Not applicable.
Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.
Carcinogenicity studies have not been conducted with Amoxival.
Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and toxicity to reproduction and development.
Carcinogenicity studies have not been conducted with amoxicillin.
Absorption
Amoxival fully dissociates in aqueous solution at physiological pH. It is rapidly and well absorbed by the oral route of administration. Following oral administration, Amoxival is approximately 70% bioavailable. The time to peak plasma concentration (Tmax) is approximately one hour.
The pharmacokinetic results for a study, in which an Amoxival dose of 250 mg three times daily was administered in the fasting state to groups of healthy volunteers are presented below.
| Cmax | Tmax * | AUC (0-24h) | T ½ |
| (μg/ml) | (h) | ((μg.h/ml) | (h) |
| 3.3 ± 1.12 | 1.5 (1.0-2.0) | 26.7 ± 4.56 | 1.36 ± 0.56 |
| *Median (range) | |||
In the range of 250 to 3000 mg the bioavailability is linear in proportion to dose (measured as Cmax and AUC). The absorption in not influenced by simultaneous food intake.
Haemodialysis can be used for elimination of Amoxival.
Distribution
About 18% of total plasma Amoxival is bound to protein and the apparent volume of distribution is around 0.3 to 0.4 l/kg.
Following intravenous administration, Amoxival has been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxival does not adequately distribute into the cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived material. Amoxival, like most penicillins, can be detected in breast milk.
Amoxival has been shown to cross the placental barrier.
Biotransformation
Amoxival is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose.
Elimination
The major route of elimination for Amoxival is via the kidney.
Amoxival has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the Amoxival is excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 mg dose of Amoxival. Various studies have found the urinary excretion to be 50-85% for Amoxival over a 24 hour period
Concomitant use of probenecid delays Amoxival excretion.
Age
The elimination half-life of Amoxival is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Gender
Following oral administration of Amoxival to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of Amoxival.
Renal impairment
The total serum clearance of Amoxival decreases proportionately with decreasing renal function.
Hepatic impairment
Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.
Absorption
Amoxicillin fully dissociates in aqueous solution at physiological pH. It is rapidly and well absorbed by the oral route of administration. Following oral administration, amoxicillin is approximately 70% bioavailable. The time to peak plasma concentration (Tmax) is approximately one hour.
The pharmacokinetic results for a study, in which an amoxicillin dose of 250 mg three times daily was administered in the fasting state to groups of healthy volunteers are presented below.
| Cmax | Tmax * | AUC (0-24h) | T ½ |
| (μg/ml) | (h) | ((μg.h/ml) | (h) |
| 3.3 ± 1.12 | 1.5 (1.0-2.0) | 26.7 ± 4.56 | 1.36 ± 0.56 |
| *Median (range) | |||
In the range 250 to 3000 mg the bioavailability is linear in proportion to dose (measured as Cmax and AUC). The absorption is not influenced by simultaneous food intake.
Haemodialysis can be used for elimination of amoxicillin.
Distribution
About 18% of total plasma amoxicillin is bound to protein and the apparent volume of distribution is around 0.3 to 0.4 l/kg.
Following intravenous administration, amoxicillin has been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.
From animal studies there is no evidence for significant tissue retention of drug-derived material. Amoxicillin, like most penicillins, can be detected in breast milk.
Amoxicillin has been shown to cross the placental barrier.
Biotransformation
Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose.
Elimination
The major route of elimination for amoxicillin is via the kidney.
Amoxicillin has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the amoxicillin is excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 mg dose of amoxicillin. Various studies have found the urinary excretion to be 50-85% for amoxicillin over a 24 hour period.
Concomitant use of probenecid delays amoxicillin excretion.
Age
The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.
Gender
Following oral administration of amoxicillin/ to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of amoxicillin.
Renal impairment
The total serum clearance of amoxicillin decreases proportionately with decreasing renal function.
Hepatic impairment
Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.
Check cap seal is intact before use.
Invert and shake bottle to loosen powder.
To prepare add 64ml of potable water and shake until all contents are dispersed
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
