Enandol 25 Mg 10 Sachets Oral Solution 10 Ml

Enandol (25 Mg 10 Sachets Oral Solution 10 Ml)

ACTION AND MECHANISM

[ANALGESIC], [ANTI-INFLAMMATORY], [ANTIPIRETIC], [INHIBITOR OF THE SYNTHESIS OF PROSTAGLANDINS (CYCLOOXYGENASE)]. 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 a decrease in prostaglandin synthesis through non-selective inhibition of cyclooxygenase. Furthermore, the inhibition of prostaglandin synthesis could have an effect on other mediators of inflammation such as quinines, exerting an indirect action that would be added to their 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. After 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 an average value of less than 0.25 l / kg, being selectively distributed throughout the body. The value of the distribution half-life was approximately 0.35 h.

- Metabolism: glucuronide conjugation.

- 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 urine, which shows that there is no conversion to the R - (-) enantiomer in humans. The elimination half-life is 1-2.7 hours.

Pharmacokinetics in special situations:

- Elderly: in healthy elderly individuals (65 years or older), the exposure was significantly higher than in young volunteers after a single dose 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], [DENTALGIA].

Parenteral forms: moderate to severe symptomatic treatment of [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 advisable to start with 50 mg daily, being able to increase to the adult dosage once the good tolerability has been verified.

DOSAGE IN KIDNEY 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 LIVER INSUFFICIENCY

"ORAL"

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

- Severe (Child-Pugh score 10-15): Not recommended for use.

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 advised.

- Sachets (powder for oral solution): Dissolve the entire content of one sachet in a glass of water; shake to help dissolve. The solution obtained must be taken immediately after reconstitution.

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

CONTRAINDICATIONS

- Known hypersensitivity to dexketoprofen or [NSAID ALLERGY].

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

- [DIGESTIVE BLEED], [ESOPHAGUS BLEED], [PEPTIC ULCER] active, [BRAIN BLEED].

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

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

PRECAUTIONS

- [RENAL INSUFFICIENCY]. It is excreted in the urine, so accumulation could occur in the event of kidney failure. In addition, it could lead to a decrease in renal blood flow with reversible acute renal failure due to the inhibition of the synthesis of vasodilator prostaglandins, and cases of nephrotic syndrome and acute interstitial nephritis have even been described with prolonged treatments. Patients with a higher risk of kidney failure are those with previous kidney failure, the elderly or situations that could reduce kidney flow, such as [HYPOVOLEMIA], [DEHYDRATION], low sodium diets, heart failure, liver failure, liver cirrhosis or treatment with diuretics, ACEI or AIIRA. In high-risk patients, during prolonged treatments,It is recommended to determine renal function (serum creatinine, CLcr) before starting treatment, and periodically. In the event of worsening kidney 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 the event of liver failure. 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 impairment (class C or Child-Pugh score 10-15) is contraindicated. On the other hand, the use of NSAIDs has been associated on occasions with the appearance of hepatic symptoms, such as an increase in transaminases, [JAUNDICE] and [HEPATITIS], which could be serious and even fatal. Due to the risk of toxicity, it is advised that patients with liver diseases use this medicine at the lowest effective dose, and periodically check the liver function (transaminases,bilirubin) to look for any signs of liver damage

- Gastrointestinal toxicity. Treatment with NSAIDs has resulted in gastroduodenal ulcers, as well as life-threatening bleeding and perforation. There is an increased risk of ulcer with treatment 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 from NSAIDs, as well as in smoking, [CHRONIC ALCOHOLISM] or elderly or debilitated patients. However, short-term treatment is not without risk either.

As a general rule of thumb 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 to associate whenever possible an antiulcer drug (anti h3 or PPI).

High-risk patients should be closely monitored, as well as those undergoing treatment with 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 a crisis.

- Cardiovascular diseases. NSAIDs could lead to fluid retention and edema, which could increase blood pressure and worsen symptoms in patients with cardiovascular disease. It is advisable to monitor blood pressure at the beginning of treatment, as well as periodically throughout it. 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 studies, the risks appear higher with selective COX-2 inhibitors (coxibes) and diclofenac, while ibuprofen and naproxen have a lower cardiovascular risk. The available data do not allow to draw definitive conclusions 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 CARDIOPATIA], [CEREBRAL ISCHEMIA], [STROKE] or [PERIPHERAL ARTERIOPATHY], 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.NSAIDs should always be used at the lowest effective dose and for the shortest period of time.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 life-threatening serious adverse reactions, such as exfoliative dermatitis, toxic epidermal necrolysis or Stevens-Johnson syndrome. These adverse reactions are usually of early onset, in the first month of treatment. In the event of symptoms of hypersensitivity, mucosal lesions or skin erythema, the treatment will be suspended.

- [HYPERSENSITIVITY REACTIONS]. The administration of any NSAID has been associated with the appearance of allergic reactions. Cases of cross hypersensitivity have been reported between different NSAIDs, as well as between NSAIDs and salicylates, therefore patients with a history of [NSAID ALLERGY] other than this active ingredient or [SALICILATE ALLERGY] 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 led to severe allergic reactions, including asthma, [NASAL POLYPS], [ANGIOEDEMA] or [RHINITIS], due to the potentially greater risk of anaphylaxis mortal.

- [ASTHMA]. Asthmatic patients are more susceptible to bronchospasm when an NSAID is administered. 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, 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 NSAID- or salicylate-induced bronchoconstriction.

- [DISORDERS OF COAGULATION]. NSAIDs have antiplatelet activity, although less than that of acetylsalicylic acid. They could increase the bleeding time and favor the development of bleeding in patients with abnormal hemostasis or in treatment with anticoagulant drugs or other antiplatelet drugs.

- [ASEPTIC MENINGITIS]. Rare cases of aseptic meningitis have been reported in patients with NSAIDs, with fever and coma, probably due to a hypersensitivity reaction, although no cross-allergy has been found between NSAIDs. This meningitis seems to be more frequent in patients with [COLLAGENOSIS] 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 pictures. NSAIDs have been linked to the appearance of eye reactions, such as blurred vision, loss of vision, alteration in color vision, scotoma or alterations of the retina. Sometimes they can be serious, such as papillitis, retrobulbar neuritis, or papilledema. These disorders could be asymptomatic, so it is advisable to carry out periodic ophthalmological examinations, and especially before 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 under study for infertility, the withdrawal of the NSAID should be considered.

PRECAUTIONS RELATING TO EXCIPIENTS

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

- This medicine contains sucrose. Its use in oral liquids and pharmaceutical forms that remain in contact with the mouth for a while can damage the teeth.

ADVICE TO THE PATIENT

- The patient should inform their doctor in case 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 he has 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 for serious gastrointestinal events. During prolonged treatments, possible signs and symptoms of ulceration or bleeding should be monitored. A history of esophagitis, gastritis, and / or peptic ulcer should also be sought to ensure complete healing before initiating 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 for 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 without increasing the 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 kidney function.

- Alendronic acid, bisphosphonates: possible increased risk of esophagitis and gastric ulcer. Described cases 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 increased anticoagulant effect, with risk of bleeding. Periodic checks of coagulation indices are advised.

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

- Antidiabetics: no interaction has been observed. However, there are isolated cases of both hypoglycemic and hyperglycemic effects from diclofenac that required a change in the dosage of hypoglycemic agents.

- Sulfonylurea antidiabetic drugs (chlorpropamide, glibenclamide, tolbutamide): possible increase in hypoglycemic effects, by reducing renal excretion.

- Antihypertensive (ACEI, Beta-blockers): possible reduction of the antihypertensive effect.

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

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

- Corticosteroids: possible increase in the incidence of gastric discomfort. However, the concomitant use with glucocorticoids in the treatment of osteoarthritis may provide additional therapeutic benefit and can reduce glucocorticoid dosage.

- 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 reduced natriuretic and diuretic effect. May reduce the 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 potentiation of the 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 the hypotensive effect.

- Iloprost: possible increased risk of bleeding.

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

- Methotrexate: possible increase in plasma levels of methotrexate, with a risk of toxicity, sometimes very serious. The severity is highly dependent 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 kidney effects.

- Zidovudine: increased risk of hematological toxicity, leading to severe anemia a week after starting treatment with NSAIDs. Clinical surveillance is advised. Check blood count and reticulocyte count one to two weeks after starting NSAID treatment.

PREGNANCY

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

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 of 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 nullify uterine contractility, delaying delivery and prolonging gestation. 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 can alter female fertility and is not recommended in women trying to conceive. In women having difficulty conceiving or undergoing fertility research, discontinuation of dexketoprofen should be considered.

LACTATION

Studies in animals have revealed that concentrations in milk are 4-5% of those in plasma. There are no data on excretion with human milk. Caution is advised in use in nursing mothers.

KIDS

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

SENIORS

The elderly appear to be more susceptible to the adverse effects of NSAIDs. The risk of suffering from 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 a reduction in the effectiveness of antihypertensive treatments. Caution is recommended in its use.

EFFECTS ON DRIVING

Dexketoprofen can cause dizziness or drowsiness of weak to moderate intensity, so patients should avoid operating dangerous machinery, including cars, until they are reasonably certain that drug treatment does not adversely affect them.

ADVERSE REACTIONS

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

- Blood and lymphatic system disorders: infrequent (0.1-1%): [ANEMIA]; very rare / isolated cases (<0.01%): [NEUTROPENIA], [THROMBOCYTOPENIA].

- Alterations of metabolism and nutrition: rare (0.01-0.1%): [HYPERGLYCAEMIA], [HYPOGLYCAEMIA], [HYPERTRIGLYCERIDEMIA].

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

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

- Ear and labyrinth disorders: (0.01-0.1%): [TINNITUS].

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

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

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

- Gastrointestinal disorders: (1-10%): [NAUSEAS], [VOMITING]; (0.1-1%): [ABDOMINAL PAIN], [DYSPEPSIA], [DIARRHEA], [CONSTIPATION], [HEMATEMESIS], [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 mild and transient [TRANSAMINASE INCREASE]. 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] cutaneous, [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%): [MUSCULAR RIGIDITY], [JOINT RIGIDITY], [MUSCULAR CRAMPS].

- Renal and urinary disorders: May [INCREASE IN UREIC NITROGEN] and [INCREASE IN SERIAL CREATININE]. In rare cases, NSAIDs may be responsible for [ACUTE KIDNEY FAILURE], [INTERSTITIAL NEPHRITIS], [GLOMERULONEFRITIS], [RENAL MEDULAR NECROSIS] or [NEPHROTIC SYNDROME], [PROTEINURIA], [HYPERPOTASEMIA], [HYPONATHREMIA] ] and edema. It has been observed in susceptible patients taking high doses of NSAIDs for long periods of time. Risk patients 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 alterations and the place of administration: (1-10%): [PAIN AT THE POINT OF INJECTION]; (0.1-1%): injection site reactions, swelling, burning or bleeding, [HEATStroke], [ASTENIA], [PAIN], [CHILLS]; rare (0.01-0.1%): [LUMBALGIA], [SYNCOPE], [CHILLS]; very rare / isolated cases (<0.01%): [ANAPHYLAXIA], [EDEMA].

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

The following adverse reactions could occur as they have been observed for other non-steroidal anti-inflammatory drugs and may be associated with prostaglandin synthesis inhibitors: [ASEPTIC MENINGITIS], which could predominantly occur in patients with systemic lupus erythematosus or mixed disease of the connective tissue, and haematological reactions ([PURPLE], [APLASIC ANEMIA] and [HEMOLYTIC ANEMIA], rarely [AGRANULOCYTOSIS] and [MEDULAR DEPRESSION]).

OVERDOSE

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

- Treatment of intoxication: stomach emptying, administration of adsorbent carbon (can be effective if administered within two hours of intoxication), monitoring and maintenance of vital signs, symptomatic treatment of gastrointestinal irritation, hypotension, respiratory depression and seizures , with monitoring of kidney and liver functions and detection in feces of possible gastrointestinal bleeding. Dexketoprofen trometamol is dialyzable.

Enandol 25 Mg 10 Sachets Oral Solution 10 Ml Leaflet