Efferalgan Codeine - (IR): composition and pharmaceutical form
The medicine comes as effervescent tablets. One tablet contains 500 mg of paracetamol and 30 mg of codeine phosphate hemihydrate. Before use the tablet is dissolved in water.
Its excipients include several that matter for particular groups of patients: sodium benzoate, sorbitol, aspartame and 380 mg of sodium (16.5 mEq) per tablet. Because of the sorbitol it is unsuitable in hereditary fructose intolerance, because of the aspartame in phenylketonuria, and the high sodium content calls for caution in reduced kidney function and on a salt-restricted diet.
How Efferalgan Codeine - (IR) works
Paracetamol inhibits the cyclooxygenase of arachidonic acid and suppresses the synthesis of prostaglandins in the central nervous system. Sensitivity to mediators such as kinins and serotonin falls and the pain threshold rises; the drop in prostaglandin levels in the hypothalamus is responsible for the antipyretic effect. Paracetamol does not affect platelet aggregation.
Codeine is a weak centrally acting analgesic. It works through the μ opioid receptors, but codeine's own affinity for them is low: the analgesic action arises after its conversion into morphine. Together with paracetamol, codeine is effective in acute nociceptive pain, and the combination of the two substances gives stronger and longer analgesia than either component alone. Codeine also suppresses the cough reflex.
Indications
The medicine is used for pain of medium and high intensity that does not pass after peripherally acting analgesics.
For adolescents from 12 years codeine is indicated in acute pain of moderate intensity not relieved by other painkillers — for example paracetamol or ibuprofen as monotherapy. On phantom and neurogenic pain the combination of paracetamol with codeine has no effect.
Method of use and dosage
The medicine is intended for adults and adolescents from 12 years weighing at least 33 kg. Adults are usually given 1 effervescent tablet per dose and 2 in severe pain; the dose may be repeated no more often than every 6 hours. As a rule no more than 6 tablets a day are needed, with a maximum of 8. Counting all products containing these substances, 4 g of paracetamol and 240 mg of codeine must not be exceeded in a day. The course is limited to three days: if the pain has not receded in that time, a doctor must be consulted.
| Patient group | Dosing scheme |
|---|---|
| Adults and adolescents over 50 kg | 1–2 tablets per dose, an interval of at least 6 hours, usually up to 6 tablets a day, a maximum of 8 |
| Adolescents aged 12 and over weighing 33–50 kg | 1 tablet per dose with an interval of at least 6 hours, no more than 4 tablets a day |
| Children under 12 and below 33 kg | The medicine is contraindicated |
| Elderly patients | The starting dose is halved and then raised according to tolerance |
| Creatinine clearance of 10–50 ml/min | 1 tablet, interval of 6 hours |
| Creatinine clearance below 10 ml/min | 1 tablet, interval of 8 hours |
When the daily paracetamol dose is limited to 2 grams
The limit of 60 mg per kilogram of body weight a day, and no more than 2 g, applies to adults under 50 kg, in chronic or compensated active liver disease, especially in mild and moderate hepatic impairment, in Gilbert's syndrome, chronic alcoholism, prolonged malnutrition with low glutathione reserves in the liver, and in dehydration. In impaired liver function the codeine dose is also reduced or the intervals between doses lengthened.
Contraindications
The medicine is not prescribed in the following cases:
- hypersensitivity to paracetamol, propacetamol, codeine or any excipient;
- children under 12 years and weighing up to 33 kg — because of the unpredictable conversion of codeine into morphine and the risk of opioid toxicity;
- the first trimester of pregnancy and the breastfeeding period;
- severe impairment of liver function or active decompensated liver disease, severe renal failure, alcoholism;
- respiratory failure of any degree and bronchial asthma — codeine depresses the respiratory centre and opioids may release histamine;
- children and adolescents under 18 having their palatine or pharyngeal tonsils removed for obstructive sleep apnoea syndrome;
- known ultra-rapid metabolism via the CYP2D6 enzyme;
- treatment with MAO inhibitors and the 14 days after it ends, and also the use of analgesics with agonist-antagonist action — buprenorphine, butorphanol, nalbuphine, nalorphine, pentazocine.
Special warnings and precautions
The main risks of the medicine are liver damage from paracetamol and respiratory depression from codeine. The recommended doses must not be exceeded and, before taking any other medicines including over-the-counter ones, you need to make sure they contain no paracetamol, codeine or other substances depressing the central nervous system. Signs of liver damage appear 1–2 days after an overdose, so the antidote is given as early as possible. Alcohol is ruled out during treatment: it raises the risk of toxic liver damage and enhances the action of codeine. Especially vulnerable are people with prolonged malnutrition, cachexia and dehydration and those who drink alcohol regularly; in glucose-6-phosphate dehydrogenase deficiency haemolytic anaemia is possible. Paracetamol can cause severe skin reactions — acute generalised exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis: with any rash or other signs of hypersensitivity the medicine is stopped.
- codeine is converted into morphine by the CYP2D6 enzyme, whose activity differs from person to person: where it is deficient there will be no analgesia, and in ultra-rapid metabolism even usual doses give dangerously high morphine concentrations;
- the signs of opioid toxicity are dizziness, deep sedation, confusion, shallow breathing, constricted pupils and vomiting; in severe cases respiratory depression and circulatory failure, dangerous to life;
- prolonged use of high doses of codeine leads to physical dependence, and abrupt withdrawal to a withdrawal syndrome; with past or present opioid dependence it is worth choosing different pain relief;
- caution is needed in head injury and raised intracranial pressure, in epilepsy, biliary tract disease, prostate adenoma, hypothyroidism and adrenal insufficiency;
- opioids mask the symptoms of acute abdominal conditions and cause constipation resistant to laxatives;
- prolonged use of painkillers raises the risk of medication-overuse headache, and with chronic opioid use hyperalgesia is possible.
The medicine reduces psychophysical reactions, causes drowsiness and impairs cognitive function, so during treatment you must not drive or operate machinery. In athletes its use may give a positive doping control result.
Drug interactions
Concomitant use with MAO inhibitors and within two 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 — raise the risk of liver damage even at recommended paracetamol doses; isoniazid and zidovudine call for caution. Phenytoin reduces the efficacy of paracetamol and increases its hepatotoxicity, so high and prolonged doses should be avoided. Probenecid slows the elimination of paracetamol almost twofold and the dose has to be reduced. Non-steroidal anti-inflammatory drugs raise the risk of impaired kidney function, and coumarin anticoagulants, warfarin included, require more frequent INR monitoring — during use and for a week after withdrawal.
The action of codeine on the central nervous system is enhanced by barbiturates, anxiolytics, antidepressants including tricyclics and SSRIs, benzodiazepines and hypnotics; combination with other morphine derivatives — analgesic, antitussive and substitution ones — and also with benzodiazepines, barbiturates and methadone raises the risk of respiratory depression, fatal in overdose. The analgesic effect of codeine is weakened by medicines metabolised by CYP2D6 or inhibiting it: paroxetine, fluoxetine, sertraline, bupropion, neuroleptics, tricyclic antidepressants, celecoxib, quinidine, dexamethasone and rifampicin, as well as naltrexone. Combination with morphine agonist-antagonists is not recommended: the analgesia weakens and the risk of a withdrawal syndrome grows. Alcohol enhances the sedative effect of opioid analgesics, and anticholinergics together with codeine slow the bowel more strongly.
Pregnancy and breastfeeding
In the first trimester of pregnancy the medicine is contraindicated; in the second and third only isolated doses are acceptable and only where clearly necessary, after weighing risk, benefit and alternatives. Epidemiological studies have found no teratogenic or toxic effect of paracetamol at usual doses. For codeine the risk of congenital malformations in humans is not confirmed but not ruled out either, and in animal studies a teratogenic effect was found. High doses, even as a short course before delivery, may depress the newborn's respiratory centre, and prolonged use in the third trimester, whatever the dose, causes a withdrawal syndrome in the child: restlessness, excessive crying, tremor, raised tone, rapid breathing, fever, vomiting and diarrhoea.
During breastfeeding the medicine is contraindicated except for a single dose. Paracetamol and codeine pass into milk in small amounts, and rash has been described in breastfed babies. If the mother converts codeine into morphine ultra-rapidly, the concentration of the active metabolite in the milk rises and the child's risk of respiratory depression, apnoea and death grows; with maternal doses above those recommended, reduced muscle tone and breathing disturbances were seen in infants. Women with ultra-rapid codeine metabolism are advised to use different pain relief.
Adverse effects
Codeine at therapeutic doses gives the same reactions as other opioids, but rarer and milder: sedation, euphoria, mood changes, drowsiness, dizziness, constricted pupils, nausea, vomiting, constipation, urinary retention, itching, urticaria and rash.
- nervous system and psychiatric — dizziness, drowsiness, tremor, paraesthesia, myoclonus, fainting, confusion, hallucinations, drug dependence and abuse of the medicine;
- respiratory — breathlessness, bronchospasm, depression of the respiratory centre;
- digestive — abdominal pain, constipation, diarrhoea, nausea, vomiting, pancreatitis;
- liver — biliary colic, hepatitis, increased activity of ALT, AST, alkaline phosphatase and γ-glutamyl transferase, changes in INR;
- kidneys — urinary retention, renal failure and, very rarely for paracetamol, renal colic and necrosis of the renal papillae;
- blood — thrombocytopenia, very rarely leucopenia and neutropenia;
- allergic reactions — reddening of the skin, rash, erythema, urticaria, angioedema, breathlessness, bronchospasm, sweating, a fall in blood pressure up to anaphylactic shock, and also severe skin reactions;
- other — weakness, malaise, oedema, a fall in blood pressure, tachycardia, rhabdomyolysis.
Acute abdominal pain from spasm of the sphincter of Oddi occurs mainly in patients whose gallbladder has been removed. Taking codeine at doses above the therapeutic ones threatens dependence and a withdrawal syndrome on abrupt discontinuation, including in a newborn if the mother was dependent on codeine.
Overdose
In paracetamol overdose the first hours bring nausea, vomiting, loss of appetite, pallor, profuse sweating, drowsiness and general weakness. The next day these may subside, although liver damage is already developing and later shows itself through fullness in the upper abdomen, returning nausea and jaundice. Taking 7.5 g of paracetamol or more in an adult, or 140 mg/kg in a child, causes cytolytic hepatitis capable of leading to complete liver necrosis, metabolic acidosis, hepatic encephalopathy, coma and death. Treatment is carried out in hospital: the blood concentration of paracetamol is determined no earlier than 4 hours after intake, activated charcoal is given and the antidote — acetylcysteine — is administered as early as possible, preferably within the first 8 hours. In most cases liver tests normalise within one to two weeks, but in severe poisoning a liver transplant may be required.
Codeine overdose shows itself as respiratory depression — from slowed breathing to apnoea with cyanosis — deep sedation from stupor to coma, and constricted pupils. Vomiting, urinary retention, bradycardia, a fall in blood pressure and seizures are possible and, less often, pulmonary oedema and signs of histamine release. In children a single intake of 2 mg/kg is considered the toxicity threshold. The affected person is taken to hospital immediately, breathing is monitored and the antidote naloxone is given repeatedly, since it is eliminated faster than the active metabolites of codeine.
How to get a prescription for Efferalgan Codeine - (IR) online
The combination of paracetamol with codeine is a prescription-only medicine: the doctor assesses the nature of the pain, the state of the liver and kidneys, respiratory function and the medicines being taken.
During the online consultation the doctor will discuss with you the dose and the length of use, which usually does not exceed three days, and if there are no contraindications will issue an electronic prescription — the medicine can be collected at a pharmacy with its code.
