Dolovanz Forte 25 Mg 10 Envelopes Oral Solution

Dolovanz Forte (25 Mg 10 Sachets Oral Solution)

dexketoprofen

Action and Mechanism

[ANALGESIC], [ANTI-INFLAMMATORY], [ANTIPYRETIC], [INHIBITOR OF PROSTAGLANDIN SYNTHESIS (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 the 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 kinins, 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 after 20 min (range 10-45 min). For single doses of 25 and 50 mg, the area under the curve has been shown to be proportional to the dose after im and iv administration.

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

- Metabolism: glucuronoconjugation.

- Elimination: it is excreted through 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 demonstrates that no conversion to the R-(-) enantiomer occurs in humans. The elimination half-life is 1-2.7 h.

Pharmacokinetics in special situations:

- Elderly: in healthy elderly individuals (65 years or older), 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 in the tmax. The elimination half-life was prolonged after single and repeated doses (up to 48%) and the apparent total clearance was reduced.

Indications for Dolovanz Forte

Dolovanz Forte is indicated for pain of mild or moderate intensity, such as musculoskeletal pain, dysmenorrhea or toothache.

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.

Dosage - How to take Dolovanz Forte?

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, and may increase to the adult dosage once good tolerability has been proven.

Polosogy in cases of kidney failure

"ORAL"

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

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

Dosage in cases of liver failure 

"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 minutes before meals. Long-term treatments are not recommended.

- Sachets (powder for oral solution): Dissolve the entire contents 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 contents must be consumed.

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 he or she has had any asthmatic reaction while taking this medication.

Contraindications

Precautions 

- [RENAL INSUFFICIENCY]. It is eliminated through urine, so accumulation could occur in cases of kidney failure. Furthermore, it could lead to a decrease in renal blood flow with reversible acute renal failure due to the inhibition of the synthesis of vasodilatory prostaglandins, and even cases of nephrotic syndrome and acute interstitial nephritis have been described with prolonged treatments. Patients at greater 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 ARAII. In high-risk patients, during prolonged treatments, it is recommended to determine renal functionality (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 failure, it is recommended to start treatment with a lower total daily dose, carefully monitoring the patient. Use in moderate or severe renal failure (CLcr < 50 ml/min) is contraindicated.

- [LIVER FAILURE]. Due to its hepatic metabolism, accumulation could occur in case 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 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 problems, such as increased transaminases, [JAUNDERY] 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 medication at the minimum effective dose, and periodically review liver function (transaminases, bilirubin) to detect 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 a greater 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 due to NSAIDs, as well as in smoking, [CHRONIC ALCOHOLISM] or elderly or weakened 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. Furthermore, in risk groups it is advisable to start treatment with the lowest possible dose, and always combine an anti-ulcer drug (anti-H2 or PPI) whenever possible.

High-risk patients should be closely monitored, as well as those who are being treated 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 suspended. 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 diseases. 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 the studies carried out, the risks seem higher with selective COX-2 inhibitors (coxibes) and diclofenac, while ibuprofen and naproxen have a lower cardiovascular risk. The available data do not allow definitive conclusions to be drawn with other NSAIDs, so cardiovascular risk cannot be ruled out. It is recommended to individually evaluate the benefit/risk relationship in patients with [ARTERIAL HYPERTENSION], [HEART FAILURE], [ISCHEMIC HEARTDIOPATHY], [CEREBRAL ISCHEMIA], [STROKE] or [PERIPHERAL ARTERIOPATHY], as well as in patients with cardiovascular risk factors. , such as [DYSLIPEMIA], [DIABETES] or [TOBACCOSM]. 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 usually begin early, in the first month of treatment. If symptoms of hypersensitivity, mucosal lesions or skin erythema are observed, treatment will be suspended.

- [HYPERSENSITIVITY REACTIONS]. The administration of any NSAID has been related to the appearance of allergic reactions. Cases of cross-hypersensitivity have been reported between different NSAIDs, as well as between NSAIDs and salicylates, 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 NSAID has previously given rise to serious 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 experiencing bronchospasm in the event of administration of an NSAID. Additionally, they could be more susceptible to suffering from 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 a reduction in respiratory function or the appearance of allergic symptoms occurs, 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 bleeding time and promote the appearance of bleeding in patients with hemostasis disorders or being treated with anticoagulant drugs or other antiplatelet agents.

- [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 common 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 related to the appearance of ocular reactions, such as blurred vision, vision loss, 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 perform periodic ophthalmological check-ups, and especially in the event of any change in vision.

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

Precautions regarding excipients

- This medicine contains ethanol. It is recommended to check 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 to 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 ([LIVER FAILURE]. ], [LIVER CIRRHOSIS], [HEPATITIS]) or [EPILEPSY].

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

- Because it contains benzyl alcohol, it should not be administered to premature children or newborns.

Doses of benzyl alcohol greater than 90 mg/kg/day can produce fatal toxic reactions in children under 3 years of age, so it is recommended to avoid exceeding these doses.

Doses of benzyl alcohol less than 90 mg/kg/day can cause anaphylactoid and toxic reactions in children under three years of age.

- This medicine contains sucrose. Patients with hereditary fructose intolerance, glucose or galactose malabsorption, or sucrase-isomaltase insufficiency should not take this medication.

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

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 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 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 risk factors for cardiovascular disease. Monitor for possible signs of hydrosaline retention (e.g. formation of edema), especially in patients with hypertension or heart failure.

- Masking of symptoms of underlying infections: Dexketoprofen may mask the symptoms of an infection, which may delay the initiation of appropriate treatment and therefore worsen the outcome of the infection. This has been observed in community-acquired bacterial pneumonia and in bacterial complications of chickenpox. When this medication is given to relieve pain related to an infection, monitoring for the infection is recommended. In non-hospital settings, the patient should consult a doctor if symptoms persist or worsen.

Interactions with other substances

- 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 kidney function (dehydrated or elderly), deterioration of kidney 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. Described cases with naproxen and alendronate.

- Quinolonic 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 rates 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 digestive bleeding.

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

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

- Antihypertensives (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 bleeding in particular. Administer with caution. 

- Corticosteroids: possible increase in the incidence of gastric discomfort. However, simultaneous use with glucocorticoids in the treatment of osteoarthritis may provide additional therapeutic benefit and allows 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. It may reduce the antihypertensive action of thiazide diuretics.

- Potassium-sparing diuretics and aldosterone antagonists: possible increased risk of hyperkalemia. 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 possible 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 increase in the 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 hematological toxicity, leading to severe anemia one week after starting treatment with the NSAID. Clinical surveillance is advised. Check blood count and reticulocyte count one to two weeks after starting NSAID treatment.

Pregnancy - Can I take Dolovanz Forte during pregnancy?

Safety in animals: Animal studies with various NSAIDs have recorded cardiovascular malformations during the organogenic period.

Safety in humans: Starting from the 20th week of pregnancy, the use of glucosamine may cause oligohydramnios as a result of fetal kidney dysfunction. This may occur shortly after initiation of treatment and is usually reversible by discontinuing treatment. Additionally, cases of constriction of the ductus arteriosus have been reported following treatment in the second trimester, most of which resolved after discontinuation of treatment. During the first and second trimesters of pregnancy, glucosamine should not be administered unless considered strictly necessary. If glucosamine is used by a woman trying to become pregnant, or during the first and second trimesters of pregnancy, the dose and duration of treatment should be reduced as much as possible. Antenatal monitoring for oligohydramnios and constriction of the ductus arteriosus should be considered after exposure to glucosamine for several days from gestational week 20 onwards. Treatment with glucosamine should be interrupted if oligohydramnios or constriction of the ductus arteriosus is found.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can expose the fetus to:

- cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);

- kidney dysfunction;

to the mother and the newborn, at the end of pregnancy, to:

- possible prolongation of bleeding time, an antiplatelet effect that can occur even at very low doses;

- inhibition of uterine contractions resulting in delayed or prolonged labor.

Effects on fertility: the use of NSAIDs can impair female fertility and is not recommended in women who are trying to conceive. In women who have difficulty conceiving or are undergoing fertility investigation, discontinuation of dexketoprofen should be considered.

Breastfeeding - How to take Dolavanz Forte while breastfeeding?

Safety in animals: no data available.

Safety in humans: It is unknown whether dexketoprofen is excreted in milk, and the consequences it could have for the nursing infant. Contraindicated.

Children

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

Advanced age

In elderly patients, it is recommended to start treatment with the lowest dose. Use with caution, due to the high probability of adverse reactions. A higher incidence of gastrointestinal adverse reactions to NSAIDs has been observed, especially bleeding and perforation. In addition, they may suffer alterations at the kidney, liver or cardiovascular level. It can reduce the effect of antihypertensives. Therefore, it should be used with caution in patients >65 years of age.

Effects on donation

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

Adverse reactions

Adverse reactions related to excipients

- Because it contains methyl parahydroxybenzoate, it may cause allergy to parabens, 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) alterations.

- Treatment of poisoning: Emptying of the stomach, administration of adsorbent charcoal (can 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 kidney and liver functions and detection of possible gastrointestinal bleeding in feces. Dexketoprofen trometamol is dialyzable.

Buy Dolovanz Forte 25 Mg 10 Envelopes Oral Solution

Dolovanz Forte 25 Mg 10 Sachets Oral Solution can be purchased without a prescription. As it is a medicine, the price of Dolovanz is set by the CIPM.

Package Leaflet Dolovanz Forte 25 Mg 10 Envelopes Oral Solution