Gramaxin

Gramaxin-600 is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media due to S. pneumoniae (penicillin MICs ≤ 2 mcg/mL), H. influenzae (including β-lactamase–producing strains), or M. catarrhalis (including β-lactamase–producing strains) characterized by the following risk factors:

• antibiotic exposure for acute otitis media within the preceding 3 months, and either of the following:
  • age ≤ 2 years
  • daycare attendance

NOTE: Acute otitis media due to S. pneumoniae alone can be treated with Amoxicillin (Gramaxin). Gramaxin-600 is not indicated for the treatment of acute otitis media due to S. pneumoniae with penicillin MIC ≥ 4 mcg/mL.

Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S. pneumoniae (penicillin MIC ≤ 2 mcg/mL) and the β-lactamase–producing organisms listed above.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gramaxin-600 and other antibacterial drugs, Gramaxin-600 should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Amoxicillin (Gramaxin) is an antibiotic in a group of drugs called penicillins. Amoxicillin (Gramaxin) fights bacteria in the body.

Clavulanate potassium is a form of Clavulanic Acid (Gramaxin), which is similar to penicillin. Clavulanate potassium fights bacteria that is often resistant to penicillins and other antibiotics.

The combination of Amoxicillin (Gramaxin) and clavulanate potassium is used to treat many different infections caused by bacteria, such as sinusitis, pneumonia, ear infections, bronchitis, urinary tract infections, and infections of the skin.

Amoxicillin (Gramaxin) and clavulanate potassium may also be used for purposes not listed in this medication guide.

Gramaxin-600, 600 mg/5 mL, does not contain the same amount of Clavulanic Acid (Gramaxin) (as the potassium salt) as any of the other suspensions of AUGMENTIN. Gramaxin-600 contains 42.9 mg of Clavulanic Acid (Gramaxin) per 5 mL, whereas the 200 mg/5 mL suspension of AUGMENTIN contains 28.5 mg of Clavulanic Acid (Gramaxin) per 5 mL and the 400 mg/5 mL suspension contains 57 mg of Clavulanic Acid (Gramaxin) per 5 mL. Therefore, the 200 mg/5 mL and 400 mg/5 mL suspensions of AUGMENTIN should not be substituted for Gramaxin-600, as they are not interchangeable.

Dosage

Pediatric patients 3 months and older: Based on the Amoxicillin (Gramaxin) component (600 mg/5 mL), the recommended dose of Gramaxin-600 is 90 mg/kg/day divided every 12 hours, administered for 10 days.

Pediatric patients weighing 40 kg and more: Experience with Gramaxin-600 (600 mg/5 mL formulation) in this group is not available.

Adults: Experience with Gramaxin-600 (600 mg/5 mL formulation) in adults is not available and adults who have difficulty swallowing should not be given Gramaxin-600 (600 mg/5 mL) in place of the 500-mg or 875-mg tablet of AUGMENTIN.

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

Directions for Mixing

Oral Suspension

Prepare a suspension at time of dispensing as follows: Tap bottle until all the powder flows freely. Add approximately 2/3 of the total amount of water for reconstitution and shake vigorously to suspend powder. Add remainder of the water and again shake vigorously.

Gramaxin-600 (600 mg/5 mL Suspension)

Each teaspoonful (5 mL) will contain 600 mg Amoxicillin (Gramaxin) as the trihydrate and 42.9 mg of Clavulanic Acid (Gramaxin) as the potassium salt.

NOTE: SHAKE ORAL SUSPENSION WELL BEFORE USING.

Information for the Pharmacist: For patients who wish to alter the taste of Gramaxin-600, immediately after reconstitution 1 drop of FLAVORx™ (apple, banana cream, bubble gum, cherry, or watermelon flavor) may be added for every 5 mL of Gramaxin-600. The resulting suspension is stable for 10 days under refrigeration. Other than the 5 flavors listed above, GlaxoSmithKline has not evaluated the stability of Gramaxin-600 when mixed with other flavors distributed by FLAVORx.

Administration: To minimize the potential for gastrointestinal intolerance, Gramaxin-600 should be taken at the start of a meal. Absorption of clavulanate potassium may be enhanced when Gramaxin-600 is administered at the start of a meal.

How supplied

Gramaxin-600, 600 mg/5 mL, for

Oral Suspension:

NDC 43598-003-69

Hypersensitivity to the Amoxicillin (Gramaxin)/clavulanate potassium to any of the penicillins or to any of the excipients of Gramaxin.

History of a severe immediate hypersensitivity reaction (eg, anaphylaxis) to another β-lactam agent (eg, a cephalosporin, carbapenem or monobactam).

History of cholestatic jaundice/hepatic dysfunction due to Amoxicillin (Gramaxin)/Clavulanic Acid (Gramaxin).

See also:
What other drugs will affect Gramaxin?

Administration of probenecid prior to dosing results in marked increase in the mean serum concentrations of Amoxicillin (Gramaxin). Probenecid decreases the renal tubular secretion of Amoxicillin (Gramaxin), but does not affect Clavulanic Acid (Gramaxin) excretion. Concurrent use with Gramaxin may result in increased and prolonged blood levels of Amoxicillin (Gramaxin) but not of Clavulanic Acid (Gramaxin).

When Amoxicillin (Gramaxin) and warfarin are taken concomitantly, the INR can be altered.

Interaction of Gramaxin with coumarin or indandione-derivative anticoagulants, heparin, NSAIDs especially aspirin, other platelet aggregation inhibitors or thrombolytic agents may be clinically significant.

Gramaxin may decrease the efficacy of oestrogen-containing oral contraceptives. Patients should be warned accordingly. The simultaneous use of Amoxicillin (Gramaxin) and an oral contraceptive might be expected to cause breakthrough bleeding or pregnancy on rare occasions because of reduced absorption owing to diarrhea, on the basis of experience with ampicillin.

The concurrent administration of allopurinol and ampicillin substantially increases the incidence of rashes in patients receiving both agents as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricaemia present in these patients. There are no data on Amoxicillin (Gramaxin)/clavulanate combination and allopurinol administered concurrently.

No information is available about the concurrent use of Gramaxin and alcohol. However, the ingestion of alcohol whilst being treated with some other β-lactam antibiotics has precipitated a disulfiram (Antabuse)-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with Gramaxin.

Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugate oestriol, oestrio-glucuronide, conjugated oestrone and oestradiol has been noted. This effect may also occur with Amoxicillin (Gramaxin) and therefore, Gramaxin.

The use of this antibiotic may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible, to demonstrate the appropriateness of therapy.

See also:
What are the possible side effects of Gramaxin?

The most frequently reported adverse effects were diarrhoea, nausea, vomiting, abdominal pain, skin rashes, urticaria and erythema multiforme, vaginitis, abnormal taste, headache, dizziness, tiredness and hot flushes. The incidence and severity of adverse effects, particularly nausea and diarrhoea, increased with the higher recommended dose and can be minimised by administering the agent at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these GI symptoms occur and a higher concentration of Amoxicillin (Gramaxin) is required, consideration should be given to administering the additional Amoxicillin (Gramaxin) separately.

Hepatitis and cholestatic jaundice have been reported with the combination of Amoxicillin (Gramaxin) and Clavulanic Acid (Gramaxin); the Clavulanic Acid (Gramaxin) component has been implicated. The events associated with Gramaxin may be severe and occur predominantly in adult or elderly patients. Signs and symptoms usually occur during or shortly after treatment, but in some cases may not become apparent until several weeks after treatment has ceased. The hepatic events are usually reversible. However, in extremely rare circumstances, death has been reported. These have almost always been cases associated with serious underlying disease or concomitant medication.

A moderate rise in aspartate transaminase and/or alanine transaminase has been noted in patients treated with Gramaxin, the significance of these findings is unknown.

The following adverse reactions have been reported for ampicillin class antibiotics and may occur with Gramaxin.

Gastrointestinal: Gastritis, stomatitis, glossitis, black hairy tongue, enterocolitis and pseudomembranous colitis. If GI reactions are evident, they may be reduced by taking Gramaxin at the start of a meal.

Amoxicillin (Gramaxin) causes hypersensitivity reactions similar to those induced by penicillin G and ampicillin, including rashes and fever. The incidence of these reaction is probably no higher than with other penicillins. Sensitivity reactions are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever or uticaria. Hypersensitivity reactions include skin rashes, urticaria, erythema multiforme, rare cases of Stevens-Johnson syndrome and less frequently exfoliative dermatitis and toxic epidermal necrolysis have been reported. Whenever such reactions occur, Gramaxin should be discontinued. Serious and occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillin.

Haematopoietic and Lymphatic: Anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leucopenia and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in patients treated with Gramaxin. Prolongation of bleeding time and prothrombin time have also been reported less frequently.

Amoxicillin (Gramaxin) alone or in combination with Clavulanic Acid (Gramaxin) has been associated with acute hepatic dysfunction. The incidence rate (95% confidence intervals) were 1.7 (1.1-2.7) (Amoxicillin (Gramaxin)-Clavulanic Acid (Gramaxin)) and 0.3 (0.2-0.5)/10,000 prescriptions (Amoxicillin (Gramaxin) alone). Risks were increased in patients receiving >1 course and in older recipients.

Central Nervous System: Reversible hyperactivity, agitation, anxiety, insomnia, confusion, behavioural changes and/or dizziness have also been reported. Depression, seizures or hallucinations.

Each film-coated tablet contains Amoxicillin (Gramaxin) trihydrate equivalent to Amoxicillin (Gramaxin) 500 mg, and potassium clavulanate equivalent to Clavulanic Acid (Gramaxin) 125 mg, respectively.

Each vial contains Amoxicillin (Gramaxin) sodium equivalent to Amoxicillin (Gramaxin) 1000 mg and clavulanate potassium equivalent to Clavulanic Acid (Gramaxin) 200 mg, respectively.

Gramaxin tablets also contains the following excipients: Microcrystalline cellulose, sodium starch glycolate, anhydrous colloidal silica, povidone (K30), eudragit E 100, isopropyl alcohol, magnesium stearate, white opadryl 03B58965, PEG400, methylene chloride.

Gramaxin is an antibacterial combination consisting of the semi-synthetic antibiotic Amoxicillin (Gramaxin) and the β-lactamase inhibitor, clavulanate potassium (the potassium salt of Clavulanic Acid (Gramaxin)). Amoxicillin (Gramaxin) is an analog of ampicillin, derived from the basic penicillin nucleus, 6-aminopenicillanic acid. Its molecular formula is C₁₆H₁₉N₃0₅S3H₂0 and the molecular weight is 419.46. Chemically, Amoxicillin (Gramaxin) is (2S, 5R, 6R)-6-[(R)-(-)-2-Amino-2-(p-hydroxyphenyl) acetamido]-3, 3-dimethyl-7-oxo-4-1-azabicyclo[3.2.1] heptane-2-carboxylic acid trihydrate.

Amoxicillin (Gramaxin): Clavulanic Acid (Gramaxin) is produced by the fermentation of Streptomyces clavuligerus. It is a β-lactam structurally related to the penicillins and possesses the ability to inactivate a wide variety of β-lactamases by blocking the active sites of these enzymes. Clavulanic Acid (Gramaxin) is particularly active against the clinically important plasmid-mediated β-lactamases frequently responsible for transferred drug resistance to penicillins and cephalosporins. The clavulanate potassium molecular formula is C₈H₈KN0₅ and the molecular weight is 237.25. Chemically, clavulanate potassium is potassium (Z)-(2R, 5R)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]-heptane-2-carboxylate.