Anazol is indicated in the prophylaxis and treatment of infections in which anaerobic bacteria have been identified or are suspected to be the cause.

Anazol is active against a wide range of pathogenic micro-organisms notably species of Bacteroides, Fusobacteria, Clostridia, Eubacteria, anaerobic cocci and Gardnerella vaginalis.

It is also active against Trichomonas, Entamoeba histolytica, Giardia lamblia and Balantidium coli. 

Anazol is indicated in adults and children for the following indications:

• The prevention of post-operative infections due to anaerobic bacteria, particularly species of Bacteroides and anaerobic streptococci;
• The treatment of septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis, and post- operative wound infections from which pathogenic anaerobes have been isolated;
• Urogenital trichomoniasis in the female (trichomonal vaginitis) and in the male;
• Bacterial vaginosis (also known as non-specific vaginitis, anaerobic vaginosis or Gardnerella vaginitis);
• All forms of amoebiasis (intestinal and extra-intestinal disease and that of symptomless cyst passers);
• Giardiasis;
• Acute ulcerative gingivitis; 
• Anaerobically-infected leg ulcers and pressure sores;
• Acute dental infections (e.g. acute pericoronitis and acute apical infections).   

Considerations should be given to official guidance on the appropriate use of antibacterial agents. 

(See Section 5.2 Pharmacokinetic properties-Special patient population) Oral route of administration.
Anazol tablets should be swallowed with water (not chewed). It is recommended that the tablets be taken during or after a meal.

• Prophylaxis against anaerobic infection: Chiefly in the context of abdominal (especially colorectal) and gynaecological surgery.

- Adults: 500 mg 8 hourly during 24 hours immediately preceding operation followed by postoperative intravenous or rectal administration until the patient is able to take tablets. 
- Children
Children < 12 years: 20 to 30 mg/kg as a single dose given 1 to 2 hours before surgery.
Newborns with a gestation age < 40 weeks: 10 mg/kg body weight as a single dose before operation.

• Anaerobic infections: The duration of a course of Anazol treatment is about 7 days but it will depend upon the seriousness of the patient's condition as assessed clinically and bacteriologically.
• Treatment of established anaerobic infection

- Adults: 750 mg followed by 500 mg 8 hourly.
- Children
Children > 8 weeks to 12 years of age: The usual daily dose is 20 to 30mg/kg/day as a single dose or divided into 7.5 mg/kg every 8 hours. The daily dose may be increased to 40 mg/kg, depending on the severity of the infection. Duration of treatment is usually 7 days.
Children < 8 weeks of age: 15 mg/kg as a single dose daily or divided into 7.5 mg/kg every 12 hours. In newborns with a gestation age < 40 weeks, accumulation of metronidazole can occur during the first week of life, therefore the concentrations of metronidazole in serum should preferable be monitored after a few days therapy. 

Protozoal and other infections 

Children and infants weighing less than 10 kg should receive proportionally smaller dosage.

Elderly: Metronidazole is well tolerated by the elderly but a pharmacokinetic study suggests cautious use of high dosage regimens in this age group.

• Eradication of Helicobacter pylori in pediatric patients: As a part of a combination therapy, 20 mg/kg/day not to exceed 500 mg twice daily for 7 to 14 days. Official guidelines should be consulted before initiating therapy

Regular clinical and laboratory monitoring (especially leucocyte count) are advised if administration of Anazol for more than 10 days is considered to be necessary and patients should be monitored for adverse reactions such as peripheral or central neuropathy (such as paraesthesia, ataxia, dizziness, convulsive seizures).

Metronidazole should be used with caution in patients with active or chronic severe peripheral and central nervous system disease due to the risk of neurological aggravation.

There is a possibility that after Trichomonas vaginalis has been eliminated a gonococcal infection might persist. 

The elimination half-life of metronidazole remains unchanged in the presence of renal failure. The dosage of metronidazole therefore needs no reduction. Such patients however retain the metabolites of metronidazole. The clinical significance of this is not known at present. 

In patients undergoing haemodialysis metronidazole and metabolites are efficiently removed during an eight hour period of dialysis. Metronidazole should therefore be re- administered immediately after haemodialysis. 

No routine adjustment in the dosage of Anazol need be made in patients with renal failure undergoing intermittent peritoneal dialysis (IDP) or continuous ambulatory peritoneal dialysis (CAPD). 

Metronidazole is mainly metabolised by hepatic oxidation. Substantial impairment of metronidazole clearance may occur in the presence of advanced hepatic insufficiency. Significant cumulation may occur in patients with hepatic encephalopathy and the resulting high plasma concentrations of metronidazole may contribute to the symptoms of the encephalopathy. Anazol should therefore, be administered with caution to patients with hepatic encephalopathy. The daily dosage should be reduced to one third and may be administered once daily. 

Patients should be warned that metronidazole may darken urine. 

Due to inadequate evidence on the mutagenicity risk in humans (See Section 5.3. Pre- clinical safety studies), the use of Anazol for longer treatment than usually required should be carefully considered.

Patients should be advised not to take alcohol during metronidazole therapy and for at least 48 hours afterwards because of the possibility of a disulfiram-like (antabuse effect) reaction. Psychotic reactions have been reported in patients who were using metronidazole and disulfiram concurrently.

Some potentiation of anticoagulant therapy has been reported when metronidazole has been used with the warfarin type oral anticoagulants. Dosage of the latter may require reducing. Prothrombin times should be monitored. There is no interaction with heparin.

Lithium retention accompanied by evidence of possible renal damage has been reported in patients treated simultaneously with lithium and metronidazole. Lithium treatment should be tapered or withdrawn before administering metronidazole. Plasma concentrations of lithium, creatinine and electrolytes should be monitored in patients under treatment with lithium while they receive metronidazole. 

Patients receiving phenobarbital or phenytoin metabolise metronidazole at a much greater rate than normally, reducing the half-life to approximately 3 hours.

Metronidazole reduces the clearance of 5 fluorouracil and can therefore result in increased toxicity of 5 fluorouracil. 

Patients receiving ciclosporin are at risk of elevated ciclosporin serum levels. Serum ciclosporin and serum creatinine should be closely monitored when coadministration is necessary. 

Plasma levels of busulfan may be increased by metronidazole which may lead to severe busulfan toxicity.

There is inadequate evidence of the safety of metronidazole in pregnancy but it has been in wide use for many years without apparent ill consequence. Nevertheless Anazol, like other medicines, should not be given during pregnancy or during lactation unless the physician considers it essential; in these circumstances the short, high-dosage regimens are not recommended.

Patients should be warned about the potential for drowsiness, dizziness, confusion, hallucinations, convulsions or transient visual disorders, and advised not to drive or operate machinery if these symptoms occur.

The following categories were used for the classification of undesirable effects: very common (≥1/10), common (1-10/100), uncommon (1-10/1000), rare (1-10/10,000), very rare (≤1/10,000), not known (cannot be estimated from the available data).

Serious adverse reactions occur rarely with standard recommended regimens. Clinicians who contemplate continuous therapy for the relief of chronic conditions, for periods longer than those recommended, are advised to consider the possible therapeutic benefit against the risk of peripheral neuropathy. 

Reporting of suspected adverse reactions

• Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.
Toll free phone: 8002490000
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc

• Other GCC States: Please contact the relevant competent authority.

Single oral doses of metronidazole, up to 12 g have been reported in suicide attempts and accidental overdoses. Symptoms were limited to vomiting, ataxia and slight disorientation. There is no specific antidote for metronidazole overdosage. In cases of suspected massive overdose, symptomatic and supportive treatment should be instituted.

• Pharmacotherapeutic group: Antibacterials for systemic use, ATC code: J01X D01. 
• Metronidazole has antiprotozoal and antibacterial actions and is effective against Trichomonas vaginalis and other protozoa including Entamoeba histolytica and Giardia lamblia and against anaerobic bacteria. 

It is readily absorbed from the gastro-intestinal tract and widely distributed in body tissues. Half-life in plasma is about 8-10 hours. About 10% is bound to plasma proteins. It penetrates well into body tissues and fluids, including vaginal secretions, seminal fluid, saliva and breast milk. Therapeutic concentrations are also achieved in cerebrospinal fluid. 

Unchanged metronidazole and several metabolites are excreted in the urine, the liver is the main site of metabolism and the major metabolites are as a result of side chain oxidation, forming glucuronides

• Carcinogenicity: Metronidazole has been shown to be carcinogenic in the mouse and in the rat following chronic oral administration however similar studies in the hamster have given negative results. Epidemiological studies have provided no clear evidence of an increased carcinogenic risk in humans.
• Mutagenicity: Metronidazole has been shown to be mutagenic in bacteria in vitro. In studies conducted in mammalian cells in vitro as well as in rodent or humans in vivo, there was inadequate evidence of a mutagenic effect of metronidazole, with some studies reporting mutagenic effects, while others studies were negative.

- Xanthan gum;
- Methyl paraben;
- Propyl paraben;
- Antifoam emulsion;
- Sugar;
- Sorbitol 70 liquid;
- Glycerin;
- Tangerine liquid flavor;
- Glicamil mono ammonium glycerhizinate;
- Purified water. 

Not applicable.

Store below 30°C.

125 ml amber plastic bottle with white 28 mm CRC cap with plug.

Shake the bottle well before use.

If a dose of fewer than 5ml is required, the suspension should be administered using an oral dosing device.