Dihydrocodeine phosphate
Also known as: Dihydrocodeine phosphate, DHC, Paracodin, Drocode, DHC Continus
Overview
Dihydrocodeine phosphate is a semi-synthetic opioid analgesic derived from codeine, primarily utilized for the management of moderate to moderately severe pain. Unlike naturally occurring opioids, it is synthesized from thebaine, an alkaloid found in the opium poppy. While its main application is pain relief, it has also been explored, particularly in some regions, for opioid substitution therapy, though evidence in this area is limited. Dihydrocodeine acts as a prodrug, meaning it is metabolized in the body into active compounds, such as dihydromorphine, which then exert their effects. It is available in both oral and injectable forms. Research on dihydrocodeine is moderate, with several randomized controlled trials (RCTs) and systematic reviews available. However, the extent of evidence is less comprehensive compared to more commonly used opioids like morphine or oxycodone, and existing studies often suffer from limitations such as small sample sizes, heterogeneity, and potential for bias.
Benefits
Dihydrocodeine phosphate offers modest benefits primarily in pain management. For acute postoperative pain, a single 30 mg dose has been shown to provide at least 50% pain relief in significantly more patients than a placebo (RR 1.59, 95% CI 1.01–2.50). However, its efficacy is inferior to non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen 400 mg for the same outcome (RR 0.17 for 30 mg DHC; RR 0.33 for 60 mg DHC), indicating that NSAIDs are superior for acute pain relief. The clinical significance of dihydrocodeine in postoperative pain is therefore questionable given the availability of more effective alternatives. Limited, low-quality evidence suggests potential utility in opioid detoxification and maintenance, showing no significant difference compared to buprenorphine or methadone in abstinence rates or treatment retention. However, the quality of this evidence is low due to high risk of bias and imprecision. There is no robust evidence to suggest unique benefits for specific patient populations, and general opioid precautions apply.
How it works
Dihydrocodeine phosphate exerts its analgesic effects primarily by binding to μ-opioid receptors located in the central nervous system (CNS). This binding inhibits the transmission of pain signals, thereby reducing the perception of pain. As a prodrug, dihydrocodeine is metabolized by the CYP2D6 enzyme system into active metabolites, notably dihydromorphine, which also contribute to its pharmacological effects. Its interaction with body systems extends beyond pain relief, affecting the CNS to induce sedation and respiratory depression, and the gastrointestinal system, commonly leading to constipation. Dihydrocodeine exhibits good oral bioavailability, with peak plasma concentrations typically achieved within 1.5 to 2 hours after administration.
Side effects
Dihydrocodeine phosphate, like other opioids, carries a risk of various side effects, dependence, tolerance, and respiratory depression, with potential for overdose. Common side effects, affecting more than 5% of users, include nausea, vomiting, constipation, dizziness, and sedation. Less common side effects (1–5%) may involve pruritus (itching), sweating, dry mouth, and urinary retention. Rare but severe side effects (less than 1%) can include profound respiratory depression, anaphylaxis, and seizures. Dihydrocodeine can interact with other medications, particularly those that depress the central nervous system, such as alcohol, benzodiazepines, and other opioids, leading to enhanced CNS depression. Inhibitors of the CYP2D6 enzyme may alter its metabolism, potentially affecting its efficacy or increasing side effects. Contraindications for its use include pre-existing respiratory depression, acute asthma, paralytic ileus, and hypersensitivity to opioids. Caution is advised when administering dihydrocodeine to elderly patients, individuals with hepatic or renal impairment, and those with a history of substance use disorder due to increased risk of adverse effects.
Dosage
The minimum effective dose of dihydrocodeine phosphate for acute pain is typically 30 mg orally. The optimal dosage range for pain management is generally 30–60 mg, taken every 4–6 hours as needed. Individual titration is crucial to achieve adequate pain relief while minimizing side effects. The maximum safe dose varies by indication and patient, but generally, a daily dose should not exceed 240 mg without specialized medical supervision. Onset of action is usually within 30–60 minutes, with effects lasting approximately 4–6 hours. Oral tablets are the most common formulation, though extended-release formulations are available in some regions. While food may delay absorption, it does not significantly impact the overall bioavailability of the drug. No specific cofactors are identified as necessary for its action.
FAQs
Is dihydrocodeine better than NSAIDs for pain?
No, high-quality evidence indicates that NSAIDs like ibuprofen are superior to dihydrocodeine for acute postoperative pain relief, making them a more effective choice.
Can dihydrocodeine be used for opioid addiction?
Limited, low-quality evidence suggests it might be comparable to buprenorphine or methadone for detoxification/maintenance, but more robust research is needed to confirm its role.
How quickly does it work?
Analgesic effects of dihydrocodeine typically begin within 30–60 minutes after administration, providing relatively quick pain relief.
What are the risks?
Key risks include dependence, respiratory depression, constipation, and sedation, which are common to opioid medications and require careful monitoring.
Is dihydrocodeine a first-line analgesic?
No, it is not considered a first-line analgesic for most acute pain conditions, as superior and safer alternatives often exist.
Research Sources
- https://pmc.ncbi.nlm.nih.gov/articles/PMC4176625/ – This systematic review found that dihydrocodeine 30 mg provided significantly more pain relief than placebo for acute postoperative pain. However, it was inferior to ibuprofen 400 mg, highlighting its modest efficacy compared to NSAIDs. The study noted limitations due to small sample sizes and few direct comparisons.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC7027221/ – This systematic review investigated dihydrocodeine's use in opioid detoxification and maintenance. It found no significant difference between dihydrocodeine and buprenorphine/methadone for abstinence or retention, but emphasized the low quality of evidence due to high risk of bias and imprecision in the included studies.
- https://www.cmaj.ca/content/193/24/e895 – This systematic review and meta-analysis, while not directly on dihydrocodeine, compared NSAIDs to codeine for postoperative pain. It concluded that NSAIDs are superior, indirectly suggesting that dihydrocodeine, as a codeine derivative, would also be less effective than NSAIDs for similar pain conditions.
