Efferalgan Codeine: composition and pharmaceutical form
Efferalgan Codeine comes as effervescent tablets; one tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate hemihydrate. The tablet is dissolved in water before use — it must not be swallowed or chewed.
The composition of the excipients matters in practice here. The tablet holds 380 mg of sodium, so the medicine is used with caution in reduced kidney function and on a salt-restricted diet. It also contains sorbitol, which makes it unsuitable in hereditary fructose intolerance, and aspartame, so it is contraindicated in phenylketonuria.
How Efferalgan Codeine works
Paracetamol has an analgesic and antipyretic action: it inhibits the cyclooxygenase of arachidonic acid and thereby the synthesis of prostaglandins in the central nervous system. Because of this, sensitivity to mediators such as kinins and serotonin falls and the pain threshold rises; the drop in prostaglandins in the hypothalamus produces the antipyretic effect. Paracetamol does not affect platelet aggregation.
Codeine is a weak centrally acting analgesic. It works through the μ opioid receptors, although its affinity for them is low, and the analgesic effect arises from the conversion of codeine into morphine. The combination of paracetamol and codeine relieves pain for longer and more strongly than either component alone. Codeine also has an antitussive action.
Indications
The medicine is used for pain of medium and high intensity that does not pass after peripherally acting painkillers. On phantom and neurogenic pain the combination of paracetamol with codeine has no effect.
In adolescents aged 12 and over codeine is indicated for acute pain of moderate intensity if it has not yielded to treatment with other analgesics — paracetamol or ibuprofen as monotherapy.
Method of use and dosage
The medicine is prescribed to adults and adolescents from 12 years with a body weight of 33 kg and above. The interval between doses cannot be shorter than 6 hours, and the recommended doses must not be exceeded. Codeine is used at the lowest effective dose and for the shortest possible course: the length of treatment is limited to 3 days, and if the pain has not receded a doctor must be consulted.
| Patient or situation | Dose |
|---|---|
| Adults and adolescents over 50 kg | 1 tablet per dose, 2 in severe pain; usually no more than 6 tablets a day, in very severe pain a maximum of 8 |
| Adolescents aged 12 and over weighing 33–50 kg | 1 tablet per dose, no more often than every 6 hours, no more than 4 tablets a day |
| Daily ceiling by substance | 4 g of paracetamol counting all medicines taken and 240 mg of codeine |
| Elderly patients | the starting dose is halved and then raised according to tolerance |
| Renal impairment | 1 tablet per dose; with creatinine clearance of 10–50 ml/min the interval is 6 hours, below 10 ml/min it is 8 hours |
| Hepatic impairment and body weight below 50 kg | the dose is reduced or the intervals lengthened; the daily dose of paracetamol is no higher than 60 mg/kg and no more than 2 g |
Children under 12 are not prescribed codeine at all: the conversion of codeine into morphine is unpredictable in them and this threatens opioid toxicity. Adolescents with renal impairment need medical supervision, intervals of at least 8 hours and possibly a reduced dose.
Contraindications
Some of the prohibitions are dictated by paracetamol — they concern the liver and kidneys — and some by codeine, which concerns breathing.
- hypersensitivity to paracetamol, propacetamol, codeine or any excipient;
- children weighing less than 33 kg and under 12 years of age;
- the first trimester of pregnancy and the breastfeeding period;
- severe impairment of liver function or active decompensated liver disease, severe renal failure, alcoholism;
- treatment with MAO inhibitors and the 14 days after it ends;
- respiratory failure of any degree and bronchial asthma;
- children and adolescents under 18 after removal of the palatine or pharyngeal tonsils for obstructive sleep apnoea syndrome;
- ultra-rapid metabolism via the CYP2D6 enzyme, and also concomitant use of analgesics with agonist-antagonist action — buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine.
Special warnings and precautions
The medicine is not taken without a doctor's prescription, and the main reason is the risk of accidental overdose. Before taking it you need to check whether your other medicines, including over-the-counter ones, contain paracetamol, codeine or other agents depressing the central nervous system. Exceeding paracetamol doses threatens very severe liver damage: its signs usually appear 1–2 days after the overdose and peak by the third or fourth day, which is why antidote treatment is started as early as possible.
Codeine: breathing and dependence
The action of opioids on the central nervous system can cause severe, life-threatening respiratory depression, and the risk rises with concomitant use of other medicines and because of pharmacogenetic features. Prolonged use of high doses of codeine leads to physical and psychological dependence, so long treatment is not recommended, and patients with current or past opioid dependence should be offered different pain relief. Codeine may increase already raised intracranial pressure, and where intracranial pathology or head injury is suspected its sedative effect complicates neurological assessment. In patients with epilepsy opioids are used with caution: they lower the seizure threshold.
Other warnings
- alcohol is ruled out during treatment: it raises the risk of toxic liver damage and enhances the action of codeine;
- the liver risk is particular in people with prolonged malnutrition and in regular drinkers;
- prolonged use of painkillers, including opioid ones, leads to medication-overuse headache;
- neurogenic pain does not respond to paracetamol with codeine — raising the dose in that situation is pointless;
- in children the medicine is used only on a doctor's instruction, after making sure there is no excessive or unusual drowsiness;
- sodium benzoate slightly irritates the skin, eyes and mucous membranes and may raise the risk of jaundice in a newborn if the mother took the medicine during pregnancy;
- with drowsiness and disturbed consciousness you must not drive or operate machinery.
Drug interactions
On the paracetamol side: concomitant use with MAO inhibitors and within 2 weeks of their withdrawal is contraindicated because of the risk of agitation and high fever. Agents that speed up hepatic metabolism — St John's wort, antiepileptics, barbiturates, rifampicin — may damage the liver even at recommended paracetamol doses; caution is needed with isoniazid and zidovudine. Phenytoin reduces the efficacy of paracetamol and raises the risk of hepatotoxicity, so patients on phenytoin should avoid high and long-used doses. Probenecid almost halves the clearance of paracetamol — the dose is worth reducing. Concomitant use with non-steroidal anti-inflammatory drugs raises the risk of impaired kidney function, and with coumarin anticoagulants, warfarin included, it slightly changes the INR, so this is monitored more often — and for a week after paracetamol is stopped. Salicylamide prolongs the elimination of paracetamol.
On the codeine side: barbiturates, anxiolytics, antidepressants including tricyclics and selective serotonin reuptake inhibitors, benzodiazepines and hypnotics enhance its depressant effect on the nervous system. Medicines metabolised by CYP2D6 or inhibiting it — paroxetine, fluoxetine, bupropion, sertraline, neuroleptics, tricyclic antidepressants, celecoxib, quinidine, dexamethasone, rifampicin — weaken the analgesia. Morphine agonist-antagonists are not recommended: they block the receptors competitively, reduce the effect and threaten a withdrawal syndrome. Naltrexone also weakens the analgesia. Other morphine derivatives — analgesics and antitussives — must be taken into account too.
Pregnancy and breastfeeding
In the first trimester the medicine is contraindicated. In the second and third, single doses are possible and only where clearly necessary. Epidemiological data have shown no teratogenic or toxic effect of paracetamol at usual doses, while for codeine the risk of congenital malformations in humans is not confirmed but not ruled out either; in animal studies codeine had a teratogenic effect.
Closer to delivery the morphine-like properties of the medicine matter: high doses of codeine, even as a short course in the perinatal period, may depress the newborn's respiratory centre, and prolonged use in the third trimester causes a withdrawal syndrome with restlessness, continuous crying, tremor, raised tone, rapid breathing, fever, vomiting and diarrhoea. During breastfeeding the medicine is contraindicated except for single use. The reason is that in women with ultra-rapid CYP2D6 metabolism more morphine ends up in the milk, and respiratory depression, apnoea and fatal outcomes have been described in the child. Such mothers are given different pain relief, and breastfeeding women are warned about the signs of opioid toxicity.
Adverse effects
Codeine at therapeutic doses gives reactions similar to other opioid ones, but rarer and milder: sedation, euphoria, mood changes, constricted pupils, urinary retention, constipation, nausea, vomiting, drowsiness and dizziness.
- nervous system: dizziness, drowsiness, fainting, tremor, paraesthesia, clonic muscle convulsions;
- psychiatric: confusion, hallucinations, abuse of the medicine and drug dependence;
- respiratory: breathlessness, bronchospasm, depression of the respiratory centre;
- digestive: abdominal pain, constipation, diarrhoea, nausea, vomiting, pancreatitis, biliary colic and spasm of the sphincter of Oddi, especially after removal of the gallbladder;
- liver and laboratory findings: hepatitis, rises in aminotransferases, alkaline phosphatase, gamma-glutamyl transferase and INR;
- kidneys and muscles: renal failure, urinary retention, rhabdomyolysis; very rarely renal colic and necrosis of the renal papillae;
- blood: thrombocytopenia, very rarely leucopenia and neutropenia;
- allergic reactions: itching, rash, urticaria, erythema, angioedema, anaphylaxis, and also severe skin reactions — acute generalised exanthematous pustulosis, Stevens-Johnson syndrome and toxic epidermal necrolysis.
Taking codeine at doses above the therapeutic ones threatens dependence and a withdrawal syndrome if it is stopped abruptly. Withdrawal symptoms are possible in a newborn too, if the mother was dependent on codeine.
Overdose
Paracetamol overdose shows itself in the first hours as nausea, vomiting, loss of appetite, pallor, sweating, drowsiness and general weakness. These symptoms may subside the next day, although liver damage is already developing and later makes itself felt through fullness in the upper abdomen, returning nausea and jaundice. A dose of 7.5 g or more in an adult, or 140 mg/kg in a child, causes cytolytic hepatitis up to irreversible necrosis with liver failure, metabolic acidosis and encephalopathy, coma and death. Especially vulnerable are the elderly, small children, emaciated people and patients with liver disease.
Treatment is carried out in hospital. After a single intake of 5 g or more, vomiting should be induced if no more than an hour has passed, and a doctor contacted immediately; 60–100 g of activated charcoal is given by mouth. The blood concentration of paracetamol is determined no earlier than 4 hours after intake — it is the main guide for antidote therapy. Oral methionine and intravenous or oral acetylcysteine are used: they are most effective in the first 10–12 hours but are useful later too. Liver tests are repeated every 24 hours; the values usually normalise within 1–2 weeks, and in the most severe cases a liver transplant is required. Codeine overdose shows itself as respiratory depression up to apnoea with cyanosis, deep sedation from stupor to coma and constricted pupils; headache, vomiting, urinary retention, slowed bowel, bradycardia and a fall in blood pressure are possible.
How to get a prescription for Efferalgan Codeine online
Efferalgan Codeine is a prescription-only medicine: it contains an opioid, and the total paracetamol dose is easily exceeded if other painkillers are taken alongside. During the online consultation the doctor will assess the nature of the pain, clarify all the medicines you take and check contraindications on the respiratory, liver and kidney side.
If the medicine is suitable, the doctor will issue an electronic prescription, set the dose and the interval and explain why the course is limited to a few days and when you need to see a doctor again.
