INN monograph
Dihydrocodeine
Central Nervous System Stimulant [EPC], Methylxanthine [EPC] · POM
Verified · Updated 01 Aug 2026 · Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Professional class pharmacology (Opioid analgesic)
Kenya market
Wholesale / list prices where loaded
Risk first
Contraindications
- CONTRAINDICATIONS: Dihydrocodeine-containing products are contraindicated for postoperative pain management in children who have undergone tonsillectomy and/or adenoidectomy.
- This combination product is contraindicated in patients with hypersensitivity to dihydrocodeine, codeine, acetaminophen, caffeine, or any of the inactive components listed above, or any situation where opioids are contraindicated including significant respiratory depression (in unmonitored settings or in the absence of resuscitative equipment), acute or severe bronchial asthma or hypercapnia, and paralytic ileus.
Precautions
- WARNINGS: Hepatotoxicity : Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death.
- Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 milligrams per day, and often involve more than one acetaminophen containing product.
- The excessive intake of acetaminophen may be intentional to cause self-harm or unintentional as patients attempt to obtain more pain relief or unknowingly take other acetaminophen-containing products.
- The risk of acute liver failure is higher in individuals with underlying liver disease and in individuals who ingest alcohol while taking acetaminophen.
- Instruct patients to look for acetaminophen or APAP on package labels and not to use more than one product that contains acetaminophen.
- Instruct patients to seek medical attention immediately upon ingestion of more than 4000 milligrams of acetaminophen per day, even if they feel well.
- Serious Skin Reactions Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal.
- Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.
- Death Related to Ultra-Rapid Metabolism of Codeine to Morphine: Respiratory depression and death have occurred in children who received codeine in the postoperative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme 2D6 or high morphine concentrations).
- Deaths have also occurred in nursing infants who were exposed to high levels of morphine in breast milk because their mothers were ultra-rapid metabolizers of codeine [see Error! Hyperlink reference not valid. ].
- Some individuals may be ultra-rapid metabolizers because of a specific CYP2D6 genotype (gene duplications denoted as *1/*1xN or *1/*2xN).
- The prevalence of this CYP2D6 phenotype varies widely and has been estimated at 0.5 to 1% in Chinese and Japanese, 0.5 to 1% in Hispanics, 1 to 10% in Caucasians, 3% in African Americans, and 16 to 28% in North Africans, Ethiopians, and Arabs.
Point of care
Dosing
Adult
DOSAGE AND ADMINISTRATION: The usual adult dosage is two (2) TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsules orally every four (4) hours, as needed. Dosage should be adjusted according to the severity of the pain and the response of the patient. No more than two (2) capsules should be taken in a 4-hour period. No more than five (5) doses, or ten (10) capsules should be taken in a 24-hour period.
Paediatric
Pediatric Use: Safety and effectiveness of TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsules in pediatric patients have not been established. Respiratory depression and death have occurred in children with obstructive sleep apnea who received codeine in the post-operative period following tonsillectomy and/or adenoidectomy and had evidence of being ultra-rapid metabolizers of codeine (i.e., multiple copies of the gene for cytochrome P450 isoenzyme CYP2D6 or high morphine concentrations). These children may be particularly sensitive to the respiratory depressant effects of codeine that has been rapidly metabolized to morphine. Dihydrocodeine-containing products are contraindicated for post-operative pain management in all pediatric patients undergoing tonsillectomy and/or adenoidectomy [see CONTRAINDICATIONS ].
Renal
Prefer fentanyl/methadone expert use over morphine in advanced CKD; reduce doses.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic
Reduce dose/frequency; avoid long-acting in decompensated disease.
Safety
Drug interactions
- WHO ladder still useful framework.
- For cancer pain use around-the-clock + breakthrough.
- Naloxone for overdose.
- Document functional goals
- review long-term opioid benefit regularly.
Safety
Adverse effects
- ADVERSE REACTIONS: Dihydrocodeine: The most frequently observed adverse reactions include light-headedness, dizziness, drowsiness, headache, fatigue, sedation, sweating, nausea, vomiting, constipation, pruritus, and skin reactions.
- With the exception of constipation, tolerance develops to most of these effects.
- Other reactions that have been observed with dihydrocodeine or other opioids include respiratory depression, orthostatic hypotension, cough suppression, confusion, diarrhea, miosis, abdominal pain, dry mouth, indigestion, anorexia, spasm of biliary tract, and urinary retention.
- Physical and psychological dependence are possibilities.
- Hypersensitivity reactions (including anaphylactoid reactions), hallucinations, vivid dreams, granulomatous interstitial nephritis, severe narcosis and acute renal failure have been reported rarely during dihydrocodeine administration.
- Acetaminophen: Acetaminophen in therapeutic doses rarely causes adverse reactions.
- The most serious adverse reaction is hepatoxicity from overdosage (see OVERDOSAGE ).
- Thrombocytopenia, leukopenia, pancytopenia, neutropenia, thrombocytopenic purpura, and agranulocytosis have been reported in patients receiving acetaminophen or p-aminophenol derivatives.
- Hypersensitivity reactions including urticarial or erythematous skin reactions, laryngeal edema, angioedema, or anaphylactoid reactions are rare.
- Caffeine: Adverse reactions associated with caffeine use include anxiety, anxiety neurosis, excitement, headaches, insomnia, irritability, lightheadedness, restlessness, tenseness, tremor, extrasystoles, palpitations, tachycardia, diarrhea, nausea, stomach pain, vomiting, diuresis, urticaria, scintillating scotoma, and tinnitus.
Use
Indications
- INDICATIONS AND USAGE: TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsulesare indicated for the relief of moderate to moderately severe pain.
- Clinical selection for Dihydrocodeine should follow culture results where relevant, Kenya STG/EML recommendations, and the current product SmPC.
- Class context: Central Nervous System Stimulant [EPC], Methylxanthine [EPC].
- Confirm site-specific dose, duration and monitoring before prescribing.
Pharmacology
Mode of action
Opioids agonise CNS mu (primarily), kappa and delta receptors, inhibiting ascending pain pathways and altering pain perception/response.
Full mechanism text
Opioids agonise CNS mu (primarily), kappa and delta receptors, inhibiting ascending pain pathways and altering pain perception/response. Also cause respiratory depression, miosis, cough suppression and reduced GI motility.
ADME
Pharmacokinetics & PD
| Onset | Minutes (IV) to hour (oral) |
|---|---|
| Duration | Hours (agent-dependent) |
| Route | ORAL / IV / IM / SC / TD / RECTAL |
Full PK/PD text
CLINICAL PHARMACOLOGY: TREZIX™ capsules contain dihydrocodeine which is a semi-synthetic narcotic analgesic related to codeine, with multiple actions qualitatively similar to those of codeine; the most prominent of these involve the central nervous system and organs with smooth muscle components. The principal action of therapeutic value is analgesia. This combination product also contains acetaminophen, a non-opiate, non-salicylate analgesic and antipyretic. This combination product contains caffeine as an analgesic adjuvant. Caffeine is also a CNS and cardiovascular stimulant.
Kenya
Brands & prices
| Brand | Company | Pack | KES |
|---|---|---|---|
| D.F. 118 | GlaxoSmithkline | Standard Commercial Pack | — |
| DHC | Cosmos Limited. | Standard Commercial Pack | 1,862.39 |
Special populations
Pregnancy & lactation
Pregnancy
Pregnancy: Teratogenic Effects – Pregnancy Category C . Animal reproduction studies have not been conducted with TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate) capsules. It is also not known whether this combination product can cause fetal harm when administered to pregnant women or can affect reproduction capacity in males and females. This combination product should be given to pregnant women only if clearly needed, especially during the first trimester.
Lactation
Nursing Mothers: Dihydrocodeine bitartrate is secreted into human milk. In women with normal dihydrocodeine metabolism (normal CYP2D6 activity), the amount of dihydrocodeine secreted into human milk is low and dose-dependent. However, some women are ultra-rapid metabolizers of dihydrocodeine. These women achieve higher-than-expected serum levels of dihydrocodeine’s active metabolite, dihydromorphine, leading to higher-than-expected levels of dihydromorphine in breast milk and potentially dangerously high serum dihydromorphine levels in their breastfed infants. Therefore, maternal use of dihydrocodeine can potentially lead to serious adverse reactions, including death, in nursing infants. The risk of infant exposure to dihydrocodeine and morphine through breast milk should be weighed against the benefits of breastfeeding for both the mother and baby. Caution should be exercised when dihydrocodeine is administered to a nursing woman. If a dihydrocodeine containing product is selected, the lowest dose should be prescribed for the shortest period of time to achieve the desired clinical effect. Mothers using dihydrocodeine should be informed about when to seek immediate medical care and how to identify the signs and symptoms of neonatal toxicity, such as drowsiness or sedation, difficulty breastfeeding, breathing difficulties, and decreased tone, in their baby. Nursing mothers who are ultra-rapid metabolizers may also experience overdose symptoms such as extreme sleepiness, confusion or shallow breathing. Prescribers should closely monitor mother-infant pairs and notify treating pediatricians about the use of dihydrocodeine-containing products during breastfeeding (See Warnings ). Acetaminophen and caffeine are also excreted in breast milk in small amounts. Because of the potential for serious adverse reactions in nursing infants from this combination product, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Diet
Food & alcohol
- Drug & food interactions (label) Drug Interactions: Dihydrocodeine with Other Central Nervous System Depressants: Patients receiving other opioid analgesics, sedatives or hypnotics, muscle relaxants, general anesthetics, centrally acting anti-emetics, phenothiazines or other tranquilizers, or alcohol concomitantly with this combination product may exhibit additive depressant effects on the central nervous system. When such combined therapy is contemplated, the dose of one or both agents should be reduced. Dihydrocodeine with Monoamine Oxidase Inhibitors: Dihydrocodeine, like all opioid analgesics, interacts with monoamine oxidase inhibitors causing central nervous system excitation and hypertension. Dihydrocodeine with Mixed Agonist/Antagonist Opioid Analgesics: Agonist/antagonist analgesics (i.e., pentazocine, nalbuphine, butorphanol and buprenorphine) may reduce the analgesic effect of this combination product. Acetaminophen Drug Interactions: Chronic and excessive consumption of alcohol may increase the hepatotoxic risk of acetaminophen. The potential for hepatotoxicity with acetaminophen also may be increased in patients receiving anticonvulsants that induce hepatic microsomal enzymes (including phenytoin, barbiturates, and carbamazepine) or isoniazide. Chronic ingestion of large doses of acetaminophen may slightly potentiate the effects of warfarin- and indandione- derivative anticoagulants. Severe hypothermia is possible in patients receiving acetaminophen concomitantly with phenothiazines. Caffeine Drug Interactions: Caffeine may enhance the cardiac inotropic effects of beta-adrenergic stimulating agents. Co-administration of caffeine and disulfiram may lead to a substantial decrease in caffeine clearance. Caffeine may increase the metabolism of other drugs such as phenobarbital and aspirin. Caffeine accumulation may occur when products or foods containing caffeine are consumed concomitantly with quinolones such as ciprofloxacin.
Trust
Sources & disclaimer
Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Professional class pharmacology (Opioid analgesic)
Last reviewed: 01 Aug 2026
Decision support only — not a substitute for clinical judgment, product SmPC, or Kenya STG/EML.