Jessica®

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT JESICA®

Composition:

Active substances: paracetamol; drotaverine hydrochloride;

One tablet contains 500 mg of paracetamol and 40 mg of drotaverine hydrochloride;

Excipients: povidone, ascorbic acid, magnesium stearate, pregelatinized starch, colloidal anhydrous silicon dioxide, talc, crospovidone, microcrystalline cellulose, iron oxide yellow (E 172).

Pharmaceutical form. Tablets.

Main physicochemical properties: beige elongated tablets with break lines on both sides and embossing "PD" on one side. Marbling is permissible.

Pharmacotherapeutic group.

Spasmolytics in combination with analgesics. ATC code A03D C.

Pharmacological properties.

Dyazica® is a combination drug that contains two components: the non-narcotic analgesic-antipyretic paracetamol and drothaverine, an isoquinoline derivative with spasmolytic activity.

Pharmacodynamics.

Paracetamol.

Paracetamol exerts analgesic and antipyretic effects primarily by inhibiting prostaglandin synthesis in the central nervous system and, to a lesser extent, in the periphery, by blocking the synthesis or action of prostaglandins and other substances that stimulate pain receptors.

Drotaverine.

Drotaverine exerts a spasmolytic effect on smooth muscle by inhibiting phosphodiesterase IV enzyme. The efficacy of drotaverine depends on the tissue content of phosphodiesterase IV enzyme, regardless of tissue type. Increased drotaverine concentration also leads to a weak inhibitory effect on calcium-dependent calmodulin.

Pharmacokinetics.

Paracetamol.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Maximum plasma concentration is reached within 30–60 minutes. The elimination half-life is 1–4 hours. It is evenly distributed throughout all body fluids. Plasma protein binding is variable. It is primarily excreted by the kidneys in the form of conjugated metabolites.

Drotaverine.

Drotaverine is rapidly and completely absorbed after oral administration. Maximum plasma concentration is achieved within 45–60 minutes after oral intake. 95–98% of drotaverine is bound to plasma proteins, mainly to albumin, α- and β-globulins. Its elimination half-life from plasma is 2.4 hours, while the biological half-life ranges from 8 to 10 hours. Drotaverine accumulates in the central nervous system, adipose tissue, myocardium, kidneys, and lungs, and crosses the placenta. It is metabolized in the liver; more than 50% is excreted in urine and approximately 30% in feces.

Paracetamol and drotaverine do not interact at the protein-binding level. An in vitro study has shown that paracetamol (at concentrations corresponding to therapeutic doses) does not specifically inhibit drotaverine metabolism but increases its unchanged form's persistence by 2–7 times. Therefore, it may also inhibit drotaverine metabolism in vivo.

Clinical characteristics.

Indications.

Relief of mild to moderate pain, including tension-type headache (both acute and chronic forms).

Contraindications.

• Hypersensitivity to any component of the drug;
• severe impairment of liver function, severe hepatic insufficiency, congenital hyperbilirubinemia, Gilbert’s syndrome;
• severe impairment of kidney function, severe renal insufficiency;
• severe heart failure (low cardiac output syndrome);
• glucose-6-phosphate dehydrogenase deficiency;
• blood disorders, marked anemia, leukopenia;
• alcoholism.

Interaction with other medicinal products and other forms of interaction.

For drotaverine.

Levodopa. The anti-Parkinson effect may be reduced when drotaverine is used concomitantly with levodopa; for example, rigidity and tremor may worsen.

For paracetamol.

The absorption rate of paracetamol may be increased when used with metoclopramide and domperidone, and decreased when used with cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced during long-term, regular daily use of paracetamol, increasing the risk of bleeding. Occasional use does not have a significant effect.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions for use").

Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, 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 hepatotoxic potential of the drugs.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Paracetamol reduces the efficacy of diuretics. Do not use concomitantly with alcohol.

Special precautions for use.

Data for paracetamol.

The product contains paracetamol; therefore, it should not be used together with other medicinal products containing paracetamol, which are used, for example, to reduce fever, relieve pain, treat flu and cold symptoms, or insomnia. Concurrent use with other paracetamol-containing products may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in death.

Consult a physician regarding the possibility of using Jessica® in patients with liver or kidney disease.

It should be noted that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol.

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.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe underlying conditions such as severe renal failure and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol and careful monitoring are recommended. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

In patients with reduced glutathione levels, the use of paracetamol increases the risk of developing 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.

If symptoms persist, consult a physician. Prolonged use without medical supervision may be dangerous.

The medicinal product should be used only when clearly necessary.

Data for drotaverine.

Jessica® should be used with particular caution in patients with arterial hypotension.

Use during pregnancy or breastfeeding.

Use is contraindicated.

Ability to influence reaction rate while driving or operating machinery.

During treatment, driving and performing tasks requiring high attention should be avoided if the medicinal product causes dizziness.

Method of administration and dosage.

The medication is intended for oral administration.

* - the drug should be used again only if necessary.

** - if treatment lasts longer than 3 days, the maximum dose of the drug should not exceed 4 tablets per day.

Maximum duration of use without consulting a doctor – 3 days.

Do not exceed the recommended dose.

Do not take together with other medicinal products containing paracetamol.

Children.

Due to the lack of sufficient clinical data on the efficacy and safety of combined drugs containing 500 mg of paracetamol and 40 mg of drotaverine in children under 18 years of age, the use of the drug Jessika® is not recommended in this age group of patients.

Overdose.

Data for paracetamol.

Paracetamol overdose may cause liver failure, which may lead to the need for liver transplantation or fatal outcome. Clinical signs of liver damage after paracetamol overdose usually appear within 24–48 hours after overdose and peak at 4–6 days.

Symptoms of overdose within the first 24 hours: pallor, nausea, vomiting, anorexia, and abdominal pain. Asymptomatic course of overdose is also possible. Paracetamol overdose after a single dose in adults and children may cause reversible or irreversible necrosis of liver cells, which may lead to disturbances in glucose metabolism, metabolic acidosis, hepatocellular insufficiency, encephalopathy, hemorrhages, hypoglycemia, coma, and fatal outcome. At the same time, elevated levels of liver transaminases (aspartate aminotransferase, alanine aminotransferase), lactate dehydrogenase, bilirubin, and prothrombin time are observed 12–48 hours after ingestion. Liver damage is likely in adults who have taken more than the recommended amount of paracetamol. It is believed that an increased amount of the paracetamol metabolite (which is normally neutralized by glutathione when standard doses of paracetamol are used) binds irreversibly to liver tissues. Acute renal failure with acute tubular necrosis may manifest as severe pain in the lumbar region, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmia and acute pancreatitis have also been reported, usually accompanied by liver function disorders and hepatotoxicity.

With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop from the hematopoietic system side. From the nervous system side — dizziness, psychomotor agitation, and disorientation; from the urinary system side — nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

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

Risk factors for paracetamol overdose are:

• prolonged treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, and other drugs that induce liver enzyme synthesis;
• chronic alcohol abuse;
• reduced glutathione levels, e.g., due to nutritional disorders, fasting, exhaustion, cystic fibrosis, HIV.

Treatment: urgent supportive and symptomatic therapy measures.

In case of overdose, immediate medical assistance is required. Treatment for overdose or even suspected overdose should be started immediately; the patient should be taken to the hospital, even if early symptoms of overdose are absent, since liver damage may not develop immediately. Paracetamol plasma concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable).

If an excessive dose of paracetamol (>150 mg/kg) was taken within 1 hour, the use of activated charcoal should be considered. Treatment with N-acetylcysteine or methionine may be beneficial. Symptomatic treatment should also be provided.

Data for drotaverine.

In case of drotaverine overdose, the following symptoms may occur: AV block, decreased excitability of the myocardium, arrhythmia. With significant drotaverine overdose, disturbances in cardiac rhythm and conduction, including complete bundle branch block and cardiac arrest, which may be fatal, have been observed.

In case of overdose, the patient should be under close medical supervision and receive symptomatic treatment, including induction of vomiting and/or gastric lavage.

In case of drotaverine overdose, symptomatic therapy must be performed.

Side effects.

The frequency of the adverse reactions listed below is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (≤ 1/10000), not known (cannot be estimated from the available data).

Data for paracetamol.

Immune system disorders.

Very rare: anaphylaxis, hypersensitivity skin reactions including rash on the skin and mucous membranes (usually generalized erythematous rash, urticaria), angioedema, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome).

Not known: pruritus, erythema multiforme.

Gastrointestinal disorders.

Not known: nausea, epigastric pain.

Endocrine system disorders.

Not known: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system disorders.

Very rare: thrombocytopenia.

Not known: agranulocytosis, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding.

Respiratory, thoracic and mediastinal disorders.

Very rare: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary disorders.

Very rare: liver function abnormalities.

Not known: increased liver enzyme activity, usually without development of jaundice.

Metabolism and nutrition disorders.

Not known: metabolic acidosis with high anion gap.

Data for drotaverine.

Immune system disorders.

Rare: allergic reactions including angioneurotic edema, urticaria, rash, pruritus, skin hyperemia, urticaria, chills, fever, weakness.

Cardiac disorders.

Rare: tachycardia, arterial hypotension.

Nervous system disorders.

Rare: headache, dizziness, insomnia.

Gastrointestinal disorders.

Rare: nausea, constipation, vomiting.

Description of selected adverse reactions.

Metabolic acidosis with high anion gap: cases of metabolic acidosis with high anion gap as a result of pyroglutamic acidosis have been observed in patients with risk factors who used paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur as a result of low glutathione levels in these patients.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store at temperature not exceeding 25 °C in the original packaging.

Keep out of reach and sight of children.

Packaging.

10 tablets in a blister; 1, 3, or 9 blisters in a cardboard package.

Prescription status.

Over-the-counter.

Manufacturer.

LLC "KUSUM PHARM".

Manufacturer's address and place of business.

54 Skryabina Street, Sumy, Sumy region, 40020, Ukraine.