Cipro, Levaquin & Avelox are a class of fluoroquinolone antibiotics that stop infection by killing and stopping the growth of bacteria. This family of antibiotics are so potent that the US Food and Drug Administration has approved them to treat a broad spectrum of bacterial infections from skin infections and urinary tract infections to pneumonia and anthrax. Throughout the years, it had been the go-to antibiotic treatment for many infections.

Prescription Name and Overview

There are six types of fluoroquinolones approved for use in the US. These are ciprofloxacin, ofloxacin, Gemifloxacin, levofloxacin, moxifloxacin, and delafloxacin. They come in the form of tablets, extended-release tablets, liquid suspension, injectables and topical creams.

The length of your treatment depends on the infection you have. It is important to follow the instructions included in your prescription. Don’t substitute one drug to another since one type of fluoroquinolone is different from another.

Generic Name and Overview

Fluoroquinolones (Cipro, Levaquin and Avelox) were first discovered by researchers in the 1960s but were not out in the market until the 1980s. From the time the drugs hit the market, doctors have been prescribing this antibiotic for a wide variety of infections because of its effectivity and reliability.

To date, there are more than 60 generic versions of the fluoroquinolone drugs.

OTC  Name and Overview

         Manufacturer

The most popular brand names for fluoroquinolone are Cipro and Cipro XR (ciprofloxacin), Avelox (moxifloxacin), and Levaquin (levofloxacin).

• Cipro

Of all the available fluoroquinolone drugs in the market, Cipro is the most common and most used. According to pharmacists S. Christopher Jones, et. al at the Office of Surveillance and Epidemiology, about 122.5 million prescriptions were written for the drug.

Cipro is a second-generation fluoroquinolone and was originally approved for use by the FDA in 1987. Bayer is the manufacturer of Cipro.

• Levaquin

The second most used fluoroquinolone is Levaquin. According to the Office of Surveillance and Epidemiology, it has been used in 88.1 million prescriptions between 2004 -2010.

Levaquin is a third-generation fluoroquinolone and has been approved for use by the FDA in 1996.

Johnson and Johnson Pharmaceuticals is the manufacturer of this drug but has discontinued making it, according the FDA. It is unclear why they have discontinued its production. Although all productions have ceased since December 2017, drugs are still in pharmacies and are expected to last until 2020.  

• Avelox

Avelox is the third most used fluoroquinolone in the US. The Office of Surveillance and Epidemiology has stated that it has been prescribed to about 24.3 million people between 2004-2010.

It  is a fourth-generation fluoroquinolone and has been approved to be manufactured by Bayer.

         Labeled Indications

Cipro is prescribed to treat mild-to-moderate urinary tract and respiratory infections. It is also prescribed to treat infectious diarrhea, anthrax, and gonorrhea.

Levaquin is also prescribed to treat urinary tract and respiratory infections. It is also used to treat plague, anthrax, pneumonia, and bronchitis.

Avelox is prescribed to treat multiple drug-resistant types of Streptococcus pneumoniae. This is the type of bacteria that causes ear infections, meningitis and pneumonia. It is also prescribed as treatment for skin infections, cellulitis, and abdominal infections. 

         Active Ingredients

• Cipro

Ciprofloxacin is the active ingredient in Cipro, Cipro XR, and Proquin XR.

• Levaquin

Levofloxacin is the active ingredient in Levaquin

• Avelox

Moxifloxacin is the active ingredient in Avelox

What Is It Used For?

Cipro, Levaquin, and Avelox (fluoroquinolones) are used to fight bacteria such as:

• Bacillus anthracis
• Salmonella typhi
• Campylobacter jejuni
• Streptococcus pneumoniae
• Enterococcus faecalis
• Klebsiella pneumoniae

         How Does it Work?

Fluoroquinolones such as Cipro, Levaquin and Avelox treat certain infections by stopping the growth of certain bacteria that can cause illnesses.

They work by “directly interfering with bacterial DNA”, according to an article by researcher Katie J. Aldred of the Dept. of Biochemistry and Dept. of Medicine at the Vanderbilt University School of Medicine.

The researchers believe “the way these medications work also makes bacteria less likely to become resistant to them versus other antibiotics such as penicillin and tetracycline, according to an article by researcher David C. Hooper in Clinical Infectious Diseases. For example, bacteria that penicillin cannot kill may be susceptible to ciprofloxacin, according to the drug’s label.”

What are the Approved Uses?

•     Skin and skin structure infections
•     Bone and joint infections
•     Complicated intra-abdominal infections
•     Infectious diarrhea
•     Typhoid fever (enteric fever)
•     Uncomplicated cervical and urethral gonorrhea
•     Chronic bacterial prostatitis
•     Lower respiratory tract infections
•     Urinary tract infections
•     Acute uncomplicated cystitis
•     Acute bacterial sinusitis
•     Acute pyelonephritis
•     Acute bacterial exacerbation of chronic bronchitis
• Chronic Bronchitis
• Acute bacterial sinusitis
• Sexually Transmitted diseases
• Prostatitis
• Pneumonia
• Lower Respiratory Tract Infections

         Production Anecdotes / History

Fluoroquinolones were first discovered in the 1960s from the antimalarial drug chloroquine. In the late 1980s, the original fluoroquinolone drugs were introduced to the market. Since then, Ciprofloxacin became one of the most commonly prescribed antibiotic in the world because it was the first one that could be taken orally.

Cipro (ciprofloxacin), Levaquin (levofloxacin), and Avelox (moxifloxacin) are different brands of fluoroquinolones that have been widely used in the U.S. alone. According to a recent survey conducted by the Centers for Disease Control and Prevention, it was  discovered that since its approval for public use in the 1980s up to 2016, about 29.8 million prescriptions of fluoroquinolones were given out by American doctors.

Precautions

Before taking Cipro, Levaquin, and Avelox, inform your doctor if you are allergic to or had severe reactions to fluoroquinolone antibiotics. Inform your doctors if you are taking other prescription, nonprescription, supplements, over-the-counter medicines, or maintenance drugs as these may interact with each other.

If you are pregnant, planning to become pregnant, or lactating, inform or call your doctor immediately as well.

Avoid strenuous physical activities, driving, operating heavy machineries, or participating in activities that are mentally and physically demanding. The medication could interfere with your coordination and judgement.

Do not expose yourself to prolonged sunlight and tanning beds as you may experience sensitivity to the sun while under medication.

Long-Term Use Considerations

• Side Effects. The long-term use considerations are the side effects such as nausea, vomiting, diarrhea, headache, confusion, phototoxicity, hepatoxicity, and cardiotoxicity. There were also concerns raised about the adverse effects on the joint, muscles, and tendons. This drug is not recommended for use in pregnant, lactating, and patients under 18 years of age.
• Bacterial Resistance. The other consideration for long time use is that there are kinds of bacteria that have been discovered to be resistant to fluoroquinolones. These may be due to DNA mutation, decrease outer membrane permeability, or the development of efflux mechanisms.

Drug Interactions

Drug interactions happen when a substance that you are taking changes or disrupts the way how a medication works. Interactions may be harmful to you or inhibit a drug from functioning properly. Always consult your doctor if you are going to start medication with a new drug to know of the full list of potential interactions.

         Can Interact with the Following

Some drugs that has interaction with fluoroquinolones are:

• NSAIDs- this causes convulsions when used with high doses of fluoroquinolones
• Theophylline- causes serious and fatal reactions
• Duloxetine- causes duloxetine toxicity
• Warfarin and other anticoagulants- causes anticoagulation and bleeding
• Antidiabetic drugs- hypoglycemia that could be serious and even fatal
• Phenytoin- causes changes in phenytoin levels and results in seizure or overdose
• Methotrexate- methotrexate toxicity
• Anagrelide, domperidone (and other drugs that prolong QT interval)- may affect the heart’s rhythm and increase the risk of irregular heartbeat
• Tretinoin-Mequinol- increases sensitivity to sunlight
• Live BCG/Selected Antimycobacterials- decreases the effectiveness of BCG vaccine or BCG treatment for bladder cancer

         Can’t Interact with the Following

Multivitamins, supplements, over-the-counter drugs (such as antacids and NSAIDs), and dairy products may affect the drug that you are taking. Always consult a health professional before taking any drug or supplement other than the one prescribed to you.

When To Stop Taking

Medlineplus recommends that healthcare professionals should:

• Avoid prescribing fluoroquinolone antibiotics to patients who have an aortic aneurysm or are at risk for an aortic aneurysm, such as patients with peripheral atherosclerotic vascular diseases, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients.
• Prescribe fluoroquinolones to these patients only when no other treatment options are available.
• Advise all patients to seek immediate medical treatment for any symptoms associated with aortic aneurysm.
• Stop fluoroquinolone treatment immediately if a patient reports side effects suggestive of aortic aneurysm or dissection.

They further recommend that patients should:

• Seek medical attention immediately by going to an emergency room or calling 911 if you experience sudden, severe, and constant pain in the stomach, chest or back.
• Be aware that symptoms of an aortic aneurysm often do not show up until the aneurysm becomes large or bursts, so report any unusual side effects from taking fluoroquinolones to your health care professional immediately.
• Inform your health professional before starting an antibiotic prescription, if you have a history of aneurysms, blockages or hardening of the arteries, high blood pressure, or genetic conditions such as Marfan syndrome or Ehlers-Danlos syndrome.
• If these symptoms are experienced, stop taking the drug and call your doctor immediately or get medical help:

o   severe diarrhea (watery or bloody stools) that may occur with or without fever and stomach cramps (may occur up to 2 months or more after your treatment)

o   rash

o   hives

o   itching

o   peeling or blistering of the skin

o   fever

o   swelling of the eyes, face, mouth, lips, tongue, throat, hands, feet, ankles or lower legs

o   hoarseness or throat tightness

o   difficulty breathing or swallowing

o   ongoing or worsening cough

o   yellowing of the skin or eyes; pale skin; dark urine; or light colored stool

o   extreme thirst or hunger; pale skin; feeling shaky or trembling; fast or fluttering heartbeat; sweating; frequent urination; trembling; blurred vision; or unusual anxiety

o   fainting or loss of consciousness

o   decreased urination

• Not stop the antibiotic without first talking to your health care professional.

Long-Term Side Effects

The long-term side effects are listed below are not exhaustive. Ask your doctor for more information before taking the drug.

• Peripheral neuropathy. WebMD defines this as damage to the nerves that send information to and from the brain and spinal cord and the rest of the body. Damage interrupts this connection, and the symptoms depend on which nerves are affected. In general, the symptoms are in the arms and legs and include numbness, tingling, burning, or shooting pain. Fluoroquinolones cause this long-lasting and potentially irreversible damage to those who are taking the medication.
• Long-term pain, numbness, weakness
• Tendonitis, joint and muscle swelling, pain
• Depression or anxiety
• Nerve damage in the hands, feet, arms, or legs
• Lowered quality of life (job loss, financial problems, family tension, due to the other effects of the drug)
• Prolonged QT interval (serious heart rhythm changes)

FDA Warnings (History Of)

Cidrap states that “the safety warning is one of several that have been issued in recent years by the FDA for fluoroquinolones, one of the most commonly prescribed classes of antibiotics worldwide. These antibiotics—which include drugs such as ciprofloxacin (Cipro), moxifloxacin (Avelox), levofloxacin (Levaquin), Gemifloxacin (Factive) and more than 60 generics—cover a broad-spectrum of gram-positive and gram-negative bacteria and are used to treat a variety of common bacterial infections.”

In 2008, the agency added a Boxed Warning that fluoroquinolone use increased the risk of tendinitis and tendon rupture. That was followed by a 2013 label update that warned that fluoroquinolones taken by mouth or by injections may cause peripheral neuropathy, a nerve condition that can cause weakness, numbness, and pain in the hands and feet.

In 2016, the FDA revised the Boxed Warning, advising that fluoroquinolone use was associated with increased risk of disabling and potentially permanent side effects involving tendons, muscles, joints, nerves, and the central nervous system, and that patients who have acute bacterial sinusitis, acute bacterial exacerbation of chronic bronchitis, and uncomplicated urinary tract infections should use the drugs only if no other options are available.

In July, the FDA announced it was updating fluoroquinolone labels to strengthen warnings about the risk of mental health side effects, including disorientation, memory impairment, and delirium. It also warned of the potential risk of hypoglycemic coma.

The agency issued another warning after reviewing adverse event reports and four observational studies that provided consistent evidence of an association between fluoroquinolone use and aortic aneurysm or dissection. Previously, in May 2017, the FDA had said patient cases and findings from published studies did not support the association. The underlying mechanism for the increased risk of aortic dissection is not yet understood, the agency said.

Other Common Side Effects

• Pins and needles sensations
• Depression, Anxiety, Thoughts of suicide
• Pain, burning, tingling, numbness, weakness
• Headache and severe dizziness
• Nausea, stomach pain, diarrhea
• Sensitivity to sun
• Confusion
• Hallucinations
• Rapid heart beat
• Heartburn
• Vaginal itching and/or discharge
• Pale skin
• Unusual tiredness
• Sleepiness
• Heart rhythm changes
• Changes in blood sugar
• Joint problems

Lawsuits

Several lawsuits have been filed against the manufacturers of the fluoroquinolone antibiotics Cipro, Levaquin and Avelox for nerve damage, also known as peripheral neuropathy, after taking the drugs. In California, lawsuits were filed against the manufacturer of Avelox (Bayer Pharmaceuticals) and Levaquin (Johnson & Johnson) in the Fall of 2014 by patients who were proven to have developed nerve damage right after taking the drug.

In 2015, a woman from Texas also filed a lawsuit against Johnson & Johnson after developing permanent nerve damage after taking Levaquin in 2006. It was prescribed to her during her heart surgery treatment.

Two additional lawsuits are faced by Johnson & Johnson in Pennsylvania by men who claimed to have developed permanent nerve damage after being prescribed Levaquin.

There are still a number of lawsuits being filed against manufacturers of Cipro, Levaquin, and Avelox. Patients who developed nerve damage, tendonitis, pain, numbness, tingling, or weakness of the extremities, and other long-term side effects after taking these drugs qualify to file a lawsuit.