Pharmacology: Pharmacodynamics: Although Clinott-P is inactive in vitro, rapid in vivo hydrolysis converts this compound to the antibacterially active Clinott-P. Clinott-P has been shown to have in vitro activity against isolates of Propionibacterium acnes cultures tested [minimum inhibitory concentration (MICs) 0.4 mcg/mL]. This may account for its usefulness in acne. Free fatty acids on the skin surface have been decreased from approximately 14-2% following application of Clinott-P.
Cross-resistance has been demonstrated between Clinott-P and lincomycin. Antagonism has been demonstrated between Clinott-P and erythromycin.
Clinott-P has no fungicidal activity.
The in vitro inactive Clinott-P is hydrolysed by phosphatases of the skin to active Clinott-P base.
Pharmacokinetics: Following multiple topical applications of Clinott-P at a concentration equivalent to Clinott-P 10 mg/mL in an isopropyl alcohol and water solution, very low levels of Clinott-P are present in the serum (0-3 ng/mL) and <0.2% of the dose is recovered in urine as Clinott-P.
Following multiple topical applications of Clinott-P at a concentration equivalent to Clinott-P 10 mg/g in the gel formulation, 0.053% (morning) and 0.07% (evening) of the administered dose was recovered in the urine as Clinott-P. Average absolute bioavailability was 1.6% and 2.2% after morning and evening doses, respectively.
Clinott-P activity has been demonstrated in comedones from acne patients. The mean concentration of antibiotic activity in extracted comedones after application of Clinott-P (10 mg/mL) in an isopropyl alcohol and water solution for 4 weeks was 597 mcg/g of comedonal material (range 0-1,490 mcg/g).
Geriatric Use: Clinical studies for topical Clinott-P did not include sufficient numbers of subjects ≥65 years to determine whether they respond differently from younger subjects.
Toxicology: Preclinical Safety Data: Carcinogenesis: Long-term studies in animals have not been performed with Clinott-P to evaluate carcinogenic potential.
Mutagenesis: Genotoxicity tests performed included a rat micronucleus test and an Ames Salmonella reversion test. Both tests were negative.
Impairment of Fertility: Fertility studies in rats treated orally with up to 300 mg/kg/day (approximately 1.1 times the highest recommended adult human dose based on mg/m2) revealed no effects on fertility or mating ability.
In oral embryofetal development studies in rats and SC embryofetal development studies in rats and rabbits, no developmental toxicity was observed except at doses that produced maternal toxicity.
Before applying Clinott-P, thoroughly wash the affected areas with warm water and soap, rinse well, and pat dry.
When applying the medicine, use enough to cover the affected area lightly. You should apply the medicine to the whole area usually affected by acne, not just to the pimples themselves. This will help keep new pimples from breaking out.
You should avoid washing the acne-affected areas too often. This may dry your skin and make your acne worse. Washing with a mild, bland soap 2 or 3 times a day should be enough, unless you have oily skin. If you have any questions about this, check with your doctor.
Topical Clinott-P will not cure your acne. However, to help keep your acne under control, keep using Clinott-P for the full time of treatment, even if your symptoms begin to clear up after a few days. You may have to continue using Clinott-P every day for months or even longer in some cases. If you stop using Clinott-P too soon, your symptoms may return. It is important that you do not miss any doses.
For patients using the topical foam form of Clinott-P:
For patients using the topical solution form of Clinott-P:
For patients using the topical suspension form of Clinott-P:
The dose of Clinott-P will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Clinott-P. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
If you miss a dose of Clinott-P, apply it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule.
Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
Keep out of the reach of children.
Do not keep outdated medicine or medicine no longer needed.
Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.
Take this medicine with a full glass of water to keep it from irritating your throat.
Measure liquid medicine with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
Take this medicine for the full prescribed length of time. Your symptoms may improve before the infection is completely cleared. Skipping doses may also increase your risk of further infection that is resistant to antibiotics. Clinott-P will not treat a viral infection such as the common cold or flu.
To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.
If you need surgery, tell the surgeon ahead of time that you are using Clinott-P. You may need to stop using the medicine for a short time.
Store at room temperature away from moisture and heat. Do not store Clinott-P liquid in the refrigerator.
Mechanism of action in acne vulgaris is unknown.
Pharmacodynamics of Clinott-P Foam is unknown.
In an open label, parallel group study in 24 subjects with acne vulgaris, 12 subjects (3 male and 9 female) applied 4 grams of Clinott-P Foam once-daily for five days, and 12 subjects (7 male and 5 female) applied 4 grams of a Clinott-P gel, 1%, once daily for five days. On Day 5, the mean Cmax and AUC(0-12) were 23% and 9% lower, respectively, for Clinott-P Foam than for the Clinott-P gel, 1%.
Following multiple applications of Clinott-P Foam, less than 0.024% of the total dose was excreted unchanged in the urine over 12 hours on Day 5.
No microbiology studies were conducted in the clinical trials with this product.
Clinott-P binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clinott-P has been shown to have in vitro activity against Propionibacterium acnes (P. acnes), an organism that has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical studies with Clinott-P Foam. P. acnes resistance to Clinott-P has been documented.
The treatment of acne with antimicrobials is associated with the development of antimicrobial resistance in P. acnes as well as other bacteria (e.g. Staphylococcus aureus, Streptococcus pyogenes). The use of Clinott-P may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing.
Resistance to Clinott-P is often associated with resistance to erythromycin.
In one multicenter, randomized, double-blind, vehicle-controlled clinical trial, subjects with mild to moderate acne vulgaris used Clinott-P Foam or the vehicle Foam once daily for twelve weeks. Treatment response, defined as the proportion of subjects clear or almost clear, based on the Investigator Static Global Assessment (ISGA), and the mean percent reductions in lesion counts at the end of treatment in this study are shown in Table 2.
Table 2: Efficacy Results at Week 12
|Efficacy Parameters||Clinott-P Foam |
|Vehicle Foam |
|Treatment response (ISGA)||31%||18%*|
|Percent reduction in lesion counts|
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Information checked by Dr. Sachin Kumar, MD Pharmacology