Action and Spectrum

Spectrum of Activity

ciprofloxacin shows activity on gram-positive aerobic bacteria, gram-negative aerobic bacteria, a few anaerobic bacteria, and other organisms like chlamydia, mycoplasma, mycobacterium, Rickettsia. Ciprofloxacin shows activity more in gram-negative bacteria than gram-positive bacteria. Ciprofloxacin is inactive against fungi and viruses.

Ciprofloxacin shows activity on Gram-positive aerobic cocci in infections against S.aureus( methicillin-susceptible ( oxacillin-susceptible), S.epidermidis( oxacillin-susceptible strains ),S.pneumoniae penicillin-susceptible strains,S. pyogenes (group A β-hemolytic streptococci,  S. epidermidis oxacillin-susceptible strains,  S.pyogenes group A beta-hemolytic streptococci,  S. saprophyticus, Enterococcus faecalis, and active in vitro activity against other staphylococci like S.haemolyticus, S.hominis. some penicillin resistant S.pneumoniae, Viridans streptococci and group C, F, G streptococci, and nonenterococcal group D streptococci.S. pyogenes (group A β-hemolytic streptococci), S. saprophyticus, and Enterococcus faecalis

Gram-positive aerobic bacilli: Active against Bacillus anthracis, Corynebacterium,  Listeria monocytogenes, and resistance to Nocardia asteroides.

Gram-negative aerobes: Active against in vitro Campylobacter jejuni, H.influenzae, H.parainfluenzae, M. cataeehalis, Ps.aeruginosa, and Some Enterobacteriaceae like Yersinia enterocolitica, Shigella, Serratia, Providencia, Salmonella, Providencia, P.mirabilis, P.Vulgaris, E. coli, Klebsiella, M.morgani, Citrobacter, Edwardsiella, Enterobacter

Active in vitro against Aeromonas, Acinebacter, Brucella, Francisella tularensis, Legionella, Vibrio, Yersinia pestis & Burkholderia cepacia, and stenotrophomonas maltophilia are resistant.

Active in vitro and clinical infections against C. pneumoniae, M. pneumoniae, M. tuberculosis, and other mycobacteria.N. gonorrhoeae with decreased susceptibility to ciprofloxacin and other fluoroquinolones (quinolone-resistant N. gonorrhea; QRNG) widely disseminated worldwide, including in the US.

Resistance to ciprofloxacin can occur due to mutation in the target DNA type II topoisomerase enzyme, which results in alterations in membrane permeability and/or efflux pumps.Few cross-resistance occurs between ciprofloxacin and other fluoroquinolones.Some cross-resistance occurs between ciprofloxacin and other fluoroquinolones.

Adult Dosage

Dosage forms

Tab

100mg, 250mg, 500mg, 750mg

ER TAB

500mg,1000mg

Suspension 

250mg per 5ml

500mg per 5ml

INJ various 

200mg/100mL 

200mg/20mL 

400mg/40mL 

400mg/200mL 

Bacterial Infection

Oral route 

Dose 250-750mg per orally every 12 hour

Info: duration varies with infection type, severity

Intravenous 

Dose 200-400mg IV every 12 hour

Severe/Complicated: 400mg IV every 8 hour

Info: duration varies with infection type, severity

Urinary Tract Infection 

Uncomplicated cystitis

Dose: 500mg ER PO every 24 hr for three days

Alt: 250mg per orally every 12 hr for three days

Patients with no alternative treatment options; refer to IDSA guidelines; do not cut/crush/chew ER tab.

Uncomplicated pyelonephritis

Dose:1000mg per orally ER every 24 hr for seven days

Alt:500 mg Per orally every 12 hr for seven days; 400mg IVx1, then 500mg Per orally every 12 hr for seven days totals; 400mg IV every

Complicated 

Dose: 1000mg ER per orally every 24 hr for 7 to 14 days

Alt:500 mg Per orally every 12 hr for 7 to 14 days; 400mg IV 12hr for 7-14 day

Info: do not cut/crush/chew ER tab

Intra-abdominal infections, complicated

Dose:500 mg Per Orally every 12hr for 7-14 days

Alt: 400 mg IV every 12h for 7-14 days

Info: Part of a multi-drug regimen

Bone/joint infections

Dose:500-750 mg Per Orally every 12 hr for 4-8wk

Alt: 400 mg IV every 8-12hr for 4-8wk

Prostatitis, Chronic Bacterial

500 mg PO q12h x28 days

Pneumonia, hospital-acquired or ventilator-assoc.

400 mg IV q8h x7 days

Info: may extend duration based on clinical response; refer to IDSA guidelines

Anthrax

systemic

Dose: 400 mg IV every 8hr for at least 2wk;

Info: 1st-line agent; part of multi-drug regimen; may use as a 1st-line agent in pregnant women; switch to PO Abx for post-exposure prophylaxis if inhalational exposure

cutaneous

Dose: 500 mg PO q12h x7-10 days; Info: for non-systemic infection; 1st-line agent; may use as 1st-line agent in pregnant women; use extended duration for post-exposure prophylaxis if bioterrorism suspected.

post-exposure prophylaxis

Dose: 500 mg PO q12h x60 days;

Info: 1st-line agent; give in combo w/ anthrax vaccine; may use as a 1st-line agent in pregnant women; may give x42 days or x14 days after last vaccine dose in immunocompetent pts 18-65 year; if anthrax vaccine regimen completed.

Typhoid fever

500 mg Per Orally every12h x2wk

Plague

500-750 mg Per Orally every 12h x2wk

Info: for prophylaxis and treatment

Chancroid

500 mg Per Orally every 12h x3 days

Salmonellosis, acute

500-750 mg Per Orally every 12h x3-7 days

Info: may extend tratment x1wk if immunocompromised

Salmonella, chronic carrier

750 mg PO every 12hr x1mo

Shigellosis, severe

500-750 mg PO every12h

Info: duration varies w/ infection severity; refer to CDC guidance

Febrile neutropenia, chemo-induced

Pediatric Dosing

Dosage Forms

Tab

100mg, 250mg, 500mg, 750mg

Suspension

250mg per 5 mL

5oomg per 5mL

INJ

200mg/100mL

200mg/20mL

400mg/40mL

400mg/200mL

Urinary Tract Infection

1-17 year

Dose: 18-30 mg/kg/day divided every 8 hr x 10-21 days

Max:400mg/dose IV; 750mg/dose PO

Alt: 20-40mg /kg/day PO divided every 12 hr

Info: for complicated UTI or pyelonephritis; not a first-line agent

Systemic anthrax

Neonates> 32wk gestation

Dose:20-30mg/kg/day IV divided every 12 hr for at least 2wk

Info: 1st line agent; part of multi-drug regimen; dose depends on gestational and postnatal age; switch to Po abx*60 days total if inhalational exposure

(1 mo and older)

Dose: 30 mg/kg/day IV divided q8h for at least 2wk; Max: 400 mg/dose; Info: 1st-line agent; part of multi-drug regimen; switch to PO abx x60 days total if inhalational exposure

Anthrax, cutaneous

(neonates >32 wk gestation)

Dose: 20-30 mg/kg/day PO divided q12h x7-10 days; Info: for non-systemic infection; 1st-line agent; dose depends on gestational and post-natal age; give abx x60 days total if bioterrorism suspected

(1 mo and older)

Dose: 30 mg/kg/day PO divided q12h x7-10 days; Max: 500 mg/dose; Info: for non-systemic infection; 1st-line agent; give abx x60 days total if bioterrorism suspected

Anthrax, post-exposure prophylaxis

(neonates >32 wk gestation)

Dose: 20-30 mg/kg/day PO divided q12h x60 days; Info: 1st-line agent; dose depends on gestational and post-natal age

[1 mo and older]

Dose: 30 mg/kg/day PO divided q12h x60 days; Max: 500 mg/dose; Info: 1st-line agent

Plague

15 mg/kg/dose PO q8-12h x10-21 days

Max: 500 mg/dose; Info: for prophylaxis and tx

Infections, bacterial

20-30 mg/kg/day PO divided q12h

Alt: 15-30 mg/kg/day IV divided q8-12h; Max: 750 mg/dose PO; 400 mg/dose IV

Resp. infections, cystic fibrosis pts

40 mg/kg/day PO divided q12h

Alt: 30 mg/kg/day IV divided q8h; Max: 750 mg/dose PO; 400 mg/dose IV

Community-acquired pneumonia, mod-severe bacterial

>3 month

Dose: 30 mg/kg/day IV divided q12h x10 days; Info: may switch to PO regimen when possible to complete course

Salmonellosis, acute

20-30 mg/kg/day PO divided q12h x3-7 days

Max: 750 mg/dose; Info: may extend tx x1wk if immunocompromised

Salmonella, chronic carrier

20-30 mg/kg/day PO divided q12h x1mo

Max: 750 mg/dose

Shigellosis, severe

1 mo and older

Dose: 30 mg/kg/day PO divided q12h; Max: 500 mg/dose; Info: duration varies w/ infection severity; refer to CDC guidance

Typhoid fever

30 mg/kg/day PO/IV divided q12h x1-2wk

Max: 500 mg/dose

Chancroid

preadolescents >45 kg and adolescents

Dose: 500 mg PO q12h x3 days

Febrile neutropenia, chemo-induced

20-40 mg/kg/day PO divided q12h

Max: 750 mg/dose; Info: for empiric tx in low-risk pts not on fluoroquinolone prophylaxis; give w/ amoxicillin/clavulanate

Meningococcal prophylaxis

1 mo and older

Dose: 20 mg/kg/dose PO x1; Info: for asymptomatic meningococcal carriers

Infection prophylaxis, surgical

1 yo and older

Dose: 10 mg/kg/dose IV x1; Start: 120min preop; Info: refer to ASHP/IDSA guidelines

Renal dosing

adjust dose frequency

CrCl 10-29: give usual divided dose q18h; CrCl <10: give usually divided dose q24h

HD: give usually divided dose q24h, on dialysis days admin. after dialysis; no supplement; PD: give usually divided dose q24h; no supplement

Hepatic Dosing

Hepatic impairment: caution advised

Drug Interaction

Adverse Reaction

Adverse Reaction

Dizziness

Restlessness

Lightheadedness

Vaginitis

Insomnia

Photosensitivity

Pruritus

Rash

Anxiety

Agitation

Confusion

Tendinitis

Arthralgia

Lfts Elevated

Myalgia

Disorientation

Attention Disturbance

Nervousness

Impaired Memory

Delirium

Paranoia

Hallucinations

Nightmares

Tremor

Hyperglycemia

Black Box Warning

Black Box Warning

SERIOUS ADVERSE REACTION

Permanent disabled adverse reaction found while using fluoroquinolones with tendinitis and tendon rupture, peripheral neuropathy, and CNS effects.

Tendinitis/tendon rupture may occur during treatment or months after discontinued treatment and risk all ages.

Risk increased in older patients aged more than 60 years.

Strictly Avoided in the patient on Corticosteroids and Kidney/Heart/Lung transplant patients.

Avoid in Myasthenia Gravis patients leads to exacerbating muscle weakness.

RESERVE USE FOR PATIENTS WITH NO ALTERNATIVE OPTIONS

ACUTE BACTERIAL SINUSITIS

ACUTE BACTERIAL EXACERBATION OF CHRONIC BRONCHITIS

UNCOMPLICATED UTI

Contraindication / Caution

Contraindication / Caution

Caution If Qt Prolongation

Caution If Congenital Long Qt Syndrome

Caution If Qt Prolongation Family Hx

Caution If Torsades De Pointes Hx

Caution If Ventricular Arrhythmias

Caution If Bradycardia

Caution If Recent Mi

Caution If CHF

Caution If Electrolyte Abnormalities

Caution If G6pd Deficiency

Caution If Tendon Disorder History

Caution If Kidney, Heart Or Lung Transplant

Caution If Peripheral Neuropathy Or History

Caution If Renal Impairment

Caution If Hepatic Impairment

Caution If Seizure Disorder

Caution If Seizure Threshold Lowered

Caution If Cns Disorder

Caution If Dehydration

Caution If Diabetes Mellitus

Caution If Recent Abx-Assoc. Colitis History

Caution If Depression Or History

Pregnancy / Lactation

Pregnancy / Lactation

Pregnancy Warning

Weigh risk/benefit during pregnancy; no known risk of teratogenicity based on human and animal data; possible risk of spontaneous abortion based on conflicting human data; risk of bone/cartilage damage based on animal data

Breastfeeding Warnings

Consider avoiding breastfeeding x3-4h after dose if anthrax use, otherwise consider avoiding breastfeeding during tx and x2 days after D/C; inadequate human data available, though the possible risk of infant C. Difficile-assoc. Diarrhea; no human data available to assess effects on milk production

Pharmacology

Pharmacology

Mechanism Of Action.

Fluoroquinolones inhibit the enzyme bacterial DNA gyrase ( Primarily active in gram-negative bacteria), which nicks double-stranded DNA, introduces negative supercoils, and then reseals the neaked ends, needed to prevent supercoiling of strands. At the same time, they separate to permit replication or transcription. The DNA gyrase Consist of Two A and Two B subunits : The A subunits carry nicking DNA, the B subunit introduces negative supercoils & then the A subunit reseals the strands. Fluoroquinolones bind to A subunits with high affinity and interfere with its strand cutting and resealing function.  In gram-positive bacteria, the primary target of   Fluoroquinolones action is a similar enzyme  topoisomerase IV which nicks and DNA replicates & separates daughter DNA strands from it. Higher the topoisomerase IV affinity confer higher potency against gram-positive bacteria. The bactericidal action probably results from the digestion of DNA by exonucleases whose production is signaled by the damaged DNA.

Mechanism of Resistance 

 Resistance was noted due to chromosomal mutation producing DNA gyrase or Topoisomerase IV with reduced affinity for Fluoroquinolones or reduced permeability /increased efflux of this drug across the bacterial membrane. Opposite to nalidixic acid, which selects single-step resistance mutants at high frequency, Fluoroquinolones resistance mutants are not easily selected; therefore, resistance to fluoroquinolones is slow to develop. However, reported increasing resistance among Salmonella, Pseudomonas, Staphylococci, Gonococci, and Pneumococci

Absorption

Bioavailability (PO): ~50-85%

Peak plasma time (PO): Immediate-release, 0.5-2 hr; extended-release, 1-2.5 hr

Distribution

Distributed widely throughout the body; tissue concentrations often exceed serum concentrations, especially in kidneys, gallbladder, liver, lungs, gynecologic tissue, and prostatic tissue; cerebrospinal fluid (CSF) concentration is 10% in noninflamed meninges and 14-37% in inflamed meninges; crosses placenta; enters breast milk.

Protein bound

20-40%

Vd: 2.1-2.7 L/kg

Metabolism

Metabolized in liver

Enzyme inhibitor: CYP1A2

Elimination

Half-life: 2-5 hr (children); 3-5 hr (adults)

Excretion: Urine (30-50%), feces (15-43%)

Adminstartion

Administration

IV Incompatibilities
Additive: Aminophylline, amoxicillin, amoxicillin-clavulanate, amphotericin, ampicillin-sulbactam, ceftazidime, cefuroxime, clindamycin, floxacillin, heparin, piperacillin, sodium bicarbonate, ticarcillin

Aminophylline, ampicillin-sulbactam, azithromycin, cefepime, dexamethasone sodium phosphate, furosemide, heparin, hydrocortisone sodium succinate, magnesium sulfate(?), methylprednisolone sodium succinate, phenytoin, potassium phosphates, propofol, sodium bicarbonate(?), sodium phosphates, total parenteral nutrition formulations, warfarin

IV Compatibilities
Solution: Compatible with most IV fluids
Additive: Amikacin, aztreonam, dobutamine, dopamine, fluconazole, gentamicin, lidocaine, linezolid, metronidazole (ready-to-use form is compatible; hydrochloride form in vial is incompatible), midazolam, potassium chloride, tobramycin
Amiodarone, calcium gluconate, clarithromycin, digoxin, diphenhydramine, dobutamine, dopamine, linezolid, lorazepam, midazolam, promethazine, quinupristin/dalfopristin, tacrolimus

IV Administration
Infuse 1-2 mg/mL (diluted in D5W or NS) into large vein over 60 minutes
When administering intermittently through Y-site, temporarily discontinue primary solution

Stability
Stable at concentration of 0.5-2 mg/mL in D5W or NS for 14 days at room temperature or refrigerated

Patient Information Leaflet

Patient Information Leaflet

Generic Name: ciprofloxacin( Oral / Inj)

Pronounced: SIP roe FLOX a sin

Why do we use Ciprofloxacin?

This drug is from the fluoroquinolone category used for different types of bacterial infection, e.g., Skin Infection, Lung or airway infection like TB, pneumonic and septicemic plague,chronic bronchitis, lower respiratory tract infection, bone infection,

Urinary tract infection, infectious diarrheas caused by E.Coli Campylobacter jejuni & shigella bacteria. Anthrax, Typhoid fever, cervical and urethral gonorrhea, cystitis

WARNING

Ciprofloxacin may cause a serious permanent effect on tendon-like tendon rupture, tendonitis, nerve problem in the leg & arm (peripheral neuropathy), and nervous system problem like depression, seizures.Contact physician if patient are on

Ciprofloxacinand.observe.the.following.symptoms:

Pain/numbness/burning/tingling/weakness in arms/hands/legs/feet, changes in senses touch, pain, temperature, vibration, body position, severe or lasting headache, vision changes, shaking ( tremors), mental/mood changes like agitation, anxiety, confusion, hallucination, depression, rare thoughts of suicide. If the patient observe any sign like pain or swelling in joints/muscles, stop exercising, take a rest and seek medical help.

Avoid patients with age more than 60yr and patients taking prednisolone ( Corticosteroids), patients with transplant (kidney, heart,lung), which leads to increased tendon problems. Ciprofloxacin worsens Myasthenia gravis condition. Consult doctor if patient has new or worsening muscle weakness such as drooping eyelids, unsteady walk, or trouble breathing. Talk to the doctor before using this medicine.

HOW TO USE

Before starting Ciprofloxacin, read the medication guide or patient information leaflet, which the Pharmacist provides. If doubts or questions related to medication, consult doctor. This medicine is either taken with or without food as directed by a doctor, usually twice a day every 12, in the morning and evening. Shake the container well for 15 seconds (apply for Liquid forms )before pouring each dose. Carefully measure

the dose using a measuring device/spoon, along with medication. Do not use the kitchen spoon, which may not get the correct dose .Do not chew the contents of the suspension. Do not use a feeding tube for suspension, which may clog the tube. The dosage and duration of treatment depend upon the patient’s condition and the response to treatment. Drink plenty of water while on medication. To avoid drug-drug interaction, patients need to tell the doctor about their medical history (for Allergies).

Administer this medicine 2 hours before or 6 hours after taking other products that may bind to it, decreasing medication effect.Avoid Dairy products & calcium-containing juices to decrease the absorption of Ciprofloxacin. Take with or without food; absorption is not affected by food. Limit caffeine intake. Take this medicine at least 2 hr before or 6hr after eating calcium-rich foods. Ask doctor/Pharmacist about using nutritional supplement/replacement with this medicine. For the best result, take the dose of medicine simultaneously to avoid missed doses.Complete the course, even if symptoms disappear after a few days. If patients do not complete the course of antibiotics, it increases the chance of the return of the infection. If patients continuously skip the medication without completing the course leads to produce resistance (drugs do not show the effect on the microorganism responsible for infection)of that medicine. If condition persists or worsens, tell to a doctor.

SIDE EFFECT

If observe nausea, diarrhea, dizziness, lightheadedness,headache, or trouble sleeping, talk to Doctor/Pharmacist. The selection of medication for patients by a doctor mostly depends on factors like patients’ history, treatment history, allergic condition, age .

Consult doctor if any side effects like unusual bruising or bleeding, signs of new or persistent fever, sore throat. Also, do not ignore if change in the urine volume, red/pink color urine, dark urine seek medical help immediately because that are the signs of kidney problems. Contact doctor/Pharmacist immediately if patient has severe dizziness,fainting,fast/irregular heartbeat, sudden pain in the Chest/stomach/shortness of breath/back/cough. This medicine rarely produces an intestinal condition due to a bacterial called C.difficile; this condition may occur during or after weeks of treatment stopped. If patient have developed: diarrhea that does not

stop, abdominal or stomach pain/cramping, blood/mucus in patient stool, tell doctor. Suppose patient have these symptoms, do not use anti-diarrhea or opioid products because they may worsen symptoms. This medication’s prolonged use leads to white patches inpatient mouth, a change in vaginal discharge, or any other new symptoms. Serious allergic reaction is rare in this medication, but the patient still find out rash/itching/swelling to the face, tongue, throat—trouble breathing severe dizziness. If patient find out other side effects which are not mentioned, contact doctor/pharmacist, Alternatively, directly report the side effects to the manufacturing company or FDA official website.

PRECAUTIONS

During a doctor visit, tell doctor/pharmacist about any medical history like diabetes, heart problem like heart attack, joint or tendon pain, kidney disease, liver disease, mental/mood disorder, myasthenia gravis, peripheral neuropathy, seizures, blood vessels related disease or condition, B.P, genetic condition, allergic condition or history of allergy with other quinolones antibiotics like norfloxacin,gemifloxacin, levofloxacin, moxifloxacin or ofloxacin. Tell the doctor if the patient has heart problems like prolonged problems. QT intervals rarely cause serious fast/irregular heartbeat and other symptoms such as severe dizziness, fainting which need medical attention. Tell all the information about ongoing treatment and past treatment to the doctor. This medication rarely causes elevated blood sugar levels; check patient blood glucose level and share report with doctors. Monitor increased urination or thirst and consulted doctor. Glyburide with Ciprofloxacin shows an increase in the glucose-lowering effect. Also, observe the symptoms of blood sugar lowering like sudden sweating, shaking, fast heartbeat, hunger, blurred vision, dizziness, or tingling hands/feet. Carry glucose tablets if a diabetic patient with Ciprofloxacin sees the above symptoms. If patient do not carry the glucose tablet, eat sugar content products to elevate the sugar level. Maintain a good sugar level with a proper diet and small meals. Do not skip a meal. doctor needs to switch to another diabetes medication if any reaction occurs. Avoid alcohol or marijuana; Ciprofloxacin already makes dizzy, and intake of alcohol or marijuana makes dizzier, lifting heavy things, driving, or any other things which require alertness. This drug is photosensitive so try to avoid tanning booths and sunlamps. Wear sunscreen and wear protective wear when outside; if patient get sunburned or have any skin-related problem, talk to the doctor. Avoid typhoid vaccine whenpatient are on Ciprofloxacin. Tell the physician/doctor that patient are on ciprofloxacin treatment before immunizations. This medicine contains sucrose so before surgery, tell doctor or dentist patient are taking Ciprofloxacin. This drug is not recommended if patient suffer from a hereditary metabolic condition such as fructose intolerance,sucrase-isomaltase deficiency,glucose-galactose malabsorption. Children are more sensitive to the side effect of this drug, especially in joint/tendon problems. An older patient may suffer more if they have tendon problems on corticosteroids, prolonged QTc interval, and sudden break or tear main blood vessel. Suppose patient nursing infant consult a doctor about treatment.

DRUG INTERACTIONS:

Drug-drug interaction may change how patient medications work, increase risk for a serious side effect, or require patient monitoring. This document does not claim all possible drug-drug interactions.Before visiting the doctor, keep a list of all products patient use,including prescribed drugs, OTC, and herbal products; share this with

doctor or Pharmacist. Without doctor’s approval, do not stop, change, or start the medicine. Some products like acenocoumarol, warfarin, strontiummay interact with Ciprofloxacin.Many drugs likeamiodarone,dofetilide,quinidine,procainamidesotalol prolonged QTc intervalbesides ciprofloxacin . Drugs like duloxetine, flibanserin, lomitapide,pirfenidone, tasimelteon, tizanidine removal of this drug slow down by

Ciprofloxacin. Avoid caffeine intake, OTC product that contains caffeine,this medicine increases the effect of caffeine.

OVERDOSE

The patient overdosed and has serious symptoms of passing out orbreathing; in the US, call 911 and call a poison control centerimmediately. Other countries call an ambulance and are admitted to the hospital.

NOTES

Do not share medicines with anyone. Depending uponmicroorganisms that cause infection in the body, doctors select medicines. This medicine is prescribed for patient current condition, and do not useit without consulting doctor for the next infection. Treatment orselection of right medication depending upon lab test or medical test such as kidney function, blood counts, cultures. This should be monitored closely for

progress or to check the side effects. Consult doctor for more detailsabout the medication. Do not change the brand of medicine without consulting the doctor; not all brands have the same effects.

MISSED DOSE:

If patient miss a dose, If it is less than 6 hours before the next dose, skip the missed dose. Do not double the dose to level up the missed dose. Take the next dose at the regular time.

STORAGE

Store the dry powder in an upright position at room temperature. Do not keep in freeze. Once mixed with water for injection, please keep it in the refrigerator or room temperature. Discard the suspension after 14 days. Keep away from children and pets. Before discarding, consult the doctor/physician if patient have any doubts or queries.