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Monday, December 28, 2015

Oseltamivir

Oseltamivir Capsules 75 mg
Antiviral

Composition
Active ingredient: oseltamivir phosphate.

Capsules containing 98.5 mg oseltamivir phosphate equivalent to 75 mg of oseltamivir
Oseltamivir is presented as hard capsule with Red cap and White body

Properties and effects
Mechanism of action
Oseltamivir phosphate is a pro-drug of a potent and selective inhibitor of influenza virus neuraminidase enzymes. Viral neuraminidase is essential for the release of recently formed virus particles from infected cells, and the further spread of infectious virus.
The active metabolite of oseltamivir inhibits neuraminidases of influenza viruses of both types A and B. Concentrations of the active metabolite required to inhibit the enzyme activity by 50% (IC50) are in the low nanomolar range. The active metabolite also inhibit influenza virus growth in-vitro and inhibits influenza virus replication and pathogenicity in-vivo.
The active metabolite reduces shedding of both influenza A and B virus by inhibiting the release of infectious virus from infected cells

Efficacy
Clinical efficacy of oseltamivir has been demonstrated in human experimental infection studies and phase III studies in naturally occurring influenza.
In studies in naturally acquired and experimental influenza, treatment with oseltamivir did not impair normal humoral antibody response to infection, Antibody response to inactivated vaccine is not expected to be affected by treatment with oseltamivir.
In phase III clinical trials, patients were treated with oseltamivir for up to 40 hours after reported onset of symptoms. In these studies, 97% of patients were infected with influenza A and 3% with influenza B. Oseltamivir treatment significantly reduced the duration of clinically relevant signs and symptoms of influenza by 32 hours. Disease severity in patients with confirmed influenza taking oseltamivir was also reduced by 38% compared to placebo. Moreover oseltamivir reduced the incidence of complications associated with influenza treated with antibiotic therapy in otherwise healthy young adults by approximately 50%. These complications include bronchitis, pneumonia, sinusitis and otitis media. In phase III clinical trials there was clear evidence of efficacy in the secondary endpoints related to antiviral activity in terms of both reduction of duration of virus shedding and reduction in the AUC of viral titres. Data from a partially recruited study in the elderly population have shown that oseltamivir 75 mg twice a day for five days was associated with a reduction in median duration of illness that was clinically relevant and similar to that seen in the adult treatment studies. In a separate partially recruited study, patients aged › 13 years with influenza and co-existing chronic cardiac and/or respiratory disease received the same regimen of either oseltamivir or placebo. No difference in the median time to alleviation of all symptoms was seen between patients taking oseltamivir or placebo however, the duration of febrile illness was reduced by approximately one day by receipt of oseltamivir. The proportion of patients shedding virus on days 2 and 4 was also markedly reduced by active treatment. There was no difference in the safety profile of oseltamivir in the at-risk populations compared to the general adult population.

Viral Resistance
The risk of emergence of drug resistance in clinical use has been extensively examined. The incidence of resistance to the active metabolite in viral isolates from clinical studies is up to 1.5% in influenza A. Patients with Viruses displaying reduced sensitivity, cleared virus normally and showed no clinical deterioration. All resistant genotypes are disadvantaged compared to the corresponding wild-type isolate and are likely to be less contagious in man There IS no evidence for resistance in influenza B in vitro or in clinical isolates.

Pharmacokinetics
Absorption
Oseltamivir is readily absorbed from the gastrointestinal tract after oral administration of oseltamivir phosphate and is extensively converted predominantly by hepatic esterases to the active metabolite. Plasma concentrations of the active metabolite, are measurable within 30 minutes. reach near maximal levels in 2 to 3 hours post dose, and substantially exceed (› 20 fold) those of the prodrug. At least 75% of an oral dose reaches the systemic circulation as the active metabolite. Plasma concentrations of active metabolite are proportional to dose and are unaffected by co-administration with food (see Dosage and Administration).

Distribution
The mean volume of distribution (Vss) of the active metabolite is approximately 23 liters in humans. The active moiety reaches all key sites of influenza infection as shown by studies in the ferret, rat and rabbit. In these studies, anti-viral concentrations of the active metabolite were seen in the lung, bronchoalveolar lavage, nasal mucosa, middle ear and trachea following oral administration of doses of oseltamivir phosphate.
The binding of the active metabolite to human plasma protein is negligible (approximately 3%). The binding of the prodrug to human plasma protein is 42%. These levels are insufficient to cause significant drug interactions.

Metabolism
Oseltamivir phosphate is extensively converted to the active metabolite by esterases located predominantly in the liver. Neither oseltamivir nor the active metabolite are substrates for or inhibitors of cytochrome P450 isoforms (see interactions).

Elimination
Absorbed oseltamivir is primarily (›90%) eliminated by conversion to the active metabolite. The active metabolite is not further metabolized and is eliminated in the urine. Peak plasma concentrations of the active metabolite decline with a half-life of 6 to 10 hours in most subjects. The active drug is eliminated entirely (›99%) by renal excretion. Renal clearance (18.8 1/h) exceeds glomerular filtration rate (7.5 1/h) indicating that tubular secretion in addition to glomerular filtration occurs. Less than 20% of an oral radio-labeled dose is eliminated in feces. Pharmacokinetics in special populations

Patients with renal impairment
Administration of 100 mg of oseltamivir twice daily for five days to patients with various degrees of renal impairment showed that exposure to the active metabolite is inversely proportional to declining renal function. No dose adjustment is necessary for patients with creatinine clearance above 30 ml/min. In patients with a creatinine clearance of 10-30 ml/min, it is recommended that the dose is reduced to 75 mg of oseltamivir once daily for 5 days (see Special dosage instructions and Precautions).

In patients with end stage renal disease (creatinine clearance ‹10 ml/min) undergoing routine hemodialysis or peritoneal dialysis treatment. predicted plasma concentrations indicate that a single dose of 75 mg oseltamivir will deliver antiviral levels for up to 5 days (see Precautions) Patients With hepatic impairment.
In-vitro studies have shown that exposure to oseltamivir is not expected to be increased significantly nor is exposure to the active metabolite expected to be significantly decreased in patients with hepatic impairment (see Special dosage instructions).

Elderly
Exposure to the active metabolite at steady state was 25-35% higher in elderly (age range 65-78) compared to young adults who were given comparable doses of oseltamivir. Half-lives observed in the elderly were similar to those seen in young adults. On the basis of drug exposure and tolerability, dosage adjustments are not required for elderly patients (see Special dosage instructions)

Children
The pharmacokinetics of oseltamivir have been evaluated in a small group of children 5 to 18 years of age after administration of a single 2 mg/kg oral dose given as an oral powder for reconstitution. The pharmacokinetic data showed that younger children cleared both the prodrug and the active metabolite faster than older children resulting in lower exposure for a given mg/kg dose. In children 5-8 years old, 2 mg/kg gives comparable exposure to that achieved in adults receiving a single 75 mg capsule dose (approximately 1 mg/kg). With advancing age, the difference in exposure between children and adults (per mg/kg dose) became less, such that exposure in children over 12 years of age was similar to that in adults.

Indications
Treatment of influenza in adults and children one year of age or older who present with symptoms typical of influenza, when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of first onset of symptoms. This Indication is based on clinical studies of naturally occurring influenza in which the predominant infection was influenza A.

Prevention of influenza
  • Post exposure prevention in adults and adolescents 13 years of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community. 
  • The appropriate use of oseltamivir for prevention of influenza should be determined on a case by case basis by the circumstances and the population requiring protection, In exceptional situations (e.g. in case of a mismatch between the circulating and vaccine virus strains, and a pandemic situation) seasonal prevention could be considered in adults and adolescents 13 years of age or older
Oseltamivir is not a substitute for influenza vaccination.
The use of antivirals for the treatment and prevention of influenza should be determined on the basis of official recommendations taking into consideration variability of epidemiology and the impact of the disease in different geographical areas and patient populations.

Dosage and administration
Oseltamivir may be taken with or without food. However, taking with food may enhance tolerability in some patients.

Treatment of influenza
Treatment should be initiated as soon as possible within the first two of days of onset of symptoms of influenza.
For adults and adolescents 13 years or older the recommended oral dose is 75 mg oseltamivir twice daily, for 5 days.
For children one year or older, oseltamivir oral suspension is available. For children with body weight above 40 kg, capsules may be prescribed at the adult dosage of 75 mg twice daily for 5 days. The safety and efficacy of oseltamivir in children less than one year of age have not been established.

Prevention of influenza
Post exposure prevention in adults and adolescents 13 years or older: The recommended dose for prevention of influenza following close contact with an infected individual is 75 mg oseltamivir once daily for at least 7 days. Therapy should begin as soon as possible within two days of exposure to an infected individual.
Prevention during an influenza epidemic in the community: The recommended dose for prevention of influenza during a community outbreak is 75 mg oseltamivir once daily for up to six weeks.
The safety and efficacy of oseltamivir for the prevention of influenza in children 12 years of younger have not been established

Special dosage instructions
Patients with renal impairment
Treatment of influenza: Dose adjustment is recommended for adults with severe renal impairment. Recommended doses are detailed in the table below.

Creatinine clearanceRecommended dose for treatment
› 30 (ml/min)75 mg twice daily
› 10 to ‹ 30 (ml/min)75 mg once daily or 30 mg suspension twice daily
‹ 10 (ml/min)Not recommended
dialysis patientsNot recommended

Prevention of influenza: Dose adjustment is recommended for adults with severe renal impairment as detailed in the table below

Creatinine clearanceRecommended dose for treatment
› 30 (ml/min)75 mg once daily
› 10 to ‹30 (ml/min)75 mg every second day or 30 mg suspension once daily
‹ 10 (ml/min)Not recommended
dialysis patientsNot recommended

Elderly
No dose adjustment is required, unless there is evidence of severe renal impairment.
Patients with hepatic impairment.
No dose adjustment is required for patients with hepatic dysfunction.
No dose adjustment is required for elderly patients.

Children
The safety and efficacy of oseltamivir in children under 12 years has not been established.
Limited pediatric pharmacokinetic information is available.

Contraindications
Hypersensitivity to oseltamivir phosphate or to any component of the product.

Precautions
Oseltamivir is effective only against illness caused by influenza viruses. There is no evidence for efficacy of oseltamivir in any illness caused by agents other than influenza viruses.
The safety and efficacy of oseltamivir treatment of children of less than one year of age have not been established.
The safety and efficacy of oseltamivir for the prevention of influenza in children 12 years or younger have not been established.
No information is available regarding the safety and efficacy of oseltamivir in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization.
The safety and efficacy of oseltamivir in either treatment or prevention of influenza in immunocompromised patiens have not been established.
Efficacy of oseltamivir in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established, No difference in the incidence of complications was observed between the treatment and placebo groups in this population.
Oseltamivir is not a substitute for influenza vaccination. Use of oseltamivir must not affect the evaluation of individuals for annual influenza vaccination. The protection against influenza lasts only as long as oseltamivir is administered. Oseltamivir should be used for the treatment and prevention of influenza only when reliable epidemiological data indicate that influenza virus is circulating in the community.

Severe renal impairment
Dose adjustment is recommended for both treatment and prevention in adults with severe renal
insufficiency. There are no data concerning the safety and efficacy of oseltamivir in children with
renal impairment.
Pregnancy and lactation
There are no adequate data from the use of oseltamivir in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal or postnatal development. Oseltamivir should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the foetus.
In lactating rats, oseltamivir and the active metabolite are excreted in the milk. It is not known whether oseltamivir or the active metabolite are excreted in human milk, Oseltamivir should be used during lactation only if the potential benefit for the mother Justifies the potential risk for the nursing infant.

Undesirable effects
Treatment of influenza in adults and adolescents: A total of 2107 patients participated in phase III studies in the treatment of influenza. The most frequently reported undesirable effects were nausea, vomiting and abdominal pain. The majority of these events were reported on a single occasion on either the first or second treatment day and resolved spontaneously within 1-2 days. All events that were reported commonly, (i.e. at an incidence of at least 1 %, irrespective of causality) in subjects receiving oseltamivir 75 mg twice daily, are included in the table below.
Treatment of influenza in elderly: In general, the safety profile in the elderly patients was similar to adults aged up to 65 years: incidence of nausea was lower in oseltamivir treated elderly persons (6.7 %) than in those taking placebo (7.8 %) whereas the incidence of vomiting was higher in those who received oseltamivir (4.7 %) than among placebo recipients (3.1 %).
The adverse event profile in adolescents and in the patients with chronic cardiac and/or respiratory disease was qualitatively similar to that of healthy young adults.
Prevention of influenza In prevention studies, where the dosage of oseltamivir was 75 mg once daily for up to 6 weeks, adverse events reported more commonly in subjects receiving oseltamivir compared to subjects receiving placebo (in addition to the events listed in the table below) were: Aches and pains, rhinorrhoea, dyspepsia and upper respiratory tract infection. There were no clinically relevant differences in the safety profile of the elderly subjects, who received oseltamivir or placebo, compared with the younger population.

Most Frequent Adverse Events in Studies in Naturally Acquired Influenza

System Organ
Class
Adverse Event
Treatment
Prevention
Placebo (N=1050)
Oseltamivir
75 mg twice
daily (N=1057)
Placebo (N=1434)
Oseltamivir
75 mg once
daily (N=1480)
Gastrointestinal
Disorders 
Vomitting1
Nausea1, 2
Diarrhoea
Abdominal Pain
3.0 % 
5.7 % 
8.0 %
2.0 %
8.0 % 
7.9 % 
5.5 %
2.2 %
1.0 % 
3.9 % 
2.6 %
1.6 %
2.1 % 
7.0 % 
3.2 %
2.0 %
Infections and InfestationsBronchitis
Bronchitis acute
5.0 %
1.0 %
3.7 %
1.0 %
1.2 %
-
0.7 %
-
General DisordersDizziness
Fatigue
3.0 %
0.7 %
1.9 %
0.8 %
1.5 %
7.5 %
1.6 %
7.9 %
Neurological DisordersHeadache
Insomnia
1.5 %
1.0 %
1.6 %
1.0 %
17.5 %
1.0 %
20.1 %
1.2 %

1Subjects who experienced nausea alone: excludes subjects who experienced nausea in association with vomiting
2The difference between the placebo and oseltamivir groups was statistically significant

Treatment of influenza in children: A total of 1032 children aged 1 to 12 years (including 695 otherwise healthy children aged 1 to 12 years and 334 asthmatic children aged 6 to 12 years) participated in phase III studies of oseltamivir given for the treatment of influenza. A total of 515 children received treatment with oseltamivir suspension. Adverse events occurring in greater than 1% of children receiving oseltamivir are listed In the table below. The most frequently reported adverse event was vomiting, Other events reported more frequently by oseltamivir treated children included abdominal pain, epistaxis, ear disorder and conjunctivitis.
These events generally occurred once, resolved despite continued dosing and did not cause discontinuation of treatment in the vast majority of cases.
Adverse Events occurring in greater than 1 % of children enrolled in Phase III studies of oseltamivir treatment of naturally acquired influenza.

System Organ Class
Adverse Event
Treatment
Placebo (N=517)
Oseltamivir
2 mg/kg (N=515)
Gastrointestinal DisordersVomiting
Diarrhoea
Abdominal pain
Nausea
9.3 %
10.6 %
3.9 %
4.3 %
15.0 %
9.5 %
4.7 %
3.3 %
Infections and InfestationsOtitis media
Pneumonia
Sinusitis
Bronchitis
11.2 %
3.3 %
2.5 %
2.1 %
8.7 %
1.9 %
1.7 %
1.6 %
Respiratory DisordersAsthma (incl. Aggravated)
Epistaxis
3.7 %

2.5 %
3.5 %

3.1 %
Disorders of the Ear and LabyrinthEar disorder
Tympanic membrane
Disorder
1.2 %
1.2 %
1.7 %
1.0 %
Skin and Subcutaneous DisordersDermatitis
1.9 %
1.0 %
Disorders of the Blood and Lymphatic SystemLymphadenopathy
1.5 %
1.0 %
Vision disordersConjunctivitis
0.4 %
1.0 %

In general, the adverse event profile in the children with asthma was qualitatively similar to that of otherwise healthy children.
Observed during clinical practice: The following adverse reactions have been reporterted during post marketing use of oseltamivir: dermatitis, rash, eczema, urticaria hypersensitivity reactions, including anaphylactic/anaphylactoid reactions, as well as very rare reports of severe skin reactions, including Stevens-Johnson Syndrome and erythema multiforme Additionally, there are very rare reports of hepatic function disorders, including hepatitis and elevated liver enzymes in patients with influenza-like illness.

Interactions
Information derived from pharmacology and pharmacokinetic studies of oseltamivir phosphate suggest that clinically significant drug interactions are unlikely, Oseltamivir phosphate is extensively converted to the active compound by esterases, located predominantly in the liver. Drug interactions involving competition for esterases have not been extensively reported in the literature. Low protein binding of oseltamivir and the active metabolite do not suggest the probability of drug displacement interactions In-vitro studies demonstrated that neither oseltamivir phosphate nor the active metabolite is a good substrate for P450 mixed-function oxidases or for glucuronyl transferases (see Pharmacokinetics). There is no mechanistic basis for an interaction with oral contraceptives
Cimetidine, a non-specific inhibitor of cytochrome P450 isoforms and competitor for renal tubular secretion of basic or cationic drugs has no effect on plasma levels of oseltamivir or its active metabolite.
Clinically important drug interactions involving competition for renal tubular secretion are unlikely due to the known safety margin for most of these drugs. the elimination characteristics of the active metabolite (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways. Co-administration of probenecid results in twofold increase in exposure to the active metabolite due to a decrease active tubular secretion in the kidney. However, due to the wide safety margin of the active metabolite, no dose adjustments are required when co-administering with probenecid.
Co-administration with amoxicillin does not alter plasma levels of either compound, indicating that competition for the anionic secretion pathway is weak.
Co-administration with paracetamol does not alter plasma levels of oseltamivir, its active metabolite, or paracetamol. In phase III clinical studies, oseltamivir has been administered with commonly used drugs such as ACE inhibitors (enalapril, captopril), thiazide diuretics (bendrofluazide) antibiotics (penicillin, cephalosporin. azithromycin, erythromycin and doxycycline), H2 receptor blockers (ranitidine, cimetidine), beta-blockers (propranolol) xanthines (theophylline), sympathomimetics (pseudoephidrine), opoids (codeine) corticosteroids, inhaled bronchodilators. and analgesic agents (aspirin, ibuprofen and paracetamol). No change in adverse event profile or frequency has been observed as a result of co-administration of oseltamivir with these compounds.

Overdose
There is no experience with overdose. However, the anticipated manifestations of acute overdose would be nausea. with or without accompanying vomiting, and dizziness. Patients should discontinue the treatment in the event of overdose. No specific antidote is known Special remarks

Stability
See outer pack for storage remark
This medicine should not be used after the expiry date (EXP) shown on the pack

Packs
Blister pack of 10's
Medicine: Keep out of reach of children

Manufactured by
HETERO DRUGS LIMITED
22-110, I.D.A., Jeedimetia, Hyderabad - 500 055, INDIA.

Imported and Distributed by
PT INDOFARMA
Bekasi Indonesia
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Sunday, December 27, 2015

Scelto Injeksi

SCELTO®
INJEKSI

Scelto® 10
Each ampoule contains : Ketorolac tromethamine 10 mg
Scelto® 30
Each ampoule contains : Ketorolac tromethamine 30 mg

DESCRIPTION
Scelto (Ketorolac tromethamine/ketorolac trometamol) is a member of the pyrollo-pyrrole group of non-steroidal anti-inflammatory drugs. The Chemical name for ketorolac tromethamine is a (±) 5-benzoyl-2,3-dihydro-1H-pyrolizine-1-carboxylic acid, 2-amino-2-(hydroxymethyl)-1,3-propanediol. Ketorolac tromethamine is soluble in water and has a pKa of 3.54. The molecular weight of ketorolac tromethamine is 376.41.
Scelto injection is available for intramuscular (IM) and intavenous (IV) administration 30 mg and 10 mg ketorolac tromethamine per ml sterile solution.
Excipients include : sodium chloride, ethanol, and water for injection.

CLINICAL PHARMACOLOGY
Pharmocodynamics
Ketorolac tromethamine is a non-narcotic analgesic. It is nonsteroidal anti-inflammatory and weak antipyretic activity. Ketorolac tromethamine inhibits synthesis of prostaglandins and may be considered a peripherally acting analgesic since it does not have any known effect on opiate receptors.

CLINICAL STUDIES
The analgesic efficacy of intramuscularly administered Scelto was investigated in several studies in two acute post-operative pain models, general surgery (orthopedic, gynecologic and abdominal) and oral surgery (removal of impacted third molars), The studies were primary single-dose, parallel trial designs, in which Scelto was compared to meperidine (pethidine) or morphine administered intramuscularly. In each pain model, patients had moderate to severe pain at baseline. When compared to meperidine 50 and 100 mg, or morphine 6 and 12 mg in patients with post-operative pain. Scelto 10, 30 and 90 mg gave pain relief similar to meperidine 100 mg and morphine 12 mg.
The time to on set of analgesic action was comparable to morphine. The duration of analgesia with Scelto 30 mg and 90 mg was longer than with narcotics. Based on consideration of efficacy and safety after refeated doses, the 30 mg dose demonstrates the best therapeutic index.
In a multicentre, multi-dose (20 doses given over 5 days), post-operative (general surgery) trial of Scelto 30 mg versus morphine 6 and 12 mg each drug given on as needed basis, the overall analgesic effect of Scelto 30 mg was in between that of morphine 6 mg and 12 mg, although the differences between Scelto 30 and morphine 12 mg were not statistically significant. No evidence of respiratory depression has been observed after administration of Scelto in controlled clinical trials. Scelto did not cause constriction. Scelto cause no more drowsiness than morphine in post-operative patients.

PHARMOKINETICS
Ketorolac tromethamine is rapidly and completely absorbed following intramuscular administration with a mean peak plasma concentration of 2.2 mcg/ml occurring an average of 50 minutes after a single 30 mg dose. The terminal plasma half-life is 5.3 hours in young adults and 7 hours in elderly subjects (mean age 72). More than 99 % of the ketorolac in patient bound over a wide concentration range. The pharmacokinetics of ketorolac mean following single or multiple intramuscular doses are linear. Steady state plasma levels are achieved after dosing every 6 hours for one day. No changes in clearance occur with chronic dosing. Following a single intravenous dose, the volume of distribution averages 0.25 L/kg, the ketorolac and its metabolites (conjugates and a parahydroxy metabolite) is in the urine (mean 91.4 %) and the reminder (mean 6.1 %) is excreted in the faeces.
Haemodynamics of patients are not altered by parenteral administration of Scelto. The mean apparent volume (VB) following complete distribution after single dose was approximately 13 litres.

INDICATIONS AND USAGE
Scelto is indicated for short therm management moderately severe, acute pain following surgical procedures. The total duration of ketorolac used should not exceed five days. It is recommended that ketorolac parenteral be used in immediate post-operative period. Patients should be switch ed to alternative analgesics as soos as possible, but Scelto therapy is not exceed 5 days. Scelto is not recommended for use as an obstetrical pre-operative medication or for obstetrical analgesia because it has not been adequately studied for use in the circumstances and because the known effects of drugs that inhibit prostaglandin bio synthesis or uterine contraction and foetal circulation.

CONTRAINDICATIONS
Scelto is contraindicated in patients who have previously established allergy to it. Because of the possibility of cross-sensitivity, Scelto is also contraindicated in patients in whom aspirin or other non steroidal anti inflammatory drugs induce serious allergic manifestation. Scelto is contraindicated in patients with active peptic ulcer.
  • Suspected or confirmed cerebrovascular disease 
  • Haemorrhagic diatheses including coagulant disorders
  • The complete or partial syndrome of nasal polyps, angio oedema or bronchospasm
  • Concurrent treatment with other NSAIDs and ASA
  • Hipovolaemia from any cause or dehydration
  • Moderate or severe renal impairment (serum creatine › 160 micromol/L)
  • A history of asthma
  • Patient who have had operations with a high risk of haemorrhage or incomplete haemostatis, patients on anticoagulants including low dose of Heparin (2500 - 5000 Unit 12 hourly).
  • Concurrent treatment with oxpentyfilline, probenecid or lithium salt. 
  • During pregnancy, labour, delivery or lactation
  • Children ‹ 16 years of age
  • Patients with a prior history of Steven-Johnson syndrome or vesicular bullous rash.
  • Neuraxial (epidural or intrathecal) administration
  • Prophylactic administration before major surgery or intraoperatively when haemostatis is critical because of the increased risk of bleeding.

WARNINGS
As with nonsteroidal anti-inflammatory analgesic agents, Scelto can cause gastrointestinal irritation, ulcers, perforation or bleeding with or without previous symptoms and should be given under close supervision to patients with a history of gastrointestinal tract disease.

PRECAUTIONS
Renal Effects: As with other drugs that inhibit prostaglandin biosynthesis, elevations of serum urea nitrogen and creatinine have been reported in clinical trials with ketorolac tromethamine.
The disposition of ketorolac in dialysis patients has not been studied. Patients who are volume depleted volume by virtue of blood loss or severe dehydration may be dependent on renal prostaglandin production to maintain renal perfusion and therefore glomerular filtration rate, volume depletion should be corrected. In such situations the use of drugs which inhibit prostaglandin synthesis might be expected to further decrease renal blood flow. Caution is advised if Scelto is used in such circumstances. Close monitoring of urine output, serum urea and serum creatinine is recommended until the patient is normovolaemic.
Haemotological Effects: Ketorolac inhibits platelet aggregation and may prolong bleeding time. Ketorolac does not affect platelet count, prothrombin time (PT) or partial thromboplastin time (PTT). Patients who have coagulation disorders or are receiving drug therapy that interferes with haemostatis should be carefully observed when Scelto is administered. Unlike the prolonged effects from aspirin, the inhibition of platelet function by ketorolac is normalized within 24 to 48 hours after the drugs is discontinued. In controlled clinical studies, the incidence of clinically significant post-operative bleeding was 5/1170 (0.4 %) compared to 1/570 (0.2 %) in the control groups receiving opiates. Hepatic Effects: Borderline elevations of one of more liver test may occur, These abnormalities may progress, may remain unchanged, or may be transient with discontinued therapy. Meaningful elevations of serum glutamic oxaloacetic transaminase (SGOT or AST) occurred in controlled clinical trials in less than 1 % of patients. If clinical signs and sympthoms consistent with liver disease develop, or if systemic manifestations occur (e.g. eosinophilia, rash, etc), Scelto should be discontinued. Patients with impaired hepatic function from cirrhosis do not have any clinically important changes in ketorolac clearance. Ketorolac tromethamine is not recommended for use as a pre-operative medication, for support of anesthesia or in obstetrical analgesia.
There are no clinical data available dealing with the safety or efficacy of concomitant use of ketorolac tromethamine with other non steroidal anti-inflammatory drugs. It is not recommended that Scelto be routinely used with other non steroidal anti-inflammatory drugs, because of potential for additive side effects.
For patient with mild renal impairment: see Dosage and Administration.
Renal function should be monitored in patients who have had more than a single i.m dosage of ketorolac, particularly in elderly patients.
Fluid retention and oedema : Fluid retention and oedema have been reported with the use of Scelto, therefore it should be used with caution in patients with cardiac decompensation, hypertension or similar conditions.

DRUG INTERACTIONS
In another study of 12 healthy subjects, co-administration of heparin 5000 U s.c. and Scelto did not show any phamacodynamic effects of the combination on template bleeding time or kaolin cephalin clotting time. Ketorolac is highly bound to human plasma protein (mean 99.2 %), and binding is independent of concentration.
The in vitro binding of warfarin to plasma proteins is only slightly reduced by ketorolac (99.5 % control vs 99.3 % binding with ketorolac). Ketorolac does not alter digoxin protein binding. In vitro studies indicated that at therapeutic concentrations of salicylate (300 mcg/ml), the binding of ketorolac was reduced from approximately 99.2 % to 97.5 %). Therapeutic concentrations of digoxin, warfarin, ibuprofen, naproxen, acetaminophen, phenytoin, tolbutamide and piroxicam did not alter ketorolac protein binding. Because ketorolac is a highly potent drug and present in low concentration in plasma, it would not be expected to displace other protein-bound drugs significantly.
There is no evidence in animal or human studies that ketorolac induces or inhibits the hepatic enzymes capable of metabolizing, itself or other drugs. Hence ketorolac tromethamine would not be expected to alter the pharmacokinetics of other drugs due to enzymes induction or inhibition mechanism.
Inhibition of renal lithium clearance leading to an increase in plasma lithium concentration and potential lithium toxicity has been reported with some prostaglandin synthesis inhibiting drugs.
Ketorolac tromethamine has not been studied in this respect.
Concomitant administration of ketorolac tromethamine and methotrexate should be done with caution since some prostaglandin synthesis inhibiting drugs have been reported to reduce the clearance of methotrexate, and thus possibly enhance the toxicity of methotrexate.

-Warfarin
The concurrent use of NSAIDs and warfarin has been associated with severe, sometime fatal, haemorrhage. The exact interaction mechanism is unknown, but may involve enhanced bleeding from NSAID-induced gastrointestinal ulceration or an additive effect of anticoagulation by warfarin and inhibition of platelet function by NSAIDs. Scelto should be used in combination with warfarin only if absolute necessary, and patients taking this is combination of drugs should be closely monitored.
-ACE inhibitor
As with other NSAIDs, ketorolac may increase the risk of renal impairment associated with the use of ACE inhibitors, particularly in patients that are actually or effectively volume depleted.
-Diuretics
Scelto reduces the diuretic response to furosemide in normovalaemic healthy subjects by approximately 20%.
-Nephrotoxic Agents
The use of drugs with nephrotoxic activity should be avoided when using Scelto aminoglycoside antibiotics.
-Anti epileptic drugs
Sporadic cases of seizures have been reported during concomitant use of Scelto and anti epileptic drugs (phenytoin, carbamazepin)
-Psychoactive drugs
Hallucination have been reported when Scelto was used in patients taking psychoactive drugs.

Carcinogenesis, Mutagenesis, and Impairment of Fertility
In animals studies, ketorolac tromethamine was not associated with tumorigenicity or mutagenicity and did not demonstrate teratogenic potential.

Pregnancy
Scelto is not recommended during pregnancy, labor or delivery.

Nursing Mothers
Scelto is not recommended for treatment of nursing mothers. Secretion of ketorolac in human milk after ingestion of scelto is limited. The milk to plasma ratio of ketorolac concentrations ranged between 0.015 and 0.037 in a study of 10 women.

Pediatric Use
Safety and efficacy in children have not been established. Therefore, Scelto is not recommended for use in children under 16 years of age.

Elderly
Patients over 65 years may be at greater risk than younger patients for adverse events. This age related risk is common to drugs that inhibit prostaglandin synthesis. As with all drugs, the lowest effective dose should be used in elderly patients.

ADVERSE REACTlONS
The adverse reactions listed below were reported to be probably related to Scelto in clinical trials in which patients received up to 20 doses in up to five days of intramuscularly administrated Scelto 30 mg.
Incidence Between 3 and 9 %
Gastrointestinal: dyspepsia, gastrointestinal pain, nausea
Central Nervous System: headache
Incidence Between 1 and 3 %
Gastrointestinal: diarrhoea
Central Nervous System: dizziness, drowsiness, sweating Body as a whole: oedema
Injection site pain was reported by 2 % of patients in multi doses studies (vs 5% for morphine control group).
Incidence 1 % or Less
Gastrointestinal: constipation, gastrointestinal fullness, liver function abnormalities, melaena, peptic ulcer, rectal bleeding, stomatitis, vomiting, flatulence.
Body as a whole: asthenia, myalgia
Hemic ad lymphatic: purpura
Central nervous system: abnormal thinking, depression, dry mouth, euphoria, excessive thirst, inability to concentrate, nervousness, paraesthesia, stimulation, vertigo.
Respiratory : asthma, dyspnoea
Dermatologic: pruritus, urticaria
Special Senses : abnormal vision
Cardiovascular : vasidillation; pallor
Urogenital: increased urinary frequency, oliguria

Drugs Abuse and Physical Dependence
Ketorolac tromethamine is not a narcotic agonist or antagonist. Subjects did not show any subjective symptoms or objective signs of drugs withdrawal upon abrupt discontinuation of intravenous or intramuscular dosing.

OVERDOSAGE
The absence of experience with acute overdosage precludes characterisation of sequalae and assessment of antidotal efficacy at this time. In a gastroscopic study of healthy subjects daily doses of 350 mg given over at 8 hour interval for each of five consecutive days (3 times the highest recommended dose) caused abdominal pain and peptic ulcers which recovered after discontinuation of dosing.

DOSAGE AND ADMINISTRATION
Scelto ampoules are for administration by intramuscular or bolus intravenous injection. Bolus intravenous doses should be given over no less than 15 seconds. Scelto ampoules should not be used, for epidural or spinal administration. The time to onset of analgesic effect following both i.v, and i.m. administration is similar and is approximately 30 minutes, with maximum analgesia occurring within 1 to 2 hours. The median duration analgesia is generally 4 to 6 hours. Dosage should be adjusted according to the severity of the pain and patients response.

Duration of treatment: The administration of continuous multiple daily doses of Scelto intramusculary and intravenously should not exceed 2 days because adverse events may increase with prolonged usage.
Adults
Ampoules : The recommended initial dose of Scelto is 10 mg followed by 10-30 mg every 4 hours to 6 hours as required. The lowest effective dose should be given. A total daily doses of 90 mg for non-elderly and 60 mg for the elderly, renally-impaired patients and patients less than 50 kg should not be exceeded. The maximum duration of treatment should not exceed 2 days. The lowest effective dose should be used for the shortest possible time in all patient population.

For patients receiving Scelto ampoules, the total combined daily dose should not exceed 90 mg (60 mg for the elderly, renally impaired patients and patients less than 50 kg).

Special dosage instructions
Elderly patients: Ampoules : For patients over 65 years, the lower end of the dosage range is recommended a total daily dose of 60 mg should not be exceeded (see Precautions).

Children: Safety and efficacy in children have not been established. Therefore, Scelto is contraindicated for use in children under 16 years of age.

Renal impairment : Since ketorolac tromethamine and its metabolites are excreted primarily by the kidney, Scelto is contraindicated in moderate to severe impairment (serum creatinine › 160 m mol/l); patients with less renal impairment should receive a reduce dose (not exceeding 60 mg/day i.v. or i.m., and their status should be closely monitored

Combination treatment (See also Incompatibilities).
Opiod analgesics (e.g. morphine, phetidine) may be used concomitantly, and may be required for optimal analgesic effect in the early post-operative period when pain is most severe. Ketorolac tromethamine does not interfere with opioid binding and exacerbate opioid-related respiratory depression or sedation. When used in association with Scelto ampoules, the daily dose of opioid is usually less than that normally required. However, opioid side effects should still be considered, especially in day-case surgery.

Special remarks
Incompatibilities:
Scelto ampoules should not be mixed in a small volume (e.g. in a syringe) with morphine sulphate, pethidine hydrochloride, promethazine hydrochloride or hydroxyzine hydrochloride as precipitation of ketorolac tromethamine will occur.

Scelto ampoules are compatible with normal saline, 5 % dextrose, Ringer's solution, Ringer-lactate solution, or Plasmalyte solution. Compatibility with other drugs is unknown.

Store at room temperaturs (25 - 30 °C). Protect from light.

On medical prescription only
HARUS DENGAN RESEP DOKTER
Medicine, keep out of reach of children

Package
Scelto Injection 10 mg/ml
Box of 5 ampoules
Reg. No.DKL0321628043A1

Scelto Injection 30 mg/ml
Box of 5 ampoules
Reg. No.DKL0321628043B1

Manufactured by :
PHAROS
JAKARTA - INDONESIA
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Saturday, December 26, 2015

Thidim

THIDIM® 
Ceftazidime
injection

Composition:
Each vial contains:
Ceftazidime Pentahydrate equivalent to Anhydrous Ceftazidime .................................................... 1 g
With Sodium Carbonate 118 mg per gram of Ceftazidime

Pharmacology:
Ceftazidime is a semysynthetic, broad-spectrum, betalactam antibiotic for parenteral administration. It is the pentahydrate of pyridinium, 1-[[7-[[(2-amino4-thiazolyl)[(1-carboxy-1-methylethoxy) imino]acetyl]amino]2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl] methyl]-hydroxide, inner salt, [6R-[6a, 7ß(Z)]]. THIDIM® (Ceftazidime for injection), is a sterile, dry, powdered mixture of ceftazidime pentahydrate and sodium carbonate. The sodium carbonate at a concentration of 118 mg/g of ceftazidime activity has been admixed to facilitate dissolution. The total sodium content of the mixture is approximately 54 mg (2.3 mEq)/g of ceftazidime activity.
THIDIM® in sterile crystalline form is supplied in vials equivalent to 1 g of anhydrous ceftazidime. Solutions of THIDIM® range in color from light yellow to amber, depending on the diluent and volume used. The pH of freshly constituted solutions usually ranges from 5-8. After i.v. administration of 500 mg and 1 g doses of ceftazidime over 5 minutes to normal adult male volunteers, mean peak serum concentrations of 45 and 90 µg/ml, respectively, were achieved.
After i.v. infusion of 500 mg, 1 g and 2 doses of Ceftazidime over 20-30 minutes to normal adult male volunteers mean peak serum concentrations of 42, 69 and 170 µg/ml, respectively, were achieved. The half-life following i.v. administration was approximately 1.9 hours. Less than 10% of ceftazidime was protein bound. The degree of protein binding was independent of concentration. There was no evidence of accumulation of ceftazidime in the serum in individuals with normal renal function following multiple i.v. doses of 1 and 2 g every 8 hours for 10 days. Following intramuscular (i.m.) administration of 500 mg and 1 g doses of ceftazidime to normal adult volunteers, the mean peak serum concentrations were 17 and 39 µg/ml, respectively, at approximately 1 hour. Serum concentrations remained above 4 µg/ml for 6 and 8 hours after the i.m. administration of 500 mg and 1 g doses, respectively. The half-life of ceftazidime in these volunteers was approximately 2 hours. The presence of hepatic dysfunction had no effect on the pharmacokinetics of ceftazidime. Therefore, a dosage adjustment from the normal recommended dosage is not required for patients with hepatic dysfunction, provided renal function is not impaired. Approximately 80%-90% of an i.m. or i.v. dose of ceftazidime is excreted unchanged by the kidneys over a 24 - hour period. After the i.v. administration of single 500 mg or 1 g doses, approximately 50% of the dose appeared in the urine in the first 2 hours. An additional 20% was excreted between 2 and 4 hours after dosing, and approximately another 12% of the dose appeared in the urine between 4 and 8 hours later. The elimination of ceftazidime by the kidneys resulted in high therapeutic concentrations in the urine.
Since ceftazidime is eliminated almost solely by the kidneys, its serum half-life is significantly prolonged in patients with impaired renal function. Consequently, dosage adjustments in such patients as described in the Dosage and administration section are suggested.
Ceftazidime is bactericidal in action, exerting its effect by inhibition of enzymes responsible for cell-wall synthesis. A wide range of gram-negative organisms is susceptible to ceftazidime in vitro, including strains resistant to gentamycin and other aminoglycosides.
Ceftazidime has been shown to be active against the following organisms both in vitro and in clinical infections.
Aerobes, Gram-negative: Citrobacter spp. including Citrobacter freundii and Citrobacter diversus, Enterobacter spp. including Enterobacter cloacae and Enterobacter aerogenes, Escherichia coli, Haemophilus influenzae including ampicillin-resistant strains, Klebsiella spp. including Klebsiella pneumoniae, Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Pseudomonas spp. (including Pseudomonas aeruginosa) and Serratia spp.
Aerobes, Gram-positive: Staphylococcus aureus including penicillinase and non-penicillinase-producing strains, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae and Streptococcus pyogenes (group A ß-hemolytic streptococci).
Anaerobes: Bacteroides spp. (NOTE: many strains of Bacteroides fragilis are resistant). Ceftazidime has been shown to be active in vitro against most strains of the following organisms; however, the clinical significance of these data is unknown: Acinetobacter spp.; Clostridium spp. (not including Clostridium difficile); Haemophilus parainfluenzae; Morganella morganii (formerly Proteus morganii); Neisseria gonorrhoeae; Peptococcus spp.; Peptostreptococcus spp.; Providencia spp. (including Providencia rettgeri, formerly Proteus rettgeri); Salmonella spp.; Shigella spp.; Staphylococcus epidermidis; and Yersinia enterocolitica. Ceftazidime and the aminoglycosides have been shown to be synergistic in vitro against Pseudomonas aeruginosa and the Enterobacteriaceae. Ceftazidime and carbenicillin have also been shown to be synergistic in vitro against Pseudomonas aeruginosa. Ceftazidime is not active in vitro against methicillin-resistant staphylococci; Streptococcus faecalis and many other enterococci; Listeria monocytogenes; Campylobacter spp.; or Clostridium difficile.

Indications:
THIDIM® (Ceftazidime for injection/ceftazidime sodium injection) is indicated for the treatment of patients with infections caused by susceptible strains of the designated organisms in the following diseases:
  1. Lower respiratory tract infections, including pneumonia, caused by Pseudomonas aeruginosa and other Pseudomonas spp.; Haemophilus influenzae, including ampicillin- resistant strains; Klebsiella spp.; Enterobacter spp.; Proteus mirabilis; Escherichia coli; Serratia spp.; Citrobacter spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin-susceptible strains).
  2. Skin and skin structure infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Escherichia coli; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Enterobacter spp.; Serratia spp.; Staphylococcus aureus (methicillin-susceptible strains); and Streptococcus pyogenes (group A ß-hemolytic streptococci).
  3. Urinary tract infections, both complicated and uncomplicated, caused by Pseudomonas aeruginosa; Enterobacter spp.; Proteus spp., including Proteus mirabilis and indole-positive Proteus; Klebsiella spp.; and Escherichia coli.
  4. Bacterial septicemia caused by Pseudomonas aeruginosa; Klebsiella spp.; Haemophilus influenzae; Escherichia coli; Serratia spp.; Streptococcus pneumoniae; and Staphylococcus aureus (methicillin susceptible strains).
  5. Bone and joint Infections caused by Pseudomonas aeruginosa; Klebsiella spp.; Enterobacter spp.; and Staphylococcus aureus (methicillin-susceptible strains).
  6. Intra-abdominal infections, including peritonitis caused by Escherichia coli, Klebsiella spp., and Staphylococcus aureus (methicillin-susceptible strains) and polymicrobial infections caused by aerobic and anaerobic organisms and Bacteroides spp. (many strains of Bacteroides fragilis are resistant).
  7. Central Nervous System Infections, including meningitis, caused by Haemophilus influenzae and Neisseria meningitidis. THIDIM® has also been used successfully in a limited number of cases of meningitis due to Pseudomonas aeruginosa and Streptococcus pneumoniae.

Contra indications:
THIDIM® (Ceftazidime) is contraindicated in patients who have shown hypersensitivity to ceftazidime or the cephalosporin group of antibiotics.

Warnings and precautions:
Before therapy with THIDIM® (Ceftazidime) is instituted, careful inquiry should be made to determine whether the patient has had previous hypersensitivity reactions to ceftazidime, cephalosporins, penicillins, or other drugs.
If this product is to be given to penicillin-sensitive patients, caution should be exercised because cross hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to THIDIM® occurs, discontinue the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, i.v. fluids, i.v. antihistamines, corticosteroids, presor amines. and airway management, as clinically indicated. Pseudomembranous colitis has been reported with nearly all antibacterial agents, including ceftazidime. The total daily dosage should be reduced when ceftazidime is administered to patients with renal insufficiency (see Dosage and Administration).
Drug/Laboratory test interactions: The administration of Ceftazidime may result in a false - positive reaction for glucose in the urine using Clinitest® tablets, Benedict's solution, or Fehling's solution. It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as Clinistix® or Tes-Tape®) be used.
Pregnancy: Teratogenic effects: Reproduction studies have revealed no evidence of impaired fertility or harm to the fetus due to THIDIM®.
There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing mothers: Ceftazidime is excreted in human milk in low concentrations. Caution should be exercised when THIDIM® is administered to a nursing woman.

Adverse reactions:
Ceftazidime is generally well tolerated. The incidence of adverse reactions associated with the administration of ceftazidime was low in clinical trials. The most common were local reactions following i.v. injection and allergic and gastrointestinal reactions. Other adverse reactions were encountered infrequently. No disulfiram like reactions were reported. The following adverse effects from clinical trials were considered to be either related to ceftazidime therapy or were of uncertain etiology:
Local effects, reported in fewer than 2% of patients, were phlebitis and inflammation at the site of injection.
Hypersensitivity reactions, reported in 2.7% of patients, were pruritus, rash, and fever. Immediate reactions, generally manifested by rash and/or pruritus. Angioedema and anaphylaxis (bronchospasm and/or hypotension) have been reported very rarely. Gastrointestinal Symptoms, reported in fewer than 2.4% of patients, were diarrhea, nausea, vomiting, and abdominal pain. Central Nervous System Reactions (fewer than 1%) included headache, dizziness and paresthesia. Seizures have been reported with several cephalosporins including ceftazidime. In addition, encephalopathy, asterixis and neuromuscular excitability have been reported in renally impaired patients treated with unadjusted dosage regimens of ceftazidime.
Less frequent adverse events (fewer than 1 %) were candidiasis (including oral thrush) and vaginitis. Hematologic: Exceedingly rare cases of hemolytic anemia have been reported.
Laboratory Test Changes were transient and included eosinophilia (1.6-3.7%), positive Coombs' test without hemolysis 4.7%, thrombocytosis 0.4% and slight elevations in one or more of the hepatic enzymes, aspartate aminotransferase (AST, SGOT) 2.8%, alanine aminotransferase (ALT, SGPT) 3.2%, and alkaline phosphatase 0.8%. As with some other cephalosporins, transient elevations of blood urea, blood urea nitrogen, and/or serum creatinine were observed occasionally. Transient leucopenia, neutropenia, agranulocytosis, thrombocytopenia, and lymphocytosis were seen very rarely. In addition to adverse reaction listed above that have been observed in patients treated with ceftazidime, the following adverse reactions and altered laboratory test have been reported for cephalosporin class antibiotics:
Adverse reactions: Urticaria, Stevens Johnson Syndrome, Erythema multiforme, Toxic nephropathy, Hepatic dysfunction including cholestasis, Aplastic anemia hemorrhage.
Altered laboratory tests: Prolonged prothrombine time, false positive test for urinary glucose, elevated bilirubin, pancytopenia.

Overdosage:
Ceftazidime overdosage has occurred in patients with renal failure. In the presence of renal insufficiency, hemodialysis or peritoneal dialysis may aid in the removal of ceftazidime from the body.

Dosage and administration:
The usual adult dosage is 1 gram administered intravenously or intramuscularly every 8 -12 hours. The dosage and route should be determined by the susceptibility of the causative organisms, the severity of infection, and the condition and renal function of the patient

Table 1 : Recommended dosage schedule
Dose
Frequency in dosing hourly
Adults
Usual recommended dosage1 gram i.v. or i.m
8 - 12 
Uncomplicated urinary tract infections250 mg i.v. or i.m.
12 
Bone and joint infections2 grams i.v.
12 
Complicated urinary tract infections500 mg i.v. or i.m.
8 - 12 
Uncomplicated pneumonia; mild skin and skin structure infections500 mg - 1 gram i.v. or i.m.
Serious gynecologic and intra-abdominal infections2 grams i.v.
Meningitis2 grams i.v.
Very severe life-threatening infections, especially in immunocompromised patients2 grams i.v.
Lung infections caused by Pseudomonas spp. in patients with cystic fibrosis with normal renal function30 - 50 mg/kg i.v.
maximum 6 grams/day
Neonates (0-4 weeks)30 mg/kg i.v.
12 
Infants and children (1month-12 years)30 - 50 mg/kg i.v.
maximum 6 grams/day

Impaired hepatic function: No adjustment in dosage is required for patients with hepatic dysfunction.
Impaired renal function: Ceftazidime, is excreted by the kidneys, almost exclusively by glomerular filtration. Therefore, in patients with impaired renal function (glomerular filtration rate [GFR] ‹ 50 ml per minute), it is recommended that the dosage of Ceftazidime be reduced to compensate for its slower excretion. In patients with suspected renal insufficiency, an initial loading dose of 1 gram of THIDIM® may be given. An estimate of GFR should be made to determine the appropriate maintenance dose. The recommended dosage is presented in the below table.
When only serum creatinine is available, the following formula (Cockcroft's equation) may be used to estimate creatinine clearance. The serum creatinine should represent a steady state of renal function

Males:
Creatinine clearance (ml/min) =
Weight (kg) x (140-age)
______________________________
72 x serum creatinine (mg/dl)

Females: 0.85 x male value


Table 2 : RECOMMENDED MAINTENANCE DOSES OF CEFTAZIDIME IN RENAL INSUFFICIENCY
Creatinine clearance ml/min
Approx serum creatinine umol/L (mg/dl)
Recommended unit dose of ceftazidime g
Frequency of dosing hourly
50 - 31
150 - 200
(1.7 - 2.3)
1.0
12
30 - 16
200 - 350
(2.3 - 4.0)
1.0
24
15 - 6
350 - 500
(4.0 - 5.6)
0.5
24
‹ 5
› 500
(› 5.6)
0.5
48

Pharmaceutical precautions:
Vials of THIDIM® for injection should be stored at a temperature below 25°C. Occasional storage at temperatures not higher than 30°C for up to 2 months is not detrimental to the product. Protect unconstituted vials from light.
Solutions of THIDIM® for injection retain satisfactory potency for 18 hours if kept below 25°C and for 7 days if refrigerated. Some increase in the colour of prepared solutions of THIDIM® for injection may occur on storage. THIDIM® for injection may be reconstituted for intramuscular administration using 0.5% or 1.0% Lignocaine Hydrochloride Injection BP the resultant solutions may be stored for 18 hours below 25°C or 7 days under refrigeration. Ceftazidime and aminoglycosides should not be mixed in the same giving set or syringe.

Instruction for reconstitution
VOLUMES OF DILUENT
Vial size
Volume of diluent + 
to be added (ml)
Approximate concentrations 
(mg/ml)
1 g intramuscular
1 g intravenous
3.0 ml
10.0 ml
250
90
NOTE: 
Addition should be in two stages (see text)
+ usually water for injections

For 500 mg i.m. or i.v., 1 g i.m, or i.v. Bolus vials


Presentation:
THIDIM® (Ceftazidime) 1 g
Box of 1 vial Reg. No. DKL9511622744B1

ON MEDICAL PRESCRIPTION ONLY. 
HARUS DENGAN RESEP DOKTER.

Store below 25°C.
Protect from light.

Manufactured by .
PT DANKOS FARMA
Jakarta - Indonesia

For:

PT KALBE FARMA Tbk.
Bekasi - Indonesia
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Friday, December 25, 2015

Simpenem Injeksi

SIMPENEM®
Serbuk injeksi steril i.v.
Meropenem 1g

KOMPOSISI
Tiap vial SIMPENEM® mengandung meropenem trihydrate 1,3344 g setara dengan meropenem 1 g

CARA KERJA OBAT 
Farmakodinamik
Meropenem adalah antibiotik karbapenem untuk penggunaan parenteral, relatif stabil terhadap dehidropeptidase-1 (DHP-1) manusia karena itu tidak diperlukan penambahan penghambat DHP-1. Efek bakterisidal meropenem adalah dengan menghambat sintesis dinding sel bakteri. Dengan kemampuannya menembus dinding sel bakteri, meropenem mempunyai tingkat stabilitas yang tinggi terhadap semua β-laktamase serine dan mempunyai afinitas yang kuat terhadap Penicilline Binding Proteins (PBP's). Hal-hal tersebut menjelaskan efek bakterisidal yang poten dan spektrum lebar dari meropenem terhadap bakteri aerob dan anaerob. Kadar bakterisidal minimal (Minimum Bactericidal Concentration, MBC) pada umumnya sama dengan Kadar Hambat Minimal (Minimum Inhibitory Concentretion, MIC). Pada 76% tes bakteri, rasio MBC : MIC adalah ‹ 2.
Meropenem, bersifat stabil pada tes-tes kepekaan dengan menggunakan metode rutin. Pada uji in-vitro meropenem menunjukkan efek yang sinergis dengan antibiotik-antibiotik lain. Meropenem juga menunjukkan efek pasca-antibiotik (post-antibiotic effect) melalui uji in-vitro maupun in-vivo.

Kriteria sensitivitas atau kepekaan kuman didasarkan atas sifat farmakokinetik dan korelasi antara efek klinis dan mikrobiologi dengan metode diameter zona dan MIC dari organisme-organisme penyebab infeksi.

Kategori
Metode pemeriksaan
Diameter Zona (mm)
MIC breakpoint (mg/L)
Peka
≥ 14
≤ 14
Intermediet
12 - 13
8
Resisten
≤ 11
≥ 16

Spektrum antimikroba secara in-vitro dari meropenem termasuk yang signifikan secara klinis yaitu bakteri gram positif, gram negatif, aerob, dan anaerob adalah:

BAKTERI AEROB GRAM POSITIF:
Bacillus spp., Corynebacterium diphteriae, Enterococcus faecalis, Enterococcus liquifaciens, Enterococcus avium, Listeria monocytogenes, Lactobacillus spp., Nocardia asteroides, Staphylococcus aureus (penicilinase negative and positive), Staphylococci-coagulase negative, termasuk Staphylococcus epidermidis, Staphylococcus saprophyticus. Staphylococcus capitis, Staphylococcus cohnii, Staphylococcus xylosus, Staphylococcus warneri, Staphylococcus hominis, Staphylococcus simulans, Staphylococcus intermedius, Staphylococcus sciuri, Staphylococcus lugdunensis, Streptococcus pneumoniae (penicilinase susceptible and resistant), Streptococcus agalactiae, Streptococcus pyogenes, Streptococcus equi, Streptococcus bovis, Streptococcus mitis, Streptococcus mitior, Streptococcus milleri, Streptococcus sanguis, Streptococcus viridans, Streptococcus salivarius, Streptococcus morbillorum, Streptococcus group G, Streptococcus group F, Rhodococcus equi.

BAKTERI AEROB GRAM NEGATIF:
Achromobacter xylosoxidans, Acinetobacter anitratus, Acinetobacter iwoffii, Acinetobacter baumannii, Aeromonas sorbria, Aeromonas caviae, Alcaligenes faecalis, Bordetella bronchiseptica, Brucella melitensis, Campylobacter coli, Campylobacter jejuni, Citrobacter freundii, Citrobecter diversus, Citrobacter koseri, Citrobacter amalonaticus, Enterobacter aerogenes, Enterobacter (Pantoea) agglomerans, Enterobacter cloacae, Enterobacter sakazakii, Escherichia coli, Escherichia hermannii, Gardnerella vaginalis, Haemophilus influenzae (termasuk β-laktamase positif dan strain resisten ampicillin), Haemophilus para influenzae, Haemophilus ducreyi, Helicobacter pylori, Neisseria meningitidis, Neisseria gonorrhoeae, (termasuk β-laktamase positif, resisten penicillin dan strain resisten spectinomycin), Hafnia alvei, Klebsiella pneumoniae, Klebsiella aerogenes, Klebsiella ozaenae, Klebsiella oxytoca, Moraxella (Branhamella) catarrhalis, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Proteus penneri, Providencia rettgeri, Providencia stuartii, Providencia alcalifaciens, Pasteurella multocida, Plesiomonas shigelloides, Pseudomonas pseudomallei, Pseudomonas acidovorans, Salmonella spp., termasuk Salmonella enteriditis/typhi, Serratia marcescens, Serratia liquefaciens, Serratia rubidaea, Shigella flexneri, shigella boydii, Shigella dysenteriae, Vibrio cholerae, Vibrio parahaemolyticus, vibrio vulnificus, Yersinia enterocolitica.

BAKTERI ANAEROB
Actinomyces odontolyticus, Actinomyces meyeri, Bacteroides spp., Prevotella spp., Porphyromonas spp., Bacteroides fragilis, Bacteroides vulgatus, Bacteroides variabilis, Bacteroides pneumosintes, Bacteroides coagulans, Bacteroides uniformis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides eggerthii, Bacteroides capsillosis, Prevotella buccalis, Bacteroides gracilis, Prevotella melaninogenica, Prevotella intermedia, Prevotella bivia, Prevotella splanchnicus, Prevotella oralis, Prevotella disiens, Prevotella rumenicola, Bacteroides ureolyticus,
Prevotella oris, Prevotella buccae, Prevotella denticola, Bacteroides levii, Porphyramonas asaccharolytica, Bifidobacterium spp., Bilophila wadsworthia, Clostridium perfringens, Clostridium bifermentans, Clostridium ramosum, Clostridium sporogenes, Clostridium cadaveris, Clostridium sordellii, Clostridium butyricum, Clostridium clostridiiformis, Clostridium innocuum, Clostridium subterminale, Clostridium tertium, Eubacterium lentum, Eubacterium aerofaciens, Fusobacterium mortiferum, Fusobacterium necrophorum, Fusobacterium nucleatum, Fusobacterium varium, Mobiluncus curtisii, Mobiluncus mulieris, Peptostreptococcus anaerobius, Peptostreptococcus micros, Peptostreptococcus magnus, Peptostreptococcus saccharolyticus, Peptococcus saccharolyticus, Peptostreptococcus assaccharolyticus, Peptostreptococcus magnus, Peptostreptococcus prevotii, Propionibacterium acnes, Propionibacterium avidum, Propionibacterium granulosum, Stenotrophomonas maltophilia, Enterococcus faecium dan Staphylococci yang resisten terhadap methicillin.

Farmakokinetik
Dalam 30 menit pemberian meropenem dosis tunggal secara infus i.v. pada relawan sehat menghasilkan kadar puncak dalam plasma kurang lebih 11 μg/ml dengan dosis 250 mg, 23 μg/ml dengan dosis 500 mg, dan 49 μg/ml dengan dosis 1 g. Tetapi tidak terdapat nilai absolut farmakokinetik yang proporsional antara dosis dengan nilai Cmax dan AUC. Selain itu terdapat data berupa penurunan klirens plasma dari 287 menjadi 205 ml/menit pada rentang dosis 250 mg - 2 g.
Kadar puncak yang dicapai setelah pemberian bolus meropenem dalam 5 menit pada relawan sehat adalah 52 μg/ml dengan dosis 500 mg dan 112 μg/ml dengan dosis 1 g. Melalui pemberian infus 1 g meropenem dalam 2 menit; 3 menit dan 5 menit menghasilkan kadar puncak berturut-turut adalah 110 μg/ml; 91 μg/ml; dan 94 μg/ml. Setelah 6 jam pemberian 500 mg meropenem i.v., terjadi penurunan kadar plasma meropenem menjadi 1 μg/ml. Dengan pemberian meropenem berulang dengan interval 8 jam pada relawan dengan fungsi ginjal normal tidak terjadi akumulasi.

Pada subyek dengan fungsi ginjal normal, waktu paruh meropenem adalah kurang lebih 1 jam. Ikatan protein plasma meropenem adalah ± 2%.
Dalam 12 jam, ± 70% meropenem diekskresi melalui urin dalam bentuk utuh. Konsentrasi meropenem dalam urin sebesar 10 μg/ml selama 5 jam setelah pemberian 500 mg. Tidak terjadi akumulasi dalam plasma maupun urin setelah pemberian 500 mg meropenem setiap 8 jam maupun 1 g meropenem setiap 6 jam pada relawan sehat.
Meropenem terdistribusi dengan baik ke berbagai cairan dan jaringan tubuh termasuk cairan serebrospinal pada penderita meningitis bakteri, yang dapat mencapai konsentrasi memadai untuk mengatasi bakteri-bakteri penyebab.

Dari suatu studi pada anak-anak menunjukkan bahwa meropenem mempunyai sifat-sifat farmakokinetik yang mirip antara anak-anak dan dewasa. Waktu paruh meropenem ± 1,5 - 2,3 jam pada anak-anak di bawah umur 2 tahun dan profil farmakokinetik tersebut bersifat linier dengan rentang dosis 10 - 40 mg/kg BB. Studi farmakokinetik pada penderita dengan insufisiensi ginjal menunjukkan klirens meropenem plasma berkorelasi dengan klirens kreatinin. Untuk penderita dengan gangguan fungsi ginjal perlu penyesuaian dosis.

Studi farmakokinetik pada orang tua menunjukkan penurunan klirens meropenem plasma yang berkorelasi dengan usia seiring dengan penurunan klirens kreatinin. Studi lain menunjukkan bahwa penyakit hati tidak mempengaruhi profil farmakokinetik meropenem.

Data studi keamanan pre-klinik
Pada studi hewan menunjukkan bahwa meropenem dapat ditoleransi dengan baik oleh ginjal, efek nefrotoksik terjadi dengan dosis tinggi (500 mg/kg BB). Efek toksik pada SSP berupa kejang pada tikus dan muntah pada anjing terjadi dengan dosis › 2000 mg/kg BB.
LD50 pada tikus / rodent melalui penyuntikan i.v. adalah 2000 mg/kg BB. Hasil dari studi pada anjing dengan dosis berulang (sampai dengan 6 bulan) hanya terjadi efek samping ringan termasuk sedikit penurunan sel darah merah dan peningkatan berat organ hati dengan dosis 500 mg/kg BB. Tidak terdapat bukti efek mutagenitas dalam 5 studi dan tidak terdapat bukti efek toksik pada fungsi reproduksi dan teratogenesitas dengan dosis tinggi pada tikus dan monyet; tidak terdapat pengaruh terhadap berat badan F1 pada tikus dengan dosis 120 mg/kg BB. Terdapat peningkatan kasus aborsi pada monyet dengan dosis 500 mg/kg melalui studi preliminari.
Tidak terdapat bukti terjadinya peningkatan sensitivitas terhadap meropenem pada hewan yuvenil dibandingkan dengan hewan dewasa.
Formulasi intravena dapat ditoleransi melalui studi pada hewan.

INDIKASI
Meropenem i.v, diindikasikan untuk dewasa dan anak-anak yang mengalami infeksi kuman baik tunggal maupun multipel yang sensitif terhadap meropenem:
  • Pneumonia dan nosokomial pneumonia 
  • Infeksi saluran kemih (ISK).
  • Infeksi intra-abdomen.
  • Infeksi ginekologis, antara lain endometritis. 
  • Infeksi kulit dan struktur kulit.
  • Meningitis.
  • Septikemia.
  • Pengobatan empirik, pada penderita dewasa yang diduga infeksi dengan gejala neutropenia febris, digunakan sebagai terapi tunggal maupun kombinasi dengan antivirus atau antijamur. Meropenem terbukti efektif sebagai terapi tunggal maupun kombinasi dengan antimikroba lain pada pengobatan infeksi polimikrobial. Belum ada bukti pada penderita anak-anak yang mengalami neutropenia atau imunodefisiensi primer atau sekunder.

KONTRAINDIKASI
Pada penderita yang menunjukkan reaksi hipersensitif terhadap meropenem.

POSOLOGI 
Dewasa
Dosis dan durasi ditentukan berdasarkan tipe, tingkat keparahan, dan kondisi penderita.
Dosis yang direkomendasikan adalah:
  • 500 mg i.v. setiap 8 jam untuk kasus pneumonia, ISK, infeksi ginekologis misalnya endometritis, infeksi kulit dan struktur kulit 
  • 1 g i.v, setiap 8 jam pada kasus pneumonia nosokomial, peritonitis, penderita yang diduga infeksi dengan gejala neutropenia, septikemia 
  • 2 g i.v. setiap 8 jam untuk kasus meningitis.
  • Seperti antibiotik lain, meropenem direkomendasikan sebagai terapi antibiotik tunggal untuk penderita yang didiagnosis atau dicurigai mengalami infeksi saluran nafas bawah yang disebabkan Pseudomonas aeruginosa dengan kondisi kritis.
  • Uji sensitivitas yang regular direkomendasikan pada pengobatan penyakit infeksi yang disebabkan Pseudomonas aeruginosa.

Dosis pada penderita dewasa dengan gangguan fungsi ginjal.
Dosis harus dikurangi pada penderita dengan klirens kreatinin kurang dari 51 ml/menit, yaitu:

Klirens kreatinin 
(ml/menit)
Dosis 
(berdasarkan unit dosis 500 mg, 1 g , 2 g)
Frekuensi
26 - 501 unit dosissetiap 12 jam
10 - 251 - ½ unit dosissetiap 12 jam
‹ 101 - % unit dosissetiap 24 jam

Meropenem akan dibersihkan melalui hemodialisis, karena itu bila akan menggunakan meropenem pada penderita yang akan atau sedang menjalani hemodialisis dianjurkan untuk menyesuaikan dosis (sesuai dengan tingkat keparahan infeksi) untuk mencapai kadar plasma yang diharapkan. Sedangkan penderita dengan peritoneal dialisis belum terdapat data atau pengalaman

Dosis pada penderita dewasa dengan insufisiensi hati
Pada penderita yang mengalami insufisiensi hati tidak memerlukan penyesuaian dosis.

Penderita lanjut usia
Pada penderita lanjut usia dengan fungsi ginjal normal atau klirens kreatinin di atas 50 ml/menit tidak memerlukan penyesuaian dosis

Anak-anak
Untuk penderita berumur 3 bulan -12 tahun, dosis yang dianjurkan adalah 10 - 20 mg/kg BB setiap 8 jam tergantung dari jenis dan tingkat keparahan infeksi, kepekaan kuman penyebab, dan kondisi penderita. Anak dengan berat badan lebih dari 50 kg dapat menggunakan dosis dewasa. Pada anak yang menderita meningitis, dosis yang direkomendasikan adalah 40 mg/kg BB setiap 8 jam. Tidak ada data atau pengalaman tentang penggunaan meropenem untuk anak-anak yang menderita penyakit ginjal.

Cara penggunaan
Meropenem i.v. dapat diberikan sebagai injeksi bolus intravena kurang lebih dalam 5 menit atau sebagai infus intravena kurang lebih dalam 15 - 30 menit.
Untuk penggunaan injeksi bolus i.v., meropenem i.v. direkonstitusi dengan 20 ml air steril untuk injeksi (konsentrasi 250 mg/5ml )
Larutan mengandung kurang lebih 50 mg/ml. Larutan hasil rekonstitusi bersifat jernih, tidak berwarna, atau berwarna kuning muda yang jernih. Untuk penggunaan infus, meropenem i.v. direkonstitusi dengan cairan infus yang kompatibel atau sesuai (50 - 200 ml).

PERINGATAN DAN PERHATIAN
Terdapat beberapa bukti klinis dan laboratorium menunjukkan adanya alergi silang yang bersifat parsial antara karbapenem lain dengan antibiotik β-laktam, yaitu penisilin dan sefalosporin. Walaupun jarang terjadi tetapi ada laporan tentang timbulnya reaksi hipersensitivitas akibat meropenern. Sebelum memberikan meropenem, harus diketahui riwayat hipersensitif terhadap antibiotik golongan &bta;-laktam.
Meropenem harus diberikan dengan hati-hati pada penderita yang memiliki riwayat alergi. Jika terjadi reaksi alergi terhadap meropenem, pemberian obat harus dihentikan dan dilakukan tindakan yang sesuai untuk mengatasinya.
Pemberian meropenem pada penderita dengan penyakit hati harus disertai dengan memonitor kadar transaminase dan bilirubin darah. Seperti halnya pada antibiotik lain, dapat terjadi pertumbuhan yang berlebihan mikroorganisme yang tidak peka, karena itu sebaiknya dilakukan pengamatan terus-menerus pada setiap penderita
Tidak direkomendasikan untuk penyakit infeksi yang disebabkan oleh bakteri Staphylococci yang resisten terhadap metisitin (MRSA).
Harus dipertimbangkan dengan seksama bila akan diberikan pada penderita yang mempunyai keluhan pada gastrointestinal, khususnya kolitis karena terdapat insiden efek samping kolitis pseudo-membranosa, walaupun jarang. Perlu diwaspadai akan kolitis pseudo-membranosa bila terjadi diare akibat penggunaan meropenem. Walaupun beberapa studi menyatakan bahwa toksin yang diproduksi oleh Clostridium difficile merupakan salah satu penyebab utama hubungan antara antibiotik dengan kolitis, penyebab lain juga harus dipertimbangkan. Penggunaan kombinasi meropenem dengan antibiotik lain yang berpotensi nefrotoksik harus dipertimbangkan dengan seksama.

Penggunaan pada pediatrik
Meropenem tidak direkomendasikan pada bayi di bawah umur 3 bulan karena belum terdapat data tentang efikasi dan tolerabilitas untuk bayi berumur tersebut. Belum ada data dan pengalaman untuk anak-anak yang menderita penyakit hati dan ginjal.

Kehamilan
Belum ada data tentang pemberian meropenem pada perempuan hamil. Melalui studi preklinik tidak terjadi efek samping pada fetus hewan percobaan. Efek samping yang timbul adalah meningkatnya insidensi keguguran pada monyet yang kemungkinan 13 kali lipat akan terjadi pada manusia.

Meropenem tidak dianjurkan untuk diberikan pada perempuan hamil kecuali setelah melalui pertimbangan mengenai resiko dan keuntungan penggunaan obat tersebut pada janin. Pada setiap kasus harus melalui pertimbangan langsung oleh dokter.

Menyusui
Meropenem terdeteksi dengan konsentrasi rendah pada air susu hewan percobaan. Karena itu meropenem tidak dianjurkan diberikan pada perempuan menyusui kecuali setelah mempertimbangkan dengan seksama potensi resiko dibandingkan dengan keuntungannya pada bayi


Efek terhadap tingkat kewaspadaan
Tidak terdapat data tentang pengaruh meropenem pada kemampuan atau tingkat kewaspadaan saat berkendaraan atau mengoperasikan mesin.

EFEK SAMPING
Efek samping yang serius jarang terjadi. Selama uji klinik insidensi efek samping yang dilaporkan terjadi adalah:
  • Reaksi lokal di area injeksi i.v.: inflamasi, tromboflebitis, nyeri pada daerah suntikan.
  • Reaksi alergi sistemik: insiden ini jarang terjadi berupa angioedema dan manifestasi anafilaksis sebagai reaksi hipersensitivitas selama pemberian meropenem.
  • Reaksi kulit: rash, pruritus, urtikaria.
  • Insiden yang jarang terjadi adalah eritema multiforme, sindroma Stevens-Johnson dan nekrolisis epidermal toksik.
  • Gastro-intestinal: nyeri abdomen, mual, muntah, diare, dan kolitis pseudomembran.
  • Darah: trombositaemia reversibel, eosinofilia, trombositopenia, leukopenia, dan neutropenia (termasuk yang sangat jarang adalah agranulositosis). Hasil positif langsung maupun tidak langsung dari tes Coomb's dapat terjadi pada beberapa subyek, juga ada laporan mengenai penurunan parsial waktu tromboplastin.
  • Fungsi hati: dapat terjadi peningkatan kadar bilirubin, transaminase, fosfatase alkali, dan LDH serum, baik sendiri-sendiri maupun kombinasi. Susunan saraf pusat sakit kepala, paraestesia. Terdapat laporan tentang kejadian kejang walaupun hubungannya dengan meropenem belum dapat diketahui pasti.
  • Lain-lain kandidiasis oral dan vagina.

INTERAKSI OBAT
Probenesid menghambat sekresi meropenem yang berakibat terjadi peningkatan waktu paruh dan kadar meropenem dalam darah. Karena potensi dan lama kerja meropenem cukup adekuat, maka tidak direkomendasikan pemberian bersama probenesid.
Ikatan protein plasma meropenem cukup rendah yaitu ± 2% sehingga tidak ada interaksi dengan senyawa lain yang mempengaruhi ikatan plasma. Walaupun belum ada data spesifik mengenai interaksi meropenem dengan pengobatan lain, berdasarkan pengalaman tidak terjadi efek samping akibat interaksi farmakologi meropenem dengan obat lain.

OVERDOSIS
Kejadian overdosis dapat terjadi selama terapi, khususnya pada penderita dengan kerusakan ginjal. Terapi overdosis harus secara simptomatis. Pada individu normal eliminasi ginjal dengan cepat akan terjadi, pada subyek dengan kerusakan ginjal hernodialisis akan membuang meropenem dan metabolitnya.

SIFAT-SIFAT FARMASETIKAL
SIMPENEM® tidak boleh dicampur dengan atau ditambahkan dengan obat lain.
SIMPENEM® kompatibel dengan cairan infus:
0,9% cairan natrium klorida, 5% atau 10% cairan glukosa, 5% cairan glukosa dengan 0,02% natrium bikarbonat, 0,9% natrium klorida dan 5% cairan glukosa, 5% glukosa dengan 0,225% cairan natrium klorida, 5% glukosa dengan 0,15% cairan kalium klorida, manitol 2,5% atau cairan 10%.

KEMASAN
SIMPENEM® serbuk injeksi 1 g: kotak @ 1 vial @ 1 g.
No. Reg. DKL 0928204644A1

HARUS DENGAN RESEP DOKTER

Simpan di tempat sejuk (15 -25 °C) dan kering.

Setelah direkonstitusi, larutan stabil selama 2 jam pada suhu di bawah 25 ° C dan selama 12 jam bila disimpan dalam lemari es.

Diproduksi oleh
PT LAPI LABORATORIES
Serang - Indonesia

untuk:
PT SIMEX PHARMACEUTICAL INDONESIA
Sukabumi - Indonesia
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Thursday, December 24, 2015

Hufagripp BP

Hufagripp® BP
Dextromethorphan HBr, Pseudoephedrin HCl, Chlorpheniramine Maleat
Netto 60 ml Syrup

  • Tidak boleh diberikan pada penderita yang peka terhadap obat simpatomimetik lain (misal efedrin, fenilpropanolamin, fenilefrin), penderita tekanan darah tinggi berat, dan yang mendapat terapi obat anti depresan tipe penghambat Monoamin Oksidase (MAO).
  • Tidak boleh melebihi dosis yang dianjurkan.
  • Hati-hati penggunaan pada penderita tekanan darah tinggi atau yang mempunyai potensi tekanan darah tinggi atau stroke, seperti pada penderita dengan berat badan berlebih (over weight) atau penderita usia lanjut.
  • Bila dalam 3 hari gejala flu tidak berkurang segera hubungi dokter atau unit pelayanan kesehatan.
  • Hentikan penggunaan obat ini jika susah tidur, jantung berdebar dan pusing.

Sediaan berbentuk cairan, berwarna merah, rasa manis, aroma tutty frutty dan strawberry

KOMPOSISI:
Tiap sendok takar (5 ml) mengandung
Dextromethorphan HBr7,5mg
Pseudoephedrin HCl                                15mg
Chlorpheniramine Maleate0,5mg

CARA KERJA OBAT:
HUFAGRIPP BP bekerja sebagai antitusif, antihistamin, dan dekongestan hidung.

INDIKASI:
Untuk meringankan batuk tidak berdahak dan pilek.

ATURAN PAKAI:
Dewasa - Anak › 12 tahun:3 x sehari 2 sendok takar
Anak 6 - 12 tahun:3 x sehari 1 sendok takar
Anak 2 - 6 tahun:3 x sehari ½ sendok takar
Anak ‹ 2 tahun:menurut petunjuk dokter


KONTRA INDIKASI:
  • Lihat box warning.
  • Penderita dengan gangguan jantung dan diabetes melitus

EFEK SAMPING:
Mengantuk, sakit kepala, insomnia, eksitasi, takikardia, aritmia, tremor, palpitasi, mulut kering, sedasi, retensi urine, gangguan saluran pencernaan, dan gangguan psikomotor.


PERINGATAN DAN PERHATIAN:
  • Lihat box warning.
  • Hati-hati untuk penderita debil dan hipoksia (kekurangan oksigen)
  • Dapat menyebabkan depresi pernafasan dan susunan saraf pusat pada penggunaan dengan dosis besar atau pada pasien dengan gangguan fungsi pernafasan (misal asma emfisema)
  • Hati-hati penggunaan pada penderita dengan hipertiroidisme, glaucoma, diabetes mellitus, penyakit jantung iskemik, hipertensi, gangguan hati dan ginjal, hipertrofi prostat
  • Tidak dianjurkan penggunaan pada bayi, anak usia di bawah 2 tahun, ibu hamil dan menyusui, kecuali atas petunjuk dokter
  • Selama minum obat ini tidak boleh mengendarai kendaraan bermotor atau menjalankan mesin.

INTERAKSI OBAT:
  • Penggunaan bersamaan dengan obat anti depresan tipe penghambat MAO dapat mengakibatkan krisis hipertensi
  • Antasida dapat meningkatkan efek Pseudoephedrin HCl
  • Penggunaan bersamaan dengan alkohol, depresan SSP, anti kolinergik dapat mengakibatkan mengantuk, pusing, hilang koordinasi otot dan kewaspadaan mental

CARA PENYIMPANAN
Simpan pada suhu kamar (25-30°C), kering dan tertutup rapat

Dapat menyebabkan kantuk.

KEMASAN:
Syrup Dus, Botol @ 60 ml
No. Reg. DTL 0607809137 A1

P. No. 1
Awas! Obat Keras
Bacalah aturan memakainya

P.T. GRATIA HUSADA FARMA
Semarang - Indonesia
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