What Are the Most Common Side Effects of Metronidazole?

Metronidazole sustained-release tablets are indicated for the treatment of bacterial vaginosis in women.

Metronidazole sustained-release tablets are indicated for the treatment of bacterial vaginosis in women.

Drug Name

Metronidazole sustained-release tablets

Drug type

prescription

Use classification

Synthetic antibacterials

Metronidazole sustained-release tablets ingredients

The active ingredient of this product is metronidazole, whose chemical name is 2-methyl-5-nitroimidazole-1-ethanol.
Its structural formula is:

Molecular formula: C ₆ H ₉ N ₃ O ₃
Molecular weight: 171.16

Metronidazole sustained-release tablets

This product is a light yellow oval film-coated tablet, which is white after removing the coating.

Metronidazole sustained-release tablets

Treatment of bacterial vaginosis in women.

Metronidazole sustained-release tablets specifications

750mg / tablet.

Metronidazole sustained-release tablets

Oral, 750mg (1 tablet) once a day, once a day for seven days, seven days as a course of treatment. Metronidazole sustained-release tablets should be swallowed whole on an empty stomach at least 1 hour before or 2 hours after a meal. Taking on an empty stomach can maintain the best sustained release properties of this product.

Metronidazole sustained-release tablets

In two multi-center clinical studies, 270 patients took metronidazole sustained-release tablets orally, 750 mg once, once a day, for 7 consecutive days. 287 patients were administered intravaginally with control drugs, once a day for 7 days.
The vast majority of adverse events were mild to moderate, with 10% of patients with metronidazole complaining of headache being severe, and less than 2% of patients with nausea being severe. 9% complained of oral metal odor.
Vulvar and vaginal candidiasis are caused by various antibacterial treatments. In this multicenter clinical trial, there was no statistically significant difference in the incidence of yeast vaginitis between the test group and the control group.
Side effects that occurred at a rate of 2% in the treatment group were as follows (whether or not related to treatment).

The following adverse reactions have also been reported in metronidazole treatment:
Central nervous system: Two serious side effects reported in patients treated with metronidazole are seizures and peripheral neuritis, the latter manifested mainly as numbness and paresthesia in the limbs. Because persistent peripheral neuritis has been reported in some patients who have been treated with metronidazole for long periods of time, these side effects should be specifically noted to patients, and any neurological symptoms should be discontinued immediately and reported to a doctor. In addition, patients also reported dizziness, dizziness, ataxia, irritability, insanity, depression, weakness, and insomnia.
Gastrointestinal tract: The most common adverse reactions are related to the gastrointestinal tract. About 12% of patients have significant nausea, sometimes accompanied by headache, anorexia, occasional vomiting, diarrhea, upper abdominal pain and upper abdominal cramping pain. Constipation has also been reported. Thick tongue coating, glossitis, and stomatitis also occur. This may be related to the sudden proliferation of Candida in the treatment process. There have been few reports of pancreatitis during drug withdrawal.
Hematopoietic system: reversible leukocytopenia and rare reversible thrombocytopenia.
Cardiovascular system: T wave is low on ECG.
Allergic symptoms: hives, erythema, facial flushing, nasal congestion, dry mouth, vagina or vulva, fever.
Kidney: symptoms of dysuria, cystitis, polyuria, urinary incontinence; and pelvic pressure. About one in 100,000 cases of dark urine was reported. Although it has not yet been determined, the pigment is almost certainly a metabolite of metronidazole, which currently does not appear to have clinical significance.
Other: Other symptoms include vaginal candidiasis, difficulty in intercourse, decreased libido, proctitis, and transient joint pain similar to serum sickness. Patients receiving metronidazole can experience abdominal pain, nausea, vomiting, facial flushing, or headache if they drink alcohol. Changes in the taste of alcoholic beverages have also been reported.
Patients with Crohn's disease have an increased incidence of gastrointestinal and parenteral tumors. Medical literature reports that breast cancer and colon cancer have been reported in Crohn's patients taking metronidazole in large doses for a long time. Crohn's disease is not a common indication for metronidazole sustained-release tablets.

Metronidazole sustained-release tablets contraindications

This product is prohibited in the following situations:
(1) Those who are allergic to metronidazole or other nitroimidazole derivatives.
(2) Women within three months of pregnancy.

Precautions for metronidazole sustained-release tablets

(1) Metronidazole is slowly metabolized in patients with severe liver disease, eventually leading to the accumulation of metronidazole and its metabolites in the plasma. Therefore, the dosage in these patients should be lower than the conventional dose, and medication should be used with caution.
(2) The symptoms of candidiasis can be aggravated during metronidazole treatment and need to be treated with antifungal drugs.
(3) Avoid alcoholic beverages during the medication and within three days after the medication.
(4) Patients with blood abnormalities or history of blood abnormalities should be cautiously administered.
(5) Mild leukopenia can be seen during metronidazole treatment. Leukocyte count and classification should be performed before and after repeated medication.
(6) Metronidazole should be discontinued as soon as abnormal neurological symptoms appear. Patients with central nervous system disease should be treated with caution.

Metronidazole sustained-release tablets for pregnant and lactating women

The pregnant mice were given metronidazole by gavage (60mg / per body surface area, approximately 10% of the clinical dosage), once a day, without fetal toxicity. However, intrauterine deaths have occurred in studies of single-dose intraperitoneal administration of animals, and it is not certain whether it is related to drug administration. Due to the lack of in-depth comparative studies on pregnant women, and animal studies do not always predict human responses, metronidazole is a carcinogen for rodents, and metronidazole can quickly enter the fetal circulation through the placental barrier. Avoid use in the third trimester of pregnancy.
Because metronidazole can be secreted through milk, the concentration is similar to that in plasma, and because the incidence of tumors increases in mice and rats after using metronidazole, the decision to stop breastfeeding or stop should be based on the importance of the drug to the mother. Medication.

Metronidazole sustained-release tablets for children

The safety of metronidazole sustained-release formulations in pediatric patients has not been determined.

Metronidazole sustained-release tablets for elderly

Decreased renal function does not change the pharmacokinetics of metronidazole in a single dose. However, the plasma clearance of metronidazole decreased in patients with decreased liver function. The pharmacokinetics of metronidazole in elderly patients may change, so it is necessary for elderly patients to monitor blood levels to adjust metronidazole dosage.

Metronidazole sustained-release tablets drug interactions

(1) Metronidazole can enhance the anticoagulant effect of warfarin and other oral coumarin anticoagulants, leading to prolonged prothrombin time.
(2) Simultaneously applying drugs that induce liver microsomal enzymes, such as phenytoin or phenobarbital, can accelerate metronidazole clearance and cause its plasma concentration to decrease. There are reports suggesting that metronidazole will reduce the clearance of phenytoin.
(3) At the same time, drugs that reduce liver microsomal enzymes, such as cimetidine, will reduce the plasma clearance of metronidazole and prolong the half-life.
(4) For patients receiving large doses of lithium, the short-term use of metronidazole will increase serum lithium, and some cases will have symptoms of lithium poisoning. A few days after metronidazole treatment, serum lithium and serum creatinine levels need to be measured to monitor elevated serum lithium concentrations that may occur before clinical symptoms of lithium poisoning appear.
(5) Psychotic symptoms have been reported in patients with alcohol abuse who use metronidazole and disulfiram at the same time. Patients who have taken disulfiram in the last two weeks should avoid metronidazole. Avoid contact with alcohol during metronidazole treatment and within three days after discontinuation, otherwise abdominal cramps, nausea, vomiting, headache and facial flushing may occur.
(6) Metronidazole can affect the determination of certain blood biochemical values, such as aspartate aminotransferase (AST, SGOT aspartate aminotransferase), alanine aminotransferase (ALT, SGPT aspartate aminotransferase), lactate dehydrogenase (LDH ), Triglyceride and hexokinase glucose, which can make the measured value 0. All affected tests are related to enzyme coupling during the coenzyme redox process (NAD = NADH). The influencing factors are due to similar absorption peaks of reduced nicotinamide dinucleotide (340nm) and metronidazole (322nm) at pH 7.

Metronidazole sustained-release tablets overdose

In a case of suicide attempt or accidental overdose, a single oral metronidazole up to 15 g has been reported. Symptoms include nausea, vomiting and ataxia. Oral metronidazole has been studied as a radiosensitizer in the treatment of malignant tumors. The next day, 6g-10.4g, for 5-7 days, reports of neurotoxicity including peripheral neuritis and seizures.
Treatment: Metronidazole overdose has no specific antidote; therefore, treatment measures include symptomatic treatment and supportive treatment.

Metronidazole sustained-release tablets pharmacology and toxicology

1 Pharmacodynamics Metronidazole is a synthetic oral antiprotozoal and antibacterial drug.
Metronidazole may exert antibacterial activity in an anaerobic environment through the following mechanism: After the drug enters the body, it is affected by intracellular ion transporters to form a concentration gradient that promotes drug transport into the cell. The drug forms free radicals in the cell, which in turn interacts with the intracellular components and ultimately causes the death of the microorganism.
In vitro tests have confirmed that when the minimum bacteriostatic concentration (MIC) of metronidazole is 8g / ml, it can fight against the following most (90%) microorganisms. However, the safety and effectiveness of metronidazole in the treatment of clinical infections caused by these microorganisms have not been established in adequate and well-controlled clinical trials.
Gram-positive anaerobic bacteria: Clostridium, Eubacteria, Pneumococcus, Digestive Streptococcus. Gram-negative anaerobic bacteria: Bacteroides fragilis [model species, Bacteroides diphtheriae, B. ovale, B. polymorpha, B. ordinaryis, Prevotella (two-way Prevotella, Prevotella lisei, Prevotella saccharolyticus)], Porphyromonas, Clostridium.
Parasitic protozoa: amoeba, trichomoniasis.
Metronidazole has little antibacterial activity against clinically relevant facultative anaerobic bacteria or other obligate aerobic bacteria isolated from the vagina.
2 Clinical studies Bacterial vaginosis is a clinical syndrome that occurs when the normal dominant lactic acid flora is replaced by other microorganisms, including Gardnerella vaginalis, Campylobacter, Mycoplasma, and anaerobic bacteria (digestive streptococci and Bacteroides) Genus).
Two randomized, multicenter, blinded (investigator's) controlled studies of metronidazole were performed in patients with bacterial vaginosis. 557 patients with vaginitis were randomly divided into a metronidazole treatment group (once a day for seven days) (n = 270) and a 2% clindamycin vaginal ointment treatment group (on a full applicator, about 5g, once a day for 7 days) ) (N = 287).
Finally, the clinical efficacy of the primary endpoint efficacy indicators of each treatment method was evaluated 28-32 days after the end of treatment. Clinical cure was defined as normal vaginal pH (4.5), no odor, and no abnormalities on cytology.
The results are shown in the table below:

Compared with the 2% clindamycin vaginal ointment group in the metronidazole treatment group, the patient's vaginal PH value recovered faster after the former treatment, and the clinical cure rate was higher after 1 month of treatment. Similarly, compared with the 2% clindamycin vaginal ointment group in the metronidazole treatment group, the vaginal dominant lactic acid flora was recovered in the majority of patients one month after the former treatment, and the two groups were 74% and 63%, respectively.
3 Toxicology (1) Teratogenicity: The teratogenicity of metronidazole, which is 6 times the maximum recommended human dose (mg / m ² ), was performed in mice.
(2) Carcinogenic and mutagenic effects: Six studies in mice have found lung tumors, including an intermittent dosing study (once every four weeks). Male mice were administered orally at 1500 mg / m ² and the incidence of liver malignancies increased. This dose is approximately three times the clinically recommended dose. Mice have increased incidence of malignant lymphoma and lung tumors throughout their lives (based on published data). Compared with the control group, the incidence of breast tumors and liver tumors was increased in female mice after oral metronidazole. Carcinogenicity studies in rats have been negative. Metronidazole in vitro studies including Ames test showed mutagenic effects. Studies in mammals have found no genetic damage.

Pharmacokinetics of metronidazole sustained-release tablets

Twenty-four healthy adult women of 28.8 ± 8.8 years old were given 750 mg metronidazole sustained-release tablets orally once a day under fasting and fasting conditions.

Compared with the fasting state, the absorption rate of metronidazole sustained-release tablets increased due to the change of the sustained-release characteristics under the condition of eating.
Metronidazole has a similar distribution in vivo when administered orally or intravenously. The average elimination half-life of this product in healthy people is 8 hours. 60% -80% of metronidazole and its metabolites were eliminated by urine, and 6% -15% were eliminated by feces. Metabolites appearing in urine are mainly oxidized side chains [1- (-hydroxyethyl) -2-hydroxymethyl-5-nitroimidazole and 2-methyl-5-nitroimidazole-1-acetic acid] and The glucuronide conjugate, the original drug accounts for about 20% of the total drug in the urine. Kidney clearance is about 10 ml / min / 1.73 square meters.
There was no significant change in the pharmacokinetics of a single oral metronidazole in patients with renal insufficiency. However, the plasma clearance of metronidazole in patients with liver dysfunction decreases.

Metronidazole sustained-release tablets

Shaded and sealed.

Metronidazole sustained-release tablets packaging

Blister packs; (1) 7 tablets / plate, 1 plate / box;
(2) 7 pieces / plate, 2 plates / box.

Metronidazole sustained-release tablets

Tentative 2 years ^[1]