Soludine-M Ointment (Povidone Iodine and Metronidazole Ointment)

Indications

• Amebiasis
• Trichomoniasis
• Giardiasis
• Anaerobic bacterial infections
• Bacterial vaginosis
• Clostridium difficile infection

Dosage

Children: For children aged 1 month to 11 years, 7.5 mg/kg every 8 hours for 7 days (maximum dose 400 mg). For children aged 12-17 years, 400 mg every 8 hours for 7 days.

Adults: 1 g three times a day for 3 days, then 1 g twice daily for a total treatment duration of 7 days. In cases of Clostridium difficile infection, treatment may extend to 10 days.

Mechanism of action

The exact mechanism of action of metronidazole is not fully established. However, it is believed that anaerobic bacteria and protozoa reduce metronidazole to reactive intermediates that bind to DNA and inhibit nucleic acid synthesis, leading to cell death. Metronidazole is selectively activated in anaerobic conditions, making it effective against obligate anaerobes.

Pharmacodynamics

Metronidazole exhibits both antibacterial and antiprotozoal activities, effectively treating infections caused by anaerobic bacteria. It demonstrates significant antibacterial activity against most obligate anaerobes but is less effective against facultative anaerobes and obligate aerobes. The drug's cytotoxic effects result from DNA strand damage in susceptible microorganisms, which can lead to cell death. Caution is advised due to the potential for peripheral neuropathy and convulsions, especially at higher doses.

Pharmacokinetics

Metronidazole is well absorbed following oral administration and is distributed widely throughout the body, including the central nervous system. It undergoes hepatic metabolism, primarily through oxidation and conjugation, and is excreted mainly in urine. The pharmacokinetic profile may vary in patients with hepatic impairment, and dosage adjustments may be necessary.

Adverse effects

• Peripheral neuropathy
• Convulsions
• Nausea
• Vomiting
• Diarrhea
• Headache
• Dizziness
• Abdominal cramps
• Metallic taste
• Skin rash

Interactions

• Metronidazole + Coumarins: Increases anticoagulant effect
• Metronidazole + Lithium: Increases concentration
• Metronidazole + Busulfan: Increases risk of toxicity (unknown)
• Metronidazole + Capecitabine: Increases risk of capecitabine toxicity (unknown)
• Metronidazole + Fluorouracil: Increases risk of toxicity (unknown)
• Metronidazole + Alkylating agents: Increases risk of toxicity (unknown)

Precautions

• Caution in patients with history of neurological disorders
• Monitor for signs of peripheral neuropathy
• Use with caution in patients with hepatic impairment
• Avoid excessive alcohol consumption during treatment

Pregnancy

No information available; manufacturer advises avoidance unless essential.

Breast-feeding

Amount in milk probably too small to be harmful.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Metronidazole 0.75% gel
• Metronidazole 0.75% cream
• Metronidazole powder and solvent for nebuliser solution
• Metronidazole injection
• Metronidazole oral tablets (various strengths)

Indications

• Iodine deficiency
• Goiter
• Hypothyroidism
• Thyroiditis
• Fibrocystic breast disease

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines based on age and weight.

Adults: Refer to the BNF for appropriate dosing guidelines based on condition and clinical judgment.

Mechanism of action

Molecular iodine inhibits the induction and promotion of carcinogenesis in mammary tissues and has shown beneficial effects in fibrocystic breast disease. It temporarily decreases thyroid hormone production through the acute Wolff-Chaikoff effect, followed by a return to normal hormone synthesis due to down regulation of the sodium-iodide symport. This mechanism can lead to a transient hypothyroid state in some individuals with underlying thyroid conditions.

Pharmacodynamics

Iodine is vital for the synthesis of thyroid hormones thyroxine (T4) and triiodothyronine (T3). It affects the metabolism of amine-derived hormones and plays a role in amino acid metabolism. The acute excess of iodide can lead to decreased circulating levels of T4 and T3 in susceptible individuals, while most people can escape this effect and maintain normal thyroid function.

Pharmacokinetics

Iodine is absorbed primarily in the gastrointestinal tract and is distributed throughout the body, particularly in the thyroid gland, where it is concentrated for hormone synthesis. The kidney plays a significant role in the excretion of excess iodine. The half-life of iodine in the body varies and can be influenced by dietary intake and underlying health conditions.

Adverse effects

• Hypothyroidism
• Hyperthyroidism
• Iodine allergy
• Gastrointestinal disturbances

Interactions

• Thyroid hormones
• Antithyroid drugs
• Lithium
• Diuretics

Precautions

• Use with caution in patients with thyroid dysfunction
• Monitor thyroid function periodically during treatment
• Pregnant or breastfeeding women should consult a healthcare provider before use

Pregnancy

Iodine is essential for fetal thyroid hormone synthesis, but excessive iodine intake should be avoided.

Breast-feeding

Iodine is excreted in breast milk; consult a healthcare provider regarding supplementation.

Storage

Store in a cool, dry place away from light.

Formulations

• Iodine solution
• Iodine tincture
• Potassium iodide tablets

Indications

• Topical antiseptic for skin disinfection
• Surgical scrubs and hand sanitizers
• Wound care management
• Pharmaceutical excipient in solid and liquid formulations

Dosage

Children: Refer to specific product guidelines for pediatric dosing recommendations, as doses can vary based on formulation and intended use.

Adults: Refer to specific product guidelines for dosing recommendations, as doses can vary based on the formulation and intended use.

Mechanism of action

Povidone acts by forming a complex with iodine when used as an antiseptic, which releases iodine slowly to exert its antimicrobial effect. The iodine disrupts microbial cell walls and interferes with protein synthesis, leading to cell death. Additionally, as a polymer, povidone can enhance drug solubility and stability by forming a hydrophilic matrix.

Pharmacodynamics

Povidone has a broad spectrum of antimicrobial activity against bacteria, viruses, and fungi. Its antiseptic properties are primarily due to the release of iodine, which is effective in reducing microbial load and preventing infection. The polymer's ability to bind to various substances allows it to be utilized in formulations that require improved stability and solubility.

Pharmacokinetics

Povidone is not absorbed systemically when applied topically, as it remains localized at the site of application. Its pharmacokinetics are largely dependent on the formulation and route of administration, with the polymer being metabolized by hydrolysis and excreted in urine as low-molecular-weight compounds. The release and activity of iodine are influenced by the concentration of povidone and the presence of organic matter.

Adverse effects

• Local irritation
• Allergic reactions
• Skin rashes
• Hypersensitivity reactions

Precautions

• Use with caution in patients with known allergies to iodine or povidone-iodine
• Avoid use in deep puncture wounds or serious burns

Pregnancy

Povidone is generally considered safe for use during pregnancy, but it is advisable to consult a healthcare professional before use.

Breast-feeding

Povidone is considered safe during breastfeeding, but it is recommended to consult a healthcare professional.

Storage

Store at room temperature, away from moisture and heat. Keep the container tightly closed.

Formulations

• Topical solution
• Ointment
• Surgical scrub
• Gauze impregnated with povidone-iodine

Mechanism of action

Molecular iodine is known to inhibit the induction and promotion of N-methyl-n-nitrosourea-induced mammary carcinogenesis, to regress 7,12-dimethylbenz(a)anthracene-induced breast tumors in rats.It has also been shown to have beneficial effects in fibrocystic human breast disease. An acute iodide excess (above the preexisting dietary intake) transiently decreases the production of thyroid hormones in the thyroid gland; this is referred to as the acute Wolff-Chaikoff effect. In normal people, this is followed by a return to normal levels of hormone synthesis, referred to as escape from the acute Wolff-Chaikoff effect, without a significant change in circulating hormone levels. Escape is thought to be the result of down regulation of the sodium-iodide symport (NIS), the iodide transporter in the thyroid gland, resulting in a decrease in the intrathyroidal iodine and the resumption of normal hormone synthesis. An acute or chronic excess of iodide can also decrease circulating T4 and T3 levels and induce a hypothyroid state in some people who have underlying thyroid disorders. These effects are the result of a failure to escape from the acute Wolff-Chaikoff effect. Most people who experience iodine-induced hypothyroidism recover when the excess iodine intake is discontinued.

Mechanism of action

The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis. After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(2-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms. Microbicidal; active against most obligate anaerobic bacteria and protozoa by undergoing intracellular chemical reduction via mechanisms unique to anaerobic metabolism. Reduced metronidazole, which is cytotoxic but short-lived, interacts with DNA to cause loss of helical structure, strand breakage, and resultant inhibition of nucleic acid synthesis and cell death. Metronidazole is bactericidal, amebicidal, and trichomonacidal in action. The exact mechanism of action of the drug has not been fully elucidated. Metronidazole is un-ionized at physiologic pH and is readily taken up by anaerobic organisms or cells. In susceptible organisms or cells, metronidazole is reduced by low-redox-potential electron transport proteins (e.g., nitroreductases such as ferredoxin) to unidentified polar product(s) which lack the nitro group. The reduction product(s) appears to be responsible for the cytotoxic and antimicrobial effects of the drug which include disruption of DNA and inhibition of nucleic acid synthesis. Metronidazole is equally effective against dividing and nondividing cells. In in vivo studies in rats given metronidazole in dosages of 2-4 mg/100 g of body weight, the drug reportedly inhibited the development of formalin-induced edema in the rat paw. In vitro in neutrophils, metronidazole has a dose-dependent inhibitory effect on generation of hydrogen peroxide and hydroxyl radicals, oxidants that may cause tissue injury at the site of inflammation. This antioxidant effect appears to be caused by a direct effect on neutrophil function and may contribute to the drug's anti-inflammatory effect in vivo. Results of in vitro studies using leukocytes obtained from patients with Crohn's disease indicate that exposing the cells to metronidazole concentrations of 10 or 50 mcg/mL improved both spontaneous and induced leukocyte migration in cells that previously exhibited reduced migration; the drug had no effect on leukocytes obtained from healthy adults or patients with Crohn's disease when the cells exhibited normal migration prior to exposure to the drug. This effect on leukocyte migration also was observed in vivo in adults with Crohn's disease who received a single 400-mg dose of metronidazole. It has been suggested that metronidazole may increase leukocyte migration by a direct effect on the leukocytes, possibly by causing the release of surface-bound immune complexes from the cell surface.

Pharmacodynamics

Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities. Metronidazole is an effective treatment for some anaerobic bacterial infections. Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action against facultative anaerobes or obligate aerobes. The nitro group reduction of metronidazole by anaerobic organisms is likely responsible for the drug's antimicrobial cytotoxic effects, causing DNA strand damage to microbes. A note on convulsions and neuropathy and carcinogenesis It is important to be aware of the risk of peripheral neuropathy and convulsions associated with metronidazole, especially at higher doses. If convulsions or numbness of an extremity occur, discontinue the drug immediately. Metronidazole has been found to be carcinogenic in mice and rats. The relevance to this effect in humans is unknown. It is advisable to only administer metronidazole when clinically necessary and only for its approved indications.