Diphenhydramine Hydrochloride + Zinc Acetate

Approved and Clinically Accepted Indications:

• Symptomatic Relief of the Common Cold and Allergies:
• Nasal congestion
• Sneezing
• Runny nose
• Watery eyes
• Postnasal drip
• Allergic rhinitis (seasonal or perennial)
• Cough Associated with Upper Respiratory Tract Infections:
• Due to minor throat and bronchial irritation
• Zinc Supplementation for Immune Support:
• Adjunct in reducing the duration and severity of cold symptoms
• Supportive management in mild viral infections to promote immune function
• Combined Use in Lozenges or Syrups:
• Diphenhydramine acts as an antihistamine and cough suppressant
• Zinc Acetate contributes to local antiviral action and mucosal immune defense

Note: While both ingredients have established individual uses, combination products are commonly used in over-the-counter preparations aimed at multi-symptom cold relief.

Route of Administration: Oral (tablet, syrup, lozenge)

Adults and Adolescents (≥12 years):

• Oral syrup/tablets: 25 mg Diphenhydramine + 5–10 mg elemental Zinc (as Zinc Acetate), every 4–6 hours as needed
• Maximum daily dose: 150 mg Diphenhydramine, not exceeding recommended zinc intake (40 mg elemental zinc/day for adults)

Pediatrics:

• 6–12 years: 12.5 mg Diphenhydramine + 2.5–5 mg elemental Zinc every 6 hours
• 2–6 years: 6.25 mg Diphenhydramine + 2.5 mg elemental Zinc every 6–8 hours
• Use under physician guidance only
• <2 years: Not recommended due to risk of respiratory depression

Geriatric:

• Use with caution; start at lower dose (e.g., 12.5–25 mg Diphenhydramine) due to increased CNS sensitivity and fall risk

Renal/Hepatic Impairment:

• No specific dosing guidelines, but start with reduced frequency and monitor for toxicity due to diphenhydramine accumulation

Diphenhydramine Hydrochloride is a first-generation H1 antihistamine that exerts its effects by competitively blocking histamine receptors in peripheral tissues and the CNS. This leads to relief from allergic symptoms and sedation. It also has anticholinergic properties that suppress the cough reflex by reducing activity in the medullary cough center.

Zinc Acetate provides elemental zinc, which supports immune function by stabilizing cell membranes, enhancing neutrophil and natural killer cell activity, and exhibiting antiviral effects. In lozenges or systemic formulations, zinc ions interfere with viral replication (especially rhinoviruses) and reduce inflammation in mucosal linings.

Diphenhydramine:

• Absorption: Rapid after oral administration; onset in 15–60 minutes
• Peak concentration: 2–3 hours
• Bioavailability: 40–60%
• Distribution: Crosses blood-brain barrier; ~80–85% protein-bound
• Metabolism: Liver (CYP2D6)
• Half-life: 4–9 hours (prolonged in elderly)
• Excretion: Renal (metabolites in urine)

Zinc Acetate:

• Absorption: Oral absorption varies (20–40%) depending on formulation and presence of food
• Peak levels: 2–3 hours post-dose
• Distribution: Distributed in all tissues; high concentration in muscle and bone
• Metabolism: Not metabolized; acts as an essential trace element
• Excretion: Primarily fecal (via bile); minor renal elimination

• Pregnancy:
• Diphenhydramine: Former FDA Category B — No evidence of fetal harm; avoid high doses, especially in late pregnancy
• Zinc Acetate: Generally regarded as safe in pregnancy when used within recommended dietary limits
• Lactation:
• Diphenhydramine: Excreted in breast milk; may cause sedation or decreased milk supply; avoid chronic use
• Zinc: Passes into breast milk in small amounts; considered safe at standard doses

• Diphenhydramine Hydrochloride: First-generation H1-antihistamine, anticholinergic, antitussive
• Zinc Acetate: Trace mineral supplement; immune modulator and antiviral adjunct

• Hypersensitivity to diphenhydramine, zinc, or any component of the formulation
• Use in neonates or premature infants
• Breastfeeding (systemic diphenhydramine not recommended)
• Concomitant use with other diphenhydramine-containing drugs
• Severe hepatic or renal dysfunction (relative contraindication)
• Known zinc toxicity or Wilson's disease (caution due to altered zinc metabolism)

• CNS depression: Drowsiness and sedation; avoid alcohol and driving
• Anticholinergic effects: Use with caution in glaucoma, prostatic hypertrophy, urinary retention, or elderly patients
• Pediatric safety: Risk of respiratory depression in children under 2 years
• Gastrointestinal disturbance: High zinc doses may cause nausea, abdominal pain, or diarrhea
• Overdose risk: Excess diphenhydramine can lead to hallucinations, seizures, or coma
• Long-term zinc overuse: Risk of copper deficiency and anemia

Diphenhydramine:

• Common:
• CNS: Drowsiness, dizziness, fatigue
• GI: Dry mouth, constipation
• Respiratory: Thickened secretions
• Serious:
• Confusion, hallucinations (high doses)
• Seizures, cardiac arrhythmias (overdose)
• Paradoxical excitation in children

Zinc Acetate:

• Common:
• Metallic taste
• Gastrointestinal upset (nausea, vomiting)
• Rare/Serious:
• Copper deficiency (chronic use)
• Pancreatitis (high-dose toxicity)

• Diphenhydramine:
• Additive sedation with alcohol, opioids, benzodiazepines
• MAO inhibitors: Increased anticholinergic effects — avoid concurrent use
• CYP2D6 inhibitors (e.g., fluoxetine): May increase diphenhydramine levels
• Zinc Acetate:
• Reduces absorption of tetracyclines, fluoroquinolones, and penicillamine — separate administration by 2 hours
• Iron and calcium supplements may interfere with zinc absorption
• Food may reduce zinc bioavailability

• Updated warnings (FDA & pediatric safety): Diphenhydramine not recommended in children under 2 years due to risk of serious respiratory events
• Zinc guidance: Recent data supports short-term zinc use (within 24 hours of symptom onset) to reduce cold duration, but excessive use discouraged
• Clinical preference: Non-sedating antihistamines preferred for allergic rhinitis; diphenhydramine reserved for short-term or symptomatic relief

• Temperature: Store between 20°C and 25°C (68°F to 77°F)
• Light/Humidity: Protect from light and moisture; keep containers tightly closed
• Liquid formulations: Do not freeze; shake well before use
• Handling: Keep out of reach of children; avoid use after expiry
• Zinc lozenges/tablets: Store in a dry place away from excessive heat