ANTIBIOTICS

1. AZITHROMYCIND (10 tab/500 mg of Azithromycin in tablet)

2. GENTAMICID (10x1 ml/80 mg of Gentamicin in ml)

3. TINIDAZOM (40 tab/500 mg of Tinidazole in tablet)

4. CLINDAMYD (60 tab/150 mg of Clindamycin in tablet)

Azithromycind (10 tab/500 mg of Azithromycin in tablet)

1. What Azithromycin is and what it is used for

Azithromycin belongs to a group of medicines called macrolide antibiotics. Antibiotics are used to treat infections caused by microorganisms like bacteria.

Azithromycin is used for the treatment of certain infections caused by bacteria that are sensitive to it, such as:

chest, throat or nasal infections (such as bronchitis, pneumonia, tonsillitis, sore throat (pharyngitis) and sinusitis)

ear infections

skin and soft tissue infections, with exception of infected burn wounds e.g. - infection of the tube that carries urine from the bladder (urethra) or the neck of the womb (cervix) caused by Chlamidia trachomatis (bacteria).

2. What you need to know before you take Azithromycin

Do not take Azithromycin if:

you are allergic to azithromycin dihydrate, erythromycin or any macrolide or ketolide antibiotic

you are allergic to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk with your doctor or pharmacist before taking Azithromycin if:

you have severe liver or kidney problems

you have severe heart problems or problems with your heart beat such as long QT syndrome (shown on an electro-cardiogram or ECG machine)

your blood levels of potassium or magnesium are too low

you develop signs of another infection

you are taking any ergot derivatives such as ergotamine (to treat migraine) as these medicines should not be taken together with azithromycin (see section “Taking other medicines”)

you have a certain type of muscle weakness called myasthenia gravis

you have nervous (neurological) or mental (psychiatric) problems.

Other medicines and Azithromycin

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

Tell your doctor or pharmacist if you are taking any of the following medicines:

antacids - used for heartburn and indigestion. Azithromycin should be taken at least 1 hour before or 2 hours after the antacid

ergotamine - (used for migraine) should not be taken at the same time as serious side effects may develop (with numbness or tingling sensations in the limbs, muscle cramps, headaches, convulsions, abdominal or chest pain)

cholesterol lowering medicines (statins)

warfarin or similar medicines - used to thin the blood. Azithromycin can thin the blood even more

cisapride - (used to treat stomach problems) should not be taken at the same time as this may cause severe heart problems (shown on an electro-cardiogram or ECG machine)

terfenadine - (used to treat hay fever) should not be taken at the same time as this may cause severe heart problems (shown on an electro-cardiogram or ECG machine)

zidovudine or nelfinavir - used to treat HIV infections. Taking nelfinavir with Azithromycin may mean that you get more of the side effects listed in this leaflet

rifabutin - used to treat tuberculosis (TB)

quinidine - used to treat heart rhythm problems

cyclosporin - used to stop your body rejecting an organ transplant. Your doctor will regularly check your blood levels of cyclosporin and may change your dose.

Tell your doctor or pharmacist if you are taking any of the following medicines. Azithromycin can make the effects of these other medicines stronger. Your doctor may change your dose:

alfentanil - a painkiller used e.g. during operations

theophylline - used for breathing problems such as asthma and chronic obstructive pulmonary disease (COPD)

digoxin - used to treat heart problems

astemizol - used to treat hay fever

pimozide - used to treat mental health problems.

Azithromycin with food and drink

This medicine can be taken with or without food.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

There is insufficient information available about the use of azithromycin during pregnancy. Therefore you should not use Azithromycin during pregnancy, unless explicitly advised by your doctor.

Azithromycin is partially passed through the mother’s milk, therefore Azithromycin should not be used if you are breastfeeding.

Driving and using machines

There are no data available about the influence of azithromycin on the ability to drive or operate machines. However azithromycin tablets may cause dizziness and seizures so make sure you are not affected before driving or operating machinery.

Azithromycin contains lactose

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take Azithromycin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

For adults and young people with a body weight of 45kg or over

500mg once daily for three days with a total dose of 1500mg. Alternatively when 250mg tablets are available your doctor may decide to prescribe the total dose of 1500mg over a period of 5 days, with 500mg the first day and 250mg on days 2 to 5.

For infections of the neck of the womb and urethra caused by Chlamydia trachomatis

One dose of 1000mg, to be taken one time.

Children and adolescents under 45kg

The tablets are not recommended. Young people with a body weight of less than 45kg should use other forms of this medicine.

Patients with kidney or liver problems

You should tell your doctor if you have kidney or liver problems as your doctor may need to alter the normal dose.

Dosage for elderly

For elderly the same dosage as for adults applies.

Administration

The tablets should be taken with ½ glass of water.

If you take more Azithromycin than you should

If you have taken too much Azithromycin, contact your doctor, pharmacist or go to your nearest hospital at once.

Symptoms of overdose are loss of hearing, feeling sick or being sick and diarrhoea. In case of overdosage admission into hospital may be necessary.

If you forget to take Azithromycin

If you forget to take Azithromycin, take your dose as soon as possible. If it is almost time for the next dose, just skip that dose and take the next one when it is due. If in doubt, please contact your doctor or pharmacist. If you have to skip a dose, still take all of your tablets. This means that you will finish your course a day later.

Do not take a double dose to make up for a forgotten dose.

If you stop taking Azithromycin

Never stop the treatment with Azithromycin on your own, but first discuss this with your doctor. If the prescribed treatment is not completely finished, the infection may come back again.

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

4. Possible side effects

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

If you have any of the following symptoms of a severe allergic reaction stop taking this medicine and tell your doctor immediately or go to the casualty department at your nearest hospital

Sudden difficulty in breathing, speaking and swallowing

Swelling of the lips, tongue, face and neck

Extreme dizziness or collapse

Severe or itchy skin rash, especially if this shows blistering and there is soreness of the eyes, mouth or genital organs.

If you experience any of the following side effects contact your doctor as soon as possible

Diarrhoea that is serious, lasts a long time or has blood in it, with stomach pain or fever. This can be a sign of a serious bowel inflammation. This is something that can rarely happen after taking antibiotics

Yellowing of the skin or whites of the eyes caused by liver problems

Inflammation of the pancreas, which causes severe pain in the abdomen and back

Increased or reduced urine output, or traces of blood in your urine

Skin rash caused by sensitivity to sunlight

Unusual bruising or bleeding

Irregular heart beat.

These are all serious side effects. You may need urgent medical attention. Serious side effects are uncommon (may affect up to 1 in 100 people) or the frequency cannot be estimated from the available data.

Other side effects include

Very common (may affect more than 1 in 10 people)

diarrhoea

abdominal pain

feeling sick (nausea)

loose wind (flatulence).

Common (may affect up to 1 in 10 people)

lack of appetite (anorexia)

feeling dizzy

headache

sensation of pins and needles or numbness (paraesthesia)

changes in your sense of taste

visual impairment

deafness

being sick (vomiting), stomach pain or cramps, loss of appetite, problems digesting your food

skin rashes and itching

joint pain (arthralgia)

fatigue

change in the quantity of the white blood cells and the concentration of bicarbonate in the blood.

Uncommon (may affect up to 1 in 100 people)

thrush (candidiasis) - a fungal infection

fungal infection

bacterial infection

inflammation of the throat (pharyngitis)

breathlessness, chest pain, wheeze and cough (respiratory disorder)

inflammation of the mucous membrane inside the nose (rhinitis)

stomach flu (gastroenteritis)

inflammation inside your vagina (vaginitis)

pneumonia

reduction in the number of white blood cells

angioedema

hypersensitivity

nervousness

reduced sense of touch (hypoaesthesia)

feeling drowsy (somnolence)

having difficulty sleeping (insomnia)

ear disorder

spinning sensation (vertigo)

hearing loss or ringing in your ears

palpitations

hot flushes

shortness of breath

nosebleed

inflammation of the lining of the stomach (gastritis)

constipation

difficulty swallowing

swollen abdomen

dry mouth

belching

mouth ulcer

increased salivary flow

liver problems such as hepatitis

allergic skin reactions such as being sensitive to sunlight, red, flaking and swollen skin

severe form of skin flushing

inflammation of the skin (dermatitis)

dry skin

increased sweating

pain, swelling and reduced motion in your joints (osteoarthritis)

muscle pain

back pain

neck pain

increase in blood urea levels

painful or difficult urination

pain in the upper back (renal pain)

spotting

testicular disorder

urticaria

chest pain

face swelling

fever

pain, numbness, muscle weakness, burning or tingling sensation (peripheral pain)

swelling (oedema)

general feeling of being unwell (malaise)

weakness (asthenia)

change in liver enzyme levels and blood levels

post procedural complications

Rare (may affect up to 1 in 1,000 people)

feeling agitated, feeling of unreality to the self and own feeling

abnormal hepatic function

allergic skin reactions

swelling of the hands, feet, lips, genitals or throat (angioneurotic oedema)

kidney problems.

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

gut (colon) infection (pseudomembranous colitis)

reduced number of red blood cells due to destruction (haemolytic anaemia); reduction in number of platelets (thrombocytopenia)

anaphylactic reaction

feeling angry, aggressive

anxiety

confusion

hallucination

fainting (syncope)

fits (convulsions)

feeling hyperactive

change in your sense of smell (anosmia, parosmia)

change in your sense of taste (ageusia)

exacerbation or aggravation of muscle weakness (myasthenia gravis)

rapid (ventricular tachycardia) or irregular heart beat, sometimes being life-threatening, changes of the heart rhythm found by an electro-cardiogram (QT prolongation and torsade de pointes)

low blood pressure

inflammation of the pancreas (pancreatitis)

your tongue and teeth changes colour

liver failure

allergic skin reactions.

The following side effects have been reported in prophylactic treatment against Mycobacterium Avium complex (MAC):

Very common (may affect more than 1 in 10 people)

diarrhoea

abdominal pain

feeling sick (nausea)

loose wind (flatulence)

abdominal discomfort

loose stools

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

lack of appetite (anorexia)

feeling dizzy

headache

sensation of pins and needles or numbness (paraesthesia)

changes in your sense of taste

visual impairment

deafness

being sick (vomiting), stomach pain or cramps, loss of appetite, problems digesting your food

skin rashes and itching

joint pain (arthralgia)

fatigue

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

reduced sense of touch (hypoaesthesia)

hearing loss or ringing in your ears

palpitations

liver problems such as hepatitis

severe form of skin flushing

allergic skin reactions such as being sensitive to sunlight, red, flaking and swollen skin

general feeling of being unwell (malaise)

weakness (asthenia)

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard. By reporting side effects you can help provide more information on the safety of this medicine.

Gentamicid (10x1 ml/80 mg of Gentamicin in ml)

Therapeutic indications

Gentamicin is an aminoglycoside antibiotic with broad-spectrum bactericidal activity. It is usually active against most strains of the following organisms : Escherichia coli, Klebsiella spp., Proteus spp. (indole positive and indole negative), Pseudomonas aeruginosa, Staphylococci, Enterobacter spp., Citrobacter spp and Providencia spp.

Gentamicin injection and gentamicin paediatric injection are indicated in urinary-tract infections, chest infections, bacteraemia, septicaemia, severe neonatal infections and other systemic infections due to sensitive organisms.

Consideration should be given to official local guidance on the appropriate use of antibacterial agents.

Posology and method of administration

ADULTS:

Serious infections: If renal function is not impaired, 5mg/kg/daily in divided doses at six or eight hourly intervals. The total daily dose may be subsequently increased or decreased as clinically indicated.

Systemic infections: If renal function is not impaired, 3-5mg/kg/day in divided doses according to severity of infection, adjusting according to clinical response and body weight.

Urinary tract infections: As “Systemic infections”. Or, if renal function is not impaired, 160mg once daily may be used.

PAEDIATRIC PATIENTS:

The daily dose recommended in children aged 1 year and above and adolescents with normal renal function, is 3-6 mg/kg body weight per day as 1 (preferred) up to 2 single doses.

The daily dose in infants after the first month of life is 4.5-7.5 mg/kg body weight per day as 1 (preferred) up to 2 single doses.

The daily dose in neonates and pre-term infants (aged 0-4 weeks old) is 4-7 mg/kg body weight per day. Due to the longer half-life, newborns are given the required daily dose in 1 single dose.

THE ELDERLY:

There is some evidence that elderly patients may be more susceptible to aminoglycoside toxicity whether secondary to previous eighth nerve impairment or borderline renal dysfunction. Accordingly, therapy should be closely monitored by frequent determination of gentamicin serum levels, assessment of renal function and signs of ototoxicity.

RENAL IMPAIRMENT:

In impaired renal function, the recommended daily dose has to be decreased and adjusted to the renal function.

Gentamicin is excreted by simple glomerular filtration and therefore reduced dosage is necessary where renal function is impaired. Nomograms are available for the calculation of dose, which depends on the patient's age, weight and renal function. The following table may be useful when treating adults.

Special warnings and precautions for use

To avoid adverse events, continuous monitoring (before, during and after) of renal function (serum creatinin, creatinin clearance), control of function of vestibule and cochlea as well as hepatic and laboratory parameters is recommended.

Ototoxicity has been recorded following the use of gentamicin. Groups at special risk include patients with impaired renal function, infants and possibly the elderly. Consequently, renal, auditory and vestibular functions should be monitored in these patients and serum levels determined so as to avoid peak concentrations above 10mg/l and troughs above 2mg/l when administrating Gentamicin twice daily and 1 mg/l for a once daily dose. As there is some evidence that risk of both ototoxicity and nephrotoxicity is related to the level of total exposure, duration of therapy should be the shortest possible compatible with clinical recovery. In some patients with impaired renal function there has been a transient rise in blood-urea-nitrogen which has usually reverted to normal during or following cessation of therapy. It is important to adjust the frequency of dosage according to the degree of renal function.

Gentamicin should only be used in pregnancy if considered essential by the physician (see section 4.6 Pregnancy and Lactation.)

Gentamicin should be used with care in conditions characterised by muscular weakness.

In cases of significant obesity gentamicin serum concentrations should be closely monitored and a reduction in dose should be considered.

Undesirable effects

Side-effects include vestibular damage or hearing loss, particularly after exposure to ototoxic drugs or in the presence of renal dysfunction. Nephrotoxicity (usually reversible) and occasionally acute renal failure, hypersensitivity, anaemia, blood dycrasias, purpura, stomatitis, convulsions and effects on liver function occur occasionally.

Rarely hypomagnesia on prolonged therapy and antibiotic–associated colitis have been reported.

Nausea, vomiting and rash have also been reported.

Central neurotoxicity, including encephalopathy, confusion, lethargy, mental depression and hallucinations, has been reported in association with gentamicin therapy but this is extremely rare.

Effects on ability to drive and use machines

Not known.

Overdose

Haemodialysis and peritoneal dialysis will aid the removal from blood but the former is probably more efficient. Calcium salts given intravenously have been used to counter the neuromuscular blockade caused by gentamicin.

Tinidazom (40 tab/500 mg of Tinidazole in tablet)

 Therapeutic indications

Treatment of the following infections:

1. Eradication of Helicobacter pylori associated with duodenal ulcers, in the presence of antibiotic and acid suppressant therapy. See Posology and Method of Administration section.

2. Anaerobic infections such as:

Intraperitoneal infections: peritonitis, abscess.

Gynaecological infections: endometritis, endomyometritis, tube-ovarian abscess.

Bacterial septicaemia.

Post-operative wound infections.

Skin and soft tissue infections.

Upper and lower respiratory tract infections: pneumonia, empyema, lung abscess.

3. Non-specific vaginitis.

4. Acute ulcerative gingivitis.

5. Urogenital trichomoniasis in both male and female patients.

6. Giardiasis.

7. Intestinal amoebiasis.

8. Amoebic involvement of the liver.

9. Prophylaxis: The prevention of post-operative infections caused by anaerobic bacteria, especially those associated with colonic, gastro-intestinal and gynaecological surgery.

 Posology and method of administration

Route: Oral administration during or after a meal.

Eradication of H. pylori associated with duodenal ulcers:

Adults: the usual dose of Fasigyn is 500mg twice daily coadministered with omeprazole 20mg twice daily and clarithromycin 250mg twice daily for 7 days.

Clinical studies using this 7 day regimen have shown similar H. pylori eradication rates when omeprazole 20mg once daily was used. For further information on the dosage for omeprazole see Astra data sheet.

Anaerobic infections:

Adults: an initial dose of 2g the first day followed by 1g daily given as a single dose or as 500mg twice daily. Treatment for 5 to 6 days will generally be adequate but clinical judgement must be used in determining the duration of therapy, particularly when eradication of infection from certain sites may be difficult. Routine clinical and laboratory observation is recommended if it is considered necessary to continue therapy for more than 7 days.

Children: < 12 years – there is no data available.

Non-specific vaginitis:

Adults: non-specific vaginitis has been successfully treated with a single oral dose of 2g. Higher cure rates have been achieved with 2g single doses on 2 consecutive days (total dose 4g).

Acute Ulcerative Gingivitis:

Adults: a single oral dose of 2g.

Urogenital trichomoniasis:

(when infection with Trichomonas vaginalis is confirmed, simultaneous treatment of the consort is recommended).

Adults: a single dose of 2g.

Children: a single dose of 50 to 75mg/kg of body weight. It may be necessary to repeat this dose.

Giardiasis:

Adults: a single dose of 2g.

Children: a single dose of 50 to 75mg/kg of body weight. It may be necessary to repeat this dose.

Intestinal Amoebiasis:

Adults: a single daily dose of 2g for 2 to 3 days.

Children: a single daily dose of 50 to 60mg/kg of body weight on each of 3 successive days.

Amoebic involvement in the liver:

Adults: total dosage varies from 4.5 to 12g, depending on the virulence of the Entamoeba histolytica.

For amoebic involvement of the liver, the aspiration of pus may be required in addition to therapy with Fasigyn.

Initiate treatment with 1.5 to 2g as a single oral daily dose for three days. Occasionally when a three day course is ineffective, treatment may be continued for up to six days.

Children: a single dose of 50 to 60 mg/kg of body weight per day for five successive days.

Use in Renal impairment

Dosage adjustments in patients with impaired renal function are generally not necessary. However, because tinidazole is easily removed by haemodialysis, patients may require additional doses of tinidazole to compensate.

Prevention of post-operative infection:

Adults: a single dose of 2g approximately 12 hours before surgery.

Children: < 12 years – there is no data available.

It is recommended that tinidazole be taken during or after a meal.

Use in the elderly: there are no special recommendations for this age group.

 Contraindications

As with other drugs of similar structure, tinidazole is contraindicated in patients having, or with a history of, blood dyscrasia, although no persistent haematological abnormalities have been noted in clinical or animal studies.

Tinidazole should be avoided in patients with organic neurological disorders.

Tinidazole, other 5-nitroimidazole derivatives or any of the components of this product should not be administered to patients with known hypersensitivity to the drug.

Use of tinidazole is contraindicated during the first trimester of pregnancy and in nursing mothers. See 4.6 Pregnancy and Lactation section.

 Special warnings and precautions for use

As with related compounds, alcoholic beverages should be avoided during Fasigyn therapy because of the possibility of a disulfiram-like reaction (flushing, abdominal cramps, vomiting, tachycardia). Alcohol should be avoided until 72 hours after discontinuing Fasigyn.

Drugs of similar chemical structure have also produced various neurological disturbances such as dizziness, vertigo, incoordination and ataxia. If during therapy with Fasigyn abnormal neurological signs develop, therapy should be discontinued.

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent. Although carcinogenicity data is not available for tinidazole, the two drugs are structurally related and therefore there is a potential for similar biologic effects. Mutagenicity results with tinidazole were mixed (positive and negative) (see section 5.3). The use of tinidazole for longer treatment than usually required should be carefully considered.

 Interaction with other medicinal products and other forms of interaction

Alcohol: Concurrent use of tinidazole and alcohol may produce a disulfiram-like reaction and should be avoided, (see section 4.4, Special warnings and precautions for use).

Anticoagulants: Drugs of similar chemical structure have been shown to potentiate the effects of oral anticoagulants. Prothrombin time should be closely monitored and adjustments to the dose of the anticoagulants should be made as necessary.

Pregnancy and lactation

Use in pregnancy:

Fertility studies in rats receiving 100mg and 300mg tinidazole/kg had no effect on fertility, adult and pup weights, gestation, viability or lactation. There was a slight, not significant, increase in resorption rate at the 300mg/kg dose.

Tinidazole crosses the placental barrier. Since the effects of compounds of this class on foetal development are unknown, the use of tinidazole during the first trimester is contraindicated. There is no evidence that Fasigyn is harmful during the latter stages of pregnancy, but its use during the second and third trimesters requires that the potential benefits be weighed against possible hazards to mother or foetus.

Use in lactation:

Tinidazole is excreted in breast milk. Tinidazole may continue to appear in breast milk for more than 72 hours after administration. Women should not nurse until at least 3 days after having discontinued taking Fasigyn.

 Effects on ability to drive and use machines

No special precautions should be necessary. However, drugs of similar chemical structure, including Fasigyn, have been associated with various neurological disturbances such as dizziness, vertigo, ataxia, peripheral neuropathy (paraesthesia, sensory disturbances, hypoaesthesia) and rarely convulsions. If any abnormal neurological signs develop during Fasigyn therapy, the drug should be discontinued.

Undesirable effects

Reported side effects have generally been infrequent, mild and self-limiting.

The reported undesirable effects are listed below according to MedDRA system organ class classification and frequency. Within each frequency category, the ADRs are presented in the order of clinical importance. Frequency categories are expressed as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (the frequency cannot be estimated from the available data).

Clindamyd (60 tab/150 mg of Clindamycin in tablet)

Therapeutic indications

Clindamycin is indicated for the treatment of severe infections caused by susceptible Gram-positive aerobic organisms, staphylococci (penicillinase / and non- penicillinase producing), streptococci (with the exception of Streptococcus faecalis) and pnuemonicocci or by susceptible anaerobic organisms.

Consideration should be given to official guidance regarding the appropriate use of antibacterial agents.

Clindamycin does not penetrate the blood/brain barrier in therapeutically effective quantities.

 Posology and method of administration

Posology

Clindamycin Capsules should always be taken orally with a glass of water withor without food.

Adults: The usual dose is 150 - 300 mg every six hours; depending on the severity of the infection your doctor may prescribe 300 – 450 mg every six hours.

Older people: The half-life, volume of distribution and clearance, and extent of absorption after administration of clindamycin hydrochloride are not altered by increased age. Analysis of data from clinical studies has not shown any age-related increase in toxicity. Dosage requirements in elderly patients should not be influenced by age alone. See section 4.4 for other factors which should be taken into consideration.

Paediatric population: The usual dose is 3 - 6 mg/kg every six hours depending on the severity of the infection.(not to exceed the adult dose).

Children under one year of age and/or under 10 kg may require a lower dose.

Neonates (0-28 days), especially if premature, require special attention to dose reductions and/or extended dose intervals due to the prolonged elimination half-life.

Clindamycin capsules are not suitable for children who are unable to swallow them whole. The capsules do not provide exact mg/kg doses therefore it may be necessary to use the parenteral formulation in some cases.

Note: In cases of beta-haemolytic streptococcal infection, treatment with Clindamycin should continue for at least 10 days to prevent subsequent rheumatic fever or glomerulonephritis.

Contraindications

Clindamycin is contra-indicated in patients previously found to be sensitive to Clindamycin, lincomycin, or to any excipient listed in Section 6.1 (List of excipients).Clindamycin should not be used in patients with existing diarrhoea.

 Special warnings and precautions for use

Warnings:

Clindamycin should only be used in the treatment of serious infections. In considering the use of the product, the practitioner should bear in mind the type of infection and the potential hazard of the diarrhoea which may develop, since cases of colitis have been reported during, or even two or three weeks following, the administration of clindamycin.

Studies indicate a toxin(s) produced by clostridia (especially Clostridium difficile) is the principal direct cause of antibiotic-associated colitis. These studies also indicate that this toxigenic clostridium is usually sensitive in vitro to vancomycin. When 125 mg to 500 mg of vancomycin are administered orally four times a day for 7 - 10 days, there is a rapid observed disappearance of the toxin from faecal samples and a coincident clinical recovery from the diarrhoea. (Where the patient is receiving cholestyramine in addition to vancomycin, consideration should be given to separating the times of administration).

Colitis is a disease which has a clinical spectrum from mild, watery diarrhoea to severe, persistent diarrhoea, leucocytosis, fever, severe abdominal cramps, which may be associated with the passage of blood and mucus. If allowed to progress, it may produce peritonitis, shock and toxic megacolon. This may be fatal.

The appearance of marked diarrhoea should be regarded as an indication that the product should be discontinued immediately. The disease is likely to follow a more severe course in older patients or patients who are debilitated. Diagnosis is usually made by the recognition of the clinical symptoms, but can be substantiated by endoscopic demonstration of pseudomembranous colitis. The presence of the disease may be further confirmed by culture of the stool for Clostridium difficile on selective media and assay of the stool specimen for the toxin(s) of C. difficile.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents 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 agents.

It is important to consider the diagnosis of CDAD in patients who present with diarrhoea subsequent to the administration of antibacterial agents. This may progress to colitis, including pseudomembranous colitis (see Section 4.8), which may range from mild to fatal colitis. If antibiotic-associated diarrhoea or antibiotic-associated colitis is suspected or confirmed, ongoing treatment with antibacterial agents, including clindamycin, should be discontinued and adequate therapeutic measures should be initiated immediately. Drugs inhibiting peristalsis are contraindicated in this situation.

Precautions:

Caution should be used when prescribing Clindamycin to individuals with a history of gastro-intestinal disease, especially colitis.

Periodic liver and kidney function tests should be carried out during prolonged therapy. Such monitoring is also recommended in neonates and infants.

Prolonged administration of Clindamycin, as with any anti-infective, may result in super-infection due to organisms resistant to clindamycin.

Care should be observed in the use of Clindamycin in atopic individuals

Since clindamycin does not diffuse adequately into cerebrospinal fluid, the drug should not be used in the treatment of meningitis.

The use of clindamycin may result in overgrowth of non-susceptible organisms, particularly yeasts.

Clindamycin 150mg Capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption should not take this medicine.

 Interaction with other medicinal products and other forms of interaction

Muscle relaxants:

Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

Antibacterial agents:

Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Due to possible clinical significance, the two drugs should not be administered concurrently.and therefore clindamycin should not be given in combination with macrolides or streptogramin antibacterial agents.

Neostigmine and pyridostigmine:

Clindamycin antagonises the effects of the above anticholinesterases.

Oestrogens:

Clindamycin possibly reduces the contraceptive effect of oestrogen. Though the risk is small, additional contraceptive precautions are recommended during concomitant use and for 7 days after discontinuing clindamycin.

Vaccines:

Oral typhoid vaccine is inactivated by concomitant administration of antibacterials. Thus, clindamycin should be avoided for 3 days before and after oral typhoid vaccination.

Vitamin K antagonists:

Increased coagulation tests (PT/INR) and/or bleeding, have been reported in patients treated with clindamycin in combination with a vitamin K antagonist (e.g. warfarin, acenocoumarol and fluindione). Coagulation tests, therefore, should be frequently monitored in patients treated with vitamin K antagonists.

Fertility, pregnancy and lactation

Pregnancy

Oral and subcutaneous reproductive toxicity studies in rats and rabbits revealed no evidence of impaired fertility or harm to the foetus due to clindamycin, except at doses that caused maternal toxicity. Animal reproduction studies are not always predictive of human response.

Clindamycin crosses the placenta. There are inadequate data regarding the safety of Clindamycin in pregnancy. Therefore, Clindamycin should only be administered to pregnant women if the potential benefit is considered to outweigh the possible risk to the foetus.

After multiple doses, amniotic fluid concentrations were approximately 30% of maternal blood concentrations.

In clinical trials with pregnant women, the systemic administration of clindamycin during the second and third trimesters has not been associated with an increased frequency of congenital abnormalities. There are no adequate and well-controlled studies in pregnant women during the first trimester of pregnancy.

Clindamycin should be used in pregnancy only if clearly needed.

Breast-feeding

Clindamycin is excreted in human milk. If possible, mothers should stop breast-feeding during therapy. Diarrhoea, fungus infection of the mucous membranes or other serious adverse events could occur in the breast-fed infant, so that nursing might have to be discontinued. The possibility of sensitivity should be borne in mind.

Orally and parenterally administered clindamycin has been reported to appear in human breast milk in ranges from 0.7 to 3.8μg/mL. Because of the potential for serious adverse reactions in nursing infants, clindamycin should not be taken by nursing mothers.

Fertility

Fertility studies in rats treated orally with clindamycin revealed no effects on fertility or mating ability.

 Effects on ability to drive and use machines

Clindamycin has no or negligible influence on the ability to drive and use machines.

 Undesirable effects

The table below lists the adverse reactions identified through clinical trial experience and post-marketing surveillance by system organ class and frequency.

The frequency grouping is defined using the following convention:

Very common (≥1/10); Common (≥ 1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥ 1/10,000 to <1/1,000); Very Rare (< 1/10,000); and Not known (cannot be estimated from the available data).