QUOFENIX 300 mg POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION

2. What you need to know before you are given Quofenix

You should not be given Quofenix

• If you are allergic to delafloxacin or any of the other ingredients of this medicine (listed in section 6).
• If you are allergic to any other antibacterial medicine of the fluoroquinolone or quinolone type.
• If you have ever had a tendon problem, such as tendonitis, related to treatment with "quinolone-type antibiotics". A tendon is the cord that connects the muscle to the skeleton.
• If you are pregnant, plan to become pregnant, or think you may be pregnant.
• If you are breast-feeding
• If you are a child or adolescent under 18 years of age.

Warnings and precautions

Before you are given this medicine

You should not be given fluoroquinolone/quinolone antibacterial medicines, including Quofenix, if you have experienced any serious side effect in the past when taking a quinolone or fluoroquinolone. In this case, you must inform your doctor as soon as possible.

When you are given this medicine

• Rarely, pain and swelling may occur in the joints, and inflammation or rupture of the tendons. Your risk increases if you are an elderly patient (over 60 years of age), have received an organ transplant, have kidney problems, or are being treated with corticosteroids. Tendon inflammation and ruptures can occur within the first 48 hours of treatment and even up to several months after stopping treatment with Quofenix. At the first sign of pain or inflammation of a tendon (e.g., in the ankle, wrist, elbow, shoulder, or knee), you should not be given Quofenix, contact your doctor, and rest the affected area. Avoid any unnecessary exercise, as this could increase the risk of tendon rupture.

• Rarely, symptoms of nerve damage (neuropathy) such as pain, burning, tingling, numbness, and/or weakness, especially in the feet and legs or hands and arms, may occur. If this happens, you should not be given Quofenix, and inform your doctor immediately to prevent the development of a potentially irreversible condition.

Tell your doctor or pharmacist or nurse before you are given Quofenix if:

• You have been diagnosed with an enlargement or bulge of a large blood vessel (aortic aneurysm or large peripheral vessel aneurysm).
• You have had a previous episode of aortic dissection (tear of the aortic wall).
• You have been diagnosed with a heart valve problem (heart valve regurgitation)
• You have a family history of aortic aneurysm or aortic dissection, congenital heart valve problems, or other risk factors or predisposing conditions (e.g., connective tissue disorders such as Marfan syndrome or Ehlers-Danlos vascular syndrome, Turner syndrome, or Sjögren's syndrome (an autoimmune inflammatory disease), or vascular disorders such as Takayasu arteritis, giant cell arteritis, Behçet's disease, high blood pressure, or atherosclerosis, rheumatoid arthritis (a joint disease), or endocarditis (a heart infection)).
• You have had tendon problems during previous treatment with a fluoroquinolone or quinolone antibiotic.
• You have or may have problems with your central nervous system (e.g., severe cerebral arteriosclerosis, epilepsy) or have other risk factors that may increase the risk of having seizures (fits). In these cases, your doctor will consider whether this treatment is the best option for you.
• You suffer from myasthenia gravis (a type of muscle weakness), as symptoms may worsen.
• You suffer from diarrhea or have previously suffered from diarrhea when taking antibiotics or up to 2 months after. Contact your doctor immediately if you have diarrhea during or after treatment. Do not take any medicine to treat diarrhea without first consulting your doctor.
• You have kidney problems.
• You have sometimes had prolonged treatment with antibiotics; this may mean that you contract another infection caused by other bacteria (superinfection) that cannot be treated with the antibiotic. Consult your doctor if you have any doubts or questions about this and about the use of Quofenix.
• You may have a severe skin reaction, such as blisters or lesions.
• You or a family member has a deficiency of glucose-6-phosphate dehydrogenase.
• You suffer from diabetes. Fluoroquinolone antibiotics, including Quofenix, may cause blood glucose levels to increase or decrease too much. If you have diabetes, you must carefully monitor your blood glucose levels.

If you feel a sudden, severe pain in your abdomen, chest, or back, which can be symptoms of aortic dissection or aneurysm, go immediately to an emergency department. The risk may increase if you are receiving systemic corticosteroid treatment.

If you start to experience sudden onset of shortness of breath, especially when lying down, or if you notice swelling in your ankles, feet, or abdomen, or the appearance of heart palpitations (feeling of rapid or irregular heartbeat), you must inform your doctor immediately.

Severe, prolonged, disabling, and potentially irreversible side effects

Fluoroquinolone/quinolone antibacterial medicines have been associated with very rare but serious side effects, some of which are long-lasting (for months or years), disabling, or potentially irreversible. This includes tendon pain, muscle and joint pain in the upper and lower limbs, difficulty walking, abnormal sensations such as tingling, numbness, or burning, sensory disorders such as impaired vision, taste, and smell, and hearing, depression, memory impairment, severe fatigue, and severe sleep disorders.

If you experience any of these side effects after receiving Quofenix, contact your doctor immediately before continuing treatment. You and your doctor will decide whether to continue treatment, also considering an antibiotic of another class.

Children and adolescents

This medicine should not be used in children and adolescents, as it has not been sufficiently studied in these groups.

Other medicines and Quofenix

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Quofenix should not be administered with any solution containing substances such as calcium and magnesium through the same intravenous route.

Pregnancy and breast-feeding

Quofenix should not be used if you are pregnant or breast-feeding. Quofenix should not be used in women of childbearing age who are not using effective contraception.

If you are pregnant or breast-feeding, think you may be pregnant, or plan to become pregnant, consult your doctor before you are given this medicine.

If you could become pregnant, you must use effective contraceptive methods during treatment with Quofenix.

Driving and using machines

Quofenix may make you feel dizzy and disoriented. Do not drive, use machines, or perform other activities that require mental alertness or coordination until you know how Quofenix affects you.

Quofenix contains cyclodextrins

This medicine contains 2480 mg of sulfobutyl betadex sodium in each vial.

Quofenix contains sodium

This medicine contains 175 mg of sodium (the main component of cooking salt) in each vial. This is equivalent to 8.8% of the maximum recommended daily intake of sodium for an adult.

3. How to use Quofenix

Quofenix will be administered to you by a nurse or doctor through an infusion (drip) into a vein.

You will be given a Quofenix infusion, which contains 300 mg of the medicine, twice a day for 5 to 14 days for skin infections and 5 to 10 days for pneumonia, according to medical judgment. Each infusion will last approximately one hour. Your doctor will decide how many days of treatment are necessary.

Tell your doctor if you have kidney problems, as you may need to have your dose adjusted.

If you have any further questions on the use of this medicine, ask your doctor.

If you are given more Quofenix than you should

Tell your doctor or nurse immediately if you are concerned that you have been given more Quofenix than you should.

If you miss a dose of Quofenix

Tell your doctor or nurse immediately if you are concerned that you have missed a dose.

If you have any other questions about the use of this medicine, ask your doctor or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Serious side effects

Please tell your doctor or nurse immediately if you experience any of these symptoms, as treatment with the medicine should be stopped and you may need urgent medical attention:

• Difficulty swallowing or difficulty breathing and coughing; swelling of the lips, face, throat, or tongue; dry throat or narrowing of the throat and severe rash. These can be signs and symptoms of a hypersensitivity reaction (allergic) and can be life-threatening. These severe reactions are uncommon side effects that may affect up to 1 in 100 people.
• Decrease in blood pressure; blurred vision; dizziness. This severe reaction is an uncommon side effect that may affect up to 1 in 100 people.
• Abdominal pain (stomach) with possible severe diarrhea, fever, and nausea. These can be signs of an intestinal infection, which should not be treated with medicines that stop the movement of the intestine. Intestinal infection (infection by Clostridioides difficile) is an uncommon side effect that may affect up to 1 in 100 people.

Other side effects may include:

Common side effects (may affect up to 1 in 10 people):

• Fungal infection
• Headache
• Vomiting
• Swelling, redness, or pain around the infusion site in the vein (infusion site reaction)
• Increased levels of liver enzymes, called transaminases, which are shown in blood tests
• Itching

Uncommon side effects (may affect up to 1 in 100 people):

• Low white blood cell count (leucopenia)
• Low hemoglobin levels (anemia)
• Allergic reaction
• High blood glucose levels
• Decreased appetite
• Insomnia
• Muscle weakness in the limbs
• Sensations such as numbness, tingling, and prickling
• Decreased sense of touch
• Altered taste
• Feeling of heartbeats (palpitations)
• High blood pressure
• Redness (e.g., in the face or neck)
• Inflammation of the stomach lining, inflammation of the internal tissues of the mouth, abdominal pain, stomach discomfort or indigestion, dry mouth, flatulence
• Abnormal sweating
• Allergic skin reaction
• Red itchy rash
• Joint pain
• Tendon pain and swelling
• Musculoskeletal pain (e.g., pain in the limbs, back pain, neck pain), muscle weakness
• Increased levels of creatine phosphokinase in the blood (an indicator of muscle damage)
• Decreased kidney function
• Feeling of tiredness
• Altered blood test results related to liver function (increased alkaline phosphatase in the blood)
• Increased body temperature (pyrexia)
• Swelling of the lower limbs

Rare side effects (may affect up to 1 in 1000 people):

• Urinary tract infection
• Inflammation of the nasal mucosa
• Low white blood cell count (reduction in the number of blood cells)
• Decrease in a special type of blood cell necessary for blood clotting
• Changes in tests that measure blood clotting
• Seasonal allergy
• Low blood glucose levels
• High levels of uric acid
• High levels of potassium in the blood
• Low levels of potassium in the blood
• Hearing things that do not exist (auditory hallucinations)
• Anxiety
• Sleep disorders
• Confusion
• Drowsiness
• Feeling of dizziness or fainting, usually due to a drop in blood pressure
• Dry eyes
• Dizziness or loss of balance (vertigo)
• Ringing in the ears (tinnitus)
• Altered balance
• Irregular or rapid heartbeat, decreased heart rate
• Swollen, red, and irritated veins (phlebitis)
• Blood clot, known as deep vein thrombosis
• Acid reflux, acid regurgitation
• Loss of sensation in the mouth
• Decreased sense of touch in the mouth
• Burning sensation in the mouth
• Change in the color of the stools
• Altered blood test results related to liver function (decreased albumin in the blood and increased gamma-glutamyltransferase)
• Cold sweat
• Nocturnal sweating
• Abnormal hair loss
• Muscle spasms
• Muscle inflammation or pain
• Joint inflammation, pain in hands or feet, back pain
• Blood in the urine
• Cloudy urine due to the presence of solid components
• Chills
• Worsening of the wound
• Peripheral edema
• Blockage of the medical device used for administration

Very rare side effects (may affect up to 1 in 10,000 people) have been associated with the administration of quinolone and fluoroquinolone antibiotics, in some cases independently of pre-existing risk factors, such as permanent or long-lasting (for months or years) reactions, including tendon inflammation, tendon rupture, joint pain, pain in the limbs, difficulty walking, abnormal sensations such as tingling, numbness, or burning, neuropathy, depression, fatigue, sleep disorders, memory impairment, as well as alterations in hearing, vision, taste, and smell.

There have been reports of increased size and weakening or tearing of the aortic wall (aneurysms and dissections), which could lead to rupture and be fatal, and heart valve problems in patients who have received fluoroquinolones. See also section 2.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the national reporting system included in Appendix V*. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Quofenix

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton or label after EXP. The expiry date refers to the last day of the month shown.

After reconstitution: The chemical and physical stability in use has been demonstrated for 24 hours between 20 to 25°C or between 2 to 8°C. From a microbiological point of view, the product should be used immediately after reconstitution and dilution. If not used immediately, the in-use storage times and conditions are the responsibility of the user and are normally not more than 24 hours at a temperature between 2 and 8°C, unless the reconstitution and dilution have been performed in controlled and validated aseptic conditions.

Do not freeze.

6. Container Contents and Additional Information

Quofenix Composition

• The active ingredient is delafloxacin. Each vial of powder contains 300 mg of delafloxacin (as meglumine).
• The other components (excipients) are meglumine, sulfobutyl betadex sodium, disodium edetate, sodium hydroxide (for pH adjustment), concentrated hydrochloric acid (for pH adjustment).

Product Appearance and Container Contents

Quofenix 300 mg powder for concentrate for solution for infusion is presented in a 20 ml transparent glass vial.

The vial contains compact light yellow powder.

It is available in packs containing 10 vials.

Marketing Authorization Holder and Manufacturer

• Menarini – Industrie Farmaceutiche Riunite – s.r.l.

Via Sette Santi 3

50131 Florence

Italy

Manufacturer

Patheon Italia S.p.A.

2° Trav. SX Via Morolense 5

03013 Ferentino (FR)

Italy

or

AlfaSigma

1 Via Enrico Fermi

65020 Alanno (PE)

Italy

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:08/2024

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website http://www.ema.europa.eu.

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This information is intended only for healthcare professionals:

For single use only.

Quofenix should be reconstituted under aseptic conditions, using 10.5 ml of dextrose 50 mg/ml (5%) injectable solution (D5W) or sodium chloride 9 mg/ml (0.9%) injectable solution per vial of 300 mg.

• The vial should be shaken vigorously until the contents are completely dissolved. The reconstituted vial contains 300 mg per 12 ml of delafloxacin, as a light yellow to amber-colored solution.
• Then, the reconstituted solution should be diluted in a 250 ml intravenous infusion bag (already containing sodium chloride 0.9% injectable solution or D5W) prior to administration.
• Prepare the required dose for intravenous infusion by withdrawing the volume of 12 ml from the reconstituted vial for Quofenix 300 mg or 8 ml for Quofenix 200 mg.

• The required dose of the reconstituted Quofenix solution should be transferred aseptically from the vial to a 250 ml intravenous infusion bag. (Any unused portion of the reconstituted solution should be discarded).
• After reconstitution and dilution, Quofenix should be administered by intravenous infusion, over a total infusion time of 60 minutes.

Quofenix should not be infused with other medicinal products. If a common intravenous line is used to administer other medicinal products in addition to Quofenix, the line should be flushed before and after each Quofenix infusion with a sodium chloride 9 mg/ml (0.9%) injectable solution or D5W. Any unused medicinal product or residue should be disposed of in accordance with local regulations.