Phenylephrine + Promethazine

Approved Indications:

• Allergic Rhinitis:
  Relief of nasal congestion, sneezing, rhinorrhea, and itching associated with seasonal or perennial allergic rhinitis.
• Common Cold and Upper Respiratory Tract Infections:
  Symptomatic management of nasal congestion, rhinorrhea, and sneezing.
• Acute and Chronic Sinusitis:
  Adjunctive treatment to relieve sinus congestion and promote drainage.
• Allergic Conjunctivitis (nasal-related):
  Used when nasal symptoms are predominant.

Clinically Accepted Off-label Uses:

• Motion Sickness (due to promethazine):
  Reduction of nausea, dizziness, and vomiting.
• Post-nasal Drip Cough:
  Management of cough secondary to nasal secretions dripping into the throat.

Route of Administration: Oral
Available Forms: Tablets, Syrup

Adults and Adolescents (≥12 years):

• Usual Dose:
  Phenylephrine HCl 10 mg + Promethazine HCl 12.5 mg orally every 6 hours as needed
  Maximum: 4 doses (in 24 hours)

Children 6 to 12 years:

• Phenylephrine HCl 5 mg + Promethazine HCl 6.25 mg orally every 6 hours
  Maximum: 4 doses daily

Children 2 to <6 years:

• Use with caution and under physician supervision only
  Typical dose: Phenylephrine HCl 2.5–5 mg + Promethazine HCl 2.5–6.25 mg orally every 6–8 hours
  Maximum: 3–4 doses per 24 hours

Children <2 years:

• Contraindicated due to risk of severe respiratory depression from promethazine

Elderly:

• Start at the lower end of the dosing range
• Monitor closely for sedation, confusion, and hypotension

Renal Impairment:

• Use with caution; no specific dosage adjustment but monitor for accumulation or prolonged effects

Hepatic Impairment:

• Use with caution due to promethazine metabolism in the liver
• Monitor for signs of CNS depression or toxicity

Phenylephrine is a selective alpha-1 adrenergic receptor agonist that causes vasoconstriction of blood vessels in the nasal mucosa, reducing swelling and nasal congestion. Promethazine is a first-generation H1-antihistamine that competitively blocks histamine H1 receptors, alleviating symptoms such as sneezing, itching, and rhinorrhea. Additionally, promethazine exhibits anticholinergic, antiemetic, and sedative effects through its action on muscarinic and dopamine receptors. The combination provides dual relief: phenylephrine relieves nasal congestion, while promethazine controls allergic symptoms and provides sedation when necessary.

Phenylephrine:

• Absorption: Moderate oral absorption with significant first-pass metabolism
• Bioavailability: ~38%
• Onset: 15–30 minutes
• Peak Plasma Time: 1–2 hours
• Half-life: ~2.5 to 3 hours
• Metabolism: Hepatic via monoamine oxidase (MAO)
• Excretion: Primarily renal, mostly as metabolites

Promethazine:

• Absorption: Rapid and complete oral absorption
• Bioavailability: High
• Onset: 20–60 minutes
• Duration: 4–6 hours
• Half-life: 10–19 hours
• Metabolism: Hepatic (CYP2D6 and others)
• Excretion: Renal, mostly as metabolites

• Pregnancy:
  Both agents should be used only if clearly needed. Promethazine has not shown teratogenicity in humans but may cause neonatal respiratory depression or extrapyramidal effects if used near term. Phenylephrine may reduce uteroplacental blood flow. Avoid use during the first trimester when possible.
• Lactation:
  Promethazine is excreted in breast milk and may cause sedation, irritability, or apnea in nursing infants. Phenylephrine may reduce milk production due to its vasoconstrictive action. Use only when benefits clearly outweigh potential risks.

• Phenylephrine: Sympathomimetic (Decongestant)
• Promethazine: First-generation H1 Antihistamine (with anticholinergic and sedative effects)

• Known hypersensitivity to phenylephrine, promethazine, or any formulation component
• Use in children under 2 years of age (risk of fatal respiratory depression)
• Concurrent use of monoamine oxidase inhibitors (within 14 days)
• Severe hypertension or coronary artery disease
• Narrow-angle glaucoma
• Severe liver dysfunction or coma
• Prostatic hypertrophy with urinary retention

• Boxed Warning (Promethazine):
  Do not use in children under 2 years due to risk of fatal respiratory depression.
• CNS Effects:
  Promethazine may cause significant sedation, impaired coordination, and confusion, especially in the elderly.
• Respiratory Depression:
  High doses or use in children may cause life-threatening respiratory suppression.
• Cardiovascular Effects:
  Phenylephrine can increase blood pressure; monitor in patients with cardiovascular disease.
• Seizure Risk:
  Promethazine may lower the seizure threshold.
• Anticholinergic Effects:
  May cause dry mouth, urinary retention, blurred vision, and constipation.
• Use with Sedatives:
  Avoid alcohol and CNS depressants due to additive sedation.

Common:

• CNS: Drowsiness, dizziness, headache
• GI: Nausea, vomiting, dry mouth, constipation
• ENT: Nasal dryness, throat irritation
• Ocular: Blurred vision

Less Common:

• Cardiovascular: Palpitations, hypertension, reflex bradycardia
• Dermatologic: Rash, urticaria, photosensitivity
• Neurological: Confusion, restlessness (especially in children or elderly)

Serious (Rare):

• Respiratory depression
• Seizures
• Hallucinations
• Neuroleptic malignant syndrome
• Extrapyramidal symptoms
• Severe allergic reactions (anaphylaxis)

• MAO Inhibitors (e.g., phenelzine, tranylcypromine): Hypertensive crisis risk; contraindicated within 14 days
• Alcohol, benzodiazepines, opioids: Additive CNS and respiratory depression
• Beta-blockers and antihypertensives: Reduced effectiveness due to phenylephrine
• Anticholinergic drugs (e.g., atropine): Increased anticholinergic side effects
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May affect promethazine metabolism

Metabolic Pathways:

• Promethazine: CYP2D6 metabolism
• Phenylephrine: Not metabolized by CYP450; metabolized by MAO

• FDA (2023):
  Reaffirmed black box warning on promethazine for children <2 years.
• AAP (American Academy of Pediatrics):
  Advises against the use of over-the-counter cough/cold medications containing antihistamines and decongestants in children under 6 years.
• NICE (UK):
  Recommends caution in use of sedating antihistamine/decongestant combinations, especially in pediatric and elderly patients.

• Tablets and Syrup:
  Store at 20°C to 25°C (68°F to 77°F)
  Allowable excursions: 15°C to 30°C
• Light and Humidity:
  Store in a dry place, protected from light and moisture
• Handling Instructions:
• Shake syrup well before use
• Keep container tightly closed
• Do not refrigerate unless directed
• Keep out of reach of children
• Do not use after expiration date