Reye's syndrome

1. Overview

Reye's (Ryes) syndrome is a rare but serious condition that causes swelling in the liver and brain. Reye's syndrome
most often affects children and teenagers recovering from a viral infection, most commonly the flu or chickenpox.
Signs and symptoms such as confusion, seizures and loss of consciousness require emergency treatment. Early
diagnosis and treatment of Reye's syndrome can save a child's life.
Aspirin has been linked with Reye's syndrome, so use caution when giving aspirin to children or teenagers. Though
aspirin is approved for use in children older than age 2, children and teenagers recovering from chickenpox or flu-like
symptoms should never take aspirin. Talk to your doctor if you have concerns.
Symptoms

In Reye's syndrome, a child's blood sugar level typically drops while the levels of ammonia and acidity in his or her
blood rise. At the same time, the liver may swell and develop fatty deposits. Swelling may also occur in the brain,
which can cause seizures, convulsions or loss of consciousness.
The signs and symptoms of Reye's syndrome typically appear about three to five days after the onset of a viral
infection, such as the flu (influenza) or chickenpox, or an upper respiratory infection, such as a cold.

2. Initial signs and symptoms

For children younger than age 2, the first signs of Reye's syndrome may include:

 Diarrhea

 Rapid breathing
For older children and teenagers, early signs and symptoms may include:

 Persistent or continuous vomiting

 Unusual sleepiness or lethargy

Additional signs and symptoms

As the condition progresses, signs and symptoms may become more serious, including:

 Irritable, aggressive or irrational behavior

 Confusion, disorientation or hallucinations

 Weakness or paralysis in the arms and legs

 Seizures

 Excessive lethargy

 Decreased level of consciousness

These signs and symptoms require emergency treatment.
When to see a doctor

Early diagnosis and treatment of Reye's syndrome can save a child's life. If you suspect that your child has Reye's
syndrome, it's important to act quickly.
Seek emergency medical help if your child:
  Has seizures or convulsions

 Loses consciousness
Contact your child's doctor if your child experiences the following after a bout with the flu or chickenpox:

 Vomits repeatedly

 Becomes unusually sleepy or lethargic

 Has sudden behavior changes

3. Causes

The exact cause of Reye's syndrome is unknown, although several factors may play a role in its development. Reye's
syndrome seems to be triggered by using aspirin to treat a viral illness or infection — particularly flu (influenza) and
chickenpox — in children and teenagers who have an underlying fatty acid oxidation disorder.
Fatty acid oxidation disorders are a group of inherited metabolic disorders in which the body is unable to break down
fatty acids because an enzyme is missing or not working properly. A screening test is needed to determine if your
child has a fatty acid oxidation disorder.
In some cases, Reye's syndrome may be an underlying metabolic condition that's unmasked by a viral illness.
Exposure to certain toxins — such as insecticides, herbicides and paint thinner — also may contribute to Reye's
syndrome.

4. Risk factors

The following factors — usually when they occur together — may increase your child's risk of developing Reye's
syndrome:

 Using aspirin to treat a viral infection, such as flu, chickenpox or an upper respiratory infection

 Having an underlying fatty acid oxidation disorder

Complications

Most children and teenagers who have Reye's syndrome survive, although varying degrees of permanent brain
damage are possible. Without proper diagnosis and treatment, Reye's syndrome can be fatal within a few days.

5. Prevention

Use caution when giving aspirin to children or teenagers. Though aspirin is approved for use in children older than
age 2, children and teenagers recovering from chickenpox or flu-like symptoms should never take aspirin. This
includes plain aspirin and medications that contain aspirin.
Some hospitals and medical facilities conduct newborn screenings for fatty acid oxidation disorders to determine
which children are at greater risk of developing Reye's syndrome. Children with known fatty acid oxidation disorders
should not take aspirin or aspirin-containing products.
Always check the label before you give your child medication, including over-the-counter products and alternative or
herbal remedies. Aspirin can show up in some unexpected places, such as Alka-Seltzer.
Sometimes aspirin goes by other names, too, such as:

 Acetylsalicylic acid

 Acetylsalicylate

 Salicylic acid
  Salicylate
If your child has the flu, chickenpox or another viral illness, use other medications — such as acetaminophen (Tylenol,
others), ibuprofen (Advil, Children's Motrin, Motrin IB, others) or naproxen (Aleve) — to reduce high fever or relieve
pain.
There's one caveat to the aspirin rule, however. Children and teenagers who have certain chronic diseases, such as
Kawasaki disease, may need long-term treatment with drugs that contain aspirin.
If your child needs aspirin therapy, make sure his or her vaccines are current — including two doses of the varicella
(chickenpox) vaccine and a yearly flu vaccine. Avoiding these two viral illnesses can help prevent Reye's syndrome.
Case definitions

Person under investigation

A person whom public health authorities have decided to investigate for possible H5N1 infection.
Suspected H5N1 case

A person presenting with unexplained acute lower respiratory illness with fever (>38 ºC ) and cough,
shortness of breath or difficulty breathing.

AND

One or more of the following exposures in the 7 days prior to symptom onset:
a. Close contact (within 1 metre) with a person (e.g. caring for, speaking with, or touching) who is a suspected,
probable, or confirmed H5N1 case;

b. Exposure (e.g. handling, slaughtering, defeathering, butchering, preparation for consumption) to poultry or
wild birds or their remains or to environments contaminated by their faeces in an area where H5N1 infections
in animals or humans have been suspected or confirmed in the last month;

c. Consumption of raw or undercooked poultry products in an area where H5N1 infections in animals or
humans have been suspected or confirmed in the last month;

d. Close contact with a confirmed H5N1 infected animal other than poultry or wild birds (e.g. cat or pig);

e. Handling samples (animal or human) suspected of containing H5N1 virus in a laboratory or other setting.
Probable H5N1 case (notify WHO)
Probable definition 1:
A person meeting the criteria for a suspected case

AND

One of the following additional criteria:

a. infiltrates or evidence of an acute pneumonia on chest radiograph plus evidence of respiratory failure
(hypoxemia, severe tachypnea)

OR

b. positive laboratory confirmation of an influenza A infection but insufficient laboratory evidence for H5N1
infection.
Probable definition 2:
A person dying of an unexplained acute respiratory illness who is considered to be epidemiologically linked
by time, place, and exposure to a probable or confirmed H5N1 case.
Confirmed H5N1 case (notify WHO)
A person meeting the criteria for a suspected or probable case

AND

One of the following positive results conducted in a national, regional or international influenza laboratory
whose H5N1 test results are accepted by WHO as confirmatory:
a. Isolation of an H5N1 virus;

b. Positive H5 PCR results from tests using two different PCR targets, e.g. primers specific for influenza A and H5
HA;

c. A fourfold or greater rise in neutralization antibody titer for H5N1 based on testing of an acute serum
specimen (collected 7 days or less after symptom onset) and a convalescent serum specimen. The convalescent
neutralizing antibody titer must also be 1:80 or higher;

d. A microneutralization antibody titer for H5N1 of 1:80 or greater in a single serum specimen collected at day
14 or later after symptom onset and a positive result using a different serological assay, for example, a horse red
blood cell haemagglutination inhibition titer of 1:160 or greater or an H5-specific western blot positive result.
 PATHOGENESIS

Microbial triggers of disease:

1. gram-negative bacteria= endotoxin, formyl peptides, exotoxins, and proteases

2. gram-positive bacteria= exotoxins, superantigens (toxic shock syndrome toxin (TSST), streptococcal pyrogenic
exotoxin A (SpeA)), enterotoxins, hemolysins, peptidoglycans, and lipotechoic acid

3. fungal cell wall material.

Sequence of events: Sepsis can be simply defined as a spectrum of clinical conditions caused by the immune
response of a patient to infection that is characterized by systemic inflammation and coagulation. It includes the full
range of response from systemic inflammatory response (SIRS) to organ dysfunction to multiple organ failure and
ultimately death.

This is a very complex sequence of events and much work still needs to be done to completely understand how a
patient goes from SIRS to septic shock. Patients with septic shock have a biphasic immunological response. Initially
they manifest an overwhelming inflammatory response to the infection. This is most likely due to the pro-
inflammatory cytokines Tumor Necrosis Factor (TNF), IL-1, IL-12, Interferon gamma (IFNgamma), and IL-6.

The body then regulates this response by producing anti-inflammatory cytokines (IL-10), soluble inhibitors [TNF
receptors, IL-1 receptor type II, and IL-1RA (an inactive form of IL-1)]. Which is manifested in the patient by a period
of immunodepression. Persistence of this hyporesponsiveness is associated with increased risk of nosocomial
infection and death.

This systemic inflammatory cascade is initiated by various bacterial products. These bacterial products (gram-
negative bacteria= endotoxin, formyl peptides, exotoxins, and proteases, gram-positive bacteria= exotoxins,
superantigens (toxic shock syndrome toxin (TSST), streptococcal pyrogenic exotoxin A (SpeA)), enterotoxins,
hemolysins, peptidoglycans, and lipotechoic acid, and fungal cell wall material) bind to cell receptors on the host's
macrophages and activate regulatory proteins [Nuclear Factor Kappa B (NFkB)]. Endotoxin activates the regulatory
proteins by interacting with several receptors. The CD receptors pool the LPS-LPS binding protein complex on the
surface of the cell and then the TLR receptors translate the signal into the cells.

The pro-inflammatory cytokines produced are tumor necrosis factor (TNF), Interleukins 1, 6 and 12 and Interferon
gamma (IFNgamma). These cytokines can act directly to affect organ function or they may act indirectly through
secondary mediators. The secondary mediators include nitric oxide, thromboxanes, leukotrienes, platelet-activating
factor, prostaglandins, and complement. TNF and IL-1 (as well as endotoxin) can also cause the release of tissue-
factor by endothelial cells leading to fibrin deposition and disseminated intravascular coagulation (DIC).

Then these primary and secondary mediators cause the activation of the coagulation cascade, the complement
cascade and the production of prostaglandins and leukotrienes. Clots lodge in the blood vessels which lowers
profusion of the organs and can lead to multiple organ system failure. In time this activation of the coagulation
cascade depletes the patient's ability to make clot resulting in DIC and ARDS.

The cumulative effect of this cascade is an unbalanced state, with inflammation dominant over antiinflammation and
coagulation dominant over fibrinolysis. Microvascular thrombosis, hypoperfusion, ischemia, and tissue injury result.
Severe sepsis, shock, and multiple organ dysfunction may occur, leading to death.
Influenza vaccines

The World Health Organization reviews the world epidemiological situation twice annually and if necessary
recommends new vaccine strain(s) in accordance with the available evidence. In general, seasonal influenza
vaccines are trivalent, containing a mixture of influenza A and B strains thought most likely to circulate in the
coming season. However, monovalent vaccines have been produced against candidate pandemic strains. It is now
common practice to use reassortant strains for production that give high yields of the appropriate surface
antigens. Reassortant strains for vaccine production have the surface glycoproteins (HA and NA) of the circulating
epidemic virus but the internal proteins of a standardized production strain, eliminating much of the risks
associated with handling pathogenic strains. The virus is grown in chick embryos or cell cultures for the
production of vaccines. Due to the need to rapidly manufacture new vaccines in response to the likely strains that
are identified, a unique set of regulatory requirements must be applied to the development, testing, and batch
release of both seasonal and pandemic response influenza vaccines. Two types of influenza vaccine are available,
an inactivated (killed) preparation that is injected and an attenuated influenza vaccine normally delivered nasally.
There are three types of inactivated vaccines, the whole virus vaccines, split virus vaccines, and subunit vaccines.
In split virus vaccines, the virus has been disrupted by a detergent. In subunit vaccines, HA and NA have been
further purified by removal of other viral components. Some formulations include adjuvants and most multidose
vials contain the preservative thiomersal. Live, attenuated influenza vaccines have been based on a temperature-
sensitive variant vaccine virus strains that replicate well in the nasopharynx but poorly in the lower respiratory
tract.

What kinds of flu vaccines are available?

CDC recommends use of injectable influenza vaccines (including inactivated influenza vaccines and recombinant
influenza vaccines) during 2017-2018. The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should
not be used during 2017-2018.

Both trivalent (three-component) and quadrivalent (four-component) flu vaccines will be available.

Trivalent flu vaccines include:

 Standard-dose trivalent shots (IIV3) that are manufactured using virus grown in eggs. Different flu shots are
approved for different age groups. Most flu shots are given in the arm (muscle) with a needle. One trivalent
vaccine formulation can be given with a jet injector, for persons aged 18 through 64 years.

 A high-dose trivalent shot, approved for people 65 and older.

 A recombinant trivalent shot that is egg-free, approved for people 18 years and older, including pregnant
women.

 A trivalent flu shot made with adjuvant (an ingredient of a vaccine that helps create a stronger immune
response in the patient’s body), approved for people 65 years of age and older (new this season).

Quadrivalent flu vaccines include:

 Quadrivalent flu shots approved for use in different age groups, including children as young as 6 months.

 An intradermal quadrivalent flu shot, which is injected into the skin instead of the muscle and uses a much
smaller needle than the regular flu shot. It is approved for people 18 through 64 years of age.

 A quadrivalent flu shot containing virus grown in cell culture, which is approved for people 4 years of age and
older.

 A recombinant quadrivalent flu shot approved for people 18 years of age and older, including pregnant
women (new this season).

Are any of the available flu vaccines recommended over others?

For the 2017-2018 flu season, the Advisory Committee on Immunization Practices (ACIP) recommends annual
influenza vaccination for everyone 6 months and older with either the inactivated influenza vaccine (IIV) or the
recombinant influenza vaccine (RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should not
be used during 2017-2018.There is no preference for one vaccine over another among the recommended, approved
injectable influenza vaccines. There are many vaccine options to choose from, but the most important thing is for all
people 6 months and older to get a flu vaccine every year. If you have questions about which vaccine is best for you,
talk to your doctor or other health care professional.
Who should get vaccinated this season?
Everyone 6 months of age and older should get a flu vaccine every season. This recommendation has been in place
since February 24, 2010 when CDC’s Advisory Committee on Immunization Practices (ACIP) voted for “universal” flu
vaccination in the United States to expand protection against the flu to more people.

Vaccination to prevent influenza is particularly important for people who are at high risk of serious complications
from influenza. See People at High Risk of Developing Flu-Related Complications for a full list of age and health
factors that confer increased risk.

Who Should Not Be Vaccinated?

CDC recommends use of a flu shot; either an inactivated influenza vaccine or (IIV) or a recombinant influenza vaccine
(RIV). The nasal spray flu vaccine (live attenuated influenza vaccine or LAIV) should not be used during 2017-2018.
Different flu vaccines are approved for use in different groups of people. Factors that can determine a person’s
suitability for vaccination, or vaccination with a particular vaccine, include a person’s age, health (current and past)
and any allergies to flu vaccine or its components.

 People who cannot get a flu shot

 People who should talk to their doctor before getting the flu shot

Why do I need a flu vaccine every year?

A flu vaccine is needed every season for two reasons. First, the body’s immune response from vaccination declines
over time, so an annual vaccine is needed for optimal protection. Second, because flu viruses are constantly
changing, the formulation of the flu vaccine is reviewed each year and sometimes updated to keep up with changing
flu viruses. For the best protection, everyone 6 months and older should get vaccinated annually.

OSELTAMIVIR
What is oseltamivir, and how does it work (mechanism of action)?

Oseltamivir is an oral medication used for treating and preventing the "flu." It is similar to zanamivir(Relenza).

Oseltamivir suppresses and decreases the spread of influenza A and B viruses, the viruses responsible for the flu. It

does this by blocking the action of neuraminidase, an enzyme produced by the viruses that enables the viruses to

spread from infected cells to healthy cells. By preventing the spread of virus from cell to cell, the symptoms and

duration of influenza infection are reduced. On average, oseltamivir reduces the duration of symptoms by one and a

half days if treatment is started within forty-eight hours of the beginning of symptoms.

What is the dosage for oseltamivir?

Oseltamivir is administered orally. For the best results, treatment should begin within 2 days of symptom onset or

exposure.

 The recommended dose for treating adults with flu is 75 mg twice daily for five days.
  Children are treated with 30-75 mg twice daily for five days. Dosing depends on body weight.

 The adult dose for prevention of flu is 75 mg daily for 10 days. Children receive 30-75 mg once daily for 10

days.

Dosage Forms & Strengths

capsule
 30mg
 45mg
 75mg
powder for oral suspension
 6mg/mL

Oseltamivir dosing information

Usual Adult Dose for Influenza:

75 mg orally twice a day for 5 days

Approved indication: Treatment of acute, uncomplicated influenza infection in patients symptomatic no more than 48
hours

Usual Adult Dose for Influenza Prophylaxis:

Following close contact with an infected individual: 75 mg orally once a day for at least 10 days
During a community outbreak of influenza: 75 mg orally once a day

Comments:
-Therapy should begin within 48 hours of exposure.
-Safety and efficacy have been established for up to 6 weeks in immunocompetent patients; duration of protection
lasts as long as dosing is continued.
-Safety has been established for up to 12 weeks in immunocompromised patients.

Usual Pediatric Dose for Influenza:

2 weeks to less than 1 year: 3 mg/kg orally twice a day

1 through 12 years:
15 kg or less: 30 mg orally twice a day
15.1 through 23 kg: 45 mg orally twice a day
23.1 through 40 kg: 60 mg orally twice a day
40.1 kg or greater: 75 mg orally twice a day

13 years or older: 75 mg orally twice a day

Duration of therapy: 5 days

Approved indication: Treatment of acute, uncomplicated influenza infection in patients (2 weeks or older)
symptomatic no more than 48 hours

(Not approved by FDA)

American Academy of Pediatrics (AAP) recommendations:

Full-term infants less than 2 weeks: 3 mg/kg orally twice a day
 Usual Pediatric Dose for Influenza Prophylaxis:

1 through 12 years:
15 kg or less: 30 mg orally once a day
15.1 through 23 kg: 45 mg orally once a day
23.1 through 40 kg: 60 mg orally once a day
40.1 kg or greater: 75 mg orally once a day

13 years or older: 75 mg orally once a day

Duration of therapy:
-After close contact with an infected individual: 10 days
-During a community outbreak of influenza: May be continued for up to 6 weeks

Comments:
-Therapy should begin within 48 hours of exposure.
-The FDA has not approved dosing for patients less than 1 year of age.

What are the possible side effects of oseltamivir (Tamiflu)?

Stop using oseltamivir and get emergency medical help if you have any of these signs of an allergic reaction: hives;
difficulty breathing; swelling of your face, lips, tongue, or throat; a red and blistering or peeling skin rash.

Some people using oseltamivir have had rare side effects of sudden confusion, delirium, hallucinations, unusual
behavior, or self-injury. These symptoms have occurred most often in children. It is not known whether oseltamivir
was the exact cause of these symptoms. However, anyone using oseltamivir should be watched closely for signs of
confusion or unusual behavior. Call a doctor at once if you or the child using oseltamivir has any of these symptoms.

Less serious side effects may include:

 nausea, vomiting, diarrhea;

 dizziness, headache;

 nosebleed;

 eye redness or discomfort;

 sleep problems (insomnia); or

 cough or other respiratory symptoms.

What is the most important information I should know about oseltamivir (Tamiflu)?

Oseltamivir is used to treat flu symptoms caused by influenza virus in patients who have had symptoms for less than
2 days. Oseltamivir may also be given to prevent influenza in people who may be exposed but do not yet have
symptoms. Oseltamivir will not treat the common cold.

Before taking oseltamivir, tell your doctor if you have received a nasal flu vaccine within the past 2 weeks, or if you
have kidney disease, heart disease, lung disease, or any other serious disease or health problem. Also tell your doctor
if you have any condition causing swelling or disorder of the brain.

Treatment with oseltamivir should start as soon as possible when flu symptoms appear, such as fever, chills, muscle
aches, sore throat, and runny or stuffy nose.
Take this medication for as many days as it has been prescribed for you even if you begin to feel better. Your
symptoms may start to improve before the infection is completely treated.

Some people using oseltamivir have had rare side effects of sudden confusion, delirium, hallucinations, unusual
behavior, or self-injury. These symptoms have occurred most often in children. It is not known whether oseltamivir
was the exact cause of these symptoms. However, anyone using oseltamivir should be watched closely for signs of
confusion or unusual behavior. Call a doctor at once if you or the child using oseltamivir has any of these symptoms.

Oseltamivir should not be used in place of getting a yearly flu shot. The Centers for Disease Control recommends an
annual flu shot to help protect you each year from new strains of influenza virus.

It is dangerous to purchase oseltamivir on the Internet or from vendors outside of the United States. Samples of
"Tamiflu" purchased on the Internet have been found to contain cloxacillin, a type of antibiotic that can have
dangerous side effects in people who are allergic to penicillin.

Amikacin

Injeksi IM/IV

Komposisi:
Amikacin injeksi 125 mg/ml
Tiap ml mengandung:
Amikasin sulfat setara dengan amikasin 125 mg

Amikacin injeksi 250 mg/ml

Tiap ml mengandung:
Amikasin sulfat setara dengan amikasin 250 mg

Farmakodinamik
Amikasin sulfat adalah antibiotik golongan aminoglikosida yang mempunyai spektrum luas yang aktif terhadap
bakteri gram negatif termasuk Pseudomonas spp, Escherichia coli, Proteus spp indol-positif dan indol-negatif,
Klebsiella-Enterobacter-Serratia spp, Salmonella, Shigella, Acinetobacter (Minea-Herellae), Citrobacter Freundii dan
Providencia spp. Beberapa strain bakteri gram negatif yang resisten terhadap gentamisin, tobramisin dan kanamisin
menunjukkan sensitivitas terhadap amikasin secara in vitro.

Bakteri gram positif yang sensitif terhadap amikasin adalah Staphylococcus spp, baik yang menghasilkan penisilinase
maupun tidak, termasuk strain yang resisten terhadap metisilin. Amikasin mempunyai aktivitas melawan bakteri
gram positif lain, termasuk strain Streptococcus pyogenes, Enterococci dan Diplococcus pneumoniae (Streptococcus
pneumoniae). Amikasin bersifat bakterisid dengan cara menghambat sintesis protein pada bakteri sensitif oleh
adanya pengikatan yang irreversible terhadap subunit ribosomal 30S.

Farmakokinetik
Pemberian amikasin melalui IM
Amikasin diabsorpsi secara cepat sesudah injeksi IM. Pada relawan dewasa normal, konsentrasi serum puncak rata-
rata sekitar 12, 16, dan 21 mcg/ml diperoleh dalam waktu 1 jam setelah pemberian IM 250 mg (3,7 mg/kg), 375 mg
(5 mg/kg), 500 mg (7,5 mg/kg) dosis tunggal, berturut-turut. Pada titik 10 jam setelah pemberian, kadar serum
masing-masing sekitar 0,3 mcg/ml; 1,2 mcg/ml; dan 2,1 mcg/ml.

Studi toleransi pada relawan normal, menyatakan amikasin ditoleransi baik secara lokal setelah pemberian IM
berulang, dan jika diberikan pada dosis maksimal yang direkomendasikan, tidak menyebabkan ototoksisitas atau
nefrotoksisitas. Juga tidak terjadi akumulasi obat dengan pemberian berulang selama 10 hari jika diberikan sesuai
dosis anjuran.
Pada fungsi ginjal normal, sekitar 91,9% diekskresi dalam bentuk utuh melalui urin dalam 8 jam pertama dan 98,2%
dalam waktu 24 jam. Konsentrasi dalam urin setelah 6 jam 563 mcg/ml pada pemberian dosis 250 mg, 697 mcg/ml
pada pemberian dosis 375 mg dan 832 mcg/ml pada pemberian dosis 500 mg.

Studi pemberian secara IM pada bayi yang baru lahir dengan berat badan yang berbeda-beda (kurang dari 1,5 kg; 1,5-
2 kg, lebih dari 2 kg) pada dosis 7,5 mg/kg, seperti aminoglikosida lainnya, memperlihatkan nilai waktu paruh serum
yang memiliki korelasi berbanding terbalik dengan usia post-natal dan bersihan ginjal dari amikasin. Penggulangan
pemberian setiap 12 jam pada kelompok di atas tidak menunjukkan akumulasi setelah 5 hari.

Pemberian amikasin melalui IV

Pemberian amikasin 500 mg sebagai dosis tunggal kepada orang dewasa normal secara infus intravena, selama
periode 30 menit menghasilkan konsentrasi serum puncak rata-rata 38 mcg/ml pada akhir pemberian infus dan kadar
24 mcg/ml; 18 mcg/ml; dan 0,75 mcg/ml pada 30 menit, 1 jam dan 10 jam setelah pemberian infus, berturut-turut.
Delapan puluh empat persen dari dosis diekskresikan melalui urin dalam waktu 9 jam dan sekitar 94% dalam waktu
24 jam. Pengulangan pemberian infus 7,5 mg/kg setiap 12 jam ditoleransi secara baik dan tidak menghasilkan
akumulasi obat.

Umum
Studi farmakokinetik pada subyek dewasa normal memperlihatkan waktu paruh serum lebih dari 2 jam dengan
volume distribusi total rata-rata sebesar 24 L (28% dari berat badan). Dengan teknik ultrafiltrasi dilaporkan ikatan
protein serum berkisar 0-11%. Laju bersihan serum rata-rata sekitar 100 ml/menit dan laju bersihan ginjal 94
ml/menit pada subyek dengan fungsi ginjal normal. Amikasin diekskresikan terutama oleh filtrasi glomerulus. Pada
pasien dengan gangguan fungsi ginjal atau tekanan filtrasi glomerulus yang berkurang, ekskresi obat menjadi lebih
lambat (efektif memperpanjang waktu paruh serum). Oleh karena itu, fungsi ginjal harus dimonitor dengan seksama
dan dilakukan penyesuaian dosis.

Amikasin dengan kadar terapeutik ditemukan pada cairan serebrospinal, cairan pleural, cairan amniotik, kavitas
peritoneal, tulang, jantung, kandung empedu dan jaringan paru-paru setelah pemberian secara parenteral.
Konsentrasi yang signifikan terdapat dalam urin, cairan empedu, sputum, sekresi bronkial, cairan interstisial, pleural
dan sinovial. Kadar dalam cairan spinal pada bayi normal mencapai 10-20% dari konsentrasi serum dan dapat
mencapai 50% ketika selaput otak mengalami inflamasi. Amikasin menembus sawar darah-plasenta, sehingga
terdapat dalam cairan amniotik dalam kadar yang bermakna. Amikasi dengan mudah terdifusi melalui cairan
ekstraselular dan diekskresikan dalam bentuk utuh melalui urin oleh filtrasi glomerulus. Cmax serum fetal sekitar 16%
dari Cmax serum maternal, dan nilai waktu paruh serum fetal sekitar 3,7 jam, sedangkan nilai waktu paruh serum
maternal sekitar 2 jam.

Indikasi
Untuk pengobatan jangka pendek pada infeksi serius yang disebabkan oleh bakteri yang sensitif baik gram negatif
dan positif.
- Septikemia (termasuk sepsis neonatal)
- Infeksi saluran pernafasan yang serius
- Infeksi tulang dan sendi
- Infeksi sistem saraf pusat (termasuk meningitis)
- Infeksi kulit dan jaringan lunak
- Infeksi intraabdominal (termasuk peritonitis)
- Infeksi pada luka bakar
- Infeksi pasca operasi (termasuk pasca bedah vaskular)
- Infeksi saluran kemih yang mengalami komplikasi dan rekuren

Kontraindikasi
Penderita yang hipersensitif terhadap amikasin dan antibiotik golongan aminoglikosida lain, karena terdapat
sensitivitas silang.

Dosis dan cara pemberian

Lama pengobatan biasanya 7-10 hari. Total dosis sehari tidak boleh melebihi 15 mg/kg/hari atau 1,5 g/hari.
Pemberian intramuskular:
Neonatus:
Dosis awal 10 mg/kgBB/hari yang diikuti dengan 7,5 mg/kgBB setiap 12 jam.
Dewasa, anak-anak dan bayi dengan fungsi ginjal normal:
15 mg/kgBB/hari terbagi 2-3 kali pemberian (pada orang dewasa sebesar 500 mg dua kali sehari).
Pemberian intravena:
Dewasa: 500 mg amikasin ke dalam 100-200 ml NaCl 0,9% atau Dekstrosa 5% dan diinfuskan selama 30-60 menit.
Anak-anak: volume infus tergantung kebutuhan , periode infus 30-60 menit.
Bayi: volume infus tergantung pada kebutuhan, periode infus 1-2 jam.

Infeksi yang mengancam kehidupan dan atau disebabkan pseudomonas dosis amikasin dapat diberikan 500 mg setiap
8 jam. Dosis maksimum 1,5 g/hari dan pemberian tidak boleh lebih dari 10 hari. Dosis total maksimum untuk
dewasa: 15 g.

Pada pasien dengan fungsi ginjal terganggu:

Dosis harian dikurangi atau interval dosis diperpanjang untuk menghindari akumulasi obat. Dosis awal 7,5 mg/kgBB.
Metoda yang dianjurkan untuk memperkirakan dosis pada pasien yang diketahui atau diduga menderita gangguan
fungsi ginjal adalah dengan cara mengalikan kadar kreatinin serum (dalam mg/100 ml) dengan 9 dan hasilnya adalah
interval dosis dalam jam.

Fungsi ginjal dapat mengalami perubahan yang cukup besar selama terapi, maka kreatinin serum sebaiknya sering
diperiksa dan dosis dimodifikasi bila perlu.

Peringatan dan perhatian

- Tidak dianjurkan untuk diberikan pada wanita hamil dan menyusui.
- Potensial terjadi nefrotoksik dan ototoksik.
- Pemakaian bersamaan dengan sefalosporin dan antibiotik aminoglikosida lain akan meningkatkan nefrotoksisitas.
- Hati-hati pada pasien dengan gagal ginjal.

Efek samping
- Reaksi hipersensitivitas terhadap amikasin termasuk ruam kulit, urtikaria, stomatitis, pruritis, rasa terbakar, demam
dan eosinofilia.
- Ototoksisitas: Gejala-gejala vestibular, seperti pusing, nistagmus, vertigo dan ataksia, dan/atau gejala auditorik,
seperti tinitus dan gangguan pendengaran sampai tuli.
- Nefrotoksisitas: Gangguan pada urin akibat iritasi ginjal (albumin, casts, sel darah putih dan merah), azotemia dan
oliguria pernah dilaporkan.
- Neurotoksisitas: Sakit kepala, parestesia, dan tremor.
- Lain-lain: Nausea, vomitus, demam dan anemia.

Interaksi obat:
- Obat-obat ototoksik, nefrotoksik dan neurotoksik.
- Hindari penggunaan bersamaan dengan obat-obat diuretik kerja cepat terutama pemberian secara IV (asam
etakrinat dan furosemid) karena dapat meningkatkan risiko ototoksisitas.