Evris

Evris Uses, Dosage, Side Effects, Food Interaction and all others data.

Clindamycin is a lincosamide antibiotic used in the treatment of infections caused by susceptible microorganisms. Clindamycin is a semisynthetic antibiotic derived from lincomycin. It has antiacne and antibacterial activity. It binds with the 50s subunit of the bacterial ribosome and inhibits the early stage of protein synthesis. It is highly potent against gram positive and anaerobic bacteria.

Microbiology: Aerobic gram-positive cocci, including: Staphylococcus aureus, Staphylococcus epidermidis (penicillinase and non-penicillinase producing strains), Streptococci, Pneumococci. Anaerobic gram-negative bacilli, including: Bacteroides species, Fusobacterium species. Anaerobic gram-positive non-spore forming bacilli, including: Propionibacterium species, Eubacterium species, Actinomyces species. Anaerobic and microaerophilic gram-positive cocci, including: Peptococcus species, Peptostreptococcus species, Microaerophilic streptococci, C. perfringes

Clindamycin exerts its bacteriostatic effect via inhibition of microbial protein synthesis. Clindamycin has a relatively short Tmax and half-life necessitating administration every six hours to ensure adequate antibiotic concentrations.

Clostridium difficile associated diarrhea (CDAD) has been observed in patients using clindamycin, ranging in severity from mild diarrhea to fatal colitis and occasionally occurring over two months following cessation of antibiotic therapy. Overgrowth of C. difficile resulting from antibiotic use, along with its production of A and B toxins, contributes to morbidity and mortality in these patients. Because of the associated risks, clindamycin should be reserved for serious infections for which the use of less toxic antimicrobial agents are inappropriate.

Clindamycin is active against a number of gram-positive aerobic bacteria, as well as both gram-positive and gram-negative anaerobes. Resistance to clindamycin may develop, and is generally the result of base modification within the 23S ribosomal RNA. Cross-resistance between clindamycin and lincomycin is complete, and may also occur between clindamycin and macrolide antibiotics (e.g. erythromycin) due to similarities in their binding sites.

Metronidazole, a nitroimidazole has an extremely broad spectrum antiprotozoal and antimicrobial activities, with high activity against anaerobic bacteria and protozoa. Metronidazole is usually completely and rapidly absorbed after oral administration. The half-life in plasma is about 8 hours. About 10% of the drug is bound to plasma proteins. Metronidazole penetrates well into body tissues and fluids. The liver is the main site of metabolism. Both unchanged Metronidazole and metabolites are excreted in various proportions in the urine after oral administration.

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.

Miconazole topical cream is a broad-spectrum antimycotic which offers a high antifungal activity against dermatophytes, yeasts and other phyco-Asco and Adelomycetes, with a potent antibacterial activity against Gram-positive bacilli and cocci. Miconazole topical cream proved to be markedly effective in secondary infected mycoses, which under other treatments were resistant or reappeared. Miconazole topical cream does not stain skin or clothes.

The active ingredient, Miconazole, is a synthetic imidazole anti-fungal agent with a broad spectrum of activity against pathogenic fungi (including yeast and dermatophytes) and gram-positive bacteria (Staphylococcus and Streptococcus spp). It may act by interfering with the permeability of the fungal cell membranes. When administered orally, Miconazole is incompletely absorbed from the gastrointestinal tract, peak plasma levels of about 1 µg per ml have been achieved after a dose of 1 gm per day. Miconazole is inactivated in the body and 10-20% of an oral dose is excreted in the urine, mainly as metabolites, within 6 days. About 50% of an oral dose may be excreted unchanged in the faeces.

Miconazole is an azole antifungal that functions primarily through inhibition of a specific demethylase within the CYP450 complex. As miconazole is typically applied topically and is minimally absorbed into the systemic circulation following application, the majority of patient reactions are limited to hypersensitivity and cases of anaphylaxis. Patients using intravaginal miconazole products are advised not to rely on contraceptives to prevent pregnancy and sexually transmitted infections, as well as not to use tampons concurrently.

Evris
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Evris
Generic	Clindamycin + Metronidazole + Miconazole
Type	Capsule
Therapeutic Class
Manufacturer	Auriga Labs
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Clindacin lotion is used for the treatment of acne vulgaris.

Other uses of topical Clindamycin lotion are:

• Skin infections such as erythrasma caused by Corynebacterium minutissimum; rosacea, periorificial dermatitis, folliculitis, stasis, chronic lymphaedema and familial pemphigus.

• Dermal ulcers.

Metronidazole is used for:

All forms of amoebiasis (intestinal and extra-intestinal disease including liver abscess and that of symptomless cyst passers)
Trichomoniasis
Giardiasis
Bacterial vaginosis
Acute ulcerative gingivitis
Anaerobic infections including septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis etc.
Anaerobically-infected leg ulcers and pressure sores
Acute dental infections (e.g. acute pericoronitis and acute apical infections)
Surgical prophylaxis (prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci
Chronic symptomatic peptic ulcer disease (as an agent of triple therapy to eradicate H. pylori-the most important aetiological factor of peptic ulcer)

Miconazole Topical Cream has an antibacterial effect on Gram-positive bacteria, it may be used in mycoses secondarily infected with such bacteria. Skin and nail infections due to dermatophytes, yeasts and other fungi such as: Tinea capitis, corporis, manuum, pedis, barbae, cruris, unguium or onychomycosis. Pityriasis versicolor, candidiasis of skin and nails, stomatitis angularis, otitis externa.

Miconazole Oral treatment and prevention of fungal infections of the oropharynx and gastrointestinal tract, and of super infections due to Gram-positive bacteria.

How Evris works

Clindamycin inhibits bacterial protein synthesis by binding to 23S RNA of the 50S subunit of the bacterial ribosome. It impedes both the assembly of the ribosome and the translation process. The molecular mechanism through which this occurs is thought to be due to clindamycin's three-dimensional structure, which closely resembles the 3'-ends of L-Pro-Met-tRNA and deacylated-tRNA during the peptide elongation cycle - in acting as a structural analog of these tRNA molecules, clindamycin impairs peptide chain initiation and may stimulate dissociation of peptidyl-tRNA from bacterial ribosomes.

The mechanism through which topical clindamycin treats acne vulgaris is unclear, but may be related to its activity against Propionibacterium acnes, a bacteria that has been associated with acne.

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.

Miconazole is an azole antifungal used to treat a variety of conditions, including those caused by Candida overgrowth. Unique among the azoles, miconazole is thought to act through three main mechanisms. The primary mechanism of action is through inhibition of the CYP450 14α-lanosterol demethylase enzyme, which results in altered ergosterol production and impaired cell membrane composition and permeability, which in turn leads to cation, phosphate, and low molecular weight protein leakage.

In addition, miconazole inhibits fungal peroxidase and catalase while not affecting NADH oxidase activity, leading to increased production of reactive oxygen species (ROS). Increased intracellular ROS leads to downstream pleiotropic effects and eventual apoptosis.

Lastly, likely as a result of lanosterol demethylation inhibition, miconazole causes a rise in intracellular levels of farnesol. This molecule participates in quorum sensing in Candida, preventing the transition from yeast to mycelial forms and thereby the formation of biofilms, which are more resistant to antibiotics. In addition, farnesol is an inhibitor of drug efflux ABC transporters, namely Candida CaCdr1p and CaCdr2p, which may additionally contribute to increased effectiveness of azole drugs.

Dosage

Evris dosage

At first wash the face or affected area gently with warm water or soap.

Clindacin lotion: When the skin is completely dried (about 30 minutes later) apply a thin film of Clindacin lotion to the entire affected area twice daily. Applied area should not be washed within 3 hours. Noticeable improvement is usually seen after about 6 weeks . However, 8 to 12 weeks of treatment may be required for maximum benefit. Eye, lip or nose contact should be avoided while applying Clindacin lotion.

Tablet and Suspension:

Amoebic dysentery: Duration 5-10 Days;

For Tablet: Adults- 750 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 800 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 200 mg q.i.d. (1-3 years) 200 mg t.i.d.

Asymptomatic amoebiasis: Duration 5-10 Days;

For Tablet: Adults- 500-750 mg t.i.d. Children- (7-10 years) 250-500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 500-800 mg t.i.d. Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Hepatic extraintestinal amoebiasis : Duration 5-10 Days (or 2days);

For Tablet: Adults- 500-750 mg t.i.d.; Children- (7-10 years) 250-500 mg t.i.d.; (3-7 years) 250 mg q.i.d.; (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 500-800 mg t.i.d.; Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Giardiasis: Duration 3 Days;

For Tablet: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 750 mg once daily; (1-3 years) 500 mg once daily.
For suspension: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 800 mg once daily; (1-3 years) 500 mg once daily.

Trichomoniasis: Duration 7 Days;

For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Trichomoniasis: Duration 1 Day;

For Tablet: Adults- 2 g single dose;
For Suspension: Adults- 2 g single dose;

Vincent's infection (Ulceration of mucous membrane of respiratory tract & mouth): Duration 3 Days;

For Tablet: Adults- 250 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Periodontal infection: Duration 3 Days;

For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Severe dental infection: Duration 3 Days;

For Tablet: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Anaerobic infection: Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.
For Suspension: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.

Postoperative anaerobic infection (specially in operation abdominal or gynecological surgery): Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.
For Suspension: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.

Bacterial vaginitis: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d.
For Suspension: Adults- 500 mg b.i.d.

Leg ulcers: Duration 1 Day;

For Tablet: Adults- 2 g as a single dose
For Suspension: Adults- 2 g as a single dose

Pressure sores: Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d.
For Suspension: Adults- 500 mg t.i.d.

H. pylori infection: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d
For Suspension: Adults-500 mg b.i.d

Antibiotic Associated Pseudomembranus colitis: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d
For Suspension: Adults- 500 mg b.i.d

Vaginal Gel:

The recommended dose is one applicator full of Metronidazole GEL (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole GEL should be administered at bedtime.

Suppository:

Anaerobic infections:

Adult: 1 g 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
Child: 5-10 yr 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

Prophylaxis of postoperative anaerobic bacterial infections:

Adult: 1 g 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
Child: 5-10 yr 500 mg 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

IV Infusion:

Metronidazole injection should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible. Treatment for 7 days should be satisfactory for most patients, but the physician might decide to prolong treatment.

For bacterial infections: Adults: 500 mg (100 ml) 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly.
For treatment before and during surgery: Adults: 500 mg (100 ml) shortly before operation, repeated 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly

For oral administration: Dosage is based on 15 mg/kg/day.

Adults: 1-2 tea-spoonfuls of gel four times daily
Children aged 6 years and over: One tea-spoonful of gel four times daily
Children aged 2-6 years: One tea-spoonful of gel twice daily
Infants under 2 years: Half tea-spoonful of gel twice daily.

For localised lesions of the mouth:

A small amount of gel may be applied directly to the affected area with a clean finger. For topical treatment of the oropharynx, the gel should be kept in the mouth for as long as possible. Treatment should be continued for up to 2 days after the symptoms have cleared.

For oral candidasis, dental prostheses:

Should be removed at night and brushed with the gel.

The dosage is same for all the ages.

For skin infections: Apply some cream to the lesions twice daily and rub it well with finger until it has fully penetrated the skin. All lesions usually disappear after 2 to 5 weeks. Prolong treatment for some 10 days to prevent relapse.

For nail infections: Clip infected nail as shortly as possible. Apply some cream once daily to the infected nail and rub with your finger, cover nail with a non-perforated occlusive plastic bandage.

Also after loosening of the infected nail (from 2-3 weeks onwards) uniterrupted treatment should be continued until the growth of a new nail has set in and definite cure can be observed (usually after seven months or more).

Clindamycin Lotion 1%: Clean the face or affected area gently with warm water or soap as recommended by the physician. After the skin is dried, apply a thin film of lotion to the affected areas twice daily, in the morning and in the evening.

Do not wash within three hours after using lotion. The treatment period is usually 6 weeks or as advised by the physician.

However, 8 to 12 weeks of treatment may be required for maximum benefit.

Clindamycin 2% Vaginal preparation: One applicator full (approximately 5 gm) intravaginally at bedtime for 7 consecutive days. In patients in whom a shorter treatment course is desirable, a 3 day regimen has been shown to be effective.

Side Effects

Side effects are usually rare. Possible side-effects may includes skin rash, itching, oily skin, dryness, erythema, burning, change in skin color, diarrhea, colitis, GI disturbance etc.

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

Topical application of Miconazole Nitrate has almost no side effect.

For oral gel: Occasionally, nausea and vomiting have been reported, and with long term treatment, diarrhoea. In rare instances, allergic reactions have been reported. There are isolated reports of hepatitis, for which the causal relationship with Miconazole has not been established.

Toxicity

The oral LD₅₀ in mice and rats is 2540 mg/kg and 2190 mg/kg, respectively.

While no cases of overdose have been reported, symptoms are expected to be consistent with the adverse effect profile of clindamycin and may therefore include abdominal pain, nausea, vomiting, and diarrhea. During clinical trials, one 3-year-old child was given a dose of 100 mg/kg daily for 5 days and showed only mild abdominal pain and diarrhea. Activated charcoal may be of value to remove unabsorbed drug, but hemodialysis and peritoneal dialysis are ineffective. General supportive measures are recommended in cases of clindamycin overdose.

LD50 information

The oral LD50 of metronidazole in rats is 5000 mg/kg

Overdose information

Adverse effects that may be exaggerated with an overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric discomfort, and vertigo, in addition to neutropenia. There is no specific antidote for metronidazole overdose. Symptomatic and supportive treatment should be employed in addition to the administration of activated charcoal to remove the unabsorbed drug from the gastrointestinal tract. In addition to the above measures, contact the local poison control center for updated information on the management of a metronidazole overdose.

Miconazole overdose has not been reported. Patients experiencing an overdose are at an increased risk of severe adverse effects such as headache, skin irritation, diarrhea, nausea, vomiting, abdominal pain, and dysgeusia. Symptomatic and supportive measures are recommended.

Miconazole has an oral LD₅₀ of 500 mg/kg in rats.

Precaution

Clindacin lotion is not for oral, ophthalmic, or Intravaginal use.

Avoid exposure to sunlight and sunlamps. Wear sunscreen daily.

Metronidazole should not be used in patients with blood dyscrasia. It is suggested that it should not be given in the first three months of pregnancy. When given in conjunction with alcohol, Metronidazole may provoke a disulphiram like effect.

If the concomitant use of Miconazole and anticoagulants is envisaged, the anticoagulant effect should be carefully monitored and titrated. It is advisable to monitor Miconazole and phenytoin levels, if they are used concomitantly. Particularly in infants and young children, caution is required to ensure that the gel does not obstruct the throat. Hence, the gel should not be applied to the back of the throat and the full dose should be divided into smaller portions. Observe the patient for possible choking.

Interaction

Clindamycin enhance the action of other neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents. Antagonism has been demonstrated between clindamycin and erythromycin in vitro. Because of possible clinical significance, these two drugs should not be administered concurrently.

Metronidazole interacts with warfarin, nicoumalone, phenytoin, phenobarbitone, fluorouracil, disulfiram, lithium, cimetidine etc.

Miconazole can inhibit the metabolism of drugs metabolised by the Cytochrome P450-3A and -2C9 families. This can result in an increase or prolongation of their effects, including side effects. Miconazole Oral Gel should not be used during treatment with the following drugs: terfenadine, astemizole,mizolastine, cisapride, triazolam, oral midazolam, dofetilide, quinidine, pimozide, CYP3A4 metabolised HMG-CoA reductase inhibitors such as simvastatin and lovastatin.

Volume of Distribution

Clindamycin is widely distributed in the body, including into bone, but does not distribute into cerebrospinal fluid. The volume of distribution has been variably estimated between 43-74 L.

Metronidazole is widely distributed throughout the body and various body fluids. They include the bile, saliva, breastmilk, cerebrospinal fluid, and the placenta. Steady-state volume distribution of metronidazole in adults ranges from 0.51 to 1.1 L/kg. It attains 60 to 100% of plasma concentrations in various tissues, such as the central nervous system, however, is not measured in high concentrations in the placental tissue.

A 1200 mg miconazole vaginal suppository resulted in a calculated apparent volume of distribution of 95 546 L while a 100 mg vaginal cream yielded an apparent volume of distribution of 10 911L.

Elimination Route

Oral bioavailability is nearly complete, at approximately 90%, and peak serum concentrations (C_max) of, on average, 2.50 µg/mL are reached at 0.75 hours (T_max). The AUC following an orally administered dose of 300mg was found to be approximately 11 µg•hr/mL. Systemic exposure from the administration of vaginal suppository formulations is 40-fold to 50-fold lower than that observed following parenteral administration and the C_max observed following administration of vaginal cream formulations was 0.1% of that observed following parenteral administration.

After the intravenous infusion of a 1.5g dose, peak concentration was reached within 1 hour and was peak level of 30-40 mg/L. When a multiple-dose regimen of 500mg three times a day administered intravenously, steady-state concentrations were achieved within about 3 days and peak concentration was measured at 26 mg/L. When administered orally in the tablet form, metronidazole is absorbed entirely absorbed, showing a bioavailability of greater than 90%. One resource indicates that Cmax after a single oral dose of 500mg metronidazole ranges from 8 to 13 mg/L, with a Tmax of 25 minutes to 4 hours. The AUC following a single 500mg oral dose of metronidazole was 122 ± 10.3 mg/L • h.

A note on the absorption of topical preparations

Insignificant percutaneous absorption of metronidazole occurs after the application of 1% metronidazole cream topically. Healthy volunteers applied one 100 mg dose of 14C-labelled metronidazole 2% cream to unbroken skin. After 12 hours, metronidazole was not detected in the plasma. Approximately 0.1% to 1% of the administered metronidazole was measured in the urine and feces.

Miconazole given to healthy volunteers as a single 50 mg oral tablet produced a mean C_max of 15.1 ± 16.2 mcg/mL, a mean AUC_0-24 of 55.2 ± 35.1 mcg*h/mL, and a median T_max of 7 hours (range 2.0-24.1). In these patients measurable plasma concentrations ranged from 0.5 to 0.83 mcg/mL.

Topical miconazole is absorbed poorly into the systemic circulation. In pediatric patients aged 1-21 months given multiple topical applications of miconazole ointment for seven days, the plasma miconazole concentration was less than 0.5 ng/mL in 88% of the patients, with the remaining patients having a concentration of 0.57 and 0.58 ng/mL, respectively. Similarly, patients. administered with a vaginal 1200 mg ovule had a mean C_max of 10.71 ng/mL, mean T_max of 18.4 hours, and mean AUC_0-96 of 477.3 ng*h/mL.

Half Life

The elimination half-life of clindamycin is about 3 hours in adults and 2.5 hours in children. Half-life is increased to approximately 4 hours in the elderly.

The elimination half-life of metronidazole is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects. Another resource indicates that the elimination half-life for metronidazole ranges from 6 to 10 hours.

Miconazole has a terminal half-life of 24 hours.

Clearance

The plasma clearance of clindamycin is estimated to be 12.3-17.4 L/h, and is reduced in patients with cirrhosis and altered in those with anemia.

Dose adjustments may be required in patients with hepatic impairment, as clearance is impaired in these patients. The clearance of metronidazole in the kidneys is estimated at 10 mL/min/1.73 m2. The total clearance from serum is about 2.1 to 6.4 L/h/kg.

Elimination Route

Approximately 10% of clindamycin bioactivity is excreted in the urine and 3.6% in the feces, with the remainder excreted as inactive metabolites.

Metronidazole and metabolites are 60 to 80% eliminated in the urine, and 6-15% excreted in the feces.

Miconazole is excreted through both urine and feces; less than 1% of unchanged miconazole is recovered in urine.

Pregnancy & Breastfeeding use

Pregnancy: There is no adequate data for safe use in pregnancy. Animal studies showed no adverse effects on the fetus.

Lactation: It is not known that whether Clindamycin is excreted through breast milk following topical administration. However, Clindacin lotion can be used during lactation with caution.

Not recommended during first & later trimesters. Breast feeding should be delayed until 48 hours after discontinuing metronidazole in the mother.

In animals, Miconazole has shown no teratogenic effects but is foetotoxic at high oral doses. The significance of this to man is unknown. However, as with other imidazoles, Miconazole Oral Gel should be avoided in pregnant women if possible. The potential hazards should be balanced against the possible benefits. It is not known whether Miconazole is excreted in human milk. Caution should be exercised when prescribing Miconazole Oral Gel to nursing mothers.

Only small amounts of Miconazole cream are absorbed following local administration. However as with other imidazoles, Miconazole nitrate should be used with caution during pregnancy.

Contraindication

Clindamycin is contraindicated in patients previously found to be sensitive to clindamycin or any of the ingredients of this medicine.

Metronidazole is contraindicated in patients with prior history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.

Miconazole is contraindicated in patients with known hypersensitivity to the active drug.

Acute Overdose

Overdosage with orally administered clindamycin has been rare. Adverse reactions similar to those seen with normal doses can be expected, however, unexpected reactions could occur. Haemodialysis and peritoneal dialysis are not effective in removing clindamycin from the serum. Overdosage should be treated with simple gastric lavage. No specific antidote is known.

In general, Miconazole is not highly toxic. In the event of accidental overdosage, vomiting and diarrhoea may occur.