Ceptomax 200 Mg/5 Ml Oral Suspension

Adults and children over 45 kg: CEPTOMAX is indicated for mild to moderate infections caused by susceptible organisms.

• lower respiratory tract infections including bronchitis due to Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pneumoniae or Staphylococcus aureus.
• pneumonia due to Streptococcus pneumoniae or Haemophilus influenzae.
• uncomplicated skin and soft tissue infections.
• sinusitis due to Haemophilus influenzae, Streptococcus pneumoniae or Staphylococcus aureus.
• and as an alternative to first line therapy of pharyngitis/tonsillitis.

Paediatric population

Children: 1 year and over (under 45 kg) CEPTOMAX is indicated for:

• pharyngitis/tonsillitis and
• otitis media caused by susceptible organisms.

Usual dose: Paediatric population

Use in children: 1 year and older

The total dose in children is 30 mg/kg which should be given as a single daily dose of 10 mg/kg for 3 days according to the following guidance:

Weight Dose and duration

• < 15 kg 10 mg/kg once daily on days 1 - 3
• 15 u2013 25 kg 200 mg (5 mL) once daily on days 1 - 3
• 26 u2013 35 kg 300 mg (7,5 mL) once daily on days 1 - 3
• 36 u2013 45 kg 400 mg (10 mL) once daily on days 1 - 3
• > 45 kg 500 mg once daily (12,5 mL) only if patient is unable to swallow tablets.

Reconstituting instructions for CEPTOMAX 200 mg/5 mL powder for oral suspension for 15 mL and 30 mL bottles:

The table below indicates the volume of water to be used for constitution:

Total deliverable volume (azithromycin content) Amount of water to be added Azithromycin concentration after reconstitution

• 15 mL (600 mg) 7,5 mL 200 mg/5 mL
• 30 mL (1200 mg) 15 mL 200 mg/5 mL

Method of administration

Shake well before each use, the oversized bottle provides shake space. CEPTOMAX suspension should be administered to children using the 5 ml oral dosing syringe or the spoon provided. CEPTOMAX suspension can be taken with food.

CEPTOMAX is contraindicated in patients with hypersensitivity to azithromycin, erythromycin, any macrolide or ketolide antibiotic, or to any of the excipients listed in section 6.1 (see also section 4.4)

Because of the theoretical possibility of ergotism, CEPTOMAX and ergot derivatives should not be co-administered.

Hypersensitivity

Azithromycin as contained in CEPTOMAX may cause serious allergic reactions, including angioedema and anaphylaxis, dermatologic reactions including acute generalised exanthematous pustulosis (AGEP), Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Some of these reactions with azithromycin as contained in CEPTOMAX have resulted in recurrent symptoms and required a longer period of observation and treatment. If an allergic reaction occurs, CEPTOMAX should be discontinued, and appropriate therapy should be instituted. Medical practitioner should be aware that reappearance of the allergic symptoms may occur when symptomatic therapy is discontinued.

Hepatic function

Since liver is the principal route of elimination for azithromycin, the use of CEPTOMAX should be undertaken with caution in patients with significant hepatic disease. Cases of fulminant hepatitis potentially leading to life-threatening liver failure have been reported with azithromycin (see section 4.8). Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicines. In case of signs and symptoms of liver dysfunction, such as rapid developing asthenia associated with jaundice, dark urine, bleeding tendency or hepatic encephalopathy, liver function tests / investigations should be performed immediately. CEPTOMAX administration should be stopped if liver dysfunction has emerged.

Ergot derivatives

In patients receiving ergot derivatives, ergotism has been precipitated by coadministration of some macrolide antibiotics. There are no data concerning the possibility of an interaction between ergot and azithromycin. However, because of the theoretical possibility of ergotism, CEPTOMAX and ergot derivatives should not be coadministered (see section 4.3).

Superinfection

Observation for signs of superinfection with non-susceptible organisms, including fungi is recommended.

Pseudomembranous colitis

Pseudomembranous colitis has been reported and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients with diarrhoea subsequent to administration of CEPTOMAX.

Clostridium difficile associated diarrhoea (CDAD)

Clostridium difficile associated diarrhoea (CDAD) has been reported with the use of azithromycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial medicines alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial medicines.

Renal impairment

In patients with severe renal impairment (GFR <10 mL/min) a 33 % increase in systemic exposure to azithromycin was observed (see Section 5.2).

Cardiovascular Events

Prolonged cardiac repolarisation and QT interval, imparting a risk of developing cardiac dysrhythmia and torsades de pointes, in treatment with macrolides including azithromycin (see section 4.8) has been reported. Therefore as the following situations may lead to an increased risk for ventricular dysrhythmia (including torsade de pointes) which can lead to cardiac arrest, CEPTOMAX should be used with caution in patients with ongoing pro dysrhythmic conditions (especially women and elderly patients) such as patients:

• With congenital or documented QT prolongation
• Currently receiving treatment with other active substances known to prolong QT interval such as anti-dysrhythmics of class IA (quinidine and procainamide) and class III (dofetilide, amiodarone and sotalol), cisapride and terfenadine; antipsychotic medicines such as pimozide; antidepressants such as citalopram; and fluoroquinolones such as moxifloxacin and levofloxacin
• With electrolyte disturbance, particularly in cases of hypokalaemia and hypomagnesemia
• With clinically relevant bradycardia, cardiac dysrhythmia or severe cardiac insufficiency

A short-term risk of dysrhythmia, myocardial infarction and cardiovascular mortality associated with macrolides including azithromycin has been identified therefore, consideration of these findings should be balanced with treatment benefits when prescribing CEPTOMAX.

Myasthenia gravis

There has been exacerbations of the symptoms of myasthenia gravis and new onset of myasthenia syndrome in patients receiving azithromycin therapy (see section 4.8).

Safety and efficacy for the prevention or treatment of Mycobacterium avium complex in children have not been established.

Paediatric population

The safety and efficacy of CEPTOMAX in children less than 1 year have not been established.

CEPTOMAX contains sucrose

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take CEPTOMAX.

Antacids

In patients receiving both CEPTOMAX and antacids, the medicines should not be taken simultaneously, as it may cause a decrease in concentration of CEPTOMAX. CEPTOMAX should be taken at least 1 hour before or 2 hours after the antacid.

Digoxin and colchicine (P-gp substrates)

Concomitant administration of macrolide antibiotics, including CEPTOMAX, with P-glycoprotein substrates such as digoxin and colchicine, has been reported to result in increased serum levels of the P-glycoprotein substrate. Therefore, if CEPTOMAX and P-gp substrates such as digoxin are administered concomitantly, the possibility of elevated serum concentrations of the substrate should be considered.

Ergot

Due to the theoretical possibility of ergotism, the concurrent use of CEPTOMAX with ergot derivatives is not recommended (see Section 4.3 and 4.4).

Pharmacokinetic studies have been conducted between CEPTOMAX and the following medicines known to undergo significant cytochrome P450 mediated metabolism.

Atorvastatin

Co-administration of atorvastatin (10 mg daily) and CEPTOMAX (500 mg daily) did not alter the plasma concentrations of atorvastatin (based on a HMG CoA-reductase inhibition assay). However, there has been cases of rhabdomyolysis in patients receiving CEPTOMAX.

Cisapride

Cisapride is metabolized in the liver by the enzyme CYP 3A4. Because macrolides inhibit this enzyme, concomitant administration of cisapride may cause the increase of QT interval prolongation, ventricular dysrhythmias and torsades de pointes.

Coumarin-Type Oral Anticoagulants (Warfarin)

In a pharmacokinetic interaction study, azithromycin did not alter the anticoagulant effect of a single 15 mg dose of warfarin administered to healthy patients. There have been reports received in the post-marketing period of potentiated anticoagulation subsequent to co-administration of azithromycin and coumarin-type oral anticoagulants. Although a causal relationship has not been established, consideration should be given to the frequency of monitoring prothrombin time when CEPTOMAX is used in patients receiving coumarin-type oral anticoagulants.

Ciclosporin

In a pharmacokinetic study with healthy patients that were administered a 500 mg/day oral dose of azithromycin for 3 days and were then administered a single 10 mg/kg oral dose of ciclosporin, the resulting ciclosporin C max and AUC 0-5 were found to be significantly elevated. Consequently, caution should be exercised before considering concurrent administration of these medicines. If co-administration of these medicines is necessary, ciclosporin levels should be monitored and the dose adjusted accordingly.

Fluconazole

Co-administration of a single dose of 1200 mg azithromycin did not alter the pharmacokinetics of a single dose of 800 mg fluconazole. Total exposure and half-life of azithromycin were unchanged by the co-administration of fluconazole, however, a clinically insignificant decrease in C max (18%) of azithromycin was observed.

Zidovudine

Single 1000 mg doses and multiple 1200 mg or 600 mg doses of azithromycin, as contained in CEPTOMAX had little effect on the plasma pharmacokinetics or urinary excretion of zidovudine or its glucuronide metabolite. However, administration of azithromycin increased the concentrations of phosphorylated zidovudine, the clinically active metabolite, in peripheral blood mononuclear cells.

Substances that prolong the QT interval

CEPTOMAX should not be used concomitantly with other active substances that prolong the QT interval (see section 4.4).

The safety and efficacy of CEPTOMAX in pregnancy and lactation have not been established.

Pregnancy

In reproduction toxicity studies in animals, azithromycin was shown to pass the placenta, but no teratogenic effects were observed. CEPTOMAX should only be used during pregnancy if clearly needed.

Breastfeeding

Azithromycin has been reported to be secreted into human breast milk, but there are no adequate and well-controlled clinical studies in breastfeeding women that have characterized the pharmacokinetics of azithromycin excretion into human breast milk. CEPTOMAX should only be used in lactating women where adequate alternatives are not available.

Fertility

In fertility studies conducted in rat, reduced pregnancy rates were noted following administration of azithromycin. The relevance of this finding to humans is unknown.

CEPTOMAX may cause dizziness which may influence the ability to drive and use machines. Patients should not drive or operate machines until they know how CEPTOMAX affects them. Visual impairment and blurred vision may have an effect on a patient's ability to drive or operate machinery (section 4.8)

Frequent Less frequent Frequency unknown

Infections and Infestations

• Candidiasis, vaginal infection, pneumonia, fungal infection, bacterial infection, pharyngitis, gastroenteritis, respiratory disorder, rhinitis, oral candidiasis

Pseudomembranous colitis (see section 4.4)

Blood and Lymphatic System Disorders

• Leukopenia, neutropenia, eosinophilia

Thrombocytopenia, haemolytic anaemia

Immune System Disorders

• Angioedema, hypersensitivity

Anaphylactic reaction (see section 4.4)

Metabolism and Nutrition Disorders

• Anorexia

Psychiatric Disorders

• Nervousness, insomnia, agitation

Aggression, anxiety, delirium, hallucination

Nervous System Disorders

• Headache

Dizziness, somnolence, dysgeusia, paraesthesia

Syncope, convulsion, hypoesthesia, psychomotor hyperactivity, anosmia, ageusia, parosmia, myasthenia gravis (see section 4.4)

Eye Disorders

• Visual impairment, blurred vision

Ear and Labyrinth Disorders

• Ear disorder, vertigo

Hearing impairment including deafness and/or tinnitus

Cardiac Disorders

• Palpitations

Torsades de pointes, (see section 4.4) dysrhythmia (see section 4.4) including ventricular tachycardia, electrocardiogram QT prolonged (see section 4.4)

Vascular Disorders

• Hot flush

Hypotension

Respiratory, thoracic and mediastinal disorders

• Dyspnoea, epistaxis

Gastrointestinal Disorders

• Diarrhoea, vomiting, abdominal pain, nausea

Constipation, flatulence, dyspepsia, gastritis

Pancreatitis, tongue discolouration

dysphagia abdominal distension, dry mouth, eructation, mouth ulceration salivary hypersecretion

Hepatobiliary Disorders

• Hepatic function abnormal, jaundice

cholestatic Hepatic failure (see section 4.4), hepatitis fulminant, hepatic necrosis

Skin and Subcutaneous Tissue Disorders

• Rash, pruritus, urticaria, dermatitis, dry skin, hyperhidrosis, photosensitivity reaction, Acute Generalised Exanthematous Pustulosis (AGEP)

Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme

Musculoskeletal and Connective Tissue Disorders

• Osteoarthritis, myalgia, back pain, neck pain

Arthralgia

Renal and Urinary Disorders

• Dysuria, renal pain

Renal failure acute, nephritis interstitial

Reproductive system and breast disorders

• Metrorrhagia, testicular disorder

General Disorders and Administration Site Conditions

• *Injection site pain, injection site inflammation

Oedema, asthenia, malaise, fatigue, face oedema, chest pain, pyrexia, pain, peripheral oedema, Investigations

Lymphocyte count decreased, Aspartate aminotransferase increased, eosinophil count increased, blood bicarbonate decreased, basophils increased, monocytes increased, neutrophils increased alanine aminotransferase increased, blood bilirubin increased, blood urea increased, blood creatinine increased, blood potassium abnormal, blood alkaline phosphatase increased, chloride increased, glucose increased, platelets increased, hematocrit decreased, bicarbonate increased, abnormal sodium

Adverse events experienced in higher than recommended doses were similar to those seen at normal doses. The typical symptoms of an overdose with macrolide antibiotics include hearing loss, severe nausea, vomiting and diarrhoea. In the event of overdosage, general symptomatic and supportive measures are indicated as required.