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COMPOSITION


Lysine Clonixinate ...................................................... 125 mg
(Equivalent in Clonixine ................................................ 80.3 mg)
Excipients c.s.p. ............................................................. 1 Comprimido


INDICATIONS :

Dorixyl® is prescribed for :
The treatment of somatic and visceral pain syndromes.

CONTRAINDICATIONS :

Hypersensitivity to Clonixinate Lysine. It is contraindicated when either active peptic or duodenal ulcer are present. Should not be administered during pregnancy, in children under age 12, or in patients with a history of bronchospasm, nasal polyps, angioedema or hives caused by acetylsalicylic acid (Aspirin®) or other NSAIDs.

PHARMACOLOGY :

Because of its content of Lysine Clonixinate, DORIXYL® is rapidly and completely absorbed, with levels reached within 15 minutes. Its mechanism of action is developed by inhibiting the synthesis of prostaglandins, specifically on the catalytic enzyme of the synthesis of prostaglandins that mediate inflammation (cyclooxygenase-2 or COX-2), with less activity on the catalytic enzyme of the synthesis of prostaglandins in the gastrointestinal mucus and kidneys (Cyclooxygenase-1 or COX-1), where these substances have a protective function. This drug has a half life of 90 minutes, and is metabolized primarily in the liver, distributing the metabolites through the blood vessels, and is eliminated through the kidneys.

PHARMACOKINETICS :

1. Application and duration :
Initial response on the application : When taken orally, analgesic effect is achieved within 15 to 30 minutes.
Duration of a single oral dose effect : Four hours for headaches.

2. Concentration levels :

Orally, the therapy concentration peak was reached in 15 minutes. The concentration peak was 46.1 ug / mL after administering a 750 mg single oral dose.

3. ADME :
Absorption : 75% orally.
Distribution : Pediatric volume of distribution 1.14 - 1.29 L. Values obtained in children 4 to 10 years of age.
Metabolism : It is metabolized in the liver forming hydroxylated and hydroxymethylized metabolites (activities are unknown).

4. Elimination :
Through the kidneys (not quantified but substantial); body level (17-26 mL / minute with values obtained in children 4-10 years of age who were given doses of 4-6 mg / kg of body weight); bile elimination (lesser amount, not quantified). The elimination occurs after 90-104 minutes.








DRUG INTERACTIONS :

Combinations with other drugs :
• Alendronate : A controlled three-year clinical trial in 2,027 patients most of whom received NSAIDs, the incidence of gastrointestinal adverse effects were similar to those developed in patients receiving Alendronate and those receiving a placebo. It is not recommended to administer Alendronate and NSAIDs simultaneously since they have been associated with gastrointestinal irritation.

• Angiotensin Converting Enzyme (ACE) Inhibitor : NSAIDs may diminish the antihypertensive and natriuretic effect of the Angiotensin Converting Enzyme. The mechanism involves attenuation of the antihypertensive effect of the secondary agent in the production of vasodilator and natriuretic prostaglandins, which are stimulated by antihypertensive agents. There is no known significant pharmacokinetic interaction between NSAIDs and Angiotensin Converting Enzyme, and its combination may produce effects such as bradycardia due to hyperkalemia. Patients suffering from hypertension, diabetes mellitus, ischemic heart disease and degenerative diseases linked to the above must be careful when taking the combination of these drugs.

• The concomitant use with Ibuprofen and antihypertensives results in a drop in blood pressure and interference in the control of blood pressure.

• Beta-Adrenergic Blockers : The concomitant use with NSAIDs results in increased blood pressure, i.e. decreases the antihypertensive effect.

• Calcium Channel Blockers :
Usually associated with an increased risk of gastrointestinal bleeding.

• Concomitant use of Clopidogrel with NSAIDs is associated with increased gastrointestinal blood loss.

• Concomitant use of Cyclosporine with NSAIDs results in increased levels of nephrotoxicity of Cyclosporine and the consequent plasma concentration of Creatinine.

• Concomitant use of Danaparoid with NSAIDs results in an increased risk of bleeding and increased risk of hematoma when used as neuraxial anesthesia.

• Concomitant use of Eptifibatide with NSAIDs may cause increased anticoagulant activity leading to risk of superficial and internal bleeding.

• Ketorolac is contraindicated in patients taking NSAIDs because of the cumulative risk associated with peptic ulcers, gastrointestinal bleeding and / or perforation.

• Concurrent use of Levofloxacin with NSAIDs, may increase the risk of the Central Nervous System stimulation and the onset of a seizure episode.

• Lisinopril / Hydrochlorothiazide : NSAIDs decrease the antihypertensive and natriuretic effect of Angiotensin Converting Enzyme inhibitors, particularly in low renin hypertensive patients.

• Diuretics :
NSAIDs reduce the diuretic and antihypertensive effects of the Thiazide Group and the rest of the Loop of Henle diuretics. The Loop of Henle diuretics act by active inhibition in the transport of chloride in the Loop of Henle and increase renal blood flow.

• Low Molecular Weight Heparin :
The risk of spinal or epidural hematoma is increased when using low molecular weight Heparin and NSAIDs.

• Concurrent use of Ofloxacin and NSAIDs may increase the risk of the Central Nervous System stimulation and the onset of a seizure event.

• Low-Potassium Diuretics : NSAIDs may reduce diuretic and antihypertensive effect of the Loop of Henle, Thiazide Group, and low-potassium diuretics. They may also cause hyperkalemia or even nephrotoxicity if used concurrently.

• Sulfonylureas :
Hypoglycemia may occur if sulfonylureas are co-administered with NSAIDs.

• Tacrolimus (Immune Suppression) : May cause anuria, oliguria, or acute kidney failure if administered with Ibuprofen.

• Thiazide Diuretic Group : Their diuretic and antihypertensive effect is reduced when used concurrently with NSAIDs.


CHANGES IN LABORATORY TESTS :

Guaiac Test.- NSAIDs may cause gastrointestinal bleeding, which can produce a positive result of fecal blood culture, thus interfere with the reading of colorectal cancer.
PRECAUTIONS :
Not to be given to patients with peptic ulcer or patients predisposed or with pre-existing nepho-therapy and acute kidney dysfunction. Patients should make regular visits to their specialist during prolonged therapy. Alcohol use increases the risk of ulceration; consult the specialist if you drink three or more alcoholic beverages. Do not take two or more NSAIDs concurrently unless the specialist evaluate the risk / benefit and prescribes it. Side effects that may occur should be evaluated if concurrent use of two NSAIDs is needed.

While preclinical toxicology studies have shown no teratogenic effects, there is insufficient experience with the administration of Lysine Clonixinate in pregnant women and, therefore, should not be administered during this period.
Studies in humans showed that the excretion of Lysine Clonixinate in breast milk is small and, therefore, the risk / benefit scenario should be assessed when administered to nursing women.

There are no clinical studies on the administration of Clonixinate Lysine to children under 12, thus, its use is contraindicated for them.

As with all anti-inflammatories, Lysine Clonixinate should be administered with caution to elderly patients as they may have impaired kidney, liver or cardiovascular function.

SIDE EFFECTS :
The main side effects in therapeutic treatment are gastrointestinal in nature (nausea, vomiting, epigastric pain). There are other side effects that affect the central nervous system (headache, dizziness, drowsiness) and, occasionally, skin reactions.

Side effects at blood level are :

• Platelet aggregation : Was observed in 9 volunteer patients who were given 500 mg of Lysine Clonixinate three times daily for three days.
• Cardiovascular Edema : Occurred in one out of every 100 patients treated with 125 mg of Lysine Clonixinate after minor dental surgery.
• Cardiovascular Hypotension : Occurred in one of 236 patients treated with 250 mg of Lysine Clonixinate.

Side effects to the central nervous system : Vertigo, dizziness, drowsiness, euphoria, fatigue, headache, insomnia, tremor.

Gastrointestinal side effects : Diarrhea, dry mouth, epigastric pain, flatulence, gastrointestinal disturbances, heartburn, nausea, vomiting.

Renal / Genitourinary side effects : Proteinuria.

Dermal side effects : Diaphoresis (excessive dry skin), flushing or redness, irritation (when applied parenterally), itching, pruritus, urticaria.

Other side effect : Cold symtoms (flu).

Should not be administered to patients with renal dysfunction, cholestasis and paresthesia.

WARNINGS :  

Not to be used in patients allergic to Aspirin or other NSAIDs. Should not be administered to pregnant or nursing women. Not recommended for children under 12 years of age. May increase the risk of toxicity in elderly patients. Closely monitor when administered with other medications such as anticoagulants, Aspirin and cephalosporins that may induce hypoprothrombinemia; on the other hand, monitor cyclosporine, lithium, methotrexate, plicamycin, probenecid, triamterene, and valproic acid.

Do not take more than the prescribed or recommended dose.

If you miss the recommended dose, which may be one or two times a day, take it as soon as possible within the first two hours. Do not take it close to the next one (this will double the dose).

Due to its content of lactose, intolerance have been reported in children and adolescents, although because of the amount of lactose present in the preparation it is unlikely to trigger symptoms of intolerance, in which case you should consult your doctor.


TREATMENT IN CASES OF OVERDOSE :

In the event of an overdose, go immediately to the nearest hospital. After a clinical evaluation of the patient, the specialist will decide the appropriate treatment : Self-induced vomiting or emesis, gastric lavage or administration of activated charcoal.

There is no specific antidote.

DOSE AND ROUTES OF ADMINISTRATION :

Dose for adults and children over 12 years :
Unless otherwise indicated : 1 coated tablet three or four times daily at regular intervals depending on pain scale.
Take the coated tablets whole without chewing, and with plenty of water.
Maximum daily dose : 6 coated tablets.

STORAGE CONDITIONS :

Store at temperatures between 15-30°C. Keep away from heat and sunlight.

PRESENTATION :

Boxes of 20, 48, 60, 80 and 100 tablets in blisters of 4 coated tablets.
Dispenser of 100 tablets in blisters of 4 coated tablets.
Envelope of 4 coated tablets in blisters.

Sold under prescription

MASTER FARMA S.A.

Address :
Calle Mariano Odicio 490,
Miraflores,
Lima 18 – Perú

Phone :
+51 (1) 446 1250
+51 (1) 242 5577

Fax :
+51 (1) 445 7701


Propiedad de MASTER FARMA S.A. ®-2006