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DRUGS & SUPPLEMENTS
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When are you taking this medicine? |
Azenam® is indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa. Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with FEV1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14) ].
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Azenam and other antibacterial drugs, Azenam should be used only to treat patients with CF known to have Pseudomonas aeruginosa in the lungs.
Azenam is a monobactam antibacterial indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa. Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with FEV1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia. (1)
The recommended dose of Azenam for both adults and pediatric patients 7 years of age and older is one single-use vial (75 mg of Azenam) reconstituted with 1 mL of sterile diluent administered 3 times a day for a 28-day course (followed by 28 days off Azenam therapy). Dosage is not based on weight or adjusted for age. Doses should be taken at least 4 hours apart.
Azenam is administered by inhalation using an Altera® Nebulizer System. Patients should use a bronchodilator before administration of Azenam.
Azenam should be administered immediately after reconstitution. Do not reconstitute Azenam until ready to administer a dose.
Take one amber glass vial containing Azenam and one diluent ampule from the carton. To open the glass vial, carefully remove the metal ring by lifting or pulling the tab and remove the gray rubber stopper. Twist the tip off the diluent ampule and squeeze the liquid into the glass vial. Replace the rubber stopper, then gently swirl the vial until contents have completely dissolved.
The empty vial, stopper, and diluent ampule should be disposed of properly upon completion of dosing.
Azenam is administered by inhalation using an Altera Nebulizer System. Azenam should not be administered with any other nebulizer. Azenam should not be mixed with any other drugs in the Altera Nebulizer Handset.
Azenam is not for intravenous or intramuscular administration.
Patients should use a bronchodilator before administration of Azenam. Short-acting bronchodilators can be taken between 15 minutes and 4 hours prior to each dose of Azenam. Alternatively, long-acting bronchodilators can be taken between 30 minutes and 12 hours prior to administration of Azenam. For patients taking multiple inhaled therapies, the recommended order of administration is as follows: bronchodilator, mucolytics, and lastly, Azenam.
To administer Azenam, pour the reconstituted solution into the handset of the nebulizer system. Turn the unit on. Place the mouthpiece of the handset in your mouth and breathe normally only through your mouth. Administration typically takes between 2 and 3 minutes. Further patient instructions on how to administer Azenam are provided in the FDA-approved patient labeling. Instructions on testing nebulizer functionality and cleaning the handset are provided in the Instructions for Use included with the nebulizer system.
A dose of Azenam consists of a single-use vial of sterile, lyophilized Azenam (75 mg) reconstituted with a 1 mL ampule of sterile diluent (0.17% sodium chloride). Reconstituted Azenam is administered by inhalation.
Azenam is contraindicated in patients with a known allergy to Azenam.
Severe allergic reactions have been reported following administration of Azenam for injection to patients with no known history of exposure to Azenam. In addition, allergic reaction with facial rash, facial swelling, and throat tightness was reported with Azenam in clinical trials. If an allergic reaction to Azenam occurs, stop administration of Azenam and initiate treatment as appropriate.
Caution is advised when administering Azenam to patients if they have a history of beta-lactam allergy, although patients with a known beta-lactam allergy have received Azenam in clinical trials and no severe allergic reactions were reported. A history of allergy to beta-lactam antibiotics, such as penicillins, cephalosporins, and/or carbapenems, may be a risk factor, since cross-reactivity may occur.
Bronchospasm is a complication associated with nebulized therapies, including Azenam. Reduction of 15% or more in forced expiratory volume in 1 second immediately following administration of study medication after pretreatment with a bronchodilator was observed in 3% of patients treated with Azenam.
In clinical trials, patients with increases in FEV1 during a 28-day course of Azenam were sometimes treated for pulmonary exacerbations when FEV1 declined after the treatment period. Healthcare providers should consider a patient's baseline FEV1 measured prior to Azenam therapy and the presence of other symptoms when evaluating whether post-treatment changes in FEV1 are caused by a pulmonary exacerbation.
Prescribing Azenam in the absence of known Pseudomonas aeruginosa infection in patients with CF is unlikely to provide benefit and increases the risk of development of drug-resistant bacteria.
To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD5, option 3 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of drugs cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Azenam was evaluated in 344 patients from two placebo-controlled trials and one open-label follow-on trial. In controlled trials, 146 patients with CF received 75 mg Azenam 3 times a day for 28 days.
Table 1 displays adverse reactions reported in more than 5% of patients treated with Azenam 3 times a day in placebo-controlled trials. The listed adverse reactions occurred more frequently in CAYSTON-treated patients than in placebo-treated patients.
Event (Preferred Term) | Placebo (N=160) n (%) | Azenam 75 mg 3 times a day (N=146) n (%) |
---|---|---|
Cough | 82 (51%) | 79 (54%) |
Nasal congestion | 19 (12%) | 23 (16%) |
Wheezing | 16 (10%) | 23 (16%) |
Pharyngolaryngeal pain | 17 (11%) | 18 (12%) |
Pyrexia | 9 (6%) | 19 (13%) |
Chest discomfort | 10 (6%) | 11 (8%) |
Abdominal Pain | 8 (5%) | 10 (7%) |
Vomiting | 7 (4%) | 9 (6%) |
Adverse reactions that occurred in less than 5% of patients treated with Azenam were bronchospasm (3%) [see Warnings and Precautions (5.2) ] and rash (2%).
In addition to adverse reactions reported from clinical trials, the following possible adverse reactions have been identified during post-approval use of Azenam. Because these events have been reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS
Arthralgia, joint swelling
No formal clinical studies of drug interactions with Azenam have been conducted.
Pregnancy Category B
No reproductive toxicology studies have been conducted with Azenam. However, studies were conducted with Azenam for injection. Azenam has been shown to cross the placenta and enter fetal circulation. No evidence of embryo or fetotoxicity or teratogenicity has been shown in studies with pregnant rats and rabbits. In rats receiving Azenam for injection during late gestation and lactation, no drug induced changes in maternal, fetal or neonatal parameters were observed. These animal reproduction and developmental toxicity studies used parenteral routes of administration that would provide systemic exposures far in excess of the average peak plasma levels measured in humans following Azenam therapy.
No adequate and well-controlled studies of Azenam for injection or Azenam in pregnant women have been conducted. Because animal reproduction studies are not always predictive of human response, Azenam should be used during pregnancy only if clearly needed.
Following administration of Azenam for injection, Azenam is excreted in human milk at concentrations that are less than one percent of those determined in simultaneously obtained maternal serum. Peak plasma concentrations of Azenam following administration of Azenam are approximately 1% of peak concentrations observed following IV Azenam (500 mg). Therefore, use of Azenam during breastfeeding is unlikely to pose a risk to infants.
Patients 7 years and older were included in clinical trials with Azenam. Fifty-five patients under 18 years of age received Azenam in placebo-controlled trials. No dose adjustments were made for pediatric patients. Pyrexia was more commonly reported in pediatric patients than in adult patients. Safety and effectiveness in pediatric patients below the age of 7 years have not been established.
Clinical trials of Azenam did not include CAYSTON-treated patients aged 65 years of age and older to determine whether they respond differently from younger patients.
Azenam is known to be excreted by the kidney. Placebo-controlled clinical trials with Azenam excluded patients with abnormal baseline renal function (defined as serum creatinine greater than 2 times the upper limit of normal range). Given the low systemic exposure of Azenam following administration of Azenam, clinically relevant accumulation of Azenam is unlikely to occur in patients with renal impairment. Therefore, Azenam may be administered to patients with mild, moderate and severe renal impairment with no dosage adjustment.
No overdoses have been reported with Azenam in clinical trials to date. In clinical trials, 225 mg doses of Azenam via inhalation were associated with higher rates of drug-related respiratory adverse reactions, particularly cough. Since the peak plasma concentration of Azenam following administration of Azenam (75 mg) is approximately 0.6 mcg/mL, compared to a serum concentration of 54 mcg/mL following administration of Azenam for injection (500 mg), no systemic safety issues associated with Azenam overdose are anticipated.
A dose of Azenam consists of a 2 mL amber glass vial containing lyophilized Azenam (75 mg) and lysine (46.7 mg), and a low-density polyethylene ampule containing 1 mL sterile diluent (0.17% sodium chloride). The reconstituted solution is for inhalation. The formulation contains no preservatives or arginine.
The active ingredient in Azenam is Azenam, a monobactam antibacterial. The monobactams are structurally different from beta-lactam antibiotics (e.g., penicillins, cephalosporins, carbapenems) due to a monocyclic nucleus. This nucleus contains several side chains; sulfonic acid in the 1-position activates the nucleus, an aminothiazolyl oxime side chain in the 3-position confers specificity for aerobic Gram-negative bacteria including Pseudomonas spp., and a methyl group in the 4-position enhances beta-lactamase stability.
Azenam is designated chemically as (Z)-2-[[[(2-amino-4-thiazolyl)[[(2S,3S)-2-methyl-4-oxo-1-sulfo-3-azetidinyl]carbamoyl]methylene]amino]oxy]-2-methylpropionic acid. The structural formula is presented below:
Azenam is a white to off-white powder. Azenam is sterile, hygroscopic, and light sensitive. Once reconstituted with the supplied diluent, the pH range is 4.5 to 6.0.
Azenam is an antibacterial drug [see Clinical Pharmacology ].
Sputum Concentrations
Sputum Azenam concentrations exhibited considerable variability between patients receiving Azenam (75 mg) in clinical trials. The mean sputum concentration 10 minutes following the first dose of Azenam (n = 195 patients with CF) was 726 mcg/g. Mean sputum concentrations of Azenam in patients receiving Azenam 3 times a day for 28 days were 984 mcg/g, 793 mcg/g, and 715 mcg/g 10 minutes after dose administration on Days 0, 14, and 28, respectively, indicating no accumulation of Azenam in sputum.
Plasma Concentrations
Plasma Azenam concentrations exhibited considerable variability between patients receiving Azenam (75 mg) in the clinical trials. The mean plasma concentration one hour following the first dose of Azenam (at approximately the peak plasma concentration) was 0.59 mcg/mL. Mean peak plasma concentrations in patients receiving Azenam 3 times a day for 28 days were 0.55 mcg/mL, 0.67 mcg/mL, and 0.65 mcg/mL on Days 0, 14, and 28, respectively, indicating no systemic accumulation of Azenam. In contrast, the serum concentration of Azenam following administration of Azenam for injection (500 mg) is approximately 54 mcg/mL.
Absorption
Evaluation of plasma and urine Azenam concentrations following administration of Azenam indicates low systemic absorption of Azenam. Approximately 10% of the total Azenam dose is excreted in the urine as unchanged drug, as compared to 60–65% following intravenous administration of Azenam for injection.
Distribution
The protein binding of Azenam in serum is approximately 56% and is independent of dose.
Metabolism
Following intramuscular administration of Azenam for injection 500 mg every 8 hours for 7 days, approximately 6% of the dose was excreted as a microbiologically inactive open β-lactam ring hydrolysis product in an 8-hour urine collection on the last day of multiple dosing.
Excretion
The elimination half-life of Azenam from plasma is approximately 2.1 hours following administration of Azenam to adult patients with CF, similar to what has been reported for Azenam for injection. Approximately 10% of the total Azenam dose is excreted in the urine as unchanged drug. Systemically absorbed Azenam is eliminated about equally by active tubular secretion and glomerular filtration. Following administration of a single intravenous dose of radiolabeled Azenam for injection, about 12% of the dose was recovered in the feces.
Mechanism of Action
Azenam exhibits activity in vitro against Gram-negative aerobic pathogens including P. aeruginosa. Azenam binds to penicillin-binding proteins of susceptible bacteria, which leads to inhibition of bacterial cell wall synthesis and death of the cell. Azenam activity is not decreased in the presence of CF lung secretions.
Susceptibility Testing
A single sputum sample from a patient with CF may contain multiple morphotypes of P. aeruginosa and each morphotype may have a different level of in vitro susceptibility to Azenam. There are no in vitro susceptibility test interpretive criteria for isolates of P. aeruginosa obtained from the sputum of CF patients.1
Development of Resistance
No changes in the susceptibility of P. aeruginosa to Azenam were observed following a 28-day course of Azenam in the placebo-controlled trials.
Cross-Resistance
No cross-resistance to other classes of antibiotics, including aminoglycosides, quinolones, and beta-lactams, was observed following a 28-day course of Azenam in the Phase 3 placebo-controlled trials or in an open-label follow-on trial of up to nine 28-day courses of 75 mg Azenam 3 times a day.
Other
No trends in the treatment-emergent isolation of other bacterial respiratory pathogens (Burkholderia cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Staphylococcus aureus) were observed in clinical trials. There was a slight increase in the isolation of Candida spp. following up to nine 28-day courses of Azenam therapy.
A 104-week rat inhalation toxicology study to assess the carcinogenic potential of Azenam demonstrated no drug-related increase in the incidence of tumors. Rats were exposed to Azenam for up to 4 hours per day. Peak plasma levels of Azenam averaging approximately 6.8 mcg/mL were measured in rats at the highest dose level. This is approximately 12-fold higher than the average peak plasma level measured in humans following Azenam therapy.
Genetic toxicology studies performed in vitro demonstrated that Azenam did not induce structural chromosome aberrations in CHO cells and did not induce mutations at the TK locus in mouse lymphoma L5178Y TK+/- cells. Likewise, genetic toxicology studies performed in vivo did not reveal evidence of mutagenic potential.
Azenam did not impair the fertility of rats when administered at doses that would provide systemic exposures far in excess of peak plasma levels measured in humans following Azenam therapy.
Azenam was evaluated over a period of 28 days of treatment in a randomized, double-blind, placebo-controlled, multicenter trial that enrolled patients with CF and P. aeruginosa. This trial was designed to evaluate improvement in respiratory symptoms. Patients 7 years of age and older and with FEV1 of 25% to 75% predicted were enrolled. All patients received Azenam or placebo on an outpatient basis administered with the Altera Nebulizer System. All patients were required to take a dose of an inhaled bronchodilator (beta-agonist) prior to taking a dose of Azenam or placebo. Patients were receiving standard care for CF, including drugs for obstructive airway diseases.
The trial enrolled 164 patients with CF and P. aeruginosa. The mean age was 30 years, and the mean baseline FEV1 % predicted was 55%; 43% were females and 96% were Caucasian. These patients were randomized in a 1:1 ratio to receive either Azenam (75 mg) or volume-matched placebo administered by inhalation 3 times a day for 28 days. Patients were required to have been off antibiotics for at least 28 days before treatment with study drug. The primary efficacy endpoint was improvement in respiratory symptoms on the last day of treatment with Azenam or placebo. Respiratory symptoms were also assessed two weeks after the completion of treatment with Azenam or placebo. Changes in respiratory symptoms were assessed using a questionnaire that asks patients to report on symptoms like cough, wheezing, and sputum production.
Improvement in respiratory symptoms was noted for CAYSTON-treated patients relative to placebo-treated patients on the last day of drug treatment. Statistically significant improvements were seen in both adult and pediatric patients, but were substantially smaller in adult patients. Two weeks after completion of treatment, a difference in respiratory symptoms between treatment groups was still present, though the difference was smaller.
Pulmonary function, as measured by FEV1 (L), increased from baseline in patients treated with Azenam. The treatment difference at Day 28 between CAYSTON-treated and placebo-treated patients for percent change in FEV1 (L) was statistically significant at 10% (95% CI: 6%, 14%). Improvements in FEV1 were comparable between adult and pediatric patients. Two weeks after completion of drug treatment, the difference in FEV1 between Azenam and placebo groups had decreased to 6% (95% CI: 2%, 9%).
Figure 1 Adjusted Mean Percent Change in FEV1 from Baseline to Study End (Days 0–42)
Each kit for a 28-day course of Azenam contains 84 sterile vials of Azenam and 88 ampules of sterile diluent packed in 2 cartons, each carton containing a 14-day supply. The four additional diluent ampules are provided in case of spillage.
Package Configuration | Dosage Strength | NDC |
---|---|---|
28-Day Kit | 75 mg | 61958-0901-1 |
Azenam vials and diluent ampules should be stored in the refrigerator at 2 °C to 8 °C (36 °F to 46 °F) until needed. Once removed from the refrigerator, Azenam and diluent may be stored at room temperature (up to 25 °C / 77 °F) for up to 28 days. Do not separate the Azenam vials from the diluent ampules. Azenam should be protected from light.
Do not use Azenam if it has been stored at room temperature for more than 28 days. Do not use Azenam beyond the expiration date stamped on the vial. Do not use diluent beyond the expiration date embossed on the ampule.
Azenam should be used immediately upon reconstitution. Do not reconstitute more than one dose at a time.
Do not use diluent or reconstituted Azenam if it is cloudy or if there are particles in the solution.
See FDA-Approved Patient Labeling
Patients should be advised that Azenam is for inhalation use only and that Azenam should only be administered using the Altera Nebulizer System. Patients should be instructed only to reconstitute Azenam with the provided diluent and not mix other drugs with Azenam in the Altera Nebulizer System.
Patients should be advised to complete the full 28-day course of Azenam even if they are feeling better. Inform the patient that if they miss a dose, they should take all 3 daily doses as long as the doses are at least 4 hours apart.
Patients should be advised to use a bronchodilator prior to administration of Azenam. Patients taking several inhaled medications should be advised to use the medications in the following order of administration: bronchodilator, mucolytics, and lastly, Azenam.
Patients should be advised to tell their doctor if they have new or worsening symptoms. Patients who believe they are experiencing an allergic reaction to Azenam should be advised to contact their doctor immediately.
Patients should be counseled that antibacterial drugs including Azenam should only be used to treat bacterial infections. They do not treat viral infection (e.g., the common cold). When Azenam is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Azenam or other antibacterial drugs in the future.
Figure 1 Figure 2, 3, 4, 5 Figure 6 Figure 7, 8 Figure 9
Manufactured by: Gilead Sciences, Inc., Foster City, CA 94404
Azenam is a trademark of Gilead Sciences, Inc. All other trademarks referenced herein are the property of their respective owners.
© 2014 Gilead Sciences, Inc. All rights reserved.
50-814-GS-002
FDA-Approved Patient Labeling
PATIENT INFORMATION
Azenam® (kay-stun)
(aztreonam for inhalation solution)
Read this Patient Information before you start taking Azenam and each time you get a refill. This information does not take the place of talking with your doctor about your medical condition or your treatment.
What is Azenam?
Azenam is a prescription inhaled antibiotic. Azenam is used to improve breathing symptoms in people with cystic fibrosis (CF) who have Pseudomonas aeruginosa (P. aeruginosa) in their lungs.
Azenam is only for infections caused by bacteria. It is not for infections caused by viruses, such as the common cold.
Azenam is used only with the Altera® Nebulizer System.
It is not known if Azenam is safe and effective in children under the age of 7.
Who should not take Azenam?
Do not take Azenam if you are allergic to Azenam (AZACTAM®).
What should I tell my doctor before taking Azenam?
Before taking Azenam, tell your doctor if you:
Tell your doctor about all the medicine you take, including prescription and non-prescription medicines, vitamins and herbal supplements.
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I take Azenam?
What are the possible side effects of Azenam?
Azenam can cause serious side effects, including:
Common side effects of Azenam include:
Other possible side effects of Azenam include:
Tell your doctor if you have any new or worsening symptoms while taking Azenam. Tell your doctor about any side effect that bothers you or that does not go away.
These are not all the possible side effects of Azenam. For more information, ask your doctor or pharmacist.
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 Azenam?
Keep Azenam and all medicines out of the reach of children.
General information about Azenam
Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Azenam for a condition for which it was not prescribed. Do not give Azenam to other people, even if they have the same symptoms that you have. It may harm them.
This Patient Information leaflet summarizes the most important information about Azenam. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Azenam that is written for health professionals.
For more information, call 1-877-7CAYSTON (1-877-722-9786).
What are the ingredients in Azenam?
Active ingredient: Azenam
Inactive ingredient: lysine, sodium chloride (diluent)
PATIENT INSTRUCTIONS FOR USE
Azenam®
(aztreonam for inhalation solution)
Be sure that you read, understand and follow the Patient Instructions for Use below for the right way to take Azenam. If you have any questions, ask your doctor or pharmacist.
You will need the following supplies (Figure 1):
Check to make sure that your Altera Nebulizer System works properly before starting your treatment with Azenam. See the manufacturer's instructions for use that comes with your Altera Nebulizer System. This should have complete information about how to put together (assemble), prepare, use, and care for your Altera Nebulizer System.
Step 1 Preparing your Azenam for inhalation
Step 2 Taking your Azenam treatment
See the manufacturer's instructions for use that comes with your Altera Nebulizer System for complete instructions on taking a treatment, and how to clean and disinfect your Altera Nebulizer Handset.
Manufactured by: Gilead Sciences, Inc., Foster City, CA 94404
Azenam is a trademark of Gilead Sciences, Inc. All other trademarks referenced herein are the property of their respective owners.
© 2014 Gilead Sciences, Inc. All rights reserved.
50-814-GS-002
Principal Display Panel - Azenam 28 Day Carton - Representative Label
NDC 61958-0901-1
GILEAD
Azenam ®
(aztreonam for
inhalation solution)
75 mg/vial
For Oral Inhalation Only
Store Refrigerated, 2 °C to 8 °C (36 °F to 46 °F)
Contains:
84 Single-Use Vials of Azenam for Inhalation Solution
88 Diluent Ampules of Sodium Chloride 0.17%, 1 mL
(4 extra ampules provided in case of spillage)
For use only with the Altera® Nebulizer System
28-Day Supply
Rx only
Depending on the reaction of the Azenam after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Azenam 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 Azenam 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.
Visitors | % | ||
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51-100mg | 1 | 100.0% |
Visitors | % | ||
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1 month | 1 | 100.0% |
Visitors | % | ||
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30-45 | 1 | 100.0% |
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The information was verified by Dr. Rachana Salvi, MD Pharmacology