Clarithromycin Hikma

PACKAGE LEAFLET: INFORMATION FOR THE USER

Clarithromycin Hikma 500 mg Powder for solution for infusion

Clarithromycin
Please read all of this leaflet carefully before you start using this medicine as it contains important information for you

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you personally. Never give it to others. It may be harmful to other people, even if their symptoms are the same as yours.
• If any of the side effects worsens, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Clarithromycin Hikma is and what it is used for
2. What you need to know before you use Clarithromycin Hikma
3. How to use Clarithromycin Hikma
4. Possible side effects
5. How to store Clarithromycin Hikma
6. Contents of the pack and other information

1. What Clarithromycin Hikma is and what it is used for

Clarithromycin is a semi-synthetic antibiotic. It belongs to the group of antibiotics known as macrolides
(Pharmacotherapeutic category: 1. Antinfective medicinal products, 1.1. Antibacterials, 1.1.8 Macrolides and ATC code:
J01FA09).
Each vial contains 500 mg of clarithromycin (as lactobionate formed in-situ).
Therapeutic indications
Clarithromycin is indicated for the treatment of the following bacterial infections when caused by clarithromycin-susceptible organisms in patients with known hypersensitivity to ß-lactam antibiotics or when ß-lactam antibiotics are inappropriate for other reasons (see section 4.4 and 5.1):

• Streptococcal pharyngitis
• Acute bacterial sinusitis (adequately diagnosed)
• Acute exacerbation of chronic bronchitis (adequately diagnosed)
• Community-acquired pneumonia
• Skin and soft tissue infections of mild to moderate severity as an alternative therapy when ß-lactam antibiotics are inappropriate.
  Official guidelines on the appropriate use of antibacterial agents should be taken into consideration.

2. What you need to know before using Clarithromycin Hikma

Do not use Clarithromycin Hikma

• If you are allergic to clarithromycin or to other macrolide antibiotics such as erythromycin or azithromycin.
• If you are currently being treated with astemizole, cisapride, pimozide, terfenadine, ergotamine or dihydroergotamine, ticagrelor or ranolazine (see “Other medicines and Clarithromycin Hikma”).
• If you have a heart condition, either congenital or acquired, that leads to changes in heart rhythm.
• If you are taking other medicines known to cause serious disturbances in heart rhythm.
• If you have low blood potassium or magnesium levels (hypokalaemia or hypomagnesaemia).
• If you are taking lovastatin or simvastatin (HMG-CoA reductase inhibitors, enzymes that limit the rate of cholesterol synthesis, commonly known as statins).
• If you are taking colchicine (commonly used for gout).

Warnings and precautions
Please consult your doctor or pharmacist before being administered Clarithromycin Hikma:

• If you have hepatic impairment.
• If you have moderate to severe renal impairment.
• If you are taking other macrolides, such as lincomycin and clindamycin.
• If you experience severe and prolonged diarrhoea during treatment with clarithromycin.

Children and adolescents

• To date, there are insufficient data to recommend intravenous administration of clarithromycin in children and adolescents under 18 years of age.

Elderly

• The use of clarithromycin in elderly patients should follow the recommendations for adults.

Use of other medicines and Clarithromycin Hikma
Please inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.
Available data indicate that clarithromycin is predominantly metabolized in the liver. The metabolism of other medicines via the same system may be inhibited by concomitant use of clarithromycin and may be associated with increased blood levels of these medicines.

• Increased blood levels of certain medicines: when clarithromycin is administered concomitantly with alprazolam, astemizole, carbamazepine, cilostazol, cyclosporine, disopyramide, digoxin, ergot alkaloids, lovastatin, methylprednisolone, midazolam, omeprazole, oral anticoagulants (e.g., warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, theophylline, terfenadine, triazolam, or vinblastine.
• Increased blood levels of certain medicines with effects on the heart: when clarithromycin is administered concomitantly with cisapride, disopyramide, quinidine, pimozide, astemizole, and terfenadine.
• Increased blood levels of clarithromycin: when clarithromycin is administered concomitantly with ritonavir; therefore, a reduction in the dose of clarithromycin may be necessary.
• Occurrence of musculoskeletal injury (rhabdomyolysis): when clarithromycin is administered concomitantly with HMG-CoA reductase inhibitors (enzymes that limit the rate of cholesterol synthesis), such as lovastatin and simvastatin.
• Vasospasm and ischemia: when clarithromycin is administered concomitantly with ergotamine or dihydroergotamine, acute toxicity may occur, characterized by reactive arterial constriction (vasospasm) or reduced blood supply (ischemia) to extremities and other tissues, including the central nervous system.
• Colchicine-related toxicity: colchicine toxicity has been reported when clarithromycin is administered concomitantly with colchicine, particularly in elderly patients. Some cases of toxicity occurred in patients with renal impairment.
• Reduced steady-state plasma levels of zidovudine: when clarithromycin is administered concomitantly with oral zidovudine in HIV-infected adults. To date, this interaction has not been observed in HIV-infected children. This interaction may not be a concern if clarithromycin is administered intravenously. It is not recommended to use clarithromycin to treat infections caused by Mycobacterium avium complex during treatment with etravirine. Some oral medicines used to lower blood glucose levels (such as nateglinide and repaglinide) or insulin may interact with clarithromycin and cause hypoglycaemia. Concomitant use of clarithromycin and calcium channel blockers (medicines commonly used to reduce blood pressure) may increase the risk of hypotension. Interactions between clarithromycin and vinorelbine, tipranavir, and aminoglycosides should also be anticipated. If you have any doubts about using this medicine with other medicines, please discuss them with your doctor or pharmacist.

Clarithromycin Hikma with food and drink
Concomitant administration of food and drink does not affect the efficacy of this medicine, as it is administered intravenously (directly into the vein).

Pregnancy and breastfeeding
If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine, as the safety of clarithromycin during pregnancy or breastfeeding is not known.

Driving and using machines
Clarithromycin may cause dizziness or drowsiness. If you experience these symptoms, do not drive or operate machinery.

3. How to use Claritromicina Hikma

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are
unsure.
The usual dose of Claritromicina Hikma is 1 g per day, divided into two doses of 500 mg.
In patients with renal impairment with creatinine clearance less than 30 ml/min, the clarithromycin dosage should
be reduced by half (250 mg twice daily).
In patients with renal impairment who are receiving concomitant treatment with ritonavir, the following dosage
adjustment must be made:
Creatinine clearance levels of 30–60 ml/min: reduce the clarithromycin dose by half;
Creatinine clearance levels below 30 ml/min: reduce the clarithromycin dose by 75%;
Clarithromycin doses higher than 1 g/day should not be administered with ritonavir.
Intravenous therapy may be administered for 2–5 days in severely ill patients and should be switched to oral therapy
as soon as possible, according to the instructions of your treating physician.
Method of administration
Claritromicina Hikma must be administered as an intravenous infusion (slow injection into a vein) over 60 minutes.
Claritromicina must not be administered as a bolus (rapid injection into a vein) or as an intramuscular injection
(injection into a muscle).
No dosage adjustment is required in patients with moderate or severe hepatic impairment who have normal renal
function.
Average duration of treatment
This varies depending on the patient and their clinical condition, and should be determined by your doctor.
If you take more Claritromicina Hikma than you should
There is no experience regarding overdose following intravenous administration of clarithromycin. If this occurs,
administration of the medicine should be discontinued and all appropriate supportive measures should be
instituted.
As with other macrolide antibiotics, serum levels of clarithromycin are not considered to be significantly altered by
haemodialysis or peritoneal dialysis.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Contact a doctor immediately if you experience a serious skin reaction: red, scaly rash with formation of pustules and blisters under the skin (exanthematous pustulosis). The frequency of this side effect is not known (cannot be estimated from the available data).

The side effects are described according to the estimated frequency with which they may occur. For this purpose, the following frequency categories and terms have been used:
Very common: may affect more than 1 in 10 people
Common: may affect 1 to 10 people in 100
Uncommon: may affect 1 to 10 people in 1,000
Rare: may affect 1 to 10 people in 10,000
Very rare: may affect fewer than 1 in 10,000 people
Not known: frequency cannot be estimated from the available data

Very common (≥ 1/10)

• Phlebitis at the injection site

Common (≥ 1/100 to < 1/10)

• Insomnia
• Dysgeusia
• Headache
• Taste disturbance
• Vasodilation
• Diarrhoea, vomiting, indigestion (dyspepsia), nausea, abdominal pain
• Abnormal liver function tests
• Rash
• Hyperhidrosis
• Pain at injection site, inflammation at injection site

Uncommon (≥ 1/1,000 to < 1/100)

• Cellulitis, candidiasis, vaginal infections
• Decreased white blood cell count (leucopenia)
• Anaphylactoid reactions, hypersensitivity
• Anorexia, decreased appetite
• Anxiety, nervousness
• Loss of consciousness, dyskinesia, dizziness, somnolence, tremor
• Dizziness
• Hearing impairment, tinnitus
• Cardiac arrest, atrial fibrillation, prolongation of the time required for ventricular activation and recovery (prolongation of QT interval on electrocardiogram), extrasystoles, palpitations
• Asthma, pulmonary embolism
• Oesophagitis, gastritis, inflammation of the oral mucosa (stomatitis), inflammation of the tongue (glossitis), constipation, dry mouth, belching, flatulence
• Increased alanine aminotransferase levels, increased aspartate aminotransferase levels
• Bullous dermatitis, pruritus, urticaria
• Musculoskeletal stiffness
• Increased blood creatinine levels, increased blood urea levels
• Asthenia
• Abnormal albumin/globulin ratio

Not known (frequency cannot be estimated from the available data)

• Severe inflammation of the large intestine (pseudomembranous colitis)
• Erysipelas
• Reduced platelet count in blood (thrombocytopenia), reduced production of a type of cells called neutrophils (agranulocytosis)
• Anaphylactic reaction
• Angioedema
• Psychosis, confusion, depersonalization, depression, disorientation, hallucinations, nightmares, mania
• Involuntary and uncoordinated muscle contractions (seizures)
• Ageusia, parosmia, anosmia, sensation of pins and needles (paraesthesia)
• Hearing loss
• Abnormal electrocardiogram trace (Torsades de pointes) and increased heart rate (ventricular tachycardia)
• Haemorrhage
• Inflammation of the pancreas (pancreatitis)
• Discoloration of the tongue and teeth
• Hepatic failure
• Hepatocellular jaundice
• Joint pain and/or eye infections (Stevens-Johnson syndrome), skin tissue detachment and peeling due to cell death (toxic epidermal necrolysis), drug rash with eosinophilia and systemic symptoms (DRESS), acne
• Rhabdomyolysis, myopathy
• Kidney damage, interstitial nephritis
• Increased international normalized ratio, prolonged prothrombin time, abnormal urine colour

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or nurse. You can also report side effects directly via the national reporting system at www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Claritromycin Hikma

Keep this medicine out of the sight and reach of children.
Store below 25°C.
Keep in the original packaging.
The reconstituted medicine must be used within 24 hours if stored below 25°C, or within 48 hours if stored between 2°C and 8°C.
The solution resulting from the final dilution must be used within 6 hours if stored below 25°C, or within 48 hours if stored between 2°C and 8°C.
Do not use Claritromycin Hikma after the expiry date stated on the container. The expiry date refers to the last day of the month indicated.
Do not use this medicine if you notice particulate matter or discoloration. Only clear solutions should be used. For single use only.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. These precautions will help protect the environment.

6. Pack contents and other information

What Claritromycin Hikma contains

• The active substance is Clarithromycin (as lactobionate formed in-situ)

What Claritromycin Hikma looks like and contents of the pack
Powder for solution for infusion (compact powder, white to off-white).
Pack containing 1 or 10 vials, each containing the equivalent of 500 mg of clarithromycin.
It is possible that not all pack sizes are marketed.

Marketing Authorisation Holder and Manufacturer
Hikma Farmacêutica (Portugal), S.A.
Estrada do Rio da Mó, nº 8, 8A – 8B
Fervença
2705 – 906 Terrugem SNT

Marketing Authorisation Holder in Italy:
Hikma Italia SpA
Viale Certosa 10
27100 Pavia

This medicinal product is authorised in EEA Member States under the following names:
Austria: Clarithromycin Hikma 500mg Pulver Zur Herstellung einer Injektionslösung
Germany: Clarithromycin Hikma 500mg Pulver zur Herstellung einer Injektionslösung
Italy: Claritromicina Hikma 500mg Polvere per soluzione per infusione
Portugal: Claritromicina Hikma 500mg Pó para solução para perfusão

This Patient Information Leaflet was last approved on

The following information is intended for medical or healthcare professionals only

The final infusion solution must be prepared as follows:

1. Reconstitution: Prepare the initial Clarithromycin Hikma solution by adding 10 ml of sterile water for injection to the 500 mg vial. Use only sterile water for injection, as other diluents may cause precipitation during reconstitution. Do not use diluents containing preservatives or inorganic salts.
2. Dilution after reconstitution: The reconstituted solution (500 mg in 10 ml of water for injectable solutions) must be added to at least 250 ml of one of the following diluents prior to administration:
   • 5% Dextrose in Lactated Ringer's
   • 5% Dextrose
   • Lactated Ringer's solution
   • 5% Dextrose in 0.3% sodium chloride solution
   • 5% Dextrose in 0.45% sodium chloride solution
   • 0.9% Sodium chloride

Incompatibilities
Clarithromycin Hikma must only be diluted with the recommended diluents. Compatibility with other intravenous diluents has not been tested.