Cetraxal

Ciprofloxacin belongs to a class of antibiotics called fluoroquinolones. Ciprofloxacin can cause side effects that may be serious or even cause death. If you get any of the following serious side effects, get medical help right away. Talk with your healthcare provider about whether you should continue to take ciprofloxacin.

1. Tendon rupture or swelling of the tendon (tendinitis)

• Tendon problems can happen in people of all ages who take ciprofloxacin. Tendons are tough cords of tissue that connect muscles to bones. Symptoms of tendon problems may include:
  • Pain, swelling, tears and inflammation of tendons including the back of the ankle (Achilles), shoulder, hand, or other tendon sites.
• The risk of getting tendon problems while you take ciprofloxacin is higher if you:
  • are over 60 years of age
  • are taking steroids (corticosteroids)
  • have had a kidney, heart or lung transplant
• Tendon problems can happen in people who do not have the above risk factors when they take ciprofloxacin. Other reasons that can increase your risk of tendon problems can include:
  • physical activity or exercise
  • kidney failure
  • tendon problems in the past, such as in people with rheumatoid arthritis (RA)
• Call your healthcare provider right away at the first sign of tendon pain, swelling or inflammation. Stop taking ciprofloxacin until tendinitis or tendon rupture has been ruled out by your healthcare provider. Avoid exercise and using the affected area. The most common area of pain and swelling is the Achilles tendon at the back of your ankle. This can also happen with other tendons.
• Talk to your healthcare provider about the risk of tendon rupture with continued use of ciprofloxacin. You may need a different antibiotic that is not a fluoroquinolone to treat your infection.
• Tendon rupture can happen while you are taking or after you have finished taking ciprofloxacin. Tendon ruptures have happened up to several months after patients have finished taking their fluoroquinolone.
• Get medical help right away if you get any of the following signs or symptoms of a tendon rupture:
  • hear or feel a snap or pop in a tendon area
  • bruising right after an injury in a tendon area
  • unable to move the affected area or bear weight

2. Worsening of myasthenia gravis (a disease which causes muscle weakness). Fluoroquinolones like ciprofloxacin may cause worsening of myasthenia gravis symptoms, including muscle weakness and breathing problems. Call your healthcare provider right away if you have any worsening muscle weakness or breathing problems.

Other serious side effects of ciprofloxacin include:

• You may have serious seizure and breathing problems when you take theophylline with ciprofloxacin. These problems may lead to death. Get emergency help right away if you have seizures or trouble breathing.
• Seizures have been reported in people who take fluoroquinolone antibiotics including ciprofloxacin. Tell your healthcare provider if you have a history of seizures. Ask your healthcare provider whether taking ciprofloxacin will change your risk of having a seizure. This serious side effect may happen as soon as after taking the first dose of ciprofloxacin.
• Talk to your healthcare provider right away if you get any of these side effects, or other changes in mood or behavior:
  • feel dizzy
  • seizures
  • hear voices, see things, or sense things that are not there (hallucinations)
  • feel restless
  • tremors
  • feel anxious or nervous
  • confusion
  • depression
  • trouble sleeping
  • nightmares
  • feel more suspicious (paranoia)
  • suicidal thoughts or acts
• ​Allergic reactions, including death, can happen in people taking fluoroquinolones, including ciprofloxacin, even after only one dose. Stop taking ciprofloxacin and get emergency medical help right away if you get any of the following symptoms of a severe allergic reaction:
  • hives
  • trouble breathing or swallowing
  • swelling of the lips, tongue, face
  • throat tightness, hoarseness
  • rapid heartbeat
  • faint
  • yellowing of the skin or eyes. Stop taking ciprofloxacin and tell your healthcare provider right away if you get yellowing of your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction to ciprofloxacin (a liver problem).
  • skin rash (Skin rash may happen in people taking ciprofloxacin even after only one dose. Stop taking ciprofloxacin at the first sign of a skin rash and call your healthcare provider. Skin rash may be a sign of a more serious reaction to ciprofloxacin.)

• Serious heart rhythm changes (QT prolongation and torsade de pointes). Tell your healthcare provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you faint. Ciprofloxacin may cause a rare heart problem known as prolongation of the QT interval. This condition can cause an abnormal heartbeat and can be very dangerous.
• The chances of this event are higher in people:
  • who are elderly
  • with a family history of prolonged QT interval
  • with low blood potassium (hypokalemia)
  • who take certain medicines to control heart rhythm (antiarrhythmics)
  • intestine infection (Pseudomembranous colitis)
• ​Pseudomembranous colitis can happen with most antibiotics, including ciprofloxacin. Call your healthcare provider right away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you have finished your antibiotic.

• Changes in sensation and nerve damage (Peripheral Neuropathy). Damage to the nerves in arms, hands, legs, or feet can happen in people who take fluoroquinolones, including ciprofloxacin. The nerve damage may be permanent. Stop ciprofloxacin and with your healthcare provider right away if you get any of the following symptoms of peripheral neuropathy in your arms, hands, legs, or feet:
  • pain
  • burning
  • tingling
  • numbness
  • weakness
• ​Low blood sugar (hypoglycemia). People who take ciprofloxacin and other fluoroquinolone medicines with the oral anti-diabetes medicine glyburide (Micronase, Glynase, Diabeta, Glucovance) can get low blood sugar (hypoglycemia) which can sometimes be severe. Tell your healthcare provider if you get low blood sugar with ciprofloxacin. Your antibiotic medicine may need to be changed.
• Sensitivity to sunlight (photosensitivity). 
• Joint Problems. Increased chance of problems with joints and tissues around joints in children under 18 years old. Tell your child’s healthcare provider if your child has any joint problems during or after treatment with ciprofloxacin.

Do not take ciprofloxacin if you:

• Have ever had a severe allergic reaction to an antibiotic known as a fluoroquinolone, or are allergic to any of the ingredients in ciprofloxacin. Ask your healthcare provider if you are not sure. 
• Also take a medicine called tizanidine (Zanaflex). Serious side effects from tizanidine are likely to happen.

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

An overdose of ciprofloxacin otic is not expected to be dangerous. Seek emergency medical attention or call the Poison Help line at 1-800-222-1222 if anyone has accidentally swallowed the medication.

Ciprofloxacin ear solution is used to treat otitis externa. Otitis externa, also known as swimmer's ear, is an infection of the outer ear canal caused by bacteria. The ear canal and outer part of the ear may be swollen, red, and painful.

Ciprofloxacin belongs to the class of medicines known as fluoroquinolone antibiotics. It works by killing the bacteria or preventing their growth.

This medicine is available only with your doctor's prescription.

Cetraxal is a quinolone antimicrobial indicated for the treatment of acute otitis externa due to susceptible isolates of Pseudomonas aeruginosa or Staphylococcus aureus.

Cetraxal is a sterile, preservative-free, otic solution of ciprofloxacin hydrochloride equivalent to 0.2 % ciprofloxacin (0.5 mg in 0.25 mL) in each single use container.

Otic Use Only

Cetraxal is for otic use only. It should not be used for injection, for inhalation or for topical ophthalmic use.

Hypersensitivity

Cetraxal should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity.

Growth of Resistant Organisms with Prolonged Use

As with other anti-infectives, use of Cetraxal may result in overgrowth of nonsusceptible organisms, including yeast and fungi. If super-infection occurs, discontinue use and institute alternative therapy.

Lack of Clinical Response

If the infection is not improved after one week of therapy, cultures may help guide further treatment.

Mechanism of Action

Ciprofloxacin is a fluoroquinolone antimicrobial (see 12.4 Clinical Pharmacology, Microbiology).

Pharmacokinetics

The plasma concentrations of ciprofloxacin were not measured following administration of 0.25 mL Cetraxal (total dose: 0.5 mg ciprofloxacin). However, the maximum plasma concentration of ciprofloxacin is anticipated to be less than 5 ng/mL.

Microbiology

The bactericidal action of ciprofloxacin results from interference with the enzyme DNA gyrase, which is needed for the synthesis of bacterial DNA.

Bacterial resistance to quinolones can develop through chromosomally- or plasmid-mediated mechanisms.

The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of macrolides. Therefore, ciprofloxacin may be active against pathogens that are resistant to these antibiotics, and these antibiotics may be active against pathogens that are resistant to ciprofloxacin. In vitro studies demonstrated cross-resistance between ciprofloxacin and some fluoroquinolones.

Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections of acute otitis externa as described in Section 1 Indications and Usage :

Usual Adult Dose for Acute Otitis Externa:

Contents of one single use container should be instilled into the affected ear twice daily (approximately 12 hours apart) for 7 days.
(ciprofloxacin 0.5 mg in 0.25 mL in each single use container).

Usual Pediatric Dose for Acute Otitis Externa:

1 year or older:
Contents of one single use container should be instilled into the affected ear twice daily (approximately 12 hours apart) for 7 days.
(ciprofloxacin 0.5 mg in 0.25 mL in each single use container).

Use the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not use extra medicine to make up the missed dose.

It is not likely that other drugs you take orally or inject will have an effect on ciprofloxacin used in the ears. But many drugs can interact with each other. Tell each of your healthcare providers about all medicines you use, including prescription and over-the-counter medicines, vitamins, and herbal products.

Summary of Use during Lactation

Amounts of ciprofloxacin in breastmilk are low. Fluoroquinolones such as ciprofloxacin have traditionally not been used in infants because of concern about adverse effects on the infants' developing joints. However, studies indicate little risk.[1] The calcium in milk might decrease absorption of the small amounts of fluoroquinolones in milk,[2] but, insufficient data exist to prove or disprove this assertion. Use of ciprofloxacin is acceptable in nursing mothers with monitoring of the infant for possible effects on the gastrointestinal flora, such as diarrhea or candidiasis (thrush, diaper rash). Avoiding breastfeeding for 3 to 4 hours after a dose should decrease the exposure of the infant to ciprofloxacin in breastmilk.

Maternal use of an ear drop or eye drop that contains ciprofloxacin presents negligible risk for the nursing infant. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.

Drug Levels

Maternal Levels. Ten lactating women (time postpartum not stated) were given ciprofloxacin 750 mg orally every 12 hours for 3 doses. Milk ciprofloxacin was measured after the third dose. The highest levels averaging 3.79 mg/L occurred 2 hours after the dose. Average milk levels then fell as follows: 2.26 mg/L at 4 hours; 0.86 mg/L at 6 hours, 0.51 mg/L at 9 hours; 0.2 mg/L at 12 hours; and 0.02 mg/L at 24 hours after the dose.[3] Using the peak milk level data from this study, an exclusively breastfed infant would receive an estimated maximum of 0.57 mg/kg daily with this maternal dosage regimen. This dosage is much lower than the 10 to 40 mg/kg daily used in treating newborn infants.[1]

One mother who was recovering from acute renal failure was given a single dose of ciprofloxacin 500 mg orally with a prenatal vitamin and ferrous sulfate which would be expected to decrease ciprofloxacin bioavailability. Milk levels were 3.5 mg/L at 4, 8 and 12 hours after the dose and 2.3 mg/L 16 hours after the dose.[4] Levels were probably elevated and elimination prolonged by the woman's impaired renal function.

A woman took ciprofloxacin 500 mg daily orally for 10 days. At 10 hours and 40 minutes after the last dose, ciprofloxacin was 0.98 mg/L in breastmilk.[5]

Infant Levels. A woman took ciprofloxacin 500 mg daily orally for 10 days. Her infant, who breastfed once 8 hours after the dose, had no detectable ciprofloxacin (<30 mcg/L) in her serum 2.7 hours after nursing.[5]

Effects in Breastfed Infants

A case of pseudomembranous colitis in a 2-month-old breastfed infant with a history of necrotizing enterocolitis was probably caused by maternal self-treatment with ciprofloxacin.[6]

Ciprofloxacin was used as part of multi-drug regimens to treat three pregnant women with multidrug-resistant tuberculosis throughout pregnancy and postpartum. Their three infants were breastfed (extent and duration not stated). At age 1.25, 1.8 and 3.9 years, the children were developing normally except for one who had failure to thrive, possibly due to tuberculosis contracted after birth.[7]

Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

Alternate Drugs to Consider

(Urinary Tract) Levofloxacin, Nitrofurantoin, Trimethoprim, (Ophthalmic) Levofloxacin, Ofloxacin

References

1. Kaguelidou F, Turner MA, Choonara I et al. Ciprofloxacin use in neonates: A systematic review of the literature. Pediatr Infect Dis J. 2011;30:e29-37. PMID: 21048525

2. Fleiss PM. The effect of maternal medications on breast-feeding infants. J Hum Lact. 1992;8:7. Letter. PMID: 1558663

3. Giamarellou H, Kolokythas E, Petrikkos G et al. Pharmacokinetics of three newer quinolones in pregnant and lactating women. Am J Med. 1989;87(suppl 5A):49S-51S. PMID: 2589384

4. Cover DL, Mueller BA. Ciprofloxacin penetration into human breast milk: a case report. DICP. 1990;24:703-4. PMID: 2375140

5. Gardner DK, Gabbe SG, Harter C. Simultaneous concentrations of ciprofloxacin in breast milk and in serum in mother and breast-fed infant. Clin Pharm. 1992;11:352-4. PMID: 1563233

6. Harmon T, Burkhart G, Applebaum H. Perforated pseudomembranous colitis in the breast-fed infant. J Pediatr Surg. 1992;27:744-6. PMID: 1501036

7. Drobac PC, del Castillo H, Sweetland A et al. Treatment of multidrug-resistant tuberculosis during pregnancy: long-term follow-up of 6 children with intrauterine exposure to second-line agents. Clin Infect Dis. 2005;40:1689-92. PMID: 15889370