Us product labeling @std template for plr
HIGHLIGHTS OF PRESCRIBING INFORMATION
----------------------- WARNINGS AND PRECAUTIONS ----------------
These highlights do not include all the information needed to use
• Colitis: Clindamycin can cause severe colitis, which may result in death.
VELTIN Gel safely and effectively. See full prescribing information for
Diarrhea, bloody diarrhea, and colitis (including pseudomembranous
colitis) have been reported with the use of clindamycin. VELTIN Gel
should be discontinued if significant diarrhea occurs. (5.1)
VELTIN® (clindamycin phosphate and tretinoin) Gel 1.2%/0.025%
Ultraviolet Light and Environmental Exposure: Avoid exposure to
For topical use only
sunlight, sunlamps, and weather extremes. Wear sunscreen daily. (5.2)
Initial U.S. Approval: 2006
------------------------------ ADVERSE REACTIONS -----------------------
--------------------------- RECENT MAJOR CHANGES --------------------
Observed local treatment-related adverse reactions (≥ 1%) in clinical
Normal text - times new roman 8 (section id)
studies with VELTIN Gel were application site reactions, including
dryness, irritation, exfoliation, erythema, pruritus, and dermatitis.
----------------------------INDICATIONS AND USAGE ---------------------
• VELTIN Gel is a lincosamide antibiotic and retinoid combination product
indicated for the topical treatment of acne vulgaris in patients 12 years
To report SUSPECTED ADVERSE REACTIONS, contact Stiefel
Laboratories, Inc. at 1-888-784-3335 or FDA at 1-800-FDA-1088 or
----------------------- DOSAGE AND ADMINISTRATION ----------------
Apply a pea size amount once daily in the evening lightly covering the
------------------------------- DRUG INTERACTIONS ------------------------
entire affected area. Avoid the eyes, lips, and mucous membranes. (2)
VELTIN Gel should not be used in combination with erythromycin-
Not for oral, ophthalmic, or intravaginal use. (2)
containing products because of its clindamycin component. (7.1)
----------------------- USE IN SPECIFIC POPULATIONS ----------------
--------------------- DOSAGE FORMS AND STRENGTHS --------------
Pediatric Use: The efficacy and safety have not been established in
Topical gel: clindamycin phosphate 1.2% and tretinoin 0.025% in 30 gram
pediatric patients below the age of 12 years. (8.4)
------------------------------- CONTRAINDICATIONS ------------------------
See 17 for PATIENT COUNSELING INFORMATION and FDA-
• VELTIN Gel is contraindicated in patients with regional enteritis,
approved patient labeling.
ulcerative colitis, or history of antibiotic-associated colitis. (4)
FULL PRESCRIBING INFORMATION: CONTENTS*
12 CLINICAL PHARMACOLOGY
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
3 DOSAGE FORMS AND STRENGTHS
13 NONCLINICAL TOXICOLOGY
5 WARNINGS AND PRECAUTIONS
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
14 CLINICAL STUDIES
5.2 Ultraviolet Light and Environmental Exposure
16 HOW SUPPLIED/STORAGE AND HANDLING
6 ADVERSE REACTIONS
17 PATIENT COUNSELING INFORMATION
6.1 Adverse Reactions in Clinical Studies
7 DRUG INTERACTIONS
Sections or subsections omitted from the full prescribing information are not
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy 8.3 Nursing Mothers 8.4 Pediatric Use 8.5 Geriatric Use
FULL PRESCRIBING INFORMATION
INDICATIONS AND USAGE
VELTIN® (clindamycin phosphate and tretinoin) Gel, 1.2%/0.025% is indicated for the
topical treatment of acne vulgaris in patients 12 years or older.
DOSAGE AND ADMINISTRATION
VELTIN Gel should be applied once daily in the evening, gently rubbing the medication
to lightly cover the entire affected area. Approximately a pea sized amount will be needed for each application. Avoid the eyes, lips, and mucous membranes.
VELTIN Gel is not for oral, ophthalmic, or intravaginal use.
DOSAGE FORMS AND STRENGTHS
VELTIN Gel, containing clindamycin phosphate 1.2% and tretinoin 0.025%, is a yellow,
opaque topical gel. Each gram of VELTIN Gel contains, as dispensed, 10 mg (1%) clindamycin as clindamycin phosphate, and 0.25 mg (0.025%) tretinoin solubilized in an aqueous based gel.
VELTIN Gel is contraindicated in patients with regional enteritis, ulcerative colitis, or
history of antibiotic-associated colitis.
WARNINGS AND PRECAUTIONS
Systemic absorption of clindamycin has been demonstrated following topical use.
Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with the use of topical clindamycin. If significant diarrhea occurs, VELTIN 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 VELTIN
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 VELTIN Gel.
Adverse Reactions in Clinical Studies
Because clinical studies are conducted under widely varying conditions, adverse reaction
rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in clinical practice.
The safety data reflect exposure to VELTIN Gel in 1,104 patients with acne vulgaris.
Patients were 12 years or older and were treated once daily in the evening for 12 weeks. Adverse reactions that were reported in ≥1% of patients treated with VELTIN Gel are presented in Table 1.
Table 1: Treatment-Related Adverse Reactions Reported by ≥1% of Subjects
Patients with at least one adverse reaction
Local skin reactions actively assessed at baseline and end of treatment with a score > 0 are presented in Table 2.
Table 2: VELTIN GEL-Treated Patients with Local Skin Reactions
During the twelve weeks of treatment, each local skin reaction peaked at week 2 and gradually reduced thereafter.
VELTIN Gel should not be used in combination with erythromycin-containing products
due to possible antagonism to the clindamycin component. In vitro
studies have shown
antagonism between these 2 antimicrobials. The clinical significance of this in vitro
is not known. 7.2
Neuromuscular Blocking Agents
Clindamycin has been shown to have neuromuscular blocking properties that may
enhance the action of other neuromuscular blocking agents. Therefore, VELTIN Gel should be used with caution in patients receiving such agents.
USE IN SPECIFIC POPULATIONS
Pregnancy Category C. There are no well-controlled studies in pregnant women treated
with VELTIN Gel. VELTIN Gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. A limit teratology study performed in Sprague Dawley rats treated topically with VELTIN Gel or 0.025% tretinoin gel at a dose of 2 mL/kg during gestation days 6 to 15 did not result in teratogenic effects. Although no systemic levels of tretinoin were detected, craniofacial and heart abnormalities were described in drug-treated groups. These abnormalities are consistent with retinoid effects and occurred at 16 times the recommended clinical dose assuming 100% absorption and based on body surface area comparison. For purposes of comparison of the animal exposure to human exposure, the recommended clinical dose is defined as 1 g of VELTIN Gel applied daily to a 50 kg person. Clindamycin
Reproductive developmental toxicity studies performed in rats and mice using oral doses
of clindamycin up to 600 mg/kg/day (480 and 240 times the recommended clinical dose based on body surface area comparison, respectively) or subcutaneous doses of clindamycin up to 180 mg/kg/day (140 and 70 times the recommended clinical dose based on body surface area comparison, respectively) revealed no evidence of teratogenicity. Tretinoin
Oral tretinoin has been shown to be teratogenic in mice, rats, hamsters, rabbits, and
primates. It was teratogenic and fetotoxic in Wistar rats when given orally at doses greater than 1 mg/kg/day (32 times the recommended clinical dose based on body surface area comparison). However, variations in teratogenic doses among various strains of rats have been reported. In the cynomologous monkey, a species in which tretinoin metabolism is closer to humans than in other species examined, fetal malformations were reported at oral doses of 10 mg/kg/day or greater,
but none were observed at 5 mg/kg/day (324 times the recommended clinical dose based on body surface area comparison), although increased skeletal variations were observed at all doses. Dose-related teratogenic effects and increased abortion rates were reported in pigtail macaques.
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 fetus is not known. 8.3
It is not known whether clindamycin is excreted in human milk following use of VELTIN
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
VELTIN Gel is administered to a nursing woman. 8.4
Safety and effectiveness of VELTIN Gel in pediatric patients below the age of 12 years
Clinical trials of VELTIN Gel included 2.086 patients 12-17 years of age with acne
vulgaris. [See Clinical Studies (14).] 8.5
Clinical studies of VELTIN Gel did not include sufficient numbers of subjects ages 65
and over to determine whether they respond differently from younger subjects.
VELTIN (clindamycin phosphate and tretinoin) Gel, 1.2%/0.025%, is a fixed
combination of two solubilized active ingredients in an aqueous based gel. Clindamycin phosphate 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 clindamycin phosphate is methyl 7-chloro-6,7,8-trideoxy-6-(1-
-octopyranoside 2-(dihydrogen phosphate). The structural formula for clindamycin phosphate is represented below:
The chemical name for tretinoin is all-trans
cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid. It is a member of the retinoid family of compounds.
The structural formula for tretinoin is represented below:
VELTIN Gel contains the following inactive ingredients: butylated hydroxytoluene,
carbomer homopolymer (type C), anhydrous citric acid, edetate disodium, methylparaben, laureth 4, propylene glycol, tromethamine, and purified water.
12.1 Mechanism of Action
[See Microbiology (12.4.]
Although the exact mode of action of tretinoin is unknown, current evidence suggests that
topical tretinoin decreases cohesiveness of folliculare epithelial cells with decreased
microcomedone formation. Additionally, tretinoin stimulates mitotic activity and increased
turnover of follicul epithelial cells causing extrusion of the comedones. 12.3 Pharmacokinetics
In an open-label study of 17 patients with moderate-to-severe acne vulgaris, topical
administration of approximately 3 grams of VELTIN Gel once daily for 5 days, clindamycin
concentrations were quantifiable in all 17 patients starting from 1 hour post dose. All plasma
clindamycin concentrations were ≤5.56 ng/mL on day 5, with the exception of one subject who
had a maximum clindamycin concentration of 8.73 ng/mL at 4 hours post-dose. There was no
appreciable increase in systemic exposure to tretinoin, as compared to the baseline value. The
average tretinoin concentration across all sampling times on day 5 ranged from 1.19 to 1.23
ng/mL compared with the corresponding baseline mean tretinoin concentration range of 1.16 to
1.30 ng/mL. 12.4 Microbiology
No microbiology studies were conducted in the clinical trials with this product.
Clindamycin binds to the 50S ribosomal subunit of susceptible bacteria and prevents
elongation of peptide chains by interfering with peptidyl transfer, thereby suppressing protein synthesis. Clindamycin 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 VELTIN Gel. P. acnes
resistance to clindamycin has been documented. Inducible Clindamycin Resistance
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 clindamycin may result in developing inducible resistance in these organisms. This resistance is not detected by routine susceptibility testing. Cross Resistance
Resistance to clindamycin is often associated with resistance to erythromycin.
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
Long-term animal studies have not been performed to evaluate the carcinogenic potential
of VELTIN Gel or the effect of VELTIN Gel on fertility. VELTIN Gel was negative for mutagenic potential when evaluated in an in vitro
reversion assay. VELTIN Gel was equivocal for clastogenic potential in the absence of metabolic activation when tested in an in vitro
chromosomal aberration assay. Clindamycin
Once daily dermal administration of 1% clindamycin as clindamycin phosphate in the
VELTIN Gel vehicle (32 mg/kg/day, 13 times the recommended clinical dose based on body surface area comparison) to mice for up to 2 years did not produce evidence of tumorigenicity. Fertility studies in rats treated orally with up to 300 mg/kg/day of clindamycin (240 times the recommended clinical dose based on body surface area comparison) revealed no effects on fertility or mating ability. Tretinoin
In two independent mouse studies where 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. However, in a dermal carcinogenicity study in mice, tretinoin applied at a dose of 5.1 μg (1.4 times the recommended clinical dose based on body surface area comparison) three times per week for 20 weeks acted as a weak promoter of skin tumor formation following a single application of dimethylbenz[α]anthracene (DMBA).
In a study in female SENCAR mice, papillomas were induced by topical exposure to
DMBA followed by promotion with 12 O tetradecanoyl-phorbol 13-acetate or mezerein for up to 20 weeks. Topical application of tretinoin prior to each application of promoting agent resulted in a reduction in the number of papillomas per mouse. However, papillomas resistant to topical tretinoin suppression were at higher risk for pre-malignant progression.
Tretinoin has been shown to enhance photoco-carcinogenicity in properly performed
specific studies, employing concurrent or intercurrent exposure to tretinoin and UV radiation. The photoco-carcinogenic potential of the clindamycin tretinoin combination is unknown. Although the significance of these studies to humans is not clear, patients should avoid exposure to sun.
The genotoxic potential of tretinoin was evaluated in an in vitro
reversion test and an in vitro
chromosomal aberration assay in Chinese hamster ovary cells. Both tests were negative.
In oral fertility studies in rats treated with tretinoin, the no-observed-effect-level was 2
mg/kg/day (64 times the recommended clinical dose based on body surface area comparison).
The safety and efficacy of VELTIN Gel, applied once daily for the treatment of acne
vulgaris, was evaluation in 12-week multicenter, randomized, blinded studies in subjects 12 years and older.
Treatment response was defined as the percent of subjects who had a two grade
improvement from baseline to Week 12 based on the Investigator’s Global Assessment (IGA) and a mean absolute change from baseline to Week 12 in two out of three (total, inflammatory and non-inflammatory) lesion counts. The IGA scoring scale used in all the clinical trials for VELTIN Gel is as follows:
Normal, clear skin with no evidence of acne vulgaris.
Skin almost clear; rare non-inflammatory lesions present, with rare
non-inflamed papules (papules must be resolving and may be
hyperpigmented, though not pink-red) requiring no further treatment in the Investigator’s opinion.
Some non-inflammatory lesions are present, with few inflammatory
lesions (papules/pustules only, no nodulo-cystic lesions).
Non-inflammatory lesions predominate, with multiple inflammatory
Moderate lesions evident; several to many comedones and papules/pustules, and
there may or may not be 1 small nodulo-cystic lesion.
Inflammatory lesions are more apparent; many comedones and
papules/pustules, there may or may not be a few nodulo-cystic lesions.
Highly inflammatory lesions predominate; variable numbers of
comedones, many papules/pustules and nodulo-cystic lesions.
In Study 1, 1649 subjects were randomized to VELTIN Gel, Clindamycin gel, Tretinoin
gel, and vehicle gel. The median age of subjects was 17 years old and 58% were females. At baseline, subjects had an average of 71 total lesions of which the mean number of inflammatory lesions was 25.5 lesions and the mean number of non-inflammatory lesions was 45.1 lesions. The majority of subjects enrolled with a baseline IGA score of 3. The efficacy results at week 12 are presented in Table 3.
Tretinoin Gel Vehicle Gel
Investigator’s Global Assessment
Percentage of subjects achieving Two Grade Improvement
Tretinoin Gel Vehicle Gel
Percentage of subjects achieving an IGA of 0 or 1 with a Two
The safety and efficacy of clindamycin-tretinoin gel was also evaluated in two additional
12-week, multi-centered, randomized, blinded, studies in patients 12 years and older. A total of 2219 subjects with mild-to-moderate acne vulgaris were treated once daily for 12 weeks. Of the 2219 subjects, 634 subjects were treated with clindamycin-tretinoin gel. These studies demonstrated consistent outcomes.
HOW SUPPLIED/STORAGE AND HANDLING
Storage and Handling
• Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F). • Protect from heat. • Protect from light. • Protect from freezing. • Keep out of reach of children. • Keep tube tightly closed.
PATIENT COUNSELING INFORMATION
17.1 Instructions for Use
• At bedtime, the face should be gently washed with a mild soap and water. After
patting the skin dry, apply VELTIN Gel as a thin layer over the entire affected area (excluding the eyes and lips).
• Patients should be advised not to use more than a pea sized amount to cover the face
and not to apply more often than once daily (at bedtime) as this will not make for faster results and may increase irritation.
• A sunscreen should be applied every morning and reapplied over the course of the day
as needed. Patients should be advised to avoid exposure to sunlight, sunlamp, ultraviolet light, and other medicines that may increase sensitivity to sunlight.
• Other topical products with a strong drying effect such as abrasive soaps or cleansers,
may cause an increase in skin irritation with VELTIN Gel.
17.2 Skin Irritation
VELTIN Gel may cause irritation such as erythema, scaling, itching, burning, or stinging.
In the event a patient treated with VELTIN Gel experiences severe diarrhea or
gastrointestinal discomfort, VELTIN Gel should be discontinued and a physician should be contacted. VEL:3PI
(clindamycin phosphate and tretinoin) Gel
IMPORTANT: For use on skin only (topical use). Do not get VELTIN Gel in your
mouth, eyes, or vagina.
Read the Patient Information that comes with VELTIN 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 medical condition or your treatment.
What is VELTIN Gel?
VELTIN Gel is prescription medicine used on the skin to treat acne in people 12 years and older.
It is not known if VELTIN Gel is safe and effective in children under 12 years of age.
Who should not use VELTIN Gel?
Do not use VELTIN Gel if you have:
• Crohn’s disease • ulcerative colitis • had inflammation of the colon (colitis) with past antibiotic use
Talk to your doctor if you are not sure if you have one of these conditions.
What should I tell my doctor before using VELTIN Gel?
Before using VELTIN Gel, tell your doctor if you:
• have any allergies
• Plan to have surgery with general anesthesia.
One of the medicines in VELTIN Gel
can affect how certain anesthesia medicines work.
• have any other medical conditions
• are pregnant or plan to become pregnant. It is not known if VELTIN Gel may
harm your unborn baby.
• are breast-feeding or plan to breast-feed.
It is not known if VELTIN Gel passes
into your breast milk. One of the medicines in VELTIN Gel contains clindamycin. When clindamycin is taken by mouth or injection, it may pass into breast milk. You and your doctor should decide if you will take VELTIN Gel or breast feed. You should not do both.
Tell your doctor about all the medicines and skin products you use. Especially tell your
doctor if you take medicine that contains erythromycin. VELTIN Gel should not be used
with products that contain erythromycin.
Know the medicines you take. Keep a list of your medicines and show it to your doctor and
pharmacist when you get a new medicine.
How should I use VELTIN Gel?
• Use VELTIN Gel exactly as prescribed.
• Your doctor will tell you how long to use VELTIN Gel.
• Do not
apply VELTIN Gel more than one time each day.
• Do not
use too much VELTIN Gel, because it may irritate your skin.
Instructions for applying VELTIN Gel:
1. At bedtime, wash your face gently with a mild soap, rinse with water. 2. Pat the skin dry.
3. Squeeze a pea sized amount of medication onto one fingertip. Then, gently rub over
the entire affected area. Do not get VELTIN Gel in your eyes, mouth, or on your
What should I avoid while using VELTIN Gel?
• Limit your time in sunlight. Avoid using tanning beds or sun lamps. If you have to be
in sunlight, wear a wide-brimmed hat or other protective clothing. Apply a sunscreen every morning and re-apply during the day as needed.
• Avoid wind and cold weather during treatment with VELTIN Gel. These may be
• Avoid using abrasive soaps and cleansers. These may cause increased skin irritation
What are the possible side effects of VELTIN Gel?
VELTIN Gel may cause serious side effects, including:
• Inflammation of the colon (colitis).
Clindamycin, one of the ingredients in VELTIN
Gel, can cause severe colitis that may lead to death. Stop taking VELTIN Gel and call your doctor if you develop severe watery diarrhea, or bloody diarrhea.
VELTIN Gel may cause your skin to become sunburned more easily. If
your face is sunburned, do not use VELTIN Gel until your sunburn is completely healed. Tretinoin, one of the medicines in VELTIN Gel, makes your skin more sensitive to sunlight. See “What should I avoid while using VELTIN Gel?”
Common side effects of VELTIN Gel include:
• Skin irritation.
VELTIN Gel may cause skin irritation such as dryness, peeling,
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 VELTIN Gel. Ask your doctor or pharmacist for more
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-
800-FDA-1088. How should I store VELTIN Gel?
• Store VELTIN Gel
at room temperature, between 59°F to 86°F (15°C to 30°C).
• Keep VELTIN Gel away from heat and light.
• Keep VELTIN Gel and all medicines out of the reach of children.
General information about VELTIN Gel
Medicines are sometimes prescribed for purposes other than those listed in the patient
information leaflet. Do not use VELTIN Gel for a condition for which it was not prescribed. Do
not give VELTIN Gel to other people, even if they have the same symptoms you have. It
may harm them.
This patient information leaflet summarizes the most important information about VELTIN Gel.
If you would like more information, talk with your doctor. You can also ask your pharmacist or
doctor for information about VELTIN Gel that is written for healthcare professionals. For more
information call 1-888-784-3335. What are the ingredients in VELTIN Gel?
clindamycin phosphate and tretinoin Inactive Ingredients:
butylated hydroxytoluene, carbomer homopolymer (type C), anhydrous
citric acid, edetate disodium, methylparaben, laureth 4, propylene glycol, tromethamine, and
Stiefel Laboratories, Inc.
Research Triangle Park, NC 27709
DPT Laboratories, Ltd.
307 E. Josephine Street
San Antonio, TX 78215
Issued May 2012
STIEFEL and STIEFEL & Design are registered trademarks of Stiefel Laboratories, Inc.
VELTIN is a registered trademark of Astellas Pharma Europe B.V. 2012 Stiefel Laboratories, Inc.
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