Paraverine

Paraverine has a combined antispasmodic and analgesic effect.

Indications Paraverine

It is used to eliminate pain sensations of mild or moderate intensity. This includes headaches of a tension nature (acute or chronic).

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Release form

The medicine is released in tablets, in the amount of 10 pieces inside a blister pack. The box contains 1, 3 or 9 such packages.

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Pharmacodynamics

Paraverine is a complex drug that contains two active ingredients: paracetamol and drotaverine, which is an isoquinoline derivative (it has antispasmodic properties).

Paracetamol.

The substance paracetamol has an antipyretic and analgesic effect, which develops by slowing down the processes of PG binding in the CNS, as well as the PNS (to a lesser extent). Paracetamol blocks the binding or effect of PG (or other components that have a stimulating effect on pain endings).

Drotaverine.

This element has a spasmolytic effect on smooth muscles - by slowing down the activity of the enzyme PDE IV. The effectiveness of drotaverine depends on the indices of the enzyme PDE IV in various tissues (the nature of these tissues is not important). This element in high concentrations also causes a weak slowing effect on calcium calmodulin.

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Pharmacokinetics

Paracetamol.

The component is almost completely and quickly absorbed in the gastrointestinal tract. Peak values in the blood plasma are noted after 0.5-1 hour.

Half-life is about 1-4 hours. The substance is evenly distributed throughout all body fluids. The level of synthesis with plasma protein is variable.

Excretion of paracetamol occurs mainly through the kidneys – in the form of conjugated metabolic products.

Drotaverine.

After oral administration, the element is completely and rapidly absorbed. Peak plasma levels are observed after 45-60 minutes. About 95-98% of the substance is synthesized with blood plasma protein (most of it with albumin, and also with α- and β-globulins).

The plasma half-life of drotaverine is 2.4 hours, and the biological half-life is within 8-10 hours. The element accumulates inside the central nervous system, myocardium with fatty tissues and lungs with kidneys, and in addition, it penetrates the placenta. Drotaverine is metabolized inside the liver.

More than 50% of the substance is excreted in the urine, and another 30% in the feces.

Both active components of the drug do not demonstrate interaction at the level of protein synthesis. In vitro tests showed that paracetamol (a dose corresponding to the medicinal dosage) does not have a specific inhibitory effect on the metabolism of the substance drotaverine, while increasing its duration of stay in an unchanged form by 2-7 times. Because of this, there is a possibility that it is capable of inhibiting the metabolism of drotaverine in in vivo processes.

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Dosing and administration

The medicine is taken orally.

Scheme of application of Paraverine:

• adolescents from 12 years of age, as well as adults: a single dose is 1-2 tablets, which are taken at intervals of 8 hours*. A maximum of 6 tablets are allowed per day**;
• Children aged 6-12 years: single dose size is 0.5 tablet, taken every 10-12 hours*. A maximum of 1 tablet is allowed per day.

*repeated administration of the drug can only be carried out if there is a clear need.

**if the therapy lasts more than 3 days, a maximum of 4 tablets per day is allowed.

Therapy without consulting a doctor can last no more than 3 days.

It is prohibited to exceed the recommended portion.

The medicine should not be combined with other medications that contain paracetamol.

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Use Paraverine during pregnancy

It is contraindicated to use Paraverine during lactation or pregnancy.

Contraindications

Main contraindications:

• the presence of intolerance to medicinal elements;
• severe liver dysfunction, as well as severe stage of liver failure, congenital hyperbilirubinemia and constitutional hyperbilirubinemia;
• severe renal failure and severe forms of renal dysfunction;
• severe heart failure (low cardiac output syndrome);
• deficiency of the element G6PD in the body;
• severe anemia, blood disease, and leukopenia;
• alcoholism.

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Side effects Paraverine

The use of the drug may lead to the appearance of some side effects.

Adverse reactions to paracetamol:

• immune manifestations: development of anaphylaxis, signs of hypersensitivity, including rashes and itching in the epidermis and mucous membranes (often generalized or erythematous rashes and urticaria), and in addition, Quincke's edema, MEE (this includes Stevens-Johnson syndrome) and TEN;
• gastrointestinal disorders: epigastric pain or nausea;
• disorders affecting the endocrine system: development of hypoglycemia, which can lead to hypoglycemic coma;
• manifestations from the lymph and hematopoietic processes: the appearance of thrombocytopenia, anemia (also hemolytic), agranulocytosis, and in addition sulf- and methemoglobinemia (dyspnea, cyanosis and pain in the heart), as well as bruises or bleeding;
• lesions affecting the respiratory system: bronchospasms in people with intolerance to aspirin and other NSAIDs;
• digestive disorders: liver dysfunction, increased activity of liver enzymes (usually without the occurrence of jaundice).

Adverse reactions to drotaverine:

• immune disorders: signs of allergy, including urticaria, Quincke's edema, skin hyperemia, itching and rashes, as well as chills, fever, a feeling of weakness and an increase in temperature;
• disorders of cardiovascular function: decreased blood pressure and heart palpitations;
• manifestations from the nervous system: dizziness along with headaches, as well as insomnia;
• gastrointestinal tract disorders: constipation or nausea appear, and also vomiting.

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Overdose

Paracetamol-related intoxication.

The development of liver damage can occur in adults who have consumed 10+ g of paracetamol, and in children who have taken 150+ mg/kg of the drug.

In people with risk factors (long-term therapy with phenobarbital, primidone, carbamazepine, and also phenytoin, St. John's wort, rifampicin or other liver enzyme inducers; constant use of ethyl alcohol in large portions; glutathione cachexia (hunger, digestive disorders, HIV infection, cystic fibrosis, and also cachexia)) the use of 5+ g of the drug can cause liver damage.

Among the signs of overdose that develop during the first 24 hours: nausea with abdominal pain, and along with this, pallor and anorexia with vomiting. Liver damage sometimes develops 12-48 hours after poisoning. Disorders of glucose metabolism processes, as well as metabolic acidosis, may be observed.

If the intoxication is severe, liver failure may develop into hemorrhages, hypoglycemia, and in addition to this, comatose state and encephalopathy. As a result, death may occur.

In acute renal failure, with acute tubular necrosis, hematuria, severe lumbar pain, and proteinuria occur. This disorder can develop even in people who do not have severe liver disease. In addition, pancreatitis and cardiac arrhythmia have been observed.

Long-term use of drugs in high doses can lead to the development of disorders of the hematopoietic function - neutro-, thrombocyto-, leukopenia or pancytopenia, as well as aplastic anemia and agranulocytosis. Regarding the function of the central nervous system - an overdose leads to a disorder of orientation, severe agitation of a psychomotor nature and dizziness. The urinary system can react by developing nephrotoxicity (capillary necrosis, renal colic and tubulointerstitial nephritis occur).

In case of poisoning, the patient will need urgent medical care. He should be taken to the hospital immediately, even if there are no early signs of intoxication. Symptoms may be limited to vomiting with nausea or may not reflect the severity of the poisoning and the degree of risk of damage to the body.

Activated charcoal therapy should be considered (if a large dose of paracetamol has been taken in the previous 60 minutes). Plasma levels should be measured 4+ hours after ingestion (earlier values will not be reliable).

N-acetylcysteine can be used for 24 hours after taking the drug, but the most complete protective effect will be observed when administered within 8 hours after taking Paraverine. After this time period, the effectiveness of the antidote is sharply weakened.

If the patient is not vomiting, oral methionine is a suitable alternative (in areas where hospital access is difficult).

Poisoning caused by drotaverine.

Due to drotaverine intoxication, the following symptoms develop: weakening of the expression of excitation of the heart muscle, AV block, and also arrhythmia. If severe intoxication is observed, a disorder of the heartbeat rhythm and conduction occurs (this includes a full block in the His bundle, and also cardiac arrest). These manifestations can cause a fatal outcome.

In case of poisoning with drotaverine, appropriate symptomatic measures are taken.

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Interactions with other drugs

Drotaverine.

Combination with levodopa leads to a weakening of the antiparkinsonian effect - an increase in tremor with rigidity is possible.

Paracetamol.

The rate of absorption of paracetamol can increase when combined with metoclopramide and domperidone; a decrease in the rate of drug absorption is observed when combined with cholestyramine.

The anticoagulant effect of warfarin and other coumarins can be potentiated by constant and prolonged combined use with paracetamol (with daily intake). This increases the likelihood of bleeding. However, if the medications are taken periodically, no significant effect is observed.

Barbiturates can weaken the antipyretic properties of paracetamol.

Anticonvulsants (including barbiturates with phenytoin and carbamazepine), which stimulate the activity of microsomal liver enzymes, can increase the toxic properties of paracetamol in relation to the liver - due to an increase in the degree of conversion of the drug into hepatotoxic metabolic products. The combined use of paracetamol and hepatotoxic drugs increases the toxic effect of drugs on the liver.

The combined use of large doses of paracetamol with isoniazid increases the likelihood of developing hepatotoxic syndrome.

Paracetamol weakens the properties of diuretics.

It is prohibited to combine the medicine with alcoholic beverages.

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Storage conditions

Paraverine should be kept in a place out of reach of children. Temperature level – maximum 25°C.

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Shelf life

Paraverine can be used for 2 years from the date of release of the drug.

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Application for children

It is prohibited to prescribe the medicine to children under 6 years of age.

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Analogues

An analogue of the drug is the medicine No-spazma.

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Reviews

Paraverin receives good reviews regarding its medicinal effectiveness. Among the advantages of the drug, its low cost is also noted.