Skudexa - (IR): composition and pharmaceutical form
Skudexa - (IR) is a combination painkiller in tablets. One tablet contains 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen, that is a centrally acting opioid analgesic and a non-steroidal anti-inflammatory drug.
One dose contains less than 1 mmol (23 mg) of sodium, so the medicine is regarded as essentially sodium-free. The warnings and precautions established for dexketoprofen and tramadol separately apply in full to their combination as well.
Indications
The medicine is used for the short-term symptomatic treatment of acute pain of moderate and severe intensity in adults.
Prescribing is limited to patients who genuinely need the combination of tramadol and dexketoprofen to relieve pain. Depending on the intensity of the pain and the response to treatment, the doctor considers switching to a single-component analgesic.
Method of use and dosage
The recommended dose is 1 film-coated tablet, which corresponds to 75 mg of tramadol hydrochloride and 25 mg of dexketoprofen. If needed, further doses are taken with an interval of at least 8 hours, but no more than 3 tablets a day in total — that is 225 mg of tramadol hydrochloride and 75 mg of dexketoprofen. The medicine is intended only for short use: treatment is limited to the period while symptoms persist and in any case does not exceed 5 days. The lowest effective dose for the shortest possible time reduces the risk of adverse reactions. Children and adolescents are not prescribed the medicine — its safety and efficacy in them have not been established.
| Patient group | Dosing particulars |
|---|---|
| Elderly patients | Start with 1 tablet, a maximum of 2 tablets a day; up to 3 tablets only if tolerance is good |
| Patients over 75 | Data are scarce, the medicine is used with caution |
| Mild and moderate impairment of liver function | Start with fewer doses — up to 2 tablets a day, with close monitoring |
| Severe impairment of liver function | The medicine is not used |
| Mild impairment of kidney function (creatinine clearance 60–89 ml/min) | The initial daily dose is reduced to 2 tablets |
| Moderate and severe impairment of kidney function (creatinine clearance of 59 ml/min or below) | The medicine is not used |
Contraindications
The contraindications of both active substances are taken into account. Dexketoprofen, like other non-steroidal anti-inflammatory drugs, is not used in:
- hypersensitivity to dexketoprofen, to other NSAIDs or to the excipients, and also if aspirin or other NSAIDs caused an asthma attack, bronchospasm, acute rhinitis, nasal polyps, urticaria or angioedema;
- photoallergic and phototoxic reactions to ketoprofen or fibrates;
- active peptic ulcer disease, gastrointestinal bleeding or suspicion of them, and also ulcer, bleeding or perforation in the past, including those linked to NSAID use;
- chronic dyspepsia, any other active bleeding and clotting disorders, haemorrhagic diathesis;
- Crohn's disease and ulcerative colitis;
- severe heart failure, severe impairment of liver function (Child-Pugh class C), moderate and severe renal impairment;
- marked dehydration from vomiting, diarrhoea or insufficient fluid intake.
Tramadol is not used in case of hypersensitivity to it or to the excipients, acute poisoning with alcohol, hypnotics, analgesics, opioids and psychotropic agents, while taking MAO inhibitors and for 14 days afterwards, in epilepsy that cannot be controlled and in severe respiratory depression. The combination medicine is also contraindicated in pregnancy and breastfeeding.
Special warnings and precautions
The main risk from dexketoprofen is gastrointestinal complications. For all NSAIDs, bleeding, ulcers and perforations with a fatal outcome have been described, which may occur at any point in treatment, with or without warning signs and even without severe complaints in the past; if bleeding or an ulcer develops the medicine is withdrawn. The risk is higher in elderly people and in those who have already had a gastric or duodenal ulcer, especially with bleeding or perforation. Before treatment starts the doctor establishes whether there has been oesophagitis, gastritis or ulcer disease and whether these were fully treated, and advises patients with stomach complaints to report any alarming symptoms immediately. Caution is also needed with the concomitant use of agents that raise the risk of ulcers and bleeding: oral corticosteroids, anticoagulants such as warfarin, SSRIs and antiplatelet agents including acetylsalicylic acid; with such patients, protection of the mucosa is discussed — misoprostol or proton pump inhibitors.
- in impaired kidney function NSAIDs may worsen its work, cause fluid retention and oedema; the risk of nephrotoxicity is higher with diuretics and in hypovolaemia, so drinking enough matters; glomerulonephritis, interstitial nephritis, necrosis of the renal papillae, nephrotic syndrome and acute renal failure have been described;
- an increase in liver enzyme activity is possible: with a significant rise in AST and ALT treatment is stopped;
- in arterial hypertension and mild or moderate heart failure monitoring is needed — fluid retention and oedema have been described; prolonged use of NSAIDs at high doses may slightly raise the risk of arterial thrombosis, so in uncontrolled hypertension, ischaemic heart disease and diseases of the peripheral and cerebral arteries the medicine is prescribed with great caution;
- non-steroidal anti-inflammatory drugs inhibit platelet aggregation and prolong bleeding time, so combination with warfarin, other coumarins and heparins is not recommended;
- very rarely severe skin reactions have been described, some fatal: exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, more often in the first month of treatment — at the first rash or mucosal lesion the medicine is withdrawn at once;
- dexketoprofen may mask the signs of infection and delay its treatment, which has been described in community-acquired pneumonia and in bacterial complications of chickenpox; in chickenpox the medicine is avoided;
- particular caution is required in acute intermittent porphyria, dehydration, immediately after major surgery, in disorders of haematopoiesis, systemic lupus erythematosus and mixed connective tissue disease;
- in patients with asthma, chronic rhinitis, sinusitis or nasal polyps the risk of intolerance to aspirin and NSAIDs is higher, and taking the medicine may provoke an asthma attack or bronchospasm.
From tramadol the main risks are respiratory depression, seizures and dependence. Caution is needed in opioid dependence, head injury, shock, disturbed consciousness of unclear origin, raised intracranial pressure and disorders of breathing and of the respiratory centre. Seizures have been described even at recommended doses, and the risk grows when the daily tramadol maximum of 400 mg is exceeded and alongside agents that lower the seizure threshold. With prolonged use tolerance and psychological and physical dependence develop, so where there is a tendency to abuse the treatment is kept short and under medical supervision and is ended by gradually lowering the dose. Combination with benzodiazepines and similar sedatives may lead to profound sedation, respiratory depression, coma and death — it is reserved for cases where there are no other options, at the minimum dose and for the minimum time. Serotonin syndrome, central sleep apnoea with a nocturnal fall in oxygen, and transient adrenal insufficiency with abdominal pain, vomiting, low blood pressure, marked fatigue and weight loss have been described. Tramadol is metabolised by the CYP2D6 enzyme: where this is deficient, which occurs in about 7% of Caucasians, there may be no analgesia, and in ultra-rapid metabolism even usual doses give signs of opioid toxicity — confusion, drowsiness, shallow breathing, constricted pupils, vomiting, constipation. Both substances cause dizziness and drowsiness, so the medicine affects the ability to drive and operate machinery, especially together with alcohol and psychotropic agents.
Drug interactions
Concomitant use of dexketoprofen with other non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors, must be ruled out. Combination with anticoagulants and other agents affecting haemostasis is not recommended — warfarin, other coumarin derivatives, heparins: the risk of bleeding rises. Oral corticosteroids, SSRIs and antiplatelet agents including acetylsalicylic acid raise the likelihood of ulcers and gastrointestinal bleeding. Diuretics and states with a reduced circulating volume increase the risk of nephrotoxicity.
Tramadol must not be combined with MAO inhibitors or used within 14 days of their withdrawal. The risk of serotonin syndrome is raised by serotonergic medicines, and the likelihood of seizures by agents that lower the seizure threshold. Other opioids, benzodiazepines, barbiturates and other medicines depressing the central nervous system intensify sedation and respiratory depression; alcohol is excluded during treatment. The interactions described for each substance separately apply to the combination too, so before starting it the doctor must be told about all the medicines being taken.
Pregnancy and breastfeeding
The medicine is contraindicated in pregnant women. There is no clinical experience of its use in pregnancy, and for the individual components the data are worrying. Suppression of prostaglandin synthesis may affect the course of pregnancy and embryonic development unfavourably: epidemiological studies point to an increased risk of miscarriage, cardiac malformations and defects of the anterior abdominal wall with the use of such agents in early pregnancy — the overall risk of cardiovascular malformations rose from below 1% to about 1.5% and increased with dose and length of treatment. In the third trimester all inhibitors of prostaglandin synthesis may cause a toxic effect on the foetus's heart and lungs with premature closure of the ductus arteriosus and pulmonary hypertension, as well as impaired kidney function up to oligohydramnios; late in pregnancy prolongation of bleeding time, an antiplatelet effect even at low doses and inhibition of uterine contractions with delayed or prolonged labour are possible.
Tramadol crosses the placenta; in animal studies high doses affected organ development, ossification and newborn survival, although no teratogenic effect was observed. Administration before and during labour does not disturb uterine contractility, but changes in the newborn's respiratory rate are possible, usually of no clinical significance, and prolonged use during pregnancy leads to a withdrawal syndrome in the child. The passage of the combination into breast milk has not been studied; tramadol and its metabolites are known to reach the milk in small amounts, and for dexketoprofen there are no data. During breastfeeding the medicine is therefore contraindicated.
Adverse effects
The most frequent in studies of the combination itself were dizziness, nausea and vomiting. In addition the adverse reactions described for dexketoprofen and tramadol separately are taken into account.
- common — dizziness, nausea, vomiting;
- uncommon — headache, drowsiness, tachycardia, a fall in blood pressure and, conversely, hypertensive crisis;
- uncommon — abdominal bloating, constipation, dyspepsia, increased activity of liver enzymes and γ-glutamyl transferase;
- uncommon — oedema of the face and the eye area, laryngeal oedema, increased sweating, urticaria;
- uncommon — asthenia, chills, discomfort and general malaise, haematuria, thrombocytosis, hypokalaemia, psychotic disorders;
- for dexketoprofen in addition — restlessness and insomnia, reduced appetite, rarely laryngeal oedema, very rarely neutropenia, thrombocytopenia and hypersensitivity reactions up to anaphylactic shock with breathlessness, bronchospasm and angioedema;
- for dexketoprofen — gastrointestinal bleeding, ulcers and perforations, as well as severe skin reactions;
- for tramadol — respiratory depression, seizures, dependence and withdrawal symptoms on abrupt discontinuation.
How to get a prescription for Skudexa - (IR) online
The combination of tramadol with dexketoprofen is a prescription-only medicine: the doctor assesses the nature of the pain, the state of the stomach, kidneys and liver, concomitant medicines and the risk of dependence.
During the online consultation the doctor will discuss with you the dose and the length of use, which does not exceed five days, and if there are no contraindications will issue an electronic prescription — the medicine can be collected at a pharmacy with its code.
