Fluconazole is a synthetic bis-triazole compound.

Fluconazole (Diflucan): Mechanism of action

Fluconazole is a potent inhibitor of ergosterol biosynthesis, through its action on the cytochrome P-450-dependent enzyme, lanosterol 14a-demethylase. Depletion of ergosterol, the principal sterol in the membrane of susceptible fungal cells, and accumulation of methylated sterols leads to alterations in a number of membrane-associated cell functions.

Fluconazole (Diflucan): Spectrum of action

Fluconazole has a broad spectrum of action including Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis. It is active against Candida albicans, C. tropicalis and C. parapsilosis, but many strains of C. krusei and Torulopsis glabrata (now reclassified as Candida glabrata) appear to be insensitive. Fluconazole is active in dermatophytosis, but appears to be ineffective in aspergillosis and mucormycosis.

In neutropenic patients, the most common manifestation of fluconazole resistance is the selection of unusual Candida species, such as C. krusei, which possess intrinsic resistance to the drug.

Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan): Acquired Resistance

There have been few reports of resistance developing in C. albicans or C. tropicalis during short-term fluconazole treatment in patients with mucosal or deep-seated forms of candidosis. In patients with AIDS, resistant strains of C. albicans often appear as a result of repeated courses of low-dose fluconazole treatment for oral or oesophageal infection. Many of these fluconazole-resistant C. albicans strains appear to be susceptible to other azoles. Resistant strains of C. neoformans have been recovered from patients with AIDS with relapsing cryptococcosis following long-term maintenance treatment with fluconazole, but this is an uncommon problem at present.

Three mechanisms of azole drug resistance have so far been recognized. The first is reduced intracellular drug accumulation. This results either from reduced drug uptake or from increased drug excretion. Recent work suggests that accelerated efflux of fluconazole, due to the action of multidrug resistance gene products, is the main reason for reduced drug access. The second resistance mechanism is structural alteration of the 14a-demethylase enzyme that results in decreased binding to azole antifungals. The third mechanism is overproduction of this target enzyme, due to gene amplification. The existence of multiple resistance mechanisms to agents with a common mode of action may explain why many fluconazole-resistant strains of C. albicans remain susceptible to other azoles.

Pharmacokinetics of Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan)

Oral administration of fluconazole leads to rapid and almost complete absorption of the drug. Identical serum concentrations are attained after oral and parenteral administration indicating that first-pass metabolism of the drug does not occur. B100d concentrations increase in proportion to dosage over a wide range of dose levels. Two hours after a single 50-mg oral dose, serum concentrations in the region of 1.0mg/l can be anticipated, but after repeated dosing this increases to about 2.0-3.0 mg/1. Administration of the drug with food does not affect absorption. Oral or parenteral administration of fluconazole results in rapid and widespread distribution of the drug. Unlike other azole antifungals, the protein binding of fluconazole is low (about 12%) resulting in high levels of circulating unbound drug. Levels of the drug in most tissues and fluids usually exceed 50% of the simultaneous blood concentration.

The main means of elimination is renal excretion of the unchanged drug. About 80% of an administered dose appears in the urine in unchanged form and concentrations of >100mg/l have been attained in patients with normal renal function. The drug is cleared through glomerular filtration, but significant tubular reabsorption occurs. Fluconazole has a serum half-life of 20-30 h, but this is prolonged in renal failure, necessitating adjustment of the dosage regimen in patients with glomerular filtration rates below 50 ml/min.

Fluconazole is removed during haemodialysis and, to a lesser extent, during peritoneal dialysis. A 3-h haemodialysis session will reduce the blood concentration by about 50%.

Metabolism of Fluconazole (Diflucan)

Unlike other azole antifungals, fluconazole is not extensively metabolized in humans. More than 90% of a given dose is eliminated in the urine: about 80% as unchanged drug and 10% as metabolites. There is no indication of significant induction or inhibition of fluconazole metabolism following repeated dosing.

Pharmaceutics of Fluconazole (Diflucan)

Fluconazole is available in oral and parenteral forms: as capsules, oral suspension and an intravenous infusion. The drug is supplied for parenteral administration at a concentration of 2.0mg/ml in 0.9% sodium chloride solution. Dosing recommendations are identical for all dosage forms.

Use and Administration of Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan)

Adverse Reactions of Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan)

Fluconazole is well tolerated. The most common side-effects are gastrointestinal in origin, such as nausea and abdominal discomfort, but these seldom necessitate discontinuation of treatment in patients receiving up to 400 mg/day. Transient asymptomatic elevations of serum transaminase levels are quite common in patients with AIDS treated with the drug, and treatment should be discontinued in patients who have symptomatic hepatitis or test findings indicative of progressive or persistent hepatic dysfunction.

Fatal exfoliative skin rashes (Stevens-Johnson syndrome) have been reported in patients with AIDS or cancer, but the causal relationship with fluconazole is unclear because of the concomitant administration of other drugs. It is advisable to discontinue fluconazole in a patient with a superficial fungal infection who develops a skin rash. Patients with deep-seated fungal infection who develop rashes should be monitored and the drug discontinued if bullous lesions or erythema multiforme develop.

Unlike ketoconazole, fluconazole, when given in recommended doses, does not inhibit human adrenal or testicular steroid metabolism.

Drug Interactions of Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan)

Therapeutic Use of Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan)

Fluconazole can be used to treat mucosal and cutaneous forms of candidosis. It is also effective in various forms of dermatophytosis and pityriasis versicolor.

It is a promising drug for treatment of deep forms of candidosis in patients without neutropenia, but should not be used as first-line treatment in neutropenic patients unless there are particular reasons for favouring it against established management. Fluconazole has proved to be a useful prophylactic treatment against candidosis in neutropenic patients. However, it is ineffective in aspergillosis and mucormycosis.

Fluconazole is a useful drug in acute cryptococcal meningitis, but should not be used as first-line treatment in patients with AIDS unless there are particular reasons for withholding amphotericin B. However, it is more effective and better tolerated than amphotericin B as maintenance treatment to prevent relapse of cryptococcosis in patients with AIDS.

Fluconazole is now the drug of choice for patients with coccidioidal meningitis. However, it must be continued for life to prevent relapse.

Fluconazole 50, 100, 150, 200 mg Tablets (Diflucan): Mode of Administration

As absorption following oral administration is good, this is the preferred method of administration. If the patient cannot take the drug by mouth, the intravenous solution can be used. This should be infused at a rate of 5-10 ml/min.

Vaginal candidosis can be treated with a single 150-mg oral dose of fluconazole. Oropharyngeal candidosis should be treated with 50-200 mg/day for 1-2 weeks. Oesophageal and mucocutaneous forms of candidosis and lower urinary tract candidosis require 100-200 mg/day for 2-4 weeks.

The recommended dose for patients with cryptococcosis or deep forms of candidosis is 400 mg/day. However, some clinicians have used higher dosages in life-threatening infections. The duration of treatment will differ from patient to patient, depending upon the nature and extent of the infection and the underlying illness. At least 6-8 weeks is usually required for successful treatment of cryptococcosis in patients without AIDS. The recommended dose for children is 1-2 mg/kg for superficial forms of candidosis and 5 mg/kg for cryptococcosis or deep forms of candidosis.

Long-term maintenance treatment with fluconazole to prevent relapse in patients with AIDS with cryptococcosis should be administered at a dosage of 200 mg/day. To prevent candidosis in neutropenic patients, the dose should be 100-400 mg/day. Patients at high risk of developing a deep-seated infection should receive 400 mg/day and this should be commenced several days before the anticipated onset of neutropenia and continued for 1 week after the neutrophil count recovers to 1 x 10⁹/1.

Patients with renal impairment should be given the normal dose for the first 48 h of treatment. Thereafter, in persons with a creatinine clearance of 21-40 ml/min, the dosage interval should be doubled to 48 h or the dose halved. Persons with a clearance of 10-20 ml/min require a 72-h interval between doses.

Patients receiving regular haemodialysis require the usual dose after each dialysis session.

Unlike itraconazole and ketoconazole, absorption of fluconazole is not reduced if it is given together with drugs that reduce gastric acid secretion. Concomitant administration of fluconazole and rifampicin has resulted in a modest reduction in blood levels of the antifungal agent. The effect is less marked than with itraconazole or ketoconazole and is due to induction of P-450 cytochrome oxidases by rifampicin with resulting enhanced hepatic metabolism of the azole drug.

Like rifampicin, phenytoin undergoes cytochrome P-450-mediated hepatic metabolism and its concomitant administration with fluconazole may reduce its clearance. If these drugs are given together, serum concentrations of phenytoin should be monitored and the phenytoin dose adjusted to maintain therapeutic levels.

Fluconazole has been shown to prolong the serum half-life, thus augmenting the hypoglycaemic effects of drugs, such as chlorpropamide, glibenclamide, glipizide and tolbutamide. Fluconazole can also increase the serum concentration of warfarin, augmenting its anticoagulant effects. Careful monitoring of prothrombin time in patients receiving concomitant treatment with fluconazole and anticoagulants is recommended.

Fluconazole may prolong the half-life of cyclosporin in transplant recipients, leading to increased blood levels of that drug. Serum concentrations of cyclosporin should be monitored if these drugs are given together.

Definition of Tinea Unguium

The term tinea unguium is used to describe dermatophyte infections of the fingernails or toenails.

Geographical distribution of Tinea Unguium

The condition is worldwide in distribution.

Causal organisms

Fungal infection of the nails (onychomycosis) may be caused by a number of dermatophytes as well as by a number of other moulds and Candida species. There is wide geographical and racial variation in the causative agents, but in the UK 85-90% of nail infections are due to dermatophytes and about 5% are due to non-dermatophyte moulds. The dermatophytes most commonly implicated are anthropophilic species, such as T. mentagrophytes var. interdigitate and T. rubrum. Their prevalence differs from one geographical region to another. Zoophilic species, such as T. erinacei, are seldom isolated and usually only from fingernails.

Tinea unguium is most prevalent between the ages of 20 and 50, but the actual incidence of the condition is difficult to assess. This is because many reports do not distinguish between dermatophytosis and other forms of onychomycosis, or between infections of the finger and toenails. It has been estimated that tinea unguium occurs in about 3% of adults in the UK.

Management of Tinea Unguium

Tinea unguium is a difficult condition to treat. Localized distal nail disease can be treated with topical antifungals, such as amorolfine or tioconazole. Amorolfine should be applied at 1-week intervals, while tioconazole must be applied each morning and evening. Amorolfine treatment must be continued for at least 6 months for success with fingernails and 9-12 months for toenails.

The allylamine terbinafine is now the treatment of choice for patients with dermatophytosis of the fingernails or toenails. Oral treatment with 250 mg/day for between 6 weeks and 3 months is often sufficient to cure a fingernail infection, but toenails may require treatment for 3 months or longer. Treatment with oral terbinafine will also clear associated cutaneous lesions without the need for additional topical treatment.

Itraconazole is another effective treatment for dermatophyte nail infection. This drug persists in nail for at least 6 months and pulsed treatment (in which a week of treatment is alternated with three weeks without treatment) has given encouraging results. Two pulses of treatment with 400 mg/ day are recommended for success with fingernails and three pulses of treatment (or more) for toenail infections. Itraconazole is also available for continuous treatment and a dosage of 200 mg/day for 3 months is the most appropriate for severe nail disease.

With griseofulvin, up to 90% of fingernail infections can be cured in 4-8 months, but its low cure rate of 40% in some toenail infections means that it is now less appropriate than terbinafine or itraconazole.

Definition of Tinea Manuum

The term tinea manuum is used to refer to dermatophyte infections of one or both hands.

Geographical distribution of Tinea Manuum

The condition is worldwide in distribution.

Causal organisms

The anthropophilic dermatophytes E. floccosum, T. mentagrophytes var. interdigitate and T. rubrutn are the most common causes of tinea manuum. Less commonly, the condition is caused by zoophilic dermatophytes, such as M. canis and T. verrucosum, or geophilic dermatophytes, such as M. gypseum.

Hand infection may be acquired as a result of contact with another person, with an animal, or with soil, either through direct contact, or via a contaminated object such as a towel or gardening tool. Autoinoculation from another site of infection can also occur. Manual work, profuse sweating and existing inflammatory conditions, such as contact eczema, are predisposing factors.

Differential diagnosis of Tinea Manuum

Tinea manuum must be distinguished from other forms of dyshidrosis. This condition, whatever its origin, is usually bilateral or even symmetrical. In its typical form, clear vesicles are grouped on the lateral and volar aspects of the fingers as well as on the palm. There is little or no inflammation of the base. Dyshidrotic eczema is usually bilateral, but mycological examination is often required to distinguish it and other conditions (such as psoriasis, whether pustular or not) from tinea manuum.

Essential investigations and their interpretation

Direct microscopic examination of infected material, such as vesicle tops and contents and skin scales, should reveal the branching hyphae characteristic of a dermatophyte infection. Isolation of the aetiological agent in culture will permit the species of fungus involved to be determined.

Management of Tinea Manuum

Local treatment with a topical imidazole, such as clotrimazole, econazole, miconazole or sulconazole, or an allylamine, such as naftifine or terbinafine, will often suffice to clear tinea manuum.

In cases that fail to respond to topical treatment, oral terbinafine (250 mg/day for 2-6 weeks), or itraconazole (100 mg/day for 4 weeks) should be prescribed.

Definition of Tinea Pedis

The term tinea pedis is used to refer to dermatophyte infections of the feet. These infections often involve the interdigital spaces, but chronic diffuse desquamation can affect the entire sole.

Geographical distribution of Tinea Pedis

The condition is worldwide in distribution.

Causal organisms

The anthropophilic dermatophytes E. floccosum, T. mentagrophytes var. interdigitale and T. rubrutn are the commonest causes of tinea pedis in the UK and North America. T. rubrutn is the principal cause of chronic tinea pedis. T. mentagrophytes usually causes more inflammatory lesions.

Tinea pedis is a very widespread condition that appears to be increasing in prevalence. It often begins in late childhood or young adult life and is most common between the ages of 20 and 50. Men are more frequently affected than women.

The infection is usually acquired by walking barefoot on contaminated floors. Hyphae and arthrospores of the causal dermatophytes can survive for long periods (> 12 months) in human skin scales. Excessive sweating and occlusive footwear are factors that favour the development of tinea pedis.

Management of Tinea Pedis

Tinea pedis will often respond to topical treatment with an imidazole compound, such as clotrimazole, econazole, miconazole or sulconazole, or an allylamine, such as naftifine or terbinafine. Terbinafine should be applied to the toe clefts and other affected sites morning and evening for at least 2 weeks. Imidazoles often need to be applied for up to 4 weeks. The patient may also benefit by applying the cream to the soles to help prevent the infection from spreading. The recurrence rate following topical treatment is quite high, and chronic infection with minor scaling that persists despite treatment is not uncommon. Exacerbations of previous infection may also occur.

Mixed fungal and bacterial infections of the feet are common. For this reason, topical antifungal preparations that are effective against dermatophytosis and candidosis, and which possess some antibacterial action (such as miconazole) are often recommended.

If the disease is extensive, involving the sole and dorsum of the foot, or there is acute inflammation, oral treatment with terbinafine (250 mg/day for 2-6 weeks) or itraconazole (100 mg/day for 4 weeks) should be given in addition to topical treatment (which should be continued for 8 weeks or longer). However, relapse is common.

Chronic tinea pedis is often associated with nail infection. Inadequate treatment of onychomycosis may result in reinfection of the feet.

Tinea pedis is a chronic condition which seldom resolves if left untreated. Exacerbations, which tend to occur in the summer, alternate with partial remissions. Nevertheless, the prognosis in general remains benign.

It is important to inform the patient of measures that may help to control or prevent the infection. Daily bathing of the feet, followed by careful drying of the toes and interdigital spaces, is important. The patient should also be advised to avoid heavy occlusive footwear, which may increase sweating, and to wear soft absorbent socks.

Once the clinical symptoms have cleared, use of an anti-fungal foot powder on the feet and inside footwear may prevent reinfection.

Definition of Tinea Cruris

The term tinea cruris is used to refer to dermatophyte infections of the groin and pubic region.

Geographical distribution of Tinea Cruris

The condition is worldwide in distribution.

Causal organisms

The dermatophytes most often encountered in tinea cruris are E. floccosum and T. rubrum. Maceration and occlusion of the skin in the groin give rise to warm moist conditions that favour the development of the infection.

Tinea cruris is a common form of dermatophytosis. It is more prevalent in men than women. It usually occurs between the ages of 18 and 60, but is most prevalent between the ages of 18 and 25, and between 40 and 50. Tinea cruris is often acquired from another infected area of the same individual. Autoinoculation from infected feet via towels is not uncommon.

Tinea of the groin is a highly contagious condition and minor epidemics often occur in schools and other communities. The infection is usually transmitted via contaminated towels or the floors of bathrooms, showers or hotel bedrooms, etc.

Management of Tinea Cruris

Most patients with tinea cruris will respond to local anti-fungal treatment within 2-4 weeks. Topical imidazoles, such as clotrimazole, econazole, miconazole or sulconazole, and allylamines, such as naftifine or terbinafine, should be applied morning and evening for at least 2 weeks. To prevent relapse, treatment should be continued for at least 1 week after the lesions have cleared.

If a patient has extensive lesions, or fails to respond to topical treatment, or has tinea pedis as well, oral treatment should be given. Itraconazole (100 mg/day for 2 weeks) and terbinafine (250 mg/day for 2-4 weeks) have proved more effective than griseofulvin (10 mg/kg per day for 2-6 weeks).

To prevent reinfection following treatment, the patient should be advised to dry the groin thoroughly after bathing and to use separate towels to dry the groin and the rest of their body. The feet should be examined and treated if tinea pedis is present. Occlusive or synthetic garments should be avoided. If the patient is obese, weight loss may be of benefit by reducing chafing and sweating.

Tinea cruris recurs in about 20-25% of patients. If this happens, patients should be given further antifungal treatment and advice about non-pharmacological control measures should be repeated.

Definition of Tinea Corporis

The term tinea corporis is used to refer to dermatophyte infections of the trunk, legs and arms, but excluding the groin, hands and feet.

Geographical distribution of Tinea Corporis

The condition is worldwide in distribution, but is most prevalent in tropical and subtropical regions.

Causal organisms

Tinea corporis is caused by E. floccosum and many species of Trichophyton and Microsporum. Infection with anthropophilic species, such as E. floccosum or T. rubrum often follows autoinoculation from another infected body site, such as the feet. Tinea corporis caused by T. tonsurans is sometimes seen in children with tinea capitis and their close contacts.

Tinea corporis commonly occurs following contact with infected household pets or farm animals, but occasional cases result from contact with wild mammals or contaminated soil. M. canis is a frequent cause of human infection, and T. verrucosutn infection is common in rural areas. Tinea corporis is more common among individuals in regular contact with animals or with the soil. Human-to-human spread of infection with geophilic or zoophilic species is unusual.

Essential investigations and their interpretation

Material for mycological investigation should be collected from the raised border of the lesion by scraping outwards with a blunt scalpel held perpendicular to the skin. If vesicles are present, the entire top should be submitted for examination.

Direct microscopic examination of infected material should reveal the branching hyphae characteristic of a dermatophyte infection.

Isolation of the aetiological agent in culture will permit the species of fungus involved to be determined. This will provide information as to the source of the infection and aid the selection of appropriate treatment.

Management of Tinea Corporis

Topical antifungal preparations are the treatment of choice for localized lesions. Four imidazoles (clotrimazole, econazole, miconazole and sulconazole) and two allylamine compounds (naftifine and terbinafine) are available in a number of topical formulations. All give similar high cure rates (70-100%) and side-effects are uncommon. These drugs should be applied morning and evening for 2-4 weeks. Treatment should be continued for at least 1 week after the lesions have cleared and the medication should be applied at least 3 cm beyond the advancing margin of the lesion.

If the lesions are extensive or the patient fails to respond to topical preparations, oral treatment is usually indicated. Itraconazole (100 mg/day for 2 weeks) and terbinafine (250 mg/day for 2-4 weeks) have proved more effective than griseofulvin (10 mg/kg per day for 4 weeks).

Definition of Tinea Capitis

The term tinea capitis is used to refer to dermatophyte infections of the scalp and hair.

Geographical distribution of Tinea Capitis

The condition is worldwide in distribution, but is most prevalent in Africa, Asia and southern and eastern Europe, where it is the most common form of dermatophytosis. Improved standards of hygiene and prompt eradication of sporadic infection have led to a marked decline in the incidence of tinea capitis in North America and western Europe. Favus used to be worldwide in distribution, but is now confined to North Africa, the Middle East and parts of southern and eastern Europe.

Causal organisms

Tinea capitis is caused by a number of Trichophyton and Microsporum species. M. canis is a frequent cause of the condition in western Europe, but T. violaceum is predominant in eastern and southern Europe and North Africa. T. tonsurans is predominant in North America, and is becoming more common in the UK.

Tinea capitis due to anthropophilic Microsporum species is a contagious disease endemic in many countries. It is primarily a disease of children, being more common in males than females, and most prevalent between 6 and 10 years of age. The disease seldom persists beyond the age of 16. Large outbreaks often occur in schools or other places where children are congregated. The zoophilic Microsporum and Trichophyton species are seldom responsible for more than minor outbreaks of human infection. Household pets, such as dogs and cats, are a common source of infection, but feral cats are another prolific source of M. canis.

Tinea capitis due to anthropophilic Trichophyton species is another contagious disease. It is most common in male children under the age of 12.

T. schoenleinii is considered to be the sole aetiological agent of favus, although infections with other dermatophytes, such as M. gypseum, T. verrucosum and T. violaceum, can sometimes produce somewhat similar lesions. Although T. schoenleinii is an anthropophilic dermato-phyte, favus is less contagious than other forms of tinea capitis due to Microsporum or other Trichophyton species. It is usually contracted in childhood and may persist into adult life. Debilitated or malnourished children, or children suffering from a chronic disease such as tuberculosis, are more susceptible to this infection. Instances have been reported in which several generations of the same family were affected.

Management of Tinea Capitis

If possible, specimens for mycological examination should be taken before starting treatment. If oral treatment is being considered, mycological confirmation of the clinical diagnosis is essential before treatment is commenced.

Terbinafine (250 mg/day for 2 weeks) and itraconazole (100 mg/day for 2 weeks) have both proved effective in the oral treatment of tinea capitis, but neither compound is licensed for this indication at present. The duration of griseofulvin treatment depends on the nature of the infection and the clinical response; some infections can take up to 3 months to clear. The usual dosage is 10 mg/kg and this should be given after food. Mycological tests should be repeated 1 month after starting treatment and again before discontinuing the drug.

Various topical imidazole preparations can be used to treat localized scalp lesions, including clotrimazole, miconazole and sulconazole. These drugs are safe and side-effects after local application are uncommon.

To prevent epidemics of anthropophilic tinea capitis due to M. audouinii from developing, all contacts of infected children should be examined with Wood’s light. Contacts of children with T. tonsurans infection can be screened using the hair brush sampling method. It is seldom practical to exclude infected children from school, in view of the long duration of treatment.

Generic Name: Clarithromycin

Information For The User

1. What Clarithromycin 125mg/5ml Oral Suspension Is And What It Is Used For

Clarithromycin 125mg/5ml oral suspension contains clarithromycin. Clarithromycin belongs to a group of antibiotics called macrolides. Clarithromycin works by destroying some types of bacteria that cause certain infections. Clarithromycin may be used to treat infections that are caused by bacteria in the chest, throat, sinuses and ear and infections of the skin and the layers of flesh just under the skin.

Clarithromycin 125mg/5ml oral Suspension is used in children 6 months to 12 years old.

2. Before You Give Clarithromycin 125mg/5ml Oral Suspension

Do not give Clarithromycin 125mg/5ml Oral Suspension to your child:

• If your child has ever had an allergic reaction to clarithromycin or to any other macrolide antibiotic (such as erythromycin or azithromycin) or to any of the other ingredients in the suspension listed at the end of the leaflet (an allergic reaction may include rash, itching, swelling of face, lips, or hands/feet or breathing difficulties).

• Is your child taking ergot derivatives such as ergotamine tablets or inhalers (used for treatment of migraine).

• Is your child taking terfenadine or astemizole (used for treatment of allergies), cisapride (used for treatment of digestive problems) or pimozide (used for treatment of mental illnesses).Clarithromycin must not be taken with any of these medicines because there is a risk that very serious disturbances in the rhythm of the heart could occur.

• If your child has phenylketonuria. Clarithromycin suspension contains aspartame, which is a source of phenylalanine. This means that the suspension is not recommended for children who have phenylketonuria.

• If your child has a serious problem with kidney(s)/liver.

• If your child has or has ever had problems with his/her heart rhythm.

• If your child has low blood potassium levels. Excessive diarrhoea can cause low potassium levels in the blood.

Take special care with Clarithromycin 125mg/5ml Oral Suspension:

• If your child has or ever had problems with their liver or their kidneys.

• If your child is allergic to lincosamide (e.g. lincomycin or clindamycin) antibacterial Agents.

• If your child is suffering from a condition known as myasthenia gravis.

Taking other medicines

Please inform your doctor or pharmacist if your child is taking, or has recently taken, any other medicines, including any that were obtained without a prescription.

Care is needed if your child is taking:

• Warfarin (a medicine that is used to stop blood clotting)

• Theophylline (an anti-asthma medicine)

• Ciclosporin, tacrolimus or sirolimus (used following organ transplants)

• Digoxin (used for treatment of heart failure)

• Disopyramide (used for treatment of certain abnormal heart rhythms)

• Midazolam, triazolam or alprazolam (used as tranquilizers)

• Phenytoin, carbamazepine or Phenobarbital (used for treating epilepsy)

• St. John’s Wort (a herb used for medicinal purposes, including treatment of depression)

• Insulin and antidiabetic medicinal products (used for treatment of diabetes)

• Rifampicin or Rifabutin (an antibiotic used for treating certain infections)

• Lovastatin or simvastatin (used for lowering blood cholesterol levels)

• Zidovudine, Ritonavir or Efavirenz (used for treating Human Immunodeficiency Virus [HIV] infections)

Giving Clarithromycin 125mg/5ml Oral Suspension with food and drink

Clarithromycin 125mg/5ml Oral Suspension may be given with or without food Pregnancy and breast-feeding.

The safety of clarithromycin in pregnancy and breast-feeding is not known and it is not usually given during pregnancy or breastfeeding unless it is considered very necessary.

If your daughter is of child-bearing age you should speak to your doctor before giving this product if pregnancy is known or suspected.

Ask the doctor or pharmacist before giving any medicine.

Driving and using machines

Clarithromycin is known to cause dizziness, vertigo, confusion, and disorientation. This may affect your ability to drive and use machines. Make sure you know how your child reacts to clarithromycin before he/ she drives, uses machines, or engages in any other activity that could be dangerous if he/ she is not alert.

Important information about some of the ingredients of Clarithromycin 125mg/5ml oral Suspension.

• Clarithromycin suspension contains aspartame, which is a source of phenylalanine. May be harmful for people with phenylketonuria.

• If you have been told by the doctor that your child has an intolerance to some sugars,

contact the doctor before giving this medicinal product This product contains 6 g of sucrose per 10ml dose. This should be taken into account in patients with diabetes mellitus.

3. How Clarithromycin 125mg/5ml Oral Suspension Is Given

Always take Clarithromycin 125mg/5ml oral suspension exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Dosage

The dose of clarithromycin depends on your child’s weight in kilograms and is usually approximately 7.5 mg for each kilogram body weight given twice each day, usually in the morning and in the evening. The suspension can be given with or without food. Clarithromycin 125mg/5ml Oral Suspension will be supplied with an oral dosing spoon or pipette (syringe) to help you measure the right amount of medicine to give to your child. Your doctor or pharmacist will advise you whether it is better to use the spoon or the pipette to give the right dose. Make sure that you are clear about this before you start to give the suspension.

The usual doses of Clarithromycin 125mg/5ml Oral Suspension to be given either with the spoon or with the pipette are shown below:

If your child weighs less than 8 kilograms, your doctor will calculate the dose for your child and this will be written on the pharmacist’s label.

In the treatment of severe infections, doses up to 500mg clarithromycin twice daily have been used.

Your doctor may prescribe a lower dose if your child has mild to moderate kidney or liver problems.

Method and/or route(s) of administration

Clarithromycin 125mg/5ml Oral Suspension is supplied with an oral dosing spoon or pipette (syringe). If you use the pipette, please follow instructions given below carefully. After use of the spoon or syringe, wash in warm soapy water and rinse well.

1. Remove the child-proof cap from the bottle by pushing down on the cap while turning it anticlockwise.

2. Take the plastic circular adaptor from the carton and push this into the neck of the bottle. This should fit tightly and once it is in place it should not be removed.

3. Take the syringe out of the carton and ensure that the plunger is pressed down inside the barrel as far as it will go. This gets rid of any air that may be inside the barrel.

4. Insert the nozzle of the syringe into the hole in the adaptor.

5. Turn the bottle upside down. Keep hold of the bottle in one hand and the syringe in the other.

6. Hold the barrel of the syringe steady and slowly, pull the plunger down until you see the medicine fill the barrel to the mark which matches the number of ml that you need to give to your child.

7. Turn the bottle the correct way up. Keeping hold of the barrel, remove the whole syringe from the adaptor.

8. Put the syringe tip into your baby’s mouth. Drip the medicine in by pushing down the plunger gently while still holding the barrel. Don’t hurry your child, allow time for him or her to swallow the medicine slowly. Alternatively, empty the measured dose from the syringe onto a spoon for your child to take the medicine from.

9. Replace the cap on the bottle of medicine.

10.Wash the syringe in warm soapy water and rinse well. Hold the syringe under water and move the plunger up and down several times to make sure the inside of the barrel is clean. Store the syringe in a hygienic place with the medicine.

Duration of treatment

Clarithromycin suspension is usually given for 5 to 10 days. Your doctor will tell you how long to give clarithromycin. Do not stop giving the suspension before your doctor tells you to, even if your child feels better, because the symptoms may return. If you have the impression that the effect of clarithromycin suspension is too strong or too weak, talk to your doctor or pharmacist.

If you give your child more clarithromycin suspension than your doctor has told you to, or if your child has accidentally swallowed some extra medicine, consult your doctor or go to the nearest hospital emergency department immediately. Take this leaflet or bottle of suspension with you so the doctor will know what your child has taken.

If you forget to give clarithromycin suspension to your child at the right time, give it as soon as you remember. However, if it is almost time for the next dose, skip the missed dose and give the next dose when it is due. Do not give a double dose to make up for forgotten individual doses.

If you have any further questions on the use of this product, ask the doctor or pharmacist.

4. Possible Side Effects of Clarithromycin

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

If any of the following happen, stop giving clarithromycin suspension and tell your doctor immediately or go to the emergency department at your nearest hospital. Your child may be having a serious allergic reaction to clarithromycin and may need urgent medical attention.

• Rashes that may be lumpy, hives, itching, tightness in the chest, difficulty breathing and shortness of breath, fever or swelling of face, lips, hands / feet, fainting.

• Severe skin rashes, with or without blisters, sores or ulcers.

You should also stop giving clarithromycin suspension and tell your doctor immediately if your child develops:

• Severe diarrhoea (which may contain blood or mucous) along with stomach cramps

• Any irregular or fast heart beat

• Fits

• Jaundice (yellowing of whites of eyes and skin)

• Easy bruising or bleeding for a long time after minor injuries. This can be due to low numbers of a type of blood cell called platelets that help blood to clot.

Other side effects that can occur are:

• Feeling or being sick, indigestion, pain in the belly, mild diarrhoea or loose stools, inflammation and discoloration of tongue, inflammation of the mouth, tooth discoloration (usually reversible with professional tooth cleaning)

• White patches inside the mouth or on the tongue (oral thrush) while taking this medicine (your doctor or pharmacist will prescribe treatment for this)

• Dizziness, unsteadiness, headache, sleep disorders, nightmares, pins and needles

• Impaired sense of taste and smell (usually returns to normal once treatment with clarithromycin is over)

• Ringing in the ears or some loss of hearing (usually returns to normal once treatment with clarithromycin is over)

• Confusion, hallucinations, marked disturbances in behaviour, mood changes, loss of sense of reality, excessive anxiety, loss of bearings

• Disturbance in the rhythm of heart

• Severe abdominal pain accompanied by nausea and vomiting, (this may be a manifestation of inflammation of the pancreas)

• Yellowing of whites of eyes and skin (jaundice), loss of appetite, pain in right upper abdomen, and general feeling of being unwell accompanied by nausea and vomiting (this may be a manifestation of inflammation of liver)

• Dark discoloration of urine, bloody or cloudy urine or any change in his/her urine output.

• Swelling of face, ankles or other parts of the body, with decrease in the amount of urine passed

• Unusual bleeding or increased tendency to bleed, persistent sore throat and frequent infections

• Joint and muscle pains.

There may be changes in the results of certain laboratory tests

• Abnormal liver-function tests

• Abnormal kidney function tests

• Decreased blood sugar

• Altered blood cell counts

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please inform the doctor or pharmacist.

5. How To Store Clarithromycin 125mg/5ml Oral Suspension

Keep clarithromycin suspension out of the reach and sight of children.

Do not give after the expiry date on the labeling.

Do not store above 25°C. Do not refrigerate or freeze. Keep the bottle tightly closed. Discard

unused portion after 14 days or return to your pharmacist, who will dispose of it.

6. Further Information

What Clarithromycin 125mg/5ml oral suspension contains

The active substance is clarithromycin. Other ingredients are microcrystalline cellulose, hypromellose, hydroxypropyl cellulose, croscarmellose sodium, alginic acid, methacrylic acid-ethyl acrylate copolymer (1:1) dispersion 30%, macrogol 1500, talc, carbomer (Carbopol 974 P), colloidal anhydrous silica, sucrose, aspartame (E951), xanthan gum, monosodium citrate, sodium benzoate (E211), titanium dioxide(E171), sodium chloride, Peppermint and Tutti Frutti flavours.

What Clarithromycin 125mg/5ml oral suspension looks like and contents of the pack

Clarithromycin 125mg/5ml oral suspension is white to off-white granular powderforming a white to off-white suspension on constitution with water. The resulting suspension has a sweet taste and fruity flavour.

The suspension is available in bottles of 50, 60,70,100 and 140 ml. Not all the pack sizes may be available.

Marketing authorisation holder and manufacturer Marketing authorisation holder:

Accord Healthcare Limited, Sage House, 319, Pinner Road, North Harrow, Middlesex, HA1 4HF, United Kingdom

Buy also with tablets (capsules, pills) no prescription:

• GETZ clarithromycin 125mg 5ml oral suspension dose