Tandrilax: what is it used for?

Tandrilax is a medicine indicated for the treatment of rheumatism (a group of diseases that can affect the joints, muscles and skeleton, characterized by pain, restricted movement and possible presence of inflammatory signs). The most common examples of this disease are: low back pain (pain in the lower back), osteoarthritis, acute attack of rheumatoid arthritis or other rheumatic arthropathies, acute attack of gout (a disease characterized by the deposition of uric acid crystals near joints and other organs), acute inflammatory states after trauma and surgery. Tandrilax is also indicated as an adjuvant in severe inflammatory processes resulting from infectious conditions.

How does Tandrilax work?

Tandrilax has a muscle relaxant , anti-inflammatory and analgesic (pain-relieving action) composition , indicated for the treatment of rheumatism, which is generally associated with complaints such as pain and inflammatory signs, such as swelling, local heat and possible limitation of mobility. Tandrilax, as it has a combination of medications in its composition, will act as follows: carisoprodol is a muscle relaxant that indirectly reduces skeletal muscle tension in humans. Caffeine is a central nervous system stimulant that produces a state of mental alertness and tends to correct the drowsiness that carisoprodol causes. Caffeine also has an action against pain, acting on the muscles and making them less susceptible to fatigue (tiredness) and improving their performance. Diclofenac sodium is an important anti-inflammatory that will also act to combat pain and reduce symptoms, such as fever and localized swelling, just as paracetamol also has an anti-inflammatory action and acts synergistically to control pain and temperature.

What are the contraindications of Tandrilax?

Tandrilax is contraindicated in patients who are hypersensitive (allergic) to any of the components of its formula; in cases of heart failure (impaired heart function), hepatic (liver) or severe renal (kidney) failure and severe arterial hypertension ( high blood pressure ). It is also contraindicated in patients who are hypersensitive to anti-inflammatory drugs (e.g. acetylsalicylic acid) with triggering of reactive conditions, such as asthmatics in which it can cause asthma attacks , hives ( itching ) or acute rhinitis ( inflammation of the nasal mucosa).

Tandrilax should only be used under medical prescription. Tell your doctor about any medications you are taking before starting or during treatment.

This medicine is intended for adult use.

Do not use any other product that contains paracetamol .

It is not recommended for children under 14 years of age, with the exception of cases of chronic juvenile arthritis.

How to use Tandrilax?

As a general rule, the recommended minimum daily dose is one tablet every 12 hours, with a maximum of one tablet taken every 8 hours, i.e. three daily doses. However, it is important to note that it is up to the doctor to individually analyze each clinical case, adapting the best dosage of medication and the duration of treatment, according to the patient’s age and general condition. The lowest effective doses should be administered and, whenever possible, the duration of treatment should not exceed 10 days.

Longer treatments require special observations.

Tandrilax tablets should be swallowed whole (without chewing), with meals, with the aid of liquid.

Follow your doctor’s instructions, always respecting the times, doses and duration of treatment.

Do not stop treatment without your doctor’s knowledge.

This medicine should not be broken or chewed.

What should I do if I forget to use Tandrilax?

If you miss a dose, you should take the tablet as soon as possible. If it is close to your next dose, skip the missed dose and wait until your usual dose is taken. You should not take two doses at the same time.

If you have any questions, seek advice from your pharmacist or doctor or dentist.

What precautions should I take when using Tandrilax?

Tandrilax should be used under medical prescription.

Safety and efficacy in pediatric patients have not been established, therefore its use in children and adolescents is not recommended.

The possibility of reactivation of peptic ulcers (injury to the esophageal-gastrointestinal mucosa) requires careful analysis when there is a previous history of dyspepsia (indigestion), gastrointestinal bleeding or peptic ulcer .

When Tandrilax is prescribed for periods longer than ten days, a blood count (blood test) and liver function tests should be performed before starting treatment and periodically thereafter. A decrease in the leukocyte and/or platelet count, or hematocrit, requires the medication to be discontinued.

Long-term use of diclofenac has been associated with serious gastrointestinal adverse events, such as ulceration ( lesions ), bleeding, and perforation of the stomach or intestines, especially in elderly and debilitated patients. Chronic use of diclofenac sodium increases the risk of kidney damage and impaired kidney function.

Acute abdominal conditions may be difficult to diagnose when taking carisoprodol. Carisoprodol may cause involuntary contraction of the sphincter of Oddi (the area of ​​greatest pressure that regulates the passage of bile into the duodenum) and reduce secretions from the bile and pancreatic ducts (ducts from the gallbladder and pancreas).

People with intracranial hypertension (high blood pressure in the brain) or traumatic brain injury (trauma to the brain) should not use Tandrilax, as should patients who have reduced cytochrome CYP2C19 activity (liver enzyme), either due to illness or the use of other medications.

Prolonged use of Tandrilax may lead to drug addiction and its discontinuation, to withdrawal syndrome, when used in high doses and for a prolonged period. Concomitant use with alcohol and central nervous system depressant drugs is not recommended.

If allergic reactions such as itching or erythematous ( redness ), fever , jaundice (yellowing of the skin), cyanosis (bluish coloration of the skin due to lack of oxygen) or blood in the stool are observed, the medication should be immediately discontinued.

Ability to drive vehicles and operate machinery

It is recommended that patients during treatment with Tandrilax avoid driving cars, motorcycles and other vehicles, as well as operating dangerous machinery, as carisoprodol may interfere with these abilities.

Cross-sensitivity

There are reports of cross-reaction between diclofenac and acetylsalicylic acid. Patients who have previously had severe allergic reactions to acetylsalicylic acid or other non-hormonal anti-inflammatory drugs (e.g. ibuprofen , ketoprofen ) should avoid using Tandrilax, due to the increased risk of bronchospasms (a disease that causes difficulty breathing).

Use in pregnancy

Although the studies carried out did not show any teratogenic effects (harm to the fetus), the use of Tandrilax is not recommended during pregnancy and lactation.

This medicine should not be used by pregnant women without medical advice. Inform your doctor immediately if you suspect you are pregnant.

What are the adverse reactions and side effects of Tandrilax?

Adverse Reactions separated by frequency of occurrence:

• Very common reactions (> 1/10): increased liver enzymes;
• Common reactions (> 1/100 and < 1/10): headache, dizziness , insomnia , tremor, pain, gastrointestinal bleeding , gastrointestinal perforation, gastrointestinal ulcers, diarrhea , indigestion, nausea, vomiting, constipation, flatulence, abdominal pain, heartburn , fluid retention, edema ( swelling ), rash, pruritus, facial edema, anemia , coagulation disorders, bronchospasm , rhinitis, tinnitus, fever, and viral disease;
• Uncommon reactions (> 1/1000 and < 1/100): hypertension, congestive heart failure, dizziness , drowsiness, agitation, depression , irritability , anxiety, alopecia, urticaria, dermatitis and eczema ;
• Rare reactions (> 1/10,000 and < 1/1,000): aseptic meningitis , convulsions, pancreatitis , fulminant hepatitis , hepatic failure , respiratory depression, pneumonia, hearing loss, agranulocytosis, aplastic anemia, hemolytic anemia, anaphylactoid reactions, exfoliative dermatitis, erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Other reactions observed with unknown frequency:

• Cardiovascular effects: cardiac arrhythmia, peripheral vasodilation (high doses), myocardial infarction , angina, increased risk of cardiovascular events, reduced splanchnic perfusion (in premature neonates), palpitations, tachyarrhythmia, widening of the QRS complex on the electrocardiogram (moderate to high doses), orthostatic hypotension and syncope;
• Dermatological effects: acute generalized exanthematous pustulosis, contact dermatitis , lichenoid dermatitis, linear bullous dermatosis , skin necrosis and necrotizing fasciitis;
• Metabolic-endocrine effects: acidosis, hypoglycemia, hyperglycemia, hydroelectrolytic disorders (hypokalemia, hyperkalemia and hyponatremia), reduction of testosterone , increase in estrone, increase in sex hormone-binding globulins, rhabdomyolysis, increased bone mass loss and hypothermia;
• Hepato and gastrointestinal effects: increased colon motor activity, liver cirrhosis , liver fibrosis, hepatotoxicity, inflammatory bowel disease , colonic ulceration, constriction of intestinal diaphragms, protein loss, esophagitis , proctitis, pseudomembranous enterocolitis , melena and jaundice;
• Genito-reproductive effects: fibrocystic breast disease, reduced conception rates and increased rates of multiple pregnancies (men);
• Hematological effects: disseminated intravascular coagulation, methemoglobinemia and acute intermittent porphyria;
• Infectious effects: sepsis ;
• Immunological effects: anaphylaxis, cross-sensitivity reaction (meprobamate) and immune hypersensitivity reaction (quadriplegia, dizziness, ataxia, diplopia, mental confusion, disorientation, angioedema and anaphylactic shock );
• Musculoskeletal effects: chronic back pain, muscle paralysis, fasciculations, acetabular destruction;
• Neurological effects: increased alertness, cerebral hemorrhage , withdrawal syndrome, reduced cognitive ability), hallucinations, psychosis, drug addiction (prolonged use), amnesia, stroke, encephalitis, myoclonus and paresthesia ;
• Ophthalmological effects: retinopathy, corneal infiltrate, blurred vision and conjunctivitis ;
• Otorhinolaryngological effects: change in voice timbre;
• Renal effects: acute renal failure , nephrotic syndrome , nephrotoxicity, papillary necrosis, cystitis , dysuria , hematuria , interstitial nephritis , oliguria, polyuria, proteinuria, and angioedema;
• Respiratory effects: dyspnea , hyperventilation, tachypnea, acute pulmonary edema and pneumonitis.

Inform your doctor, dentist or pharmacist if you experience any undesirable reactions due to the use of the medication. Also inform the company through its customer service department.

Inform the company about the appearance of undesirable reactions and problems with this medicine, by contacting the Consumer Service Center (CAC).

Tandrilax Special Population

Use in the elderly

Use in elderly patients (patients who are generally more sensitive to medications) should be carefully monitored. Elderly people using Tandrilax should be monitored carefully, as they are at greater risk of respiratory depression and gastrointestinal adverse events.

Patients with cardiovascular disease (heart disease)

Tandrilax should be used with caution in patients with cardiovascular disease, due to the risk of cardiovascular thrombotic events (formation of thrombi in the circulation), such as heart attack or stroke, due to the presence of diclofenac in the formula. In patients with cardiovascular disease, the possibility of sodium retention and edema (swelling) should be considered.

Dehydrated patients may be at greater risk of hypotension (low blood pressure) when taking carisoprodol.

Patients with liver or kidney disease

Tandrilax should be used with caution in patients with liver or kidney damage, as the action of this medication may change and pose greater risks during use. In these cases, it is important to evaluate each clinical situation and the dose to be taken is appropriate for the patient.

The half-life of caffeine is increased in patients with liver disease such as cirrhosis (destruction of liver tissue) and viral hepatitis (inflammation of the liver caused by viruses). Therefore, dosage adjustments should be made for these patients. In high doses, caffeine can cause chronic back pain, trigger underlying psychiatric illnesses, and increase the frequency and severity of adverse effects. Patients taking medications containing caffeine should be advised to limit their intake of other sources of caffeine such as foods , beverages, and other medications containing caffeine.

Patients with obstructive or restrictive lung diseases

Tandrilax should be used with caution in patients with chronic obstructive or restrictive pulmonary diseases , due to the risk of respiratory depression.

Tandrilax Presentations

Tablets with 30 mg of caffeine + 125 mg of carisoprodol + 50 mg of diclofenac sodium + 300 mg of paracetamol

Packages with 4, 15 or 30 tablets.

Oral use.

Adult use only.

What is the composition of Tandrilax?

Each Tandrilax tablet contains:

Caffeine	30 mg
Carisoprodol	125 mg
Sodium diclofenac	50 mg
Paracetamol	300 mg

Excipients: starch, microcrystalline cellulose, magnesium stearate, crospovidone, FDC yellow dye no. 6 aluminum lake, silicon dioxide and dibasic calcium phosphate dihydrate.

Overdose: What happens if I take a higher dose of Tandrilax than recommended?

Signs of a possible overdose include:

• Confusion, drowsiness, rapid or irregular heartbeat, loss of appetite , nausea, vomiting, stomach pain, low blood pressure, tremors. Many of these effects can occur normally and may not require medical attention, but if in doubt, consult your doctor. These undesirable effects may disappear during treatment as your body adjusts to the medication.

Your doctor can tell you about the nature of your symptoms. Your doctor will also be able to tell you about ways to prevent or reduce many of these effects. Talk to your doctor if any of these effects persist.

Serious poisoning may present with more intense symptoms or others such as convulsions, agitation, respiratory inability, fainting, liver and kidney changes. If serious poisoning is suspected , the patient must be taken immediately to a hospital for life support measures and continuous monitoring of vital signs.

If you suspect drug poisoning, seek medical help immediately.

If you use a large amount of this medicine, seek medical help quickly and take the medicine packaging or leaflet with you, if possible.

In case of poisoning, call 0800 722 6001 if you need further guidance on how to proceed.

Drug interactions: what are the effects of taking Tandrilax with other medications?

Drug interactions related to diclofenac sodium

Drug-Drug Interaction

Major Gravity

There is an increased risk of bleeding with the combined use of ardeparin, clovoxamine, dalteparin, desirudin, enoxaparin, escitalopram, famoxetine, flesinoxan, fluoxetine, fluvoxamine, nadroparin, nefazodone, parnaparin, paroxetine, pentoxifylline , reviparin, sertraline, tinzaparin, zimeldine.

Increased toxicity of some medications such as methotrexate and pemetrexed may occur, with the risk of myelosuppression, renal and gastrointestinal toxicity. The associated use with tacrolimus may lead to acute renal failure.

Moderate severity

Increased plasma concentrations of diclofenac may occur with the use of voriconazole , just as ciprofloxacin may also cause an increase in its own plasma concentration.

The associated use of levofloxacin , norfloxacin or ofloxacin may cause an increased risk of seizures.

The associated use of antihypertensives from the beta-blocker class (e.g. atenolol ) and the ACE inhibitor class (Angiotensin Converting Enzyme, e.g. captopril ) and enalapril) may have their antihypertensive effect reduced.

The association with acetohexamide, chlorpropamide , gliclazide , glimepiride , glipizide , gliquidone, glyburide, tolazamide or tolbutamide may lead to an increased risk of hypoglycemia.

Increased risk of developing gastric mucosal lesions is associated with the use of desvenlafaxine, dicumarol, duloxetine, acenocoumarol, anisindione, citalopram, clopidogrel, eptifibatide, milnacipran, phenindione, phenprocoumon , ginkgo, prasugrel, venlafaxine, warfarin and meadowsweet.

Amiloride, canrenoate, spironolactone , triamterene may have reduced diuretic effect, hyperkalemia, possible nephrotoxicity when associated with diclofenac, as well as chlorothiazide, chlorthalidone , furosemide , hydrochlorothiazide , indapamide will also have their diuretic and antihypertensive efficacy impaired.

Losartan and valsartan may have reduced antihypertensive effect and increased risk of renal failure.

The association of diclofenac with cyclosporine may increase its toxicity, potentially leading to risks of renal dysfunction , cholestasis and paresthesia, just as the use of digoxin may also increase toxicity associated with nausea, vomiting and arrhythmias.

There is a risk of lithium poisoning in case of combination, which can cause symptoms such as weakness, tremors, excessive thirst and confusion.

The use of feverfew may cause an increased risk of adverse events associated with non-hormonal anti-inflammatory drugs.

The use of the drugs colestipol and cholestyramine may cause a decrease in the bioavailability of diclofenac.

Minor Gravity

Increased risk of gastrointestinal bleeding and/or antagonism of hypotensive effect may occur when used in combination with amlodipine , bepridil, diltiazem, felodipine , flunarizine, galopamil, isradipine, lacidipine , lidoflazine, manidipine, nicardipine, nifedipine , nilvadipine, nimodipine , nisoldipine, nitrendipine , pranidipine and verapamil.

Drug-Laboratory Test Interaction

When using diclofenac, the fecal occult blood test can potentially give a false-positive result.

Drug interactions related to carisoprodol

Drug-Drug Interaction

Major Gravity

There is a potential risk of respiratory depression when used in conjunction with medications such as adinazolam, alprazolam , amobarbital, anileridine, aprobarbital, bromazepam , brotizolam, butalbital, ketazolam, chlordiazepoxide, chlorzoxazone, clobazam , clonazepam , clorazepate, codeine, dantrolene, diazepam , estazolam , ethchlorvynol, phenobarbital , fentanyl , flunitrazepam , flurazepam , halazepam, chloral hydrate, hydrocodone, hydromorphone, levorphanol, lorazepam , lormetazepam, medazepam, meperidine, mephenesin, mephobarbital, meprobamate, metaxalone, methocarbamol, methohexital, midazolam, morphine, nitrazepam , nordazepam, oxazepam, sodium oxybate, oxycodone , oxymorphone, pentobarbital, prazepam, primidone , propoxyphene, quazepam, remifantanil, secobarbital, sufentanil, liposomal morphine sulfate, temazepam, thiopental and triazolam. There is also a risk of central nervous system depression with the use of Kava.

Caffeine-related drug interactions

Drug-Drug Interaction

Moderate severity

Medications such as:

• Ciprofloxacin, echinacea, enoxacin, grepafloxacin, norfloxacin and verapamil when associated with caffeine can lead to an increase in its plasma concentration and consequent stimulation of the central nervous system.

The associated use with clozapine may cause an increased risk of toxicity with risks of sedation , convulsions and hypotension.

Desogestrel in combination with caffeine may lead to increased stimulation of the central nervous system, just as phenylpropanolamine, pipemidic acid and terbinafine may cause increased plasma concentrations of caffeine leading to symptoms such as anxiety, irritability, insomnia or increased diuresis .

The association with theophylline may also lead to an increase in its plasma concentrations.

Minor Gravity

Caffeine may cause a reduction in the therapeutic effect of adenosine . It may potentially lead to a reduction in the sedative and anxiolytic effect of drugs such as adinasolam, alprazolam, bromazepam, brotizolam, chlordiazepoxide, clobazam, clonazepam, clorazepate, diazepam, estazolam, flunitrazepam, flurazepam, halazepam, lorazepam, midazolam, nitrazepam, oxazepam, prazepam, quazepam, quetazolam, temazepam and triazolam.

There may eventually be an increased risk of cardiovascular and cerebral excitation associated with high concentrations of caffeine if combined with the use of disulfiram .

Methylxanthine may enhance the effects of caffeine, increasing the risk of caffeine-related adverse events.

Drug-Laboratory Test Interaction

Minor Gravity

Caffeine may cause a false reduction in serum phenobarbital levels.

Drug interactions related to paracetamol

Drug-Drug Interaction

Moderate severity

Medicines such as zidovudine , carbamazepine , diflunisal and isoniazid in association with paracetamol present a risk of hepatotoxicity and neutropenia, just as phenytoin may also present an increased risk of hepatotoxicity and decreased efficacy of paracetamol.

The association with warfarin may cause a risk of bleeding, just as acenocoumarol may have its anticoagulant effect potentiated.

Minor Gravity

The association with chloramphenicol may increase its toxicity, leading to symptoms such as vomiting, hypotension and hypothermia.

Drug-Food Interaction

Major Gravity

Alcohol consumption may increase the risk of hepatotoxicity from the medication.

Drug-Laboratory Test Interaction

Moderate severity

The use of paracetamol can lead to changes in tests such as a false increase in serum uric acid levels and false positive results in the 5-hydroxyindoleacetic acid test.

Inform your doctor or dentist if you are taking any other medication.

Do not use medication without your doctor’s knowledge. It can be dangerous to your health.

What is the action of the substance Tandrilax (Caffeine + Carisoprodol + Diclofenac Sodium + Paracetamol)?

Efficacy Results

Caffeine + Carisoprodol + Diclofenac sodium + Paracetamol is a medicine composed of the combination of caffeine, carisoprodol, diclofenac sodium and paracetamol which, when combined, help to relieve pain, increasing the analgesic potential of each of the substances and reducing their adverse effects, by allowing the use of smaller doses of each of the drugs.

In a systematic review of the scientific literature from 1964 to 1984, 30 clinical studies involving more than 10,000 patients were analyzed with the aim of evaluating the use of caffeine as an analgesic adjuvant. The studies analyzed data from patients with episiotomy pain, postpartum uterine cramps, post-oral surgery pain, and headache. In 21 of 25 studies, the estimated relative potency of an analgesic containing caffeine compared with an analgesic without caffeine is greater than 1. The estimated relative potency for each of the categories of analgesics in combination with caffeine is significantly greater than 1. The overall relative potency is 1.41 (95% CI 1.23 to 1.63), which means that for a caffeine-free analgesic to obtain the same response as the same analgesic associated with caffeine, an approximately 40% higher dose of medication is required (Laska, 1984).

The combination of carisoprodol (200 mg), phenacetin (160 mg) and caffeine (32 mg) was compared to carisoprodol alone, phenacetin with caffeine and placebo in a double-blind and randomized study with 336 patients with painful musculoskeletal conditions of acute onset. In the global evaluation of symptom improvement, performed by physicians, the studied combination was more effective than its components (P=0.033 for the comparison with carisoprodol; P=0.01 for the comparison with phenacetin with caffeine) and it was observed that the phenacetin and caffeine components contributed significantly to the effectiveness of the combination. The symptomatic improvement reported by the patient pairs, such as relief of pain and spasms as well as improvement in range of motion, showed results very similar to those observed by the physicians. No changes in sleep patterns or improvement in sleep disorders initially reported were observed in any of the groups studied. Of all patients studied, 20% presented adverse effects of mild to moderate intensity. The majority complained of dizziness and gastrointestinal alterations that disappeared with the end of treatment or with a reduction in the dose. Only 2 patients discontinued the medication (1 in the carisoprodol group alone and 1 in the combination group).

The intensity of migraine headache was significantly reduced 1 to 6 hours after ingestion of a medication containing paracetamol (250 mg), acetylsalicylic acid (250 mg) and caffeine (65 mg), when compared to placebo. Data from 3 randomized, double-blind, placebo-controlled studies with a total of 1,220 patients were evaluated. Pain intensity was reduced to mild or absent 2 hours after ingestion of the medication in 59.3% of the 602 patients treated with the combination of substances, compared with 32.8% of the 618 patients who received placebo (P < 0.001; 95% CI 55%-63% for the combination and 95% CI 29%-37% for placebo). Six hours after tablet ingestion, 79% of patients receiving the combination versus 52% of patients receiving placebo had a reduction in pain to mild to absent intensity (P < 0.001; 95% CI 75%-82% versus 48%-56%) and 50.8% were pain-free in the treated group, compared with 23.5% in the placebo group (P < 0.001, 95% CI 47%-55% versus 20%-27%, respectively). Other symptoms such as nausea, photophobia, phonophobia, and functional disability showed improvement after 2 and 6 hours in the treatment group, compared with the placebo group (P < 0.01).

In a multicenter, randomized, double-blind, placebo-controlled study, the efficacy of the combination of paracetamol (250 mg), acetylsalicylic acid (250 mg), and caffeine (65 mg) was compared to the efficacy of ibuprofen (200 mg) and placebo in the treatment of migraine headache. Patients were randomized and allocated as follows: 669 patients in the treatment group with the combination of drugs, 666 patients in the treatment group with ibuprofen, and 220 patients in the control group. The 3 groups had similar characteristics regarding demographic profile, headache history, and symptoms at the onset of the attack. Both drug treatment groups showed significantly better results than the placebo group in relieving pain and associated symptoms. The combination of drugs was superior to ibuprofen in the sum of pain relief scores after 2 hours of starting treatment, in reducing pain intensity, in the time to onset of significant pain improvement, and in the time to achieve total absence of pain. Pain relief scores at 2 hours were 2.7, 2.4, and 2.0 for combination, ibuprofen, and placebo, respectively (P < 0.03). The mean time to onset of significant pain improvement was 20 minutes earlier for combination compared with ibuprofen (P < 0.036), showing superior efficacy and faster onset of effect of combination compared with ibuprofen.

Aiming to test the efficacy and safety of the combination of diclofenac (50 mg), paracetamol (300 mg), carisoprodol (125 mg) and caffeine (30 mg) in the treatment of acute low back pain and lumbosciatica, compared to the efficacy and safety of cyclobenzaprine, a multicenter, randomized, double-blind and comparative clinical trial was conducted. The medications were administered 3 times a day, for a period of 7 days, in 108 patients diagnosed with acute low back pain and lumbosciatica, with onset of symptoms in the last 7 days, who were randomized, with 54 in each group. The primary efficacy criteria selected for the study were the visual analogue scale for pain and the Roland Morris questionnaire, whose results before and after treatment were compared. The secondary criteria were the global assessment of the treatment by the patient and the investigator, and the use of rescue analgesic medication. The safety criteria were tolerability analysis, medication discontinuation due to adverse events and laboratory tests. There was no statistical difference between the groups in relation to efficacy in any of the outcomes analyzed. Both medications were shown to be safe and tolerable in the treatment of acute low back pain and lumbosciatica. Rigorous statistical analysis showed a difference in the two groups only with regard to adverse events, which were more frequent in the group treated with cyclobenzaprine.

The combination of analgesic, anti-inflammatory and muscle relaxant agents present in Caffeine + Carisoprodol + Diclofenac sodium + Paracetamol has demonstrated efficacy and safety for use in various conditions accompanied by pain and inflammation. .

Bibliographic references:

Garcia Filho RJ, Korukian M, Santos FPE, Viola DCM, Puertas EB. A randomized, double-blind clinical trial, comparing the combination of caffeine, carisoprodol, sodium diclofenac and paracetamol versus cyclobenzaprine, to evaluate efficacy and safety in the treatment of patients with acute low back pain and lumboischialgia. Acta Ortop Bras 2006; 14(1):11-6.
Goldstein J, Silberstein SD, Saper JR, Ryan RE, Lipton RB. Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute migraine: results from a multicenter, double-blind, randomized, parallel-group, single-dose, placebo-controlled study. Headache 2006; 46:444-53.
Laska EM, Sunshine A, Mueller F, Elvers W, Siegel C, Rubin A. Caffeine as an analgesic adjuvant. JAMA 1984; 251:1711-8. Lipton RB, Stewart WF, Ryan RE, Saper J, Silberstein S, Sheftell F. Efficacy and safety of acetaminophen, aspirin, and caffeine in alleviating migraine headache pain. Arch Neurol 1998; 55:210-7.
Soyka JP, Maestripieri LR. Soma compound (carisoprodol plus phenacetin and caffeine) in the treatment of acute, painful musculoskeletal conditions. 1979; 24(2):165-80.

Pharmacological Characteristics

Carisoprodol

Carisoprodol is a centrally acting skeletal muscle relaxant , chemically related to meprobamate, which indirectly reduces skeletal muscle tension in humans. The mode of action by which carisoprodol relieves acute muscle spasm of local origin may be related to the fact that it preferentially depresses polysynaptic reflexes, showing efficacy in the treatment of discomfort resulting from skeletal muscle spasm. In high doses, monosynaptic reflexes may be inhibited. Meprobamate has barbiturate-like activity, making carisoprodol an indirect agonist of GABA receptors, with effects on the conductance of chloride channels in the Central Nervous System, similar to benzodiazepines. Sedation is also a consequence of the use of skeletal muscle relaxants.

Carisoprodol is well absorbed after oral administration, with a rapid onset of therapeutic action within 30 minutes and a peak action within 4 hours. Its time to maximum concentration is 1.98 ± 1.16 hours, reaching a peak concentration of 2.29 ± 0.68 mcg/mL and an area under the curve of 10.33 ± 3.87 mcg/mL/hour. The clearance of carisoprodol is 39.52 ± 16.83 L/hour. Carisoprodol is metabolized in the liver and excreted in the urine with an elimination half-life of 8 hours. Only small amounts of carisoprodol are excreted unchanged in the urine. The maximum serum concentration of meprobamate (the major metabolite of carisoprodol) is 2.08 ± 0.48 mcg/mL and exceeds the serum concentrations of carisoprodol within 2.5 hours. It is used in combination with analgesics for the relief of pain and discomfort resulting from acute musculoskeletal conditions.

Caffeine

Caffeine is a Central Nervous System stimulant, belonging to the methylxanthine class, which produces a state of mental alertness and tends to correct the drowsiness caused by carisoprodol. Caffeine is also an analgesic adjuvant, which acts on striated muscles, increasing their tone, making them less susceptible to fatigue and improving their performance. Caffeine affects all systems through the Central Nervous System. With the use of caffeine, mild euphoria, a feeling of absence of fatigue, increased flow of thoughts and increased alertness may occur. Caffeine increases gastric secretion through a direct stimulatory effect. The myocardium is stimulated by caffeine, resulting in an increase in cardiac output and coronary blood flow. Systemic blood pressure remains, in most cases, unchanged with usual doses of caffeine intake. Caffeine dilates certain blood vessels and constricts others, resulting in no gain or loss of total blood pressure. Caffeine is a competitive inhibitor of phosphodiesterase, the enzyme responsible for the inactivation of cyclic 3′,5′-adenosine monophosphate (cAMP). Increased intracellular levels of cAMP function as a mediator of cellular activities, such as the relaxation of smooth muscle cells and the release of histamine from mast cells, according to studies conducted “ in vitro ”.

Caffeine also increases calcium permeability in the sarcoplasmic reticulum and competitively blocks adenosine receptors. Caffeine is well absorbed orally, with peak plasma levels of 6 to 10 mg/L after oral administration of 10 mg of caffeine, occurring between 30 and 120 minutes, regardless of the dose. The onset of its therapeutic action occurs between 15 and 45 minutes after oral administration. Peak plasma concentrations are significantly higher after ingestion of 500 mg of caffeine (17.3 mcg/mL) compared with ingestion of 250 mg of caffeine (7 mcg/mL). The area under the concentration-time curve is significantly reduced in smokers, when compared with nonsmokers, after administration of a single dose of 600 mg of slow-release caffeine. In adults, caffeine is 36% bound to plasma proteins.

Caffeine is widely distributed throughout all tissues of the body, with concentration levels in cerebrospinal fluid similar to plasma levels. Its volume of distribution is 35 to 40 L (0.53 to 0.56 L/kg), which is reduced in patients with compensated cirrhosis (average of 0.38 L/kg, between 0.19 and 0.49 L/kg). It is metabolized in the liver, with transformation into the metabolites paraxanthine, theobromine and theophylline. During pregnancy, caffeine metabolism is reduced, with increased plasma concentrations, despite stable intake. Its elimination half-life is 4 to 5 hours and it is excreted renally.

Sodium diclofenac

Diclofenac sodium, a non-steroidal anti-inflammatory drug with analgesic and antipyretic properties, is an inhibitor of prostaglandin synthesis via the cyclooxygenase pathway. Due to its anti-inflammatory and analgesic properties, diclofenac sodium promotes a satisfactory response to the treatment of rheumatic conditions , characterized by a significant improvement in signs and symptoms. It acts quickly to relieve pain, edema and inflammation resulting from trauma of all forms. It exerts a prolonged and pronounced analgesic effect on moderate and acute painful conditions of non-rheumatic origin.

The onset of therapeutic response to diclofenac depends on the underlying condition to which it is being applied. The analgesic potential can be noted within 30 minutes of ingestion of diclofenac sodium and the response for rheumatic inflammatory processes, such as arthritis, is observed in 3 days or more. Diclofenac sodium is well absorbed from the gastrointestinal tract after oral administration with analgesia in 30 minutes and peak action in 1 hour. The time to reach maximum plasma concentration after oral administration of diclofenac sodium is 2.3 hours (range 1 to 6.5 hours). Diclofenac binds to serum proteins, mainly albumin, in more than 99%. After 2 hours of administration of 75 mg of diclofenac, the concentrations of the substance in the synovial fluid are 70% of the plasma concentration, being higher in the synovial fluid than in the plasma, from 4 hours after administration. The volume of distribution of diclofenac sodium is 1.4 L/kg. Approximately 50% of the dose is metabolized in its first passage through the liver, and its biotransformation occurs through glucuronidation and sulfation. Although almost 100% of diclofenac metabolism is performed by the liver, there is insufficient information to recommend dose adjustments in patients with hepatic insufficiency. Cytochrome CYP2C9 participates in the production of the main metabolite of diclofenac, 4-hydroxydiclofenac, which has very weak pharmacological activity.

Other recognizable metabolites are 5-hydroxydiclofenac, 3′-hydroxydiclofenac, 4′,5-dihydroxydiclofenac and 3’hydroxy-4’methoxydiclofenac. Approximately 65% ​​of the administered dose is excreted in the urine in the form of conjugated metabolites. Approximately 1% is excreted in the urine ” in natura “. The remainder (35%) is eliminated in the bile, in the feces. The elimination half-life of diclofenac is approximately 2 hours. The half-life of the drug in the synovial fluid is 3 times longer than the plasma half-life. Age differences do not cause relevant changes in the absorption, metabolism and excretion of diclofenac sodium.

Paracetamol

Paracetamol or acetaminophen is a para-aminophenol derivative with defined analgesic and antipyretic action. Specifically, paracetamol is a potent inhibitor of cyclooxygenase in the Central Nervous System and, to a lesser extent, blocks the generation of pain impulses in the periphery. Its peripheral action is also due to the inhibition of prostaglandin synthesis and the inhibition of the synthesis or action of other substances that sensitize pain receptors through chemical or mechanical stimulation. As an antipyretic, paracetamol acts centrally on the thermoregulatory center of the hypothalamus, producing peripheral vasodilation, which increases blood flow to the skin, with sweating and heat loss. Because it acts preferentially on prostaglandins in the hypothalamic thermoregulatory center in the Central Nervous System, it does not alter coagulation, bleeding time or platelet aggregation.

It has little effect on the gastric mucosa, even in large doses. It is believed that its use with caffeine leads to a faster onset of action and improves pain relief with lower analgesic doses, without interfering with the antipyretic action. Its analgesic action begins in 30 minutes, generally lasting 4 hours. After oral administration, it is rapidly absorbed by the gastrointestinal tract, reaching maximum serum concentrations between 30 and 60 minutes, with a plasma half-life of approximately 2 to 4 hours and an elimination half-life of 4 to 5 hours. Paracetamol is rapidly absorbed, occurring in 4.5 minutes, with bioavailability of 60% to 98%. Specific conditions, such as migraine headache and spinal cord injury, reduce the absorption rate, probably due to increased gastric emptying time and nausea. Paracetamol absorption is not affected by pregnancy. Its therapeutic concentration for analgesia is around 10mg/L. Paracetamol binds to plasma proteins in 10% to 30% of its plasma concentration, which can reach 20% to 50% in overdose.

This medication crosses the placenta and the blood-brain barrier, reaching peak concentration in the cerebrospinal fluid 2 to 3 hours after administration. Its volume of distribution is 1 to 2 L/kg. Biotransformation results in glucuronide, sulfate and cysteine ​​conjugated metabolites, as well as hydroxylated and deacetylated metabolites, excreted via the urinary and biliary routes. Approximately 25% of the drug is metabolized in the first hepatic passage. Paracetamol metabolites are excreted by the kidneys, with clearance of 13.5 L/hour, of which 1% to 4% is excreted ” in natura “. Up to 2.6% of the drug can be excreted via the biliary tract. The elimination half-life of paracetamol is 2 to 4 hours. In the presence of liver failure, the elimination half-life is increased, and may reach 17 hours in cases of overdose. Renal dysfunction does not alter its elimination half-life. Hemodialysis considerably reduces the half-life of paracetamol by 40% to 50%, but peritoneal dialysis is ineffective in removing the medication.

How should I store Tandrilax?

Store at room temperature (between 15 and 30ºC). Protect from light and moisture.

Batch number and manufacturing and expiry dates: see packaging.

Do not use medicine after its expiration date. Store it in its original packaging.

Characteristics of the drug

Tandrilax tablets are round, orange in color, biconvex and with a crease on one side and the Aché logo engraved on the other side.

Before using, check the appearance of the medicine. If it is within its expiration date and you notice any change in its appearance, consult your pharmacist to find out if you can use it.

All medicines must be kept out of the reach of children.