Instructions for use Dalacin vaginal suppositories 100 mg No. 3
Composition
active ingredient: clindamycin;
1 suppository contains clindamycin phosphate in an amount equivalent to 100 mg of clindamycin;
excipient: solid fat.
Dosage form
Vaginal suppositories.
Main physicochemical properties: solid suppositories of almost white color with a smooth surface.
Pharmacotherapeutic group
Antimicrobial and antiseptic agents used in gynecology, except combined medicinal products containing corticosteroids. Antibiotics. ATX code G01A A10.
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 affects the translation process. Although clindamycin phosphate is inactive in vitro, in vivo it is rapidly hydrolyzed to clindamycin, which exhibits antibacterial activity.
Clindamycin, like most protein synthesis inhibitors, has a predominantly bacteriostatic effect, its effectiveness is related to the duration of time when the concentration of the active substance remains above the MIC (minimum inhibitory concentration) of the infectious agent.
Resistance to clindamycin most often arises through modification of the target site on the ribosome, usually by chemical modification of RNA bases or point mutations in RNA or sometimes in proteins. Cross-resistance has been demonstrated in some organisms in vitro between lincosamides, macrolides, and streptogramin B. Cross-resistance has been demonstrated between clindamycin and lincomycin.
In vitro susceptibility: Clindamycin has been shown to be active in vitro against the following strains of organisms known to be associated with bacterial vaginosis: Bacteroides spp., Gardnerella vaginalis, Mobiluncus spp., Mycoplasma hominis, Peptostreptococcus spp.
Standard methodology for susceptibility testing of potential bacterial vaginosis pathogens, Gardnerella vaginalis and Mobiluncus spp. has not been established. Breakpoints for susceptibility of Gram-negative and Gram-positive anaerobes to clindamycin have been published by EUCAST. Clinical isolates that are susceptible to clindamycin and resistant to erythromycin should also be tested for induced resistance to clindamycin using the D-test. However, the breakpoints are intended to guide systemic antibiotic treatment rather than topical therapy.
Pharmacokinetics
Absorption The systemic absorption of clindamycin was evaluated following intravaginal administration of 1 suppository of clindamycin phosphate once daily (equivalent to 100 mg of clindamycin) to 11 healthy female volunteers for 3 days. Approximately 30% (range 6% to 70%) of the administered dose was systemically absorbed by day 3 of administration as measured by the area under the concentration-time curve (AUC). Systemic absorption was investigated following intravenous administration of a subtherapeutic dose of 100 mg of clindamycin phosphate as a comparison to the same volunteers administered a vaginal cream containing 100 mg of clindamycin phosphate. The mean area under the curve (AUC) after 3 days of suppository administration was 3.2 μg h/mL (range 0.42 to 11 μg h/mL). Cmax was observed on the 3rd day of suppository administration and averaged 0.27 μg/ml (range 0.03 to 0.67 μg/ml) and was observed approximately 5 hours after administration (range 1 to 10 hours). In comparison, the area under the curve and Cmax after a single intravenous administration averaged 11 μg·h/ml (range 5.1 to 26 μg·h/ml) and 3.7 μg/ml (range 2.4 to 5 μg/ml), respectively. The mean elimination half-life after suppository administration was 11 hours (range 4 to 35 hours) and is believed to be absorption-limited.
The results of this study showed that the systemic exposure of clindamycin (based on AUC) when administered as a suppository was on average 3-fold lower than after a single intravenous administration of a subtherapeutic dose of 100 mg of clindamycin. Compared with a similar dose of clindamycin administered as a vaginal cream, the systemic absorption of the suppository was approximately 7-fold higher than that of the vaginal cream, for which the mean AUC and Cmax values were 0.4 μg h/mL (range 0.13 to 1.16 μg h/mL) and 0.02 μg/mL (range 0.01 to 0.07 μg/mL), respectively. In addition, the recommended daily and total dose of clindamycin in suppositories for intravaginal administration is much lower than that typically used with oral or parenteral clindamycin (when 100 mg of clindamycin is administered daily for 3 days as a suppository, the amount of clindamycin absorbed is about 30 mg per day compared with 600–2700 mg per day for 10 days or more with oral or parenteral administration). In general, the systemic exposure to clindamycin from vaginal suppositories is much lower than the systemic exposure from a therapeutic dose after oral clindamycin hydrochloride (2–20 times lower) or parenteral clindamycin phosphate (40–50 times lower).
Indication
Treatment of bacterial vaginosis (previous names: haemophilic vaginitis, gardnerella vaginitis, nonspecific vaginitis, corynebacterial vaginitis or anaerobic vaginosis).
Contraindication
Hypersensitivity to the active substance, lincomycin, or to any of the excipients listed in the "Composition" section.
Dalacin is also contraindicated in patients with a history of antibiotic-associated colitis.
Interaction with other medicinal products and other types of interactions
There is no information on the simultaneous use of Dalacin with other vaginal medications.
When administered systemically, clindamycin phosphate has neuromuscular blocking properties that may potentiate the effects of other neuromuscular blocking agents. Therefore, it should be used with caution in patients taking such agents (see sections 4.8 and 5.2).
It is not recommended to use latex condoms during treatment with Dalacin in the form of vaginal suppositories.
Application features
Before or immediately after starting Dalacin, it may be necessary to conduct laboratory tests for the presence of other infectious agents, including Trichomonas vaginalis, Candida albicans, Chlamydia trachomatis and gonococci.
The use of Dalacin may lead to overgrowth of microorganisms insensitive to the drug, including yeast.
Symptoms suggestive of pseudomembranous colitis may occur during or after the use of antimicrobial agents (see section 4.8). 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 should be considered in patients who develop diarrhea after the use of antibacterial agents. In moderate cases, improvement is observed after discontinuation of the drug.
In case of pseudomembranous diarrhea, clindamycin should be discontinued. Appropriate antibacterial treatment should be prescribed. Drugs that inhibit peristalsis are contraindicated in this case.
It is recommended to prescribe Dalacin with caution to patients with inflammatory bowel diseases, such as Crohn's disease or ulcerative colitis.
As with any vaginal infection, sexual intercourse is not recommended during the use of Dalacin in the form of vaginal suppositories. The base of vaginal suppositories may weaken the strength of latex condoms and contraceptive diaphragms (see section "Interaction with other medicinal products and other types of interactions"). It is not recommended to use such products within 72 hours after treatment with the drug, as their contraceptive efficacy and protective properties against sexually transmitted diseases may be reduced.
During the period of use of the drug Dalacin in the form of vaginal suppositories, the use of other products intended for intravaginal administration (such as tampons, douching agents) is not recommended.
Special precautions during handling and disposal of the drug.
Do not use this medicine if the foil package containing the vaginal suppositories is damaged, opened, or not sealed properly.
Use during pregnancy or breastfeeding
Pregnancy.
Reproductive toxicity has been demonstrated in animal studies.
Use during the first trimester of pregnancy is not recommended, as there are no adequate well-controlled studies on the use of the drug in pregnant women during this period.
According to clinical studies, the use of Dalacin in a dosage form for vaginal use in women during the second trimester of pregnancy and the systemic use of clindamycin phosphate during the second and third trimesters did not lead to the development of congenital anomalies.
Dalacin can be used in the 2nd and 3rd trimesters of pregnancy only if clearly needed. During pregnancy, it is recommended to insert vaginal suppositories without using an applicator.
Breast-feeding.
It is not known whether clindamycin is excreted in human milk after vaginal administration. Although used at much lower doses than systemic clindamycin, approximately 30% (range 6% to 70%) is absorbed into the systemic circulation. Clindamycin has been reported to be present in human milk after systemic administration at concentrations ranging from < 0.5 to 3.8 mcg/mL.
When systemic clindamycin is administered to breastfeeding women, there is a risk of adverse effects on the gastrointestinal microflora of the breastfed infant, such as diarrhea or blood in the stool, or rash. The use of Dalacin vaginal suppositories in breastfeeding women may be considered if the expected benefit to the mother outweighs the risks to the child.
Fertility.
Animal studies have not shown any effect on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
The effect of Dalacin on the ability to drive or operate other mechanisms is absent or negligible.
Method of administration and doses
Dosage.
The recommended dose is 1 suppository intravaginally before bedtime for 3 consecutive days.
Method of application.
Dalacin is used intravaginally.
Remove the suppository from the foil.
Lie on your back and pull your knees to your chest.
Insert the suppository into the vagina using your middle finger as deeply as possible, but so as not to cause discomfort.
Use in elderly patients.
The use of Dalacin in the form of vaginal suppositories in patients over 65 years of age has not been studied.
Use in patients with renal impairment.
The use of Dalacin in the form of vaginal suppositories in patients with impaired renal function has not been studied.
Attention should be paid to official recommendations regarding the appropriate use of antibacterial agents.
Children
The safety and efficacy of Dalacin vaginal suppositories in children have not been established.
Overdose
No cases of overdose with Dalacin in the form of vaginal suppositories have been reported.
Clindamycin phosphate, contained in the drug and applied vaginally, can be absorbed in an amount sufficient to develop systemic effects.
In case of overdose, general symptomatic and supportive treatment is indicated, if necessary.
Accidental ingestion of the drug may cause effects similar to those that occur with oral administration of therapeutic doses of clindamycin.
Side effects
The safety of clindamycin vaginal suppositories has been evaluated in clinical trials in non-pregnant patients. The following adverse reactions have been reported: common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100).
Infections and invasions.
Common: fungal infections, candida infections.
Nervous system disorders.
Common: headache.
Gastrointestinal disorders.
Common: abdominal pain, diarrhea, nausea.
Uncommon: vomiting.
Skin and subcutaneous tissue disorders.
Common: itching (not at the application site).
Uncommon: rash.
Musculoskeletal and connective tissue disorders.
Uncommon: flank pain.
Kidney and urinary system disorders.
Uncommon: pyelonephritis, dysuria.
Disorders of the genitals and mammary glands.
Common: vulvovaginal candidiasis, vulvovaginal pain, vulvovaginal disorder. Uncommon: vaginal infection, vaginal discharge, menstrual disorder.
General disorders and administration site conditions.
Uncommon: application site pain, application site itching, local swelling, pain, fever.
Pseudomembranous colitis is a phenomenon characteristic of the entire class of antibacterial agents.
Reporting of suspected adverse reactions.
It is very important to report suspected adverse reactions after the registration of a medicinal product. This ensures continuous monitoring of the benefit-risk balance of the medicinal product. We ask healthcare professionals to report any suspected adverse reactions in accordance with legal requirements.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C, out of the reach of children.
Packaging
3 suppositories in a laminated foil (strip) in a cardboard box.
Vacation category
according to the recipe.
Producer
Pharmacy and Upjohn Company LLC.
Location of the manufacturer and its business address
7000 Portage Road, Kalamazoo, Michigan (MI) 49001, USA.
