Trichopol®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TRIXOPOL® (TRICHOPOL®)

Composition:

Active substance: metronidazolum;

One vaginal tablet contains 500 mg of metronidazole;

Excipients: microcrystalline cellulose, povidone, crospovidone, colloidal anhydrous silicon dioxide, stearic acid.

Medicinal form. Vaginal tablets.

Main physicochemical characteristics: elongated, biconvex tablets, white or slightly yellowish in color.

Pharmacotherapeutic group.

Antimicrobial and antiseptic agents used in gynecology. Imidazole derivatives.

ATC code G01AF01.

Pharmacological properties.

Pharmacodynamics.

Metronidazole belongs to nitro-5-imidazoles and has a broad spectrum of activity. The drug is active against: Peptostreptococcus spp., Clostridium spp., Bacteroides spp., Fusobacterium spp., Prevotella spp., Veilonella. Metronidazole inhibits the growth of protozoa – Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica.

Organisms with variable sensitivity to the drug: Bifidobacterium spp., Eubacterium spp. Resistant microbial strains: Propionibacterium, Actinomyces, Mobiluncus.

Pharmacokinetics.

After vaginal administration, systemic absorption is minimal.

The elimination half-life from blood plasma is 8–10 hours. Plasma protein binding is low (less than 20%). Rapid and pronounced diffusion into lungs, kidneys, liver, bile, cerebrospinal fluid, skin, saliva, and vaginal secretions. It crosses the placental barrier and is excreted into breast milk.

Metabolism occurs mainly in the liver, producing two non-conjugated oxidized active metabolites (5–30% of the parent compound's activity).

Excretion is primarily renal: 35–65% of the administered dose is excreted in urine as metronidazole and its oxidized metabolites.

Clinical characteristics.

Indications.

Local treatment of trichomonal vaginitis and nonspecific vaginitis.

Contraindications.

Hypersensitivity to metronidazole or to any other component of the drug.

Hypersensitivity to imidazole derivatives.

Concomitant use in combination with disulfiram or alcohol (see section "Interaction with other medicinal products and other types of interactions").

Cockayne syndrome (see section "Side effects").

Interaction with other medicinal products and other types of interactions.

Disulfiram-like reaction. There are many medicinal products that trigger a disulfiram-like reaction to alcohol, and their concomitant use with alcohol is not recommended.

Combinations not recommended.

Alcohol: disulfiram-like reaction (flushing, erythema, vomiting, tachycardia). Consumption of alcoholic beverages and medicinal products containing alcohol should be avoided.

Disulfiram: risk of developing reversible psychotic episodes or confusion after discontinuation of the drug.

Busulfan: when high doses of busulfan are used: doubling of busulfan concentrations in patients receiving metronidazole.

Combinations requiring precautions during use.

Oral anticoagulant therapy (warfarin-like): enhanced effects of oral anticoagulants and increased risk of hemorrhagic complications due to slowed metabolism in the liver. Prothrombin levels and INR (International Normalized Ratio) should be monitored more frequently. Dose adjustment of the oral anticoagulant is recommended during metronidazole treatment and for 8 days after its discontinuation.

Anticonvulsants that are enzyme inducers (carbamazepine, fosphenytoin, phenobarbital, phenytoin, primidone). Decreased plasma concentrations of metronidazole due to stimulation of its hepatic metabolism by the inducer.

Clinical monitoring should be performed during and after treatment with the inducer. Dose adjustment of metronidazole may be necessary.

Rifampicin: decreased plasma concentrations of metronidazole due to stimulation of its hepatic metabolism by rifampicin.

Clinical monitoring should be performed during and after treatment with rifampicin. Dose adjustment of metronidazole may be necessary.

Lithium: plasma lithium levels may increase during metronidazole administration and reach toxic levels. Close monitoring of plasma lithium concentrations, creatinine, and electrolytes is required in patients receiving lithium and metronidazole concomitantly; dose adjustment of lithium may be necessary if needed.

Cyclosporine: risk of increased plasma levels of cyclosporine. If concomitant use is necessary, plasma levels of cyclosporine and creatinine should be closely monitored.

Combinations requiring special attention.

Fluorouracil (as well as tegafur and capecitabine): reduced clearance of fluorouracil leads to increased toxicity of 5-fluorouracil.

Disturbance of INR (International Normalized Ratio).

Numerous cases of enhanced activity of oral anticoagulants have been reported in patients receiving antibacterial therapy. Risk factors predisposing to this complication include presence of infection or marked inflammation, patient's age, and general health status. Under these circumstances, it is difficult to determine to what extent the disturbance in INR balance is due to the infection itself or its treatment. However, some classes of antibiotics play a greater role in this, particularly: fluoroquinolones, macrolides, tetracyclines, co-trimoxazole, and certain cephalosporins.

Laboratory test results. Metronidazole may immobilize treponemes, leading to a false-positive Nelson test.

Special precautions for use.

In patients with severe, chronic, or progressive diseases of the peripheral or central nervous system, the risk of exacerbation of neurological status should be taken into account.

Patients with a history of hematological disorders or those receiving the drug in high doses and/or for a prolonged period should have regular blood tests, especially leukocyte count monitoring.

During prolonged treatment with the drug, patients should be monitored for the development of adverse reactions such as central or peripheral neuropathy (paresthesia, ataxia, dizziness, seizures).

Patients should be informed that metronidazole may darken the urine (due to the active metabolite).

The use of vaginal suppositories together with condoms or diaphragms increases the risk of latex rupture.

Hypersensitivity/reactions related to skin and its derivatives. Allergic reactions, including life-threatening anaphylactic shock, may occur (see section "Adverse Reactions"). In such cases, metronidazole treatment must be discontinued and appropriate therapy initiated.

If generalized erythema and pustular rash accompanied by fever occur at the beginning of treatment, acute generalized exanthematous pustulosis (AGEP) should be suspected (see section "Adverse Reactions"); in case of such reaction, treatment with the drug must be stopped, and further use of metronidazole, either as monotherapy or in combination with other drugs, is contraindicated.

Central nervous system disorders. If symptoms characteristic of encephalopathy or cerebellar syndrome occur, the patient's treatment should be immediately reassessed and metronidazole therapy discontinued.

Cases of encephalopathy have been reported during post-marketing surveillance. In addition, MRI changes associated with encephalopathy have been observed (see section "Ad游戏副本 Reactions"). Lesions are most commonly localized in the cerebellum (especially in the dentate nucleus) and the corpus callosum. In most cases, encephalopathy and MRI changes resolve after discontinuation of the drug. Very rare fatal cases have been reported.

Patients should be monitored for possible signs of encephalopathy or worsening of symptoms in the presence of central nervous system disorders.

If aseptic meningitis develops during treatment with the drug, re-administration of metronidazole is not recommended. In patients with serious infectious diseases, a re-evaluation of the benefit-risk ratio is required.

Peripheral nervous system disorders. Patients should be monitored for possible signs of peripheral neuropathy, especially during long-term treatment or in the presence of severe, chronic, or progressive peripheral neuropathy.

Psychiatric disorders. Psychotic reactions, including self-harming behavior, may occur after the first dose of the drug, particularly in patients with a history of psychiatric disorders (see section "Adverse Reactions"). In such cases, metronidazole treatment should be discontinued, the physician should be informed, and appropriate therapeutic measures should be taken immediately.

Hematological effects. Patients with a history of blood system disorders and those receiving the drug in high doses and/or for a prolonged period should undergo regular blood tests, especially monitoring of leukocyte count.

Continuation of treatment with the drug in patients with leukopenia depends on the severity of the infectious disease.

Interaction with other medicinal products. Concomitant use of metronidazole and alcohol is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use of metronidazole and busulfan is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use of metronidazole and disulfiram is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Metronidazole has no direct effect on aerobic or facultative anaerobic bacteria.

In patients undergoing hemodialysis, metronidazole and its metabolites are removed during 8 hours of hemodialysis; therefore, metronidazole should be administered immediately after hemodialysis.

Dose adjustment is not required in patients with renal insufficiency undergoing peritoneal dialysis.

Metronidazole is primarily metabolized by hepatic oxidation. Marked impairment of metronidazole clearance may occur in patients with hepatic insufficiency. Significant accumulation may occur in patients with hepatic encephalopathy, and consequently, high plasma concentrations of metronidazole may contribute to encephalopathy symptoms. Therefore, metronidazole should be used with caution in patients with hepatic encephalopathy. The daily dose should be reduced by one-third and may be administered once daily.

There is a risk of persistence of gonococcal infection after elimination of trichomoniasis.

The elimination half-life of metronidazole is not altered in renal insufficiency. Therefore, dose adjustment is not required. However, metabolites of metronidazole accumulate in such patients. The clinical significance of this is currently unknown.

Use during pregnancy or breastfeeding.

Pregnancy. Animal studies have not demonstrated teratogenic effects. Since teratogenic effects are not observed in animals, malformations in humans are not expected. According to available data, substances causing developmental malformations in humans also show teratogenic effects in animals in adequately conducted studies on two species. Numerous clinical data have not demonstrated any specific teratogenic or fetotoxic effects associated with the use of metronidazole during pregnancy. However, the absence of such risk can only be confirmed by epidemiological studies. Therefore, metronidazole should be prescribed during pregnancy only if clearly necessary.

Breastfeeding. Metronidazole is excreted in breast milk. Therefore, the use of this medicinal product should be avoided during breastfeeding.

Ability to affect reaction speed when driving vehicles or operating machinery.

Patients should be warned about the risk of dizziness, confusion, hallucinations, seizures, and visual disturbances. If such symptoms occur, patients should not drive vehicles or operate machinery.

Method of Administration and Dosage

The medication is permitted for use in the treatment of adult patients only.

Trichomonas vaginitis. Administer 1 vaginal tablet once daily for 10 days. Before insertion into the vagina, the tablet should be slightly moistened with cooled boiled water. Treatment should be carried out concurrently with oral administration of Trichopol® tablets. Treatment should not be discontinued during menstruation.

Non-specific vaginitis. Insert 1 vaginal tablet deeply into the vagina once daily for 7 days. If necessary, oral administration of Trichopol® tablets may be prescribed.

Simultaneous treatment of the patient's sexual partner is recommended, even in the absence of infection symptoms.

The maximum duration of treatment should not exceed 10 days; the number of treatment courses should not exceed 2–3 per year.

Children

The medication is contraindicated in pediatric patients.

Overdose

Cases of single-dose intake up to 12 g have been reported, occurring during suicide attempts and accidental overdoses. Ataxia, vomiting, and mild disorientation may occur. As there is no specific antidote for metronidazole, symptomatic therapy is recommended.

Adverse reactions.

Blood and lymphatic system disorders:

• agranulocytosis, neutropenia, thrombocytopenia, pancytopenia;
• leukopenia.

Metabolism and nutrition disorders:

• anorexia.

Psychiatric disorders:

• hallucinations;
• psychotic reactions with paranoia and/or delirium, which in isolated cases may be accompanied by suicidal ideation or suicide attempts (see section "Special warnings and precautions for use");
• depressive mood.

Nervous system disorders:

− peripheral sensory neuropathy;

− headache, dizziness, confusion, seizures;

• aseptic meningitis (see section "Special warnings and precautions for use");
• encephalopathy, which may be associated with changes on MRI, usually reversible. Very rare fatal cases have been reported (see section "Special warnings and precautions for use");
• subacute cerebellar syndrome (ataxia, dysarthria, gait disturbance, nystagmus, tremor) (see section "Special warnings and precautions for use").

Eye disorders:

• transient visual disturbances, such as blurred vision, diplopia, myopia, decreased visual acuity, color vision changes;
• optic neuropathy/neuritis.

Ear and labyrinth disorders:

• hearing impairment/hearing loss (including sensorineural), tinnitus.

Gastrointestinal disorders:

− mild gastrointestinal disturbances (epigastric pain, nausea, vomiting, diarrhea);

• glossitis with dry mouth, stomatitis, taste disturbances;
• cases of pancreatitis, which are reversible;
• changes in color or appearance of the tongue (fungal infection).

Hepatobiliary disorders:

• increased levels of liver enzymes (AST, ALT, alkaline phosphatase); very rare cases of acute cholestatic or mixed hepatitis and hepatocellular liver injury, sometimes with jaundice, have been reported. Isolated cases of hepatocellular failure requiring liver transplantation have been reported;
• cases of severe hepatotoxicity / acute liver failure, including fatal outcomes, have been reported shortly after initiation of systemic medicinal products containing metronidazole in patients with Cockayne syndrome (see section "Contraindications").

Skin and subcutaneous tissue disorders:

− flushing with hyperemia, pruritus, rash, which may be accompanied by sweating;

− urticaria, angioedema, anaphylactic shock (see section "Special warnings and precautions for use");

• very rare cases of acute generalized exanthematous pustulosis (see section "Special warnings and precautions for use");

− toxic epidermal necrolysis;

− fixed drug eruption;

− Stevens-Johnson syndrome.

Musculoskeletal and connective tissue disorders:

• myalgia, arthralgia.

Renal and urinary disorders:

• urine may turn reddish-brown due to the presence of water-soluble pigments, which are metabolites of metronidazole.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging.

10 tablets in a blister; 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Pharmaceutical Works «POLPHARMA» S.A.

Manufacturer's address.

19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.