IV: immediate; IM: 20 to 30 minutes; Oral: 15 to 30 minutes (Gravol Canadian labeling 2016).
Duration: Oral: 4 to 6 hours (Gravol Canadian labeling 2016).
Absorption: Well absorbed.
Distribution: Oral: 3 to 4 L/kg (Gravol Canadian labeling 2016).
Protein binding: Oral: 70% to 85% (Gravol Canadian labeling 2016).
Metabolism: Extensive in the liver to metabolites (diphenyl-methoxy-ethylamine, diphenyl-methoxy-acetic, diphenyl-methoxy-N-methylamine) (Gravol Canadian labeling 2016).
Half-life elimination: Oral: 5 to 8 hours (Gravol Canadian labeling 2016).
Excretion: Renal (Gravol Canadian labeling 2016).
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