INSTRUCTION

for medical use of the medicinal product

 

 RAPIMAX

 

Composition:

active substance: paracetamol, caffeine;

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

excipients: lactose, monohydrate; microcrystalline cellulose; corn starch; povidone; magnesium stearate; talc; colloidal anhydrous silicon dioxide; croscarmellose sodium; pregelatinized corn starch.

 

Pharmaceutical form. Tablets.

Basic physical and chemical properties:white tablets, in the form of caplets with a score line on one side.

 

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol, combination without psycholeptics.

ATC code N02B E51

 

Pharmacological properties.

Pharmacodynamics.

Paracetamol is an analgesic-antipyretic agent. The effect is based on inhibiting the synthesis of prostaglandins in the central nervous system (CNS). Caffeine increases the effectiveness of analgesia due to its stimulating effect on the central nervous system.

Pharmacokinetics.

After oral administration, paracetamol is quickly and completely absorbed. The peak concentration in blood serum is reached 30–90 minutes after application. The half-life of paracetamol is 2-3 hours on average. Thus, the administered dose of paracetamol is excreted in the urine within 24 hours mainly in the form of conjugates of glucuronic and sulfuric acids.

Paracetamol penetrates through the placenta and excretes into breast milk.

Caffeine is quickly and almost completely absorbed after oral administration. The maximum concentration in the blood plasma is reached after approximately 15–20 minutes, the use of 5–8 mg/kg of body weight gives a concentration of caffeine in the blood plasma at the level of 8–10 mg/l.

The main metabolites of caffeine: 1-methyluric acid, l-methylxanthine and 5-actylamino-6-amino-3-methyluracil are excreted in the urine.

The main metabolite excreted in the faeces is 1.7-dimethyluric acid.

The half-life of caffeine is on average 4 to 6 hours, mainly with urine (86%), not more than 2% of caffeine is eliminated unchanged.

Caffeine penetrates through the placenta and excretes into breast milk.

 

Indications.

Symptomatic treatment of headache, migraine, back pain, toothache, rheumatic pain, muscle pain and period pain, relief of cold, flu and sore throat symptoms.

 

Contraindications.

Hypersensitivity to the components of the medicinal product; severe liver and kidney dysfunction; alcoholism; congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, blood disorders, Gilbert's syndrome, severe anaemia, leukopenia, thrombosis, thrombophlebitis, agitation; sleep disorders; severe arterial hypertension; organic cardiovascular diseases (including atherosclerosis); glaucoma; old age; epilepsy, pronounced increase in blood pressure, hyperthyroidism, decompensated heart failure, conduction disorder, paroxysmal tachycardia, myocardial infarction, severe atherosclerosis, susceptibility to vascular spasms, ischemic heart disease, acute pancreatitis, benign prostatic hyperplasia, and diabetes mellitus. Do not use along with monoamine oxidase inhibitors (MAO) and within 2 weeks after discontinuing MAO inhibitors. The medicinal product is contraindicated for patients taking tricyclic antidepressants or beta-blockers.

 

Interaction with other medicinal products and other forms of interaction.

When co-administered with metoclopramide and domperidone, paracetamol absorption increases, but when used in combination with cholestyramine, it decreases.

Prolonged co-administration of the drug with acetylsalicylic acid or other non-steroidal anti-inflammatory drugs may cause kidney damage.

With long-term regular use of paracetamol, the anticoagulant effect of warfarin and other coumarins may be intensified, increasing the risk of bleeding.

Barbiturates reduce the fever-reducing effect of paracetamol.

Medications that stimulate the activity of hepatic microsomal enzymes (including phenytoin, barbiturates, carbamazepine) may enhance the toxic effects of paracetamol on the liver due to increased conversion of the drug into hepatotoxic metabolites. When paracetamol is co-administered with hepatotoxic substances, the likelihood of paracetamol accumulation increases, and the toxic effects of paracetamol and these drugs on the liver are also increased. Paracetamol in high doses when used with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.

Paracetamol increases the levels of acetylsalicylic acid and chloramphenicol in the blood plasma.

Probenecid affects the concentration of paracetamol in the plasma and its excretion.

Inducers of hepatic microsomal enzymes (rifampicin and phenobarbital) increase the toxicity of paracetamol, as a large amount of toxic epoxy is formed during its biotransformation. Paracetamol may reduce the bioavailability of lamotrigine, reducing its effect due to possible induction of its metabolism in the liver. When paracetamol is co-administered with zidovudine, the risk of neutropenia is increased.

Caffeine, when co-administered with MAO inhibitors, may cause a dangerous rise in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesics-antipyretics, and potentiates the effects of xanthine derivatives, alpha- and beta-adrenomimetics, psychostimulants, and other CNS depressants.

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

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives, acting as a CNS depressant antagonist, which is a competitive antagonist to adenosine and adenosine triphosphate (ATP) drugs. When caffeine is co-administered with ergotamine, the absorption of ergotamine from the gastrointestinal tract (GIT) is improved. The thyroid effect is increased with the co-administration of thyroid agents.

Caffeine reduces the concentration of lithium in the blood. Caffeine may enhance the excretion of lithium from the body. Therefore, the co-administration of this drug with lithium preparations is not recommended.

Do not use with alcohol.

 

Precautions for use.

Before using the drug, it is necessary to consult with a doctor. Do not use the drug in combination with other products containing paracetamol. Concurrent use with other paracetamol-containing medications may lead to overdose. Paracetamol overdose can cause liver insufficiency, which may necessitate a liver transplant or result in a fatal outcome.

Caution should be used when treating patients with mild to moderate kidney and liver function impairments. Patients with liver or kidney impairments should consult with a doctor before using the drug. Limitations on the use of the drug in such patients are primarily due to the paracetamol composition.

Alcoholic beverages should not be consumed during the treatment. Paracetamol can be toxic to the liver in doses exceeding 6-8 g per day, but negative effects on the liver can also occur with significantly lower doses when alcohol is consumed, or when inducers of liver enzymes or other substances that have a toxic impact on the liver are used. This is also true in cases of non-cirrhotic alcoholic liver disease. Prolonged alcohol consumption significantly increases the risk of hepatotoxic effects of paracetamol. Patients with impaired liver function, as well as those who take high doses of paracetamol for an extended period are recommended to regularly undergo liver function tests.

Patients who take analgesics daily for mild arthritis should consult with a doctor before using the drug.

Cases of liver dysfunction/liver insufficiency have been reported in patients with reduced glutathione levels, such as in cases of severe debilitation, anorexia, low body mass index, chronic alcoholism, or sepsis.

Patients with reduced glutathione levels are at an increased risk of developing metabolic acidosis when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention is necessary if these symptoms appear.

During the treatment with the drug, it is not recommended to consume beverages containing caffeine in excess (e.g., tea, coffee). This can lead to sleep disorders, tremors, tension, irritability, and an uncomfortable feeling in the chest due to palpitations.

Do not exceed the specified doses and treatment duration.

If symptoms persist, consult your doctor.

Before using the drug, consult with your doctor if you are taking warfarin or similar drugs with anticoagulant effects. When using oral anticoagulants along with high doses of paracetamol, prothrombin time should be monitored.

The drug may affect the results of laboratory tests for blood glucose and uric acid levels. If your headache becomes persistent, consult your doctor.

The drug contains lactose monohydrate. If you have intolerance to certain sugars, consult your doctor before taking the drug.

 

Pregnancy and lactation.

It is not recommended for use during pregnancy, as it increases the risk of spontaneous abortion associated with caffeine consumption.

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

 

Effects on ability to drive and use machines.

In cases where dizziness is observed during drug treatment, one should refrain from driving vehicles and working with mechanisms.

 

Method of administration and dosage.

Adults and children over 12 years of age. RAPIMAX is taken orally, 1 tablet 3-4 times a day. The tablets should be taken with an adequate amount of fluid.

The drug should be administered with an interval of not less than 4 hours. The maximum dose is 4 tablets per day. The duration of the treatment course is determined individually by a doctor but should be as short as possible due to the potential development of paracetamol's toxic effect.

Do not exceed the recommended dose.

 

Children.

RAPIMAX should not be prescribed to children under 12 years of age.

 

Overdose.

In case of an overdose, increased sweating, psychomotor agitation or CNS depression, drowsiness, altered consciousness, heart rhythm disturbances, tachycardia, extrasystoles, tremors, hyperreflexia, and seizures may be observed. These are symptoms of acetaminophen overdose. Within the first 24 hours: pallor, nausea, vomiting, anorexia, abdominal pain, hepatonecrosis, increased "liver" transaminase activity, and an increase in the prothrombin index. Clinical symptoms of liver damage typically become apparent around 24-48 hours after the overdose and peak at around 4-6 days.

Acetaminophen overdose can lead to liver failure, which may require liver transplantation or result in a fatal outcome. Acute pancreatitis has been observed, usually concomitant with liver dysfunction and hepatotoxicity. Liver damage can occur in adults who have ingested 10 g or more of acetaminophen and in children who have ingested more than 150 mg/kg of body weight. In patients with risk factors (prolonged treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, starvation, cachexia) taking 5 g or more of acetaminophen can lead to liver damage.

Disturbances in glucose metabolism and metabolic acidosis may occur. In severe poisoning, liver function impairment can progress to encephalopathy, coma, and a fatal outcome. Acute kidney dysfunction with acute tubular necrosis may manifest with severe flank pain, haematuria, proteinuria, even in the absence of severe liver damage. Cardiac arrhythmia and pancreatitis have also been reported.

With prolonged use of high doses, aplastic anaemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, and leukopenia are possible. CNS disturbances (dizziness, psychomotor agitation, orientation and attention disorders, insomnia, tremors, nervousness, anxiety) and renal toxicity (renal colic, interstitial nephritis, papillary necrosis) can also occur.

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

Treatment. In case of overdose, prompt medical assistance is necessary, even if overdose symptoms are not observed. If overdose is confirmed or suspected, the patient should be taken to the nearest medical facility where they can receive urgent care and qualified treatment. This should be done even if overdose symptoms are absent, due to the risk of delayed liver damage. Consider administering activated charcoal if an excessive dose of acetaminophen has been taken within 1 hour. The plasma concentration of acetaminophen should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine can be applied up to 24 hours after acetaminophen ingestion, but the maximum protective effect occurs when it is administered within 8 hours after ingestion. The efficacy of the antidote sharply decreases after this time. If necessary, N-acetylcysteine should be administered intravenously according to recommended dosages. If there is no vomiting, methionine can be administered orally as an alternative in remote areas outside a hospital. General supportive measures are also necessary.

Symptoms of caffeine overdose. High doses of caffeine can cause increased respiration, extrasystoles, dizziness, mood swings, epigastric pain, vomiting, diuresis, tachycardia, or arrhythmia, central nervous system stimulation (insomnia, restlessness, agitation, increased reflex excitability, headache, tremors, seizures, nervousness, and irritability).

Clinically significant caffeine overdose symptoms are also associated with severe liver damage from acetaminophen, which can occur when taking such a quantity of the drug that causes caffeine overdose.

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

 

Adverse reactions.

The following adverse reactions were identified through post-marketing observations. Since the patient population size is unknown, it is challenging to determine the frequency, but these reactions are most likely rare (< 1/10000).

Adverse reactions caused by paracetamol:

Blood and lymphatic system disorders: thrombocytopenia, neutropenia, leukopenia, agranulocytosis, pancytopenia, anaemia, sulfhemoglobinemia, and methemoglobinemia (cyanosis, dyspnoea, chest pain), haemolytic anaemia, bruising, and bleeding.

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

Immune system disorders: anaphylaxis, hypersensitivity, including skin and mucous membrane rashes (including generalized erythematous rashes), urticaria, angioedema, Stevens-Johnson syndrome, skin itching, toxic epidermal necrolysis (Lyell's syndrome), acute generalized exanthematous pustulosis, and angioedema.

Digestive system disorders: nausea, vomiting, epigastric pain, elevated liver enzymes, usually without 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 non-steroidal anti-inflammatory drugs.

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

Skin and subcutaneous tissue disorders: itching, haemorrhage, oral mucosal ulceration.

Kidneys and urinary system disorders: renal colic.

Nervous system disorders: headache.

Adverse reactions caused by caffeine:

Central nervous system disorders: nervousness, dizziness.

Cardiovascular system disorders: increased heart rate, oedema.

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

Psychic disorders: insomnia, restlessness, anxiety, and irritability.

Skin and subcutaneous tissues disorders: itching, rashes, sweating, purpura, urticaria.

 

The co-administration of the medicinal product at recommended doses with products containing caffeine may intensify the adverse effects caused by caffeine, such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disorders, and increased heart rate.

 

Shelf life.

3 years.

 

Storage conditions.

Store in the original package at a temperature not exceeding 25 °C. Keep out of reach of children

 

Packaging.

10 tablets in a blister, 1 blister in a carton.

10 tablets in a blister, 10 blisters in a carton.

 

Terms of dispensing.

Without prescription – tablets No.10.

On prescription – tablets No.100 (10 × 10).

 

Manufacturer.

Bafna Pharmaceuticals Ltd., India.

 

Manufacturer’s registered address.

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

 

Applicant. SCAN BIOTECH LTD, India.

 

Applicant’s registered address.

E-4/300, Arera Colony Extension, 462016, Bhopal, India.