Minolexin® capsules 100 mg

Instructions for use of Minolexin® capsules 100 mg

International Nonproprietary Name: Minocycline

Trade Name: Minolexin^®

Dosage Form: capsules

Composition per one capsule:

Active substance: minocycline hydrochloride dihydrate (calculated as minocycline) 50.0 mg or 100.0 mg.

Excipients: microcrystalline cellulose (73.5 mg/147.0 mg), povidone K-17 (8.75 mg/17.5 mg), potato starch (7.0 mg/14.0 mg), magnesium stearate (1.75 mg/3.5 mg), lactose monohydrate (up to the capsule content weight of 175.0 mg/350.0 mg).

Hard gelatin capsules:

for 50 mg: water (13-16 %), quinoline yellow dye (0.5833-0.75 %), sunset yellow FCF (E110) (0.0025-0.0059 %), titanium dioxide (0.9740-2.0 %), gelatin (up to 100 %).

for 100 mg: water (13-16 %), titanium dioxide (2.0-2.1118 %), gelatin (up to 100 %).

Description:

Hard gelatin capsules size #2 with yellow body and cap (for 50 mg dosage), size #0 with white body and cap (for 100 mg dosage). The capsule contents are a yellow powder.

Pharmacotherapeutic Group:  Antibiotic - tetracycline.

ATC Code: J01AA08

Pharmacological Properties:

Pharmacodynamics

A semi-synthetic antibiotic from the tetracycline group. It has a bacteriostatic effect on cells of susceptible microbial strains by reversibly inhibiting protein synthesis at the level of the 30S ribosomal subunit. It has a broad spectrum of antibacterial activity.

Microorganism Susceptibility:

Aerobic Gram-positive:

Some of the microorganisms listed below have shown resistance to minocycline, therefore laboratory susceptibility testing is recommended prior to use. Tetracycline antibiotics are not recommended for the treatment of streptococcal and staphylococcal infections unless susceptibility to minocycline is demonstrated.

• Bacillus anthracis
• Listeria monocytogenes
• Staphylococcus aureus
• Streptococcus pneumoniae

Aerobic Gram-negative:

• Bartonella bacilliformis
• Brucella species
• Calymmatobacterium granulomatis
• Campylobacter fetus
• Francisella tularensis
• Haemophilus ducreyi
• Vibrio cholerae
• Yersinia pestis

For the microorganisms listed below, susceptibility testing against minocycline is strongly recommended:

• Acinetobacter species
• Enterobacter aerogenes
• Escherichia coli
• Haemophilus influenzae
• Klebsiella species
• Neisseria gonorrhoeae
• Neisseria meningitidis
• Shigella species

Additionally:

• Actinomyces species
• Borrelia recurrentis
• Chlamydia psittaci
• Chlamydia trachomatis
• Clostridium species
• Entamoeba species
• Fusobacterium nucleatum subspecies fusiforme
• Mycobacterium marinum
• Mycoplasma pneumoniae
• Propionibacterium acnes
• Rickettsiae
• Treponema pallidum subspecies pallidum
• Treponema pallidum subspecies pertenue
• Ureaplasma urealyticum

Pharmacokinetics

Food intake does not significantly affect the extent of minocycline absorption. Minocycline has high lipid solubility and low affinity for Ca²⁺ binding. It is rapidly absorbed from the gastrointestinal tract proportionally to the administered dose. The maximum plasma concentration (C_max) of minocycline after a single 200 mg oral dose is 3.5 mg/l and is reached (t_max) within 2-4 hours.

Protein binding is 75%; the influence of various diseases on this parameter has not been studied.

The volume of distribution is 0.7 l/kg. Minocycline penetrates well into organs and tissues: within 30 – 45 minutes after oral administration, it is detected in therapeutic concentrations in the kidneys, spleen, eye tissues, pleural and ascitic fluids, synovial exudate, exudate of the maxillary and frontal sinuses, and gingival sulcus fluid. It penetrates well into the cerebrospinal fluid (20 – 25% of the plasma level). It crosses the placenta and enters breast milk.

With repeated administration, the drug may accumulate. It accumulates in the reticuloendothelial system and bone tissue. In bones and teeth, it forms insoluble complexes with Ca²⁺. It undergoes enterohepatic recirculation; 30-60%  of the administered dose is excreted in the intestinal contents; 30% is excreted by the kidneys over 72 hours (of which 20–30% is unchanged), and only 1–5% in severe chronic renal failure. The elimination half-life (T_1/2) of minocycline is approximately 16 hours.

Indications for Use:

Minocycline hydrochloride is used to treat the following diseases, provided the pathogenic microorganisms are susceptible:

• Acne vulgaris
• Skin infections
• Spotted fever, typhus fever, endemic typhus, Q fever, rickettsialpox and tick fever
• Respiratory tract infections
• Lymphogranuloma venereum
• Psittacosis
• Trachoma (infectious keratoconjunctivitis)
• Inclusion conjunctivitis (paratrachoma)
• Non-gonococcal urethritis, infections of the cervical canal and anus in adults
• Relapsing fever
• Chancroid
• Plague
• Tularemia
• Cholera
• Brucellosis
• Bartonellosis
• Granuloma inguinale
• Syphilis
• Gonorrhea
• Yaws
• Listeriosis
• Anthrax
• Vincent's angina
• Actinomycosis

In cases of acute intestinal amebiasis, minocycline may be used as an adjunct to amebicidal drugs.

For severe acne, minocycline can be used as adjunctive therapy.

The use of minocycline is indicated for the eradication of meningococci from the nasopharynx in asymptomatic carriers of Neisseria meningitidis.

To prevent the development of resistance, the use of minocycline is recommended in accordance with the results of laboratory tests, including serotyping and susceptibility testing of pathogens. For the same reason, the use of minocycline for prophylaxis in cases of high risk of meningococcal meningitis is not recommended.

Clinical experience shows the effectiveness of minocycline in the treatment of Mycobacterium marinum infections; however, these data are not currently confirmed by the results of controlled clinical studies.

Contraindications:

• Hypersensitivity to minocycline, other tetracyclines, or any component of the drug
• Porphyria
• Severe hepatic and renal impairment
• Leukopenia
• Pregnancy
• Breastfeeding
• Systemic lupus erythematosus
• Children under 8 years of age (tooth development period)
• Concurrent use with isotretinoin
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption

Use with Caution:

Impaired liver or kidney function, concurrent use with hepatotoxic drugs.

Use During Pregnancy and Lactation:

Minocycline during pregnancy is recommended only when the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding should be discontinued during minocycline treatment.

Dosage and Administration:

Orally, after meals. It is recommended to take with plenty of fluid (milk is acceptable) to reduce the risk of esophageal irritation and ulceration.

The initial dose of Minolexin^® is 200 mg (2 capsules of 100 mg or 4 capsules of 50 mg), followed by 100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) every 12 hours (twice daily).

The maximum daily dose should not exceed 400 mg.

Genitourinary and anogenital infections caused by chlamydia and ureaplasma: 100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) every 12 hours for 7-10 days.

Acute pelvic inflammatory disease in women:  100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) every 12 hours, sometimes in combination with cephalosporins. 

Primary syphilis in patients hypersensitive to penicillins:  100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) twice daily for 10 – 15 days.

Gonorrhea: 100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) twice daily  for 4-5 days, or a single dose of 300 mg.

Uncomplicated gonococcal infections (excluding urethritis and anorectal infections) in men: initial dose – 200 mg (2 capsules of 100 mg or 4 capsules of 50 mg), maintenance dose – 100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) every 12 hours for at least 4 days, followed by microbiological  assessment of cure 2-3 days after discontinuation of the drug. 

Uncomplicated gonococcal urethritis in men: 100 mg (1 capsule of 100 mg or 2 capsules of 50 mg) every 12 hours for 5 days.

Acne: 50 mg (1 capsule of 50 mg) once daily, as a prolonged course of 6–12 weeks.

Due to the anti-anabolic effect inherent to tetracycline drugs, an increase in plasma urea levels may be observed during administration. In patients with normal renal function, this does not require discontinuation of the drug. In patients with significantly impaired renal function, azotemia, hyperphosphatemia, and acidosis may develop. In this situation, monitoring of plasma urea  and creatinine levels is necessary, and the maximum daily dose  of minocycline should not exceed 200 mg.

The pharmacokinetics of minocycline in patients with renal failure (creatinine clearance less than 80 ml/min) have not been sufficiently studied to draw conclusions about the need for dose adjustment.

Use with caution in patients with impaired liver function.

Children over 8 years with infections caused by minocycline-susceptible pathogens: initial dose  – 4 mg/kg, then 2 mg/kg every 12 hours.

Adverse Reactions:

The spectrum of adverse reactions associated with minocycline use does not differ from that of other tetracyclines.

Gastrointestinal disorders: anorexia, nausea, vomiting, diarrhea, dyspepsia, stomatitis, glossitis, dysphagia, tooth enamel hypoplasia, enterocolitis, pseudomembranous colitis, pancreatitis, inflammatory (including fungal) lesions in the oral cavity and anogenital area, hyperbilirubinemia, cholestasis, increased liver enzyme levels, hepatic failure, including fatal, hepatitis, including autoimmune.

Renal and urinary disorders: candidal vulvovaginitis, interstitial nephritis, dose-dependent increase in plasma urea levels.

Skin and subcutaneous tissue disorders: alopecia, erythema nodosum, nail pigmentation, pruritus, toxic epidermal necrolysis, vasculitis, maculopapular and erythematous rash, Stevens-Johnson syndrome, exfoliative dermatitis, balanitis.

Respiratory, thoracic and mediastinal disorders: dyspnea, bronchospasm, exacerbation of asthma, pneumonia.

Musculoskeletal and connective tissue disorders: arthralgia, arthritis, joint immobility and swelling, bone discoloration, myalgia.

Immune system disorders: urticaria, angioedema, polyarthralgia, anaphylactic reactions (including shock), anaphylactoid purpura (Henoch-Schönlein purpura), pericarditis, exacerbation of systemic lupus, pulmonary infiltration accompanied by eosinophilia.

Blood and lymphatic system disorders: agranulocytosis, hemolytic anemia, thrombocytopenia, leukopenia, neutropenia, pancytopenia, eosinopenia, eosinophilia.

Nervous system disorders: convulsions, dizziness, numbness (including of extremities), lethargy, vertigo, increased intracranial pressure in adults, headache.

Ear and labyrinth disorders: tinnitus and hearing impairment.

Endocrine disorders: Thyroid gland: single case of malignant neoplasm, discoloration (based on pathological findings), functional impairment.

General disorders and administration site conditions:

Discoloration of the oral cavity (tongue, gums, palate), tooth enamel discoloration, fever, discoloration of secretions (e.g., sweat).

Overdose:

Symptoms: Most commonly reported are dizziness, nausea, and vomiting. Treatment: No specific antidote for minocycline is currently known.

In case of overdose, discontinue the drug, provide symptomatic and supportive treatment. Hemodialysis and peritoneal dialysis remove minocycline only minimally.

Drug Interactions:

Tetracyclines may decrease plasma prothrombin activity, which may necessitate dose reduction of anticoagulants in patients, on anticoagulant therapy.

Because bacteriostatic drugs may interfere with the bactericidal action of penicillins, concurrent use of penicillins and tetracyclines should be avoided.

Absorption of tetracyclines is impaired by concurrent administration of antacids containing aluminum, calcium, magnesium or iron-containing preparations, which may lead to reduced antibiotic efficacy.

Cases of fatal renal toxicity have been reported with concurrent use of methoxyflurane and tetracyclines.

Concurrent use of tetracycline antibiotics and oral contraceptives may reduce the effectiveness of contraception.

Isotretinoin should not be taken immediately before, during, or immediately after minocycline therapy, as both drugs can cause benign intracranial hypertension.

Concurrent use of tetracyclines with ergot alkaloids and their derivatives increases the risk of ergotism.

Special Warnings and Precautions:

With prolonged use of minocycline, periodic monitoring of peripheral blood cell count, liver function tests, and serum nitrogen and urea levels should be performed.

When using estrogen-containing contraceptives during minocycline therapy, additional or alternative methods of contraception should be used.

False elevation of urinary catecholamine levels may occur when measured by fluorescence.

When examining thyroid gland biopsy specimens from patients long-term treated with tetracyclines, the possibility of dark brown staining of tissue in microslides should be considered.

Diarrhea caused by Clostridium difficile (pseudomembranous colitis) may develop during or up to 2-3 weeks after treatment. In mild cases, discontinuation of treatment and administration of ion-exchange resins (cholestyramine, colestipol) may suffice; in severe cases, fluid, electrolyte, and protein replacement, and administration of vancomycin, bacitracin, or metronidazole are indicated. Drugs that inhibit intestinal peristalsis should not be used.

To avoid the development of resistance, minocycline should be used only in accordance with the results of susceptibility testing of pathogenic microorganisms. If susceptibility testing is not possible, the epidemiology and susceptibility profile of microorganisms in the specific region should be considered.

In cases of venereal diseases, when concomitant syphilis is suspected, dark-field microscopic examination should be performed before initiating treatment. Serological testing of blood serum is recommended at least every four months.

Periodic laboratory diagnosis of body functions, including hematopoietic, renal, and hepatic status, is necessary.

Action Algorithm for Specific Adverse Reactions:

In case of superinfection,  discontinue minocycline and institute appropriate therapy.

In case of increased intracranial pressure, discontinue minocycline.

Diarrhea is a common disorder associated with antibiotic use. If diarrhea occurs during minocycline treatment, consult a doctor immediately.

Tetracycline antibiotics cause increased sensitivity to direct sunlight and ultraviolet radiation. If erythema occurs, discontinue the antibiotic.

Effects on Ability to Drive and Use Machines:

Caution should be exercised when driving vehicles or engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions, due to the potential side effect of dizziness (see "Adverse Reactions" section).

Packaging:

Capsules 50 mg and 100 mg.

10 capsules in a blister strip made of PVC film and aluminum foil.

2 or 3 blister strips, along with the instructions for use, are placed in a cardboard carton.

Shelf Life:

2 years. Do not use after the expiration date.

Storage Conditions:

Store in a dry place, protected from light, at a temperature not exceeding 25 ^oC. Keep out of reach of children.

Legal Status:

Prescription only.

Marketing Authorization Holder / Organization for Claims:

JSC "AVVA RUS", Russia, 121614,

 Moscow, ul. Krylatskie Kholmy, 30, building 9.

Tel/Fax: (495) 956-75-54.

avva.com.ru

Production Site Address:

JSC "AVVA RUS", Russia, 610044, Kirov region, Kirov, ul. Luganskaya, 53a.

Tel: +7 (8332) 25-12-29; +7 (495) 956-75-54.