Citramarine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Citramarine: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Citramarin

ATX code: N02BA51

Active ingredient: acetylsalicylic acid (Acetylsalicylic acid) + caffeine (Caffeine) + paracetamol (Paracetamol)

Producer: JSC "Marbiopharm" (Russia)

Description and photo update: 2020-13-04

Citramarine is a combined analgesic agent.

Release form and composition

The drug is produced in the form of a powder for preparing a solution for oral administration (orange, lemon): a pale yellow granular powder with yellow and white blotches, the presence of easily crumbling lumps is possible; after dissolving in hot water, an opalescent solution with a yellow tint is formed, having the smell of orange or lemon (13 g each in a heat-sealable bag made of a combined packaging material; in a cardboard box 10 bags and instructions for using Citramarine).

Composition for 1 package:

active substances: caffeine - 0.045 g; paracetamol - 0.27 g; acetylsalicylic acid (ASA) - 0.36 g;
additional components: aspartame - 0.0125 g; low molecular weight povidone - 0.0105 g; lemon or orange flavoring (food flavoring "lemon durar" or "orange durar") - 0.02 g; sodium bicarbonate (sodium bicarbonate) - 0.28 g; citric acid monohydrate (citric acid monohydrate food) - 0.35 g; sucrose (sugar) - 11.644 g.

Pharmacological properties

Pharmacodynamics

Citramarine is a combined drug, the pharmacological effectiveness of which is due to the properties of its active substances:

ASA: has an antipyretic and anti-inflammatory effect, reduces pain, mainly associated with inflammation, and also promotes moderate suppression of platelet aggregation and thrombus formation, enhances microcirculation in the focus of inflammation;
paracetamol: demonstrates analgesic, antipyretic and weak anti-inflammatory effect, which is caused by the effect of the substance on the thermoregulation center located in the hypothalamus and a slight inhibition of the production of prostaglandins (Pg) produced in peripheral tissues;
caffeine: provides an increase in the reflex excitability of the spinal cord, stimulates the respiratory and vasomotor centers, promotes the expansion of the blood vessels of the heart, brain, skeletal muscles, kidneys; reduces platelet aggregation, reduces fatigue and drowsiness, increases physical and mental performance; the active substance contained in a low dose in Citramarine has practically no stimulating effect on the central nervous system (CNS), but takes part in the normalization of the vascular tone of the brain and causes an acceleration of blood flow.

Pharmacokinetics

The main pharmacokinetic characteristics of ASA:

absorption: when taken orally, the substance is absorbed almost completely and quickly. The maximum concentration (C _max) is observed 2 hours after administration. In the intestinal wall, ASA undergoes presystemic elimination, and in the liver - systemic (deacetylated). The presence of food in the stomach significantly alters absorption;
distribution: circulates in the body (binding to albumin by 75-90%) in the form of the anion of salicylic acid - salicylate, which easily penetrates into most tissues and body fluids, including peritoneal, spinal and synovial. It is found in low concentrations in brain tissue, in trace amounts in sweat, bile, and feces. It penetrates through the placental barrier quickly, excreted in breast milk in small quantities;
metabolism: ASA is metabolized mainly in the liver to salicylic acid, with further conjugation with glycine or glucuronide 4 metabolites are formed, the concentration of which in the blood plasma is variable;
excretion: the substance is excreted mainly through active secretion in the kidney tubules in the form of salicylate (up to 60%) and its metabolites. The elimination of unchanged salicylate is influenced by the pH of urine - against the background of alkalinization of urine, ionization of salicylates increases, their reabsorption decreases and excretion significantly increases. The half-life (T _1/2) of ASA is no more than 15–20 minutes. The rate of excretion of salicylate depends on the dose: when using small doses, T _1/2 is 2-3 hours, with an increase in the dose, it can increase to 15-30 hours. The excretion of salicylate in newborns is much slower than in adults.

The main pharmacokinetic characteristics of paracetamol:

absorption: well absorbed, its C _max is 5–20 μg / ml, the time required to reach it is 0.5–2 hours;
distribution: the drug binds to plasma proteins by 15%, crosses the blood-brain barrier (BBB). Less than 1% of the dose is passed into breast milk. In blood plasma, the therapeutic effective concentration of the active component is achieved when it is administered at a dose of 10–15 mg / kg;
metabolism: biotransformation takes place in the liver (90–95%); approximately 80% of the substance is involved in conjugation reactions with the formation of inactive sulfates and glucuronides. About 17% of the product undergoes hydroxylation with the formation of 8 active metabolites conjugated with glutathione, resulting in the formation of inactive metabolites. In the case of a lack of glutathione, these metabolites can inhibit the enzyme systems of hepatocytes and lead to their necrosis. The metabolism of the drug is also provided by isoenzymes CYP2E1, CYP1A2 and, to a small extent, CYP3A4;
excretion: excreted by the kidneys in the form of metabolites, mainly conjugates, and unchanged (less than 5%). T _1/2 - 1-4 h.

The main pharmacokinetic characteristics of caffeine are:

absorption: when taken orally, there is a good absorption of caffeine throughout the intestine, which is carried out mainly as a result of lipophilicity rather than water solubility. C _{max of the} active substance is 1.6-1.8 mg / l, the period of reaching C _max after oral administration is 50-75 minutes;
distribution: caffeine easily penetrates the placenta and the BBB, is intensively distributed in all organs and tissues of the body. In adults, the volume of distribution is 0.4-0.6 l / kg, in newborns - 0.78-0.92 l / kg. The connection of the drug with albumin (blood proteins) varies from 25 to 36%;
metabolism: over 90% of the substance is biotransformed in the liver, in children of the first years of life - no more than 10-15%. On average, in adults, 80% of the dose is metabolized to paraxanthine, 10% to theobromine and 4% to theophylline. These compounds are then demylylated to monomethylxanthines, and further to methylated uric acids;
excretion: in adults T _1/2 - 3.9-5.3 hours, in some cases - up to 10 hours. Caffeine and its metabolites are excreted mainly by the kidneys; in adults, 1–2% is eliminated unchanged.

Indications for use

pain syndrome of various origins of mild and moderate severity: toothache, headache, migraine, arthralgia, myalgia, neuralgia, algodismenorrhea;
febrile syndrome accompanying acute respiratory diseases (ARI), influenza.

Contraindications

Absolute:

erosive and ulcerative pathologies of the gastrointestinal tract (GIT) during an exacerbation, gastrointestinal bleeding or perforation; a history of peptic ulcer;
full / partial combination of bronchial asthma, recurrent polypous rhinosinusitis and intolerance to ASA or other non-steroidal anti-inflammatory drugs (NSAIDs), including a history of data;
arterial hypertension of the III degree;
chronic heart failure (CHF) III – IV functional class according to the classification of the New York Heart Association (NYHA);
blood clotting disorders, including hemophilia;
hypoprothrombinemia, hemorrhagic diathesis;
severe renal and / or hepatic impairment;
portal hypertension;
vitamin K deficiency;
sleep disturbance, excessive nervous irritability;
deficiency of glucose-6-phosphate dehydrogenase;
surgical interventions that cause profuse bleeding (including tooth extraction), since ASA slows down blood clotting;
glaucoma;
age up to 15 years - with the elimination of pain syndrome, up to 18 years - with a febrile syndrome;
pregnancy and lactation;
the combined use of methotrexate at a dose above 15 mg / week;
hypersensitivity to any component of the drug.

Relative (it is recommended to use Citramarine powder with extreme caution):

mild to moderate renal and / or hepatic failure;
epilepsy and a predisposition to seizures;
ischemic heart disease (CHD);
CHF I – II functional class according to NYHA;
peripheral arterial lesions;
cerebrovascular diseases;
smoking, alcoholism;
gout;
chronic obstructive pulmonary disease (COPD);
elderly age;
combined use with methotrexate at a dose of up to 15 mg / week;
concomitant anticoagulant treatment;
simultaneous use with NSAIDs, glucocorticosteroids (GCS), selective serotonin reuptake inhibitors (SSRIs), antiplatelet agents.

Citramarine, instructions for use: method and dosage

Citramarine powder is taken orally after meals, dissolving the contents of 1 packet in 100 ml of hot water. A freshly prepared solution should be used.

Recommended dosage regimen:

headache: 1-2 packets, with a severe headache after 4-6 hours, you can take Citramarine in the same dose; maximum course - 4 days;
migraine: 2 packets at the onset of symptoms, if necessary, you can take it again after 4-6 hours, the maximum course is 4 days;
pain syndrome: 1-2 packets; average daily dose - 3-4 packets;
febrile syndrome: 1 packet 3-4 times a day.

The interval between doses should be at least 4 hours. The maximum daily dose is no more than 6 packets.

Citramarine should not be used for more than 5 days as a pain reliever and for more than 3 days as an antipyretic.

Side effects

Possible adverse drug reactions due to the use of Citramarin in therapeutic doses:

metabolism and nutritional disorders: rarely - loss of appetite;
parasitic and infectious diseases: rarely - pharyngitis;
nervous system: often - dizziness; infrequently - tremor, headache, paresthesia; rarely - pain in the paranasal sinuses, attention disorder, taste disorder, impaired coordination of movement, amnesia, hyperesthesia;
mental disorders: often - nervousness; infrequently - insomnia; rarely - a feeling of inner tension, euphoric mood, anxiety;
cardiovascular system (CVS): infrequently - arrhythmia; rarely - hyperemia, peripheral circulatory disorders;
organ of hearing: infrequently - tinnitus;
organ of vision: rarely - visual impairment;
digestive system: often - abdominal discomfort, nausea; infrequently - dry mouth, vomiting, diarrhea; rarely - increased salivation, belching, dysphagia, flatulence, paresthesia in the mouth;
respiratory system, chest and mediastinal organs: rarely - epistaxis, rhinorrhea, hypoventilation;
musculoskeletal system: rarely - muscle spasms, musculoskeletal stiffness, back / neck pain;
general disorders: infrequently - increased excitability, excessive fatigue; rarely - asthenia, a feeling of heaviness in the chest;
skin and subcutaneous tissues: rarely - itching, urticaria, hyperhidrosis;
others: infrequently - an increase in heart rate.

Violations of Citramarine recorded during post-registration observation:

CCC: sensation of palpitations; lowering blood pressure (BP);
immune system: hypersensitivity;
skin and subcutaneous tissues: rash, erythema, erythema multiforme, angioedema;
nervous system: drowsiness, migraine;
mental disorders: anxiety;
digestive system: abdominal pain, dyspepsia, epigastric pain, gastrointestinal bleeding (including bleeding from the upper gastrointestinal tract, from the stomach and rectum), stomach ulcers, duodenal ulcers; erosive and ulcerative lesions of the gastrointestinal tract, including ulcers of the stomach, colon, 12 duodenal ulcer and peptic ulcer; liver failure;
respiratory system, chest and mediastinal organs: shortness of breath, bronchospasm;
general disorders: discomfort, malaise.

Many of the above adverse events were clearly dose-dependent and could vary significantly.

Aggravation of the threat of bleeding after using ASA persists for 4-8 days. It is extremely rare to develop severe, life-threatening bleeding (for example, cerebral hemorrhage), mainly in people with untreated arterial hypertension and / or with the combined use of anticoagulants.

Overdose

ASK

In the case of mild ASA intoxication (at a plasma level of 50–300 mcg / ml), symptoms such as increased sweating, tinnitus, dizziness, headache, deafness, nausea, vomiting, and confusion are possible. A dose reduction or drug withdrawal is recommended.

When the ASA content is above 300 μg / ml, severe intoxication develops, the manifestations of which are fever, anxiety, hyperventilation, ketoacidosis, metabolic acidosis, and respiratory alkalosis. CNS suppression can cause coma, cardiovascular collapse and respiratory failure are also possible. The threat of developing chronic intoxication increases in children and the elderly when ASA is used for several days at a daily dose of more than 100 mg / kg.

If you suspect taking salicylates at a dose of more than 120 mg / kg during the last hour, multiple intake of activated carbon is prescribed for therapy. If the plasma level of a substance exceeds 500 μg / ml, sodium bicarbonate is administered intravenously (i.v.). With a plasma concentration of more than 700 μg / ml or against a background of severe metabolic acidosis, hemodialysis or hemoperfusion is prescribed.

Paracetamol

In case of paracetamol overdose, especially in children, elderly patients, patients with liver damage, malnutrition, as well as the use of inducers of liver microsomal enzymes, intoxication may develop, manifested by fulminant hepatitis, cytolytic / cholestatic hepatitis, liver failure, sometimes with a fatal outcome. Overdose symptoms include pale skin, decreased appetite, nausea, vomiting, abdominal pain, and / or abdominal discomfort. After administration of the drug, signs of acute overdose develop within 24 hours. With simultaneous use by adults at a dose of 7500 mg or more, or children - over 140 mg / kg, cytolysis of hepatocytes occurs with complete and irreversible liver necrosis, liver failure, metabolic acidosis and encephalopathy,with possible subsequent coma and death. 12–48 hours after administration, there is an increase in the activity of lactate dehydrogenase (LDH), microsomal liver enzymes, an increase in the content of bilirubin and a decrease in prothrombin. After an overdose, the symptoms of liver damage are recorded after 48 hours and reach a maximum on days 4–6.

For the treatment of intoxication, urgent hospitalization is required. It is necessary to determine the level of plasma content of paracetamol at an earlier date after an overdose. In the first eight hours, the most effective administration of SH-group donors, methionine and acetylcysteine - precursors of glutathione synthesis. At the beginning of therapy and then every 24 hours, the activity of liver microsomal enzymes should be determined, as a rule, this indicator reaches the norm within 7-14 days. In extremely severe cases, liver transplantation may be necessary.

Caffeine

The most common symptoms of a caffeine overdose are pyrexia, tinnitus, headache, increased tactile / pain sensitivity, agitation, anxiety, nervousness, insomnia, delirium, anxiety, mental agitation, increased urination, muscle twitching, dehydration, gastralgia, nausea and vomiting (in some cases with blood), confusion, convulsions. With a significant overdose, hyperglycemia, tachycardia and arrhythmias may develop.

Treatment: reducing the dose of the drug or canceling it.

special instructions

Citramarin should not be used concurrently with other drugs that include ASA or paracetamol.

Before starting therapy for suspected migraine in patients who have not previously been diagnosed with migraine, or in whom the manifestations of this disease are atypical, care must be taken to exclude possible other serious neurological disorders.

Citramarin should not be used if vomiting develops during more than 20% of migraine attacks, or if more than 50% of migraine attacks require bed rest.

In the case when after taking 2 packets of analgesic it is not possible to stop the migraine, you need to consult a doctor.

You should not use Citramarine if you have had more than 10 headache attacks during the last 3 months during the month.

With extreme caution, it is required to take the drug before or after major surgery, in the presence of risk factors for dehydration, such as vomiting and diarrhea, as well as in patients with diabetes mellitus, uncontrolled arterial hypertension, against the background of metro- or menorrhagia.

Before surgical intervention, the doctor should be warned about drug treatment.

Citramarine can mask the symptoms and signs of infection.

Patients with blood clotting disorders during the period of therapy need careful monitoring.

ASA can distort the results of laboratory tests of the activity of the thyroid gland as a result of a false positive low content of triiodothyronine (T3) and levothyroxine (T4).

Paracetamol is able to influence the results of laboratory studies regarding the level of concentration in the blood of uric acid (using the method using phosphotungstic acid) and glucose (using the glucose oxidase-peroxidase method).

While taking Citramarine, it is recommended to reduce the consumption of products that include caffeine, since its excessive intake can provoke irritability, nervousness, insomnia, and sometimes heart palpitations.

1 bag of powder contains 1 grain unit (XE).

Influence on the ability to drive vehicles and complex mechanisms

During treatment with Citramarine, special care should be taken when driving vehicles and controlling complex mechanisms, due to the possible development of undesirable effects in the form of drowsiness or dizziness.

Application during pregnancy and lactation

Citramarin therapy for pregnant and lactating women is contraindicated.

Pediatric use

It is contraindicated to use the drug as an analgesic for patients under 15 years of age.

As an antipyretic, Citramarine is not prescribed to patients under 18 years of age, since in the case of a viral infectious disease, the ASA contained in the preparation can aggravate the risk of Reye's syndrome. Symptoms of this side effect may be prolonged vomiting, hyperpyrexia, metabolic acidosis, liver dysfunctions, hepatomegaly, mental and nervous system disorders, acute encephalopathy, convulsions, respiratory failure, coma.

With impaired renal function

In severe renal impairment, Citramarin is contraindicated.

Patients with mild / moderate renal impairment should use the drug with caution.

For violations of liver function

With severe violations of the liver, taking Citramarin is contraindicated.

For mild to moderate liver failure, an antipyretic analgesic may be used with caution.

Use in the elderly

In elderly patients, paracetamol clearance decreases and T _1/2 increases. Elderly people, especially those with low body weight, should take Citramarine with caution.

Drug interactions

ASK

Combinations not recommended:

GCS, other NSAIDs, ethanol: the damaging effect on the gastrointestinal mucosa is aggravated, the threat of gastrointestinal bleeding increases;
oral anticoagulants (including coumarin derivatives), heparin: the effect of these drugs is potentiated, monitoring of prothrombin time and bleeding period is required;
thrombolytics: the threat of bleeding increases; during the first 24 hours after an acute stroke, the use of ASA is not recommended;
SSRIs: increases the risk of bleeding in general, and gastrointestinal bleeding in particular, due to the effect on blood clotting and platelet function;
platelet aggregation inhibitors (paracetamol, ticlopidine, cilostazol, clopidogrel): the likelihood of bleeding increases; laboratory and clinical monitoring of bleeding time is necessary.

Possible interaction reactions with the combined use of ASA and other drugs:

valproic acid: the connection with plasma proteins is disrupted, which can cause an increase in its toxicity; control of the plasma level of this substance is necessary;
phenytoin: ASA helps to increase its plasma concentration;
spironolactone, canrenoate and other aldosterone antagonists: their activity may decrease as a result of impaired sodium excretion, blood pressure control is required;
loop diuretics (furosemide): glomerular filtration is impaired due to inhibition of Pg production in the kidneys, which leads to a decrease in the activity of these agents; development of acute renal failure is possible, aggravated by dehydration, sufficient rehydration should be provided, and blood pressure and renal function should be monitored, especially at the beginning of combination therapy;
angiotensin II receptor antagonists, angiotensin-converting enzyme (ACE) inhibitors, slow calcium channel blockers (BMCC) and other antihypertensive drugs: their activity is weakened, the risk of acute renal failure in dehydrated or elderly patients is aggravated; when combined with verapamil, the bleeding period must be controlled;
methotrexate (at a dose of ≤ 15 mg / week): the plasma concentration increases and, as a result, the toxicity of this substance; it is necessary to monitor, at least in the first days of therapy, a general blood test, liver and kidney function;
probenecid, sulfinpyrazone (uricosuric agents): the activity of these agents decreases due to the suppression of tubular reabsorption, which causes a high plasma concentration of ASA;
derivatives of sulfonylurea and insulin: their hypoglycemic effect increases; when using salicylates in high doses, a dose reduction of these drugs may be required; it is necessary to monitor blood glucose levels more often.

Paracetamol

Combinations not recommended:

probenecid: the clearance of paracetamol decreases, because of this, a decrease in its dose is required;
zidovudine: the tendency to develop neutropenia increases, the indicators of hematological tests should be monitored; combination therapy is possible only as directed by a doctor;
ethanol, isoniazid, rifampicin, antiepileptic and hypnotics (phenobarbital, carbamazepine) are potentially hepatotoxic substances or inducers of microsomal liver enzymes: they aggravate the toxicity of paracetamol, the risk of liver damage increases even with the use of its non-toxic doses;
chloramphenicol: the likelihood of increased concentration of this substance increases.

Interaction reactions that are possible when combining paracetamol with other drugs:

metoclopramide and other drugs that accelerate the evacuation of stomach contents: the rate of absorption of paracetamol increases and, accordingly, its effectiveness;
indirect anticoagulants: the effect of these drugs increases with repeated use of paracetamol for more than 7 days; occasional intake of the drug does not have a significant effect;
propantheline and other drugs that inhibit evacuation from the stomach: the rate of absorption of paracetamol decreases, which can slow down the onset of its therapeutic effect;
cholestyramine: the activity of absorption of paracetamol decreases, if maximum analgesia is required, cholestyramine should be taken no earlier than 1 hour after taking paracetamol.

Caffeine

Combinations not recommended:

lithium: the plasma level of this substance increases with the abolition of caffeine, since the latter contributes to an increase in renal clearance of lithium: when you stop taking caffeine, you may need to reduce the dose of lithium;
benzodiazepines, H1-histamine receptor blockers, barbiturates and other hypnotics: hypnotic or anticonvulsant effects may be weakened; if it is necessary to take it simultaneously, it is advisable to use this combination in the morning;
ephedrine-like substances: the threat of drug dependence is increasing;
disulfiram: the risk of aggravation of alcohol withdrawal syndrome increases due to the stimulating effect of caffeine on the central nervous system and cardiovascular system;
clozapine: the serum concentration of this substance increases, monitoring of its content in the serum is required;
sympathomimetics, levothyroxine: the chronotropic effect is enhanced as a result of mutual potentiation.

Other possible interaction reactions:

antibiotics from the quinoline group (enoxacin, ciprofloxacin, pipemidic acid), cimetidine, fluvoxamine, terbinafine, oral contraceptives: as a result of the suppression of liver cytochrome P450, the T _{1/2 of} caffeine increases, so you should avoid taking it against the background of violations of liver function and heart rhythm, and also latent epilepsy;
theophylline: excretion of this substance is weakened;
nicotine, phenylpropanolamine, phenytoin: the terminal T _{1/2 of} caffeine decreases.

Analogs

Citramarine analogues are Askofen-P, Kofitsil-plus, Citramon-MFF, Aquacitramon, Citramon P, Citramon P Medisorb, Citrapar, Citramon Ultra, Citramon-LecT, Excedrin, etc.

Terms and conditions of storage

Store at a temperature not exceeding 25 ° C, in a place protected from moisture and light and out of reach of children.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Available without a prescription.

Reviews of Citramarine

Reviews of Citramarine, left on specialized sites, are in most cases positive. Patients claim that the drug quickly lowers the high temperature, relieves the symptoms of colds and acute respiratory infections, and effectively relieves pain.

Sometimes they note the lack of a positive result in the treatment of migraines and headaches. Citramarine is also not always effective for relieving febrile syndrome with prolonged colds.

Price for Citramarine in pharmacies

The price of Citramarine in the form of a powder for the preparation of an orange solution for oral administration (13 g in a sachet) can be 140–180 rubles. for 10 sachets.

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!