DRUGS & SUPPLEMENTS
1 INDICATIONS & USAGE
Ziana gel 1.2% / 0.025% is indicated for the topical treatment of acne vulgaris in patients 12 years or older.
Ziana gel 1.2% / 0.025% is a lincosamide antibiotic and retinoid combination product indicated for the topical treatment of acne vulgaris in patients 12 years or older. (1)
2 DOSAGE & ADMINISTRATION
At bedtime, squeeze a pea-sized amount of medication onto one fingertip, dot onto the chin, cheeks, nose, and forehead, then gently rub over the entire face. Ziana gel should be kept away from the eyes, the mouth, angles of the nose, and mucous membranes.
Ziana gel is not for oral, ophthalmic, or intravaginal use.
3 DOSAGE FORMS & STRENGTHS
Ziana gel, a combination of a lincosamide antibiotic and a retinoid, contains Ziana, USP 1.2% and tretinoin, USP 0.025%, formulated as a topical gel. Each gram of Ziana gel contains, as dispensed, 10 mg (1%) clindamycin as phosphate, USP, and 0.25 mg (0.025%) tretinoin, USP in an aqueous based gel. Ziana gel is available in 30 gram and 60 gram tubes.
Topical gel: Ziana, USP 1.2% and tretinoin, USP 0.025% gel in 30 and 60 gram tubes. (3)
Ziana gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic-associated colitis.
Ziana gel is contraindicated in patients with regional enteritis, ulcerative colitis, or history of antibiotic–associated colitis. (4)
5 WARNINGS AND PRECAUTIONS
Systemic absorption of clindamycin has been demonstrated following topical use of this product. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. When significant diarrhea occurs, Ziana gel should be discontinued.
Severe colitis has occurred following oral or parenteral administration of clindamycin with an onset of up to several weeks following cessation of therapy. Antiperistaltic agents such as opiates and diphenoxylate with atropine may prolong and/or worsen severe colitis. Severe colitis may result in death.
Studies indicate a toxin(s) produced by clostridia is one primary cause of antibiotic-associated colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps and may be associated with the passage of blood and mucus. Stool cultures for Clostridium difficile and stool assay for C. difficile toxin may be helpful diagnostically.
5.2 Ultraviolet Light and Environmental Exposure
Exposure to sunlight, including sunlamps, should be avoided during the use of Ziana gel, and patients with sunburn should be advised not to use the product until fully recovered because of heightened susceptibility to sunlight as a result of the use of tretinoin. Patients who may be required to have considerable sun exposure due to occupation and those with inherent sensitivity to the sun should exercise particular caution. Daily use of sunscreen products and protective apparel (e.g., a hat) are recommended. Weather extremes, such as wind or cold, also may be irritating to patients under treatment with Ziana gel.
6 ADVERSE REACTIONS
Observed local adverse reactions in patients treated with Ziana gel were skin erythema, scaling, itching, burning, and stinging. Other most commonly reported adverse events were nasopharyngitis, pharyngolaryngeal pain, dry skin, cough, and sinusitis. (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-432-8534 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Studies Experience
Because clinical trials are conducted under prescribed conditions, adverse reaction rates observed in the clinical trial may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse reactions that appear to be related to drug use for approximating rates.
The safety data presented in Table 1 (below) reflects exposure to Ziana gel in 1,853 patients with acne vulgaris. Patients were 12 years and older and were treated once daily for 12 weeks. Adverse reactions that were reported in ≥ 1% of patients treated with Ziana gel were compared to adverse reactions in patients treated with Ziana 1.2% in vehicle gel, tretinoin 0.025% in vehicle gel, and the vehicle gel alone:
Cutaneous safety and tolerance evaluations were conducted at each study visit in all of the clinical trials by assessment of erythema, scaling, itching, burning, and stinging:
At each study visit, application site reactions on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe), and the mean scores were calculated for each of the local skin reactions. In Studies 1 and 2, 1277 subjects enrolled with moderate to severe acne, 854 subjects treated with Ziana gel and 423 treated with vehicle. Analysis over the twelve week period demonstrated that cutaneous irritation scores for erythema, scaling, itching, burning, and stinging peaked at two weeks of therapy, and were slightly higher for the Ziana and tretinoin-treated group, decreasing thereafter.
One open-label 12-month safety study for Ziana gel showed a similar adverse reaction profile as seen in the 12-week studies. Eighteen out of 442 subjects (4%) reported gastrointestinal symptoms.
7 DRUG INTERACTIONS
7.1 Concomitant Topical Medication
Concomitant topical medication, medicated or abrasive soaps and cleansers, soaps and cosmetics that have a strong drying effect, and products with high concentrations of alcohol, astringents, spices or lime should be used with caution. When used with Ziana gel, there may be increased skin irritation.
Ziana gel should not be used in combination with erythromycin-containing products due to its clindamycin component. In vitro studies have shown antagonism between these two antimicrobials. The clinical significance of this in vitro antagonism is not known.
7.3 Neuromuscular Blocking Agents
Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other neuromuscular blocking agents. Therefore, Ziana gel should be used with caution in patients receiving such agents.
8 USE IN SPECIFIC POPULATIONS
Pregnancy Category C. There are no well-controlled trials in pregnant women treated with Ziana gel. Ziana gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Ziana gel was tested for maternal and developmental toxicity in New Zealand White Rabbits with topical doses of 60, 180 and 600 mg/kg/day. Ziana gel at 600 mg/kg/day was considered to be the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity following dermal administration of Ziana gel for two weeks prior to artificial insemination and continuing until gestation day 18, inclusive. For purposes of comparisons of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of Ziana gel applied daily to a 60 kg person.
Teratology (Segment II) studies using clindamycin were performed orally in rats (up to 600 mg/kg/day) and mice (up to 100 mg/kg/day) (583 and 49 times amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) or with subcutaneous doses of clindamycin up to 180 mg/kg/day (175 and 88 times the amount of clindamycin in the recommended clinical dose based on a body surface area comparison, respectively) revealed no evidence of teratogenicity.
In oral Segment III studies in rats with tretinoin, decreased survival of neonates and growth retardation were observed at doses in excess of 2 mg/kg/day (~ 78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).
With widespread use of any drug, a small number of birth defect reports associated temporally with the administration of the drug would be expected by chance alone. Thirty cases of temporally associated congenital malformations have been reported during two decades of clinical use of another formulation of topical tretinoin. Although no definite pattern of teratogenicity and no causal association have been established from these cases, 5 of the reports describe the rare birth defect category, holoprosencephaly (defects associated with incomplete midline development of the forebrain). The significance of these spontaneous reports in terms of risk to the fetus is not known.
Dermal tretinoin has been shown to be fetotoxic in rabbits when administered in doses 40 times the recommended human clinical dose based on a body surface area comparison. Oral tretinoin has been shown to be fetotoxic in rats when administered in doses 78 times the recommended clinical dose based on a body surface area comparison.
8.3 NURSING MOTHERS
It is not known whether clindamycin is excreted in human milk following use of Ziana gel. However, orally and parenterally administered clindamycin has been reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. It is not known whether tretinoin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Ziana gel is administered to a nursing woman.
8.4 PEDIATRIC USE
Safety and effectiveness of Ziana gel in pediatric patients under the age of 12 have not been established.
Clinical trials of Ziana gel included patients 12 to 17 years of age.
8.5 GERIATRIC USE
Clinical studies of Ziana gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.
Ziana gel 1.2% / 0.025%, is an antibiotic and retinoid combination gel product with two active ingredients. Ziana, USP is a water-soluble ester of the semi-synthetic antibiotic produced by a 7(S)-chloro-substitution of the 7(R)-hydroxyl group of the parent antibiotic lincomycin.
The chemical name for Ziana, USP is Methyl 7-chloro-6,7,8-trideoxy-6-(1-methyl-trans-4- propyl-L-2-pyrrolidinecarboxamido)-1-thio-L-threo-α-D-galacto-octopyranoside 2-(dihydrogen phosphate). The structural formula for Ziana, USP is represented below:
Molecular Formula: C18H34ClN2O8PS Molecular Weight: 504.97
The chemical name for tretinoin, USP is 3,7-Dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8- nonatetraenoic acid (all-trans form). The structural formula for tretinoin, USP is represented below:
Molecular Formula: C20H28O2 Molecular Weight: 300.44
Ziana gel 1.2% / 0.025% contains the following inactive ingredients: anhydrous citric acid, butylated hydroxytoluene, edetate disodium, hydroxyethyl cellulose, glycerin, methylparaben, polysorbate 80, propylparaben, purified water, tromethamine and xanthan gum.
12 CLINICAL PHARMACOLOGY
12.1 MECHANISMS OF ACTION
Although the exact mode of action of tretinoin is unknown, current evidence suggests that topical tretinoin decreases cohesiveness of follicular epithelial cells with decreased microcomedo formation. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells causing extrusion of the comedones.
In an open-label, multiple-dose study treating 12 subjects with moderate to severe acne, the percutaneous absorption of tretinoin following 14 consecutive daily applications of approximately 4 g of Ziana gel was minimal. Quantifiable tretinoin plasma concentrations ranged from 1.0 to 1.6 ng/mL, with unquantifiable plasma concentrations in 50% to 92% of subjects at any given timepoint following administration. The plasma concentrations of the key tretinoin metabolites, 13- cis -retinoic acid and 4-oxo-13-cis-retinoic acid, ranged from 1.0 to 1.4 ng/mL and from 1.6 to 6.5 ng/mL, respectively. Plasma concentrations for clindamycin generally did not exceed 3.5 ng/mL, with the exception of one subject whose plasma concentration reached 13.1 ng/mL.
Clindamycin binds to the 50S ribosomal subunits of susceptible bacteria and prevents elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing bacterial protein synthesis. Clindamycin has been shown to have in vitro activity against Propionibacterium acnes, an organism which has been associated with acne vulgaris; however, the clinical significance of this activity against P. acnes was not examined in clinical trials with Ziana gel. P acnes resistance to clindamycin has been documented. Resistance to clindamycin is often associated with resistance to erythromycin.
13 NONCLINICAL TOXICOLOGY
13.1 CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
Carcinogenicity, mutagenicity and impairment of fertility testing of Ziana gel have not been performed in any species.
The carcinogenicity of a 1% Ziana gel similar to Ziana gel was evaluated by daily application to mice for two years. The daily doses used in this study were approximately 13 and 72 times higher than the human dose of Ziana from Ziana gel, assuming complete absorption and based on a body surface area comparison. No significant increase in tumors was noted in the treated animals. For purposes of comparisons of the animal exposure to human exposure, the recommended human topical clinical dose is defined as 1 g of Ziana gel applied daily to a 60 kg person.
Fertility (Segment 1) studies in rats treated orally with up to 300 mg/kg/day of clindamycin (approximately 290 times the amount of clindamycin delivered from the recommended clinical dose for Ziana gel, based on a body surface area comparison) revealed no effects on fertility or mating ability.
In two independent studies with long-term topical application of tretinoin in mice, carcinogenicity was not observed. In both studies, tretinoin was administered topically (0.025% or 0.1%) three times per week for up to two years. No carcinogenicity was observed with maximum effects of dermal amyloidosis in the basal layer of the skin.
Tretinoin has been shown to enhance photoco-carcinogenicity in properly performed specific studies, employing concurrent or intercurrent exposure to the drug and UV radiation. The contribution of clindamycin to that effect is unknown. Although the significance of these studies to humans is not clear, patients should minimize exposure to sun.
The genotoxic potential of tretinoin was evaluated in an in vitro Ames Salmonella reversion test and an in vitro chromosomal aberration assay in Chinese hamster ovary cells. Both tests were negative.
In oral Segment 1 studies in rats treated with tretinoin, the no-observed-effect-level was 2 mg/kg/day (~78 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison).
14 CLINICAL STUDIES
The safety and efficacy of once daily use of Ziana gel for treatment of acne vulgaris were assessed in three 12-week prospective, multi-center, randomized, blinded studies in patients 12 years and older. Studies 1 and 2 were of identical design, and compared Ziana gel to clindamycin in the vehicle gel, tretinoin in the vehicle gel, and the vehicle gel alone. Patients with mild, moderate, or severe acne were enrolled in the studies. The co-primary efficacy variables were:
(1) Mean percent change from baseline at Week 12 in
(2) Percent of subjects who cleared or almost cleared at Week 12 as judged by an Evaluator’s Global Severity (EGS) score.
The EGS scoring scale used in all of the clinical trials for Ziana gel is as follows:
In Study 1, a total of 1,252 patients were enrolled, and in Study 2, a total of 1,288 patients were enrolled. The combined results are presented in Table 3.
In Study 3, Ziana gel was compared to clindamycin gel in a total of 2,010 patients with moderate or severe acne vulgaris. As with Studies 1 and 2, the co-primary endpoints were mean percent reduction in lesion counts (inflammatory, non-inflammatory and total) and the Evaluator’s Global Severity score. In Study 3, success on the EGS score was assessed by the percentage of subjects who had at least 2 grades of improvement from Baseline to Week 12.
16 HOW SUPPLIED/STORAGE AND HANDLING
Ziana gel 1.2% / 0.025% is supplied as follows:
30 gram tube NDC 0472-1790-30
60 gram tube NDC 0472-1790-60
Storage and Handling
Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F). Protect from light. Protect from freezing. Keep away from heat.
Keep tube tightly closed.
Keep out of the reach of children.
17 PATIENT COUNSELING INFORMATION
17.1 Instructions for Use
17.2 Skin Irritation
Ziana gel may cause irritation such as erythema, scaling, itching, burning, or stinging.
In the event a patient treated with Ziana gel experiences severe diarrhea or gastrointestinal discomfort, Ziana gel should be discontinued and a physician should be contacted.
G&W laboratories, Inc.
111 Coolidge Street
South Plainfield, NJ 07080 USA
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Revised – September 2015
I600-6210/11 GW 7047
17.4 FDA-Approved Patient Labeling
Ziana (klin-da-MYE-sin FOS-fate and TRET-i-noyn)
Gel 1.2% / 0.025%
IMPORTANT: Not for mouth, eye, or vaginal use.
Read the Patient Information that comes with Ziana gel before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your acne or treatment.
What is Ziana gel?
Ziana gel is an antibiotic and retinoid combination medicine used for the skin treatment of acne in patients 12 years and older.
Who should not use Ziana gel?
Do not use Ziana gel if you:
Tell your doctor:
How should I use Ziana gel?
Use Ziana gel exactly as prescribed. It may take some time for you to see improvement of your acne with Ziana gel. Your doctor will tell you how long to use Ziana gel.
In the morning:
If your face becomes sunburned, stop Ziana gel until your skin has healed.
What are possible side effects with Ziana gel?
Talk to your doctor about any side effect that bothers you or that does not go away.
These are not all the side effects with Ziana gel. Ask your doctor or pharmacist for more information.
How should I store Ziana gel?
General information about Ziana gel
Medicines are sometimes prescribed for purposes other than those listed in patient information leaflet. Do not use Ziana gel for a condition for which it was not prescribed. Do not give Ziana gel to other people, even if they have the same symptoms you have. It may harm them.
This leaflet summarizes the most important information about Ziana gel. If you would like more information, talk with your doctor. You can also ask your pharmacist or doctor for information about Ziana gel that is written for healthcare professionals.
If you have questions about Ziana gel you can also call Actavis at 1-800-432-8534.
What are the ingredients in Ziana gel?
Active Ingredients: Ziana, USP 1.2% and tretinoin, USP 0.025%
Inactive Ingredients: anhydrous citric acid, butylated hydroxytoluene, edetate disodium, hydroxyethyl cellulose, glycerin, methylparaben, polysorbate 80, propylparaben, purified water, tromethamine and xanthan gum.
G&W laboratories, Inc.
111 Coolidge Street
South Plainfield, NJ 07080 USA
Actavis Pharma, Inc.
Parsippany, NJ 07054 USA
Revised – September 2015
I600-6210/11 GW 7047
Ziana pharmaceutical active ingredients containing related brand and generic drugs:
Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.
Ziana available forms, composition, doses:
Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.
Ziana destination | category:
Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.
Ziana Anatomical Therapeutic Chemical codes:
A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.
Ziana pharmaceutical companies:
Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.
Frequently asked QuestionsCan i drive or operate heavy machine after consuming Ziana?
Depending on the reaction of the Ziana after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Ziana not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.Is Ziana addictive or habit forming?
Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
Reviewsdrugs.com conducted a study on Ziana, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Ziana consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.
Visitor reported usefulNo survey data has been collected yet
Visitor reported side effectsNo survey data has been collected yet
Visitor reported price estimatesNo survey data has been collected yet
Visitor reported frequency of useNo survey data has been collected yet
Visitor reported dosesNo survey data has been collected yet
One visitor reported time for resultsWhat is the time duration Ziana drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed > 3 month to notice the result from using Ziana drug. The time needed to show improvement in health condition after using the medicine Ziana need not be same for all the users. It varies based on other factors.
Visitor reported administrationNo survey data has been collected yet
Visitor reported ageNo survey data has been collected yet
The information was verified by Dr. Arunabha Ray, MD Pharmacology