Dalacin vaginal cream

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DALACIN VAGINAL CREAM (DALACIN VAGINAL CREAM)

Composition:

Active substance: clindamycin;

1 g of cream contains clindamycin phosphate in an amount equivalent to clindamycin 20 mg;

Excipients: sorbitan stearate, polysorbate 60, propylene glycol, stearic acid, cetylstearyl alcohol, cetyl palmitate, mineral oil, benzyl alcohol, purified water.

Pharmaceutical form. Vaginal cream.

Main physicochemical properties: white soft cream.

Pharmacotherapeutic group. Antimicrobial and antiseptic agents for gynecological use, excluding combined preparations containing corticosteroids.

ATC code G01A A10.

Pharmacological Properties

Pharmacodynamics

Mechanism of Action

Clindamycin is a lincosamide antibiotic that inhibits bacterial protein synthesis at the level of the bacterial ribosome. The antibiotic primarily binds to the 50S ribosomal subunit and interferes with the translation process. Although clindamycin phosphate is inactive in vitro, rapid in vivo hydrolysis converts this compound into the antibacterially active clindamycin.

Pharmacokinetic/Pharmacodynamic Relationship

Like other protein synthesis inhibitors, efficacy is related to the duration of time during which the concentration of clindamycin remains above the MIC (minimum inhibitory concentration) of the infecting organism.

Mechanism of Resistance

Resistance to clindamycin is most often due to modification of ribosomal target sites, usually through chemical modification of ribosomal RNA bases or point mutations in RNA, or occasionally mutations in proteins. In vitro, cross-resistance among lincosamides, macrolides, and streptogramin B has been demonstrated in certain organisms.

Cross-resistance has been demonstrated between clindamycin and lincomycin.

Breakpoints

Standard methodology for testing susceptibility of potential causative agents of bacterial vaginosis (Gardnerella vaginalis and Mobiluncus species) has not been established. Susceptibility testing methods for Bacteroides species, gram-positive anaerobic cocci, and Mycoplasma species are described by the Clinical and Laboratory Standards Institute (CLSI). Breakpoints for clindamycin susceptibility of gram-negative and gram-positive anaerobes have been published by both EUCAST (European Committee on Antimicrobial Susceptibility Testing) and CLSI. However, these breakpoints are primarily intended to guide systemic antibiotic therapy rather than topical treatment.

Microbiological Susceptibility

Clindamycin is active in vitro against most strains of microorganisms reported to be associated with bacterial vaginosis: Bacteroides species; Gardnerella vaginalis; Mobiluncus species; Mycoplasma hominis; Peptostreptococcus species.

Pharmacokinetics

Following intravaginal administration of 100 mg clindamycin phosphate as 2% vaginal cream once daily for 7 days in 6 healthy female volunteers, systemic absorption of the active substance averaged 4% of the administered dose (range: 0.6% to 11%). Peak serum clindamycin concentration on day 1 averaged 18 ng/mL (range: 4 to 47 ng/mL), and on day 7 averaged 25 ng/mL (range: 6 to 61 ng/mL). These peak concentrations were observed approximately 10 hours (range: 4 to 24 hours) after dosing.

Following intravaginal administration of 100 mg clindamycin phosphate as 2% vaginal cream once daily for 7 consecutive days in 5 patients with bacterial vaginosis, absorption was slower and variability lower compared to healthy women. Systemic absorption amounted to approximately 4% (range: 2% to 8%) of the dose. Peak serum clindamycin concentration on day 1 averaged 13 ng/mL (range: 6 to 34 ng/mL), and on day 7 averaged 16 ng/mL (range: 7 to 26 ng/mL). These peak concentrations were observed approximately 14 hours (range: 4 to 24 hours) after administration.

Repeated (over 7 days) vaginal administration of clindamycin phosphate as 2% vaginal cream was not associated with significant systemic accumulation of clindamycin. The systemic elimination half-life ranged from 1.5 to 2.6 hours.

Geriatric Patients

Clinical studies of clindamycin phosphate 2% vaginal cream did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients.

Clinical characteristics.

Indications.

Treatment of bacterial vaginosis.

Contraindications.

Dalacin Vaginal Cream is contraindicated in patients with a history of hypersensitivity to clindamycin, lincomycin, or any excipient listed in the section "Composition". Dalacin Vaginal Cream is also contraindicated in patients with a history of intestinal inflammation or antibiotic-associated colitis.

Interaction with other medicinal products and other forms of interaction.

Clindamycin, when administered systemically, has been shown to block neuromuscular transmission and may potentiate the effect of other neuromuscular blockers. Therefore, clindamycin should be used with caution in patients receiving such agents (see section "Overdose").

There is no information regarding the concomitant use of clindamycin with other vaginal products.

Special precautions.

Before or after starting clindamycin treatment, it may be necessary to perform appropriate laboratory tests for other infections, including Trichomonas vaginalis, Candida albicans, Chlamydia trachomatis, and gonococcal infections.

Use of clindamycin may lead to overgrowth of nonsusceptible microorganisms, including yeasts.

Symptoms indicative of pseudomembranous colitis may occur during or after antibiotic therapy (see section "Adverse Reactions"). Pseudomembranous colitis has been reported with nearly all antibacterial agents, including clindamycin, and may range in severity from mild to life-threatening. Therefore, this possibility must be considered in patients who develop diarrhea following antibiotic use. In cases of mild to moderate severity, improvement may be observed after discontinuation of the drug.

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

Clindamycin should be prescribed with caution in patients with intestinal inflammatory diseases such as Crohn's disease or ulcerative colitis.

As with any vaginal infections, sexual intercourse is not recommended during treatment. The suppository base used in clindamycin vaginal cream may reduce the effectiveness of latex condoms and diaphragms upon contact. Use of these contraceptive methods is not recommended within 72 hours after treatment with clindamycin vaginal cream, as such use may be associated with reduced contraceptive effectiveness or protection against sexually transmitted infections.

During treatment, use of other products intended for intravaginal administration (such as tampons, douching products) is not recommended.

Excipients.

Dalacin Vaginal Cream contains propylene glycol, cetostearyl alcohol, and benzyl alcohol (see section "Composition").

Cetostearyl alcohol may cause local skin reactions (e.g., contact dermatitis).

Benzyl alcohol may cause allergic reactions and mild local irritation.

Geriatric patients.

Clinical studies of 2% clindamycin phosphate vaginal cream did not include sufficient numbers of patients aged 65 years and older to determine whether they respond differently from younger patients.

Use during pregnancy or breastfeeding.

Pregnancy.

Clindamycin is not recommended during the first trimester due to lack of adequate and well-controlled studies in pregnant women during this period.

Clinical data on the use of the vaginal formulation during the second trimester of pregnancy and systemic use of clindamycin phosphate during the second and third trimesters have not shown an association with congenital anomalies.

Dalacin Vaginal Cream may be used during the second and third trimesters of pregnancy only if clearly needed.

In clinical studies involving pregnant women during the second trimester, Dalacin Vaginal Cream was effective in the treatment of bacterial vaginosis and was not associated with any adverse effects in newborns. However, as with any medication used during pregnancy, a careful assessment of benefit versus risk should be performed.

Breastfeeding period.

It is not known whether clindamycin is excreted in human breast milk following vaginal administration of Dalacin Vaginal Cream. Clindamycin has been reported to be present in human breast milk at concentrations ranging from <0.5 to 3.8 mcg/mL following systemic administration. Clindamycin may cause adverse effects on the gastrointestinal flora of a breastfed infant, such as diarrhea, bloody stools, or rash. If a breastfeeding mother requires oral or intravenous clindamycin, this should not automatically necessitate discontinuation of breastfeeding; however, an alternative agent may be preferable. The benefits of breastfeeding for infant development and health, the mother's clinical need for clindamycin, and any potential adverse effects of clindamycin or the underlying maternal condition on the breastfed infant should all be considered.

Ability to influence the ability to drive vehicles or operate machinery.

There have been no systematic studies evaluating the effect of clindamycin on the ability to drive vehicles or operate machinery.

Method of administration and dosage.

Apply 1 full applicator (approximately 5 g) intravaginally before bedtime for 7 consecutive days.

It has been shown that in patients for whom a shorter treatment course is recommended, a 3-day treatment regimen is effective.

Children.

The safety and efficacy of the medicinal product in pediatric practice have not been established.

Overdose.

There have been no reports of clindamycin overdose. Dalacin vaginal cream may be absorbed in amounts sufficient to cause systemic effects when administered vaginally.

In case of overdose, general symptomatic and supportive measures should be taken as needed.

In case of accidental oral ingestion, effects similar to those occurring with oral administration of therapeutic doses of clindamycin may develop.

Adverse Reactions

The adverse reactions listed below, identified during clinical trials and post-marketing surveillance, are presented by system organ classes and frequency. Adverse reactions identified during post-marketing use are indicated in italics. Frequency grouping is defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); frequency not known (cannot be estimated from available data). Within each frequency group, adverse events are listed in order of decreasing severity.

The safety of Dalacin Vaginal Cream has been studied in non-pregnant and pregnant women during the second and third trimesters of pregnancy.

Infections and infestations

Common: fungal infections, infections caused by Candida species.
Uncommon: bacterial infections.
Frequency not known: skin candidiasis.

Immune system disorders

Uncommon: hypersensitivity reactions.

Endocrine disorders

Frequency not known: hyperthyroidism.

Nervous system disorders

Common: headache, dizziness, dysgeusia.

Ear and labyrinth disorders

Uncommon: vertigo.

Respiratory, thoracic and mediastinal disorders

Common: upper respiratory tract infections.
Uncommon: epistaxis.

Gastrointestinal disorders

Common: abdominal pain, constipation, diarrhoea, nausea, vomiting.
Uncommon: abdominal distension, halitosis, flatulence.
Frequency not known: gastrointestinal disorders, pseudomembranous colitis*, dyspepsia.

Skin and subcutaneous tissue disorders

Common: pruritus (not at application site), rash.
Uncommon: erythema, urticaria.
Frequency not known: maculopapular rash.

Musculoskeletal and connective tissue disorders

Common: back pain.

Renal and urinary disorders

Common: urinary tract infections, glucosuria, proteinuria.
Uncommon: dysuria.

Reproductive system and breast disorders

Very common: vulvovaginal candidiasis.
Common: vulvovaginitis, vulvovaginal disorders, menstrual irregularities, vulvovaginal pain, metrorrhagia, vaginal discharge.
Uncommon: trichomonal vulvovaginitis, vaginal infections, pelvic pain.
Frequency not known: endometriosis.

Pregnancy, puerperium and perinatal period

Common: pathological delivery.

General disorders and administration site conditions

Frequency not known: pain, inflammation.

Investigations

Uncommon: abnormal microbiological test results.

*Adverse reactions identified during the post-marketing period.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions.

Keep out of reach and sight of children. Store at a temperature not exceeding 25 °C.
Do not freeze.

Packaging.

20 g of cream in a tube, 1 tube with 3 applicators in a cardboard box.

Prescription category. Prescription only.

Manufacturer.

Pharmacia and Upjohn Company LLC, USA.

Manufacturer's address and location of operations.

7000 Portage Road, Kalamazoo, Michigan (MI) 49001, USA.