Banbakt®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BANBAKT® (BANBAKT®)

Composition:

Active substance: clindamycin;

Each suppository contains clindamycin phosphate equivalent to 100 mg of clindamycin;
Excipient: hard fat.

Pharmaceutical form. Vaginal suppositories.

Main physicochemical properties: suppositories are white to light yellow, torpedo-shaped.

Pharmacotherapeutic group. Antimicrobial and antiseptic agents used in gynecology, excluding combined medicinal products containing corticosteroids. Antibiotics. Clindamycin. ATC code G01AA10.

Pharmacological properties.

Pharmacodynamics.

Mechanism of action. Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis by acting on bacterial ribosomes. The antibiotic binds primarily to the 50S ribosomal subunit and interferes with the initiation phase of protein chain formation. Although clindamycin phosphate is inactive in vitro, it is rapidly hydrolyzed in vivo to clindamycin, which exhibits antibacterial activity.

Like most inhibitors of protein synthesis, clindamycin exerts primarily a bacteriostatic effect, and its efficacy is related to the duration of time during which the concentration of the active substance remains above the minimum inhibitory concentration (MIC) of the infecting organism.

Resistance to clindamycin most commonly arises due to modification of the ribosomal target site, usually via chemical modification of ribosomal RNA bases or point mutations in RNA, or sometimes in ribosomal proteins. Cross-resistance has been demonstrated in vitro between lincosamides, macrolides, and streptogramin B in certain organisms. Cross-resistance between clindamycin and lincomycin has also been demonstrated.

In vitro susceptibility. Clindamycin demonstrates in vitro activity against the following registered microbial strains associated with bacterial vaginosis: Bacteroides spp., Gardnerella vaginalis, Mobiluncus spp., Mycoplasma hominis, Peptostreptococcus spp.

Standard methodology for testing susceptibility of potential pathogens in bacterial vaginosis, namely Gardnerella vaginalis and Mobiluncus spp., has not been established. Breakpoints for clindamycin susceptibility of gram-negative and gram-positive anaerobes have been published by EUCAST. For clinical isolates found to be susceptible to clindamycin but resistant to erythromycin, testing for inducible clindamycin resistance using the D-test should also be performed. However, these breakpoints are intended primarily to guide systemic antibiotic therapy rather than topical treatment.

Pharmacokinetics.

Absorption. Systemic absorption of clindamycin following intravaginal administration of one suppository containing clindamycin phosphate once daily (equivalent to 100 mg of clindamycin) was evaluated over 3 days in 11 healthy female volunteers. Approximately 30% (range: 6–70%) of the administered dose underwent systemic absorption on day 3, based on area under the concentration-time curve (AUC) measurements. Systemic absorption was also assessed following intravenous administration of a subtherapeutic dose of 100 mg clindamycin phosphate as a comparator in the same volunteers who received a vaginal cream containing 100 mg clindamycin phosphate. Mean AUC after three days of suppository administration was 3.2 µg•h/mL (range: 0.42–11 µg•h/mL). Peak serum concentration occurred on day 3, 5 hours (range: 1–10 hours) after suppository administration, averaging 0.27 µg/mL (range: 0.03–0.67 µg/mL). For comparison, AUC and peak concentration (Cmax) following single intravenous administration averaged 11 µg•h/mL (range: 5.1–26 µg•h/mL) and 3.7 µg/mL (range: 2.4–5 µg/mL), respectively. The mean elimination half-life after suppository administration was 11 hours (range: 4–35 hours), which is considered to be absorption-rate limited.

Results of this study showed that systemic exposure to clindamycin (based on AUC) following suppository administration was on average about 3-fold lower than after single intravenous administration of a subtherapeutic 100 mg dose of clindamycin. Systemic absorption of clindamycin from suppositories was approximately 7-fold higher than with the vaginal cream containing an equivalent dose, for which mean AUC and Cmax values were 0.4 µg•h/mL (range: 0.13–1.16 µg•h/mL) and 0.02 µg/mL (range: 0.01–0.07 µg/mL), respectively.

Furthermore, the recommended daily and total dose of clindamycin in vaginal suppositories is substantially lower than that typically used during oral or parenteral administration of clindamycin (with 100 mg clindamycin administered daily for 3 days in suppository form resulting in approximately 30 mg absorbed per day, compared to 600–2700 mg per day for 10 days or more with oral or parenteral administration). Overall, systemic exposure to clindamycin from vaginal suppositories is 2–20 times lower than that achieved with therapeutic doses of oral clindamycin hydrochloride and 40–50 times lower than therapeutic doses of parenteral clindamycin phosphate.

Clinical characteristics.

Indications.

Treatment of bacterial vaginosis (previous names: haemophilus vaginitis, gardnerella vaginitis, nonspecific vaginitis, corynebacterial vaginitis, or anaerobic vaginosis).

Contraindications.

Hypersensitivity to the active substance, lincomycin, or to any excipient listed in the section "Composition".

The medicinal product Banbakt® is also contraindicated in patients with a history of antibiotic-associated colitis.

Interaction with other medicinal products and other forms of interaction.

There is no information available regarding concomitant use of Banbakt® with other vaginal medicinal products.

When administered systemically, clindamycin phosphate exhibits neuromuscular blocking properties, which may enhance and prolong the effect of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such medicinal products (see sections "Pharmacokinetics" and "Overdose").

The use of latex condoms is not recommended during treatment with clindamycin in the form of vaginal suppositories.

Special precautions for use.

Before or immediately after starting treatment with Banbact®, it may be necessary to perform laboratory tests to detect other infectious agents, including Trichomonas vaginalis, Candida albicans, Chlamydia trachomatis, and gonococci.

Use of Banbact® may lead to overgrowth of microorganisms not sensitive to the drug, particularly yeasts.

Symptoms indicative of pseudomembranous colitis may occur during or after antimicrobial therapy (see section "Adverse reactions"). Cases of pseudomembranous colitis have been reported with nearly all antibacterial agents, including clindamycin; the severity may range from mild to life-threatening. Therefore, this diagnosis should be considered in patients who develop diarrhea following antibacterial therapy. In moderate cases, improvement is usually observed after discontinuation of the drug.

If pseudomembranous colitis occurs, clindamycin should be discontinued. Appropriate antibacterial therapy should be initiated. Antiperistaltic agents are contraindicated in this situation.

Banbact® should be prescribed with caution in patients with inflammatory bowel diseases such as Crohn's disease or non-specific ulcerative colitis.

As with any vaginal infections, sexual intercourse is not recommended during treatment with Banbact® vaginal suppositories. The suppository base may weaken latex condoms and diaphragms (see section "Interaction with other medicinal products and other forms of interaction"). It is not recommended to use such contraceptive methods within 72 hours after treatment, as their contraceptive effectiveness and protection against sexually transmitted infections may be reduced.

During treatment with Banbact® vaginal suppositories, the use of other intravaginal products (such as tampons or douching preparations) is not recommended.

Acute kidney injury

Rare cases of acute kidney injury, including acute renal failure, have been reported. Therefore, in patients receiving prolonged clindamycin therapy who have impaired renal function or are taking concomitant nephrotoxic drugs, monitoring of renal function should be considered (see section "Adverse reactions").

Special precautions for handling and disposal of the medicinal product

Do not use this medicinal product if the packaging containing the vaginal suppositories is damaged, opened, or not hermetically sealed.

Use during pregnancy or breastfeeding

Pregnancy

Reproductive toxicity has been demonstrated in animal studies.

Use of Banbact® during the first trimester of pregnancy is not recommended, as there are no adequate and well-controlled studies on the use of this medicinal product in pregnant women during this period.

Clinical data indicate that use of clindamycin in a vaginal formulation during the second trimester of pregnancy and systemic use of clindamycin phosphate during the second and third trimesters of pregnancy have not resulted in congenital anomalies.

Banbact® may be used during the second and third trimesters of pregnancy only if clearly needed.

Breastfeeding period

It is unknown whether clindamycin passes into breast milk after vaginal administration. Although administered at significantly lower doses than systemic clindamycin, approximately 30% (ranging from 6% to 70%) is absorbed into systemic circulation. After systemic administration, clindamycin has been detected in human breast milk at concentrations ranging from <0.5 to 3.8 µg/mL. With systemic use of clindamycin in breastfeeding women, there is a risk of adverse effects on the gut flora of the breastfed infant (diarrhea, blood in stool, or rash). Use of Banbact® vaginal suppositories in breastfeeding women may be considered if the expected benefit to the mother outweighs the potential risk to the infant.

Fertility

Animal studies have not shown any effect on fertility.

Ability to influence the ability to drive and use machines.

The influence of Banbact® on the ability to drive or operate machinery is absent or negligible.

Method of Administration and Dosage

Dosage

The recommended dose is 1 vaginal suppository administered intravaginally at bedtime for 3 consecutive days.

Method of Administration

The medicinal product Banbact® is administered intravaginally.

Administration Procedure

• Remove the suppository from the blister pack.
• Lie on your back and draw your knees up toward your chest.
• Insert the suppository into the vagina as deeply as possible using the middle finger of your hand, taking care not to cause discomfort.

Use in Elderly Patients

Use of Banbact® in the form of vaginal suppositories in patients aged 65 years and older has not been studied.

Use in Patients with Renal Impairment

Use of Banbact® in the form of vaginal suppositories in patients with impaired renal function has not been studied.

Please pay attention to official recommendations regarding the appropriate use of antibacterial agents.

Children

The safety and efficacy of Banbact® in the form of vaginal suppositories in children have not been established.

Overdose

There have been no reports of overdose with Banbact® in the form of vaginal suppositories.

Clindamycin phosphate contained in the product and administered vaginally may be absorbed in amounts sufficient to produce systemic effects.

In case of overdose, general symptomatic and supportive treatment should be administered, if necessary.

Accidental oral ingestion of the product may result in effects similar to those observed following oral administration of therapeutic doses of clindamycin.

Adverse Reactions

The safety of clindamycin administered as vaginal suppositories was evaluated in clinical trials involving non-pregnant patients. The following frequencies of adverse reactions were reported: common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100); frequency not known (cannot be estimated based on available data).

Infections and infestations: common – fungal infections, Candida infections; frequency not known – Clostridioides difficile-associated colitis.

Immune system disorders: frequency not known – hypersensitivity reactions*; drug-induced eosinophilia with systemic symptoms (DRESS syndrome).

Nervous system disorders: common – headache.

Gastrointestinal disorders: common – abdominal pain, diarrhea, nausea; uncommon – vomiting; frequency not known – pseudomembranous colitis**.

Skin and subcutaneous tissue disorders: common – itching (not at the application site); uncommon – rash.

Musculoskeletal and connective tissue disorders: uncommon – flank pain; frequency not known – polyarthritis.

Renal and urinary disorders: uncommon – pyelonephritis, dysuria; frequency not known – acute kidney injury, including acute renal failure (see section "Special precautions for use").

Reproductive system and breast disorders: common – vulvovaginal candidiasis, vulvovaginal pain, vulvovaginal disorders; uncommon – vaginal infections, vaginal discharge, menstrual cycle disturbances.

General disorders and administration site conditions: uncommon – application site pain, itching (at application site), local swelling, pain, fever.

*Maculopapular rashes and urticaria have been observed during treatment with clindamycin. Generalized mild to moderate skin rashes were the most frequently reported adverse reactions. Cases of acute generalized exanthematous pustulosis, erythema multiforme, some resembling Stevens-Johnson syndrome, have been associated with clindamycin use. There have been reports of several cases of anaphylactoid reactions. If a hypersensitivity reaction occurs, the drug should be discontinued.

**Pseudomembranous colitis is a condition associated with the entire class of antibacterial agents.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after marketing authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

3 suppositories per strip. 1 strip per cardboard package.

Prescription status.

Prescription only.

Manufacturer.

Kusum Healthcare Pvt Ltd.

Manufacturer's address and location of operations.

SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.