Levofloxacin: Tendons, Aorta, Mental Health — the Fluoroquinolone Warnings in Everyday Life

1. At a glance: technical data sheet

2. How it works: strong against bacteria, not without traces in connective tissue

When bacteria divide, they constantly have to untangle, copy and repackage their genetic material. For this they need two enzymes: DNA gyrase and topoisomerase IV. Levofloxacin blocks both — the bacteria can no longer divide and die (bactericidal effect).^¹ Levofloxacin is the active half of the older substance ofloxacin and, like ciprofloxacin and moxifloxacin, belongs to the fluoroquinolones. The general background on this group and on the Rote-Hand-Brief (red hand letter, an official safety notice to healthcare professionals) is described in the ciprofloxacin article; this article is about what is different with levofloxacin and about the warning signs in everyday life.

• Strengths: levofloxacin works well against typical respiratory pathogens such as pneumococci and reaches high levels in the lungs, kidneys and prostate. It is almost completely absorbed, which is why the tablet works as strongly as the infusion. One dose a day is often enough.
• Weaknesses: fluoroquinolones do not only act on bacteria. They apparently also interfere with connective tissue, nerves and the brain. For the damage to the aorta, the authorities suspect a breakdown of collagen, the supporting protein of tendons and blood vessel walls.^² This explains the feared side effects affecting tendons, blood vessels and heart valves.
• Resistance: many gut bacteria that cause urinary tract infections have become insensitive to fluoroquinolones. Every unnecessary use makes the problem worse — more in the guide antibiotic resistance.

3. Dosing: once a day, but only for certain infections

The following information reflects the SmPC and is not a dosing instruction. The right dose and duration are set by the treating practice according to the infection, the pathogen and your kidney function.^¹

* For these infections, according to the SmPC, levofloxacin should only be used if other antibiotics usually recommended for them are considered unsuitable.^¹ Other uses such as inhalational anthrax play no role in everyday life.

• Impaired kidney function: from a creatinine clearance (a measure of kidney performance) of 50 ml/min or less, the dose is considerably reduced or the interval extended after a normal first dose. Dialysis barely removes levofloxacin; additional doses afterwards are not needed.^¹
• Liver: no adjustment needed, because levofloxacin is hardly broken down in the liver.
• Older people: apart from kidney function, no separate dose adjustment — but particular caution because of the risks to tendons and heart rhythm.
• Children and adolescents who are still growing: contraindicated according to the SmPC.

4. Taking it day to day: spacing, sun, cortisone

1. At the same time every day. With once-daily dosing, a fixed time helps; with twice-daily dosing, an interval of about twelve hours. The tablet is swallowed whole with enough fluid; it may be split at the score line to adjust the dose.^¹
2. With or without food. According to the SmPC, there is no clinically relevant interaction with food, and calcium salts have only a minimal effect on absorption.^¹ Unlike with ciprofloxacin, you therefore do not have to strictly avoid dairy products — background in the guide medications and dairy.
3. Two hours apart from minerals. Iron and zinc supplements, heartburn remedies containing magnesium or aluminium, and sucralfate should be taken at least 2 hours before or after levofloxacin; otherwise considerably less antibiotic is absorbed. This also applies to multivitamin products containing zinc.^¹
4. Avoid the sun and sunbeds. During treatment and for up to 48 hours afterwards, the skin should not be exposed to unnecessarily strong sunlight or UV radiation.^¹ More in the guide medications and sun.
5. Mention cortisone. If you take cortisone as a tablet, for example prednisolone, this increases the risk of tendon rupture and aortic damage. According to the SmPC, using both at the same time should be avoided. But do not stop your cortisone on your own — speak to your practice straight away.
6. Complete the course — except with warning signs. Normally, the prescribed duration is completed in full. With levofloxacin there is an important exception: at the first signs of a serious side effect, it should be stopped immediately and the practice contacted.^¹ Which signs these are is set out in section 6. General rules in the guide taking antibiotics correctly.

5. Side effects: from sleep problems to tendon rupture

Most people tolerate treatment with levofloxacin without major problems. The SmPC gives these frequencies:^¹

• Common: sleeplessness, headache, light-headedness, nausea, vomiting, diarrhoea, raised liver values.
• Uncommon: anxiety, nervousness, confusion, drowsiness, tremor, taste disturbances, vertigo, shortness of breath, abdominal pain, constipation, skin rash, itching, sweating, joint and muscle pain, fungal infections.
• Rare: tendon inflammation, muscle weakness, palpitations and a racing heart, seizures, tingling, psychotic reactions, depression, restlessness, nightmares, delirium, low blood sugar, visual disturbances, ringing in the ears, severe allergic reactions.
• Frequency not known: tendon rupture, nerve damage (polyneuropathy), suicidal thoughts, heart rhythm disorders with a prolonged QT interval, sensitivity of the skin to light, severe skin reactions, liver failure, inflammation of the pancreas, disorders of hearing and smell.

Diarrhoea while taking antibiotics is usually harmless. But if it is severe, persistent or bloody — even weeks after treatment — an infection with Clostridioides difficile may be behind it. In that case, do not take anti-diarrhoeal medicines such as loperamide; have it checked by a doctor instead.^¹ More under diarrhoea.

You can report side effects yourself to the BfArM (Federal Institute for Drugs and Medical Devices) — with fluoroquinolones in particular, this helps to assess the risk better. The guide reporting side effects explains how.

6. Tendons, nerves, mental health, aorta: the fluoroquinolone warnings

This is the most important section of this article. Between 2018 and 2020, the manufacturers, in agreement with the European Medicines Agency and the BfArM, sent out three red hand letters on fluoroquinolones.^²,³,⁴ In 2023, the EMA and the Drug Commission of the German Medical Association (AkdÄ) again drew attention to the restrictions on use, because fluoroquinolones were still too often prescribed outside the recommended situations. For you as a patient, one thing matters above all: knowing the warning signs and knowing when you need to act immediately.

Tendons: as early as 48 hours, and still months later

According to the SmPC, tendon inflammation and tendon rupture — mainly, but not only, of the Achilles tendon, sometimes on both sides — can occur within the first 48 hours and up to several months after stopping the medicine.^¹ The risk is increased in older age, with kidney dysfunction, after an organ transplant, with daily doses of 1,000 mg and with simultaneous cortisone treatment. First signs are pain, swelling or a pulling sensation above the heel — see also heel pain. Then: stop levofloxacin, call the practice, rest the affected tendon, no sport and no cortisone injected into the tendon.

Nerves: take tingling seriously

Fluoroquinolones can cause polyneuropathy (damage to the nerves in the arms and legs), which can be permanent. The SmPC requires you to inform the practice before the next tablet if pain, burning, tingling, numbness or weakness occur.^¹

Mental health: even after a single tablet

Sleep problems, restlessness and anxiety are more common than many people expect. Rarely, psychotic reactions, confusion or depression occur, and very rarely even suicidal thoughts and self-endangering behaviour — according to the SmPC, sometimes after just a single dose.^¹ If you feel “not like yourself” while taking levofloxacin, take it seriously and do not dismiss it as a consequence of the infection. Particular caution is needed if you have a history of mental illness.

Aorta and heart valves

Epidemiological studies show an increased risk of bulges (aneurysms) and tears (dissections) of the main artery, especially in older people, and of leaking aortic and mitral valves.^²,⁴ According to the SmPC, fluoroquinolones should therefore only be used after careful consideration if an aneurysm or heart valve disease is known or runs in the family, with connective tissue disorders such as Marfan or Ehlers-Danlos syndrome, with inflammation of the blood vessels, known atherosclerosis, high blood pressure, rheumatoid arthritis or Sjögren's syndrome.^¹ If any of these applies to you, say so before the first tablet.

Blood sugar

Levofloxacin can derail blood sugar in both directions; cases of hypoglycaemic coma are known, especially in older people with diabetes who take tablets such as glibenclamide or insulin.^¹ If you have diabetes, measure more often during treatment. If values are abnormal, levofloxacin should be stopped according to the SmPC and a different antibiotic considered.

How common such long-lasting symptoms are cannot be stated precisely: the SmPC speaks of very rare cases that lasted for months or years and affected the musculoskeletal system, nerves, mental health and the senses — sometimes regardless of age and risk factors.^¹ For the individual, the risk is small. But it is large enough that levofloxacin is not meant for a cold, a simple bladder infection or an infection that would clear up on its own.