Amisine Actions

• Actions of Amisine in details
• Amisine administration
• Amisine pharmacology
• Amisine reviews

Actions of Amisine in details

Pharmacology: Amisine is bactericidal in action. It appears to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.

Microbiology: Gram-Negative: Amisine is active in vitro against Pseudomonas sp, Escherichia coli, Proteus sp (indole-positive and indole-negative), Providencia sp, Klebsiella-Enterobacter-Serratia spp, Acinetobacter and Citrobacter freundii.

Many strains of the previously mentioned organisms that are resistant to other aminoglycosides are susceptible to Amisine in vitro. Amisine resists degradation by most aminoglycoside-inactivating enzymes known to affect gentamicin, tobramycin and kanamycin.

Gram-Positive: Amisine is active in vitro against penicillinase- and nonpenicillinase-producing Staphylococcus sp, including methicillin-resistant strains. However, aminoglycosides, in general, have low activity against other gram-positive organisms, eg Streptococcus pyogenes, Enterococci and Streptococcus pneumoniae.

Amisine, combined with a β-lactam antibiotic or penicillin-type drug, acts synergistically against many clinically significant gram-negative organisms.

Pharmacokinetics: Absorption: Following IM administration of a single dose of Amisine 7.5 mg/kg (500 mg) in adults with normal renal function, peak plasma concentrations of 17-25 mcg/mL are attained within 45 min to 2 hrs; peak plasma concentrations of the drug average 2.1 mcg/mL at 10 hrs. When the same dose is administered by IV infusion over 1 hr, peak plasma concentrations of the drug average 38 mcg/mL immediately following the infusion, 5.5 mcg/mL at 4 hrs and 1.3 mcg/mL at 8 hrs. About 84% of an administered dose is excreted in the urine in 9 hrs and about 94% within 24 hrs. Repeat infusions of 7.5 mg/kg every 12 hrs caused no drug accumulation.

Distribution: The mean serum t_½ is about 2 hrs with apparent volume of distribution of 24 L (28% of body weight). Serum protein-binding ranges from 0-11%. The renal clearance rate is 94 mL in subjects with normal renal function.

Following administration of the recommended dose, therapeutic levels of the drug are found in bone, heart, gallbladder and lung tissue in addition to significant concentrations in urine, bile, sputum, bronchial secretions, interstitial, pleural and synovial fluids.

Amisine crosses the placental barrier and yields significant concentrations in amniotic fluid. The peak fetal serum concentration is about 16% of the peak maternal serum concentration and maternal and fetal serum t_½ values are about 2 and 3.7 hrs, respectively.

Excretion: Amisine is excreted primarily by glomerular filtration. Newborn and low birthweight infants, and patients with impaired renal function excrete the drug more slowly, therefore, renal function should be monitored closely and dosage adjusted accordingly.

How should I take Amisine?

If you are injecting Amisine at home, your healthcare provider will give you detailed instructions on how and where to inject the medication. If you do not understand these directions, do not attempt to inject the medication. Contact your healthcare provider for further instructions.

Do not use any Amisine that is discolored, has particles in it, or looks different from your previous doses. Throw away any unused Amisine after the amount of time determined by your pharmacist or doctor.

Adequate hydration is important during treatment with Amisine. Fluids may be administered intravenously during treatment.

It is important that the medication be given on a regular schedule and for the entire amount of time prescribed by your doctor.

Amisine may cause damage to the kidneys and/or nerves. Kidney function and drug levels in the blood may be monitored with blood tests during treatment. Tell your doctor if you experience hearing loss, dizziness, numbness, skin tingling, muscle twitching, or seizures which may be signs of nerve damage.

Dispose of used needles and syringes in a puncture resistant container out of the reach of children.

Your healthcare provider will store Amisine as directed by the manufacturer or give you detailed storage instructions if you are storing the medication at home.

Amisine administration

IM: Administer IM injection in large muscle mass.

IV: Infuse over 30 to 60 minutes.

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while Amisine has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered.

Intrathecal/Intraventricular (off-label route): Reconstitute with preservative-free diluent (NS) only to a final volume of 3 mL (Corpus 2004; Preston 1993). When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow Amisine solution to equilibrate in the CSF (IDSA [Tunkel 2017).

Inhalation (off-label route): Nebulization: Use with standard jet nebulizer connected to an air compressor or ultrasonic nebulizer; administer with mouthpiece or face mask (Le 2010)

Amisine pharmacology

Intramuscular Administration

Amisine is rapidly absorbed after intramuscular administration. In normal adult volunteers, average peak serum concentrations of about 12, 16, and 21 mcg/mL are obtained 1 hour after intramuscular administration of 250 mg (3.7 mg/kg), 375 mg (5 mg/kg), 500 mg (7.5 mg/kg), single doses, respectively. At 10 hours, serum levels are about 0.3 mcg/mL, 1.2 mcg/mL, and 2.1 mcg/mL, respectively.

Tolerance studies in normal volunteers reveal that Amisine is well tolerated locally following repeated intramuscular dosing, and when given at maximally recommended doses, no ototoxicity or nephrotoxicity has been reported. There is no evidence of drug accumulation with repeated dosing for 10 days when administered according to recommended doses.

With normal renal function, about 91.9% of an intramuscular dose is excreted unchanged in the urine in the first 8 hours, and 98.2% within 24 hours. Mean urine concentrations for 6 hours are 563 mcg/mL following a 250 mg dose, 697 mcg/mL following a 375 mg dose, and 832 mcg/mL following a 500 mg dose.

Preliminary intramuscular studies in newborns of different weights (less than 1.5 kg, 1.5 to 2.0 kg, over 2.0 kg) at a dose of 7.5 mg/kg revealed that, like other aminoglycosides, serum half-life values were correlated inversely with post-natal age and renal clearances of Amisine. The volume of distribution indicates that Amisine, like other aminoglycosides, remains primarily in the extracellular fluid space of neonates. Repeated dosing every 12 hours in all the above groups did not demonstrate accumulation after 5 days.

Intravenous Administration

Single doses of 500 mg (7.5 mg/kg) administered to normal adults as an infusion over a period of 30 minutes produced a mean peak serum concentration of 38 mcg/mL at the end of the infusion, and levels of 24 mcg/mL, 18 mcg/mL, and 0.75 mcg/mL at 30 minutes, 1 hour, and 10 hours post-infusion, respectively. Eighty-four percent of the administered dose was excreted in the urine in 9 hours and about 94% within 24 hours.

Repeat infusions of 7.5 mg/kg every 12 hours in normal adults were well tolerated and caused no drug accumulation.

General

Pharmacokinetic studies in normal adult subjects reveal the mean serum half-life to be slightly over 2 hours with a mean total apparent volume of distribution of 24 liters (28% of the body weight). By the ultrafiltration technique, reports of serum protein binding range from 0 to 11%. The mean serum clearance rate is about 100 mL/min and the renal clearance rate is 94 mL/min in subjects with normal renal function.

Amisine is excreted primarily by glomerular filtration. Patients with impaired renal function or diminished glomerular filtration pressure excrete the drug much more slowly (effectively prolonging the serum half-life). Therefore, renal function should be monitored carefully and dosage adjusted accordingly.

Following administration at the recommended dose, therapeutic levels are found in bone, heart, gallbladder, and lung tissue in addition to significant concentrations in urine, bile, sputum, bronchial secretions, interstitial, pleural, and synovial fluids.

Spinal fluid levels in normal infants are approximately 10 to 20% of the serum concentrations and may reach 50% when the meninges are inflamed. Amisine has been demonstrated to cross the placental barrier and yield significant concentrations in amniotic fluid. The peak fetal serum concentration is about 16% of the peak maternal serum concentration and maternal and fetal serum half-life values are about 2 and 3.7 hours, respectively.

Microbiology

Mechanism of Action

Amisine, an aminoglycoside, binds to the prokaryotic ribosome, inhibiting protein synthesis in susceptible bacteria. It is bactericidal in vitro against Gram-positive and Gram-negative bacteria.

Mechanism of Resistance

Aminoglycosides are known to be ineffective against Salmonella and Shigella species in patients. Therefore, in vitro susceptibility test results should not be reported.

Amisine resists degradation by certain aminoglycoside inactivating enzymes known to affect gentamicin, tobramycin, and kanamycin.

Aminoglycosides in general have a low order of activity against Gram-positive organisms other than Staphylococcal isolates.

Interaction with Other Antimicrobials

In vitro studies have shown that Amisine sulfate combined with a beta-lactam antibiotic acts synergistically against many clinically significant Gram-negative organisms.

Antimicrobial Activity

Amisine has been shown to be active against the following bacteria, both in vitro and in clinical infections.

Gram-positive Bacteria

Staphylococcus species

Gram-negative Bacteria

Pseudomonas species

Escherichia coli

Proteus species (indole-positive and indole-negative)

Klebsiella species

Enterobacter species

Serratia species

Acinetobacter species

Amisine has demonstrated in vitro activity against the following bacteria. The safety and effectiveness of Amisine in treating clinical infections due to these bacteria have not been established in adequate and well-controlled trials.

Citrobacter freundii

Susceptibility Test Methods

When available, the clinical microbiology laboratory should provide cumulative results of the in vitro susceptibility tests for antimicrobial drugs used in local hospitals and practice areas to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting the most effective antimicrobial.

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimal inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method.1,3 Standardized procedures are based on a dilution method (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of Amisine powder. The MIC values should be interpreted according to the criteria provided in Table 1.

Diffusion Techniques

Quantitative methods that require measurement of zone diameters also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure requires the use of standardized inoculum concentrations and paper disks impregnated with 30 mcg of Amisine.2,3 The disk diffusion values should be interpreted according to the criteria provided in Table 1.

Table 1: Susceptibility Test Interpretive Criteria for Amisine

S = susceptible, I = intermediate, R = resistant
a For Salmonella and Shigella spp., aminoglycosides may appear active in vitro but are not effective clinically; the results should not be reported as susceptible.
b For staphylococci that test susceptible, aminoglycosides are used only in combination with other active agents that test susceptible.
Pathogen	Minimum Inhibitory Concentrations (mcg/mL)			Disk Diffusion Zone Diameters (mm)
	S	I	R	S	I	R
Enterobacteriaceaea	≤ 16	32	≥ 64	≥ 17	15 to 16	≤ 14
Pseudomonas aeruginosa	≤ 16	32	≥ 64	≥ 17	15 to 16	≤ 14
Acinetobacter spp.	≤ 16	32	≥ 64	≥ 17	15 to 16	≤ 14
Other Non-Enterobacteriaceae	≤ 16	32	≥ 64	-	-	-
Staphylococcus spp.b	≤ 16	32	≥ 64	≥ 17	15 to 16	≤ 14

A report of “Susceptible” indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentration at the infection site necessary to inhibit growth of the pathogen. A report of “Intermediate” indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.

Quality Control

Standardized susceptibility test procedures require the use of laboratory controls to monitor and ensure the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1,2,3 Standard Amisine powder should provide the following range of MIC values provided in Table 2. For the diffusion technique using the 30-mcg Amisine disk the criteria provided in Table 2 should be achieved.

Table 2: Acceptable Quality Control Ranges for Amisine

Quality Control Organism	Minimum Inhibitory Concentrations (mcg/mL)	Disk Diffusion Zone Diameters (mm)
Escherichia coli ATCC 25922	0.5 to 4	19 to 26
Pseudomonas aeruginosa ATCC 27853	1 to 4	18 to 26
Staphylococcus aureus ATCC 25923	Not Applicable	20 to 26
Staphylococcus aureus ATCC 29213	1 to 4	Not Applicable
Enterococcus faecalis ATCC 29212	64 to 256	Not Applicable

References

1. DailyMed. "AMIKACIN SULFATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
2. NCIt. "Amikacin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
3. EPA DSStox. "Amikacin: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Amisine are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Amisine. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

User reports

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Information checked by Dr. Sachin Kumar, MD Pharmacology