Cipro

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: Listeria monocytogenes and resistance to Nocardia asteroides.Bacillus anthracis, corynebacterium.

 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 M. pneumoniae, M. tuberculosis, C. pneumoniae, N. gonorrhoeae with decreased susceptibility to ciprofloxacin. In the U.S, quinolone-resistant N.gonorrhea widely disseminated. Resistance to ciprofloxacin can occur due to mutation in the target DNA type II topoisomerase enzyme, which results in alterations in membrane permeability and efflux pumps. Few cross-resistance occurs between ciprofloxacin and other fluoroquinolones. Some cross-resistance occurs between ciprofloxacin and other fluoroquinolones.

Drug Interaction

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

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

Aortic Aneurysm Risk (Unless No Other Options)

Marfan Syndrome (Unless No Other Options)

Ehlers-Danlos Syndrome (Unless No Other Options)

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 Warning 

According to data no evidence of the risk of a teratogenic effect on humans and animals. Risk of abortion in human data and bone cartilage damage in animal data.

Breastfeeding Warnings

After a dose of anthrax, avoid breastfeeding for 3 to 4 hrs. Avoid breastfeeding during treatment or 2 days after discontinuation.No data is available for infant C.Difficile assoc. Diarrhea as well as effects on milk production.

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 consists 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 

Adminstartion

IV compatibilities 

Infuse 1-2 mg/mL in Dextrose or normal saline into large vein for 60 min.

When administering intermittently through Y-site, temorarily discontinue primary solution.

IV Incompatibilities

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

Y-site: 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

Y-site: Amiodarone, calcium gluconate, clarithromycin, digoxin, diphenhydramine, dobutamine, dopamine, linezolid, lorazepam, midazolam, promethazine, quinupristin/dalfopristin, tacrolimus

Storage 

Stable at 0.5-2mg/mL in dextrose five or normal saline for 14 days at room temprature or in freeze.

Patient Information Leaflet

Generic Name: Ciprofloxacin( Oral) 

Pronounced: SIP roe FLOX a sin 

Why do we use Ciprofloxacin?

This drug is from fluoroquinolone category used for different types of bacterial infection, e.g., Skin Infection, Lung or airway infection like T.B., 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 severe permanent effect on tendon-like tendon rupture, tendonitis, nerve problem in the leg & arm ( peripheral neuropathy), and nervous system problem like depression seizures. Contact your physician if you are on Ciprofloxacin and 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 you 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 your doctor if you have 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 your 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 for 15 seconds (apply for Liquid forms )before pouring each dose. Carefully measure the amount using a measuring device/spoon, which is given along with medication. Don’t use the kitchen spoon, which may not get the correct dose. Don’t chew the contents of the suspension. Do not use a feeding tube for rest, which may clog the pipe.

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 the medication effect. Avoid Dairy products & calcium-containing juices to reduce 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 your 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 period 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 your condition persists or worsens, tell your doctor. 

SIDE EFFECT 

If you observe nausea, diarrhea, dizziness, lightheadedness, headache, or trouble sleeping, talk to your Doctor/Pharmacist. The selection of medication for patients by a doctor mostly depends on factors like patients’ history, treatment history, allergic condition, age, etc. Consult your doctor if there are any side effects like unusual bruising or bleeding, signs of new or persistent fever, sore throat. Also, don’t 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 your doctor/Pharmacist directly if you have 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 you have developed: diarrhea that doesn’t stop, abdominal or stomach pain/cramping, blood/mucus in your stool, tell your doctor. Suppose you have these symptoms, don’t use anti-diarrhea or opioid products because they may worsen symptoms. This medication’s prolonged use leads to white patches in your mouth, a change in vaginal discharge, or any other new symptoms. Severe allergic reaction is infrequent in this medication, but still, you find out rash/itching/swelling to the face, tongue, throat—trouble breathing severe dizziness. If you find other side effects that are not mentioned, contact your doctor/pharmacist or directly report the side effects to the manufacturing company or FDA official website.

PRECAUTIONS

During a doctor visit, tell your 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 your doctor if you have problems related to heart problems like prolonged. Q.T. intervals rarely cause fast severe/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 your blood glucose level and share report with doctors. Monitor increased urination or thirst and consult your 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 you don’t 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. Your 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 you get sunburned or have any skin-related problem, talk to the doctor.

Avoid typhoid vaccine when you are on Ciprofloxacin. Tell the physician/doctor that you are on ciprofloxacin treatment before immunizations. This medicine contains sucrose so before surgery, tell your doctor or dentist you are taking Ciprofloxacin. This drug is not recommended if you 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 your nursing infant consult a doctor about treatment. 

DRUG INTERACTIONS

Drug-drug interaction may change how your medications work, increase your risk for a severe 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 you use, including prescribed drugs, OTC, and herbal products; share this with your doctor or Pharmacist. Without your doctor’s approval, don’t stop, change, or start the medicine. Some products like acenocoumarol, warfarin, strontium may interact with Ciprofloxacin.Many drugs like amiodarone,dofetilide,quinidine,procainamidesotalol prolonged QTc interval besides 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 severe symptoms of passing out or breathing; in the U.S., call 911 and call a poison control center immediately. Other countries call an ambulance and are admitted to the hospita 

NOTES 

Don’t share your medicines with anyone. You depend upon microorganisms that cause infection in the body medicines selected by doctors. This medicine is prescribed for your current condition, and don’t use it without consulting your doctor for the subsequent infection. Treatment or selection of proper 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 your doctor for more details about the medication. Don’t change the brand of medicine without consulting the doctor; not all brands have the same effect   

MISSED DOSE 

If you miss a dose, If it’s 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 tim  

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 you have any doubts or queries.