Dorenta

Approved Indications:

• Allergic Conditions:
• Seasonal allergic rhinitis (hay fever)
• Perennial allergic rhinitis
• Urticaria (hives)
• Allergic conjunctivitis
• Mild angioedema
• Adjunct in anaphylaxis (with epinephrine)
• Allergic skin reactions (e.g., insect bites, contact dermatitis)
• Motion Sickness:
• Prevention and treatment of nausea, vomiting, and dizziness due to motion sickness
• Insomnia:
• Occasional short-term treatment of insomnia
• Parkinsonism and Extrapyramidal Symptoms:
• Management of mild parkinsonism
• Treatment of drug-induced extrapyramidal disorders (e.g., dystonia, akathisia)
• Cough and Cold:
• Temporary relief of cough, sneezing, runny nose, and watery eyes associated with upper respiratory infections and the common cold (in combination products)

Clinically Accepted Off-Label Uses:

• Acute dystonic reactions
• Migraine-associated nausea and vomiting (in combination therapy)
• Adjunctive sedation in intensive care units
• Local anesthetic alternative in lidocaine-allergic patients (rare)

Route of Administration: Oral, Intravenous (IV), Intramuscular (IM), Topical, Rectal (rare)

Adults:

• Allergic reactions: 25–50 mg orally every 4–6 hours; maximum 300 mg/day
• Motion sickness: 25–50 mg orally 30 minutes before travel, then every 4–6 hours as needed
• Insomnia: 50 mg orally at bedtime
• Parkinsonism or EPS: 25–50 mg orally 3–4 times daily
• IV/IM (e.g., anaphylaxis adjunct): 10–50 mg IV/IM every 4–6 hours; maximum 400 mg/day

Pediatric:

• 2 to <6 years: 6.25 mg every 4–6 hours; maximum 37.5 mg/day
• 6–12 years: 12.5–25 mg every 4–6 hours; maximum 150 mg/day
• ≥12 years: Adult dosage
• Motion sickness: 1 mg/kg/dose orally before travel; not exceeding 50 mg per dose

Geriatric:

• Use lower initial doses (e.g., 25 mg at bedtime); avoid long-term use due to increased risk of cognitive impairment, confusion, and falls

Renal or Hepatic Impairment:

• Use with caution; dose reduction may be necessary
• Monitor for enhanced central and anticholinergic side effects

Diphenhydramine Hydrochloride is a first-generation H1 histamine receptor antagonist. It exerts its therapeutic effects by competitively inhibiting histamine binding at peripheral and central H1 receptors. This reduces capillary permeability, vasodilation, and smooth muscle contractions associated with allergic reactions. It also possesses significant anticholinergic and central nervous system depressant activity due to its action on muscarinic receptors and ability to cross the blood-brain barrier. These properties explain its additional efficacy in treating motion sickness, inducing sedation, and relieving extrapyramidal symptoms.

• Absorption: Rapidly absorbed after oral administration
• Onset of Action:
• Oral: 15–60 minutes
• IM: 20–30 minutes
• IV: Immediate
• Peak Plasma Concentration: 2–3 hours after oral intake
• Bioavailability: ~40–60% (subject to first-pass metabolism)
• Distribution: Widely distributed; crosses placenta and blood-brain barrier; ~80–85% protein bound
• Metabolism: Hepatic metabolism via CYP2D6
• Half-life:
• Adults: 4–9 hours
• Children: ~5–7 hours
• Elderly: Up to 13.5 hours
• Elimination: Primarily renal, as metabolites and conjugates

• Pregnancy: Former FDA Category B
• No proven fetal risk in humans, but should be used during pregnancy only if clearly needed
• Crosses the placenta; caution in the third trimester due to potential neonatal effects (e.g., sedation)
• Lactation:
• Excreted into breast milk
• May cause sedation, irritability, or decreased milk supply in the infant
• Occasional, short-term use may be acceptable; prolonged use is not recommended

• Primary Class: First-generation H1-antihistamine
• Subclass: Ethanolamine derivative
• Pharmacological Properties: Anticholinergic, sedative, antiemetic

• Hypersensitivity to diphenhydramine or any excipients
• Use in neonates or premature infants
• Breastfeeding (when administered systemically)
• Concomitant use with other diphenhydramine-containing products
• Acute asthma attacks (when used alone)
• Use in elderly with dementia-related psychosis (due to increased CNS adverse effects)

• CNS Effects: May cause sedation, dizziness, and confusion; avoid alcohol and sedatives
• Anticholinergic Effects: Caution in patients with glaucoma, urinary retention, prostatic hypertrophy, or GI obstruction
• Respiratory Risk: Caution in patients with COPD or asthma
• Seizure Disorders: May reduce seizure threshold
• Geriatric Caution: High risk of cognitive impairment, delirium, and falls
• Pediatric Use: Not recommended for children under 2 years due to risk of fatal respiratory depression
• Overdose Risk: Narrow safety margin in young children

Common (≥1%):

• Central Nervous System: Drowsiness, dizziness, headache, sedation
• Gastrointestinal: Dry mouth, nausea, vomiting, constipation
• Respiratory: Thickened bronchial secretions

Less Common:

• Blurred vision
• Difficulty urinating
• Euphoria or paradoxical excitation (especially in children)

Serious and Rare:

• Seizures (in overdose or predisposed patients)
• Cardiac arrhythmias
• Hallucinations or psychosis (high doses)
• Anaphylactic reactions
• Hypotension

• CNS Depressants: Alcohol, benzodiazepines, opioids — additive sedative effects
• MAO Inhibitors: Enhanced anticholinergic and sedative toxicity — avoid combination
• Anticholinergic Drugs (e.g., TCAs, antipsychotics): Increased risk of constipation, urinary retention, blurred vision, and confusion
• CYP2D6 Inhibitors (e.g., fluoxetine, paroxetine): May increase diphenhydramine levels

• Beers Criteria (2023 Update): Diphenhydramine is listed as potentially inappropriate in older adults due to strong anticholinergic effects and risk of cognitive decline and delirium
• FDA Pediatric Safety Advisory: Strong warning against use in children under 2 years for any indication
• Preferred Antihistamine Guidance: Second-generation, non-sedating antihistamines (e.g., loratadine, cetirizine) are now recommended as first-line treatment for allergic rhinitis and urticaria due to better safety profile

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity and Light Protection: Store in a dry place away from light and moisture
• Liquid Formulations: Do not freeze; shake well before use
• Topical Preparations: Store at room temperature; avoid direct contact with eyes or mucous membranes
• Handling Precautions: Keep out of reach of children to prevent accidental ingestion or overdose