(dye fen HYE dra meen)
Symptomatic relief of allergic symptoms caused by histamine release including nasal allergies and allergic dermatosis; adjunct to epinephrine in the treatment of anaphylaxis; insomnia, occasional; prevention or treatment of motion sickness; antitussive; management of Parkinsonian syndrome including drug-induced extrapyramidal symptoms (dystonic reactions) alone or in combination with centrally acting anticholinergic agents
Hypersensitivity to diphenhydramine, other structurally related antihistamines, or any component of the formulation; neonates or premature infants; breast-feeding
Additional contraindications: Parenteral: Use as a local anesthetic
OTC labeling: When used for self-medication, do not use in children <6 years, to make a child sleep, or with any other diphenhydramine-containing products (including topical products)
Allergic reactions:
Oral: 25 to 50 mg every 4 to 8 hours; maximum: 300 mg daily
IM, IV: 10 to 50 mg per dose; single doses up to 100 mg may be used if needed; not to exceed 400 mg daily
Antitussive: Oral: 25 mg every 4 hours; maximum: 150 mg daily
Motion sickness: Note: When used for prophylaxis, administer 30 minutes before motion.
Oral (treatment or prophylaxis): 25 to 50 mg every 6 to 8 hours
IM, IV (treatment): 10 to 50 mg per dose; single doses up to 100 mg may be used if needed; maximum: 400 mg daily
Insomnia, occasional: Oral: 50 mg at bedtime
Parkinsonism:
Oral: 25 to 50 mg 3 or 4 times daily
IM, IV: 10 to 50 mg per dose; single doses up to 100 mg may be used if needed; maximum: 400 mg daily
Rhinitis, sneezing due to common cold: Oral: 25 to 50 mg every 4 to 6 hours; maximum: 300 mg daily
Allergic reactions: Infants, Children, and Adolescents: IM, IV, Oral: 5 mg/kg/day in divided doses every 6 to 8 hours: maximum: 300 mg daily
Alternate dosing by age: Oral:
2 to <6 years (off-label use): 6.25 mg every 4 to 6 hours; maximum: 37.5 mg daily (Kleigman, 2011)
6 to <12 years: 12.5 to 25 mg every 4 to 6 hours; maximum: 150 mg daily
≥12 years: Refer to adult dosing.
Anaphylaxis (adjunct to epinephrine)/allergic reaction (off-label use): Infants, Children, and Adolescents: IM, IV, Oral: 1 to 2 mg/kg/dose; maximum: 50 mg/dose (Hegenbarth, 2008; Kliegman, 2011; Liberman, 2008; Lieberman, 2010; Simons, 2011)
Antitussive: Children ≥12 years: Refer to adult dosing.
Dystonic reactions (off-label use): Infants, Children, and Adolescents: IM, IV: 1 to 2 mg/kg/dose; maximum single dose: 50 mg (Hegenbarth, 2008; Kliegman, 2011)
Insomnia, occasional: Oral:
Children 2 to 12 years, weighing 10 to 50 kg (off-label use): Limited data available: 1 mg/kg administered 30 minutes before bedtime; maximum single dose: 50 mg (Russo, 1976)
Children ≥12 years and Adolescents: Refer to adult dosing.
Motion sickness:
Prophylaxis: Oral:
Manufacturers labeling: Infants, Children, and Adolescents: Note: Administer 30 minutes before motion
Weight-directed dosing: 5 mg/kg/day divided into 3 to 4 doses; maximum: 300 mg daily
Fixed dosing: 12.5 to 25 mg 3 to 4 times daily
Alternate dosing: Children 2 to 12 years: Limited data available: 0.5 to 1 mg/kg/dose every 6 hours; maximum single dose: 25 mg. First dose should be administered 1 hour before travel (CDC, 2014).
Treatment: Infants, Children, and Adolescents:
IV, IM: 5 mg/kg/day divided into 4 doses; maximum: 300 mg daily
Oral:
Weight-directed dosing: 5 mg/kg/day divided into 3 to 4 doses; maximum: 300 mg daily
Fixed dosing: 12.5 to 25 mg 3 to 4 times daily
Rhinitis, sneezing due to common cold: Oral:
Children 6 to <12 years: 12.5 to 25 mg every 4 to 6 hours; maximum: 150 mg daily
Children ≥12 years and Adolescents: Refer to adult dosing.
There are no dosage adjustments provided in the manufacturer 's labeling.
There are no dosage adjustments provided in the manufacturer 's labeling.
When used to prevent motion sickness, first dose should be given 30 minutes prior to exposure. When used for occasional insomnia, dose should be given 30 minutes before bedtime.
Injection solution is for IV or deep IM administration only. For IV administration, inject at a rate ≤25 mg/minute. Local necrosis may result with SubQ or intradermal use.
Some products may contain sodium and/or phenylalanine.
Injection: Store at room temperature of 20 � �C to 25 � �C (68 � �F to 77 � �F); protect from light and freezing.
Oral: Store at room temperature. Protect capsules and tablets from moisture. Protect oral solution from freezing and light.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hydrochloride:
Allergy Relief: 25 mg [contains brilliant blue fcf (fd&c blue #1), butylparaben, edetate calcium disodium, fd&c blue #2 (indigotine), fd&c red #40, fd&c yellow #10 (quinoline yellow), methylparaben, polysorbate 80, propylparaben]
Banophen: 25 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40, fd&c yellow #6 (sunset yellow), methylparaben, propylparaben]
Banophen: 50 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Benadryl: 25 mg
Benadryl Allergy: 25 mg [dye free]
Benadryl Dye-Free Allergy: 25 mg [dye free]
Diphenhist: 25 mg [DSC] [contains brilliant blue fcf (fd&c blue #1), butylparaben, fd&c red #40, methylparaben, propylparaben]
Diphenhist: 25 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Genahist: 25 mg
Geri-Dryl: 25 mg
GoodSense Allergy Relief: 25 mg [dye free]
Ormir: 50 mg [contains fd&c yellow #10 (quinoline yellow), fd&c yellow #6 (sunset yellow)]
Pharbedryl: 25 mg, 50 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Q-Dryl: 25 mg [contains brilliant blue fcf (fd&c blue #1), butylparaben, fd&c red #40, methylparaben, propylparaben]
ZzzQuil: 25 mg [contains brilliant blue fcf (fd&c blue #1), fd&c red #40]
Generic: 25 mg, 50 mg
Elixir, Oral, as hydrochloride:
Altaryl: 12.5 mg/5 mL (120 mL, 480 mL, 3840 mL) [contains alcohol, usp]
Generic: 12.5 mg/5 mL (5 mL, 10 mL)
Liquid, Oral, as hydrochloride:
Allergy Relief Childrens: 12.5 mg/5 mL (118 mL, 480 mL) [alcohol free; contains fd&c red #40, sodium benzoate]
Banophen: 12.5 mg/5 mL (118 mL) [alcohol free; cherry flavor]
Banophen: 12.5 mg/5 mL (473 mL) [alcohol free, sugar free; cherry flavor]
Benadryl Allergy Childrens: 12.5 mg/5 mL (118 mL, 236 mL) [alcohol free; contains fd&c red #40, sodium benzoate]
Benadryl Allergy Childrens: 12.5 mg/5 mL (5 mL, 236 mL) [alcohol free; contains fd&c red #40, sodium benzoate; cherry flavor]
Benadryl Allergy Childrens: 12.5 mg/5 mL (118 mL) [alcohol free, dye free, sugar free; contains saccharin sodium, sodium benzoate]
Diphenhist: 12.5 mg/5 mL (118 mL, 473 mL) [alcohol free; contains fd&c red #40, saccharin sodium, sodium benzoate; fruit flavor]
Naramin: 12.5 mg/5 mL (5 mL) [alcohol free; contains fd&c red #40, sodium benzoate; cherry flavor]
PediaCare Childrens Allergy: 12.5 mg/5 mL (118 mL) [alcohol free; contains fd&c red #40, sodium benzoate]
Q-Dryl: 12.5 mg/5 mL (118 mL, 237 mL, 473 mL) [alcohol free; contains fd&c red #40, saccharin sodium, sodium benzoate; cherry flavor]
Scot-Tussin Allergy Relief: 12.5 mg/5 mL (118.3 mL, 240 mL, 480 mL, 3780 mL) [alcohol free, dye free, saccharin free, sodium free, sorbitol free, sugar free]
Siladryl Allergy: 12.5 mg/5 mL (118 mL, 237 mL, 473 mL) [alcohol free, sugar free; contains fd&c red #40, methylparaben, propylene glycol, propylparaben, saccharin sodium; cherry flavor]
Total Allergy Medicine: 12.5 mg/5 mL (118 mL) [alcohol free]
ZzzQuil: 50 mg/30 mL (177 mL, 354 mL) [contains alcohol, usp, brilliant blue fcf (fd&c blue #1), fd&c red #40, propylene glycol, saccharin sodium, sodium benzoate; berry flavor]
ZzzQuil: 50 mg/30 mL (354 mL) [contains alcohol, usp, brilliant blue fcf (fd&c blue #1), fd&c red #40, propylene glycol, saccharin sodium, sodium benzoate; vanilla cherry flavor]
ZzzQuil: 50 mg/30 mL (177 mL, 354 mL) [alcohol free; contains brilliant blue fcf (fd&c blue #1), propylene glycol, saccharin sodium, sodium benzoate; mango berry flavor]
Solution, Injection, as hydrochloride:
Generic: 50 mg/mL (1 mL, 10 mL)
Solution, Injection, as hydrochloride [preservative free]:
Generic: 50 mg/mL (1 mL)
Strip, Oral, as hydrochloride:
Triaminic Cough/Runny Nose: 12.5 mg (14 ea) [contains alcohol, usp, brilliant blue fcf (fd&c blue #1), fd&c red #40]
Triaminic Cough/Runny Nose: 12.5 mg (16 ea) [contains alcohol, usp, brilliant blue fcf (fd&c blue #1), fd&c red #40; grape flavor]
Suspension Reconstituted, Oral, as hydrochloride:
Dicopanol FusePaq: 5 mg/mL (150 mL) [contains sodium benzoate]
Dicopanol RapidPaq: 5 mg/mL (150 mL) [dye free, paraben free, sugar free; contains sodium benzoate]
Syrup, Oral, as hydrochloride:
Altaryl: 12.5 mg/5 mL (120 mL, 480 mL, 3785 mL) [alcohol free; cherry flavor]
Quenalin: 12.5 mg/5 mL (120 mL) [fruit flavor]
Silphen Cough: 12.5 mg/5 mL (118 mL, 237 mL, 473 mL) [contains alcohol, usp, fd&c red #40, menthol, methylparaben, propylene glycol, propylparaben; strawberry flavor]
Tablet, Oral, as hydrochloride:
Aler-Dryl: 50 mg
Allergy Relief: 25 mg [contains polysorbate 80]
Anti-Hist Allergy: 25 mg
Banophen: 25 mg
Benadryl: 25 mg
Benadryl Allergy: 25 mg
Benadryl Allergy: 25 mg [contains edetate calcium disodium, fd&c red #40, methylparaben, polysorbate 80, propylparaben]
Complete Allergy Medication: 25 mg
Complete Allergy Relief: 25 mg
Diphen: 25 mg
Diphenhist: 25 mg
Geri-Dryl: 25 mg
Nighttime Sleep Aid: 25 mg [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake, polysorbate 80]
Nighttime Sleep Aid: 50 mg [DSC] [contains fd&c blue #1 aluminum lake]
Nytol: 25 mg
Nytol Maximum Strength: 50 mg
QlearQuil Nighttime Allergy: 25 mg [contains fd&c blue #1 aluminum lake, fd&c blue #2 aluminum lake]
Simply Allergy: 25 mg
Simply Sleep: 25 mg [contains brilliant blue fcf (fd&c blue #1)]
Sleep Tabs: 25 mg [scored; contains fd&c blue #1 aluminum lake]
Sominex: 25 mg [contains fd&c blue #1 aluminum lake]
Sominex Maximum Strength: 50 mg [contains fd&c blue #1 aluminum lake, polysorbate 80]
Tetra-Formula Nighttime Sleep: 50 mg [contains fd&c blue #1 aluminum lake]
Total Allergy: 25 mg
Generic: 25 mg
Tablet Chewable, Oral, as hydrochloride:
Benadryl Allergy Childrens: 12.5 mg [contains aspartame, fd&c blue #1 aluminum lake; cherry flavor]
Benadryl Allergy Childrens: 12.5 mg [contains aspartame, fd&c blue #1 aluminum lake; grape flavor]
Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5W, D10W, fat emulsion 10%, LR, 1/2NS, NS.
Y-site administration: Incompatible with allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, foscarnet, pantoprazole.
Compatibility in syringe: Incompatible with diatrizoate meglumine 52% and diatrizoate sodium 8%, furosemide, haloperidol, iodipamide meglumine, ioxaglate meglumine 39.3% and ioxaglate sodium 19.6%, pantoprazole, pentobarbital, thiopental.
AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Monitor therapy
Analgesics (Opioid): Anticholinergic Agents may enhance the adverse/toxic effect of Analgesics (Opioid). Specifically, the risk for constipation and urinary retention may be increased with this combination. Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy
ARIPiprazole: CYP2D6 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. Monitor therapy
Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). 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. Consider therapy modification
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification
Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy
Dimethindene: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy
Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Hyaluronidase: Antihistamines may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving antihistamines (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification
HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Consider starting with a 20% to 30% lower hydrocodone dose when using together with any other CNS depressant. Dose reductions in the other CNS depressant may also be warranted. Consider therapy modification
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy
Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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 adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy
Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: When oxycodone is combined with another CNS depressant, a dose reduction of one or both agents should be considered. The extended release oxycodone starting dose should be reduced 50% to 67% when initiated in patients already receiving CNS depressants. Consider therapy modification
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification
Perhexiline: CYP2D6 Inhibitors (Weak) may increase the serum concentration of Perhexiline. Monitor therapy
Piribedil [INT]: CNS Depressants may enhance the CNS depressant effect of Piribedil [INT]. Monitor therapy
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. Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy
RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid using drugs with substantial anticholinergic effects in patients receiving secretin whenever possible. If such agents must be used in combination, monitor closely for a diminished response to secretin. Consider therapy modification
Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy
Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. 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. Consider therapy modification
Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Start tapentadol at a dose of one-third to one-half of the normal dose if being initiated in a patient who is taking another drug with CNS depressant effects. Monitor closely for evidence of excessive CNS depression. Consider therapy modification
Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination
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. Consider therapy modification
Relief of symptoms, mental alertness
May interfere with urine detection of methadone and phencyclidine (false-positives); may cause false-positive serum TCA screen; may suppress the wheal and flare reactions to skin test antigens
Frequency not defined.
Cardiovascular: Chest tightness, extrasystoles, hypotension, palpitations, tachycardia
Central nervous system: Ataxia, chills, confusion, dizziness, drowsiness, euphoria, excitement, fatigue, headache, insomnia, irritability, nervousness, neuritis, paradoxical excitation, paresthesia, restlessness, sedation, seizure, vertigo
Dermatologic: Diaphoresis
Endocrine & metabolic: Menstrual disease (early menses)
Gastrointestinal: Anorexia, constipation, diarrhea, dry mucous membranes, epigastric distress, nausea, vomiting, xerostomia
Genitourinary: Difficulty in micturition, urinary frequency, urinary retention
Hematologic & oncologic: Agranulocytosis, hemolytic anemia, thrombocytopenia
Hypersensitivity: Anaphylactic shock
Neuromuscular & skeletal: Tremor
Ophthalmic: Blurred vision, diplopia
Otic: Labyrinthitis (acute), tinnitus
Respiratory: Constriction of the pharynx, nasal congestion, thickening of bronchial secretions, wheezing
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).
Disease-related concerns:
- Asthma: Use with caution in patients with a history of asthma.
- Cardiovascular disease: Use with caution in patients with cardiovascular disease (including hypertension and ischemic heart disease).
- 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, bladder neck obstruction, and/or GU obstruction.
- Pyloroduodenal obstruction: Use with caution in patients with pyloroduodenal obstruction (including stenotic peptic ulcer).
- Thyroid dysfunction: Use with caution in patients with thyroid dysfunction.
Concurrent drug therapy issues:
- Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.
- Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
- Pediatric: Antihistamines may cause excitation in young children. Toxicity (overdose) in pediatric patients may result in hallucinations, convulsions, or death; neonates and young children are highly sensitive to depressive effects of diphenhydramine; use is contraindicated in neonates and premature infants.
Dosage form specific issues:
- Alcohol: Some oral liquid products may contain alcohol.
- 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 [Inactive" 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.
- Oral liquid: Oral solutions are available in two concentrations (ie, 12.5 mg/5 mL and 50 mg/30 mL [eg, ZzzQuil]); precautions should be taken to verify and avoid confusion between the different concentrations; dose should be clearly presented as mg"; the 50 mg/30 mL oral solution is indicated for the occasional treatment of insomnia.
- Parenteral: Subcutaneous or intradermal use has been associated with tissue necrosis; administer IV or IM only.
- 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 hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP [Inactive" 1997]; Zar, 2007).
- Soy protein: Some preparations contain soy protein; avoid use in patients with soy protein or peanut allergies.
Other warnings/precautions:
- Self-medication (OTC use): Do not use with other products containing diphenhydramine, even ones used on the skin. Oral products are not for OTC use in children <6 years of age.
B
Adverse events have not been observed in animal reproduction studies. Diphenhydramine crosses the placenta. Maternal diphenhydramine use has generally not resulted in an increased risk of birth defects; however, adverse events (withdrawal symptoms, respiratory depression) have been reported in newborns exposed to diphenhydramine in utero. Antihistamines are recommended for the treatment of rhinitis, urticaria, and pruritus with rash in pregnant women (although second generation antihistamines may be preferred). Antihistamines are not recommended for treatment of pruritus associated with intrahepatic cholestasis in pregnancy.
Competes with histamine for H1-receptor sites on effector cells in the gastrointestinal tract, blood vessels, and respiratory tract; anticholinergic and sedative effects are also seen
Vd: Children: 22 L/kg (range: 15 to 28 L/kg); Adults: 17 L/kg (range: 13 to 20 L/kg); Elderly: 14 L/kg (range: 7 to 20 L/kg) (Blyden, 1986; Simons, 1990)
Extensively hepatic n-demethylation via CYP2D6; minor demethylation via CYP1A2, 2C9 and 2C19; smaller degrees in pulmonary and renal systems; significant first-pass effect (Akutsu, 2007)
Urine (as metabolites and unchanged drug) (Albert, 1975; Maurer, 1988)
Serum: ~2 hours (Blyden, 1986; Simons, 1990)
Histamine-induced wheal suppression: ≤10 hours (Simons, 1990)
Histamine-induced flare suppression: ≤12 hours (Simons, 1990)
Children: 5 hours (range: 4 to 7 hours); Adults: 9 hours (range: 7 to 12 hours); Elderly: 13.5 hours (range: 9 to 18 hours) (Blyden, 1986; Simons, 1990)
98.5% (Vozeh, 1988)
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience fatigue, thickening of mucus, anxiety, vomiting, or nausea. Have patient report immediately to prescriber severe dizziness, passing out, or change in balance (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.