Usage
This combination is prescribed for the short-term treatment of moderate to severe acute pain, particularly when pain is not relieved by paracetamol or ibuprofen alone. It’s frequently used for conditions such as headache, migraine, back pain, period pain, toothache, pain from arthritis, and sprains and strains.
Its pharmacological classifications include:
- Analgesic: Relieves pain.
- Anti-inflammatory: Reduces inflammation (ibuprofen component).
- Antipyretic: Reduces fever (paracetamol component).
- Opioid Analgesic: Codeine belongs to this class and acts on the central nervous system.
Mechanism of Action: Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), inhibits cyclooxygenase (COX) enzymes, reducing prostaglandin synthesis, which are mediators of pain and inflammation. Paracetamol is thought to inhibit COX enzymes in the central nervous system, providing analgesic and antipyretic effects. Codeine, a weak opioid, is metabolized to morphine, which binds to opioid receptors in the brain and spinal cord, altering pain perception and response.
Alternate Names
There is no single international non-proprietary name (INN) for this combination. It is often referred to by the names of its components.
Brand Names: Nurofen Plus, some generic brands.
How It Works
Pharmacodynamics: The combination produces synergistic analgesia by addressing pain through multiple pathways. Ibuprofen reduces inflammation peripherally, paracetamol centrally, and codeine modifies pain perception at the level of the central nervous system.
Pharmacokinetics:
- Absorption: All three components are readily absorbed orally. Food can delay ibuprofen absorption but may reduce gastrointestinal side effects.
- Metabolism: Ibuprofen is metabolized in the liver by CYP enzymes. Paracetamol is primarily metabolized in the liver through glucuronidation and sulfation pathways. Codeine is metabolized by the liver, primarily by CYP2D6, to morphine, its active metabolite. Genetic variations in CYP2D6 activity can influence codeine’s effectiveness and side effect profile.
- Elimination: Ibuprofen and its metabolites are primarily excreted renally. Paracetamol metabolites are excreted in the urine. Codeine and its metabolites, including morphine, are also primarily eliminated by the kidneys.
Mode of Action: Ibuprofen inhibits COX-1 and COX-2 enzymes, decreasing prostaglandin production. Paracetamol’s mechanism is not fully understood but is thought to involve central COX inhibition and other pathways. Morphine, the active metabolite of codeine, binds primarily to mu-opioid receptors in the central nervous system, inhibiting pain transmission.
Dosage
Standard Dosage
Adults:
One or two tablets every four to six hours as needed. The maximum daily dose should not exceed six tablets in a 24-hour period.
Children:
This combination is contraindicated in children under 12 years of age. For adolescents aged 12-18 years, this combination should only be used if other analgesics (paracetamol or ibuprofen alone) have not provided adequate pain relief. Dosing should be carefully determined based on the individual’s weight and clinical condition.
Special Cases:
- Elderly Patients: Lower doses may be required due to age-related decline in renal and hepatic function.
- Patients with Renal Impairment: Dose adjustments are necessary based on the degree of impairment.
- Patients with Hepatic Dysfunction: Dose reduction is required in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: Caution is advised in patients with asthma, cardiovascular disease, gastrointestinal ulcers, bleeding disorders, or respiratory conditions.
Clinical Use Cases
The use of this combination in clinical settings like intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations is not routinely recommended. In these contexts, pain management is usually tailored to the individual patient and situation, and stronger opioid analgesics may be preferred.
Dosage Adjustments
Dosage adjustments are essential based on individual patient factors, such as renal or hepatic dysfunction, age, and concomitant medications.
Side Effects
Common Side Effects
Constipation, drowsiness, nausea, vomiting, dizziness, headache, indigestion, abdominal pain.
Rare but Serious Side Effects
Respiratory depression, allergic reactions, Stevens-Johnson syndrome, gastrointestinal bleeding, seizures.
Long-Term Effects
Tolerance to codeine, dependence, opioid-induced constipation.
Adverse Drug Reactions (ADR)
Severe allergic reactions (anaphylaxis), acute liver failure (paracetamol overdose), respiratory depression (codeine).
Contraindications
Hypersensitivity to any of the components, severe asthma, respiratory depression, paralytic ileus, acute abdominal conditions, severe hepatic impairment, pregnancy (especially the third trimester), breastfeeding, use in children under 12.
Drug Interactions
Other opioid analgesics, CNS depressants (alcohol, benzodiazepines), anticoagulants (warfarin), antihypertensives, antidepressants (SSRIs, MAOIs), other NSAIDs, some antibiotics (quinolones).
Pregnancy and Breastfeeding
Codeine is generally contraindicated during pregnancy and breastfeeding. Ibuprofen is generally avoided in the third trimester of pregnancy. Paracetamol is considered safe during pregnancy and breastfeeding.
Drug Profile Summary
- Mechanism of Action: Combined analgesic, anti-inflammatory, and antipyretic effects.
- Side Effects: Constipation, drowsiness, nausea, GI upset.
- Contraindications: Hypersensitivity, respiratory depression, severe hepatic impairment, children <12 years.
- Drug Interactions: Opioids, CNS depressants, anticoagulants, NSAIDs.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: Adults: 1-2 tablets every 4-6 hours, max 6 tablets/24 hours. Children <12 years: Contraindicated.
- Monitoring Parameters: Pain scores, respiratory rate, blood pressure, liver function tests (if long-term use).
Popular Combinations
This combination itself is considered a popular combination for pain relief when single agents are insufficient.
Precautions
Assess renal and hepatic function, monitor for respiratory depression and allergic reactions, avoid alcohol, caution in patients with asthma or gastrointestinal disorders, inform patients about potential drowsiness and driving restrictions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Codeine + Ibuprofen + Paracetamol?
A: Adults: 1-2 tablets every 4-6 hours, not exceeding 6 tablets in 24 hours. Children under 12: Contraindicated.
Q2: Can this combination be used in pregnant or breastfeeding women?
A: It is generally contraindicated due to the risks associated with codeine.
Q3: What are the common side effects?
A: Constipation, drowsiness, nausea, vomiting, and dizziness are common.
Q4: What are the serious side effects that require medical attention?
A: Respiratory depression, allergic reactions, severe gastrointestinal bleeding, or signs of liver toxicity.
Q5: Can I take this medication with other painkillers?
A: Avoid concomitant use with other NSAIDs or opioid analgesics. Consult a physician or pharmacist before combining with other medications.
Q6: How long can I take this combination?
A: It is intended for short-term use, typically not exceeding three days. Consult a physician if pain persists beyond three days.
Q7: What should I do if I miss a dose?
A: Take the missed dose as soon as you remember, unless it is close to the time for your next dose. Do not double the dose.
Q8: Can I drink alcohol while taking this medicine?
A: Alcohol should be avoided as it can exacerbate drowsiness and increase the risk of other side effects.
Q9: What if I experience stomach upset while on this medication?
A: Taking the medication with food can often help mitigate gastrointestinal side effects. If upset persists, consult with a healthcare professional.
Q10: Are there any long-term risks associated with this combination?
A: Prolonged use can lead to tolerance to codeine and potential dependence. Long-term use of ibuprofen can also increase the risk of gastrointestinal complications.
