Levofloxacin side effects and how to avoid them

Muscle pain, tendinitis, kidney injury, and allergic reactions are less common but possible levofloxacin side effects

By Georgia C. Yalanis, MD | Jul. 27, 2021 Medically reviewed by Anne Jacobson, MD, MPH

Levofloxacin is a fluoroquinolone antibiotic. Fluoroquinolone antibiotics work by inhibiting the enzymes used by bacteria in the synthesis of bacterial DNA. This action prevents the bacteria from replicating. Other fluoroquinolone antibiotics include ciprofloxacin, ofloxacin, and moxifloxacin. You may have seen or heard this drug referred to by the brand name, Levaquin, which was manufactured by Janssen Pharmaceuticals but is now discontinued in the United States.

Fluoroquinolones are highly effective and used to treat many types of bacterial infections and infectious diseases, including infections caused by antibiotic-resistant bacteria. You may be prescribed levofloxacin for bronchitis, sinus infections, pneumonia, sexually transmitted infections, prostatitis, urinary tract infections, or certain skin infections. Levofloxacin is also an effective treatment for anthrax and plague.

The U.S. Food and Drug Administration (FDA) has approved levofloxacin for use in adults and for special cases in children as young as 1 month old. Levofloxacin is not an over-the-counter medication. It is available only by prescription as a tablet, oral solution, or liquid for injection. This article will cover some of the side effects, warnings, and interactions associated with levofloxacin use as well as how to avoid them.

Common side effects of levofloxacin

Levofloxacin use is associated with several common side effects. These side effects are usually not serious and often resolve on their own. Notify your healthcare provider if any of the side effects below become concerning while taking levofloxacin.

Gastrointestinal symptoms including nausea, vomiting, dyspepsia or indigestion, diarrhea, constipation, and abdominal pain
General symptoms of malaise including headache, dizziness, restlessness, lightheadedness, or disorientation
Trouble sleeping including insomnia or nightmares
Psychiatric symptoms including anxiety, agitation, confusion, nervousness, delirium, paranoia, or hallucinations
Vaginitis (vaginal inflammation, discharge, or itching)
Photosensitivity and other skin issues such as rashes or itching
Pain or inflammation in the tendons (tendinitis)
Central nervous system effects such as attention disturbances or impaired memory
Tremor
Hyperglycemia (elevated blood glucose)

Serious side effects of levofloxacin

In a 2016 safety review, the FDA found that systemic (throughout the body) fluoroquinolone use is associated with uncommon, but potentially permanent and disabling adverse effects in the tendons, muscles, joints, nerves, and central nervous system (CNS). Some of these serious side effects have even occurred together including tendinitis with tendon rupture, combination peripheral neuropathies, and multiple central nervous system effects. Notify your healthcare provider immediately if you are taking levofloxacin and experience any of these serious side effects. It is very likely your healthcare provider will discontinue the use of levofloxacin immediately, and avoid future use of fluoroquinolones in anyone who experiences one or more of these serious adverse effects.

Peripheral nervous system effects including peripheral neuropathy or nerve damage to peripheral nerves, which may feel like numbness, tingling, or a prickling sensation similar to “pins and needles” in the arms and legs
Musculoskeletal effects including tendinitis, tendon rupture, muscle weakness, muscle pain, joint pain, joint swelling, or arthropathy
Central nervous system effects including increased intracranial pressure (ICP) and seizures
Psychiatric disturbances including toxic psychosis, suicidality, and depression
Worsening of myasthenia gravis
Severe hypersensitivity reactions and immune responses including severe skin rashes or skin reactions, anaphylaxis, jaundice (yellowing of the skin or eyes), and serum sickness
Cardiac system effects including aortic dissection, aortic aneurysm, and vasculitis
Heart rhythm problems including irregular heartbeat, a long QT interval, and torsades de pointes
Severe hypoglycemia (low blood sugar)
Disorders of the blood including blood dyscrasias and myelosuppression
Kidney injury from renal system involvement including crystals in the urine (crystalluria) and nephrotoxicity
Other bacterial infections including bacterial superinfection and Clostridium difficile-associated diarrhea
Liver problems secondary to hepatotoxicity
Phototoxicity (sensitivity to sunlight)
Uveitis (painful red-eye and blurry vision)

Muscle pain and weakness

Levofloxacin and other quinolone antibiotics may worsen symptoms of muscle pain, weakness, and muscle fatigue associated with myasthenia gravis or unmask a previously undiagnosed case. The mechanisms behind this symptom worsening are complex and believed to include oxidative stress (imbalances in the accumulation of reactive oxygen species) and mitochondrial toxicity within skeletal muscle, resulting in muscle blockade, impaired muscle performance, or even atrophy of the muscle, which may be experienced as muscle pain or weakness.

Since fluoroquinolones are routinely avoided in individuals with myasthenia gravis, there are limited numbers of reported cases of worsening myasthenia gravis associated with fluoroquinolone use. One retrospective study implicated levofloxacin specifically in nine out of 37 reported cases. Notably, most cases of muscle pain or weakness demonstrate rapid improvement after withdrawal of the antibiotic. Speak with your healthcare provider if you experience muscle pain or weakness while taking any fluoroquinolone antibiotic, including levofloxacin.

Tendon rupture

Fluoroquinolones, including levofloxacin, are known to be associated with tendon rupture. Tendon rupture is a very serious, potentially disabling, adverse effect that may additionally occur with tendinitis, peripheral neuropathy, and concomitant CNS effects. Tendon rupture may occur during treatment or even months after treatment.

The risk of tendon rupture is increased in all ages, and this risk further increases with a higher dosage, in patients older than 60 years of age, patients taking corticosteroids, and patients with kidney, heart, or lung transplants. Levofloxacin use should be immediately discontinued and future use potentially avoided in individuals who experience any type of adverse reaction.

A recent study performed in the UK identified 4,836 tendon rupture events in a 1,351,780 adult patient cohort treated with fluoroquinolones.

Kidney injury

Kidney injury is a relatively rare complication associated with fluoroquinolone use. While the absolute incidence is not clearly reported, a study of men in the United States found a 2.18-fold higher relative risk of kidney injury associated with fluoroquinolone use when compared with no use. Crystal-induced acute kidney injury is caused by the precipitation of crystals within the tubules of the kidney, resulting in obstruction, inflammation, and kidney injury.

Pre-existing renal dysfunction, high doses of levofloxacin, and advanced age are risk factors for kidney injury while taking levofloxacin. While kidney function can begin to improve within days of discontinuing the medication, it is important to inform your healthcare provider if you experience any kidney or other urinary tract symptoms while taking this medication.

Levofloxacin allergy

It is uncommon to have an allergic response to levofloxacin, however, there has been an increase in individuals reporting hypersensitivity reactions to quinolone antibiotics, including levofloxacin. While it is difficult to extrapolate to the general population, and data available on the true prevalence of allergic reactions to quinolones is unknown, a review in the International Journal of Clinical Pharmacy reported a 2% quinolone allergy in hospitalized patients in a single institution study.

While it is very rare to have a severe or life-threatening allergic reaction to fluoroquinolones like levofloxacin, it is a good idea to know what signs of a very serious allergic reaction are. If you are taking levofloxacin and notice any of the signs or symptoms of anaphylaxis below, you should seek medical attention right away.

Hives or an itchy skin rash
Swelling under the skin or in the face
Pale, cold skin, or clammy skin
Flushing, fever, or unprovoked sweating and shaking
Itching, swelling, or edema in the mucous membranes like the eyes, nose, tongue, lips, or mouth
Nausea, vomiting, or diarrhea with severe stomach pain
Trouble breathing, rapid breathing, wheezing, or coughing
Difficulty swallowing or speaking
Rapid heart beating
Weak pulse
Fainting, dizziness, lightheadedness, collapsing, or losing consciousness
Mental confusion or agitation

Consumers are encouraged to report adverse events to the FDA by calling 1-800-FDA-1088.

Levofloxacin side effects in seniors

Levofloxacin is contraindicated for use unless there are no other treatment options available for individuals older than 60 years of age. This age group is at an increased risk for developing severe tendon disorders, including tendon rupture, when being treated with fluoroquinolones like levofloxacin. This risk is increased in older patients who are taking corticosteroids. Patients should be informed of this very serious side effect and notify their healthcare provider immediately if any symptoms of tendinitis or tendon rupture occur.

In post-market reporting, severe and sometimes fatal cases of hepatotoxicity in older adults were reported. Levofloxacin should be discontinued immediately if signs and symptoms of hepatitis develop. These may include fever, fatigue, loss of appetite, nausea or vomiting, brown or very dark urine, stool changes, and jaundice or yellowing of the skin and eyes.

Seniors are more likely to experience heart problems secondary to drug-associated effects on the QT interval. Caution should be taken when using levofloxacin in older individuals taking Class IA or Class III antiarrhythmics or in individuals with risk factors for torsades de pointes, which include known QT prolongation or uncorrected low serum potassium (hypokalemia) or magnesium.

In general, older adults are more likely to have decreased renal function. Since levofloxacin is known to be substantially excreted by the kidney, extreme care should be taken when considering this medication in elderly individuals.

How long do levofloxacin side effects last?

Possible side effects associated with levofloxacin use typically begin shortly after starting the first dose of the medication and may continue throughout the course of treatment. While some mild (nausea, vomiting, diarrhea,) and even serious (cardiac) side effects usually resolve with discontinuation of the medication, it is important to note that some serious side effects may be permanent (tendon rupture, neuropathy) or even fatal (anaphylaxis). Some serious side effects (tendinitis, tendon rupture) have been reported to occur even in the months after treatment with levofloxacin has been discontinued.

Levofloxacin use should be immediately discontinued if any signs or symptoms associated with peripheral neuropathy or hypersensitivity occur.

Levofloxacin contraindications and warnings

Abuse and dependence

Levofloxacin is not habit-forming or addictive. There have been no documented withdrawal symptoms associated with discontinuing the use of levofloxacin. As with any medication, you should speak with your healthcare provider before you stop taking the medication on your own.

Overdose

The maximum dose of levofloxacin varies according to the condition it is being used to treat, with weight additionally being a consideration in pediatric patients. Generally, the maximum dose of levofloxacin does not exceed 750 mg per dose. As with any medication, especially antibiotics, levofloxacin should only be taken in the dosage, form, and frequency that it is prescribed by your healthcare provider. Taking more medication than is prescribed may result in acute renal failure or even a serious intestinal infection by the bacterium Clostridium difficile.

Restrictions

Levofloxacin has restricted use in certain individuals and has had recent updates by the FDA to strengthen the black box warnings label. A black box warning is the FDA’s most stringent warning for drugs. It is meant to provide important drug information to the public and healthcare professionals related to serious side effects such as injury or death.

Levofloxacin is contraindicated for use in the following individuals:

Those with hypersensitivity to fluoroquinolones
People with myasthenia gravis (see warning below)
People with prolonged QT segment on EKG
People with significant uncorrected electrolyte abnormalities

Levofloxacin is contraindicated for use unless there is no other treatment option available in the following individuals:

Individuals older than 60 years of age
Those with a history or high risk of aortic aneurysm
Individuals with peripheral atherosclerotic vascular disease
Individuals with hypertension (elevated blood pressure)
Patients with Marfan syndrome or Ehlers-Danlos syndrome

FDA black box warnings

The FDA added a boxed warning to fluoroquinolones, including levofloxacin, for tendinitis and tendon rupture in July 2008. A warning of worsening symptoms for patients with myasthenia gravis was added to the boxed warning in 2011. In 2013, the FDA also updated the labeling to include the possibility of irreversible peripheral neuropathy. In 2016, the FDA determined that fluoroquinolones should only be used in patients with no alternative treatment options for chronic bronchitis, sinusitis, and uncomplicated urinary tract infections. Additionally, in 2018, the FDA required safety label changes for fluoroquinolones to include warnings about the risks of mental health side effects and instances of hypoglycemic coma.

Disabling, potentially irreversible side effects

Fluoroquinolones, including ciprofloxacin, are associated with tendinitis and tendon rupture, peripheral neuropathy, and CNS effects that may occur together. Tendinitis and tendon rupture may occur during treatment or months after treatment discontinues. The risk of tendinitis or tendon rupture is increased in all ages, this risk further increases in patients over 60 years of age, patients taking corticosteroids, and patients with kidney, heart, and lung transplants. Discontinue use immediately and avoid fluoroquinolones in patients with adverse reactions.

Avoid in myasthenia gravis

Fluoroquinolones may exacerbate muscle weakness in patients with myasthenia gravis.

Reserve fluoroquinolone use

Fluoroquinolone use should be limited to individuals who have no alternative treatment options for the following indications:

Acute bacterial exacerbation of chronic bronchitis
Acute uncomplicated cystitis or uncomplicated urinary tract infections (UTIs)
Acute bacterial sinusitis

Pregnancy and breastfeeding

Levofloxacin was not demonstrated to be teratogenic (the cause of abnormalities in fetal development) in high doses in animal studies. However, there are no adequate, well-controlled studies in pregnant women. It is recommended that the risk/benefit ratio be discussed between pregnant women and their healthcare providers before starting levofloxacin.

Based on data from other fluoroquinolones and very limited data on levofloxacin, it is assumed that levofloxacin does not exert an effect on milk production, but will be present in human milk. It is recommended that breastfeeding be avoided during treatment and for up to two days after treatment has been discontinued as there is an increased risk of infant C. difficile-associated diarrhea. If ciprofloxacin is being used to treat anthrax exposure in a nursing mother, it is then recommended to consider avoiding breastfeeding for three to four hours after the medication has been administered.

Pediatric use

Quinolones, including levofloxacin, cause arthropathy and osteochondrosis in juvenile animals of several species and have been demonstrated to cause musculoskeletal disorders in clinical studies. Pediatric patients should only be prescribed levofloxacin for inhalational anthrax treatment, for pneumonic and septicemic plague treatment, for prophylaxis for Yersinia pestis, or for serious infections in a monitored setting. If being considered for use in a pediatric patient, the risk/benefit ratio should be evaluated due to the potential risk for musculoskeletal disorders.

The safety and effectiveness of levofloxacin in pediatric patients younger than 6 months of age have not been established.

Levofloxacin interactions

Levofloxacin has known interactions with several medications and caution should be used when administering levofloxacin with the following medications:

Multivalent cation-containing products

There are several medications that contain multivalent cations including antacids, magnesium preparations, aluminum preparations including sucralfate, and didanosine. The absorption of levofloxacin is decreased when levofloxacin is taken within two hours of these preparations.

Warfarin

Warfarin is a blood thinner medication used to help prevent blood clots and stroke. Taking levofloxacin while taking warfarin could lead to a serious drug interaction with side effects such as severe bleeding events. Unless the prothrombin time can be monitored every other day, levofloxacin should generally not be prescribed to individuals taking warfarin.

Antidiabetic agents

Levofloxacin has been shown to increase blood concentrations of certain diabetes medications. People with diabetes who are taking oral hypoglycemic medications should notify their healthcare provider before starting levofloxacin as careful monitoring of blood glucose should occur throughout the duration of treatment with levofloxacin to avoid potentially life-threatening low blood sugar.

NSAIDs (non-steroidal anti-inflammatory drugs)

Many common medicines for pain relief are NSAIDs. Taking an NSAID while you take levofloxacin or other fluoroquinolones may increase the risk of serious central nervous system effects and seizures. It is important to notify your healthcare provider of any medications you may start taking after you have already begun treatment with levofloxacin.

Other drug interactions

Ciprofloxacin is absolutely contraindicated for use with the following medications:

Cisapride
Dronedarone
Pimozide
Thioridazine

How to avoid levofloxacin side effects

1. Follow medical advice while taking this medication

Take only the dose prescribed by a healthcare professional. Do not take more medication and do not take less. Take all of the doses how and when they are prescribed. If you miss a dose, take the next dose as soon as you remember. Patients should continue taking the medication as prescribed even if they feel better after the first few doses.

2. Watch out for look-alike, sound-alike drugs

Levofloxacin is on the look-alike, sound-alike drug list (LASA), meaning that it may be confused with ciprofloxacin, gatifloxacin, levetiracetam, levocarnitine, levodopa, and levothyroxine. Verify that your prescription label includes the correct drug name before taking your medication.

3. Patients should disclose a full medication list, health history, and allergies before taking levofloxacin

This includes all medications and supplements, any medical conditions the patient has, or any allergic reactions they have had to medications in the past.

4. Store the medication correctly

Levofloxacin should be stored at room temperature (68 to 77 degrees Fahrenheit) and away from intense ultraviolet light.

5. Swallow the tablet whole or take the liquid exactly as it was prepared

Do not crush, break or chew the tablet or dilute the liquid.

6. Avoid taking levofloxacin with high-fat meals

While the overall bioavailability of levofloxacin is not affected by food, the rate of absorption is slightly delayed when this medication is co-administered with food.

7. Avoid taking levofloxacin with dairy products

It is okay to eat dairy products during the course of treatment with levofloxacin, however, it is best to avoid consuming dairy or other high-calcium or calcium-fortified foods at the time the medication is taken as these foods can delay the absorption of levofloxacin. Wait at least two hours before or after eating these types of foods and taking levofloxacin.

8. Avoid taking levofloxacin with antacids

Antacids that contain magnesium and aluminum salts will reduce the absorption of levofloxacin. Talk to your healthcare provider about alternative antacids if you are on an antacid treatment while taking levofloxacin.

9. Levofloxacin, and antibiotics in general, should only be taken for the exact amount of time recommended by your healthcare provider

For most bacterial infections, levofloxacin is taken daily for three to 14 days.

10. Avoid unnecessary sun exposure, sunbathing, or use of tanning beds

Levofloxacin can cause some individuals to experience sunburn due to an increased sensitivity to sunlight. You should use sunscreen when you are outside and wear sun-protective clothing like hats and long-sleeves while taking levofloxacin.

11. Seek medical care immediately in the event of an allergic reaction to this medication

Allergic responses and hypersensitivity reactions to fluoroquinolones could be fatal and should be reported and treated as early as possible.