Drugs List

Therapeutic Indications

Uses

Lower respiratory tract infections
Skin and soft tissue infections
Upper respiratory tract infections

Treatment of infections caused by susceptible organisms. Types of infection include:

Lower respiratory tract infections - acute and chronic bronchitis, pneumonia
Upper respiratory tract infections - Tonsillitis, sinusitis and pharyngitis
Mild to moderate skin and soft tissue infections - folliculitis, cellulitis, erysipelas

Clarithromycin is usually effective against the following:
Gram positive bacteria - Staphylococcus aureus (methicillin susceptible), Streptococcus pyogenes (Group A beta-haemolytic streptococci), alpha-haemolytic streptococcus (viridans group), Streptococcus (Diplococcus) pneumoniae, Streptococcus agalactia, Listeria monocytogenes.
Gram negative bacteria - Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae; Legionella pneumophila, Bordetella pertussis, Campylobacter jejuni.
Mycoplasma - Mycoplasma pneumoniae; Ureaplasma urealyticum.
Other organisms - Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae, Chlamydia pneumoniae
Anaerobes - Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionbacterium acnes.

Administration

For oral administration to be taken with food at the same time each day. Tablets must be swallowed whole and not chewed.

Contraindications

Children under 12 years
Family history of long QT syndrome
Electrolyte imbalance
Galactosaemia
History of torsade de pointes
History of ventricular arrhythmias
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Long QT syndrome
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepato-renal syndrome
Ventricular arrhythmias

Precautions and Warnings

Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Glucose-galactose malabsorption syndrome
Hepatic impairment
Lactose intolerance
Myasthenia gravis
Pregnancy
Renal impairment - creatinine clearance 30-60ml/minute

May exacerbate myasthenia gravis
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Ineffective for H. influenzae infections with concurrent tipranavir
Contains lactose
Take cultures for sensitivity testing before and regularly during treatment
Consider pseudomembranous colitis if patient presents with severe diarrhoea
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Prolonged use may result in superinfection with non-susceptible organisms
Discontinue if overgrowth of resistant organisms occurs
Discontinue if severe hypersensitivity reactions occur
Discontinue if symptoms of hepatic disease occur
Discontinue therapy if marked diarrhoea occurs
Advise patient not to take St John's wort concurrently

Due to a risk of prolonged QT interval, clarithromycin should not be used in patients with the following conditions:
Coronary artery disease
History of ventricular arrhythmia
Severe cardiac impairment
Hypomagnesaemia
Bradycardia (less than 50 bpm)
Electrolyte disturbances

Sensitivity testing should be performed when prescribing clarithromycin for community-acquired pneumonia due to emerging resistance of Streptococcus pneumoniae to macrolides. In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics.

Before initiating treatment for skin and soft tissue infections of mild to moderate severity, sensitivity testing should be performed. Skin and soft tissue infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes, both of which may be resistant to macrolides. Currently, macrolides are only considered appropriate in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimum (erythrasma), acne vulgaris, erysipelas and in situations where penicillin treatment cannot be used.

Cases of fatal hepatic failure have been reported. Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop, such as anorexia, jaundice, dark urine, pruritis, or tender abdomen.

Clarithromycin inhibits the enzyme CYP3A4, which is involved in the metabolism of colchicine. Therefore if these drugs are given concurrently, colchicine toxicity may occur. Toxicity is more likely to occur in the elderly or in those with renal impairment and death has occurred in some cases. If these drugs are administered concurrently, the patient should be monitored for signs of colchicine toxicity.

Clarithromycin may cause antibiotic-associated diarrhoea (including Clostridium difficile associated diarrhoea), colitis and pseudomembranous colitis. If diarrhoea occurs during or soon after treatment then these diagnoses should be considered. Careful medical history is necessary since Clostridium difficile associated diarrhoea has been reported to occur over two months after the administration of antibacterial agents. If severe or bloody diarrhoea occurs during treatment, clarithromycin should be discontinued and appropriate therapy instituted. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of Clostridium difficile, and surgical evaluation should be instituted as clinically indicated.

Pregnancy and Lactation

Pregnancy

Use clarithromycin with caution during pregnancy.

Briggs reports the available human pregnancy data on the use of clarithromycin during pregnancy suggests that the risk, if it exists, is low. However the animal reproduction data suggest high risk. Schaefer suggests clarithromycin is a second choice macrolide for use during pregnancy. The manufacturers suggest clarithromycin should not be used during pregnancy unless the benefits outweigh the risks.

Safety in human pregnancy has not been established. Clarithromycin crosses the human placenta. The mean transplacental transfer of clarithromycin was 6.1% in an in vitro experiment using perfused term placentas. The possibility of adverse effects on embryofoetal development cannot be excluded based on variable results obtained from studies in mice, rats, rabbits and monkeys.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use clarithromycin with caution in breastfeeding.

Drugs and Lactation Database (LactMed) considers clarithromycin acceptable during breastfeeding due to low levels of clarithromycin in breast milk. The small amounts in milk are unlikely to cause adverse effects in the infant. However, the infant should be monitored for possible effects on the gastrointestinal flora, such as diarrhoea, thrush or nappy rash. Unconfirmed epidemiologic evidence indicates that the risk of hypertrophic pyloric stenosis in infants might be increased by maternal use of macrolide antibiotics during breastfeeding. The manufacturers suggest clarithromycin should not be used in breastfeeding unless the benefits outweigh the risks.

Clarithromycin and its active metabolite are excreted in human breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal INR
Acne
Ageusia
Agranulocytosis
Alanine aminotransferase increased
Altered liver function tests
Anaphylactic reaction
Anaphylaxis
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Aspartate aminotransferase increased
Asthenia
Asthma
Blood urea increased
Candidiasis
Cardiac disorders
Cellulitis
Chest pain
Chills
Cholestasis
CNS effects
Confusion
Convulsions
Decreased appetite
Depersonalisation
Depression
Diarrhoea
Discolouration of teeth and tongue
Disorientation
Dizziness
Dream abnormalities
Dyspepsia
Eosinophilia
Epistaxis
Exacerbation of myasthenia gravis
Fatigue
Gastro-enteritis
Gastro-intestinal symptoms
Gastroesophageal reflux disease
Glossitis
Haemorrhage
Hallucinations
Headache
Hearing loss
Hepatic failure
Hepatic impairment
Hepatitis
Hyperhidrosis
Hypersensitivity reactions
Hypoglycaemia
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Loss of consciousness (transient)
Malaise
Musculoskeletal disturbances
Nausea
Nervousness
Neutropenia
Overgrowth by non-susceptible organisms
Pancreatitis
Paraesthesia
Parosmia
Prolongation of QT interval
Prothrombin time increased
Pseudomembranous colitis
Psychotic disorder
Pulmonary embolism
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Serum creatinine increased
Skin disorder
Smelling disturbances
Somnolence
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Urine abnormality
Urticaria
Vasodilatation
Ventricular tachycardia
Vertigo
Vomiting
Vulvovaginal infections

Presentation

Modified release tablets containing clarithromycin

Drugs List

Therapeutic Indications

Uses

Lower respiratory tract infections
Skin and soft tissue infections
Upper respiratory tract infections

Treatment of infections caused by susceptible organisms. Types of infection include:

Lower respiratory tract infections - acute and chronic bronchitis, pneumonia
Upper respiratory tract infections - Tonsillitis, sinusitis and pharyngitis
Mild to moderate skin and soft tissue infections - folliculitis, cellulitis, erysipelas

Clarithromycin is usually effective against the following:
Gram positive bacteria - Staphylococcus aureus (methicillin susceptible), Streptococcus pyogenes (Group A beta-haemolytic streptococci), alpha-haemolytic streptococcus (viridans group), Streptococcus (Diplococcus) pneumoniae, Streptococcus agalactia, Listeria monocytogenes.
Gram negative bacteria - Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella (Branhamella) catarrhalis, Neisseria gonorrhoeae; Legionella pneumophila, Bordetella pertussis, Campylobacter jejuni.
Mycoplasma - Mycoplasma pneumoniae; Ureaplasma urealyticum.
Other organisms - Chlamydia trachomatis; Mycobacterium avium; Mycobacterium leprae, Chlamydia pneumoniae
Anaerobes - Macrolide-susceptible Bacteroides fragilis; Clostridium perfringens; Peptococcus species; Peptostreptococcus species; Propionbacterium acnes.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Administration

For oral administration to be taken with food at the same time each day. Tablets must be swallowed whole and not chewed.

Contraindications

Children under 12 years
Family history of long QT syndrome
Electrolyte imbalance
Galactosaemia
History of torsade de pointes
History of ventricular arrhythmias
Hypocalcaemia
Hypokalaemia
Hypomagnesaemia
Long QT syndrome
Renal impairment - creatinine clearance below 30 ml/minute
Severe hepato-renal syndrome
Ventricular arrhythmias

Precautions and Warnings

Bradycardia with pulse rate at rest < 50 beats per minute
Breastfeeding
Glucose-galactose malabsorption syndrome
Hepatic impairment
Lactose intolerance
Myasthenia gravis
Pregnancy
Renal impairment - creatinine clearance 30-60ml/minute

May exacerbate myasthenia gravis
Advise ability to drive/operate machinery may be affected by side effects
Consult national/regional policy on the use of anti-infectives
Ineffective for H. influenzae infections with concurrent tipranavir
Contains lactose
Take cultures for sensitivity testing before and regularly during treatment
Consider pseudomembranous colitis if patient presents with severe diarrhoea
Advise patients to report signs of hepatic damage (malaise, jaundice etc.)
Prolonged use may result in superinfection with non-susceptible organisms
Discontinue if overgrowth of resistant organisms occurs
Discontinue if severe hypersensitivity reactions occur
Discontinue if symptoms of hepatic disease occur
Discontinue therapy if marked diarrhoea occurs
Advise patient not to take St John's wort concurrently

Due to a risk of prolonged QT interval, clarithromycin should not be used in patients with the following conditions:
Coronary artery disease
History of ventricular arrhythmia
Severe cardiac impairment
Hypomagnesaemia
Bradycardia (less than 50 bpm)
Electrolyte disturbances

Sensitivity testing should be performed when prescribing clarithromycin for community-acquired pneumonia due to emerging resistance of Streptococcus pneumoniae to macrolides. In hospital-acquired pneumonia, clarithromycin should be used in combination with additional appropriate antibiotics.

Before initiating treatment for skin and soft tissue infections of mild to moderate severity, sensitivity testing should be performed. Skin and soft tissue infections are most often caused by Staphylococcus aureus and Streptococcus pyogenes, both of which may be resistant to macrolides. Currently, macrolides are only considered appropriate in some skin and soft tissue infections, such as those caused by Corynebacterium minutissimum (erythrasma), acne vulgaris, erysipelas and in situations where penicillin treatment cannot be used.

Cases of fatal hepatic failure have been reported. Some patients may have had pre-existing hepatic disease or may have been taking other hepatotoxic medicinal products. Patients should be advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop, such as anorexia, jaundice, dark urine, pruritis, or tender abdomen.

Clarithromycin inhibits the enzyme CYP3A4, which is involved in the metabolism of colchicine. Therefore if these drugs are given concurrently, colchicine toxicity may occur. Toxicity is more likely to occur in the elderly or in those with renal impairment and death has occurred in some cases. If these drugs are administered concurrently, the patient should be monitored for signs of colchicine toxicity.

Clarithromycin may cause antibiotic-associated diarrhoea (including Clostridium difficile associated diarrhoea), colitis and pseudomembranous colitis. If diarrhoea occurs during or soon after treatment then these diagnoses should be considered. Careful medical history is necessary since Clostridium difficile associated diarrhoea has been reported to occur over two months after the administration of antibacterial agents. If severe or bloody diarrhoea occurs during treatment, clarithromycin should be discontinued and appropriate therapy instituted. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of Clostridium difficile, and surgical evaluation should be instituted as clinically indicated.

Pregnancy and Lactation

Pregnancy

Use clarithromycin with caution during pregnancy.

Briggs reports the available human pregnancy data on the use of clarithromycin during pregnancy suggests that the risk, if it exists, is low. However the animal reproduction data suggest high risk. Schaefer suggests clarithromycin is a second choice macrolide for use during pregnancy. The manufacturers suggest clarithromycin should not be used during pregnancy unless the benefits outweigh the risks.

Safety in human pregnancy has not been established. Clarithromycin crosses the human placenta. The mean transplacental transfer of clarithromycin was 6.1% in an in vitro experiment using perfused term placentas. The possibility of adverse effects on embryofoetal development cannot be excluded based on variable results obtained from studies in mice, rats, rabbits and monkeys.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Use clarithromycin with caution in breastfeeding.

Drugs and Lactation Database (LactMed) considers clarithromycin acceptable during breastfeeding due to low levels of clarithromycin in breast milk. The small amounts in milk are unlikely to cause adverse effects in the infant. However, the infant should be monitored for possible effects on the gastrointestinal flora, such as diarrhoea, thrush or nappy rash. Unconfirmed epidemiologic evidence indicates that the risk of hypertrophic pyloric stenosis in infants might be increased by maternal use of macrolide antibiotics during breastfeeding. The manufacturers suggest clarithromycin should not be used in breastfeeding unless the benefits outweigh the risks.

Clarithromycin and its active metabolite are excreted in human breast milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal INR
Acne
Ageusia
Agranulocytosis
Alanine aminotransferase increased
Altered liver function tests
Anaphylactic reaction
Anaphylaxis
Angioedema
Anorexia
Anxiety
Arrhythmias
Arthralgia
Aspartate aminotransferase increased
Asthenia
Asthma
Blood urea increased
Candidiasis
Cardiac disorders
Cellulitis
Chest pain
Chills
Cholestasis
CNS effects
Confusion
Convulsions
Decreased appetite
Depersonalisation
Depression
Diarrhoea
Discolouration of teeth and tongue
Disorientation
Dizziness
Dream abnormalities
Dyspepsia
Eosinophilia
Epistaxis
Exacerbation of myasthenia gravis
Fatigue
Gastro-enteritis
Gastro-intestinal symptoms
Gastroesophageal reflux disease
Glossitis
Haemorrhage
Hallucinations
Headache
Hearing loss
Hepatic failure
Hepatic impairment
Hepatitis
Hyperhidrosis
Hypersensitivity reactions
Hypoglycaemia
Increase in alkaline phosphatase
Increase in lactate dehydrogenase
Increases in hepatic enzymes
Insomnia
Interstitial nephritis
Jaundice
Leucopenia
Loss of consciousness (transient)
Malaise
Musculoskeletal disturbances
Nausea
Nervousness
Neutropenia
Overgrowth by non-susceptible organisms
Pancreatitis
Paraesthesia
Parosmia
Prolongation of QT interval
Prothrombin time increased
Pseudomembranous colitis
Psychotic disorder
Pulmonary embolism
Pyrexia
Rash
Renal failure
Rhabdomyolysis
Serum creatinine increased
Skin disorder
Smelling disturbances
Somnolence
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Tinnitus
Torsades de pointes
Toxic epidermal necrolysis
Tremor
Urine abnormality
Urticaria
Vasodilatation
Ventricular tachycardia
Vertigo
Vomiting
Vulvovaginal infections

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: September 2013

Reference Sources

British National Formulary, 66th Edition (September 2013-March 2014) Pharmaceutical Press, London.

BNF for Children (2013-2014) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Summary of Product Characteristics: Febzin XL tablets. Actavis. Revised November 2011.
Summary of Product Characteristics: Klaricid XL tablets. Abbott Laboratories Limited. Revised September 2016.
Summary of Product Characteristics: Xetinin XL tablets. Morningside Healthcare. Revised February 2011.

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Clarithromycin. Last revised: September 7, 2013
Last accessed: September 10, 2013.