HP Kit

Amoxicillin:

• Pharmacological action
• Pharmacokinetics
• Why is HP Kit prescribed?
• Dosage and administration
• HP Kit (Amoxicillin) side effects, adverse reactions
• Contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• Precautionary measures
• HP Kit drug interactions
• HP Kit in case of emergency / overdose
• HP Kit (Amoxicillin) reviews

Pharmacological action

HP Kit is an antibiotic of group semisynthetic penicillins a wide spectrum of action. It is a 4-hydroxyl analog of ampicillin. It has bactericidal action. HP Kit (Amoxicillin) is active against aerobic gram-positive bacteria: Staphylococcus spp. (except strains producing penicillinase), Streptococcus spp; aerobic gram-negative bacteria: Neisseria Gonorrhoeae, Neisseria Meningitidis, Escherichia Coli, Shigella spp., Salmonella spp., Klebsiella spp.

Microorganisms producing penicillinase is resistant to HP Kit (Amoxicillin).

In combination with metronidazole HP Kit (Amoxicillin) is active against Helicobacter Pylori. It is believed that inhibits the development of HP Kit (Amoxicillin) resistance of Helicobacter pylori to metronidazole.

There is a cross-resistance between amoxycillin and ampicillin.

The spectrum of antibacterial action while expanding the application of HP Kit (Amoxicillin) and beta-lactamase inhibitor clavulanic acid. This combination increased the activity of HP Kit (Amoxicillin) against Bacteroides spp., Legionella spp., Nocardia spp., Pseudomonas (Burkholderia) Pseudomallei. However, Pseudomonas Aeruginosa, Serratia Marcescens, and many other gram-bacteria are resistant.

Pharmacokinetics

When HP Kit (Amoxicillin) administered orally HP Kit (Amoxicillin) rapidly and completely absorbed from the gastrointestinal tract and is not destroyed in the acidic environment of the stomach. C_max of HP Kit (Amoxicillin) in the blood plasma is reached after 1-2 h. When increasing doses of 2 times the concentration also increased by 2 times. In the presence of food in the stomach does not reduce the overall removals. Similar concentrations of HP Kit (Amoxicillin) reached in the blood when administered orally, IV and IM.

The binding of HP Kit (Amoxicillin) to plasma proteins is about 20%.

Widely distributed in tissues and body fluids. Reported high concentrations of HP Kit (Amoxicillin) in the liver.

T1/2 from the plasma is 1-1.5 h. About 60% of the dose adopted by mouth, is excreted unchanged in the urine by glomerular filtration and tubular secretion, with a dose of 250 mg of HP Kit (Amoxicillin) concentration in urine exceeds 300 micrograms / ml. A number of HP Kit (Amoxicillin) is determined in feces.

T1/2 for Newborns and the elderly can be longer.

In renal insufficiency T1/2 may be 7-20 hours.

In small quantities HP Kit (Amoxicillin) penetrates through BBB in inflammation of the pia mater.

HP Kit (Amoxicillin) is removed by hemodialysis.

Why is HP Kit prescribed?

For use HP Kit (Amoxicillin) as monotherapy and in combination with clavulanic acid: an infectious-inflammatory diseases caused by susceptible microorganisms, including bronchitis, pneumonia, tonsillitis, pyelonephritis, urethritis, infections of the gastrointestinal tract, gynecological infections, infections of the skin and soft tissue, listeria, leptospirosis, gonorrhea.

For use HP Kit (Amoxicillin) in combination with metronidazole: chronic gastritis in acute, peptic ulcer and duodenal ulcer in acute, associated with Helicobacter Pylori.

Dosage and administration

Individual. For oral single dose for adults and children over 10 years is 250-500 mg, in case of serious illness - up to 1 g. For children aged 5-10 years, a single dose of 250 mg in age from 2 to 5 years - 125 mg for children aged under 2 years of daily dose is 20 mg / kg. For adults and children interval is 8 h. In the treatment of acute uncomplicated gonorrhea - 3 g once (in combination with probenecid). Patients with impaired renal function in creatinine clearance 10-40 ml / min interval between doses should be increased to 12 h and if creatinine clearance is less than 10 ml / min interval between doses should be 24 hours.

When parenteral use in adults IM - 1 g 2 times / day, IV (with normal renal function) - 2.12 g / day. Children IM 50 mg / kg / day, single dose - 500 mg, the frequency of administration - 2 times / day; IV - 100-200 mg / kg / day. Patients with impaired renal function the dose and the interval between the injections need to be adjusted in accordance with the values of creatinine clearance.

HP Kit (Amoxicillin) side effects, adverse reactions

Allergic reactions: urticaria, erythema, edema Quincke, rhinitis, conjunctivitis, rarely - fever, joint pain, eosinophilia, in rare cases - anaphylactic shock.

Side effects associated with chemotherapy effect: possible development of super-infection (particularly in patients with chronic diseases or low resistance of the organism).

With prolonged use at high doses: dizziness, ataxia, confusion, depression, peripheral neuropathy, seizures.

Mostly when HP Kit (Amoxicillin) used in combination with metronidazole: nausea, vomiting, anorexia, diarrhea, constipation, epigastric pain, glossitis, stomatitis; rarely - hepatitis, pseudomembranous colitis, allergic reactions (urticaria, angioedema), interstitial nephritis, a violation of hematopoiesis.

Mostly when HP Kit (Amoxicillin) used in combination with clavulanic acid: cholestatic jaundice, hepatitis, rarely - erythema multiforme, toxic epidermal necrolysis, exfoliative dermatitis.

Contraindications

Infectious mononucleosis, lymphatic leukemia, severe gastrointestinal infections, accompanied by diarrhea or vomiting, respiratory viral infection, allergic diathesis, bronchial asthma, hay fever, sensitivity to penicillin and / or cephalosporins.

For use in combination with metronidazole: diseases of the nervous system; hemodyscrasia, lymphocytic leukemia, an infectious mononucleosis; Hypersensitivity to nitroimidazole derivatives.

For use in combination with clavulanic acid: a history of instructions for liver problems and jaundice, associated with the reception of HP Kit in combination with clavulanic acid.

Using during pregnancy and breastfeeding

HP Kit (Amoxicillin) crosses the placenta, in small amounts excreted in breast milk.

If necessary the use of HP Kit (Amoxicillin) during pregnancy should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus.

With careful use HP Kit (Amoxicillin) during lactation (breastfeeding).

Special instructions

With caution used in patients prone to allergic reactions.

HP Kit in combination with metronidazole is not recommended to use in patients younger than 18 years should not be used for liver diseases.

In the combined therapy with metronidazole is recommended not to drink alcohol.

Precautionary measures

Treatment must continue 48-72 hours after the disappearance of clinical signs of disease, with streptococcal infections - 10 days.

During the course treatment is necessary to control the state functions of hematopoiesis, liver and kidneys.

Perhaps the development of superinfection due to growth insensitive to the drug microflora. In the case of superinfection requires removal of HP Kit (Amoxicillin) and the corresponding change in antibiotic therapy. When treating patients with bacteremia may develop bacteriolysis reaction (reaction of Jarisch-Herxheimer).

Patients who have an increased sensitivity to penicillin, may be cross-allergic reactions to cephalosporin antibiotics.

In the treatment of mild diarrhea at the background of the treatment should be avoided antidiarrhoeal drugs that reduce intestinal motility; can use kaolin or attapulgite containing antidiarrhoeal stuff. Patients with severe diarrhea should consult a doctor.

With simultaneous use of HP Kit (Amoxicillin) and oral contraceptives estrogensoderzhaschih and HP Kit (Amoxicillin) should if possible to use additional methods of contraception.

HP Kit drug interactions

HP Kit (Amoxicillin) may decrease the effectiveness of contraceptives for oral administration.

With the simultaneous use of HP Kit (Amoxicillin) with bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) appears synergies; with bacteriostatic antibiotic (including macrolides, chloramphenicol, lincosamides, tetracyclines, sulphonamide) - antagonism.

HP Kit (Amoxicillin) increases the effects of indirect anticoagulants inhibiting intestinal microflora, reduces the synthesis of vitamin K and prothrombin index.

HP Kit (Amoxicillin) reduces the effect of drugs, in the process of metabolism that produce PABA.

Probenecid, diuretics, allopurinol, phenylbutazone, NSAIDs decrease the tubular secretion of HP Kit (Amoxicillin), which can be accompanied by an increase in its concentration in blood plasma.

Antacids, glucosamine, laxatives, aminoglycosides, slow down and reduce, and ascorbic acid increases the absorption of HP Kit (Amoxicillin).

With the combined use of HP Kit (Amoxicillin) and clavulanic acid pharmacokinetics of both components unchanged.

HP Kit in case of emergency / overdose

Symptoms: nausea, vomiting, diarrhea, disruption of water and electrolyte balance (as a result of vomiting and diarrhea); for prolonged use at high doses - neurotoxic reactions and thrombocytopenia (these phenomena are reversible and disappear after drug withdrawal).

Treatment: gastric lavage, the prescription of activated charcoal, saline laxatives, correction of water and electrolyte balance; hemodialysis.

Omeprazole:

• Pharmacological action
• Pharmacokinetics
• Why is HP Kit prescribed?
• Dosage and administration
• HP Kit (Omeprazole) side effects, adverse reactions
• HP Kit contraindications
• Using during pregnancy and breastfeeding
• Special instructions
• HP Kit drug interactions
• HP Kit in case of emergency / overdose
• HP Kit (Omeprazole) reviews

Pharmacological action

HP Kit is an inhibitor of H+ K+ ATPase. This medication inhibits the activity of H+-K+-ATPase in gastric parietal cells and thus blocks the final stage of hydrochloric acid secretion. This leads to a reduction in basal and stimulated secretion, regardless of the nature of the stimulus. Due to the reduction of acid secretion HP Kit (Omeprazole) reduces or normalizes the effects of acid in the esophagus in patients with reflux esophagitis.

HP Kit (Omeprazole) has a bactericidal effect on Helicobacter pylori. Eradication of H. pylori when HP Kit (Omeprazole) used with antibiotics allows to quickly arrest the symptoms, to take a high degree of healing of damaged mucosa and persistent long-term remission and reduce the likelihood of bleeding from the gastrointestinal tract.

Pharmacokinetics

After oral administration HP Kit (Omeprazole) is rapidly absorbed from the gastrointestinal tract. This drug penetrates the parietal cells of gastric mucosa. Plasma protein binding is about 95% (predominantly albumin). HP Kit (Omeprazole) is biotransformed in the liver. Excreted by the kidneys - 72-80%, in the faeces - about 20%. T_1/2 is 0.5-1 h. In patients with chronic liver diseases T_1/2 increases up to 3 hours.

Why is HP Kit prescribed?

Gastric ulcer and duodenal ulcer in acute phase (including associated with Helicobacter pylori), reflux esophagitis, Zollinger-Ellison syndrome, erosive and ulcerative lesions of gastric and duodenal ulcers associated with taking NSAIDs.

Dosage and administration

The dosing regimen of HP Kit is individual. When this medication is administered orally of the single dose is 20-40 mg. The daily dose is 20-80 mg, the frequency of use is 1-2 times / day. The duration of treatment is 2-8 weeks.

HP Kit (Omeprazole) side effects, adverse reactions

Digestive system: rarely - nausea, diarrhea, constipation, abdominal pain, flatulence.

CNS: rarely - headache, dizziness, weakness.

Hemopoietic system: in some cases - anemia, eosinopenia, neutropenia, thrombocytopenia.

Urinary system: in some cases - hematuria, proteinuria.

Musculoskeletal system: in some cases - arthralgia, muscle weakness, myalgia.

Allergic reactions: rarely - skin rash.

HP Kit contraindications

Chronic liver disease (including in history), hypersensitivity to HP Kit (Omeprazole).

Using during pregnancy and breastfeeding

In the absence of clinical experience with HP Kit it is not recommended to use this drug during pregnancy. If necessary to use during HP Kit (Omeprazole) lactation it should been solve the issue of termination of breastfeeding.

Category effects on the fetus by FDA - C.

Special instructions

Before the treatment with HP Kit (Omeprazole) it is necessary to exclude the possibility of a malignant process (especially gastric ulcer) because HP Kit (Omeprazole) treatment can mask symptoms and delay the correct diagnosis.

Therapy with HP Kit (Omeprazole) may affects results of laboratory studies of liver and gastrin concentrations in blood plasma.

Due to lack of experience in clinical application of HP Kit (Omeprazole) this medicine is not recommended for children.

HP Kit drug interactions

This medication alters the bioavailability of any drug, absorption depends on pH (ketoconazole, iron salts, etc.). HP Kit (Omeprazole) slows down the elimination of drugs metabolized in the liver by microsomal oxidation (warfarin, diazepam, phenytoin, etc.).

HP Kit (Omeprazole) enhances the action of coumarin and diphenine, does not change - NSAIDs. This drug increases (relative) the concentration of clarithromycin in the blood; may increases the leukopenic and thrombocytopenic effects of depressants hematopoiesis drugs. Substance for intravenous infusion is compatible only with saline and dextrose (using other solvents may decrease the stability of HP Kit (Omeprazole) due to changes in pH of infusion medium).

HP Kit in case of emergency / overdose

Symptoms: dry mouth, nausea, blurred vision, headache, increased sweating, flushing, tachycardia, drowsiness, confusion.

Treatment: symptomatic, dialysis is ineffective.

Tinidazole:

• Warning: potential risk for carcinogenicity
• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• Patient counseling information
• HP Kit (Tinidazole) reviews

WARNING: POTENTIAL RISK FOR CARCINOGENICITY

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent ( 13.1). Although such data have not been reported for HP Kit (Tinidazole), the two drugs are structurally related and have similar biologic effects. Its use should be reserved for the conditions described in INDICATIONS AND USAGE ( 1).

WARNING: POTENTIAL RISK FOR CARCINOGENICITY

See full prescribing information for complete boxed warning.

Carcinogenicity has been seen in mice and rats treated chronically with metronidazole, another nitroimidazole agent ( 13.1). Although such data have not been reported for HP Kit (Tinidazole), the two drugs are structurally related and have similar biologic effects. Use should be limited to approved indications only.

Indications and Usage, Bacterial Vaginosis ( 1.4) 5/2007

Dosage and Administration, Bacterial Vaginosis ( 2.6) 5/2007

1 INDICATIONS AND USAGE

HP Kit is a nitroimidazole antimicrobial indicated for:

• Trichomoniasis ( 1.1)
• Giardiasis: in patients age 3 and older ( 1.2)
• Amebiasis: in patients age 3 and older ( 1.3)
• Bacterial Vaginosis: in non-pregnant, adult women ( 1.4, 8.1)

1.1 Trichomoniasis

HP Kit (Tinidazole) is indicated for the treatment of trichomoniasis caused by Trichomonas vaginalis. The organism should be identified by appropriate diagnostic procedures. Because trichomoniasis is a sexually transmitted disease with potentially serious sequelae, partners of infected patients should be treated simultaneously in order to prevent re-infection .

1.2 Giardiasis

HP Kit is indicated for the treatment of giardiasis caused by Giardia duodenalis (also termed G. lamblia) in both adults and pediatric patients older than three years of age .

1.3 Amebiasis

HP Kit (Tinidazole) is indicated for the treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in both adults and pediatric patients older than three years of age. It is not indicated in the treatment of asymptomatic cyst passage .

1.4 Bacterial Vaginosis

HP Kit (Tinidazole) is indicated for the treatment of bacterial vaginosis (formerly referred to as Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, or anaerobic vaginosis) in non-pregnant women .

Other pathogens commonly associated with vulvovaginitis such as Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans and Herpes simplex virus should be ruled out.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of HP Kit (Tinidazole) and other antibacterial drugs, HP Kit (Tinidazole) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

2 DOSAGE AND ADMINISTRATION

• Trichomoniasis: a single 2 g oral dose taken with food. Treat sexual partners with the same dose and at the same time
• Giardiasis: Adults: a single 2 g dose taken with food. Pediatric patients older than three years of age: a single dose of 50 mg/kg (up to 2 g) with food ( 2.4)
• Amebiasis, Intestinal: Adults: 2 g per day for 3 days with food. Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3 days with food ( 2.5). Amebic liver abscess: Adults: 2 g per day for 3-5 days with food. Pediatric patients older than three years of age: 50 mg/kg/day (up to 2 g per day) for 3-5 days with food ( 2.5)
• Bacterial vaginosis: Non-pregnant, adult women: 2 g once daily for 2 days taken with food, or 1 g once daily for 5 days taken with food ( 2.6)

2.1 Dosing Instructions

It is advisable to take HP Kit (Tinidazole) with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of HP Kit (Tinidazole) .

Alcoholic beverages should be avoided when taking HP Kit (Tinidazole) and for 3 days afterwards .

2.2 Compounding of the Oral Suspension

For those unable to swallow tablets, HP Kit tablets may be crushed in artificial cherry syrup to be taken with food.

Procedure for Extemporaneous Pharmacy Compounding of the Oral Suspension: Pulverize four 500 mg oral tablets with a mortar and pestle. Add approximately 10 mL of cherry syrup to the powder and mix until smooth. Transfer the suspension to a graduated amber container. Use several small rinses of cherry syrup to transfer any remaining drug in the mortar to the final suspension for a final volume of 30 mL. The suspension of crushed tablets in artificial cherry syrup is stable for 7 days at room temperature. When this suspension is used, it should be shaken well before each administration.

2.3 Trichomoniasis

The recommended dose in both females and males is a single 2 g oral dose taken with food. Since trichomoniasis is a sexually transmitted disease, sexual partners should be treated with the same dose and at the same time.

2.4 Giardiasis

The recommended dose in adults is a single 2 g dose taken with food. In pediatric patients older than three years of age, the recommended dose is a single dose of 50 mg/kg with food.

2.5 Amebiasis

Intestinal: The recommended dose in adults is a 2 g dose per day for 3 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3 days with food.

Amebic Liver Abscess: The recommended dose in adults is a 2 g dose per day for 3-5 days taken with food. In pediatric patients older than three years of age, the recommended dose is 50 mg/kg/day (up to 2 g per day) for 3-5 days with food. There are limited pediatric data on durations of therapy exceeding 3 days, although a small number of children were treated for 5 days without additional reported adverse reactions. Children should be closely monitored when treatment durations exceed 3 days.

2.6 Bacterial Vaginosis

The recommended dose in non-pregnant females is a 2 g oral dose once daily for 2 days taken with food or a 1 g oral dose once daily for 5 days taken with food. The use of HP Kit (Tinidazole) in pregnant patients has not been studied for bacterial vaginosis.

3 DOSAGE FORMS AND STRENGTHS

• 500 mg tablets are pink, oval, scored tablets, with TM debossed on one side and 500 on the other

4 CONTRAINDICATIONS

The use of HP Kit (Tinidazole) is contraindicated:

• In patients with a previous history of hypersensitivity to HP Kit (Tinidazole) or other nitroimidazole derivatives. Reported reactions have ranged in severity from urticaria to Stevens-Johnson syndrome .
• During first trimester of pregnancy .
• In nursing mothers: Interruption of breast-feeding is recommended during HP Kit (Tinidazole) therapy and for 3 days following the last dose .

• Prior history of hypersensitivity to HP Kit (Tinidazole) or other nitroimidazole derivatives ( 4, 6.1, 6.2)
• First trimester of pregnancy ( 4, 8.1)
• Nursing mothers, unless breast-feeding is interrupted during HP Kit (Tinidazole) therapy and for 3 days following the last dose ( 4, 8.3)

5 WARNINGS AND PRECAUTIONS

• Seizures and neuropathy have been reported. Discontinue HP Kit if abnormal neurologic signs develop ( 5.1)
• Vaginal candidiasis may develop with HP Kit (Tinidazole) and require treatment with an antifungal agent ( 5.2)
• Use HP Kit (Tinidazole) with caution in patients with blood dyscrasias. HP Kit (Tinidazole) may produce transient leukopenia and neutropenia ( 5.3, 7.3)

5.1 Neurological Adverse Reactions

Convulsive seizures and peripheral neuropathy, the latter characterized mainly by numbness or paresthesia of an extremity, have been reported in patients treated with HP Kit (Tinidazole). The appearance of abnormal neurologic signs demands the prompt discontinuation of HP Kit (Tinidazole) therapy.

5.2 Vaginal Candidiasis

The use of HP Kit may result in Candida vaginitis. In a clinical study of 235 women who received HP Kit (Tinidazole) for bacterial vaginosis, a vaginal fungal infection developed in 11 (4.7%) of all study subjects .

5.3 Blood Dyscrasia

HP Kit (Tinidazole) should be used with caution in patients with evidence of or history of blood dyscrasia .

5.4 Drug Resistance

Prescribing HP Kit (Tinidazole) in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

6 ADVERSE REACTIONS

Most common adverse reactions for a single 2 g dose of HP Kit (incidence >1%) are metallic/bitter taste, nausea, weakness/fatigue/malaise, dyspepsia/cramps/epigastric discomfort, vomiting, anorexia, headache, dizziness and constipation ( 6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Mission Pharmacal Company at 1-855-778-0177or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

6.1 Clinical Studies 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 to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Among 3669 patients treated with a single 2 g dose of HP Kit (Tinidazole), in both controlled and uncontrolled trichomoniasis and giardiasis clinical studies, adverse reactions were reported by 11.0% of patients. For multi-day dosing in controlled and uncontrolled amebiasis studies, adverse reactions were reported by 13.8% of 1765 patients. Common (≥ 1% incidence) adverse reactions reported by body system are as follows. (Note: Data described in Table 1 below are pooled from studies with variable designs and safety evaluations.)

Other adverse reactions reported with HP Kit (Tinidazole) include:

Central Nervous System: Two serious adverse reactions reported include convulsions and transient peripheral neuropathy including numbness and paresthesia . Other CNS reports include vertigo, ataxia, giddiness, insomnia, drowsiness.

Gastrointestinal: tongue discoloration, stomatitis, diarrhea

Hypersensitivity: urticaria, pruritis, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema

Renal: darkened urine

Cardiovascular: palpitations

Hematopoietic: transient neutropenia, transient leukopenia

Other: Candida overgrowth, increased vaginal discharge, oral candidiasis, hepatic abnormalities including raised transaminase level, arthralgias, myalgias, and arthritis.

	2 g single dose	Multi-day dose
GI: Metallic/bitter taste	3.7%	6.3%
Nausea	3.2%	4.5%
Anorexia	1.5%	2.5%
Dyspepsia/cramps/epigastric discomfort	1.8%	1.4%
Vomiting	1.5%	0.9%
Constipation	0.4%	1.4%
CNS: Weakness/fatigue/malaise	2.1%	1.1%
Dizziness	1.1%	0.5%
Other: Headache	1.3%	0.7%
Total patients with adverse reactions	11.0% (403/3669)	13.8% (244/1765)

Rare reported adverse reactions include bronchospasm, dyspnea, coma, confusion, depression, furry tongue, pharyngitis and reversible thrombocytopenia.

Adverse Reactions in Pediatric Patients: In pooled pediatric studies, adverse reactions reported in pediatric patients taking HP Kit (Tinidazole) were similar in nature and frequency to adult findings including nausea, vomiting, diarrhea, taste change, anorexia, and abdominal pain.

Bacterial vaginosis: The most common adverse reactions in treated patients (incidence >2%), which were not identified in the trichomoniasis, giardiasis and amebiasis studies, are gastrointestinal: decreased appetite, and flatulence; renal: urinary tract infection, painful urination, and urine abnormality; and other reactions including pelvic pain, vulvo-vaginal discomfort, vaginal odor, menorrhagia, and upper respiratory tract infection .

6.2 Postmarketing Experience

The following adverse reactions have been identified and reported during post-approval use of HP Kit (Tinidazole). Because the reports of these reactions are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.

Severe acute hypersensitivity reactions have been reported on initial or subsequent exposure to HP Kit (Tinidazole). Hypersensitivity reactions may include urticaria, pruritis, angioedema, Stevens-Johnson syndrome and erythema multiforme.

7 DRUG INTERACTIONS

Although not specifically identified in studies with HP Kit, the following drug interactions were reported for metronidazole, a chemically-related nitroimidazole. Therefore, these drug interactions may occur with HP Kit (Tinidazole).

The following drug interactions were reported for metronidazole, a chemically-related nitroimidazole and may therefore occur with HP Kit (Tinidazole):

• Warfarin and other oral coumarin anticoagulants: Anticoagulant dosage may need adjustment during and up to 8 days after HP Kit (Tinidazole) therapy ( 7.1)
• Alcohol-containing beverages/preparations: Avoid during and up to 3 days after HP Kit (Tinidazole) therapy ( 7.1)
• Lithium: Monitor serum lithium concentrations ( 7.1)
• Cyclosporine, tacrolimus: Monitor for toxicities of these immunosuppressive drugs ( 7.1)
• Fluorouracil: Monitor for fluorouracil-associated toxicities ( 7.1)
• Phenytoin, fosphenytoin: Adjustment of anticonvulsant and/or HP Kit (Tinidazole) dose(s) may be needed ( 7.1, 7.2)
• CYP3A4 inducers/inhibitors: Monitor for decreased HP Kit (Tinidazole) effect or increased adverse reactions ( 7.2)

7.1 Potential Effects of HP Kit (Tinidazole) on Other Drugs

Warfarin and Other Oral Coumarin Anticoagulants: As with metronidazole, HP Kit (Tinidazole) may enhance the effect of warfarin and other coumarin anticoagulants, resulting in a prolongation of prothrombin time. The dosage of oral anticoagulants may need to be adjusted during HP Kit (Tinidazole) co-administration and up to 8 days after discontinuation.

Alcohols, Disulfiram: Alcoholic beverages and preparations containing ethanol or propylene glycol should be avoided during HP Kit (Tinidazole) therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur. Psychotic reactions have been reported in alcoholic patients using metronidazole and disulfiram concurrently. Though no similar reactions have been reported with HP Kit (Tinidazole), HP Kit (Tinidazole) should not be given to patients who have taken disulfiram within the last two weeks.

Lithium: Metronidazole has been reported to elevate serum lithium levels. It is not known if HP Kit (Tinidazole) shares this property with metronidazole, but consideration should be given to measuring serum lithium and creatinine levels after several days of simultaneous lithium and HP Kit (Tinidazole) treatment to detect potential lithium intoxication.

Phenytoin, Fosphenytoin: Concomitant administration of oral metronidazole and intravenous phenytoin was reported to result in prolongation of the half-life and reduction in the clearance of phenytoin. Metronidazole did not significantly affect the pharmacokinetics of orally-administered phenytoin.

Cyclosporine, Tacrolimus: There are several case reports suggesting that metronidazole has the potential to increase the levels of cyclosporine and tacrolimus. During HP Kit (Tinidazole) co-administration with either of these drugs, the patient should be monitored for signs of calcineurin-inhibitor associated toxicities.

Fluorouracil: Metronidazole was shown to decrease the clearance of fluorouracil, resulting in an increase in side-effects without an increase in therapeutic benefits. If the concomitant use of HP Kit (Tinidazole) and fluorouracil cannot be avoided, the patient should be monitored for fluorouracil-associated toxicities.

7.2 Potential Effects of Other Drugs on HP Kit

CYP3A4 Inducers and Inhibitors: Simultaneous administration of HP Kit (Tinidazole) with drugs that induce liver microsomal enzymes, i.e., CYP3A4 inducers such as phenobarbital, rifampin, phenytoin, and fosphenytoin (a pro-drug of phenytoin), may accelerate the elimination of HP Kit (Tinidazole), decreasing the plasma level of HP Kit (Tinidazole). Simultaneous administration of drugs that inhibit the activity of liver microsomal enzymes, i.e., CYP3A4 inhibitors such as cimetidine and ketoconazole, may prolong the half-life and decrease the plasma clearance of HP Kit (Tinidazole), increasing the plasma concentrations of HP Kit (Tinidazole).

Cholestyramine: Cholestyramine was shown to decrease the oral bioavailability of metronidazole by 21%. Thus, it is advisable to separate dosing of cholestyramine and HP Kit (Tinidazole) to minimize any potential effect on the oral bioavailability of HP Kit (Tinidazole).

Oxytetracycline: Oxytetracycline was reported to antagonize the therapeutic effect of metronidazole.

7.3 Laboratory Test Interactions

HP Kit (Tinidazole), like metronidazole, may interfere with certain types of determinations of serum chemistry values, such as aspartate aminotransferase (AST, SGOT), alanine aminotransferase (ALT, SGPT), lactate dehydrogenase (LDH), triglycerides, and hexokinase glucose. Values of zero may be observed. All of the assays in which interference has been reported involve enzymatic coupling of the assay to oxidation-reduction of nicotinamide adenine dinucleotide (NAD ⁺↔ NADH). Potential interference is due to the similarity of absorbance peaks of NADH and HP Kit (Tinidazole).

HP Kit (Tinidazole), like metronidazole, may produce transient leukopenia and neutropenia; however, no persistent hematological abnormalities attributable to HP Kit (Tinidazole) have been observed in clinical studies. Total and differential leukocyte counts are recommended if re-treatment is necessary.

8 USE IN SPECIFIC POPULATIONS

• Pediatric Use: Data on HP Kit use in children is limited to treatment of giardiasis and amebiasis in patients age 3 and older ( 8.4)
• Hemodialysis patients: If HP Kit (Tinidazole) is administered the same day and prior to hemodialysis, administer an additional ½ dose after end of hemodialysis ( 8.6, 12.3)

See 17 for PATIENT COUNSELING INFORMATION

Revised: 5/2007

8.1 Pregnancy

Teratogenic effects: Pregnancy Category C

The use of HP Kit (Tinidazole) in pregnant patients has not been studied. Since HP Kit (Tinidazole) crosses the placental barrier and enters fetal circulation it should not be administered to pregnant patients in the first trimester.

Embryo-fetal developmental toxicity studies in pregnant mice indicated no embryo-fetal toxicity or malformations at the highest dose level of 2,500 mg/kg (approximately 6.3-fold the highest human therapeutic dose based upon body surface area conversions). In a study with pregnant rats a slightly higher incidence of fetal mortality was observed at a maternal dose of 500 mg/kg (2.5-fold the highest human therapeutic dose based upon body surface area conversions). No biologically relevant neonatal developmental effects were observed in rat neonates following maternal doses as high as 600 mg/kg (3-fold the highest human therapeutic dose based upon body surface area conversions). Although there is some evidence of mutagenic potential and animal reproduction studies are not always predictive of human response, the use of HP Kit (Tinidazole) after the first trimester of pregnancy requires that the potential benefits of the drug be weighed against the possible risks to both the mother and the fetus.

8.3 Nursing Mothers

HP Kit is excreted in breast milk in concentrations similar to those seen in serum. HP Kit (Tinidazole) can be detected in breast milk for up to 72 hours following administration. Interruption of breast-feeding is recommended during HP Kit (Tinidazole) therapy and for 3 days following the last dose.

8.4 Pediatric Use

Other than for use in the treatment of giardiasis and amebiasis in pediatric patients older than three years of age, safety and effectiveness of HP Kit (Tinidazole) in pediatric patients have not been established.

Pediatric Administration: For those unable to swallow tablets, HP Kit (Tinidazole) tablets may be crushed in artificial cherry syrup, to be taken with food .

8.5 Geriatric Use

Clinical studies of HP Kit did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. In general, dose selection for an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

8.6 Renal Impairment

Because the pharmacokinetics of HP Kit (Tinidazole) in patients with severe renal impairment (CrCL < 22 mL/min) are not significantly different from those in healthy subjects, no dose adjustments are necessary in these patients.

Patients undergoing hemodialysis: If HP Kit (Tinidazole) is administered on the same day as and prior to hemodialysis, it is recommended that an additional dose of HP Kit (Tinidazole) equivalent to one-half of the recommended dose be administered after the end of the hemodialysis .

8.7 Hepatic Impairment

There are no data on HP Kit (Tinidazole) pharmacokinetics in patients with impaired hepatic function. Reduced elimination of metronidazole, a chemically-related nitroimidazole, has been reported in this population. Usual recommended doses of HP Kit (Tinidazole) should be administered cautiously in patients with hepatic dysfunction .

10 OVERDOSAGE

There are no reported overdoses with HP Kit (Tinidazole) in humans.

Treatment of Overdosage: There is no specific antidote for the treatment of overdosage with HP Kit (Tinidazole); therefore, treatment should be symptomatic and supportive. Gastric lavage may be helpful. Hemodialysis can be considered because approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session.

11 DESCRIPTION

HP Kit (Tinidazole) is a synthetic antiprotozoal and antibacterial agent. It is 1-[2-(ethylsulfonyl)ethyl]-2-methyl-5-nitroimidazole, a second-generation 2-methyl-5-nitroimidazole, which has the following chemical structure:

HP Kit (Tinidazole) pink oral tablets contain 500 mg of HP Kit (Tinidazole). Inactive ingredients include croscarmellose sodium, FD&C Red 40 lake, FD&C Yellow 6 lake, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized corn starch, titanium dioxide, and triacetin.

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12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

HP Kit is an antiprotozoal, antibacterial agent. .

12.3 Pharmacokinetics

Absorption: After oral administration, HP Kit (Tinidazole) is rapidly and completely absorbed. A bioavailability study of HP Kit (Tinidazole) tablets was conducted in adult healthy volunteers. All subjects received a single oral dose of 2 g (four 500 mg tablets) of HP Kit (Tinidazole) following an overnight fast. Oral administration of four 500 mg tablets of HP Kit (Tinidazole) under fasted conditions produced a mean peak plasma concentration (C _max) of 47.7 (±7.5) µg/mL with a mean time to peak concentration (T _max) of 1.6 (±0.7) hours, and a mean area under the plasma concentration-time curve (AUC, 0-∞) of 901.6 (± 126.5) µg/hr/mL at 72 hours. The elimination half-life (T _1/2) was 13.2 (±1.4) hours. Mean plasma levels decreased to 14.3 µg/mL at 24 hours, 3.8 µg/mL at 48 hours and 0.8 µg/mL at 72 hours following administration. Steady-state conditions are reached in 2½ - 3 days of multi-day dosing.

Administration of HP Kit (Tinidazole) tablets with food resulted in a delay in T _max of approximately 2 hours and a decline in C _max of approximately 10% _, compared to fasted conditions. However, administration of HP Kit (Tinidazole) with food did not affect AUC or T _1/2 in this study.

In healthy volunteers, administration of crushed HP Kit (Tinidazole) tablets in artificial cherry syrup, [prepared as described in Dosage and Administration ( 2.2) ] after an overnight fast had no effect on any pharmacokinetic parameter as compared to tablets swallowed whole under fasted conditions.

Distribution: HP Kit (Tinidazole) is distributed into virtually all tissues and body fluids and also crosses the blood-brain barrier. The apparent volume of distribution is about 50 liters. Plasma protein binding of HP Kit (Tinidazole) is 12%. HP Kit (Tinidazole) crosses the placental barrier and is secreted in breast milk.

Metabolism: HP Kit (Tinidazole) is significantly metabolized in humans prior to excretion. HP Kit (Tinidazole) is partly metabolized by oxidation, hydroxylation, and conjugation. HP Kit (Tinidazole) is the major drug-related constituent in plasma after human treatment, along with a small amount of the 2-hydroxymethyl metabolite.

HP Kit (Tinidazole) is biotransformed mainly by CYP3A4. In an in vitro metabolic drug interaction study, HP Kit (Tinidazole) concentrations of up to 75 µg/mL did not inhibit the enzyme activities of CYP1A2, CYP2B6, CYP2C9, CYP2D6, CYP2E1, and CYP3A4.

The potential of HP Kit (Tinidazole) to induce the metabolism of other drugs has not been evaluated.

Elimination: The plasma half-life of HP Kit (Tinidazole) is approximately 12-14 hours. HP Kit (Tinidazole) is excreted by the liver and the kidneys. HP Kit (Tinidazole) is excreted in the urine mainly as unchanged drug (approximately 20-25% of the administered dose). Approximately 12% of the drug is excreted in the feces.

Patients with impaired renal function: The pharmacokinetics of HP Kit (Tinidazole) in patients with severe renal impairment (CrCL < 22 mL/min) are not significantly different from the pharmacokinetics seen in healthy subjects. However, during hemodialysis, clearance of HP Kit (Tinidazole) is significantly increased; the half-life is reduced from 12.0 hours to 4.9 hours. Approximately 43% of the amount present in the body is eliminated during a 6-hour hemodialysis session . The pharmacokinetics of HP Kit (Tinidazole) in patients undergoing routine continuous peritoneal dialysis have not been investigated.

Patients with impaired hepatic function: There are no data on HP Kit (Tinidazole) pharmacokinetics in patients with impaired hepatic function. Reduction of metabolic elimination of metronidazole, a chemically-related nitroimidazole, in patients with hepatic dysfunction has been reported in several studies .

12.4 Microbiology

Mechanism of Action: HP Kit (Tinidazole) is an antiprotozoal, antibacterial agent. The nitro- group of HP Kit (Tinidazole) is reduced by cell extracts of Trichomonas. The free nitro- radical generated as a result of this reduction may be responsible for the antiprotozoal activity. Chemically reduced HP Kit (Tinidazole) was shown to release nitrites and cause damage to purified bacterial DNA in vitro. Additionally, the drug caused DNA base changes in bacterial cells and DNA strand breakage in mammalian cells. The mechanism by which HP Kit (Tinidazole) exhibits activity against Giardia and Entamoeba species is not known.

Antibacterial: Culture and sensitivity testing of bacteria are not routinely performed to establish the diagnosis of bacterial vaginosis ; standard methodology for the susceptibility testing of potential bacterial pathogens, Gardnerella vaginalis, Mobiluncus spp. or Mycoplasma hominis, has not been defined. The following in vitro data are available, but their clinical significance is unknown. HP Kit (Tinidazole) is active in vitro against most strains of the following organisms that have been reported to be associated with bacterial vaginosis:

• Bacteroides spp.
• Gardnerella vaginalis
• Prevotella spp.

HP Kit (Tinidazole) does not appear to have activity against most strains of vaginal lactobacilli.

Antiprotozoal: HP Kit (Tinidazole) demonstrates activity both in vitro and in clinical infections against the following protozoa: Trichomonas vaginalis; Giardia duodenalis (also termed G. lamblia); and Entamoeba histolytica.

For protozoal parasites, standardized susceptibility tests do not exist for use in clinical microbiology laboratories.

Drug Resistance: The development of resistance to HP Kit (Tinidazole) by G. duodenalis, E. histolytica, or bacteria associated with bacterial vaginosis has not been examined.

Cross-resistance: Approximately 38% of T. vaginalis isolates exhibiting reduced susceptibility to metronidazole also show reduced susceptibility to HP Kit (Tinidazole) in vitro. The clinical significance of such an effect is not known.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of HP Kit (Tinidazole) and other antibacterial drugs, HP Kit (Tinidazole) should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Metronidazole, a chemically-related nitroimidazole, has been reported to be carcinogenic in mice and rats but not hamsters. In several studies metronidazole showed evidence of pulmonary, hepatic, and lymphatic tumorigenesis in mice and mammary and hepatic tumors in female rats. HP Kit carcinogenicity studies in rats, mice or hamsters have not been reported.

HP Kit (Tinidazole) was mutagenic in the TA 100, S. typhimurium tester strain both with and without the metabolic activation system and was negative for mutagenicity in the TA 98 strain. Mutagenicity results were mixed (positive and negative) in the TA 1535, 1537, and 1538 strains. HP Kit (Tinidazole) was also mutagenic in a tester strain of Klebsiella pneumonia. HP Kit (Tinidazole) was negative for mutagenicity in a mammalian cell culture system utilizing Chinese hamster lung V79 cells (HGPRT test system) and negative for genotoxicity in the Chinese hamster ovary (CHO) sister chromatid exchange assay. HP Kit (Tinidazole) was positive for in vivo genotoxicity in the mouse micronucleus assay.

In a 60-day fertility study, HP Kit (Tinidazole) reduced fertility and produced testicular histopathology in male rats at a 600 mg/kg/day dose level (approximately 3-fold the highest human therapeutic dose based upon body surface area conversions). Spermatogenic effects resulted from 300 and 600 mg/kg/day dose levels. The no observed adverse reaction level for testicular and spermatogenic effects was 100 mg/kg/day (approximately 0.5-fold the highest human therapeutic dose based upon body surface area conversions). This effect is characteristic of agents in the 5-nitroimidazole class.

13.2 Animal Toxicology and/or Pharmacology

In acute studies with mice and rats, the LD ₅₀ for mice was generally > 3,600 mg/kg for oral administration and was > 2,300 mg/kg for intraperitoneal administration. In rats, the LD ₅₀ was > 2,000 mg/kg for both oral and intraperitoneal administration.

A repeated-dose toxicology study has been performed in beagle dogs using oral dosing of HP Kit (Tinidazole) at 100 mg/kg/day, 300 mg/kg/day, and 1000 mg/kg/day for 28-days. On Day 18 of the study, the highest dose was lowered to 600 mg/kg/day due to severe clinical symptoms. The two compound-related effects observed in the dogs treated with HP Kit (Tinidazole) were increased atrophy of the thymus in both sexes at the middle and high doses, and atrophy of the prostate at all doses in the males. A no-adverse-effect level (NOAEL) of 100 mg/kg/day for females was determined. There was no NOAEL identified for males because of minimal atrophy of the prostate at 100 mg/kg/day (approximately 0.9-fold the highest human dose based upon plasma AUC comparisons).

14 CLINICAL STUDIES

14.1 Trichomoniasis

HP Kit (2 g single oral dose) use in trichomoniasis has been well documented in 34 published reports from the world literature involving over 2,800 patients treated with HP Kit (Tinidazole). In four published, blinded, randomized, comparative studies of the 2 g HP Kit (Tinidazole) single oral dose where efficacy was assessed by culture at time points post-treatment ranging from one week to one month, reported cure rates ranged from 92% (37/40) to 100% (65/65) (n=172 total subjects). In four published, blinded, randomized, comparative studies where efficacy was assessed by wet mount between 7-14 days post-treatment, reported cure rates ranged from 80% (8/10) to 100% (16/16) (n=116 total subjects). In these studies, HP Kit (Tinidazole) was superior to placebo and comparable to other anti-trichomonal drugs. The single oral 2 g HP Kit (Tinidazole) dose was also assessed in four open-label trials in men (one comparative to metronidazole and 3 single-arm studies). Parasitological evaluation of the urine was performed both pre- and post-treatment and reported cure rates ranged from 83% (25/30) to 100% (80/80) (n=142 total subjects).

14.2 Giardiasis

HP Kit (Tinidazole) (2 g single dose) use in giardiasis has been documented in 19 published reports from the world literature involving over 1,600 patients (adults and pediatric patients). In eight controlled studies involving a total of 619 subjects of whom 299 were given the 2 g × 1 day (50 mg/kg × 1 day in pediatric patients) oral dose of HP Kit (Tinidazole), reported cure rates ranged from 80% (40/50) to 100% (15/15). In three of these trials where the comparator was 2 to 3 days of various doses of metronidazole, reported cure rates for metronidazole were 76% (19/25) to 93% (14/15). Data comparing a single 2 g dose of HP Kit (Tinidazole) to usually recommended 5-7 days of metronidazole are limited.

14.3 Intestinal Amebiasis

HP Kit use in intestinal amebiasis has been documented in 26 published reports from the world literature involving over 1,400 patients. Most reports utilized HP Kit (Tinidazole) 2 g/day × 3 days. In four published, randomized, controlled studies (1 investigator single-blind, 3 open-label) of the 2 g/day × 3 days oral dose of HP Kit (Tinidazole), reported cure rates after 3 days of therapy among a total of 220 subjects ranged from 86% (25/29) to 93% (25/27).

14.4 Amebic Liver Abscess

HP Kit (Tinidazole) use in amebic liver abscess has been documented in 18 published reports from the world literature involving over 470 patients. Most reports utilized HP Kit (Tinidazole) 2 g/day × 2-5 days. In seven published, randomized, controlled studies (1 double-blind, 1 single-blind, 5 open-label) of the 2 g/day × 2-5 days oral dose of HP Kit (Tinidazole) accompanied by aspiration of the liver abscess when clinically necessary, reported cure rates among 133 subjects ranged from 81% (17/21) to 100% (16/16). Four of these studies utilized at least 3 days of HP Kit (Tinidazole).

14.5 Bacterial Vaginosis

A randomized, double-blind, placebo-controlled clinical trial in 235 non-pregnant women was conducted to evaluate the efficacy of HP Kit (Tinidazole) for the treatment of bacterial vaginosis. A clinical diagnosis of bacterial vaginosis was based on Amsel's criteria and defined by the presence of an abnormal homogeneous vaginal discharge that (a) has a pH of greater than 4.5, (b) emits a "fishy" amine odor when mixed with a 10% KOH solution, and (c) contains ≥20% clue cells on microscopic examination. Clinical cure required a return to normal vaginal discharge and resolution of all Amsel's criteria. A microbiologic diagnosis of bacterial vaginosis was based on Gram stain of the vaginal smear demonstrating (a) markedly reduced or absent Lactobacillus morphology, (b) predominance of Gardnerella morphotype, and (c) absent or few white blood cells, with quantification of these bacterial morphotypes to determine the Nugent score, where a score ≥4 was required for study inclusion and a score of 0-3 considered a microbiologic cure. Therapeutic cure was a composite endpoint, consisting of both a clinical cure and microbiologic cure. In patients with all four Amsel's criteria and with a baseline Nugent score ≥4, HP Kit (Tinidazole) oral tablets given as either 2 g once daily for 2 days or 1 g once daily for 5 days demonstrated superior efficacy over placebo tablets as measured by therapeutic cure, clinical cure, and a microbiologic cure.

Outcome	HP Kit (Tinidazole) 1 g × 5 days (n=76)	HP Kit (Tinidazole) 2 g × 2 days (n=73)	Placebo (n=78)
	% Cure	% Cure	% Cure
Therapeutic Cure Difference 2 97.5% CI 3	36.8 31.7 (16.8, 46.6)	27.4 22.3 (8.0, 36.6)	5.1
Clinical Cure Difference 2 97.5% CI 3	51.3 39.8 (23.3, 56.3)	35.6 24.1 (7.8, 40.3)	11.5
Nugent Score Cure Difference 2 97.5% CI 3	38.2 33.1 (18.1, 48.0)	27.4 22.3 (8.0, 36.6)	5.1

¹Modified Intent-to-Treat defined as all patients randomized with a baseline

Nugent score of at least 4

²Difference in cure rates (Tindamax-placebo)

³CI: confidence interval

p-values for both HP Kit (Tinidazole) regimens vs. placebo for therapeutic, clinical and

Nugent score cure rates for both 2 and 5 days <0.001

The therapeutic cure rates reported in this clinical study conducted with HP Kit (Tinidazole) were based on resolution of 4 out of 4 Amsel's criteria and a Nugent score of <4. The cure rates for previous clinical studies with other products approved for bacterial vaginosis were based on resolution of either 2 or 3 out of 4 Amsel's criteria. At the time of approval for other products for bacterial vaginosis, there was no requirement for a Nugent score on Gram stain, resulting in higher reported rates of cure for bacterial vaginosis for those products than for those reported here for HP Kit (Tinidazole).

17 PATIENT COUNSELING INFORMATION

17.1 Administration of Drug

Patients should be told to take HP Kit with food to minimize the incidence of epigastric discomfort and other gastrointestinal side-effects. Food does not affect the oral bioavailability of HP Kit (Tinidazole).

17.2 Alcohol Avoidance

Patients should be told to avoid alcoholic beverages and preparations containing ethanol or propylene glycol during HP Kit (Tinidazole) therapy and for 3 days afterward because abdominal cramps, nausea, vomiting, headaches, and flushing may occur.

17.3 Drug Resistance

Patients should be counseled that antibacterial drugs including HP Kit (Tinidazole) should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When HP Kit (Tinidazole) 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 exactly 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 HP Kit (Tinidazole) or other antibacterial drugs in the future.

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