What Are the Risks of Combining Tramadol and Alcohol?

Paracetamol tramadol tablets, the indication is for the treatment of moderate to severe acute pain.

Paracetamol tramadol tablets, the indication is for the treatment of moderate to severe acute pain.

Drug Name

Paracetamol and tramadol tablets

Drug type

Prescription drugs, medicines for medical workers' injuries

Special medicine

Psychotropic drugs

Paracetamol tramadol tablets ingredients

This product is a compound preparation, its components are: each tablet contains tramadol hydrochloride 37.5mg, acetaminophen 325mg.

Paracetamol tramadol traits

This product is a light yellow coated tablet with a white or off-white core.

Paracetamol tramadol tablets indications

This product is used for the treatment of moderate to severe acute pain.

Paracetamol and tramadol tablets specifications

Each tablet contains:
Tramadol hydrochloride 37.5mg
Acetaminophen 325mg

Paracetamol and tramadol tablets

oral.
Take this product as described below, or as directed by your doctor.
Adults and children over 16 years old take 1 to 2 tablets every 4 to 6 hours according to the need for pain relief, and a maximum of 6 tablets daily.
No need to consider the impact of food.
Child (Child under 16)
There is no information on the safety and effectiveness of this product for children (under 16 years).
Elderly patients The dosage of elderly patients should be carefully selected, and the potential risks that may occur should be fully considered.
Patients with renal insufficiency have no research data on patients with renal impairment and should be used with caution. If it must be used, patients with creatinine clearance of 30m1 / min are advised to extend the interval between medications, and the dosage should not exceed 2 tablets in 12 hours.
Patients with liver dysfunction have no research data on patients with liver dysfunction and are not recommended.

Paracetamol tramadol tablets adverse reactions

The most common are adverse events of the central nervous system and gastrointestinal system.
The most common adverse events were nausea, dizziness, and lethargy.
In addition, the following adverse reactions are more common, but the incidence is lower:
-Whole body: fatigue, fatigue, hot flashes-Central and peripheral nervous system: headache, tremor-Gastrointestinal system: abdominal pain, constipation, diarrhea, indigestion, flatulence, dry mouth, vomiting-Mental system: anorexia, anxiety, Confusion, euphoria, insomnia, nervousness-skin and appendages: itching, rash, sweating Uncommon adverse reactions that may be related to this product include:
-Whole body: chest pain, tonicity, syncope, withdrawal syndrome-Cardiovascular system: hypertension, exacerbation of hypertension, hypotension-Central and peripheral nervous system: ataxia, convulsions, increased tension, migraine, exacerbation of migraine, Involuntary muscle contraction, paresthesia, stiffness, dizziness-gastrointestinal system: difficulty swallowing, black stools, tongue edema-hearing and vestibules: tinnitus-heart rate and heart rhythm: arrhythmia, palpitations, tachycardia-liver and biliary system : Abnormal liver function tests-metabolism and nutrition: weight loss-mental system: forgetfulness, disintegration of personality, depression, substance abuse, emotional instability, hallucinations, impotence, nightmare, abnormal thinking-blood system: anemia-respiratory system: dyspnea -Urinary system: proteinuria, dysuria, oliguria, urinary retention-Vision: visual abnormalities Tramadol hydrochloride Other adverse reactions in clinical trials or after marketing: Reported adverse reactions with tramadol products include: Orthostatic hypotension, allergies (including: allergies and urticaria, history syndrome), cognitive impairment, suicidal ideation and hepatitis. Laboratory abnormalities reported include elevated creatinine. When tramadol is used in combination with other serotonin drugs (such as selective serotonin reuptake inhibitors and monoamine oxidase inhibitors), serotonin syndrome (symptoms including fever, excitement, tremor, and agitation) has been reported. Post-market surveillance shows rare reports of tramadol affecting warfarin, including prolonged clotting times.
Other adverse reactions to acetaminophen in clinical trials or after marketing; rare allergic reactions (mainly rashes) or secondary allergic reactions, usually symptoms can be controlled after drug withdrawal or symptomatic treatment when necessary. Some reports indicate that acetaminophen may cause hypothrombinemia when used in combination with warfarin. Other studies have shown no change in clotting time.

Paracetamol and tramadol tablets contraindications

Patients who are allergic to tramadol, acetaminophen, or other ingredients or opioids in this product are contraindicated.
Alcohol, sleeping pills, narcotics, central analgesics, opioids or psychotropic drugs are not allowed in patients with acute poisoning.

Precautions for Paracetamol and Tramadol Tablets

1. Epilepsy Taking a recommended dose of tramadol has reported seizures. Postmarketing spontaneous reports show increased seizure risk in patients taking tramadol above the recommended dose. Tramadol increases the risk of seizures with the following drugs: selective serotonin reuptake inhibitors (SSRI antidepressants or weight loss drugs), tricyclic antidepressants, and other tricyclic drugs (such as: Cyclobenzaprine, promethazine, etc.) or opioids.
Tramadol increases the risk of seizures when taken with the following medications: monoamine oxidase inhibitors, tranquilizers, and other medications that lower the seizure threshold.
People with epilepsy, people with a history of epilepsy, or people considered to be at risk for seizures (such as: brain trauma, metabolic abnormalities, withdrawal from alcohol and drugs, central nervous system infection) are at increased risk of convulsions. When tramadol is overdose, the use of naloxone may increase the risk of seizures.
2. Allergic reactions Patients with a history of allergies to codeine and other opioids have an increased risk of allergic reactions and should not use this product.
3. Respiratory suppression Use this product with caution in patients at risk for respiratory depression. When large doses of tramadol are taken with anesthetic or alcohol at the same time, it may cause respiratory depression, which can be treated as an overdose. If you use naloxone, you should be careful, because it can cause epilepsy.
4. Concurrent use with central nervous system sedatives When patients use central nervous system sedatives (such as: alcohol, opioids, anesthetics, phenothiazines, sedatives or sedative hypnotics), use this product with caution or reduce the dose.
5. Use this product with caution in patients with elevated intracranial pressure or brain trauma.
6. Opioid dependent patients This product should not be used in patients with opioid dependence. In patients with a history of dependence on other opioids, the use of tramadol may cause body dependence again.
7. Alcohol-dependent patients who have long-term severe alcohol abuse who take too much acetaminophen may increase the risk of liver toxicity.
8. Sudden discontinuation If you stop taking this product suddenly, withdrawal symptoms may occur. Sudden discontinuation of tramadol hydrochloride has been reported with rare panic attacks, severe anxiety, hallucinations, paresthesia, tinnitus, and central nervous system symptoms. Clinical experience has shown that gradual reduction in dose can reduce withdrawal symptoms.
9. Patients taking monoamine oxidase inhibitors with monoamine oxidase inhibitors and serotonin reuptake inhibitors should use this product with extreme caution. Taking tramadol together with a monoamine oxidase inhibitor or a selective serotonin reuptake inhibitor may increase the risk of adverse reactions, including epilepsy and serotonin syndrome.
10. Patients with kidney disease have not conducted research on this product for patients with impaired renal function. For patients with creatinine clearance of less than 30ml / min, it is recommended to extend the interval between medications, taking no more than 2 tablets every 12 hours.
11. This product is not recommended for patients with liver disease.
12. Other taking this product should not exceed the recommended dose.
It should not be taken at the same time as other drugs containing tramadol or acetaminophen.
This product may affect your ability to perform potentially hazardous tasks such as driving a car or operating a machine.
Keep them out of reach of children.

Paracetamol and tramadol tablets for pregnant and lactating women

Tramadol passes through the placenta.
There are no adequate formal studies for pregnant women.
Medication safety in pregnant women has not been established. As there is no research on the safety of infants and newborns, it is not recommended to use this product during pregnancy and lactation.

Paracetamol and tramadol tablets for children

There is no information on the safety and effectiveness of this product for children (under 16 years) and should not be used.

Paracetamol and tramadol tablets for elderly

The dosage of elderly patients should be selected with due care and full consideration of potential risks that may occur.

Paracetamol and tramadol tablets drug interactions

Monoamine oxidase inhibitors have been reported to interact with some central-acting drugs.
The simultaneous use of tramadol hydrochloride and carbamazepine can significantly increase the metabolism of tramadol. For patients taking carbamazepine, the analgesic effect of tramadol in this product may be significantly reduced.
Tramadol is metabolized to the metabolite M1 by the CYP2D6 enzyme. The simultaneous use of quinidine and tramadol can lead to an increase in blood tramadol concentration. The clinical significance of this finding is unknown.
According to clinical needs, patients who take this product and warfarin drugs at the same time should be regularly checked for coagulation time, because some patients report increased prothrombin time.
In vitro drug interaction studies in human liver microsomes have shown that simultaneous administration with CYP2D6 enzyme inhibitors (such as fluoxetine, paroxetine and amitriptyline) may inhibit tramadol metabolism.
Studies on the simultaneous use of this product with cimetidine have not been conducted. The simultaneous administration of tramadol and cimetidine did not cause clinically significant pharmacokinetic changes of tramadol.

Paracetamol tramadol tablets overdose

This product is a compound preparation. The clinical manifestations of overdose may include symptoms and signs of tramadol poisoning, acetaminophen poisoning, or a combination of both. The initial symptoms of tramadol overdose include: respiratory depression and / or epilepsy. Symptoms of paracetamol over 24 hours are: gastrointestinal irritation, loss of appetite, nausea, vomiting, discomfort, paleness, and sweating.
Serious consequences of tramadol overdose include: respiratory depression, drowsiness, coma, epilepsy, cardiac arrest and death.
Large doses of paracetamol may cause liver toxicity in some patients. Early symptoms include gastrointestinal irritation, loss of appetite, nausea, vomiting, malaise, paleness, and sweating. The clinical symptoms and laboratory results of liver poisoning may not appear until 48 to 72 hours after taking the drug.
Both single and multiple doses of overdose can be life-threatening and it is recommended to consult an expert immediately.
Naloxone may relieve some (but not all) of the symptoms caused by tramadol overdose, but at the same time may increase the risk of seizures. According to experience with tramadol, hemodialysis is not very helpful in treating overdose because 4 hours of dialysis Only less than 7% of tramadol was cleared.
In the treatment of overdose of this product, in addition to giving routine supportive care, care should be taken to ensure that breathing is unobstructed and measures are taken to reduce drug absorption. In conscious patients (reflex swallowing is present), vomiting is performed using physical methods or syrup. After gastric emptying, oral activated carbon (1g / kg) should be taken with an appropriate laxative for the first time. If repeated administration is required, it can be taken with the laxative and the dose adjusted. Insufficient blood volume can cause hypotension, and should be rehydration, and Use vasopressors and other supportive treatments as needed. Tracheal intubation should be performed prior to gastric lavage in unconscious patients and assisted breathing should be provided if necessary.
Adults and children should take acetaminophen in plasma at unknown doses or when the timing is imprecise, and treat with acetylcysteine. If blood concentration testing is not available and the estimated dose of acetaminophen exceeds 7.5-10 g (adults and adolescents) or 150 mg / kg (children), N-acetylcysteine should be used and used throughout the treatment process .

Paracetamol and tramadol tablets pharmacology and toxicology

Pharmacological effects Tramadol is a central opioid analgesic. There are at least two mechanisms of action, namely, the tramadol prototype and its metabolite M1 bind to opioid receptors, and re-evaluate noradrenaline and serotonin. Weak inhibition. Paracetamol is a non-steroidal antipyretic and analgesic, and its exact site of action and analgesic mechanism are unknown.
Animal model studies have shown that the combined use of tramadol and acetaminophen has a synergistic effect.
Toxicological studies tramadol / acetaminophen: There is no animal and laboratory research data on the carcinogenicity, mutagenicity and fertility of this compound. Oral administration of tramadol and paracetamol in rats did not observe any drug-related teratogenic effects. When tramadol / acetaminophen reached the maternal toxicity dose (50 / 434mg / kg, which is 8.3 times the maximum human dose), it showed embryo toxicity and fetal toxicity, including a decrease in fetal weight and an increase in the number of pararibs. No teratogenic effect at the dose. No doses of maternal toxicity and less maternal toxicity (tramadol and acetaminophen at 10/87 and 25/217 mg / kg) did not produce embryo and fetal toxicity.
Tramadol hydrochloride:
Genotoxicity: in Ames microsomal activation test, CHO / HPRT mammalian cell test, mouse lymphocyte test (without metabolic activation), mouse dominant lethal mutation test, Chinese hamster chromosome aberration test, and mouse and Chinese hamster bone marrow In micronucleus tests, tramadol did not show genotoxic effects.
The mouse micronucleus lymphoma test and rat micronucleus test under metabolic activation conditions showed that tramadol has weak mutagenic effect. Overall, these trials show that tramadol does not pose a genotoxic risk to humans.
Fertility toxicity: Male rats take trama as much as 50mg / kg orally and female rats reach 75mg / kg. No effect on fertility was found.
Studies of the effects of tramadol on rats before and after birth show that the oral dose of pregnant rats reaches 50 mg / kg or more, and the weight of the pups decreases. At 80 mg / kg (6 to 10 times the maximum human dose), the pups in the early stage of lactation Survival decreases. At doses of 8, 10, 24, 25 or 40 mg / kg, no toxicity was observed to the pups. At these doses, maternal toxicity is produced, and only when more severe maternal toxicity is produced, will it have a significant effect on the pups.
Carcinogenicity: In the carcinogenicity study of tramadol for 2 consecutive years, when the oral dose of mice, especially elderly rats, reached 30 mg / kg (non-maximum tolerated dose), two common murine tumors (lung and liver) There was a statistically significant increase in the incidence. The discovery does not imply a carcinogenic risk to humans. No similar findings were found in rat carcinogenicity studies.

Pharmacokinetics of Paracetamol and Tramadol Tablets

According to foreign research data, tramadol in this product is a racemic body, and L- and D-body of tramadol and its metabolite M1 can be detected in blood. Table 1 lists the pharmacokinetic parameters of tramadol and acetaminophen taken 1 tablet of this product. Compared to acetaminophen, tramadol has a slower absorption and a longer half-life.
A single dose of 1 tablet of this product (tramadol 37.5mg / acetaminophen 325mg). The plasma concentrations of tramadol and acetaminophen reach their peaks after 1.8 hours and 0.9 hours, respectively. The peak plasma concentrations were 64.3ng / ml and 55.5ug / ml, respectively, and the peak plasma concentrations of acetaminophen were 4.2 g / ml. The average elimination half-life of dextro- and levodomalado was 5.1 hours and 4.7 hours, and acetaminophen was 2.5 hours.
Pharmacokinetic studies of single and multiple doses of this product in healthy subjects showed no significant drug interaction between tramadol and acetaminophen.

Absorption of a single dose of 100 mg of tramadol orally, the average absolute bioavailability is about 75%. Healthy adults take 2 tablets of this product orally. The racemic form of tramadol racemate and its metabolite M1 reach the average plasma concentration peak 2-3 hours after taking the medicine. After oral administration, acetaminophen was quickly and completely absorbed, and the plasma concentration peaked after 1 hour, and tramadol was not affected by the same administration.
Food effects: Taken with food, it has no significant effect on the peak plasma concentration and absorption of tramadol or acetaminophen. Therefore, there is no need to consider food effects when taking this product orally.
100 mg tramadol was administered intravenously. The volume of tramadol distribution in male and female subjects was 2.6 L / kg and 2.9 L / kg, respectively. The binding rate of tramadol and human plasma proteins was about 20%.
Paracetamol is widely distributed in most tissues except adipose tissue, and its apparent volume of distribution is about 0.9L / kg.
The plasma protein binding rate of acetaminophen is relatively low (~ 20%).
Metabolism Compared with tramadol alone, plasma concentrations of tramadol and its metabolite M1 did not change significantly in healthy subjects after oral administration of this product.
About 30% of tramadol is excreted in the urine in its original form, and 60% of tramadol is excreted as a metabolite. The main metabolic pathways are N- and O-demethylation and glucuronidation or sulfation in the liver. Tramadol is extensively metabolized by a variety of pathways, including the CYP2D6 enzyme.
Paracetamol is mainly metabolized by the first-pass action of the liver, including three main pathways,
-Binding to glucuronide-Binding to sulfate-Oxidation by cytochrome P450 enzymes.
Elimination of tramadol and its metabolites is mainly eliminated by the kidneys. The plasma elimination half-lives of the racemic form of tramadol and its metabolite M1 are 6 hours and 7 hours, respectively. On repeated administration, the plasma elimination half-life of tramadol racemate increased from 6 hours to 7 hours.
The acetaminophen half-life in adults is about 2 to 3 hours, the half-life in children is slightly shorter, and the half-life in neonates and patients with liver cirrhosis is slightly longer. Paracetamol is eliminated from the body mainly in the form of a combination of glucuronide and sulfate, and is dose-dependent. Less than 9% of acetaminophen is excreted in the urine in its original form.

Paracetamol and tramadol tablets storage

Keep sealed.

Paracetamol tramadol tablet packaging

Packed in aluminum-plastic blister board; 10 pcs / board / box.

Expiration date of paracetamol and tramadol tablets

Tentative 36 months.

Paracetamol and tramadol tablets

YBH08182005 ^[1]