6 ADVERSE REACTIONS The following serious and otherwise important adverse reaction is described in greater detail in the Warnings and Precautions section of the label: Anaphylactic Reactions [see Warnings and Precautions [5.1)] The most common adverse reactions (≥3%) for CEFTIN tablets are diarrhea, nausea/vomiting, Jarisch‑Herxheimer reaction, and vaginitis (early Lyme disease). (6.1) The most common adverse reactions (≥2%) for CEFTIN for oral suspension are diarrhea, dislike of taste, diaper rash, and nausea/vomiting. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Tablets Multiple‑Dose Dosing Regimens with 7 to 10 Days’ Duration: In multiple-dose clinical trials, 912 subjects were treated with CEFTIN (125 to 500 mg twice daily). It is noted that 125 mg twice daily is not an approved dosage. Twenty (2.2%) subjects discontinued medication due to adverse reactions. Seventeen (85%) of the 20 subjects who discontinued therapy did so because of gastrointestinal disturbances, including diarrhea, nausea, vomiting, and abdominal pain. The percentage of subjects treated with CEFTIN who discontinued study drug because of adverse reactions was similar at daily doses of 1,000, 500, and 250 mg (2.3%, 2.1%, and 2.2%, respectively). However, the incidence of gastrointestinal adverse reactions increased with the higher recommended doses. The adverse reactions in Table 5 are for subjects (n = 912) treated with CEFTIN in multiple‑dose clinical trials. Table 5. Adverse Reactions (≥1%) after Multiple‑Dose Regimens with CEFTIN Tablets Adverse Reaction CEFTIN (n = 912) Blood and lymphatic system disorders Eosinophilia 1% Gastrointestinal disorders Diarrhea 4% Nausea/Vomiting 3% Investigations Transient elevation in AST 2% Transient elevation in ALT 2% Transient elevation in LDH 1% The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 912) treated with CEFTIN in multiple-dose clinical trials. Immune System Disorders: Hives, swollen tongue. Metabolism and Nutrition Disorders: Anorexia. Nervous System Disorders: Headache. Cardiac Disorders: Chest pain. Respiratory Disorders: Shortness of breath. Gastrointestinal Disorders: Abdominal pain, abdominal cramps, flatulence, indigestion, mouth ulcers. Skin and Subcutaneous Tissue Disorders: Rash, itch. Renal and Urinary Disorders: Dysuria. Reproductive System and Breast Disorders: Vaginitis, vulvar itch. General Disorders and Administration Site Conditions: Chills, sleepiness, thirst. Investigations: Positive Coombs’ test. Early Lyme Disease with 20-Day Regimen: Two multicenter trials assessed CEFTIN 500 mg twice daily for 20 days. The most common drug‑related adverse experiences were diarrhea (10.6%), Jarisch‑Herxheimer reaction (5.6%), and vaginitis (5.4%). Other adverse experiences occurred with frequencies comparable to those reported with 7 to 10 days’ dosing. Single‑Dose Regimen for Uncomplicated Gonorrhea: In clinical trials using a single 1,000-mg dose of CEFTIN, 1,061 subjects were treated for uncomplicated gonorrhea. The adverse reactions in Table 6 were for subjects treated with a single dose of 1,000 mg CEFTIN in U.S. clinical trials. Table 6. Adverse Reactions (≥1%) after Single‑Dose Regimen with 1,000-mg CEFTIN Tablets for Uncomplicated Gonorrhea Adverse Reaction CEFTIN (n = 1,061) Gastrointestinal disorders Nausea/Vomiting 7% Diarrhea 4% The following adverse reactions occurred in less than 1% but greater than 0.1% of subjects (n = 1,061) treated with a single dose of CEFTIN 1,000 mg for uncomplicated gonorrhea in U.S. clinical trials. Infections and Infestations: Vaginal candidiasis. Nervous System Disorders: Headache, dizziness, somnolence. Cardiac Disorders: Tightness/pain in chest, tachycardia. Gastrointestinal Disorders: Abdominal pain, dyspepsia. Skin and Subcutaneous Tissue Disorders: Erythema, rash, pruritus. Musculoskeletal and Connective Tissue Disorders: Muscle cramps, muscle stiffness, muscle spasm of neck, lockjaw-type reaction. Renal and Urinary Disorders: Bleeding/pain in urethra, kidney pain. Reproductive System and Breast Disorders: Vaginal itch, vaginal discharge. Oral Suspension In clinical trials using multiple doses of CEFTIN, pediatric subjects (96.7% were younger than 12 years) were treated with CEFTIN (20 to 30 mg/kg/day divided twice daily up to a maximum dose of 500 or 1,000 mg/day, respectively). Eleven (1.2%) U.S. subjects discontinued medication due to adverse reactions. The discontinuations were primarily for gastrointestinal disturbances, usually diarrhea or vomiting. Thirteen (1.4%) U.S. pediatric subjects discontinued therapy due to the taste and/or problems with drug administration. The adverse reactions in Table 7 are for U.S. subjects (n = 931) treated with CEFTIN in multiple‑dose clinical trials. Table 7. Adverse Reactions (≥1%) after Multiple‑Dose Regimens with CEFTIN for Oral Suspension Adverse Reaction CEFTIN (n = 931) Gastrointestinal disorders Diarrhea 9% Dislike of taste 5% Nausea/vomiting 3% Skin and subcutaneous tissue disorders Diaper rash 3% The following adverse reactions occurred in less than 1% but greater than 0.1% of U.S. subjects (n = 931) treated with CEFTIN for oral suspension in multiple‑dose clinical trials. Infections and Infestations: Gastrointestinal infection, candidiasis, viral illness, upper respiratory infection, sinusitis, urinary tract infection. Blood and Lymphatic System Disorders: Eosinophilia. Psychiatric Disorders: Hyperactivity, irritable behavior. Gastrointestinal Disorders: Abdominal pain, flatulence, ptyalism. Skin and Subcutaneous Tissue Disorders: Rash. Musculoskeletal and Connective Tissue Disorders: Joint swelling, arthralgia. Reproductive System and Breast Disorders: Vaginal irritation. General Disorders and Administration Site Conditions: Cough, fever. Investigations: Elevated liver enzymes, positive Coombs’ test. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of CEFTIN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders Hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia. Gastrointestinal Disorders Pseudomembranous colitis [see Warnings and Precautions (5.2)]. Hepatobiliary Disorders Hepatic impairment including hepatitis and cholestasis, jaundice. Immune System Disorders Anaphylaxis, serum sickness‑like reaction. Investigations Increased prothrombin time. Nervous System Disorders Seizure, encephalopathy. Renal and Urinary Disorders Renal dysfunction. Skin and Subcutaneous Tissue Disorders Angioedema, erythema multiforme, Stevens‑Johnson syndrome, toxic epidermal necrolysis, urticaria.