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Special Alerts
FDA Recommendation: OTC Cough and Cold Medications Should Not Be Used in Infants and Children <2 Years of Age - January, 2008
The Food and Drug Administration (FDA) has issued a Public Health Advisory reminding patients and caregivers that over-the-counter (OTC) cough and cold medications should not be used to treat infants and children <2 years of age. This is in response to the Centers for Disease Control and Prevention (CDC) report released in January of 2007. The FDA Nonprescription Drugs Advisory Committee and the Pediatric Advisory Committee met October 18-19, 2007 to discuss the safety and efficacy of OTC cough and cold products in children <12 years of age. They recommend that these drugs not be used to treat children <2 years of age due to serious and potentially life-threatening side effects related to their use. The review of use of OTC cough and cold products in children 2-12 years is ongoing.
In January 2007, the CDC released a report concerning the use of cough and cold medications in children <2 years of age. Products containing nasal decongestants (eg, pseudoephedrine), antihistamines (eg, carbinoxamine), cough suppressants (eg, dextromethorphan), and expectorants are often used in this age group, however, safety and efficacy data is limited in this population. The CDC notes that during 2004 and 2005, ~1519 children <2 years of age were seen in emergency departments for adverse effects, including overdose, associated with these medications. In October of 2007, several manufacturers voluntarily removed these products in order to help reduce dosing errors and overdose in this age group. The FDA strongly supported this action.
Based on the agencies' review of the safety data, the FDA strongly recommends the following changes for these agents:
- List active ingredients, medication strength, and concentration on the label;
- Remove “Doctor Recommended” and all similar statements from the front panel;
- Remove all pictures of infants, babies, and children from the box;
- Indicate which patients should NOT take the product; and
- State that individuals should not simultaneously be given more than one product with the same ingredient.
For additional information, refer to the following websites:
http://www.fda.gov/medwatch/safety/2008/safety08.htm#cough
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5601a1.htm, Centers for Disease Control, “Infant Deaths Associated with Cough and Cold Medications ? Two States, 2005,” MMWR Morb Mortal Wkly Rep, 2007, 56(01):1-4.
http://www.Otcsafety.org
http://www.fda.gov/ohrms/dockets/ac/07/minutes/2007-4323m1-Final.pdf
Medication Safety Issues
Sound-alike/look-alike issues:
DiphenhydrAMINE may be confused with desipramine, dicyclomine, dimenhyDRINATE
Benadryl® may be confused with benazepril, Bentyl®, Benylin®, Caladryl®
Pronunciation
(dye fen HYE dra meen)
U.S. Brand Names
Index Terms
Generic Available
Yes: Excludes chewable tablet, gel, orally-disintegrating tablet, stick, strip
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Symptomatic relief of allergic symptoms caused by histamine release including nasal allergies and allergic dermatosis; adjunct to epinephrine in the treatment of anaphylaxis; nighttime sleep aid; prevention or treatment of motion sickness; antitussive; management of Parkinsonian syndrome including drug-induced extrapyramidal symptoms; topically for relief of pain and itching associated with insect bites, minor cuts and burns, or rashes due to poison ivy, poison oak, and poison sumac
Use: Dental
Symptomatic relief of nasal mucosal congestion
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not observed in animal studies. Diphenhydramine crosses the human placenta. One retrospective study showed an increased risk of cleft palate formation following maternal use of diphenhydramine during the 1st trimester of pregnancy; however, later studies have not confirmed this finding. Signs of toxicity and symptoms of withdrawal have been reported in infants following high doses or chronic maternal use close to term. Diphenhydramine has been evaluated for the treatment of hyperemesis gravidarum. It is generally not considered the antihistamine of choice for treating allergic rhinitis or nausea and vomiting during pregnancy.
Lactation
Enters breast milk/contraindicated
Breast-Feeding Considerations
Infants may be more sensitive to the effects of antihistamines. Use while breast-feeding is contraindicated by the manufacturer.
Contraindications
Hypersensitivity to diphenhydramine or any component of the formulation; acute asthma; neonates or premature infants; breast-feeding; use as a local anesthetic (injection)
Warnings/Precautions
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 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:
• Sedatives: Effects may be potentiated when used with other sedative drugs or ethanol.
Special populations:
• Elderly: Use with caution in the elderly; may be more sensitive to adverse effects.
• Pediatrics: Antihistamines may cause excitation in young children.
Dosage form specific issues:
• Phenylalanine: Some products may contain phenylalanine.
• 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. Topical products should not be used on large areas of the body, or on chicken pox or measles. Healthcare provider should be contacted if topical use is needed for >7 days. Topical products are not for OTC use in children <2 years of age.
Adverse Reactions
Frequency not defined.
Cardiovascular: Chest tightness, extrasystoles, hypotension, palpitation, tachycardia
Central nervous system: Chills, confusion, convulsion, disturbed coordination, dizziness, euphoria, excitation, fatigue, headache, insomnia, irritability, nervousness, paradoxical excitement, restlessness, sedation, sleepiness, vertigo
Dermatologic: Photosensitivity, rash, urticaria
Endocrine & metabolic: Menstrual irregularities (early menses)
Gastrointestinal: Anorexia, constipation, diarrhea, dry mucous membranes, epigastric distress, nausea, throat tightness, vomiting, xerostomia
Genitourinary: Difficult urination, urinary frequency, urinary retention
Hematologic: Agranulocytosis, hemolytic anemia, thrombocytopenia
Neuromuscular & skeletal: Neuritis, paresthesia, tremor
Ocular: Blurred vision, diplopia
Otic: Labyrinthitis (acute), tinnitus
Respiratory: Nasal stuffiness, thickening of bronchial secretions, wheezing
Miscellaneous: Anaphylactic shock, diaphoresis
Metabolism/Transport Effects
Inhibits CYP2D6 (moderate)
Drug Interactions
Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central). Acetylcholinesterase Inhibitors (Central) may diminish the therapeutic effect of Anticholinergics. If the anticholinergic action is a side effect of the agent, the result may be beneficial. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Amphetamines: May diminish the sedative effect of Antihistamines. Risk C: Monitor therapy
Anticholinergics: May enhance the adverse/toxic effect of other Anticholinergics. Exceptions: Paliperidone. Risk C: Monitor therapy
Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine. Risk C: Monitor therapy
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Codeine: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of Codeine. These CYP2D6 inhibitors may prevent the metabolic conversion of codeine to its active metabolite morphine. Risk C: Monitor therapy
CYP2D6 Substrates: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of CYP2D6 Substrates. Exceptions: Tamoxifen. Risk C: Monitor therapy
Nebivolol: CYP2D6 Inhibitors (Moderate) may increase the serum concentration of Nebivolol. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Anticholinergics. These effects are specific to the GI tract. Risk D: Consider therapy modification
Tamoxifen: CYP2D6 Inhibitors (Moderate) may decrease the metabolism of Tamoxifen. Specifically, CYP2D6 inhibitors may decrease the formation of highly potent active metabolites. Risk D: Consider therapy modification
TraMADol: CYP2D6 Inhibitors (Moderate) may diminish the therapeutic effect of TraMADol. These CYP2D6 inhibitors may prevent the metabolic conversion of tramadol to its active metabolite that accounts for much of its opioid-like effects. Risk C: Monitor therapy
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (may increase CNS depression).
Herb/Nutraceutical: Avoid valerian, St John's wort, kava kava, gotu kola (may increase CNS depression).
Storage
Injection: Store at room temperature of 15°C to 30°C (59°F to 86°F). Protect from light and freezing
Compatibility
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: Compatible: Acyclovir, aldesleukin, amifostine, amsacrine, aztreonam, ciprofloxacin, cisatracurium, cisplatin, cladribine, cyclophosphamide, cytarabine, docetaxel, doxorubicin, doxorubicin liposome, etoposide phosphate, famotidine, filgrastim, fluconazole, fludarabine, gatifloxacin, gemcitabine, granisetron, heparin, hydrocortisone sodium succinate, idarubicin, linezolid, melphalan, meperidine, meropenem, methotrexate, ondansetron, paclitaxel, piperacillin/tazobactam, potassium chloride, propofol, remifentanil, sargramostim, sufentanil, tacrolimus, teniposide, thiotepa, vinorelbine, vitamin B complex with C. Incompatible: Allopurinol, amphotericin B cholesteryl sulfate complex, cefepime, foscarnet.
Compatibility in syringe: Compatible: Atropine, butorphanol, chlorpromazine, cimetidine, diatrizoate meglumine, diatrizoate meglumine 34.3% and diatrizoate sodium 35%, diatrizoate sodium, diatrizoate sodium 75%, dimenhydrinate, droperidol, fentanyl, fluphenazine, glycopyrrolate, hydromorphone, hydroxyzine, iohexol, iopamidol, iothalamate meglumine, iothalamate meglumine 60%, iothalamate sodium 80%, meperidine, metoclopramide, midazolam, morphine, nalbuphine, pentazocine, perphenazine, prochlorperazine edisylate, promazine, promethazine, ranitidine, scopolamine, sufentanil. Incompatible: Diatrizoate meglumine 52% and diatrizoate sodium 8%, diatrizoate sodium 60%, haloperidol, iodipamide meglumine, iodipamide meglumine 52%, ioxaglate meglumine 39.3% and ioxaglate sodium 19.6%, pentobarbital, thiopental. Variable (consult detailed reference): Dexamethasone sodium phosphate, diatrizoate meglumine 52% and diatrizoate sodium 8%.
Compatibility when admixed: Compatible: Amikacin, aminophylline, ascorbic acid injection, bleomycin, buprenorphine, colistimethate, erythromycin lactobionate, hydrocortisone sodium succinate, lidocaine, methyldopate, nafcillin, netilmicin, penicillin G potassium , penicillin G sodium, polymyxin B, vitamin B complex with C. Incompatible: Amobarbital, amphotericin B, dexamethasone sodium phosphate with lorazepam and metoclopramide, iodipamide meglumine, phenytoin, phenobarbital, thiopental. Variable (consult detailed reference): Heparin in solution.
Mechanism of Action
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
Pharmacodynamics/Kinetics
Onset of action: Maximum sedative effect: 1-3 hours
Duration: 4-7 hours
Distribution: Vd: 3-22 L/kg
Protein binding: 78%
Metabolism: Extensively hepatic n-demethylation via CYP2D6; minor demethylation via CYP1A2, 2C9 and 2C19; smaller degrees in pulmonary and renal systems; significant first-pass effect
Bioavailability: Oral: ~40% to 70%
Half-life elimination: 2-10 hours; Elderly: 13.5 hours
Time to peak, serum: 2-4 hours
Excretion: Urine (as unchanged drug)
Dosage
Note: Dosages are expressed as the hydrochloride salt.
Children:
Allergic reactions or motion sickness: Oral, I.M., I.V.: 5 mg/kg/day or 150 mg/m2/day in divided doses every 6-8 hours, not to exceed 300 mg/day
Alternate dosing by age: Oral:
2 to <6 years: 6.25 mg every 4-6 hours; maximum: 37.5 mg/day
6 to <12 years: 12.5-25 mg every 4-6 hours; maximum: 150 mg/day
?12 years: 25-50 mg every 4-6 hours; maximum: 300 mg/day
Night-time sleep aid: Oral: Children ?12 years: 50 mg at bedtime
Antitussive: Oral:
2 to <6 years: 6.25 mg every 4 hours; maximum 37.5 mg/day
6 to <12 years: 12.5 mg every 4 hours; maximum 75 mg/day
?12 years: 25 mg every 4 hours; maximum 150 mg/day
Treatment of dystonic reactions: I.M., I.V.: 0.5-1 mg/kg/dose
Relief of pain and itching: Topical: Children ?2 years: Apply 1% or 2% to affected area up to 3-4 times/day
Adults:
Allergic reactions or motion sickness: Oral: 25-50 mg every 6-8 hours
Antitussive: Oral: 25 mg every 4 hours; maximum 150 mg/24 hours
Nighttime sleep aid: Oral: 50 mg at bedtime
Allergic reactions or motion sickness: I.M., I.V.: 10-50 mg per dose; single doses up to 100 mg may be used if needed; not to exceed 400 mg/day
Dystonic reaction: I.M., I.V.: 50 mg in a single dose; may repeat in 20-30 minutes if necessary
Relief of pain and itching: Topical: Apply 1% or 2% to affected area up to 3-4 times/day
Elderly: Initial: 25 mg 2-3 times/day increasing as needed
Dental Usual Dosing
Symptomatic relief of nasal mucosal congestion: Adults: Oral: 25-50 mg every 6-8 hours
Administration: Oral
When used to prevent motion sickness, first dose should be given 30 minutes prior to exposure.
Administration: I.V.
Injection solution: For I.V. or I.M. administration only. Local necrosis may result with SubQ or intradermal use. For I.V. administration, inject at a rate ?25 mg/minute.
Administration: I.V. Detail
pH: 5-6
Monitoring Parameters
Relief of symptoms, mental alertness
Reference Range
Antihistamine effects at levels >25 ng/mL
Drowsiness at levels 30-40 ng/mL
Mental impairment at levels >60 ng/mL
Therapeutic: Not established
Toxic: >0.1 mcg/mL
Test Interactions
May suppress the wheal and flare reactions to skin test antigens
Dietary Considerations
Benadryl® Allergy strips contain sodium 4 mg per 25 mg strip.
Benadryl® Children's Allergy chewable tablets contain phenylalanine 4.2 mg, magnesium 15 mg, and sodium 2 mg per 12.5 mg tablet.
Benadryl® Children's Allergy Fastmelt® contains phenylalanine 4.5 mg/tablet and soy protein isolate (contraindicated in patients with soy protein allergies; use caution in peanut allergic individuals, ~10% are estimated to also have soy protein allergies).
Dytan™ chewable tablets contain phenylalanine.
Patient Education
Take as directed; do not exceed recommended dose. Avoid use of other depressants, alcohol, or sleep-inducing medications unless approved by prescriber. You may experience drowsiness or dizziness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or dry mouth, nausea, or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking hard candy may help). Report persistent sedation, confusion, or agitation; changes in urinary pattern; blurred vision; sore throat, respiratory difficulty, or expectorating (thick secretions); or lack of improvement or worsening or condition. Breast-feeding precaution: Do not breast-feed.
Geriatric Considerations
Diphenhydramine has high sedative and anticholinergic properties, so it may not be considered the antihistamine of choice for prolonged use in the elderly. Its use as a sleep aid is discouraged due to its anticholinergic effects; interpretive guidelines from the Centers for Medicare and Medicaid Services (CMS) discourage the use of diphenhydramine as a sedative or anxiolytic in long-term care facilities.
Additional Information
Diphenhydramine citrate 19 mg is equivalent to diphenhydramine hydrochloride 12.5 mg
Anesthesia and Critical Care Concerns/Other Considerations
Diphenhydramine's use as a sleep aid is discouraged due to its anticholinergic effects.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and dry mucous membranes. Chronic use of antihistamines will inhibit salivary flow, particularly in elderly patients; may contribute to periodontal disease and oral discomfort. See Dental Comment.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Dental Comment
25-50 mg of diphenhydramine orally every 4-6 hours can be used to treat mild dermatologic manifestations of allergic reactions to penicillin and other antibiotics. Diphenhydramine is not recommended as local anesthetic for either infiltration route or nerve block since the vehicle has caused local necrosis upon injection. A 50:50 mixture of diphenhydramine liquid (12.5 mg/5 mL) in Kaopectate® or Maalox® is used as a local application for recurrent aphthous ulcers; swish 1 tablespoonful for 2 minutes 4 times/day.
Mental Health: Comment
Along with benztropine, considered the drug of choice for patients with acute dystonic reactions. The usual adult dosage is I.M. 50 mg. In an emergency situation (laryngeal spasm), it should be given intravenously. It is the most sedating antihistamine used to treat drug-induced EPS.
Nursing: Physical Assessment/Monitoring
Assess effectiveness and interactions of other medications patient may be taking. Monitor effectiveness of therapy and adverse reactions at beginning of therapy and periodically with long-term use. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Caplet, as hydrochloride: 25 mg, 50 mg
Aler-Dryl, AllerMax®, Compoz® Nighttime Sleep Aid, Sleep-ettes D, Sominex® Maximum Strength, Twilite®: 50 mg
Nytol® Quick Caps, Simply Sleep®: 25 mg
Capsule, as hydrochloride: 25 mg, 50 mg
Aler-Cap, Banophen®, Benadryl® Allergy, Diphen®, Diphenhist, Genahist®: 25 mg
Sleepinal®: 50 mg
Capsule, softgel, as hydrochloride: 50 mg
Benadryl® Dye-Free Allergy: 25 mg [dye-free]
Compoz® Nighttime Sleep Aid, Nytol® Quick Gels, Sleepinal®, Unisom® Maximum Strength SleepGels®: 50 mg
Captab, as hydrochloride:
Diphenhist®: 25 mg
Cream, as hydrochloride: 2% (30 g)
Banophen® Anti-Itch: 2% (30 g) [contains zinc acetate 0.1%]
Benadryl® Itch Stopping: 1% (30 g) [contains zinc acetate 0.1%]
Benadryl® Itch Stopping Extra Strength: 2% (30 g) [contains zinc acetate 0.1%]
Diphenhist®: 2% (30 g) [contains zinc acetate 0.1%]
Elixir, as hydrochloride:
Altaryl: 12.5 mg/5 mL (120 mL, 480 mL, 3840 mL) [cherry flavor]
Banophen®: 12.5 mg/5 mL (120 mL)
Diphen AF: 12.5 mg/5 mL (240 mL, 480 mL) [alcohol free; cherry flavor]
Gel, topical, as hydrochloride:
Benadryl® Itch Stopping Extra Strength: 2% (120 mL)
Injection, solution, as hydrochloride: 50 mg/mL (1 mL, 10 mL)
Liquid, as hydrochloride:
AllerMax®: 12.5 mg/5 mL (120 mL)
Benadryl® Allergy: 12.5 mg/5 mL (120 mL, 240 mL) [alcohol free; contains sodium benzoate; cherry flavor]
Benadryl® Children's Dye-Free Allergy: 12.5 mg/5 mL (120 mL) [alcohol free, dye free, sugar free; contains sodium benzoate; bubble gum flavor]
Genahist®: 12.5 mg/5 mL (120 mL) [alcohol free, sugar free; contains sodium benzoate; cherry flavor]
Hydramine®: 12.5 mg/5 mL (120 mL, 480 mL) [alcohol free]
Siladryl® Allergy: 12.5 mg/5 mL (120 mL, 240 mL, 480 mL) [alcohol free, sugar free; black cherry flavor]
Liquid, topical, as hydrochloride [stick]:
Benadryl® Itch Stopping Extra Strength: 2% (14 mL) [contains zinc acetate 0.1% and alcohol]
Solution, oral, as hydrochloride:
Diphenhist: 12.5 mg/5 mL (120 mL, 480 mL) [alcohol free; contains sodium benzoate]
Solution, topical, as hydrochloride [spray]:
Benadryl® Itch Stopping Extra Strength: 2% (60 mL) [contains zinc acetate 0.1% and alcohol]
Dermamycin®: 2% (60 mL) [contains menthol 1%]
Strips, oral, as hydrochloride:
Benadryl® Allergy: 25 mg (10s) [contains sodium 4 mg/strip; vanilla mint flavor]
Benadryl® Children's Allergy: 12.5 mg (10s) [vanilla mint flavor]
Triaminic® Thin Strips™ Cough and Runny Nose: 12. 5 mg (16s) [grape flavor]
Suspension, as tannate:
Ben-Tann: 25 mg/5 mL (120 ml) [contains sodium benzoate; strawberry flavor]
Dytan™: 25 mg/5 mL (120 mL) [strawberry flavor] [DSC]
Syrup, as hydrochloride:
Silphen® Cough: 12.5 mg/5 mL (120 mL, 240 mL, 480 mL) [contains alcohol; 5%; strawberry flavor]
Tablet, as hydrochloride: 25 mg, 50 mg
Aler-Tab, Benadryl® Allergy, Genahist®, Sominex®: 25 mg
Tablet, chewable, as hydrochloride:
Benadryl® Children's Allergy: 12.5 mg [contains phenylalanine 4.2 mg, magnesium 15 mg, and sodium 2 mg per tablet; grape flavor]
Tablet, chewable, as tannate:
Dytan™: 25 mg [contains phenylalanine; strawberry flavor]
Tablet, orally disintegrating, as citrate:
Benadryl® Children's Allergy Fastmelt®: 19 mg [equivalent to diphenhydramine hydrochloride 12.5 mg; contains phenylalanine 4.5 mg/tablet and soy protein isolate; cherry flavor]
Pricing: U.S. (www.drugstore.com)
Capsules (DiphenhydrAMINE HCl)
25 mg (100): $11.99
50 mg (100): $13.99
Chewable (Dytan)
25 mg (60): $76.55
Liquid (Q-Dryl)
12.5 mg/5 mL (473): $13.01
Solution (DiphenhydrAMINE HCl)
50 mg/mL (25): $35.99
References
ACOG (American College of Obstetricians and Gynecologists) “Practice Bulletin: Nausea and Vomiting of Pregnancy,” Obstet Gynecol, 2004, 103(4):803-14.
Akutsu T, Kobayashi K, Sakurada K, et al, “Identification of Human Cytochrome P450 Isozymes Involved in Diphenhydramine N-Demethylation,” Drug Metab Dispos, 2007, 35(1):72-8.
Becker DE, “Management of Immediate Allergic Reactions,” Dent Clin North Am, 1995, 39(3):577-86
Blyden GT, Greenblatt DJ, Scavone JM, et al, “Pharmacokinetics of Diphenhydramine and a Demethylated Metabolite Following Intravenous and Oral Administration,” J Clin Pharmacol, 1986, 26(7):529-33.
Corre KA, Niemann JT, Bessen HA, et al, “Extended Therapy for Acute Dystonic Reactions,” Ann Emerg Med, 1984, 13(3):194:7.
Doenecke AL and Heuermann RC, “Treatment of Haloperidol Abuse With Diphenhydramine,” Am J Psychiatry, 1980, 137(4):487-8.
Eigenmann, PA, Burks, AW, Bannon GA, et al, “Identification of Unique Peanut and Soy Allergens in Sera Adsorbed With Cross-Reacting Antibodies,” J Allergy Clin Immunol, 1996, 98 (5 Pt 1):969-78.
Garnett WR, “Diphenhydramine,” Am Pharm, 1986, NS26(2):35-40.
Lindsay CA, Williams GD, and Levin DL, “Fatal Adult Respiratory Distress Syndrome After Diphenhydramine Toxicity in a Child: A Case Report,” Crit Care Med, 1995, 23(4):777-81.
Miller AA, “Diphenhydramine Toxicity in a Newborn: A Case Report,” J Perinatol, 2000, 20(6):390-1.
Parkin DE, “Probable Benadryl Withdrawal Manifestations in a Newborn Infant,” J Pediatr, 1974, 85(4):580.
Sampson HA, Munoz-Furtong A, Campbell RL, et al, “Second Symposium on the Definition and Management of Anaphylaxis: Summary Report -- Second National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium,” Ann Emerg Med, 2006, 7(4):373-80.
Saxen I, “Letter: Cleft Palate and Maternal Diphenhydramine Intake,” Lancet, 1974, 1(7854):407-8.
Seto A, Einarson T, and Koren G, “Pregnancy Outcome Following First Trimester Exposure to Antihistamines: meta-analysis,” Am J Perinatol, 1997, 14(3):119-24.
Simons KJ, Watson WT, Martin TJ, et al, “Diphenhydramine: Pharmacokinetics and Pharmacodynamics in Elderly Adults, Young Adults, and Children,” J Clin Pharmacol, 1990, 30(7):665-71.
Sridhar KS and Donnelly E, “Combination Antiemetics for Cisplatin Chemotherapy,” Cancer, 1988, 61(8):1508-17.
Stancavage M, Osterhoudt KC, and Henretig FM, “Caladryl Ingestion: A New Poisoning From a Common Household Product,” Clin Toxicol, 1995, 33(5):520.
Tsavaris N, Zamanis N, Zinelis A, et al, “Diphenhydramine for Nausea and Vomiting Related to Cancer Chemotherapy With Cisplatin,” J Pain Symptom Manage, 1991, 6(8):461-5.
Weston MV, “Lovelorn and Snakebite,” Hosp Pract (Off Ed), 1986, 21(3A):140-3.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
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