Clindamycin Hydrochloride Capsules USP 150mg Taj Pharma

1. Name of the medicinal product

Clindamycin Hydrochloride Capsules USP 75mg Taj Pharma
Clindamycin Hydrochloride Capsules USP 150mg Taj Pharma
Clindamycin Hydrochloride Capsules USP 300mg Taj Pharma

2. Qualitative and quantitative composition

a) Clindamycin Hydrochloride Capsules USP 75mg
Each capsule contains:
Clindamycin hydrochloride
(equivalent to clindamycin)            75mg
Excipients                                         q.s

b) Clindamycin Hydrochloride Capsules USP 150mg
Each capsule contains:
Clindamycin hydrochloride
(equivalent to clindamycin)            150 mg
Excipients                                            q.s

c) Clindamycin Hydrochloride Capsules USP 300mg
Each capsule contains:
Clindamycin hydrochloride
(equivalent to clindamycin)             300 mg
Excipients                                            q.s

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Capsule.

Clindamycin capsules are hard capsules.

4. Clinical particulars

4.1 Therapeutic indications

Clindamycin is indicated for the treatment of:

Serious infections caused by anaerobic bacteria, including intra-abdominal infections, skin and soft tissue infections. As needed, clindamycin should be administered in conjunction with another antibacterial agent that is active against gram negative aerobic bacteria.

– Tonsillitis

– Dental infection

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

4.2 Posology and method of administration

Posology

Adults

The usual dose is 150-450 mg every six hours, depending on the severity of the infection.

Elderly patients

Dosage requirements in elderly patients should not be influenced by age alone

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).

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 an alternative formulation in some cases.

Renal impairment

No dose adjustment is necessary in patients with mild to moderate impairment of renal function. In patients with severe renal impairment or anuria, plasma concentration should be monitored. Depending on the results, this measure can make a reduction in dosage or an increase in the dose interval of 8 or even 12 hours necessary.

Hepatic impairment

In patients with moderate to severe hepatic impairment, elimination half-life of clindamycin is prolonged. A reduction in dosage is generally not necessary if clindamycin is administered every 8 hours. However, the plasma concentration of clindamycin should be monitored in patients with severe hepatic impairment. Depending on the results, this measure can make a reduction in dosage or an increase in the dose intervals necessary.

Method of administration

Clindamycin capsules are given orally. The product should always be taken with a full glass of water in an upright position.

Absorption of Clindamycin capsules is not appreciably modified by the presence of food.

4.3 Contraindications

Hypersensitivity to the active substance, lincomycin or to any of the excipients listed in section 6.1

4.4 Special warnings and precautions for use

Severe hypersensitivity reactions, including severe skin reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP) have been reported in patients receiving clindamycin therapy. If a hypersensitivity or severe skin reaction occurs, clindamycin should be discontinued and appropriate therapy should be initiated (see sections 4.3 and 4.8).

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 mucous. 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 diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including clindamycin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C difficile.

1. 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.

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

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

Laboratory tests for renal and hepatic function should be carried out during prolonged therapy.

Close monitoring is also recommended in patients with renal or hepatic insufficiency and in neonates and infants, all of whom may require dose reduction and/or an extended interval between doses.

Prolonged administration of Clindamycin capsules, 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 capsules in atopic individuals.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The choice of clindamycin should be based on factors such as severity of the infection, the prevalence of resistance to other suitable agents and the risk of selecting clindamycin-resistant bacteria

4.5 Interaction with other medicinal products and other forms of interaction

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

Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance the two drugs should not be administered concurrently.

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.

4.6 Fertility, pregnancy and lactation

Pregnancy

Clindamycin crosses the placenta in humans. 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.

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.

Breast-feeding

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

Fertility

In animal studies, clindamycin had no effect on fertility or mating ability (see Section 5.3).

4.7 Effects on ability to drive and use machines

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

4.8 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). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

* ADR identified post-marketing.

# See section 4.4.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

4.9 Overdose

The serum biological half-life of clindamycin is 2.4 hours. Clindamycin cannot readily be removed from the blood by haemodialysis or peritoneal dialysis.

If an allergic adverse reaction occurs, therapy should be with the usual emergency treatments, including corticosteroids, adrenaline and antihistamines.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Lincosamides

Mechanism of action

Clindamycin is a lincosamide antibiotic with a primarily bacteriostatic action against Gram-positive aerobes and a wide range of anaerobic bacteria. Lincosamides such as clindamycin bind to the 50S subunit of the bacterial ribosome similarly to macrolides such as erythromycin and inhibit the early stages of protein synthesis. The action of clindamycin is predominantly bacteriostatic although high concentrations may be slowly bactericidal against sensitive strains.

Mechanism of resistance

Resistance to clindamycin usually occurs via macrolide-lincosamide-streptogramin B (MLS_B) type of resistance, which may be constitutive or inducible.

Breakpoints

The minimum inhibitory concentrations (MIC) breakpoints are as follows:

Eucast

Staphylococci: sensitive ≤ 0.5 resistant > 0.5

Streptococci ABCG and pneumoniae: sensitive ≤ 0.5 resistant > 0.5

Gram positive anaerobes: sensitive ≤ 4 resistant > 4

Gram negative anaerobes: ≤ 4 resistant > 4

Susceptibility

The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

*Up to 50% of methicillin-susceptible S. aureus have been reported to be resistant to clindamycin in some areas. More than 90% of methicillin-resistant S.aureus (MRSA) are resistant to clindamycin and it should not be used while awaiting susceptibility test results if there is any suspicion of MRSA.

5.2 Pharmacokinetic properties

Absorption

After oral administration clindamycin is absorbed quickly and almost completely (>90%). The absorption is not affected by food. The peak plasma concentration is achieved within approximately 45 minutes after oral administration. The bioavailability is non-linear and decreases with increasing doses. Following a 600 mg dose the absolute bioavailability is 53±14%.

Distribution

Clindamycin is widely distributed in body fluids and tissues. It diffuses across the placenta but not the healthy blood-brain barrier. 68 – 93 % of clindamycin in the circulation is bound to plasma proteins. Clindamycin is distributed very highly intracellular due to the lipophilic properties. The intracellular concentrations are 10-50 times higher than the extracellular concentrations.

Biotransformation

Clindamycin undergoes metabolism, presumably in the liver, to the active N-demethyl and sulphoxide metabolites, and also some inactive metabolites and about 4% in the faeces: the remainder is excreted as inactive metabolites.

Elimination

Half-life is approximately two and a half hour in children and approximately 3 hours in adults. Clindamycin is excreted as biological active and biological inactive metabolites in faeces, urine and bile. Faecal excretion is predominant. About 10% of the drug is excreted in the urine as active drug and about 4% in the faeces; the remainder is excreted as inactive metabolites.

Characteristics in patients

Elderly:

The half-life, volume of distribution and clearance, and extent of absorption after administration of clindamycin phosphate are not altered by increased age.

Patients with renal impairment:

In the presence of renal impairment, elimination half-life is prolonged; however, a dosage reduction is unnecessary in the event of mild to moderate impairment of renal function.

Patients with hepatic impairment:

In patients with moderate to severe hepatic impairment the half life is prolonged, but when giving the dose every 8 hours, accumulation is rarely seen. Dose reduction is normally not necessary in patients with hepatic impairment.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on studies of repeat dose toxicity, reproductive toxicity or genotoxicity. Carcinogenicity studies have not been conducted.

In dogs, repeated high oral doses produced ulceration of the mucosa of the stomach and gall bladder.

6. Pharmaceutical particulars

6.1 List of excipients

Lactose monohydrate, Maize starch, Talc, Magnesium Stearate

Capsule shell

Gelatin, Titanium dioxide

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

36 months.

6.4 Special precautions for storage

Do not store above 30°C.

Store in the original package in order to protect from light.

6.5 Nature and contents of container

The blister pack (PVC/aluminium) contains 20, 24, 28, 30, 32 or 100 capsules, respectively.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

Clindamycin Hydrochloride Capsules USP 75mg/150mg/300mg Taj Pharma

(Clindamycin hydrochloride)

Package leaflet: Information for the user

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

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

                                                                           Clindamycin Hydrochloride Capsules USP 75mg/150mg/300mg Taj Pharma

(Clindamycin hydrochloride)

1.What Clindamycin is and what it is used for

The active substance of Clindamycin belongs to the group of antibiotics and it is used in the treatment of serious bacterial infections.

2.What you need to know before you take Clindamycin Do not take Clindamycin

If you are allergic (hypersensitive) to Clindamycin, lincomycin or to any of the other ingredients in this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or pharmacist before using Clindamycin if:

• You have diarrhoea or usually get diarrhoea when you take antibiotics or have ever suffered from problems with your stomach or intestines. If you develop severe or prolonged or bloody diarrhoea during or after using Clindamycin tell your doctor immediately since it may be necessary to interrupt the treatment. This may be a sign of bowel inflammation (pseudomembranous colitis) which can occur following treatment with antibiotics. You suffer from problems with your kidneys or liver.
• You suffer from asthma, eczema or hayfever.
• You develop any severe skin reactions or hypersensitivity to Clindamycin.

Other medicines and Clindamycin

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

• Muscle relaxants used for operations (neuromuscular blockers).
• Oral contraceptive pills. You should use extra contraception such as condoms whilst taking Clindamycin and for seven days after taking Clindamycin.
• Warfarin or similar medicines – used to thin the blood. You may be more likely to have a bleed. Your doctor may need to take regular blood tests to check how well your blood can clot.
• CYP3A4 or CYP3A5 inducers like rifampicin may impact effectiveness of the medicine.

Clindamycin with food, drink and alcohol

The capsules may be taken either before or after a meal.

Pregnancy and breast-feeding Pregnancy

If you are pregnant or think you might be pregnant, you should contact your doctor before

taking Clindamycin.

Ask your doctor or pharmacist for advice before taking any medicine.

Breast-feeding

Tell your doctor if you will be breast-feeding while taking Clindamycin, as clindamycin may be passed into breast milk. Your doctor will decide if Clindamycin is appropriate for you. If you continue to take Clindamycin, you should stop breast-feeding.

Driving and using machines

No effects on the ability to drive or use machines have been seen with Clindamycin.

Clindamycin Capsules contains lactose

Clindamycin Capsules contains lactose a type of sugar. If you have been told that you have intolerance to some sugars, contact your doctor before taking this medicinal product.

3. How to take Clindamycin

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

You should swallow the whole capsule with some liquid. It can be taken with or without food, according to your preference. Do not crush the capsules.

Adults and Elderly Patients

The recommended dose of Clindamycin is between 150 and 450 mg (1 to 3 capsules) every 6 hours, depending on the severity of your infection.

Use in Children

This medicine is used for children who are able to swallow capsules. The recommended dose in children is between 12 and 25 mg / kg /day of bodyweight, divided into six hourly doses, depending on the severity of the infection. Your doctor will work out the number of capsules that your child should have. If your child is unable to swallow capsules, talk to your doctor or pharmacist.

Long term use of Clindamycin

If you have to take Clindamycin for a long time, your doctor may arrange regular liver, kidney and blood tests. Do not miss these check-ups with your doctor.

Long term use can also make you more likely to get other infections that do not respond to Clindamycin treatment.

If you take more Clindamycin than you should

If you have taken too many Clindamycin or if a child has accidently taken clindamycin contact your doctor at once or go to the nearest hospital casualty department. Always take the labelled medicine package with you, whether there are any Clindamycin left or not. Do not take any more capsules until your doctor tells you to.

If you forget to take Clindamycin

If you forget to take a dose at the usual time, take it as soon as you remember, unless it is time to take your next dose.

Do not take a double dose to make up for a forgotten dose. If you are in doubt, always consult your doctor or pharmacist.

If you stop taking Clindamycin

If you stop taking the medicine too soon your infection may come back again or get worse. Do not stop taking Clindamycin unless your doctor tells you to.

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.

Tell your doctor immediately if you develop:

• Severe, persistent or bloody diarrhoea (which may be associated with stomach pain or fever). This is an uncommon side effect which may occur during or after completing treatment with antibiotics and can be a sign of serious bowel inflammation or pseudomembranous colitis.
• Signs of a severe allergic reaction such as sudden wheeziness, difficulty in breathing, dizziness, swelling of the eyelids or face or lips or throat or tongue, rash or itching (especially affecting the whole body).
• blistering and peeling of large areas of skin, fever, cough, feeling unwell and swelling of the gums, tongue or lips.
• yellowing of the skin and whites of the eyes (jaundice).
• Potentially life threatening skin rashes:
• a widespread rash with blistering and peeling of large areas of skin, particularly around the mouth, nose, eyes or genitals, known as Stevens-Johnson syndrome, or a more severe form with extensive peeling of the skin (more than 30% of the body surface) known as toxic epidermal necrolysis,
• a rare skin eruption that is characterised by the rapid appearance of areas of red skin studded with small pustules (small blisters filled with white/yellow fluid) (Acute Generalised Exanthematous Pustulosis (AGEP),
• skin rash, which may blister, and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge – erythema multiforme),
• widespread red skin rash with small pus-containing blisters (bullous exfoliative dermatitis),
• fever, swollen lymph nodes or skin rash, these may be symptoms of a condition known as DRESS (Drug reaction with eosinophilia and systemic symptoms) and can be severe and life-threatening.

Other possible side effects may include;

• Common (may affect up to 1 in 10 people):
• abnormal liver function tests (poor liver function)
• pain in the stomach / abdomen, diarrhoea.
• Uncommon (may affect up to 1 in 100 people)
• feeling sick or being sick
• rash- characterized by a flat red area on the skin that is covered with small bumps, hives,
• Frequency cannot be estimated from the available data:
• infection inside and around the vagina
• inflammation of the large intestine which causes abdominal pain, fever or diarrhoea due to infection by Clostridium difficile,
• effects on your blood system: reduced numbers of blood cells which may cause bruising or bleeding or weaken the immune system,
• changes in the way things taste,
• inflammation of the lining of the oesophagus (gullet), open sores or lesions in the lining of the oesophagus (gullet),
• yellowing of the skin and whites of the eyes (jaundice),
• red or scaly skin (exfoliative dermatitis), red measles-like rash (rash morbilliform), itching.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly.

By reporting side effects you can help provide more information on the safety of this medicine.

5.How to store Clindamycin

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and blister labels. The expiry date refers to the last day of that month.
• Do not store above 25°C.
• Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6.Contents of the pack and other information What Clindamycin capsules contain

The active substance is clindamycin hydrochloride.

Each 75 mg capsule contains clindamycin hydrochloride equivalent to 75 mg of clindamycin.

Each 150 mg capsule contains clindamycin hydrochloride equivalent to 150 mg of clindamycin.

Each 300 mg capsule contains clindamycin hydrochloride equivalent to 300 mg of the active substance clindamycin.

The other ingredients are lactose monohydrate, maize starch, talc and magnesium stearate. 75 mg capsule shell: gelatin, FD&C approved colors

150 mg capsule shell: gelatin, FD&C approved colours.

300 mg capsule shell: gelatin, FD&C approved colours.

What Clindamycin Capsules looks like and contents of the pack

Clindamycin 75 mg capsules, are hard gelatin capsules filled with white to off- white granular powder. Approximately 16 mm in length.

Clindamycin 150 mg capsules, are hard gelatin capsules, filled with white to off- white granular powder. Approximately 18 mm in length.

Clindamycin 300 mg capsules, are hard gelatin capsules, filled with white to off-white granular powder. Approximately 21 mm in length.

Clindamycin 75 mg, 150 mg and 300 mg capsules, hard are available in blister packs of 6, 10, 12, 24, 30 and 100 capsules.

Not all pack sizes may be marketed.

7. Manufactured in India by:
TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com