Endolex 25Mg 12 Tablets

Endolex (25 Mg 12 Tablets)

Dexketoprofen 25mg

ACTION AND MECHANISM

[ANALGESIC], [ANTI-INFLAMMATORY], [ANTIPIRETIC], [PROSTAGLANDIN SYNTHESIS INHIBITOR (CYCLOOXIGENASE)]. Dexketoprofen trometamol is the tromethamine salt of S-(+)-2-(3-benzoylphenyl)propionic acid, belonging to the family of non-steroidal anti-inflammatory drugs derived from propionic acid. The mechanism of action of non-steroidal anti-inflammatory drugs is related to the decrease in prostaglandin synthesis through the non-selective inhibition of cyclooxygenase. In addition, the inhibition of prostaglandin synthesis could have an effect on other inflammatory mediators such as kinins, exerting an indirect action that would be added to its direct action.

PHARMACOKINETICS

- Absorption: it is rapidly absorbed through the gastrointestinal tract after oral administration, obtaining the maximum plasma concentration in 0.5-0.75 h (Tmax). Oral absorption is good. Following im administration in humans, Cmax is reached within 20 min (range 10-45 min). For single doses of 25 and 50 mg, the area under the curve has been shown to be dose proportional after im and iv administration.

- Distribution: Like other drugs with high plasma protein binding (99%), the volume of distribution has a mean value of less than 0.25 l/Kg, being selectively distributed in the body. The distribution half-life value was approximately 0.35 h.

- Metabolism: glucuronoconjugation.

- Elimination: it is excreted via the kidneys (80%) in the form of metabolites conjugated with glucuronic acid. After administration of dexketoprofen trometamol, only the S(+) enantiomer is obtained in the urine, demonstrating that no conversion to the R-(-) enantiomer occurs in humans. The elimination half-life is 1-2.7 hours.

Pharmacokinetics in special situations:

- Elderly: in healthy elderly subjects (65 years and over), exposure was significantly higher than in young volunteers after single and repeated doses administered orally (up to 55%), while there were no significant differences in Cmax nor at tmax. The elimination half-life was prolonged after single and repeated doses (up to 48%) and the apparent total clearance was reduced.

INDICATIONS

- Pain of mild or moderate intensity, such as [OSTEOMUSCULAR PAIN], [DYSMENORRHEA], [ODONTALGIA].

Parenteral forms: symptomatic treatment of moderate to severe [ACUTE PAIN], when oral administration is not appropriate, such as postoperative pain, moderate to severe renal colic, and low back pain.

POSOLOGY

Orally:

- Adults: 12.5 mg/4-6 h or 25 mg/8 h, without exceeding 75 mg/day.

- Elderly: it is recommended to start with 50 mg daily, and may increase to the adult dosage once good tolerability has been verified.

DOSAGE IN RENAL INSUFFICIENCY

"ORAL"

- CrCl 50–80 ml/min: the initial dose should not exceed 50 mg/day.

- ClCr <50 ml/min: Use not recommended.

DOSAGE IN HEPATIC INSUFFICIENCY

"ORAL"

- Mild to moderate: the initial dose should not exceed 50 mg/day, with careful monitoring.

- Severe (Child-Pugh score 10-15): Its use is not recommended.

RULES FOR CORRECT ADMINISTRATION

Administer together with meals to alleviate possible gastric irritation, however, in case of acute pain it can be administered 30 min before meals. Long-term treatments are not recommended.

- Envelopes (powder for oral solution): Dissolve the total content of an envelope in a glass of water; shake to help dissolve. The solution obtained must be taken immediately after reconstitution.

- Envelopes (oral solution): press the envelope several times before opening. The oral solution can be taken directly or diluted in a glass of water and taken immediately. Once the envelope is opened, its entire content must be consumed.

CONTRAINDICATIONS

- Known hypersensitivity to dexketoprofen or to [NSAID ALLERGY].

- Patients with a history of hypersensitivity to acetylsalicylic acid or other NSAIDs, which include patients who have experienced asthma attacks, acute rhinitis, urticaria or angioneurotic edema after using acetylsalicylic acid or other NSAIDs.

- [DIGESTIVE HEMORRHAGE], [ESOPHAGUS HEMORRHAGE], [PEPTIC ULCER] active, [CEREBRAL HEMORRHAGE].

- Renal insufficiency: patients with moderate to severe renal insufficiency (ClCr < 50 ml / min).

- Hepatic insufficiency: patients with severe hepatic dysfunction (Child-Pugh score 10 - 15).

PRECAUTIONS

- [RENAL INSUFFICIENCY]. It is eliminated in the urine, so in case of renal insufficiency accumulation could occur. In addition, it could lead to a decrease in renal blood flow with reversible acute renal failure due to the inhibition of vasodilator prostaglandin synthesis, and cases of nephrotic syndrome and acute interstitial nephritis have even been described with prolonged treatment. Patients with a higher risk of kidney failure are those with previous kidney failure, the elderly or situations that could reduce renal flow, such as [HYPOVOLEMIA], [DEHYDRATION], low sodium diets, heart failure, liver failure, liver cirrhosis or treatment with diuretics, ACEI or ARB. In high-risk patients, during prolonged treatment, it is recommended to determine renal function (serum creatinine, CLcr) before starting treatment, and periodically. In case of worsening renal function, a dose reduction may be necessary.

In patients with mild renal insufficiency, it is recommended to start treatment with a lower total daily dose, carefully monitoring the patient. The use in moderate or severe renal insufficiency (CLcr < 50 ml/min) is contraindicated.

- [LIVER FAILURE]. Due to its hepatic metabolism, accumulation could occur in hepatic insufficiency. In patients with mild to moderate insufficiency (Child-Pugh class A or B), an initial dose of no more than 50 mg/day is recommended, with careful monitoring of the patient. Use in severe insufficiency (class C or Child-Pugh score 10-15) is contraindicated. On the other hand, the use of NSAIDs has sometimes been related to the appearance of liver conditions, such as increased transaminases, [JAUNDICE] and [HEPATITIS], which could become serious and even fatal. Due to the risk of toxicity, it is recommended that patients with liver disease use this drug at the minimum effective dose, and regularly check liver function (transaminases,

- Gastrointestinal toxicity. NSAID treatment has led to gastroduodenal ulcers, as well as life-threatening bleeding and perforation. There is an increased risk of ulcer with treatments with high doses or for long periods of time, with a history of peptic ulcer, especially if they have already had gastrointestinal bleeding or perforation by NSAIDs, as well as in smoking, [CHRONIC ALCOHOLISM] or elderly or debilitated patients. However, short-term treatment is not without risks either.

As a general rule to reduce gastric damage, it is advisable to administer any NSAID with food. In addition, in risk groups it is advisable to start treatment with the lowest possible dose, and always associate an anti-ulcer drug (anti-h3 or PPI) whenever possible.

High-risk patients should be closely monitored, as well as those receiving drugs that may promote or aggravate gastrointestinal bleeding, such as oral anticoagulants, antiplatelet agents, corticosteroids or SSRIs. If a peptic ulcer or gastrointestinal bleeding appears, treatment will be discontinued. On the other hand, it should be used with caution in people with [INFLAMMATORY BOWEL DISEASE], in whom NSAIDs could precipitate an attack.

- Cardiovascular diseases. NSAIDs could lead to fluid retention and edema, which could increase blood pressure and worsen symptoms in patients with cardiovascular diseases. It is advisable to monitor blood pressure at the start of treatment, as well as periodically throughout treatment. Its use has been associated with the appearance of thrombotic processes, stroke and myocardial infarction, especially in patients treated with high doses for prolonged periods. Based on the studies carried out, the risks seem greater with selective COX-2 inhibitors (coxibs) and with diclofenac, while ibuprofen and naproxen have a lower cardiovascular risk. Available data do not allow definitive conclusions to be drawn with other NSAIDs, therefore cardiovascular risk cannot be ruled out. It is recommended to individually assess the benefit/risk ratio in patients with [ARTERIAL HYPERTENSION], [HEART FAILURE], [ISCHEMIC HEART DISEASE], [CEREBRAL ISCHEMIA], [STROKE] or [PERIPHERAL ARTERY DISEASE], as well as in patients with cardiovascular risk factors , such as [DYSLIPEMIA], [DIABETES] or [SMOKING]. NSAIDs should always be used at the lowest effective dose and for the shortest period of time.

- Skin reactions. The use of NSAIDs has caused very rare but potentially fatal serious adverse reactions such as exfoliative dermatitis, toxic epidermal necrolysis, or Stevens-Johnson syndrome. These adverse reactions are usually early onset, within the first month of treatment. If symptoms of hypersensitivity, mucosal lesions or skin erythema are observed, treatment will be discontinued.

- [HYPERSENSITIVITY REACTIONS]. The administration of any NSAID has been related to the appearance of allergic reactions. Cases of cross-hypersensitivity between different NSAIDs, as well as between NSAIDs and salicylates, have been reported, so patients with a history of [ALLERGY TO NSAIDs] other than this active ingredient or [ALLERGY TO SALICYLATES] should use this active ingredient with extreme caution. .

It is recommended to avoid its use in those patients in whom a salicylate or an NSAID has previously given rise to severe allergic reactions, including asthma, [NASAL POLYPOS], [ANGIOEDEMA] or [RHINITIS], because there is an increased risk of potentially anaphylaxis. mortal.

- [ASTHMA]. Asthmatic patients are more likely to experience bronchospasm in the event of administration of an NSAID. They could also be more susceptible to anaphylactic symptoms after the administration of an NSAID. As a general rule, it is advisable to avoid administering NSAIDs and salicylates in asthmatic patients unless the expected benefits outweigh the possible risks. If its use is necessary, the respiratory function and the possible appearance of allergy symptoms will be closely monitored. If there is a reduction in respiratory function or the appearance of allergic symptoms, naproxen will be discontinued and symptomatic treatment will be instituted. Treatment should not be initiated in patients who have previously experienced allergic symptoms or severe bronchoconstriction induced by NSAIDs or salicylates.

- [COAGULATION ALTERATIONS]. NSAIDs have antiplatelet activity, although less than that of acetylsalicylic acid. They could increase the bleeding time and favor the appearance of bleeding in patients with hemostasis disorders or in treatment with anticoagulant drugs or with other platelet antiaggregants.

- [ASEPTIC MENINGITIS]. Rare cases of aseptic meningitis have been reported in patients taking NSAIDs, with fever and coma, probably due to a hypersensitivity reaction, although no cross-allergy between NSAIDs has been found. This meningitis seems to be more frequent in patients with [COLAGENOSIS] such as [SYSTEMIC LUPUS ERYTHEMATOSUS], although it has also been reported in some patients who did not suffer from these pathologies. In patients treated with NSAIDs who develop symptoms of meningitis, the possibility of aseptic meningitis should be considered.

- Ophthalmological charts. NSAIDs have been related to the appearance of ocular reactions, such as blurred vision, loss of vision, alteration in color vision, scotoma or retinal alterations. Sometimes they could be serious, such as papillitis, retrobulbar neuritis or papilledema. These disorders could be asymptomatic, so it is advisable to carry out periodic ophthalmological check-ups, and especially in the event of any change in vision.

- [FEMALE INFERTILITY]: Like other NSAIDs, it can decrease female fertility and its use is not recommended in women who wish to become pregnant. In women who have difficulties conceiving or who are being studied for infertility, withdrawal of the NSAID should be considered.

PRECAUTIONS RELATED TO EXCIPIENTS

- This medicine contains sucrose. Patients with hereditary [FRUCTOSE INTOLERANCE], glucose-galactose malabsorption, or sucrase-isomaltase insufficiency should not take this drug.

- This medicine contains ethanol. It is recommended to review the composition to know the exact amount of ethanol per dose.

* Amounts less than 100 mg/dose are considered small and are not usually harmful, especially in children.

* Amounts greater than 100 mg/dose may be harmful for people with [CHRONIC ALCOHOLISM], and should also be taken into account in pregnant and lactating women, children, and in high-risk groups, such as patients with liver disease ([HEPATIC INSUFFICIENCY ], [LIVER CIRRHOSIS], [HEPATITIS]) or [EPILEPSY].

* The amount of alcohol in this medication (much less than the 3 g/dose limit) is not expected to impair the ability to drive or operate machinery, or interfere with the effects of other medications.

- This medicine contains sucrose. Its use in oral liquids and pharmaceutical forms that remain in contact with the mouth for some time can harm teeth.

ADVICE TO THE PATIENT

- The patient should inform their doctor if they experience skin rashes, symptoms that could be related to a gastroduodenal ulcer (such as epigastric pain or dark stools), visual disturbances, weight gain, edema or prolonged headache.

- The patient should notify the doctor if they have had an asthmatic reaction while taking this medicine.

SPECIAL WARNINGS

- Gastrointestinal risk: NSAIDs are associated with an increased risk of gastrointestinal irritation, ulceration, bleeding or gastrointestinal perforation. Lesions can appear at any time during treatment. The elderly are at increased risk of serious gastrointestinal events. During prolonged treatment, possible signs and symptoms of ulceration or bleeding should be monitored. A history of oesophagitis, gastritis and/or peptic ulcer disease should also be sought to ensure complete cure before starting treatment with an NSAID.

- Cardiovascular risk: NSAIDs are associated with an increased risk of cardiovascular events, including myocardial infarction and new cases of hypertension or worsening of existing ones. The risk may increase with the duration of treatment, especially in patients with cardiovascular disease or with risk factors for cardiovascular disease. Monitor possible signs of hydrosaline retention (eg, edema formation), especially in patients with hypertension or heart failure.

INTERACTIONS

- NSAIDs, including low doses of acetylsalicylic acid: the simultaneous use of more than one NSAID should be avoided due to the risk of adverse effects appearing without increasing therapeutic efficacy. Additionally, acetylsalicylic acid produces a decrease in plasma levels of piroxicam of up to 80%.

- Alcohol: toxicity can be enhanced.

-Aliskiren: possible reduction of the antihypertensive effect of aliskiren (NSAIDs act on the renin-angiotensin system). In patients with compromised renal function (dehydrated or elderly) deterioration of renal function may be precipitated (possible acute renal failure, usually reversible). Caution, especially in the elderly, monitoring the antihypertensive effect and renal function.

- Alendronic acid, bisphosphonates: possible increased risk of esophagitis and gastric ulcer. Cases described with naproxen and alendronate.

- Quinolone antibacterials: there are isolated reports of seizures that may have been due to the concomitant use of quinolones and non-steroidal anti-inflammatory drugs.

- Oral anticoagulants, heparin: possible increase in anticoagulant effect, with risk of bleeding. Periodic controls of coagulation indices are recommended.

- SSRI antidepressants (fluoxetine, paroxetine, sertraline, citalopram): there is an increased risk of bleeding in general, and gastrointestinal bleeding in particular, especially in the elderly and patients with a history of gastrointestinal bleeding.

- Antidiabetics: no interaction has been observed. However, there are isolated cases of both hypoglycemic and hyperglycemic effects due to diclofenac that required modifying the dosage of the hypoglycemic agents.

- Antidiabetic sulfonylureas (chlorpropamide, glibenclamide, tolbutamide): possible increase in hypoglycemic effects, by reducing renal excretion.

- Antihypertensives (ACE inhibitors, Beta-blockers): possible reduction of the antihypertensive effect.

- Cyclosporine: the effect of NSAIDs on renal prostaglandins can increase the nephrotoxicity of cyclosporine.

- Platelet antiaggregants, including pentoxifylline: there is an increased risk of bleeding in general, and gastrointestinal bleeding in particular. Administer with caution. 

- Corticosteroids: possible increase in the incidence of gastric discomfort. However, concurrent use with glucocorticoids in the treatment of osteoarthritis may provide additional therapeutic benefit and allow the glucocorticoid dosage to be reduced.

- Digitalis (digoxin): possible increase in plasma concentrations of digitalis (in neonates). There is also a risk of worsening heart failure and reduced kidney function.

- Diuretics (thiazides, high ceiling diuretics): risk of reduction of the natriuretic and diuretic effect. May reduce antihypertensive action of thiazide diuretics.

- Potassium-sparing diuretics and aldosterone antagonists: possible increased risk of hyperkalaemia. Frequent monitoring of serum potassium levels is advised.

- Glitazones (pioglitazone, rosiglitazone): theoretical risk of increased edema that both glitazones and NSAIDs can cause. Caution and monitor for signs of fluid retention and heart failure (swollen ankles, dyspnea).

- Hydralazine: possible decrease in hypotensive effect.

- Iloprost: possible increased risk of bleeding.

- Lithium, salts: possible increased toxicity of lithium due to a reduction in its elimination.

- Methotrexate: possible increase in plasma levels of methotrexate, with risk of toxicity, sometimes very serious. The severity depends largely on the doses of methotrexate used. The risk of interaction is reduced with low doses of methotrexate such as those used in psoriasis and rheumatoid arthritis.

- Paracetamol: the simultaneous and prolonged use of paracetamol and NSAIDs may cause an increased risk of adverse renal effects.

- Zidovudine: increased risk of haematological toxicity, leading to severe anemia one week after starting NSAID treatment. Clinical monitoring is advised. Check blood count and reticulocyte count one to two weeks after initiation of NSAID treatment.

PREGNANCY

Animal Safety : Animal studies with various NSAIDs have reported dystocia, increased post-implantation loss, and delayed delivery.

Safety in humans : There are no adequate and well-controlled studies in humans. Occasional use, except shortly before delivery, does not appear to produce adverse fetal effects. However, with chronic use during the 3rd trimester, they could theoretically produce premature closure of the ductus arteriosus in the fetus, due to inhibition of prostaglandin synthesis. They can also produce an antiplatelet effect, which could complicate or prolong maternal bleeding and predispose the newborn. Before delivery, they can reduce or even cancel uterine contractility, delaying delivery and prolonging pregnancy. The use of these drugs, especially during the third trimester, is only accepted in the absence of safer therapeutic alternatives.

Effects on fertility : the use of NSAIDs may impair female fertility and is not recommended in women trying to conceive. In women with difficulties conceiving or undergoing fertility investigation, discontinuation of dexketoprofen should be considered.

LACTATION

Animal studies have revealed that concentrations in milk are 4-5% of those in plasma. There are no data on excretion in breast milk. Caution is advised in use by nursing mothers.

CHILDREN

Safety and efficacy have not been established in this age group. Use not recommended.

ELDERLY

The elderly seem to be more susceptible to the adverse effects of NSAIDs. The risk of severe ulcer disease is increased in those over 65 years of age, and appears to be dose-dependent. They can also cause fluid retention, which can lead to cardiovascular complications and reduce the effectiveness of antihypertensive treatments. Caution is advised in its use.

EFFECTS ON DRIVING

Dexketoprofen may cause dizziness or drowsiness of mild to moderate intensity, so patients should avoid operating dangerous machinery, including automobiles, until they are reasonably certain that pharmacological treatment does not affect them adversely.

ADVERSE REACTIONS

Adverse reactions reported as at least possibly related to the administration of dexketoprofen trometamol in clinical trials are tabulated below, by system organ class and by frequency:

- Alterations of the blood and lymphatic system: uncommon (0.1-1%): [ANEMIA]; very rare / isolated cases (<0.01%): [NEUTROPENIA], [THROMBOCYTOPENIA].

- Metabolism and nutrition disorders: rare (0.01-0.1%): [HYPERGLYCEMIA], [HYPOGLYCEMIA], [HYPERTRIGLYCERIDEMIA].

- Alterations of the nervous system: (0.1-1%): [CEFALEA], [MAREO], [INSOMNIA], [SOMNOLENCE]; (0.01-0.1%): [PARESTHESIA].

- Eye disorders: (0.1-1%): [BLURRED VISION].

- Alterations of the ear and labyrinth: (0.01-0.1%): [TINNITUS].

- Cardiac disorders: (0.01-0.1%): [EXTRASISTOLE], [TAQUICARDIA].

- Vascular alterations: infrequent (0.1-1%): [HYPOTENSION], [FLUSHING]; (0.01-0.1%): [ARTERIAL HYPERTENSION], [MALEOLAR EDEMA], superficial [THROMBOPHLEBITIS].

- Respiratory, thoracic and mediastinal disorders: (0.01-0.1%): bradypnea ([RESPIRATORY FAILURE]); very rare / isolated cases (<0.01%): [BRONCHIAL SPASM], [DYSPNEA].

- Gastrointestinal disorders: (1-10%): [NAUSEA], [VOMITING]; (0.1-1%): [ABDOMINAL PAIN], [DYSPEPSIA], [DIARRHEA], [CONSTIPATION], [HEMATHEMESIS], [DRY MOUTH]; (0.01-0.1%): [GASTRIC ULCER] or [DUODENAL ULCER], [DIGESTIVE HEMORRHAGE] or [INTESTINAL PERFORATION], [ANOREXIA]; very rare / isolated cases (<0.01%): [PANCREATITIS].

- Hepatobiliary disorders: (0.01-0.1%): NSAID-induced hepatotoxicity is rare and generally mild; It usually manifests as a mild and transient [INCREASE IN TRANSAMINASE]. Very rarely it manifests as anorexia, asthenia, nausea and [JAUNDICE]; (<0.01%): [HEPATITIS].

- Alterations of the skin and subcutaneous tissue: (0.1-1%): [DERMATITIS], [PRURITO], [EXANTEMATIC ERUPTIONS] skin, [HYPERHIDROSIS]; (0.01-0.1%): [URTICARIA], [ACNE]; very rare / isolated cases (<0.01%): severe mucocutaneous reactions ([STEVENS-JOHNSON SYNDROME], [TOXIC EPIDERMAL NECROLYSIS]), [ANGIOEDEMA], [PHOTOSENSITIVITY REACTIONS].

- Musculoskeletal, connective tissue and bone disorders: (0.01-0.1%): [MUSCLE STIFFNESS], [JOINT STIFFNESS], [MUSCLE CRAMPS].

- Renal and urinary disorders: It can [INCREASE IN UREIC NITROGEN] and [INCREASE IN SERUM CREATININE]. In exceptional cases, NSAIDs may be responsible for [ACUTE RENAL INSUFFICIENCY], [INTERSTITIAL NEPHRITIS], [GLOMEULONEPHRITIS], [RENAL MEDULLARY NECROSIS] or [NEPHROTIC SYNDROME], [PROTEINURIA], [HYPERPOTASEMIA], [HIPONATREMIA], [POLYURIA ] and oedema. It has been observed in susceptible patients taking high doses of NSAIDs for prolonged periods of time. Patients at risk are those with heart, kidney, or liver failure, ascites, hyperreninemia, hyperaldosteronemia, shock, sepsis, systemic lupus erythematosus, dehydration, those treated with ACE inhibitors or diuretics, and the elderly.

- Reproductive system disorders: (0.01-0.1%): [MENSTRUAL CYCLE DISORDERS], prostate disorders.

- General disorders and administration site: (1-10%): [PAIN AT THE INJECTION POINT]; (0.1-1%): reactions, inflammation, itching or bleeding at the injection site, [HEAT STROKE], [ASTHENIA], [PAIN], [CHILLS]; rare (0.01-0.1%): [LOW BACK PAIN], [SYNCOPE], [CHILLS]; very rare / isolated cases (<0.01%): [ANAPHYLAXIS], [EDEMA].

- Investigations (laboratory tests): rare (0.01-0.1%): [KETONURIA], [PROTEINURIA].

The following adverse reactions may occur as they have been observed for other NSAIDs and may be associated with prostaglandin synthesis inhibitors: [ASEPTIC MENINGITIS], which may predominantly occur in patients with systemic lupus erythematosus or mixed liver disease. connective tissue, and hematological reactions ([PURPURA], [APLASTIC ANEMIA] and [HEMOLYTIC ANEMIA], rarely [AGRANULOCITOSIS] and [MEDULLAR DEPRESSION]).

ADVERSE REACTIONS RELATED TO EXCIPIENTS

- Because it contains methyl parahydroxybenzoate, it can cause [HYPERSENSITIVITY REACTIONS] (possibly delayed).

OVERDOSE

- Symptoms: The symptoms of overdose are unknown. Similar drugs have produced gastrointestinal (vomiting, anorexia, abdominal pain) and neurological (drowsiness, vertigo, disorientation, headache) disturbances.

- Treatment of poisoning: emptying of the stomach, administration of carbon adsorbent (may be effective if administered within two hours of poisoning), monitoring and maintenance of vital signs, symptomatic treatment of gastrointestinal irritation, hypotension, respiratory depression and seizures , with monitoring of renal and hepatic function and fecal detection of possible gastrointestinal bleeding. Dexketoprofen trometamol is dialyzable.

Leaflet Endolex 25Mg 12 Tablets