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codeine/chlorpheniramine/pseudoephedrine (Dihistine DH, Zodryl DAC Liquid, Ryna-C)

 

Classes: Antitussives, Narcotic Combos

Dosing and uses of Dihistine DH, Zodryl DAC Liquid (codeine/chlorpheniramine/pseudoephedrine)

 

Adult dosage forms and strengths

codeine/chlorpheniramine/pseudoephedrine

oral liquid: Schedule V

  • (10mg/2mg/30mg)/5mL

oral suspension: Schedule V

  • (5mg/1.665mg/25mg)/5mL
  • (5mg/1.43mg/21.43mg)/5mL
  • (5mg/1.25mg/18.75mg)/5mL
  • (5mg/1.11mg/16.665mg)/5mL
  • (5mg/2mg/30mg)/5mL
  • (5mg/1.43mg/20mg)/5mL
  • (5mg/1mg/15mg)/5mL

 

Allergic Rhinitis, Cough, Sinus Congestion

10 mL PO q4-6hr, up to 40 mL/24 hr

 

Pediatric dosage forms and strengths

codeine/chlorpheniramine/pseudoephedrine

oral liquid: Schedule V

  • (10mg/2mg/30mg)/5mL

oral suspension: Schedule V

  • (5mg/1.665mg/25mg)/5mL
  • (5mg/1.43mg/21.43mg)/5mL
  • (5mg/1.25mg/18.75mg)/5mL
  • (5mg/1.11mg/16.665mg)/5mL
  • (5mg/2mg/30mg)/5mL
  • (5mg/1.43mg/20mg)/5mL
  • (5mg/1mg/15mg)/5mL

 

Allergic Rhinitis, Cough, Sinus Congestion

<6 years: not recommended

6-12 years: 5 mL PO q4-6hr, up to 20 mL/24 hr

>12 years: 10 mL PO q4-6hr, up to 40 mL/24 hr

Zodryl DAC dosing 2 to <6 years

  • >10.5-13 kg: Zodryl DAC 25 liquid 3 mL PO q4-6hr, up to 12 mL/24 hr
  • >13-15 kg: Zodryl DAC 35 liquid 4 mL PO q4-6hr, up to 16 mL/24 hr
  • >17-19 kg: Zodryl DAC 40 liquid 4.5 mL PO q4-6hr, up to 18 mL/24 hr

Zodryl DAC dosing 6 to <12 years

  • >19-25.5 kg: Zodryl DAC 50 liquid 5 mL PO q4-6hr, up to 20 mL/24 hr
  • >25.5-32 kg: Zodryl DAC 60 liquid 7.5 mL PO q4-6hr, up to 30 mL/24 hr
  • >32-40 kg: Zodryl DAC 80 liquid 10 mL PO q4-6hr, up to 40 mL/24 hr

 

Dihistine DH, Zodryl DAC Liquid (codeine/chlorpheniramine/pseudoephedrine) adverse (side) effects

>10%

Codeine

  • Drowsiness
  • Constipation

 

1-10%

Codeine

  • Bradycardia, hypotension, tachycardia
  • Confusion, dizziness, false feeling of well being, headache, lightheadedness, malaise, paradoxical CNS stimulation, restlessness, weakness
  • Rash, urticaria
  • Anorexia, nausea, vomiting, xerostomia
  • LFT's increased
  • Ureteral spasm, urination decreased
  • Dyspnea
  • Burning at injection site, blurred vision, histamine release

 

Frequency not defined

Chlorpheniramine

  • Anticholinergic
  • Somnolence
  • Constipation
  • Diarrhea
  • Nausea
  • Vomiting
  • Blurred vision

Codeine (serious)

  • Hypotension, With IV use
  • Seizure, With excessive doses
  • Anaphylactoid reaction (rare)
  • Respiratory depression

Pseudoephedrine

  • CNS (tremor, restlessness, etc)
  • Insomnia
  • Nausea
  • Vomiting

 

Warnings

Contraindications

Codeine

  • Absolute: acute abdominal condition, diarrhea associated w/ toxins, pseudomembranous colitis, respiratory depression
  • Relative: asthma (acute), inflammatory bowel disease, respiratory impairment

Chlorpheniramine

  • Acute asthma, sleep apnea

Pseudoephedrine

  • Hypsesensitivity
  • Severe HTN, severe CAD
  • Nonselective MAO inhibitors: risk of hypertensive reaction
  • Newborns, preemies

 

Cautions

Codeine

  • Cardiac arrhythmias, drug abuse/dependence, emotional lability, gallbladder dz, head injury, hepatic impairment, hypothyroidism, incr ICP, prostatic hypertrophy, renal impairment, seizures w/ epilepsy, urethral stricture, urinary tract surgery
  • Risk of life threatening side effects in nursing babies, especially if mother is an ultra rapid metabolizer of codeine
  • Ibuprofen is more effective than codeine for pain from musculoskeletal injuries in children

Chlorpheniramine

  • Chlor Trimeton non-drowsy contains no chlorpheniramine, only pseudoephedrine

Pseudophedrine

  • Mild-mod HTN, cardiac dz, hyperthyroidism, hyperglycemia, BPH, DM, glaucoma
  • Many combo formulations are switching to phenylephrine d/t restrictions arising from easy conversion to methamphetamine (The Combat Methamphetamine Epidemic Act of 2005 bans OTC sales of cold medicines that contain ingredients commonly used to make methamphetamine such as pseudoephedrine)
  • Lactation

 

Pregnancy and lactation

Pregnancy category: C

Lactation: codeine, chlorpheniramine and pseudoephedrine excreted in breast milk, use caution

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Dihistine DH, Zodryl DAC Liquid (codeine/chlorpheniramine/pseudoephedrine)

Codeine

Half-Life: 3-4 hr

Onset: 30-60 min

Metabolism: Inactive but metabolized to morphine by CYP2D6 (missing in 5-10% of population)

Duration: 4-6 hr

Peak Plasma Time: 0.5-1 hr

Protein Bound: 25%

Excretion: urine, feces

 

Chlorpheniramine

Half-Life: 12-43 hr

Duration: 24 hr

Onset: 6 hr

Peak Plasma Time: 2-6 hr

Protein Bound: 69-72%

Vd: 2.5-3.2 L/kg

Metabolism: GI mucosa, liver

Metabolites: monodesmethylchlorpheniramine, didesmethylchlorpheniramine

Excretion: urine

Sedative effect: low

Antihistamine activity: moderate

Anticholinergic acitivity: moderate

 

Pseudoephedrine

Half-Life: 5-8 hr

Onset: 30 min

Duration: 4-6 hr

Peak PlasmaTime: 1.97 hr

Metabolism: liver, by N-demethylation

Metabolites: inactive

Clearance: 7.3-7.6 mL/min/kg

Excretion: urine

 

Mechanism of action

Codeine: Narcotic agonist analgesic with antitussive activity, mu receptor agonist

Chlorpheniramine: Histamine H1-receptor antagonist

Pseudoephedrine: Alpha adrenergic agonist