Ampicillin capsules 500

(i) ROUTE OF ADMINISTRATION

Oral

DOSAGE AND ADMINISTRATION
Adults :250 -500 mg every 6 hourly.
Children 50-100 mg per kg body weight per day given in 4 divided doses.
In severe infections doses may be increased or high doses administered parenterally. HEALTH 2000 AmpicillIn 500 mg Capsules should be taken 30 minutes to 1 hour before meals. In patients with renal impairment dosage may be reduced if required.

(ii) THERAPEUTIC / DIAGNOSTIC CLAIMS

RESPIRATORY TRACT INFECTIONS
Pharyngitis, laryngitis, tonsillitis, sinusitis, acute and chronic bronchitis, pneumonia, bronchopneumonia, lung abscess, bronchiectasis, otitis media.

GENITOURINARY TRACT INFECTIONS
Urethritis, cystitia, pyelonephritis, prostatitis, salpingitis, salpingooophoritis, orchitis, gonorrhoea, chancroid.

SKIN AND SOFT TISSUE INFECTIONS
Abscesses, carbuncles, obstetrical infections, boils, wound infections, pyoderma, cellulitis, impetigo, erysipelas.

ENTERIC INFECTIONS
Bacterial diarrhoea, bacillary dysentery, shigellosis, salmonellosis, typhoid and
paratyphoid fevers and carriers, cholecystitis and cholangitis.

Helicobacter pylori INFECTIONS
In acid-peptic disorders.

DENTAL INFECTIONS
Post orosurgical and periodontal procedures. Bacterial infections of the mouth, throat and mucositis.

SERIOUS INFECTIONS
Bacterial meningitis, bacterial septicaemia.
Treatment and prevention of bacterial endocarditis.
SURGICAL INFECTIONS
Dosage depends on the severity of the infection and sensitivity of the pathogen.

(iii) DESCRIPTION OF DOSAGE FORM

Ampicillin trihydrate is a semi synthetic penicillin which exerts its bacterial action by inhibition of cell wall synthesis. It acts against a broadspectrum of gram-positive and gram-negative microorganisms.

(iv) CONTRAINDICATIONS

Hypersensitivity reactions to penicillins

WARNING AND PRECAUTIONS
DRUG INTERACTIONS
Allopurinol: A significant increase in skin rashes is observed when allopurinol and ampicillin are given concurrently. A similar interaction can occur with ampicillin. Bacteriostafic drugs like chloramphenicol, erythromycin and tetracyclines may reduce the bactericidal action of ampicilin.

PREGNANCY
The drug can be used safely throughout pregnancy at the normal adult doses.

NURSING MOTHERS
Ampicillin is secreted into breast milk in small amounts. The potential risk is for sensitisation and skin rash in the child.

IN IMPAIRED RENAL FUNCTION
The dosage should be modified in patients with severe renal impairment, by increasing the intervals between dosage. With a creatinine clearance between 10 and 50 ml/min. The dosing interval can be upto 12 hours and if the clearance is less than 10 ml/min. The interval can be 16 hours.

OTHERS
Serious and occasionally fatal anaphylactoid reactions have been reported in patients taking penicillins. Though such reactions are more common with parenteral therapy, they have occurred with oral penicillins also. Before prescribing penicillins, patients or relatives should be questioned about any previous allergic reactions to penicillins, cephalosporins or other allergens. Ampicillin should be withdrawn it any allergic reaction occurs and appropriate therapy instituted.
Crosssensitivity occurs among penicillins and cephalosporins. Ampicillin should preferably not be given to patients with infective mononucleosis because of greater occurrence of rash in such patients.
(v) SIDE EFFECTS
As with penicillins, adverse reactions to ampicillin are generally those related to allergic response. These are more common in patients with a previous history of penicillin allergy or asthma, hay fever or urticaria. Skin reactions are the commonest allergic reactions. Nausea, vomiting and diarrhoea are less common with ampicillin.
Reversible hyperactivity, agitation, anxiety, insomnia, confusion, behavioural changes and dizziness have been reported rarely.

(vi) TOXIC EFFECTS

TERATOGENICITY
A teratogenicity study in rats with sodium chlorate
Rats, 24/dose group, were given sodium chlorate, 100% purity, at 0 (distilled water), 10, 100 or 1000 mg/kg/day by oral gavage in 5 ml/kg, days 6 - 15 of gestation. No treatment-related effects were reported on body weight, food consumption, clinical signs or developmental parameters. Maternal and developmental NOEL = 1000 mg/kg/day. No adverse effects. ACCEPTABLE.

CARCINOGENICITY & MUTAGENICITY

Carcinogenesis studies of ampicillin trihydrate (97%-99% pure) were conducted by administering the chemical in corn oil by gavage to groups of 50 F344/N rats and 50 B6C3F1 mice of each sex, 5 days per week for 103 weeks. Male and female rats received doses of 0, 750, or 1,500 mg/kg, and male and female mice received doses of 0, 1,500, or 3,000 mg/kg. Doses selected for the 2-year studies were based on the lack of body weight effects and histopathologic effects at 2,400 mg/kg in the 14-day studies and 3,000 mg/kg in the 13-week studies. Clinical signs in the 13-week studies included diarrhea at 3,000 mg/kg in male and female rats and male mice. Corn oil suspensions containing more than 300 mg ampicillin trihydrate/ml were too viscous to be administered by gavage; therefore, a high dose of 1,500 mg/kg was selected for rats and a high dose of 3,000 mg/kg was selected for mice.
During the 2-year studies, mean body weights of male and female rats were similar to or slightly increased over those of the corresponding vehicle control groups. Mean body weights of low dose and high dose male mice were similar to those of the corresponding vehicle group during year 1 of the study but were slightly below those of the vehicle control group during the last half of the study. Mean body weights of low dose and high dose female mice were greater than those of the vehicle controls throughout most of the study. No significant differences in survival were observed in groups of rats or mice of either sex. Clinical signs observed in dosed rats included diarrhea, excessive urination, and chromodacryorrhea and in dosed mice included increased salivation and decreased activity.
In male rats, administration of ampicillin trihydrate was associated with an increased incidence of mononuclear cell leukemia (vehicle control, 5/50; low dose, 14/50; high dose, 13/50). Malignant lymphomas were observed in one additional vehicle control male rat and two low dose male rats. Lymphocytic leukemia was seen in one high dose rat. High dose male rats showed increased incidences of pheochromocytomas of the adrenal gland medulla (13/50; 12/50; 23/49). Malignant pheochromocytomas were observed in 1/50 vehicle control, 5/50 low dose, and 1/49 high dose male rats. The incidence of adrenal gland medullary hyperplasia was not increased in male rats (14/50; 10/50; 8/49). There were increased incidences of C-cellhyperplasia of the thyroid gland in low dose male and high dose female rats. High dose male rats showed increased incidences of hyperkeratosis and acanthosis of the forestomach.
In male and female mice, ampicillin trihydrate administration was associated with increased incidences of forestomach lesions, including ulcers, inflammation, hyperkeratosis, acanthosis, and evidence of fungal infection.
Ampicillin trihydrate was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 in the presence or absence of Aroclor 1254-induced male Syrian hamster or male Sprague-Dawley rat liver S9 when tested according to preincubation protocol. Ampicillin trihydrate was not mutagenic in L5178Y mouse lymphoma cells with or without metabolic activation. Ampicillin trihydrate did not cause chromosomal aberrations or sister-chromatid exchanges in Chinese hamster ovary cells with or without metabolic activation.
An audit was conducted for these 2-year studies. Animal/carcass identification discrepancies were observed in rats and mice. The most common findings were the failure to clip some toes in rats and opened ear holes in mice. A review of the inlife data (including body weights, clinical observations, and dosing records) indicated that animals had not been interchanged among groups. The data are considered adequate to support the conclusions.
Under the conditions of these 2-year gavage studies, there was equivocal evidence of carcinogenicity of ampicillin trihydrate for male F344/N rats as shown by increased incidences of pheochromocytomas of the adrenal medulla and by marginally increased incidences of mononuclear cell leukemia. There was no evidence of carcinogenicity for female F344/N rats receiving 750 or 1,500 mg/kg or for male and female B6C3F1 mice receiving 1,500 or 3,000 mg/kg per day. Nonneoplastic lesions of the forestomach were seen in male rats and male and female mice