KODELMIKST

Active material: codeine, Paracetamol
When ATH: N02BE51
CCF: Analgesics, antipyretics combined structure
ICD-10 codes (testimony): G43, K08.8, M25.5, M79.1, M79.2, R51, R52.0, R52.2
When CSF: 03.02.01.03
Manufacturer: RUSAN PHARMA Ltd. (India)

Pharmaceutical form, composition and packaging

◊ Pills white, round, flat, with beveled edges and a notch on one side.

Excipients: pre-gelatinized starch, corn starch, magnesium stearate, sodium bisulfite, povidone K-30.

10 PC. – blisters (1) – packs cardboard.

Pharmacological action

Combined preparation, action is due to the effects of its constituent components.

Paracetamol – non-opioid analgesics, It has analgesic and antipyretic action. Blocking COX-1 and COX-2 mainly in CNS, acting on centers pain thermoregulation. In inflamed tissues cellular peroxidase neutralize the effect of paracetamol on COX, which explains the almost complete absence of anti-inflammatory effect. The absence of a blocking effect on prostaglandin synthesis in peripheral tissues causes lack of a negative effect on water-salt exchange (sodium retention and water) and gastrointestinal mucosa.

Codeine It has a central antitussive effect (by suppressing the excitability of the cough center), and analgesic effect, due to the excitation of opioid receptors in various parts of the central nervous system and peripheral tissues, resulting in stimulation of antinociceptive system and change the emotional perception of pain. To a lesser extent, than morphine, respiratory depression, less likely to cause cramps, nausea, vomiting and constipation (Activation of opioid receptors in the gut causes the relaxation of smooth muscles, decrease motility and spasm of the sphincter).

The duration of analgesic effect – 4 no, antitussive – 4-6 no.

Pharmacokinetics

Paracetamol

Absorption and distribution

Paracetamol well and completely absorbed from the gastrointestinal tract. C_max achieved through 0.5-2 h and is 5-20 ug / ml.

Relationship to plasma proteins – 15%. It penetrates through the BBB. Less 1% adopted by a nursing mother dose of paracetamol passes into breast milk.

The therapeutically effective concentration of paracetamol in plasma achieved when administered in a dose of 10-15 mg / kg.

Metabolism and excretion

It is metabolized in the liver (90-95%): 80% enters into the conjugation reaction with glucuronic acid sulfates to form inactive metabolites, 17% undergoes hydroxylation to form 8 active metabolite, which is conjugated with glutathione to form inactive metabolites have. With a lack of glutathione, these metabolites may block the enzyme systems of hepatocytes and cause their death. The metabolism of the drug is also involved isoenzyme CYP2E1.

T_1/2 – 1-4 no. Excreted by the kidneys as metabolites, mainly conjugates, only 3% in unchanged form.

Pharmacokinetics in special clinical situations

In elderly patients with reduced drug clearance and increased T_1/2.

Codeine

Absorption and distribution

Codeine After intake of rapidly absorbed from the gastrointestinal tract.

Relationship to plasma proteins – 30%. C_max reached through 2-4 no.

Metabolism and excretion

It is metabolized in the liver to active metabolites; in the metabolism of the drug is involved isoenzyme CYP 2D6. 10% by demethylation proceeds in morphine.

Report the news (5-15% in unchanged the form and 10% in the form of morphine and its metabolites) and the bile. T_1/2 – 2.5-4 no.

Testimony

Pain syndrome mild to moderate intensity:

- Headache;

- Migraine;

- Myalgia;

- Neuralgia;

-arthralgia;

- Algomenorrhea;

- toothache;

- post-traumatic pain.

Colds, flu (as an antipyretic and antitussive).

Dosage regimen

Adults and children over 12 years appoint 1-2 tab. every 4 no, but not more 8 tab. / day.

As an antipyretic not recommend taking Kodelmiksta^® without consulting a doctor more 3 d, as well as an analgesic – more 5 d. Do not exceed the recommended dose.

Side effect

From the central and peripheral nervous system: often – drowsiness; sometimes – blurred vision, double vision, feeling tired, headache, dizziness, convulsions, involuntary muscle contractions or muscle rigidity, hallucinations, nightmares, depression, feeling of uneasiness, a sense of euphoria.

From the digestive system: often – constipation; sometimes – nausea, vomiting, dry mouth, epigastric pain, anorexia.

Allergic reactions: sometimes – skin rash, itch, angioedema.

Cardio-vascular system: sometimes – flushing of the face, bradycardia / tachycardia, hypotension.

From the hematopoietic system: rarely – anemia, thrombocytopenia, metgemoglobinemiâ.

Other: sometimes – Sweating, difficulty breathing; rarely – of the liver and kidneys.

Chronic administration Kodelmiksta^® its efficiency is reduced. It can also be addictive due to the contained codeine. Upon termination of treatment the symptoms of anxiety and irritability may appear.

Contraindications

- Severe renal insufficiency;

- Severe hepatic impairment;

- A violation of hematopoiesis;

- genetically determined deficiency of glucose-6-phosphate dehydrogenase;

- infringement due to respiratory depression of the respiratory center;

- Bronchial asthma;

- pulmonary insufficiency;

- heart failure;

-increased intracranial pressure;

- head injury history;

- acute abdominal pain of unknown etiology;

- the risk of functional intestinal obstruction;

- administration of drugs, soderzhashtih paracetamol;

- MAO inhibitors within the last 14 days;

- Alcoholism;

- Pregnancy;

- Lactation;

- Children up to age 12 years;

- Hypersensitivity to components of the preparation.

FROM caution should be prescribed the drug for hypotension, aritmijax, cholelithiasis, myasthenia, diseases of the adrenal glands, prostatic hyperplasia, convulsions, Drug Dependence (incl. history), and elderly patients.

Pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Cautions

It should not take the drug for more than 3 days without consulting a doctor.

Codeine, contained in the product Kodelmikst^® It can be addictive.

Avoid drinking alcohol during treatment Kodelmikstom^®, tk. codeine potentiates the effect of ethanol.

Avoid coadministration Kodelmiksta^®with other drugs, containing paracetamol, as well as expectorant drugs.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment must be careful when driving and occupation of other potentially hazardous activities, require high concentration and speed of psychomotor reactions, tk. there is the risk of drowsiness.

Overdose

Symptoms: excitation, nausea, heaviness in the head, insomnia, gipoglikemiâ, gemoliticheskaya anemia, cyanosis, bronchospasm, can accelerate the development of severe respiratory failure. When applied in high dose paracetamol (more 10 g / day) or when long-term treatment of 3-4 g / day there are necrosis of liver and kidney damage. In high doses paracetamol is metabolized to N-acetyl-p-benzoquinone, which causes liver damage.

Treatment: gastric lavage, reception Activated Carbon.

Drug Interactions

Simultaneous reception Koldemiksta^® with MAO inhibitors causes ataksiyu, hypotension, paresthesia, ccomodation.

Koldemikst^® while the use of antiplatelet agents enhances the action, what may result the appearance of adverse reactions.

Long-term regular intake of paracetamol increases the anticoagulant effect of warfarin and other coumarin, which may increase the risk of bleeding; a unit receiving a significant effect It does not have.

Codeine increases the effects of ethanol on psychomotor function.

Codeine can slow the absorption of mexiletine and quinidine, thus, reduce its antiarrhythmic affect.

Receiving metoclopramide, domperidone or cisapride may increase the rate of absorption of paracetamol.

Cholestyramine reduces the absorption of paracetamol.

Drugs, CNS depressants, sedative effect and the inhibitory effect of codeine on the respiratory center.

Inductors of microsomal oxidation (barbiturates, protivoepileticheskie drugs, rifampicin and ethanol) while the use of Koldemikstom^®increase the risk of gepatotoksichnosti.

Oral contraceptives decrease the rate of metabolism of paracetamol 20-30%.

Conditions of supply of pharmacies

The drug is resolved to application as an agent Valium holidays.

Conditions and terms

The drug should be stored in a dry, protected from light, inaccessible to children at temperature not exceeding 25 ° C. Shelf life – 3 year.