Brufen plus (ibuprofen + codeine): Uses, Dosage & Side Effects

What it's for (Indications)

This fixed-dose combination medication, containing ibuprofen and codeine, is primarily indicated for the short-term management of acute, moderate to severe pain when treatment with an opioid analgesic is appropriate and alternative treatments are inadequate.
Such pain conditions may include post-operative pain, dental pain, severe musculoskeletal pain, and pain associated with trauma.
The combination leverages the analgesic and anti-inflammatory properties of ibuprofen with the central opioid analgesic effects of codeine to provide enhanced pain relief compared to either agent alone.
Careful consideration of the patient's individual pain intensity and response to therapy is crucial, ensuring its use is restricted to situations where less potent analgesics are insufficient to control pain effectively, and where the benefits are deemed to outweigh the significant risks associated with opioid and NSAID use.

Dosage Information

Type	Guideline
Standard	Dosage for ibuprofen + codeine must be individualized based on the severity of pain, patient response, and prior analgesic experience, always using the lowest effective dose for the shortest possible duration. For adults, a common starting dosage involves taking one or two tablets containing 200 mg ibuprofen and 12.8 mg codeine phosphate, or similar strength, orally every four to six hours as needed for pain, not exceeding four doses in any 24-hour period. The maximum daily dose for ibuprofen typically should not exceed 1200 mg (or 2400 mg in specific cases under strict medical supervision), and for codeine, it should not exceed 240 mg. Renal or hepatic impairment necessitates dose reduction and increased monitoring due to altered drug metabolism and excretion, particularly for codeine and its active metabolites. This medication is not recommended for prolonged use due to the risks associated with both components, including dependence, gastrointestinal adverse events, and cardiovascular risks.

Type

Guideline

Standard

Dosage for ibuprofen + codeine must be individualized based on the severity of pain, patient response, and prior analgesic experience, always using the lowest effective dose for the shortest possible duration. For adults, a common starting dosage involves taking one or two tablets containing 200 mg ibuprofen and 12.8 mg codeine phosphate, or similar strength, orally every four to six hours as needed for pain, not exceeding four doses in any 24-hour period. The maximum daily dose for ibuprofen typically should not exceed 1200 mg (or 2400 mg in specific cases under strict medical supervision), and for codeine, it should not exceed 240 mg. Renal or hepatic impairment necessitates dose reduction and increased monitoring due to altered drug metabolism and excretion, particularly for codeine and its active metabolites. This medication is not recommended for prolonged use due to the risks associated with both components, including dependence, gastrointestinal adverse events, and cardiovascular risks.

Safety & Warnings

Common Side Effects

The combination of ibuprofen and codeine can lead to a broad spectrum of side effects, reflecting the individual profiles of each component.
Common adverse effects attributable to ibuprofen include gastrointestinal disturbances such as nausea, vomiting, dyspepsia, abdominal pain, diarrhea, and constipation, with a risk of more serious events like gastrointestinal bleeding, ulceration, and perforation.
Renal impairment, fluid retention, edema, and hypertension are also possible.
For codeine, frequently observed side effects include dizziness, drowsiness, sedation, constipation, nausea, vomiting, pruritus, and dry mouth.
More serious, albeit less common, side effects associated with codeine involve respiratory depression, circulatory depression, orthostatic hypotension, urinary retention, and the potential for psychological and physical dependence, and withdrawal symptoms upon abrupt cessation.
Hypersensitivity reactions, including skin rashes, angioedema, and anaphylaxis, can occur with either component.
Patients should be advised to report any concerning symptoms promptly to their healthcare provider.

Serious Warnings

Black Box Warning: WARNING: ADDICTION, ABUSE, AND MISUSE; RISK EVALUATION AND MITIGATION STRATEGY (REMS); RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; ULTRA-RAPID METABOLISM OF CODEINE AND OTHER RISK FACTORS FOR LIFE-THREATENING RESPIRATORY DEPRESSION IN CHILDREN; NEONATAL OPIOID WITHDRAWAL SYNDROME; INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES; and CARDIOVASCULAR AND GASTROINTESTINAL RISKS. Addiction, Abuse, and Misuse: Ibuprofen + codeine exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Healthcare providers must assess each patient’s risk for opioid addiction, abuse, or misuse prior to prescribing and monitor all patients receiving ibuprofen + codeine for the development of these behaviors and conditions. REMS: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. This REMS includes requirements for drug labeling, an Elements to Assure Safe Use (ETASU), and a timeline for assessing the REMS. Life-Threatening Respiratory Depression: Serious, life-threatening, or fatal respiratory depression may occur with the use of ibuprofen + codeine. Patients must be monitored closely, especially during initiation or following a dose increase. Accidental Ingestion: Accidental ingestion of ibuprofen + codeine, especially by children, can result in a fatal overdose of codeine. Ultra-Rapid Metabolism of Codeine and Other Risk Factors for Life-Threatening Respiratory Depression in Children: Life-threatening respiratory depression and death have occurred in children who received codeine. Most cases occurred in children with obstructive sleep apnea who received codeine following tonsillectomy and/or adenoidectomy, and in some of these children, there was evidence of being an ultra-rapid metabolizer of codeine due to a CYP2D6 polymorphism. Ibuprofen + codeine is contraindicated in children younger than 12 years of age and in adolescents younger than 18 years of age following tonsillectomy and/or adenoidectomy. Neonatal Opioid Withdrawal Syndrome: Prolonged use of ibuprofen + codeine during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Interactions with Drugs Affecting Cytochrome P450 Isoenzymes: The concomitant use of ibuprofen + codeine with benzodiazepines or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Limit dosage and duration of concomitant use. Co-administration of CYP3A4 inhibitors or inducers may lead to clinically significant changes in codeine plasma concentrations. Cardiovascular Thrombotic Events (Ibuprofen): Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use. Ibuprofen + codeine is contraindicated in the setting of coronary artery bypass graft (CABG) surgery. Gastrointestinal Risk (Ibuprofen): NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events.
Multiple significant warnings accompany the use of ibuprofen + codeine due to the inherent risks of both an NSAID and an opioid.
Patients should be cautioned against concurrent use with alcohol or other central nervous system (CNS) depressants, including benzodiazepines, sedatives, hypnotics, tranquilizers, and other opioids, due to the exacerbated risk of profound sedation, respiratory depression, coma, and death.
The ibuprofen component carries warnings regarding increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal.
This risk may occur early in treatment and may increase with duration of use and in patients with pre-existing cardiovascular disease.
Serious gastrointestinal adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, can occur at any time, often without warning symptoms.
The codeine component presents risks of addiction, abuse, and misuse, which can lead to overdose and death.
Life-threatening respiratory depression is a primary concern with codeine, particularly in pediatric patients, elderly individuals, and those with compromised respiratory function.
Cases of ultrarapid metabolization of codeine to morphine have resulted in serious adverse events and death, especially in children following tonsillectomy and/or adenoidectomy.
Neonatal Opioid Withdrawal Syndrome can occur if used during pregnancy.
Renal papillary necrosis and other renal injury can result from long-term NSAID use.
Patients with asthma, particularly aspirin-sensitive asthma, are at higher risk for NSAID-induced bronchospasm.
Driving or operating heavy machinery is contraindicated due to potential for impaired mental and physical abilities.

How it Works (Mechanism of Action)

The therapeutic efficacy of the ibuprofen + codeine combination stems from the complementary analgesic mechanisms of its two active constituents. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), exerts its primary pharmacological action by reversibly inhibiting the cyclooxygenase (COX) enzymes, specifically both COX-1 and COX-2 isoforms. This inhibition leads to a reduction in the synthesis of prostaglandins, which are lipid compounds involved in mediating pain, inflammation, and fever. By decreasing prostaglandin production, ibuprofen effectively reduces inflammation, alleviates pain, and lowers fever through peripheral mechanisms. Codeine, on the other hand, is an opioid analgesic and a prodrug. Its analgesic effect is primarily mediated through its metabolism by the cytochrome P450 2D6 (CYP2D6) enzyme into morphine, its active metabolite. Morphine then binds to mu-opioid receptors in the central nervous system, particularly in areas involved in pain perception, modulating the perception of pain and the emotional response to it. This binding inhibits ascending pain pathways, alters the perception of and response to pain, and produces general central nervous system depression. The combined effect of peripherally acting ibuprofen and centrally acting codeine provides a more potent analgesic effect than either drug administered alone, addressing different facets of the pain pathway for comprehensive pain relief.

Commercial Brands (Alternatives)

No other brands found for this formula.