Acetaminophen with Codeine (Tylenol® with Codeine No.3)

Controlled Substances

Only midwives who have completed the “Opioids and Benzodiazepines: Safe Prescribing for Midwives” course may independently prescribe controlled substances.

An analgesic, combined opioid which peripherally blocks pain impulses as synthesis of prostaglandins in the CNS is inhibited.

Binding to opiate receptors in the CNS alters perception and response to pain which causes generalized CNS depression. Produces antipyresis and binds to opiate receptors in the CNS, altering perception and response to pain.

Indications and Clinical Use:

Acetaminophen and codeine combined is used for < 72 hours to relieve moderate to severe pain in the postpartum period following vaginal and/or operative delivery.

Note: a number of non-codeine-containing pain medications taken at regularly scheduled intervals in the first few days postpartum often will provide adequate pain relief without the risks or side effects of codeine exposure.

Contraindications:

Hypersensitivity to acetaminophen, codeine, or any component found in the formulation. Contraindicated in patients with respiratory depression, bronchial asthma, hypercapnia, paralytic ileus, or known CYP2D6 ultra-metabolizers who are breastfeeding due to risk of neonatal poisoning.

Warnings and Precautions:

Due to the potential neonatal adverse effects of codeine acetaminophen with codeine should NOT be taken during lactation. If a pain medication is required, a different narcotic is preferred. Acetaminophen and codeine may also contain caffeine which can cause CNS and cardiovascular stimulation. Use with caution in patients with a history of peptic ulcer or GERD. May cause hepatotoxicity in the following: excessive use >4 g/day of acetaminophen-containing medications, alcohol use, pre-existing liver disease or chronic daily use.

Caution:

Metabolism of the codeine portion is variable. Codeine must be metabolized to its active metabolite, morphine, to have a pain-relieving effect. Some people are rapid metabolizers, and may experience enhanced effect but also enhanced adverse effects such as drowsiness and sedation. Where there is a genetic predisposition to rapid metabolizing (CYP 2D6 enzyme) and increased conversion to morphine, breastfed neonates can be at significant, even life-threatening, risk. Given that an ultra-rapid metabolizer genotype occurs in 1% in Caucasians and up to 30% in some parts of Asia and Africa, this polymorphism is clinically important. One case of neonatal death has been reported and multiple cases of neonatal apnea have occurred with the use of the medication in lactation. Exposure to acetaminophen with codeine during breastfeeding is not recommended.

Note: Some people cannot metabolize codeine to morphine, so for these people, codeine is not effective.

Pregnancy:

Acetaminophen – Human Data Suggest Low Risk

Codeine – Human Data Suggest Risk

There is a risk of congenital birth defects if exposure occurs during organogenesis. There is evidence of fetal and neonate toxicity if addicted to codeine or other opioids, or if high doses of these agents during the later half of pregnancy or close to delivery are consumed. Avoid in the 1st and 3rd trimesters of pregnancy.

Lactation:

Acetaminophen – Category L1 – Compatible

Codeine – Category L4 – Limited Data – Possibly Hazardous

Codeine is not recommended for use in lactation or the pediatric population because of its variable metabolism, via the CYP 2D6 enzyme, to its active metabolite (morphine). In addition, about 9-35% of an adult dose of morphine is known to enter breastmilk, the amount of morphine that would enter milk after codeine ingestion can be highly variable based on metabolism. There have been case reports of apnea and respiratory depression causing death with use of this medication in lactation. If ongoing narcotic is required postpartum consider other alternative agents such as hydromorphone.

Adverse Reactions:

In greater than 10%: Dizziness, lightheadedness, sedation, nausea, vomiting, dyspnea.

In 1% to 10%: Dysphoria, pruritus, abdominal pain, constipation.

Dosage and Administration:

Acetaminophen 300 mg and codeine phosphate 30 mg;

Based on codeine (30 – 60 mg/dose) every 4-6 hours,

Maximum dose:

Codeine 240 mg/24 hours and Acetaminophen 4000 mg/24 hours;

Dose adjustment/titration should be made according to appropriate analgesic effect as long a maximum dose is not exceeded.

Onset of Action:

30-60minutes

Time to peak effect: 60-90 minutes

Half-Life:

Adult – PO: 2 hours for acetaminophen, 3 hours for codeine and.5 hours for caffeine

Neonate – 7 hours for acetaminophen, 4.5-13.3 active metabolite morphine, 72-96 hours for caffeine

Elimination:

In urine as metabolites

Prescription:

Acetaminophen with codeine no.3 may be prescribed in hospital or in the community. It does not require a duplicate prescription pad. A prescription cannot exceed three days. No refills. Please be sure to follow the guidelines on page 2 of this document.