4.1. Therapeutic indications

Clindamycin 150 mg/ml solution for injection/infusion is indicated for the treatment of the following severe infections caused by clindamycin sensitive bacteria in adults and children from the age of 1 month (see sections 4.2 and 5.1):

‒ Bone and joint infections

‒ Chronic sinusitis caused by anaerobic microorganisms

‒ Infections of the lower respiratory tract

‒ Complicated intra‑abdominal infections

‒ Pelvic and female genital infections

‒ Complicated skin and soft tissue infections.

Clindamycin may be used for prophylaxis in surgery in case of allergy to beta‑lactams.

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

4.2. Posology and method of administration

The dosage and method of administration should be determined depending on the severity of infection, patient condition and the susceptibility of the microorganism causing the disease. Local guidance should be taken into consideration.

Posology

Adults

Intramuscular or intravenous administration: 1200‑2700 mg/day divided into 2‑4 doses.

The usual dose for infections of intra-abdominal area, female pelvic area or other severe infections is 2400‑2700 mg daily IV or IM administered in 2, 3 or 4 equal doses (without exceeding the maximum recommended single dose of 1200 mg IV or 600 mg IM).

For the treatment of less complicated infections due to more susceptible microorganisms that may respond to lower doses: the dose is 1200‑1800 mg daily IV or IM administered in 3 or 4 equal doses.

In life‑threatening infections the intravenous dose may be increased up to 4800 mg daily.

Prophylaxis in surgery

The dosage should be determined depending on type and duration of the surgical procedure.

The usual dose is 600-900 mg given every 4-8 hours, until the end of the procedure.

Paediatric population

Children over 1 month to 12 years of age

20‑40 mg/kg daily IV or IM administered in 3 or 4 equal doses (see section 4.4).

The dose of clindamycin in children should be based on total body weight regardless of obesity (see section 5.2). In severe infections, it is recommended that children be given no less than 300 mg/day regardless of body weight. The total daily dose should not exceed the maximum recommended daily dose for adults.

Adolescents over 12 years of age

Doses in adolescents over 12 years of age should be the same as in adults, taking into account possible dose adjustments based on liver function. In underweight adolescent patients, between the ages of 12 and 18 it is not recommended to exceed the maximum dose of 40 mg/kg/day. The total daily dose should not exceed the maximum recommended daily dose for adults.

Infants less than 1 month of age

The safety and efficacy of Clindamycin in infants less than one month of age have not been established. No data are available.

Elderly patients

No dose adjustment is required in the elderly with normal hepatic and renal function (see section 5.2).

Hepatic impairment

The elimination half‑life is prolonged in patients with moderate to severe hepatic impairment (see sections 4.4 and 5.2). However, when clindamycin is administered every 8 hours, accumulation occurs only rarely. In patients with severe hepatic impairment, it is recommended to monitor hepatic function and the patient's progress, and monitoring of plasma levels of clindamycin is recommended, where possible. Depending on the results, the dose or dosing intervals should be adjusted, if necessary.

Renal impairment

The elimination half‑life is prolonged in patients with renal impairment (see sections 4.4 and 5.2). However, no dose adjustment is necessary in patients with mild to moderate renal impairment. In patients with severe renal impairment, it is recommended to monitor renal function and the patient's progress.

Clindamycin cannot be removed by haemodialysis. Therefore, no additional dose is necessary before or after haemodialysis.

Method of administration

Intramuscular injection (IM) or intravenous infusion (IV).

For intramuscular administration, Clindamycin should be used undiluted. Intramuscular administration of more than 600 mg at once is not recommended.

Intramuscular administration is indicated when intravenous infusion is not possible for any reasons.

For intravenous administration, Clindamycin must be diluted prior IV administration and should be infused over at least 10‑60 minutes. The concentration should not exceed 18 mg clindamycin per ml solution and the infusion rate should not exceed 30 mg/min. It must never be given as intravenous bolus injection (may cause serious adverse events, see section 4.8). Intravenous infusions of more than 1200 mg in one hour are not recommended.

Table 1 The usual infusion rates

Dose

Diluent

Concentration of clindamycin

Minimum infusion-time

300 mg

50 ml

6 mg/ml

10 minutes

600 mg

50 ml

12 mg/ml

20 minutes

900 mg

50‑100 ml

9 mg/ml to 18 mg/ml

30 minutes

1200 mg

100 ml

12 mg/ml

40 minutes

For compatible diluents, see section 6.6.

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

Hypersensitivity reactions

Severe hypersensitivity reactions can occur even after the first administration. In case hypersensitivity reaction occur, treatment with clindamycin must be discontinued immediately and the appropriate standard emergency measures initiated (see sections 4.3 and 4.8).

Under certain circumstances, clindamycin therapy may be an alternative form of treatment in patients with a penicillin allergy (penicillin hypersensitivity). There have been no reports of a cross‑allergy between clindamycin and penicillin and, based on the structural differences between the substances, this is not to be expected. However, in individual cases, information does exist on anaphylaxis (hypersensitivity) towards clindamycin in persons with an already existing penicillin allergy. This should be taken into consideration in a course of clindamycin treatment in patients with a penicillin allergy.

Severe cutaneous adverse reactions

Severe cutaneous adverse reactions such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP), which could be life-threatening or fatal, have been reported in patients receiving clindamycin. These can occur even after the first administration. If signs and symptoms of severe skin reactions appear, treatment with clindamycin must be discontinued immediately and the appropriate standard emergency measures initiated. If the patient has developed a serious reaction such as DRESS, SJS, TEN or AGEP with the use of clindamycin, treatment with clindamycin must not be restarted in this patient at any time (see sections 4.3 and 4.8).

Gastrointestinal disorders

Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of Clostridioides difficile. This has been reported with use of nearly all antibacterial agents, including clindamycin. C. difficile produces toxins A and B which contribute to the development of C. difficile associated diarrhoea (CDAD) and is a primary cause of 'antibiotic‑associated colitis'.

It is important to consider the diagnosis of CDAD in patients who develop 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. Medicinal products inhibiting peristalsis are contraindicated in this situation.

Clindamycin therapy has been associated with a pseudomembranous colitis during and until 2 to 3 weeks after the treatment with clindamycin which may be fatal, and which is associated with severe and persistent diarrhoea. Care should be taken when prescribing clindamycin to a patient who has a tendency towards gastrointestinal illnesses, in particular colitis. Antibiotic‑associated colitis and diarrhoea are more frequent and severe in debilitated and/or elderly patients (> 60 years).

Disturbances in neuromuscular transmission

Caution should be exercised in patients with disturbances in neuromuscular transmission (e.g. myasthenia gravis, Parkinson's disease) since clindamycin has been associated with neuromuscular blockade and prolongation of blockage (see sections 4.5 and 4.8). In vitro, clindamycin has been shown to inhibit nicotinic acetylcholine receptors.

Hepatic and renal impairment

During long-term treatment, liver and kidney function should be regularly monitored.

The elimination half‑life is prolonged in patients with renal impairment and patients with moderate to severe hepatic impairment (see sections 4.2 and 5.2).

Acute kidney injury, including acute renal failure, has been reported infrequently. In patients suffering from pre-existing renal dysfunction or taking concomitant nephrotoxic drugs, monitoring of renal function should be considered (see section 4.8).

Overgrowth of non‑susceptible organisms

The use of clindamycin may also result in the overgrowth of non‑susceptible organisms, particularly yeasts.

Diffusion into cerebrospinal fluid

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

Other

Caution should be exercised in patients with atopic diseases.

Sodium

This medicinal product contains 6.5 mg sodium per ml of solution, equivalent to 0.33 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5. Interaction with other medicinal products and other forms of interaction

Neuromuscular blocking agents

Clindamycin may potentiate the action of neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.

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 antagonists (e.g. warfarin, acenocoumarol and fluindione). Coagulation tests should, therefore, be frequently monitored in patients treated with vitamin K antagonists.

Other antibacterial agents

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

CYP enzyme inhibitors and inducers

Clindamycin is metabolized predominantly by CYP3A4, and to a lesser extent by CYP3A5, to the major metabolite clindamycin sulfoxide and minor metabolite N‑desmethylclindamycin.

Therefore, inhibitors of CYP3A4 and CYP3A5 may decrease clearance of clindamycin.

Inducers of CYP3A4 and CYP3A5 may increase clearance of clindamycin. Patients should be observed for reduced treatment efficacy if clindamycin is used together with strong CYP3A4 inducers such as rifampicin.

In vitro studies indicate that clindamycin does not inhibit CYP1A2, CYP2C9, CYP2C19, CYP2E1 or CYP2D6 and only moderately inhibits CYP3A4. Therefore, clinically important interactions between clindamycin and co‑administered medicines metabolized by these CYP enzymes are unlikely.

Immunosuppressive agents

Clindamycin may impact blood concentrations of ciclosporin and tacrolimus. Monitoring ciclosporin/tacrolimus serum levels during treatment with clindamycin is recommended.

4.6. Fertility, pregnancy and lactation

Pregnancy

In clinical studies in pregnant women, systemic administration of clindamycin during the 2nd and 3rd trimesters was not associated with an increased incidence of congenital abnormalities. There are no adequate, well-controlled studies in pregnant women during the first trimester of pregnancy. Clindamycin crosses the placenta in humans.

Clindamycin should only be used if absolutely necessary during pregnancy.

Breast-feeding

After systemic administration, clindamycin has been reported to appear in human breast milk ranging from < 0.5 to 3.8 μg/ml. Clindamycin can potentially have a negative effect on the intestinal flora of the breast‑fed infant with symptoms such as diarrhoea or blood in the stool or rash. It is not recommended to use clindamycin during breastfeeding, and a decision must be made to either stop breast‑feeding or choose another treatment option. The benefits of breast-feeding for the infant should be weighed against the mother's clinical need for clindamycin.

Fertility

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (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 2 below lists the adverse reactions identified through clinical trial experience and post‑marketing experience. Adverse reactions are ranked by MedDRA system organ class and frequency as follows: 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 (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

The most frequent side effects are gastrointestinal, predominantly diarrhoea. Gastrointestinal side effects occur in approx. 8 % of patients.

Table 2 Adverse reactions

System Organ

Class

Common

Uncommon

Rare

Very rare

Not known

Infections and infestations

Pseudomembranous colitis*#

Clostridioides difficile colitis*#, vaginal infection*

Blood and lymphatic system disorders

Eosinophilia

Granulocytopenia

Agranulocytosis*, neutropenia*, thrombocytopenia*, leucopenia*, thrombocytopenic purpura

Immune system disorders

Angioedema

Anaphylactic shock*, anaphylactoid reaction*#, anaphylactic reaction*, hypersensitivity*+

Nervous system disorders

Dysgeusia, neuromuscular blocking effect

Changes in smell

Cardiac disorders

Cardio-respiratory arrest§

Vascular disorders

Thrombophlebitis ****

Hypotension§

Gastrointestinal disorders

Inflammation of the oral mucosa, diarrhoea**

Abdominal pain, oesophagitis, nausea, vomiting

Dyspepsia

Hepatobiliary disorders

Jaundice*

Skin and subcutaneous tissue disorders

Maculo‑papular rash

Urticaria, erythema multiforme, pruritus

Toxic epidermal necrolysis (TEN)*#, Stevens‑Johnson syndrome (SJS)*#, drug reaction/drug exanthem with eosinophilia and systemic symptoms (DRESS)*#, acute generalised exanthematous pustulosis (AGEP)*#, exfoliative dermatitis*, dermatitis bullous*, morbilliform rash*

Renal and urinary disorders

Acute kidney injury#

General disorders and administration

site conditions

Induration at the injection site***

Pain at the injection site, sterile abscess at the injection site***

Irritation at the injection site*

Investigations

Liver function tests abnormal, serum transaminases increased

* Adverse reactions identified from post-marketing experience.

** Often mild in nature and often resolve during or after discontinuation of treatment. These side effects depend on the method of administration and the dosage.

*** May occur locally after IM injection.

**** After IV administration.

+ After a rapid IV injection, hypersensitivity reactions in the form of flushing or feeling of nausea may occur.

# See section 4.4.

§ Cases of cardio-respiratory arrest and hypotension have been reported following too rapid IV administration.

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 via the Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms of overdose are nausea, vomiting and diarrhoea.

Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum.