minocycline and Nausea

Safety, tolerability, and pharmacokinetics of tigecycline in 76 healthy Japanese subjects were determined in three randomized, double-blind, placebo-controlled studies. Subjects in an ascending single-dose study (n = 40) received 25-150 mg intravenously, whereas subjects in two multiple-dose studies received every 12-hour (q12h) dosing with 25 mg (n = 10) or 25, 50, or 100 then 50 mg (n = 30). Serial blood samples and urine were collected, drug concentrations determined, and pharmacokinetic parameters calculated. Fecal samples were also collected in the second multiple-dose study. After 10 days of tigecycline 50 mg q12h, mean ± standard deviation pharmacokinetics in 8/10 subjects were: maximum concentration 1,118 ± 127 ng/mL, area under the concentration-time curve 0-12 hours 3,261 ± 937 ng h/mL, clearance 0.25 ± 0.05 L/h/kg, half-life 60.7 ± 23.4 hours, and volume of distribution 11.9 ± 2.3 L/kg. The most common adverse events were nausea and vomiting. Changes in total bilirubin were also observed. Enterococci in the intestinal microflora were reduced, whereas the number of Enterobacteriaceae and Bacteroides remained relatively constant. Several strains of Bacteroides spp. resistant to tigecycline treatment were found in fecal samples on days 30 and 31. The pharmacokinetic profile of tigecycline was similar to non-Japanese subjects; tolerability and change in intestinal microflora were also similar.

Topics: Adult; Anti-Bacterial Agents; Asian People; Bacterial Load; Bacteroides; Double-Blind Method; Enterobacteriaceae; Enterococcus; Feces; Healthy Volunteers; Humans; Intestines; Male; Microbiota; Middle Aged; Minocycline; Nausea; Tigecycline; Vomiting; Young Adult

A phase 3, randomized, double-blind trial was conducted in subjects with diabetic foot infections without osteomyelitis (primary study) or with osteomyelitis (substudy) to determine the efficacy and safety of parenteral (intravenous [iv]) tigecycline (150 mg once-daily) versus 1 g once-daily iv ertapenem ± vancomycin. Among 944 subjects in the primary study who received ≥1 dose of study drug, >85% had type 2 diabetes; ~90% had Perfusion, Extent, Depth/tissue loss, Infection, and Sensation infection grade 2 or 3; and ~20% reported prior antibiotic failure. For the clinically evaluable population at test-of-cure, 77.5% of tigecycline- and 82.5% of ertapenem ± vancomycin-treated subjects were cured. Corresponding rates for the clinical modified intent-to-treat population were 71.4% and 77.9%, respectively. Clinical cure rates in the substudy were low (<36%) for a subset of tigecycline-treated subjects with osteomyelitis. Nausea and vomiting occurred significantly more often after tigecycline treatment (P = 0.003 and P < 0.001, respectively), resulting in significantly higher discontinuation rates in the primary study (nausea P = 0.007, vomiting P < 0.001). In the primary study, tigecycline did not meet criteria for noninferiority compared with ertapenem ± vancomycin in the treatment of subjects with diabetic foot infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactams; Diabetic Foot; Drug-Related Side Effects and Adverse Reactions; Ertapenem; Female; Humans; Male; Middle Aged; Minocycline; Nausea; Osteomyelitis; Tigecycline; Treatment Outcome; Vancomycin; Vomiting; Young Adult

We report the largest clinical experience using tigecycline-containing regimens for salvage treatment of patients with Mycobacterium abscessus and Mycobacterium chelonae.. Data were collected from 52 patients on emergency/compassionate use (n = 38) or two open-label studies (n = 7 patients each). Based on information that was available, 46 (88.5%) of the subjects received antibiotic therapy prior to treatment with tigecycline. Treatment groups were evaluated based on length of tigecycline therapy (<1 and ≥1 month). ClinicalTrials.gov identifiers: Study 205, NCT00600600 and Study 310, NCT00205816.. The most commonly used concomitant antimicrobials were macrolides, amikacin and linezolid. Pulmonary disease was the most common presentation (36/52; 69.2%), and 58.3% of these patients had underlying cystic fibrosis. The majority were M. abscessus complex (n = 30) or M. chelonae/abscessus (n = 4). With therapy ≥1 month (mean, 255.0 ± 265.7 days), 10/15 patients (66.7%) with cystic fibrosis and 16/26 (61.5%) overall were considered improved. Skin/soft-tissue/bone infections were the most common extrapulmonary infections. With therapy ≥1 month (mean, 143 ± 123 days), 9/12 patients (75.0%) were considered improved. Nine of the 16 cases reported as failures regardless of site of infection occurred in patients who stopped treatment due to adverse events. There were eight deaths; none was related to tigecycline.. Tigecycline given for ≥1 month as part of a multidrug regimen resulted in improvement in >60% of patients with M. abscessus and M. chelonae infections, including those with underlying cystic fibrosis, despite failure of prior antibiotic therapy. Adverse events were reported in >90% of cases, the most common being nausea and vomiting.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antitubercular Agents; Child; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Minocycline; Mycobacterium Infections, Nontuberculous; Nausea; Nontuberculous Mycobacteria; Salvage Therapy; Tigecycline; Treatment Outcome; Young Adult

To compare the monotherapy of tigecycline with vancomycin-aztreonam in hospitalized patients from India and Taiwan with complicated skin and skin structure infections (cSSSIs).. Safety and efficacy data were analyzed for Indian (n = 86) and Taiwanese (n = 41) patients hospitalized with cSSSIs who participated in two international Phase 3, randomized, double-blind studies.. Patients were treated for 5-14 days. Cure rates at the test-of-cure assessment (12-92 days post-therapy) were generally similar between tigecycline and vancomycin-aztreonam in the clinically evaluable populations (India, 83.3% vs. 75.8%; Taiwan, 78.6% vs. 90%) and in the clinical modified intent-to-treat populations (India, 78.6% vs. 66.7%; Taiwan, 73.3% vs. 75.0%). Nausea and vomiting occurred more frequently with tigecycline, but overall safety and tolerability were comparable between the two treatments.. Tigecycline monotherapy is a safe and effective therapy for cSSSIs in geographically distinct populations in Asia.

Topics: Adult; Aged; Anti-Bacterial Agents; Aztreonam; Double-Blind Method; Drug Therapy, Combination; Female; Humans; India; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Nausea; Skin Diseases, Bacterial; Taiwan; Tigecycline; Vancomycin; Vomiting

Tigecycline, an expanded broad-spectrum glycylcycline, exhibits in vitro activity against many common pathogens associated with community-acquired pneumonia (CAP), as well as penetration into lung tissues that suggests effectiveness in hospitalized CAP patients. The aim of the present study was to compare the efficacy and safety of intravenous (IV) tigecycline with IV levofloxacin in hospitalized adults with CAP.. In this prospective, double-blind, non-inferiority phase 3 trial, eligible patients with a clinical diagnosis of CAP supported by radiographic evidence were stratified by Fine Pneumonia Severity Index and randomized to tigecycline or levofloxacin for 7-14 days of therapy. Co-primary efficacy endpoints were clinical response in the clinically evaluable (CE) and clinical modified intent-to-treat (c-mITT) populations at test-of-cure (Day 10-21 post-therapy).. Of the 428 patients who received at least one dose of study drug, 79% had CAP of mild-moderate severity according to their Fine score. Clinical cure rates for the CE population were 88.9% for tigecycline and 85.3% for levofloxacin. Corresponding c-mITT population rates were 83.7% and 81.5%, respectively. Eradication rates for Streptococcus pneumoniae were 92% for tigecycline and 89% for levofloxacin. Nausea, vomiting, and diarrhoea were the most frequently reported adverse events. Rates of premature discontinuation of study drug or study withdrawal because of any adverse event were similar for both study drugs.. These findings suggest that IV tigecycline is non-inferior to IV levofloxacin and is generally well-tolerated in the treatment of hospitalized adults with CAP.. NCT00081575.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Community-Acquired Infections; Diarrhea; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infusions, Intravenous; Levofloxacin; Male; Middle Aged; Minocycline; Nausea; Ofloxacin; Pneumonia, Bacterial; Prospective Studies; Severity of Illness Index; Tigecycline; Treatment Outcome; Vomiting; Young Adult

To compare the effect of tigecycline monotherapy, a first-in-class, expanded broad spectrum glycylcycline, with the combination of vancomycin and aztreonam (V + A) in the treatment of complicated skin and skin structure infections (cSSSI).. A phase 3, double-blind study conducted in 8 countries enrolled adults with cSSSI who required intravenous (IV) antibiotic therapy for > or =5 days. Patients were randomly assigned (1:1) to receive either tigecycline or V + A for up to 14 days. Primary endpoint was the clinical cure rate at the test-of-cure visit. Secondary endpoints included microbiologic efficacy and in vitro susceptibility to tigecycline of bacteria that cause cSSSI. Safety was assessed by physical examination, laboratory analyses, and adverse event reporting.. A total of 596 patients were screened for enrollment, 573 were analyzed for safety, 537 were included in the clinical modified intent-to-treat (c-mITT) population, 397 were clinically evaluable (CE), and 228 were microbiologically evaluable (ME). At test-of-cure, cure rates were similar between tigecycline and V + A groups in the CE population (82.9% versus 82.3%, respectively) and in the c-mITT population (75.5% versus 76.9%, respectively). Microbiologic eradication rates (subject level) at test-of-cure in the ME population were also similar between tigecycline and V + A. Frequency of adverse events was similar between groups, although patients receiving tigecycline had higher incidence of nausea, vomiting, dyspepsia, and anorexia, while increased ALT/SGPT, pruritus, and rash occurred significantly more often in V + A-treated patients.. This study demonstrates that the efficacy of tigecycline monotherapy for the treatment of patients with cSSSI is statistically noninferior to the combination of V + A.

Topics: Anti-Bacterial Agents; Aztreonam; Double-Blind Method; Drug Therapy, Combination; Female; Gram-Positive Cocci; Humans; India; Injections, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Nausea; North America; Skin Diseases, Bacterial; South America; Streptococcus pyogenes; Tigecycline; Treatment Outcome; Vancomycin; Vomiting

In addition to tetracyclines, zinc may constitute an alternative treatment in inflammatory lesions of acne.. To evaluate the place of zinc gluconate in relation to antibiotics in the treatment of acne vulgaris.. Zinc was compared to minocycline in a multicenter randomized double-blind trial. 332 patients received either 30 mg elemental zinc or 100 mg minocycline over 3 months. The primary endpoint was defined as the percentage of the clinical success rate on day 90 (i.e. more than 2/3 decrease in inflammatory lesions, i.e. papules and pustules).. This clinical success rate was 31.2% for zinc and 63.4% for minocycline. Minocycline nevertheless showed a 9% superiority in action at 1 month and one of 17% at 3 months, with respect to the mean change in lesion count. Regarding safety, the majority of the adverse effects of zinc gluconate and of minocycline concerned the gastrointestinal system and were moderate (5 dropouts with zinc gluconate and 4 with minocycline).. Minocycline and zinc gluconate are both effective in the treatment of inflammatory acne, but minocycline has a superior effect evaluated to be 17% in our study.

Topics: Abdominal Pain; Acne Vulgaris; Adolescent; Adult; Anti-Bacterial Agents; Arthralgia; Dermatitis, Seborrheic; Double-Blind Method; Female; Gluconates; Humans; Hypersensitivity; Male; Minocycline; Nausea; Patient Compliance; Patient Dropouts; Patient Satisfaction; Skin; Treatment Outcome; Urticaria; Vomiting; Zinc

The incidence of side effects due to two dosage regimens of minocycline was examined over a 5-day period. A total of 60 normal women volunteers were randomly assigned in a double-blind manner to either a group who took 100 mg of minocycline twice a day or a group who took 75 mg of minocycline twice a day for 5 days. Both groups were comparable from the standpoints of age, size, race, and the use of oral contraception, nicotine, and ethanol. They were seen on a daily basis, and symptoms were evaluated by both volunteers (from diaries) and physicians. Minocycline serum concentrations were determined on blood samples taken 2 h after the a.m. dose. Volunteers taking 150 mg of minocycline per day had significantly lower serum antibiotic concentrations than those taking 200 mg per day. However, both low- and high-dose groups exhibited similar incidence and prevalence of recorded symptoms, with the single exception of nausea, where the low-dose group had fewer symptoms than the high-dose group (P = 0.035). Symptomatic volunteers did not have higher serum concentrations of minocycline than their asymptomatic counterparts. When either weight or surface area was examined with antibiotic serum concentration there was a significant inverse correlation between the two on day 2 for both groups and also on day 4 for the low-dose group. It is concluded that, in women, a dose of 150 mg of minocycline per day is associated with the same degree of side effects as a dose of 200 mg per day.

Topics: Adolescent; Adult; Body Surface Area; Dissociative Disorders; Double-Blind Method; Drug Administration Schedule; Female; Humans; Minocycline; Nausea; Sex Factors; Tetracyclines; Vestibule, Labyrinth

A high rate of side effects (mostly vestibular) was found among 83 people receiving prophylaxis with minocycline because of contact with a patient who had died of meningitis due to Neisseria meningitidis. Three groups of contacts received different lots of minocycline and different dosage regimens. Seventy-eight percent of these people had symptoms temporally related to ingestion of minocycline. These symptoms, which included dizziness, nausea, vomiting, vertigo, anorexia, and headache, generally commenced soon after initiation of chemoprophylaxis; the total dosage of minocycline was low. The high rate of vestibular side effects of minocycline militates against widespread use of minocycline for prophylaxis of meningococcal infection.

Topics: Adult; Anorexia; Clinical Trials as Topic; Female; Headache; Humans; Meningitis, Meningococcal; Minocycline; Nausea; Neisseria meningitidis; Tetracyclines; Vertigo; Vestibule, Labyrinth; Vomiting

We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M. hominis infections are prone to being misdiagnosed and undertreated. M. hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail.

Topics: Abscess; Adult; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Bronchoscopy; Cardiomyopathy, Restrictive; Debridement; Dyspnea; Glucocorticoids; Graft Rejection; Heart-Lung Transplantation; Humans; Hypertension, Pulmonary; Levofloxacin; Male; Methylprednisolone; Minocycline; Mycoplasma hominis; Nausea; Plasmapheresis; Postoperative Complications; Respiratory Insufficiency; Sternum; Surgical Wound Infection; Tomography, X-Ray Computed; Young Adult

Topics: Abdominal Pain; Anti-Bacterial Agents; Female; Humans; Middle Aged; Minocycline; Nausea; Pancreatitis; Tigecycline; Vomiting

Tigecycline, the first in a new class of glycylcyclines, has been approved for the treatment of complicated skin and skin structure and intraabdominal infections in adults. However, clinical data on its safety and effectiveness in cancer patients are lacking. We reviewed the records of all cancer patients treated with tigecycline for more than 48 hours between June 2005 and September 2006 at our institution and identified 110 consecutive cases (median age, 58 yr; range, 18-81 yr). We collected data on demographics, cancer type, tigecycline indication, microbiologic characteristics, side effects, and outcome. Sixty-four (58%) patients had hematologic malignancies; 27 patients had undergone hematopoietic stem cell transplantation. Thirty-one (28%) patients had neutropenia, and 62 (56%) were in the intensive care unit at the start of therapy. Most patients (106 [96%]) received tigecycline as a second-line agent (after not responding to other broad-spectrum antibiotics), and 101 (92%) received it in combination with an antipseudomonal drug. The mean duration of therapy was 11 days (range, 3-35 d). Sixty-six (60%) patients received tigecycline for refractory pneumonia, 19 (17%) had bacteremia, 9 (8%) had intraabdominal infections, and 7 (6%) had complicated skin and soft tissue infections. Fifty (45%) patients had microbiologically documented infections, and the remaining patients had negative cultures at the start of therapy.An overall clinical response was noted in 70 (64%) patients. More clinical responses were seen in patients with bacteremia than in those with pneumonia (79% vs. 51%; p = 0.029). Patients with microbiologically documented infections had significantly higher clinical response rates than patients with non-microbiologically documented infections (73% vs. 55%; p = 0.047). Forty (36%) patients did not respond to treatment; 36 of these patients died of active infection during tigecycline therapy. Patients with pneumonia had a significantly higher mortality rate than patients with bacteremia (44% vs. 16%; p = 0.026). During the 60 days of follow-up from the date of clinical response, patients with pneumonia had significantly shorter survival durations than patients with other infections. Of the 42 patients who were not on antiemetics or ventilator support at the start of tigecycline therapy, 2 (5%) experienced mild nausea, and 1 (2%) experienced nausea and vomiting. Only 4 (4%) patients overall experienced diarrhea during tigecycline therapy, all

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Female; Hematopoietic Stem Cell Transplantation; Humans; Kaplan-Meier Estimate; Leukemia; Lymphoma; Male; Middle Aged; Minocycline; Nausea; Pneumonia, Bacterial; Retrospective Studies; Tigecycline; Treatment Outcome; Vomiting; Young Adult

Tigecycline exposure (area under the concentration-time curve [AUC((0-infinity))] and maximum serum concentration [C(max)]) and first occurrence of nausea and vomiting were evaluated in 136 healthy subjects after 12.5- to 300-mg single doses. Nausea was more frequent in females (46%, 10/22) compared with males (31%, 11/36) after 100-mg doses. Most nausea (vomiting) events occurred < or =4 h (<6 h) after tigecycline. For doses < or =100 mg, the median duration of nausea and vomiting was approximately 5 h. Based on logistic regression, increased exposure (AUC((0-infinity)) >C(max)) to tigecycline results in an increased rate of nausea (P < or = .0001; = .0022) and vomiting (P < or = .0001; = .0006). At the median AUC((0-infinity)) (C(max)) for the 50-mg dose group, the probability of nausea and vomiting was 0.26 (0.29) and 0.07 (0.11), respectively. Model-predicted rates of nausea and vomiting were comparable with those observed for the tetracycline class of antibiotics, with tolerable rates predicted after 50-mg doses of tigecycline.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Female; Humans; Male; Middle Aged; Minocycline; Nausea; Tigecycline; Time Factors; Vomiting; Young Adult

A new broad spectrum antibiotic with activity against many drug-resistant organisms.

Topics: Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Humans; Infusion Pumps; Minocycline; Nausea; Skin Diseases; Tigecycline; Vomiting

The WHO MDT regimens have proved highly successful in preventing relapse of leprosy cases. It has indirectly lad to marked reduction in prevalence of disabilities. For PB leprosy, rifampicin 600 mg monthly and 100 mg dapsone daily for a total of 6 months therapy is required. For MB leprosy clofazimine 300 mg once monthly, supervised and 50 mg daily self administered is added. For single skin lesion the current WHO recommendation is 600 mg rifampicin + 400 mg ofloxacin + 100 mg minocycline given as a single dose for adults. Dose adjustment for children and clinical information have been discussed in a nutshell. A number of trials are going on, some are yet to be completed which do offer the prospect of perhaps simplifying therapy and improving with shorter duration.

Topics: Anti-Bacterial Agents; Clofazimine; Dapsone; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Hypersensitivity; India; Leprosy; Minocycline; Nausea; Ofloxacin; Rifampin; Secondary Prevention; Tuberculosis; World Health Organization

Topics: Abdominal Pain; Adolescent; Anti-Bacterial Agents; Back Pain; Diagnosis, Differential; Diplopia; Emergency Nursing; Female; Humans; Medical History Taking; Minocycline; Nausea; Nursing Assessment; Physical Examination; Pseudotumor Cerebri

Cogan's syndrome is a rare clinical entity defined by the association of a nonsyphilitic interstitial keratitis and vestibuloauditory dysfunction, typically Menière's disease-like; the condition has been reported in association with a variety of cutaneous diseases. We now report a case of pyoderma gangrenosum complicating Cogan's syndrome in a 57-year-old woman, which then healed dramatically, as more interestingly did the associated uveitis with minocycline therapy.

Topics: Ataxia; Deafness; Female; Humans; Keratitis; Meniere Disease; Middle Aged; Minocycline; Nausea; Pyoderma Gangrenosum; Syndrome; Uveitis; Vertigo; Vomiting

A 15-year-old girl, who had been treated with minocyclin for acne for 2 months, was admitted for investigation of headache, nausea and papilledema. A space-occupying lesion was ruled out by computerized brain tomography. The diagnosis of benign intracranial pressure (pseudo-tumor cerebri) was made because of elevated cerebrospinal fluid pressure with normal biochemistry and cytology. Tetracyclines, especially minocyclin, commonly used for treating acne in adolescents, can cause benign intracranial pressure.

Topics: Acetazolamide; Adolescent; Anti-Bacterial Agents; Diuretics; Female; Headache; Humans; Minocycline; Nausea; Papilledema; Pseudotumor Cerebri

Minocycline hydrochloride is a tetracycline derivative that has been advocated as the drug of choice in the treatment of meningococcal carriers. Recently, we studied a group of 30 patients who experienced a large number of side-effects after receiving minocycline for treatment of meningococcal meningitis. Twenty-seven of 30 (90%) suffered from dizziness, vertigo, ataxia, weakness, nausea, and vomiting. These symptoms appeared within the first 72 hours of taking minocycline, and disappeared within 48 hours of stopping the medication.

Topics: Adult; Ataxia; Child; Female; Humans; Male; Meningitis, Meningococcal; Minocycline; Nausea; Tetracyclines; Vertigo; Vomiting