Rapimax

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT RAPIMAX (RAPIMAX)

Composition:

Active substances: paracetamol, caffeine;

One tablet contains: paracetamol 650 mg, caffeine 50 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; maize starch; povidone; magnesium stearate; talc; colloidal anhydrous silicon dioxide; sodium croscarmellose; pregelatinized maize starch.

Pharmaceutical form. Tablets.

Main physicochemical properties: white-colored, capsule-shaped tablets with a score line on one side.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol, combinations without psychotropic agents.

ATC code N02BE51.

Pharmacological Properties.

Pharmacodynamics.

Paracetamol is an analgesic and antipyretic. Its effect is based on inhibition of prostaglandin synthesis in the central nervous system (CNS). Caffeine enhances analgesic efficacy due to its stimulatory effect on the CNS.

Pharmacokinetics.

After oral administration, paracetamol is rapidly and completely absorbed. Peak plasma concentration is reached within 30–90 minutes after administration. The elimination half-life of paracetamol averages 2–3 hours. Thus, the administered dose of paracetamol is excreted in urine within 24 hours, primarily as glucuronic and sulfuric acid conjugates.

Paracetamol crosses the placenta and is excreted into breast milk.

Caffeine is rapidly and almost completely absorbed after oral administration. Maximum plasma concentrations are achieved approximately within 15–20 minutes; administration of 5–8 mg/kg body weight results in plasma caffeine concentrations of 8–10 mg/L.

Main caffeine metabolites—1-methyluric acid, 1-methylxanthine, and 5-acetylamino-6-amino-3-methyluracil—are excreted in urine.

The primary metabolite excreted in feces is 1,7-dimethyluric acid.

The elimination half-life of caffeine averages 4 to 6 hours. It is excreted mainly via the kidneys (86%); no more than 2% of caffeine is excreted unchanged.

Caffeine crosses the placenta and is excreted into breast milk.

Indications.

Symptomatic treatment of headache, migraine, back pain, toothache, rheumatic pain, muscle pain, and menstrual pain; relief of symptoms associated with cold, influenza, and sore throat.

Contraindications.

Hypersensitivity to the components of the drug; severe hepatic or renal dysfunction; alcoholism; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; blood disorders; Gilbert's syndrome; severe anemia; leukopenia; thrombosis; thrombophlebitis; states of increased excitability; sleep disorders; severe arterial hypertension; organic cardiovascular diseases (including atherosclerosis); glaucoma; elderly age; epilepsy; marked increase in blood pressure; hyperthyroidism; decompensated heart failure; cardiac conduction disorders; paroxysmal tachycardia; myocardial infarction; severe atherosclerosis; tendency to vascular spasm; ischemic heart disease; acute pancreatitis; prostate hyperplasia; diabetes mellitus. Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs. Contraindicated in patients taking tricyclic antidepressants or beta-blockers.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of paracetamol with metoclopramide and domperidone increases the absorption rate of paracetamol, whereas coadministration with cholestyramine reduces it.

Prolonged concomitant use of the drug with acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs may lead to kidney damage.

With prolonged regular use of paracetamol, the anticoagulant effect of warfarin and other coumarins may be enhanced, increasing the risk of bleeding.

Barbiturates reduce the antipyretic effect of paracetamol.

Drugs that stimulate hepatic microsomal enzyme activity (including phenytoin, barbiturates, carbamazepine) may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the likelihood of paracetamol accumulation and enhances the hepatotoxic effects of both paracetamol and these agents. High-dose paracetamol used concomitantly with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.

Paracetamol increases plasma levels of acetylsalicylic acid and chloramphenicol.

Probenecid affects plasma concentration and excretion of paracetamol.

Inducers of hepatic microsomal enzymes (rifampicin and phenobarbital) increase the toxicity of paracetamol, as a greater amount of toxic epoxide is formed during its biotransformation. Paracetamol may reduce lamotrigine bioavailability, decreasing its effect, likely due to induction of its hepatic metabolism. Concomitant use of paracetamol and zidovudine increases the risk of developing neutropenia.

Caffeine, when used concomitantly with MAO inhibitors, may cause a dangerous increase in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents and potentiates the effects of xanthine derivatives, alpha- and beta-adrenergic agonists, and psychostimulants.

Cimetidine, hormonal contraceptives, and isoniazid enhance the action of caffeine.

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives. It acts as an antagonist of anesthetic agents and other drugs that depress the CNS, and as a competitive antagonist of adenosine and adenosine triphosphate (ATP) preparations. Concomitant use of caffeine with ergotamine improves ergotamine absorption from the gastrointestinal tract (GIT); with thyroid-stimulating agents, it enhances thyroid effects.

Caffeine reduces lithium blood concentration. Caffeine may enhance lithium excretion from the body. Therefore, concomitant use of the drug with lithium preparations is not recommended.

Do not use with alcohol.

Special precautions for use.

Before using the medicinal product, consult a physician. Do not use the drug in combination with other products containing paracetamol. Concurrent use with other paracetamol-containing drugs may lead to overdose. Paracetamol overdose may cause liver failure, which may necessitate liver transplantation or result in fatal outcome.

Use with caution when treating patients with mild to moderate impairment of kidney or liver function. Patients with impaired liver or kidney function should consult a physician before using the drug. Restrictions on the use of the drug in such patients are primarily due to the presence of paracetamol.

Alcoholic beverages must not be consumed during treatment. Paracetamol doses exceeding 6–8 g per day may be hepatotoxic; however, adverse effects on the liver may also occur at significantly lower doses when alcohol is consumed, when hepatic enzyme inducers or other hepatotoxic substances are used, or in cases of non-cirrhotic alcoholic liver disease. Prolonged alcohol use significantly increases the risk of hepatotoxic effects of paracetamol. In patients with impaired liver function, as well as in those taking high doses of paracetamol for prolonged periods, regular liver function tests are recommended.

Patients who take analgesics daily for mild forms of arthritis should consult a physician before use.

Cases of impaired liver function/liver failure have been reported in patients with reduced glutathione levels, such as in severe malnutrition, anorexia, low body mass index, chronic alcoholism, or sepsis.

In patients with reduced glutathione levels, paracetamol use increases the risk of metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention should be sought if these symptoms occur.

During treatment with the drug, avoid excessive consumption of beverages containing caffeine (e.g., tea, coffee). This may cause sleep disturbances, tremor, tension, irritability, and chest discomfort due to palpitations.

Do not exceed the recommended dosage or duration of treatment.

If symptoms persist, consult a physician.

Consult a physician before use if you are taking warfarin or similar drugs with anticoagulant effects. When treating with oral anticoagulants and simultaneously taking high doses of paracetamol, monitoring of prothrombin time is required.

The drug may affect laboratory test results for blood glucose and uric acid levels. If headache becomes persistent, consult a physician.

The medicinal product contains lactose monohydrate. If you have been diagnosed with intolerance to certain sugars, consult your physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Use during pregnancy is not recommended, as caffeine intake increases the risk of spontaneous abortion.

Paracetamol and caffeine pass into breast milk, but in clinically insignificant amounts when taken at recommended doses. The use of the drug during breastfeeding is not recommended. Caffeine may have a stimulating effect on infants during breastfeeding, although significant toxicity has not been observed.

Ability to influence reaction rate when driving or operating machinery.

If dizziness occurs during treatment with the drug, refrain from driving or operating machinery.

Method of Administration and Dosage.

For adults and children aged 12 years and older: RAPIMAX should be administered orally, 1 tablet 3–4 times daily. Tablets should be taken with sufficient fluid.

Administer at intervals of no less than 4 hours. Maximum daily dose – 4 tablets. The duration of treatment should be individually determined by a physician and should be as short as possible due to the potential toxic effects of paracetamol.

Do not exceed the recommended dose.

Children.

RAPIMAX is contraindicated in children under 12 years of age.

Overdose.

In case of overdose, symptoms may include increased sweating, psychomotor agitation or CNS depression, drowsiness, impaired consciousness, cardiac arrhythmia, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures.

Symptoms of paracetamol overdose. Within the first 24 hours: pallor, nausea, vomiting, anorexia, and abdominal pain. Hepatonecrosis may occur, along with elevated activity of hepatic transaminases and increased prothrombin index. Clinical experience shows that signs of liver damage typically become apparent within 24–48 hours after overdose and usually peak within 4–6 days.

Paracetamol overdose may lead to liver failure, which may require liver transplantation or result in death. Acute pancreatitis has been reported, usually occurring simultaneously with liver dysfunction and hepatotoxicity. Liver damage is possible in adults who have ingested 10 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. In patients with risk factors [long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs that induce liver enzymes; chronic excessive alcohol consumption; glutathione depletion (due to malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)], ingestion of 5 g or more of paracetamol may lead to liver damage.

Disorders of glucose metabolism and metabolic acidosis may occur. In severe poisoning, liver dysfunction may progress to encephalopathy, coma, and death. Acute kidney injury with acute tubular necrosis may occur, presenting as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

With prolonged use of high doses, aplastic anemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, and leukopenia are possible. CNS disorders may include dizziness, psychomotor agitation, disorientation and attention disturbances, insomnia, tremor, nervousness, anxiety, and restlessness. Urinary system disorders may include nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Symptoms of overdose may be limited to nausea and vomiting or may not reflect the severity of the overdose or the risk of organ damage.

Treatment. In case of overdose, prompt medical intervention is required. Immediate medical attention is necessary even if no symptoms of overdose are present. If overdose is confirmed or even suspected, the patient should be taken to the nearest medical facility for emergency care and appropriate treatment. This should be done even in the absence of symptoms due to the risk of delayed liver damage.

Administration of activated charcoal may be considered if excessive paracetamol intake occurred within the past hour. Plasma paracetamol concentration should be measured at least 4 hours (or later) after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol intake, but maximum protective effect is achieved when administered within 8 hours. The efficacy of the antidote decreases significantly after this period. If required, N-acetylcysteine should be administered intravenously according to the recommended dosage. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside hospital settings. General supportive measures are also necessary.

Symptoms of caffeine overdose. High doses of caffeine may cause rapid breathing, extrasystoles, dizziness, mood disturbances, epigastric pain, vomiting, diuresis, tachycardia or cardiac arrhythmia, and stimulation of the central nervous system (insomnia, restlessness, agitation, anxiety, syndrome of increased neuropsychiatric excitability, headache, tremor, seizures, nervousness, and irritability).

Clinically significant symptoms of caffeine overdose may also be associated with severe liver damage caused by paracetamol, which may occur when the amount of the drug ingested leads to caffeine overdose.

Treatment. There is no specific antidote. Beta-adrenergic receptor antagonists may help alleviate cardiotoxic effects. Gastric lavage is indicated. Oxygen therapy is recommended. In case of seizures, diazepam should be administered. Symptomatic therapy is required.

Side effects

Information on the adverse reactions listed below was obtained from post-marketing surveillance. As the population of patients is of unknown size, the frequency of these adverse reactions cannot be accurately determined; however, they are likely to be rare (< 1/10,000).

Adverse reactions associated with paracetamol:

Blood and lymphatic system disorders: thrombocytopenia, neutropenia, leukopenia, agranulocytosis, pancytopenia, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising and bleeding.

Cardiovascular system disorders: tachycardia, arrhythmia, increased blood pressure.

Immune system disorders: anaphylaxis, hypersensitivity reactions including skin and mucosal rashes (including generalized, erythematous), urticaria, angioedema, Stevens-Johnson syndrome, pruritus, erythema multiforme, toxic epidermal necrolysis (Lyell's syndrome), acute generalized exanthematous pustulosis, angioedema.

Gastrointestinal disorders: nausea, vomiting, heartburn, epigastric pain, increased activity of liver enzymes, usually without development of jaundice, hepatonecrosis (dose-dependent effect).

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary system disorders: liver function abnormalities, hepatic failure, liver necrosis, jaundice.

Skin and subcutaneous tissue disorders: pruritus, hemorrhages, oral mucosal ulcers.

Renal and urinary system disorders: renal colic.

Nervous system disorders: headache.

Adverse reactions associated with caffeine:

Central nervous system disorders: nervousness, dizziness.

Cardiovascular system disorders: tachycardia, edema.

Gastrointestinal tract disorders: gastrointestinal discomfort, abdominal pain, diarrhea, nausea, vomiting.

Psychiatric disorders: insomnia, restlessness, anxiety, irritability.

Skin and subcutaneous tissue disorders: pruritus, rash, sweating, purpura, urticaria.

Concomitant use of the medicinal product at recommended doses with caffeine-containing products may enhance caffeine-related side effects such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25°C, in a place inaccessible to children.

Packaging.

10 tablets in a blister, 1 blister in a cardboard pack.

10 tablets in a blister, 10 blisters in a cardboard pack.

Supply category.

Over-the-counter – pack No. 10.

By prescription only – pack No. 100 (10 × 10).

Manufacturer.

Bafna Pharmaceuticals Ltd., India / Bafna Pharmaceuticals Ltd., India.

Manufacturer's address.

147, Madhavaram Red Hills Road, Grantlyon Village, Vadakarai, Chennai, Tamil Nadu IN 600052, India / 147, Madhavaram Red Hills Road, Grantlyon Village, Vadakarai, Chennai, Tamil Nadu IN 600052, India.

Marketing authorization holder: JIVDHARA PHARMA PRIVATE LIMITED.

Address of the marketing authorization holder:

504, Block-B, Shiv Angan Complex, Sallaiya, Bhopal, Bhopal, Madhya Pradesh, 462026, India / 504, Block-B, Shiv Angan Complex, Sallaiya, Bhopal, Bhopal, Madhya Pradesh, 462026, India.