codeine/pseudoephedrine (Rx)

>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
• Blurred vision, histamine release

Frequency Not Defined

Codeine (serious)

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

Pseudoephedrine

• Insomnia
• Restlessness
• Tremor
• Nausea
• Vomiting

Contraindications

Codeine

• Hypsesensitivity
• Absolute: acute abdominal condition, diarrhea associated with toxins, pseudomembranous colitis, respiratory depression
• Relative: Asthma (acute), inflammatory bowel disease, respiratory impairment

Pseudoephedrine

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

Cautions

Codeine

• Caution in cardiac arrhythmias, drug abuse/dependence, emotional lability, gallbladder dz, head injury, hepatic impairment, hypothyroidism, increased ICP, prostatic hypertrophy, renal impairment, seizures with 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

Pseudophedrine

• Mild-mod HTN, cardiac disease, hyperthyroidism, hyperglycemia, BPH, DM, glaucoma
• Many combo formulations are switching to phenylephrine due to 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 category: C

Lactation: codeine 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.

Mechanism of Action

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

Pseudoephedrine: Alpha adrenergic agonist

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

Bioavailability: 53%

Peak Plasma Time: 0.5-1 hr

Protein Bound: 25%

Excretion: Urine (90%); feces

Pseudoephedrine

Half-Life: 3 hr (children); 9-16 hr (adults)

Onset: 30 min (decongestant)

Duration: 3-8 hr

Peak PlasmaTime: 1.97 hr

Metabolism: Liver, by N-demethylation

Vd: 2.5 L/kg (children); 2.64-3.51 L/kg

Metabolites: inactive

Clearance: 7.3-7.6 mL/min/kg

Excretion: Urine (43-96%)