Go PLR Articles Directory Brunei: May 2012

Thursday 31 May 2012

Ropinirole 0.25 mg Film-Coated Tablets (Actavis UK Ltd)

1. Name Of The Medicinal Product

Ropinirole 0.25 mg Film-Coated Tablets

2. Qualitative And Quantitative Composition

Each film-coated tablet contains ropinirole hydrochloride equivalent to 0.25 mg ropinirole base.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Film-coated tablet.

Ropinirole 0.25 mg Film-Coated Tablets are white, round (7mm in diameter), biconvex, and embossed with R0.25 on one side.

4. Clinical Particulars

4.1 Therapeutic Indications

Ropinirole is indicated for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome (see Section 5.1).

4.2 Posology And Method Of Administration

Oral use.

Adults

Individual dose titration against efficacy and tolerability is recommended.

Ropinirole should be taken just before bedtime, however the dose can be taken up to 3 hours before retiring. Ropinirole may be taken with food, to improve gastrointestinal tolerance.

Treatment initiation (week 1)

The recommended initial dose is 0.25 mg once daily (administered as above) for 2 days. If this dose is well tolerated the dose should be increased to 0.5 mg once daily for the remainder of week 1.

Therapeutic regimen (week 2 onwards)

Following treatment initiation, the daily dose should be increased until optimal therapeutic response is achieved. The average dose in clinical trials, in patients with moderate to severe Restless Legs Syndrome, was 2.0 mg once a day.

The dose may be increased to 1.0 mg once a day at week 2. The dose may then be increased by 0.5 mg per week over the next two weeks to a dose of 2.0 mg once a day. In some patients, to achieve optimal improvement, the dose may be increased gradually up to a maximum of 4.0 mg once a day. In clinical trials the dose was increased by 0.5 mg each week to 3.0 mg once a day and then by 1.0 mg up to the maximum recommended dose of 4.0 mg once a day as shown in Table 1.

Doses above 4.0 mg once daily have not been investigated in Restless Legs Syndrome patients.

Table 1 – Dose titration

Week	2	3	4	5*	6*	7*
Dose (mg) / once daily	1.0	1.5	2.0	2.5	3.0	4.0

* To achieve optimal improvement in some patients.

The patient's response to ropinirole should be evaluated after 3 months treatment (see Section 5.1). At this time the dose prescribed and the need for continued treatment should be considered. If treatment is interrupted for more than a few days it should be re-initiated by dose titration carried out as above.

Children and Adolescents

Ropinirole is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy.

Elderly

The clearance of ropinirole is decreased in patients over 65 years of age. Any increase in dosage should be gradual and titrated against the symptomatic response.

Renal impairment

No dosage adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/min).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Severe renal impairment (creatinine clearance < 30ml/min).

Severe hepatic impairment.

4.4 Special Warnings And Precautions For Use

Ropinirole should not be used to treat neuroleptic akathisia, tasikinesia (neuroleptic-induced compulsive tendency to walk), or secondary Restless Legs Syndrome (e.g. caused by renal failure, iron deficiency anaemia or pregnancy).

During treatment with ropinirole, paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed. If this occurs, treatment should be reviewed and dosage adjustment or discontinuation of treatment may be considered.

In Parkinson's disease, ropinirole has been associated uncommonly with somnolence and episodes of sudden sleep onset (see Section 4.8) however in Restless Legs Syndrome, this phenomenon is very rare. Nevertheless, patients must be informed of this phenomenon and advised to exercise caution while driving or operating machines during treatment with ropinirole. Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered.

Patients with major psychotic disorders should not be treated with dopamine agonists unless the potential benefits outweigh the risks.

Impulse control disorders including pathological gambling and hypersexuality, and increased libido, have been reported in patients treated with dopamine agonists, including ropinirole, principally for Parkinson's disease. Those disorders were reported especially at high doses and were generally reversible upon reduction of the dose or treatment discontinuation. Risk factors such as a history of compulsive behaviours were present in some cases (see section 4.8).

Ropinirole should be administered with caution to patients with moderate hepatic impairment. Undesirable effects should be closely monitored.

Due to the risk of hypotension, patients with severe cardiovascular disease (in particular coronary insufficiency) should be treated with caution.

Ropinirole Film-Coated Tablets contain lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Ropinirole is principally metabolised by the cytochrome P450 isoenzyme CYP1A2. A pharmacokinetic study (with a ropinirole dose of 2 mg, three times a day) revealed that ciprofloxacin increased the C_max and AUC of ropinirole by 60% and 84% respectively, with a potential risk of adverse events. Hence, in patients already receiving ropinirole, the dose of ropinirole may need to be adjusted when medicinal products known to inhibit CYP1A2, e.g. ciprofloxacin, enoxacin or fluvoxamine, are introduced or withdrawn.

A pharmacokinetic interaction study between ropinirole (at a dose of 2 mg, three times a day) and theophylline, a substrate of CYP1A2, revealed no change in the pharmacokinetics of either ropinirole or theophylline. Therefore, it is not expected that ropinirole will compete with the metabolism of other medicinal products which are metabolised by CYP1A2.

Based on in-vitro data, ropinirole has little potential to inhibit cytochrome P450 at therapeutic doses. Hence, ropinirole is unlikely to affect the pharmacokinetics of other medicinal products, via a cytochrome P450 mechanism.

Smoking is known to induce CYP1A2 metabolism. Therefore, if patients stop or start smoking during treatment with ropinirole, dose adjustment may be required.

Increased plasma concentrations of ropinirole have been observed in patients treated with hormone replacement therapy. In patients already receiving hormone replacement therapy, ropinirole treatment may be initiated in the usual manner. However, it may be necessary to adjust the ropinirole dose, in accordance with clinical response, if hormone replacement therapy is stopped or introduced during treatment with ropinirole.

No pharmacokinetic interaction has been seen between ropinirole and domperidone (a medicinal product used to treat nausea and vomiting) that would necessitate dosage adjustment of either medicinal product. Domperidone antagonises the dopaminergic actions of ropinirole peripherally and does not cross the blood-brain barrier. Hence its value as an anti-emetic in patients treated with centrally acting dopamine agonists

Neuroleptics and other centrally active dopamine antagonists, such as sulpiride or metoclopramide, may diminish the effectiveness of ropinirole and, therefore, concomitant use of these medicinal products with ropinirole should be avoided.

4.6 Pregnancy And Lactation

There are no adequate data from the use of ropinirole in pregnant women.

Studies in animals have shown reproductive toxicity (see section 5.3). As the potential risk for humans is unknown, it is recommended that ropinirole is not used during pregnancy unless the potential benefit to the patient outweighs the potential risk to the foetus.

Ropinirole should not be used in nursing mothers as it may inhibit lactation.

4.7 Effects On Ability To Drive And Use Machines

Patients being treated with ropinirole and presenting with somnolence and/or sudden sleep episodes must be informed to refrain from driving or engaging in activities where impaired alertness may put themselves or others at risk of serious injury or death (e.g. operating machines) until such effects have resolved (see also Section 4.4).

4.8 Undesirable Effects

Adverse drug reactions are listed below by system organ class and frequency. Frequencies from clinical trials are determined as excess incidence over placebo and are classed as Very Common (> 1/10) or Common (> 1/100 to < 1/10) or uncommon (> 1/1000 to < 1/100).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Use of ropinirole in Restless Legs Syndrome

In Restless Legs Syndrome clinical trials the most common adverse drug reaction was nausea (approximately 30% of patients). Undesirable effects were normally mild to moderate and experienced at the start of therapy or on increase of dose and few patients withdrew from the clinical studies due to undesirable effects.

Table 2 lists the adverse drug reactions reported for ropinirole in the 12-week clinical trials at

Table 2 - Adverse drug reactions reported in 12-week Restless Legs Syndrome clinical trials (ropinirole n=309, placebo n=307)

Psychiatric Disorders
Common:	Nervousness
Uncommon:	Confusion
Nervous System Disorders
Common:	Syncope, Somnolence, Dizziness (including vertigo)
Vascular Disorders
Uncommon:	Postural hypotension, hypotension
Gastrointestinal Disorders
Very Common:	Vomiting, Nausea
Common:	Abdominal pain
General Disorders and Administration Site Conditions
Common:	Fatigue

Hallucinations were reported uncommonly in the open label long-term studies.

Paradoxical worsening of Restless Legs Syndrome symptoms occurring with earlier onset (augmentation), and reoccurrence of symptoms in the early morning hours (early morning rebound), may be observed during treatment with ropinirole.

Management of undesirable effects

Dose reduction should be considered if patients experience significant undesirable effects. If the undesirable effect abates, gradual up-titration can be re-instituted. Anti-nausea medicinal products that are not centrally active dopamine antagonists, such as domperidone, may be used if required.

Other experience with Ropinirole

Ropinirole is also indicated for the treatment of Parkinson's disease. The adverse drug reactions reported in patients with Parkinson's disease on ropinirole monotherapy and adjunct therapy at doses up to 24 mg/day at excess incidence over placebo are described below.

Table 3 - Adverse drug reactions reported in Parkinson's disease clinical trials at doses up to 24 mg/day

Psychiatric Disorders
Common:	Hallucinations, Confusion
Uncommon:	Increased libido
Nervous System Disorders
Very Common:	Syncope, Dyskinesia, Somnolence
Gastrointestinal Disorders
Very Common:	Nausea
Common:	Vomiting, Abdominal pain, Heartburn
General Disorders and Administration Site Conditions
Common:	Leg oedema

Post marketing reports

Hypersensitivity reactions (including urticaria, angioedema, rash, pruritus)

Psychotic reactions (other than hallucinations) including delirium, delusion, paranoia have been reported.

Impulse control disorders including pathological gambling and hypersexuality, and increased libido, have been reported (see section 4.4).

In Parkinson's disease, ropinirole is associated with somnolence and has been associated uncommonly (>1/1,000, <1/100) with excessive daytime somnolence and sudden sleep onset episodes, however, in Restless Legs Syndrome, this phenomenon is very rare (<1/10,000).

Following ropinirole therapy, postural hypotension or hypotension has been reported uncommonly (>1/1,000, <1/100), rarely severe.

Very rare cases of hepatic reactions (<1/10,000), mainly increase of liver enzymes, have been reported.

4.9 Overdose

It is anticipated that the symptoms of ropinirole overdose will be related to its dopaminergic activity. These symptoms may be alleviated by appropriate treatment with dopamine antagonists such as neuroleptics or metoclopramide.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Dopamine agonist

ATC code: N04BC04

Mechanism of action

Ropinirole is a non-ergoline D2/D3 dopamine agonist which stimulates striatal dopamine receptors.

Clinical efficacy

Ropinirole Film-coated Tablets should only be prescribed to patients with moderate to severe idiopathic Restless Legs Syndrome. Moderate to severe idiopathic Restless Legs Syndrome is typically represented by patients who suffer with insomnia or severe discomfort in the limbs.

In the four 12-week efficacy studies, patients with Restless Legs Syndrome were randomised to ropinirole or placebo, and the effects on the IRLS scale scores at week 12 were compared to baseline. The mean dose of ropinirole for the moderate to severe patients was 2.0 mg/day. In a combined analysis of moderate to severe Restless Legs Syndrome patients from the four 12-week studies, the adjusted treatment difference for the change from baseline in IRLS scale total score at week 12 Last Observation Carried Forward (LOCF) Intention To Treat population was -4.0 points (95% CI -5.6, -2.4, p<0.0001; baseline and week 12 LOCF mean IRLS points: ropinirole 28.4 and 13.5; placebo 28.2 and 17.4).

A 12-week placebo-controlled polysomnography study in Restless Legs Syndrome patients examined the effect of treatment with ropinirole on periodic leg movements of sleep. A statistically significant difference in the periodic leg movements of sleep was seen between ropinirole and placebo from baseline to week 12.

Although sufficient data is not available to adequately demonstrate the long term efficacy of ropinirole in Restless Legs Syndrome (see Section 4.2), in a 36-week study, patients who continued on ropinirole demonstrated a significantly lower relapse rate compared with patients randomised to placebo (33% versus 58%, p=0.0156).

A combined analysis of data from moderate to severe Restless Legs Syndrome patients, in the four 12-week placebo-controlled studies, indicated that ropinirole-treated patients reported significant improvements over placebo on the parameters of the Medical Outcome Study Sleep Scale (scores on 0-100 range except sleep quantity). The adjusted treatment differences between ropinirole and placebo were: sleep disturbance (-15.2, 95% CI -19.37, -10.94; p<0.0001), sleep quantity (0.7 hours, 95% CI 0.49, 0.94; p<0.0001), sleep adequacy (18.6, 95% CI 13.77, 23.45; p<0.0001) and daytime somnolence (-7.5, 95% CI -10.86, -4.23; p<0.0001).

A rebound phenomenon following discontinuation of ropinirole treatment (end of treatment rebound) cannot be excluded. In clinical trials, although the average IRLS total scores 7-10 days after withdrawal of therapy were higher in ropinirole-treated patients than in placebo-treated patients, the severity of symptoms following withdrawal of therapy generally did not exceed the baseline assessment in ropinirole-treated patients.

In clinical studies most patients were of Caucasian origin.

Study of the effect of ropinirole on cardiac repolarisation

A thorough QT study conducted in male and female healthy volunteers who received doses of 0.5, 1, 2 and 4 mg of ropinirole film-coated (immediate release) tablets once daily showed a maximum increase of the QT interval duration at the 1mg dose of 3.46 milliseconds (point estimate) as compared to placebo. The upper bound of the one sided 95% confidence interval for the largest mean effect was less than 7.5 milliseconds. The effect of ropinirole at higher doses has not been systematically evaluated.

The available clinical data from a thorough QT study do not indicate a risk of QT prolongation at doses of ropinirole up to 4 mg/day.

5.2 Pharmacokinetic Properties

Absorption

The bioavailability of ropinirole is about 50% (36% to 57%), with C_max reached on average 1.5 hours after the dose. A high fat meal decreases the rate of absorption of Ropinirole, as shown by a delay in median T_max by 2.6 hours and an average 25% decrease in C_max.

Distribution

Plasma protein binding of ropinirole is low (10 – 40%). Consistent with its high lipophilicity, ropinirole exhibits a large volume of distribution (approx. 7 l/kg).

Metabolism

Ropinirole is primarily cleared by the cytochrome P450 enzyme, CYP1A2, and its metabolites are mainly excreted in the urine. The major metabolite is at least 100 times less potent than ropinirole in animal models of dopaminergic function.

Elimination

Ropinirole is cleared from the systemic circulation with an average elimination half-life of approximately 6 hours. No change in the oral clearance of ropinirole is observed following single and repeated oral administration. Wide inter-individual variability in the pharmacokinetic parameters has been observed.

Linearity

The pharmacokinetics of ropinirole are linear overall (C_max and AUC) in the therapeutic range between 0.25 mg and 4 mg, after a single dose and after repeated dosing.

Population-related characteristics

In patients over 65 years of age, a reduction in the systemic clearance of ropinirole by about 30% is possible.

In patients with mild to moderate renal impairment (creatinine clearance between 30 and 50 ml/min), no change in the pharmacokinetics of ropinirole is observed. No data is available in patients with severe renal impairment.

Paediatric population

Limited pharmacokinetic data obtained in adolescents (12-17 years, n=9) showed that the systemic exposure following single doses of 0.125 mg and 0.25 mg was similar to that observed in adults (see also section 4.2; subparagraph “Children and adolescents).

5.3 Preclinical Safety Data

Toxicology: The toxicology profile is principally determined by the pharmacological activity of the drug: behavioural changes, hypoprolactinaemia, decrease in blood pressure and heart rate, ptosis and salivation. In the albino rat only, retinal degeneration was observed in a long term study at a high dose (50 mg/kg), probably associated with an increased exposure to light.

Genotoxicity: Genotoxicity was not observed in the usual battery of in vitro and in vivo tests.

Carcinogenicity: From two-year studies conducted in the mouse and rat at dosages up to 50 mg/kg/day there was no evidence of any carcinogenic effect in the mouse. In the rat, the only drug-related lesions were Leydig cell hyperplasia and testicular adenoma resulting from the hypoprolactinaemic effect of ropinirole. These lesions are considered to be a species specific phenomenon and do not constitute a hazard with regard to the clinical use of ropinirole.

Reproductive Toxicity: Administration of ropinirole to pregnant rats at maternally toxic doses resulted in decreased foetal body weight at 60 mg/kg/day (approximately 15 times the AUC at the maximum dose in humans), increased foetal death at 90 mg/kg/day (approximately 25 times the AUC at the maximum dose in humans) and digit malformations at 150 mg/kg/day (approximately 40 times the AUC at the maximum dose in humans). There were no teratogenic effects in the rat at 120 mg/kg/day (approximately 30 times the AUC at the maximum dose in humans) and no indication of an effect on development in the rabbit.

Safety Pharmacology: In vitro studies have shown that ropinirole inhibits hERG-mediated currents. The IC₅₀ is 5-fold higher than the expected maximum plasma concentration in patients treated at the highest recommended dose (4 mg/day), see section 5.1.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Tablet core:

Lactose monohydrate

Microcrystalline cellulose

Pregelatinised starch

Magnesium stearate

Film coating:

Opadry II 85F18378 (Polyvinyl alcohol, Titanium dioxide, Macrogol 3350, Talc)

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Do not store above 25°C

Store in the original package in order to protect from light

HDPE tablet containers only:

Keep the container tightly closed in order to protect from moisture

6.5 Nature And Contents Of Container

Aluminium/Aluminium blister or induction sealed HDPE tablet containers of 2, 5, 7, 10, 12, 14, 20, 21, 28, 30, 50, 56, 60, 84, 100, 126 and 210 tablets.

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Caduceus Pharma Limited

6^th Floor,

94 Wigmore Street,

London

W1U 3RF

8. Marketing Authorisation Number(S)

PL 24668/0078

9. Date Of First Authorisation/Renewal Of The Authorisation

21/01/2011

10. Date Of Revision Of The Text

25/03/2011

Monday 28 May 2012

Tinidazole

Class: Antiprotozoals, Miscellaneous
VA Class: AP109
Chemical Name: 1-[2-(Ethylsulfonyl)ethyl]-2-methyl-5-nitro-1H-imidazole
Molecular Formula: C₈H₁₃N₃O₄S
CAS Number: 19387-91-8
Brands: Tindamax

Metronidazole (a nitroimidazole anti-infective chemically similar to tinidazole) is carcinogenic in mice and rats.¹ ³¹

Carcinogenic potential of tinidazole not evaluated in animal studies to date.¹

Avoid unnecessary use; reserve for use in approved indications.¹ (See Uses.)

Introduction

Antiprotozoal and antibacterial; ¹ ⁵⁸ ⁵⁹ ⁶³ ⁶⁴ ⁶⁵ ⁶⁸ nitroimidazole derivative.¹ ⁵⁸ ⁵⁹ ⁶³ ⁶⁴ ⁶⁵ ⁶⁸

Uses for Tinidazole

Amebiasis

Treatment of intestinal amebiasis and amebic liver abscess caused by Entamoeba histolytica in adults and children >3 years of age.¹ ¹⁸ ²⁵ ²⁶ ²⁷ ²⁸ ²⁹ ³⁰ ³⁴ ⁴³ ⁴⁷ ⁴⁸ ⁴⁹ ⁵⁰ ⁵¹ ⁵² ⁵³ ⁵⁴ ⁶⁹ Designated an orphan drug by FDA for treatment of amebiasis.²

Oral tinidazole or oral metronidazole followed by a luminal amebicide (iodoquinol, paromomycin) is the regimen of choice for mild to moderate or severe intestinal disease and for amebic hepatic abscess.¹⁸ ²⁴ ²⁵ ²⁶ ²⁷ ³⁴ ⁴⁷

Not recommended for treatment of asymptomatic cyst passers;¹ ¹⁸ ⁴⁷ these patients should be treated with a luminal amebicide such as iodoquinol, paromomycin, or diloxanide furoate (not commercially available in the US).¹⁸ ²⁵ ²⁶ ²⁷

Giardiasis

Treatment of giardiasis caused by Giardia duodenalis (also known as G. lamblia or G. intestinalis) in adults and children >3 years of age.¹ ¹⁸ ²⁰ ²¹ ²² ²³ ²⁴ ³⁴ ⁴⁰ ⁴¹ ⁴³ ⁴⁴ ⁴⁵ ⁴⁶ ⁵⁶ ⁵⁷ Designated an orphan drug by FDA for use in this condition.²

Drugs of choice are metronidazole,¹⁷ ¹⁸ ²⁰ tinidazole,¹⁷ ¹⁸ ²⁰ or nitazoxanide;¹⁷ ¹⁸ alternatives are paromomycin (especially in pregnant women),¹⁷ ¹⁸ ²⁰ furazolidone (not commercially available in the US),¹⁷ ¹⁸ ²⁰ or quinacrine (not commercially available in the US).¹⁷ ¹⁸

Treatment of asymptomatic carriers of giardiasis† not recommended, except possibly to prevent transmission from carriers in households of patients with hypogammaglobulinemia or cystic fibrosis or pregnant women with toddlers.¹⁸

Trichomoniasis

Treatment of symptomatic and asymptomatic trichomoniasis in men and women in whom Trichomonas vaginalis has been demonstrated by an appropriate diagnostic procedure (e.g., wet smear and/or culture, OSOM Trichomonas Rapid Test, Affirm VP III).¹ ³ ⁴ ⁵ ⁹ ¹¹ ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁸ ³⁵ ³⁶ ³⁸ ³⁹ ⁶⁷ ⁶⁸

Drug of choice is metronidazole or tinidazole.⁹ ¹⁷ ¹⁸ Tinidazole may be effective in some patients who do not respond to metronidazole,³ ⁶² but some T. vaginalis isolates with reduced susceptibility to metronidazole may also have reduced susceptibility to tinidazole.¹ ⁶¹ ⁶²

Goal of treatment is to provide symptomatic relief, achieve microbiologic cure, and reduce transmission.¹ ⁷ ⁸ ⁹ ¹⁵ To achieve this goal, both the index patient and sexual (particularly steady) partner(s) should be treated simultaneously;¹ ⁷ ⁸ ⁹ ¹⁵ treat sexual contacts presumptively even if they are asymptomatic and/or T. vaginalis has not been demonstrated.⁶⁷

Bacterial Vaginosis

Treatment of bacterial vaginosis (formerly called Haemophilus vaginitis, Gardnerella vaginitis, nonspecific vaginitis, Corynebacterium vaginitis, or anaerobic vaginosis) in nonpregnant women.¹ ⁷² ⁷³ Rule out other pathogens commonly associated with vulvovaginitis (e.g., Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeae, Candida albicans, herpes simplex viruses).¹

CDC recommends treatment of bacterial vaginosis in all symptomatic nonpregnant women.⁹ Routine treatment of sex partners not recommended.⁹

Nongonococcal Urethritis

Treatment of recurrent and persistent urethritis† in patients with nongonococcal urethritis who have already been treated with a recommended regimen.⁹

For treatment of nongonococcal urethritis in adults, CDC recommends a single oral dose of azithromycin or a 7-day regimen of doxycycline; alternative regimens are a 7-day regimen of oral erythromycin base or ethylsuccinate or a 7-day regimen of oral ofloxacin or oral levofloxacin.⁹ Patients are instructed to abstain from sexual intercourse until 7 days after initiation of treatment and to return for evaluation if symptoms persist or recur after completion of therapy; symptoms alone (without documentation of signs or laboratory evidence of urethral inflammation) are not sufficient basis for retreatment.⁹

Patients with persistent or recurrent urethritis who were not compliant with the treatment regimen or were reexposed to untreated sexual partner(s) should be retreated with the initial regimen.⁹ If patient with recurrent and persistent urethritis was compliant with the regimen and reexposure can be excluded, CDC recommends a single oral dose of metronidazole or tinidazole given in conjunction with a single oral dose of azithromycin (if azithromycin was not used in the initial regimen).⁹

Tinidazole Dosage and Administration

Administration

Oral Administration

Administer orally once daily with food.¹

Administration with meals may reduce incidence of adverse GI effects.¹

Do not consume alcohol during or for 3 days after completion of tinidazole therapy.¹

For children and other patients unable to swallow tablets, an oral suspension may be prepared extemporaneously using the tablets.¹

Extemporaneous Oral Suspension

To prepare an oral suspension containing 66.7 mg/mL, grind 2 g (four 500-mg tablets) to a fine powder with a mortar and pestle.¹ Add approximately 10 mL of cherry syrup to the powder and mix until smooth.¹ Transfer suspension to a graduated amber container;¹ use several small rinses of the cherry syrup to transfer any remaining drug in the mortar to provide a suspension with a final volume of 30 mL.¹

Shake suspension well prior to administration of each dose.¹

Dosage

Pediatric Patients

Amebiasis

Entamoeba histolytica Infections

Oral

Children >3 years of age (intestinal amebiasis): 50 mg/kg (up to 2 g) once daily given for 3 days;¹ ¹⁷ follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).¹ ¹⁸ ²⁵ ⁴⁷

Children >3 years of age (amebic liver abscess): 50 mg/kg (up to 2 g) once daily given for 3–5 days;¹ ¹⁷ follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).¹ ¹⁸ ²⁵ ⁴⁷

Giardiasis

Oral

Children >3 years of age: 50 mg/kg (up to 2 g) given as a single dose.¹ ¹⁷

Trichomoniasis†

Oral

Children >3 years of age†: 50 mg/kg (up to 2 g) given as a single dose.¹⁷

Adults

Amebiasis

Entamoeba histolytic Infections

Oral

Intestinal amebiasis: 2 g once daily given for 3 days;¹ ¹⁷ follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).¹ ¹⁸ ²⁵ ⁴⁷

Amebic liver abscess: 2 g once daily for 3–5 days;¹ ¹⁷ follow-up with an oral luminal amebicide (e.g., iodoquinol, paromomycin).¹ ¹⁸ ²⁵ ⁴⁷

Giardiasis

Oral

2 g given as a single dose.¹ ¹⁷

Trichomoniasis

Oral

2 g given as a single dose.¹ ⁹ ¹⁷

Treat sexual partners of the patient simultaneously using the same dosage.¹ ⁹ ⁶⁷

For treatment failure following a metronidazole regimen (e.g., single 2-g dose of metronidazole), CDC recommends retreatment with a single 2-g dose of tinidazole; if retreatment fails, CDC recommends tinidazole 2 g once daily for 5 days.⁹ If multiple-dose regimen fails, consult a specialist.⁹

Bacterial Vaginosis

Nonpregnant Women

Oral

2 g once daily for 2 days or 1 g once daily for 5 days.¹

Nongonococcal Urethritis†

Oral

CDC recommends a single 2-g dose of tinidazole in conjunction with a single1-g dose of oral azithromycin (if azithromycin not used in the initial regimen) for treatment of recurrent and persistent urethritis in patients who previously received a recommended regimen. (See Nongonococcal Urethritis under Uses.)⁹

Prescribing Limits

Pediatric Patients

Oral

Children >3 years of age: Maximum 50 mg/kg (up to 2 g) daily or as a single dose.¹ ¹⁷

Special Populations

Hepatic Impairment

Data insufficient to make specific dosage recommendations.¹ Use usual dosage with caution.¹ (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustments not needed, unless patient is undergoing hemodialysis.¹ ⁶⁰

If given on a day that hemodialysis is performed, administer an additional dose (equivalent to 50% of the recommended dose) after the dialysis session.¹ ⁶⁰

Geriatric Patients

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Cautions for Tinidazole

Contraindications

History of hypersensitivity reaction to tinidazole or other nitroimidazole derivatives.¹

First trimester of pregnancy.¹

Breast-feeding.¹ (See Lactation under Cautions.)

Warnings/Precautions

Warnings

Carcinogenicity

Carcinogenic effects reported in mice and rats following chronic oral administration of metronidazole (a chemically related nitroimidazole anti-infective).¹ ³¹ (See Boxed Warning). Similar animal studies using tinidazole have not been reported to date.¹

Because of potential risks, tinidazole should be reserved for approved indications only and unnecessary use avoided.¹

Nervous System Effects

Convulsive seizures and peripheral neuropathy (characterized by numbness or paresthesia of an extremity) reported with tinidazole and other nitroimidazoles (e.g., metronidazole).¹ ³¹

If abnormal neurologic signs develop, promptly discontinue drug.¹

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., urticaria, pruritus, rash, flushing, sweating, dryness of mouth, fever, burning sensation, thirst, salivation, angioedema, bronchospasm, dyspnea, Stevens-Johnson syndrome, erythema multiforme) reported.¹ ⁵⁵

General Precautions

Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of tinidazole and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

History of Blood Dyscrasia

Use with caution in patients with evidence or history of blood dyscrasia.¹ ⁵⁸

As with other nitroimidazoles (e.g., metronidazole), transient leukopenia and neutropenia may occur; persistent hematologic abnormalities not reported to date.¹ ³¹ ⁵⁸

If retreatment is necessary, perform total and differential leukocyte counts.¹

Candidiasis

Vaginal candidiasis reported; treat with an appropriate antifungal.¹

Specific Populations

Pregnancy

Category C (second and third trimesters).¹

Contraindicated during first trimester.¹

Not evaluated for treatment of bacterial vaginosis in pregnant women.¹

Lactation

Distributed into milk in concentrations similar to serum concentrations.¹ ⁶⁶ Interrupt breast-feeding during therapy and for 72 hours following the last dose.¹ ⁶⁶

Pediatric Use

Safety and efficacy not established in pediatric patients ≤3 years of age.¹ Some data available regarding safety and efficacy for treatment of giardiasis in pediatric patients <3 years of age†.¹⁸ ²³ ³² ⁴² ⁴³ ⁴⁴ ⁵⁷

Safety and efficacy in pediatric patients >3 years of age established only for treatment of amebiasis or giardiasis.¹ ¹⁸

Monitor pediatric patients closely if duration of therapy is >3 days (e.g., for treatment of amebic liver abscess)¹ since only limited data available.¹ ³² ⁶⁹

Adverse effects reported in pediatric patients generally similar in nature and frequency to those reported in adults.¹

Geriatric Use

Experience in those ≥65 years of age insufficient to determine whether they respond differently than younger adults.¹

Select dosage with caution because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.¹

Hepatic Impairment

Use with caution;¹ pharmacokinetics not evaluated.¹

Studies using metronidazole (a chemically similar nitroimidazole) indicate reduced elimination and increased plasma concentrations in severe hepatic dysfunction.¹ ³¹

Renal Impairment

Dosage adjustment may be needed in patients undergoing hemodialysis.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (metallic/bitter taste, nausea, anorexia, dyspepsia/cramps/epigastric discomfort, vomiting, constipation), nervous system effects (weakness/fatigue/malaise, dizziness, headache).¹

Interactions for Tinidazole

Metabolized principally by CYP3A4.¹

Does not inhibit CYP1A2, 2B6, 2C9, 2D6, 2E1, or 3A4 in vitro.¹

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma tinidazole concentrations).¹

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma tinidazole concentrations).¹

Specific Drugs and Laboratory Tests

No formal drug interaction studies performed with tinidazole to date; interactions reported with metronidazole (a chemically similar nitroimidazole) may occur with tinidazole.¹

Drug or Test	Interaction	Comments
Alcohol	Alcoholic beverages or preparations containing alcohol or propylene glycol may cause abdominal cramps, nausea, vomiting, headaches, and flushing ¹	Avoid alcoholic beverages and preparations containing alcohol or propylene glycol during or for 3 days following completion of tinidazole therapy¹
Anticoagulants, oral (warfarin)	Possible increased PT and enhanced anticoagulant effects¹	Monitor PT and warfarin dosage carefully during concomitant use and for up to 8 days after the last tinidazole dose¹ ³²
Antifungal agents (ketoconazole)	Possible prolonged half-life, decreased clearance, and increased plasma concentrations of tinidazole¹
Cholestyramine	Studies using metronidazole indicate cholestyramine decreases oral bioavailability of the nitroimidazole by 21%¹	Give tinidazole and cholestyramine doses at separate times¹
Cimetidine	Possible prolonged half-life, decreased clearance, and increased plasma concentrations of tinidazole¹
Disulfiram	Experience with metronidazole and disulfiram indicates psychotic reactions can occur; such reactions not reported to date with tinidazole ¹ ³¹	Do not use concomitantly; do not initiate tinidazole until 2 weeks after disulfiram is discontinued¹
Fluorouracil	Experience with metronidazole and fluorouracil indicates decreased fluorouracil clearance, increased fluorouracil-associated adverse effects, no increased therapeutic benefit¹	If concomitant use of tinidazole and fluorouracil is unavoidable, monitor for fluorouracil toxicity¹
Immunosuppressive agents (cyclosporine, tacrolimus)	Experience with metronidazole indicates increased plasma concentrations of cyclosporine or tacrolimus¹	Monitor for cyclosporine or tacrolimus toxicity if tinidazole used concomitantly with one of these drugs¹
Lithium	Experience with metronidazole and lithium indicates increased lithium concentrations;¹ not reported to date with tinidazole¹	Measure serum lithium and creatinine concentrations after several days of concomitant lithium and tinidazole therapy to detect potential lithium intoxication¹
Phenobarbital	Possible increased elimination and decreased plasma concentrations of tinidazole¹
Phenytoin or fosphenytoin	Experience with oral metronidazole and IV phenytoin indicates prolonged phenytoin half-life and reduced phenytoin clearance;¹ not reported with oral phenytoin and oral metronidazole¹ Possible increased elimination and decreased plasma concentrations of tinidazole¹
Rifampin	Possible increased elimination and decreased plasma concentrations of tinidazole¹
Tests based on ultraviolet (UV) absorbance	Falsely decreased serum concentrations (including undetectable concentrations) of AST, ALT, LDH, triglycerides, or hexokinase glucose may be reported during tinidazole therapy if results are based on decreases in UV absorbance that occur during oxidation-reduction of NADH/NAD¹ UV absorbance peaks of NADH and tinidazole are similar¹	Use caution when interpreting test results based on UV absorbance during tinidazole therapy¹
Tetracyclines	Experience with metronidazole indicates oxytetracycline (no longer commercially available in the US) may inhibit therapeutic effects of the nitroimidazole¹

Tinidazole Pharmacokinetics

Absorption

Bioavailability

Estimated oral bioavailability >90%.⁶³

Rapidly absorbed following oral administration; peak plasma concentrations usually attained within about 2 hours.¹ ³² ⁶³ ⁶⁸

Pharmacokinetic parameters reported with extemporaneous oral suspension containing 66.7 mg/mL (prepared using crushed 500-mg tablets and cherry syrup) in healthy individuals after an overnight fast similar to those reported with tablets swallowed whole under fasted conditions.¹ ³²

Food

Administration with food delays time to peak plasma concentrations by approximately 2 hours and decreases peak plasma concentrations by 10%,¹ ³² but does not affect AUC or elimination half-life.¹ ³²

Distribution

Extent

Distributed into virtually all body tissues and body fluids.¹ ³² ⁶³

Crosses blood-brain barrier.¹ ³² ⁶³

Crosses placenta and is distributed into breast milk.¹

Plasma Protein Binding

12%.¹ ³² ⁶³

Elimination

Metabolism

Extensively metabolized prior to elimination.¹ ⁶³ ¹

Partially metabolized via oxidation, hydroxylation, and conjugation.¹ ⁶³ Metabolized principally by CYP3A4.¹

Present in plasma principally as unchanged drug with small amounts of the 2-hydroxymethyl metabolite.¹ ³² ⁶³

Elimination Route

Eliminated by the liver and kidneys.¹

Excreted in urine as unchanged drug (20–25%) and in feces (12%).¹ ³² ⁶³ ⁶⁸

Removed by hemodialysis.¹ ⁶⁰

Not known whether removed by CAPD.¹

Half-life

Approximately 12–14 hours.¹ ³² ⁵⁸ ⁶³ ⁶⁸

Special Populations

Hepatic impairment: Pharmacokinetics not evaluated.¹ Studies using metronidazole (a chemically similar nitroimidazole) indicate reduced elimination and increased plasma concentrations in severe hepatic impairment.¹ ³¹

Severe renal impairment: Pharmacokinetics not affected by severe impairment (Cl_cr <22 mL/min).¹

Hemodialysis patients: Clearance increased and elimination half-life decreased (from 12 hours to 4.9 hours).¹ ⁶⁰ (See Renal Impairment under Dosage and Administration.)

Stability

Storage

Oral

Tablets

20–25°C (may be exposed to 15–30°C);¹ protect from light.¹

Extemporaneous Oral Suspension

Suspension containing 66.7 mg/mL: Stable for 7 days at room temperature.¹ (See Extemporaneous Oral Suspension under Dosage and Administration.)

Actions and SpectrumActions

Amebicidal, trichomonacidal, and bactericidal.¹ ³² ⁵⁸ ⁵⁹ ⁶³ ⁶⁴ ⁶⁵ ⁶⁸

Cell extracts of Trichomonas appear to reduce the nitroimidazole group of tinidazole and generate the free nitro radical, which may be responsible for the drug’s anti-infective activity.¹ ³² ⁵⁹ ⁶⁵ Mechanism of activity against Giardia and Entamoeba histolytica not known.¹

Protozoa: Active in vitro and in clinical infections against Trichomonas vaginalis, G. duodenalis (also known as G. lamblia or G. intestinalis), and E. histolytica.¹ ⁵⁸ ⁵⁹ ⁶⁵

Anaerobes: Active in vitro against many anaerobic bacteria including some Bacteroides⁵⁸ ⁶⁴ (e.g., B. fragilis,³² ⁵⁹ ⁶³ ⁶⁴ ⁶⁵ ⁶⁸ B. melaninogenicus⁶³ ), some Clostridium³² ⁵⁹ ⁶³ (e.g., C. difficile,³² C. perfringens⁶³ ⁶⁴ ), Prevotella,³² Fusobacterium,⁶³ ⁶⁴ ⁶⁸ Peptococcus,³² ⁵⁸ ⁵⁹ ⁶³ and Peptostreptococcus.³² ⁵⁸ ⁵⁹ ⁶³

Other organisms: Active against Helicobacter pylori ³² and Gardnerella vaginalis.³² ⁵⁹ ⁶⁵ Inactive against most Lactobacillus normally resident in vagina.¹ ³²

Potential for development of resistance in Giardia, E. histolytica, or bacteria associated with bacterial vaginosis not evaluated.¹

Although clinical importance unclear,⁶¹ some T. vaginalis with reduced susceptibility to metronidazole also have reduced susceptibility to tinidazole in vitro.¹ ⁶¹ ⁶² ⁶¹

Advice to Patients

Importance of taking with food to reduce the incidence of adverse GI effects (e.g., epigastric discomfort).¹

Advise patients to avoid alcoholic beverages and preparations containing alcohol or propylene glycol during and for at least 3 days after receiving tinidazole.¹

Advise patients to promptly discontinue tinidazole and contact clinician if abnormal neurologic signs occur.¹

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.¹

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

Importance of advising patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Tinidazole
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	250 mg	Tindamax (scored)	Mission
		500 mg	Tindamax (scored)	Mission

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Tindamax 500MG Tablets (MISSION): 20/$195.88 or 60/$556.36

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions July 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Mission Pharmacal. Tindamax (tinidazole tablets) prescribing information. San Antonio, TX; 2007 Jul.

2. Food and Drug Administration. Orphan designation pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act. (P.L. 97-414). Rockville, MD; From FDA website (). Accessed 2004 Aug.

3. Hager WD. Treatment of metronidazole-resistant Trichomonas vaginalis with tinidazole: case reports of three patients. Sex Transm Dis. 2004; 31:343-5. [PubMed 15167642]

4. Gulmezoglu AM, Garner P. Trichomoniasis treatment in women: a systematic review. Trop Med Int Health. 1998; 3:553-8. [IDIS 412104] [PubMed 9705189]

5. O-Prasertsawat P, Jetsawangsri T. Split-dose metronidazole or single-dose tinidazole for the treatment of vaginal trichomoniasis. Sex Transm Dis. 1992; 19:295-7. [IDIS 521309] [PubMed 1411848]

7. Lossick JG. Treatment of sexually transmitted vaginosis/vaginitis. Rev Infect Dis. 1990; 12(Suppl 6):S665-81. [IDIS 300932] [PubMed 2201078]

8. Heine P, McGregor JA. Trichomonas vaginalis: a reemerging pathogen. Clin Obstet Gynecol. 1993; 36:137-44. [PubMed 8435938]

9. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-95.

10. Lossick JG. Treatment of Trichomonas vaginalis infections. Rev Infect Dis. 1982; 4(Suppl):S801-18.

11. Lossick JG, Kent HL. Trichomoniasis: trends in diagnosis and management. Am J Obstet Gynecol. 1991; 165:1217-22. [IDIS 290714] [PubMed 1951578]

13. Anjaeyulu R, Gupte SA, Desai DB. Single-dose treatment of trichomonal vaginitis: a comparison of tinidazole and metronidazole. J Int Med Res. 1977; 5:438-41. [PubMed 590601]

14. Bloch B, Smyth E. The treatment of Trichomonas vaginalis vaginitis: an open controlled prospective study comparing a single dose of metronidazole tablets, benzoyl metronidazole suspension and tinidazole tablets. S Afr Med J. 1985; 67:455-7. [IDIS 200360] [PubMed 3885425]

15. Lyng J, Christensen J. A double-blind study of the value of treatment with a single dose tinidazole of partners to females with trichomoniasis. Acta Obstet Gynecol Scand. 1981; 60:199-201. [PubMed 7018164]

16. Chaudhuri P, Drogendijk AC. A double-blind controlled clinical trial of carnidazole and tinidazole in the treatment of vaginal trichomoniasis. Eur J Obstet Gynecol Reprod Biol. 1980; 10:325-8. [PubMed 6995193]

17. Anon. Drugs for parasitic infections. From the Medical Letter web site (). Aug 2008.

18. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

19. Hill DR. Giardiasis: issues in diagnosis and management. Infect Dis Clin North Am. 1993; 7:503-25. [PubMed 8254157]

20. Ortega YR, Adam RD. Giardia: overview and update. Clin Infect Dis. 1997; 25:545-50. [IDIS 393721] [PubMed 9314441]

21. Nigam P, Kapoor KK, Kumar AJ et al. Clinical profile of giardiasis and comparison of its therapeutic response to metronidazole and tinidazole. J Assoc Physicians India. 1991; 39:613-5. [PubMed 1814877]

22. Gupta JP, Jain AK, Nanivadekar AS. Efficacy of tinidazole (Fasigyn) in giardiasis by parasitologic, biochemical, and gut transit studies. Indian J Gastroenterol. 1989; 8:103-4. [PubMed 2707840]

23. Cervetto JL, Ramonet M, Nahmod LH et al. Giardiasis. Functional, immunological and histological study of the small bowel: therapeutic trial with a single dose of tinidazole. Arg Gastroenterol. 1987; 24:102-12.

24. Speelman P. Single-dose tinidazole for the treatment of giardiasis. Antimicrob Agents Chemother. 1985; 27:227-9. [IDIS 196181] [PubMed 3985604]

25. Ravdin JI. Amebiasis. Clin Infect Dis. 1995; 20:1453-66. [IDIS 349015] [PubMed 7548493]

26. Aucott JN, Ravdin JI. Amebiasis and “nonpathogenic” intestinal protozoa. Infect Dis Clin North Am. 1993; 7:467-85. [PubMed 8254155]

27. Reed SL. Amebiasis: an update. Clin Infect Dis. 1992; 14:385-93. [IDIS 292053] [PubMed 1554822]

28. Lim JK. Clinical trial of tinidazole (Fasigyn) in acute and chronic intestinal Amoebiasis. Kisaengchunghak Chapchi. 1974; 12:135-140. [PubMed 12913475]

29. Salles JM, Bechara C, Tavares AM et al. Comparative study of the efficacy and tolerability of secnidazole suspension (single dose) and tinidazole suspension (two days dosage) in the treatment of amebiasis in children. Braz J Infect Dis. 1999; 3:80-88. [PubMed 11098194]

30. Boonyapisit S, Chinapak O, Plengvanit U. Amoebic liver abscess in Thailand, clinical analysis of 418 cases. J Med Assoc Thai. 1993;76:243-6.

31. G.D. Searle. Flagyl (metronidazole tablets) prescribing information. Chicago, IL; 2003 Aug.

32. Presutti Laboratories, Arlington Heights, IL: personal communication.

34. Centers for Disease Control and Prevention. Health information for international travel, 2005–2006. Atlanta, GA: US Department of Health and Human Services; 2005. Updates available from CDC website ().

35. Forna F, Gulmezoglu AM. Interventions for treating Trichomoniasis in women (Cochrane review). In: The Cochrane Library. Issue 2. Oxford, United Kingdom: update software 2004.

36. Gabriel G, Robertson E, Thin RN. Single dose treatment of trichomoniasis. J Int Med Res. 1982;10:129-30.

37. Rees PH, McGlashan HE, Mwega V. Single-dose treatment of vaginal trichomoniasis with tinidazole. East Afr Med J. 1974;51:782-5.

38. Mati JK, Wallace RJ. The treatment of trichomonal vaginitis using a single dose of tinidazole by mouth. East Afr Med J. 1974;51:883-8.

39. Sobel JD. Vaginitis. N Engl J Med.1997;337:1896-903.

40. Zaat JO, Mank T, Assendelft WJ. Drugs for treating giardiasis (Cochrane Database). In: The Cochrane Library. Issue 3. Oxford, United Kingdom: update software 2004.

41. Jokipii L, Jokipii AMM. Single-dose metronidazole and tinidazole as therapy for giardiasis: success rates, side effects, and drug absorption and elimination. J Infect Dis. 1979;140:984-88.

42. Danzig S, Hatchuel WLF. Single-dose treatment of giardiasis with tinidazole. S Afr Med J. 1974; 52:708.

43. Bakshi JS, Ghiara JM, Nanivadekar AS. How does tinidazole compare with metronidazole? Drugs. 1978;4315:33-42.

44. Gazder AJ & Banerjee M: Single-dose treatment of giardiasis in children: a comparison of tinidazole and metronidazole. Curr Med Res Opin. 1977; 5:164-68.

45. Centers for Disease Control and Prevention. CDC surveillance summaries: giardiasis surveillance United States, 1992–1997. MMWR CDC Surveill Summ. 2000;49:1-13.

46. Kyronseppa H, Pettersson T. Treatment of giardiasis: relative efficacy of metronidazole as compared with tinidazole. Scand J Inf Dis. .1981; 13:311-12.

47. Haque R, Huston CD, Hughes M, et al. Amebiasis. N Engl J Med. 2003;348:1565-73.

48. Mabadadeje AF, Oredugba. Single-dose tinidazole treatment of amebic dysentery. Curr Ther Res. 1977;21:685-8.

49. Swami B, Lavakusulu D, Devi CS. Tinidazole and metronidazole in the treatment of intestinal amoebiasis. Curr Med Res Opin. 1977;5:152-6.

50. Ahmed T, Ali F, Sarwar SG. Clinical evaluation of tinidazole in amoebiasis in children. Arch Dis Childhood. 1976;51:388-89.

51. Singh G, Kumar S. Short course of single daily dosage treatment with tinidazole and metronidazole in intestinal amoebiasis: a comparative study. Curr Med Res Opin. 1977;5:157-60.

52. Islam N, Hasan K. Tinidazole and metronidazole

Sunday 27 May 2012

Tasmar

Generic Name: tolcapone (TOLE ka pone)

Brand Names: Tasmar

What is Tasmar (tolcapone)?

When used with carbidopa and levodopa (Atamet, Parcopa, Sinemet), tolcapone increases levels of levodopa in the body.

Tolcapone is used together with carbidopa and levodopa to treat symptoms of Parkinson's disease, such as stiffness, tremors, muscle spasms, and poor muscle control.

This medication is usually reserved for use only in people who have used carbidopa and levodopa without success in treating their Parkinson's disease.

Tolcapone is usually given to people who are already taking carbidopa and levodopa but have not had successful treatment of symptoms.

Tolcapone may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Tasmar (tolcapone)?

You should not use this medication if you are allergic to tolcapone, if you have liver disease, or if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days.

Serious or fatal side effects on the liver have occurred in some people taking this medication. You may be required to read and sign a Patient Consent form before you get a prescription for tolcapone.

Call your doctor at once if you have nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes). Drinking alcohol can increase certain side effects of tolcapone. Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by tolcapone. Tell your doctor if you regularly use any of these other medicines. Do not stop using tolcapone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using tolcapone.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medication. Talk with your doctor if you believe you have any intense or unusual urges while taking tolcapone.

What should I discuss with my healthcare provider before taking Tasmar (tolcapone)?

You should not use this medication if you are allergic to tolcapone, or if you have taken a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), phenelzine (Nardil), or tranylcypromine (Parnate) in the last 14 days.

Serious or fatal side effects on the liver have occurred in some people taking tolcapone. You may be required to read and sign a Patient Consent form before you get a prescription for tolcapone.

You should not use tolcapone if you are allergic to it, or if you have:

liver disease; or

if you have ever had muscle damage or fever and confusion caused by a medication.

If you have any of these other conditions, you may need a tolcapone dose adjustment or special tests:

low blood pressure; or

kidney disease.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking tolcapone. It is not known whether the medicine actually causes this effect. Talk with your doctor if you believe you have any intense or unusual urges while taking tolcapone.

Tolcapone may cause hallucinations (the sensation of hearing or seeing something that is not there), most commonly among elderly people. Call your doctor if you experience hallucinations.

Some people taking Parkinson's disease medications have developed skin cancer (melanoma). However, people with Parkinson's disease may have a higher risk of melanoma. Talk to your doctor about this risk and what skin symptoms to watch for. You may need to have regular skin exams.

FDA pregnancy category C. It is not known whether tolcapone will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.. It is not known whether tolcapone passes into breast milk or if it could harm a nursing baby. Do not take tolcapone without telling your doctor if you are breast-feeding a baby.

How should I take Tasmar (tolcapone)?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label.

Tolcapone must be taken together with carbidopa and levodopa. Tolcapone used alone will not treat symptoms of Parkinson's disease.

Your doctor may occasionally change your dose to make sure you get the best results.

Tolcapone is usually taken three times a day. The first dose is taken with your first daily dose of carbidopa and levodopa. The second and third doses of tolcapone are taken 6 and 12 hours later.

Tolcapone may be taken with or without food.

To be sure this medicine is not causing harmful effects, your blood will need to be tested often. Your liver and kidney function may also need to be tested. Visit your doctor regularly.

Call your doctor if your symptoms do not improve after 3 weeks of using tolcapone.

Do not stop using tolcapone suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to avoid withdrawal symptoms when you stop using tolcapone. Store at room temperature in a tightly closed container, away from moisture and heat.

See also: Tasmar dosage (in more detail)

What happens if I miss a dose?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Overdose symptoms may include nausea, vomiting, and dizziness.

What should I avoid while taking Tasmar (tolcapone)?

Tolcapone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

Drinking alcohol can increase certain side effects of tolcapone.

Tasmar (tolcapone) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have any of these serious side effects:

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

feeling like you might pass out;

fever, stiff muscles, confusion, and sweating (especially when you first start taking tolcapone);

hallucinations;

tremors (uncontrolled shaking);

tight feeling in your chest, trouble breathing;

pain or burning when you urinate;

severe or ongoing diarrhea; or

muscle pain, tenderness, or weakness with fever or flu symptoms and dark colored urine.

Less serious side effects may include:

diarrhea or constipation;

dry mouth;

headache, tired feeling;

unusual skin changes;

dizziness, drowsiness;

cold symptoms such as stuffy nose, sneezing, sore throat;

sleep problems (insomnia), dreaming more than usual; or

agitation or anxiety.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Tasmar (tolcapone)?

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by tolcapone. Tell your doctor if you regularly use any of these other medicines, or any other Parkinson's medications..

Tell your doctor about all other medicines you use, especially:

apomorphine (Apokyn);

a blood thinner such as warfarin (Coumadin);

desipramine (Norpramin);

dobutamine (Dobutrex);

epinephrine (Epi-Pen, and others);

isoproterenol (Isuprel, Medihaler-Iso); or

methyldopa (Aldomet).

This list is not complete and other drugs may interact with tolcapone. Tell your doctor about all medications you use. This includes prescription, over the counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More Tasmar resources

Tasmar Side Effects (in more detail)
Tasmar Dosage
Tasmar Use in Pregnancy & Breastfeeding
Drug Images
Tasmar Drug Interactions
Tasmar Support Group
0 Reviews for Tasmar - Add your own review/rating

Tasmar Prescribing Information (FDA)

Tasmar MedFacts Consumer Leaflet (Wolters Kluwer)

Tasmar Monograph (AHFS DI)

Tasmar Advanced Consumer (Micromedex) - Includes Dosage Information

Tolcapone Professional Patient Advice (Wolters Kluwer)

Compare Tasmar with other medications

Parkinson's Disease

Where can I get more information?

Your pharmacist can provide more information about tolcapone.

See also: Tasmar side effects (in more detail)

Q-Gesic

Generic Name: acetaminophen and phenyltoloxamine (a seet a MIN oh fen and FEN il toe LOX a meen)

Brand Names: Aceta-Gesic, Acuflex, Alpain, Apagesic, BeFlex, BP Poly-650, Dologesic, Flextra-650, Flextra-DS, Genasec, Hyflex-650, Hyflex-DS, Lagesic, Major-gesic, Percogesic, Phenagesic, Phenylgesic, Q Flex, Q-Gesic, Relagesic, RhinoFlex, RhinoFlex 650, Staflex, Vistra, Vitoxapap

What is Q-Gesic (acetaminophen and phenyltoloxamine)?

Acetaminophen is a pain reliever and a fever reducer.

Phenyltoloxamine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Acetaminophen and phenyltoloxamine is used to treat runny nose, sneezing, and pain or fever caused by the common cold, flu, or seasonal allergies.

Acetaminophen and phenyltoloxamine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Q-Gesic (acetaminophen and phenyltoloxamine)?

Do not use acetaminophen and phenyltoloxamine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take acetaminophen and phenyltoloxamine before the MAO inhibitor has cleared from your body. Acetaminophen and phenyltoloxamine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Do not take more of this medication than is recommended. An overdose of acetaminophen can cause damage to your liver. If you drink more than three alcoholic beverages per day, do not take acetaminophen without your doctor's advice, and never take more than 2 grams (2000 mg) of acetaminophen per day. Do not take this medication without your doctor's advice if you have ever had alcoholic liver disease (cirrhosis). You may not be able to take acetaminophen.

What should I discuss with my healthcare provider before taking Q-Gesic (acetaminophen and phenyltoloxamine)?

You should not take this medication if you are allergic to acetaminophen or phenyltoloxamine. Do not use acetaminophen and phenyltoloxamine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take acetaminophen and phenyltoloxamine before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist about taking acetaminophen and phenyltoloxamine if you have:

liver or kidney disease;

diabetes;

glaucoma;

urination problems;

an enlarged prostate;

heart disease or high blood pressure;

a stomach ulcer; or

an overactive thyroid.

Tell your doctor if you drink more than three alcoholic beverages per day or if you have ever had alcoholic liver disease (cirrhosis). You may not be able to take medication that contains acetaminophen.

It is not known whether acetaminophen and phenyltoloxamine is harmful to an unborn baby. Do not take this medication without telling your doctor if you are pregnant. Acetaminophen and phenyltoloxamine can pass into breast milk and may harm a nursing baby. Do not take this medication without telling your doctor if you are breast-feeding a baby.

How should I take Q-Gesic (acetaminophen and phenyltoloxamine)?

Use this medication exactly as directed on the label, or as prescribed by your doctor. Do not use it in larger amounts or for longer than recommended.

Do not take more than 1 gram (1000 mg) of acetaminophen per dose or 4 grams (4000 mg) per day. An acetaminophen overdose can damage your liver. Know the amount of acetaminophen in the product you are taking.

Call your doctor if your symptoms do not improve, or if you have a fever for longer than 3 days.

This medication can cause you to have unusual results with certain medical tests. Tell any doctor who treats you that you are taking acetaminophen and phenyltoloxamine.

Store this medication at room temperature away from moisture and heat.

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, wait until then to take the medicine and skip the missed dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

Seek emergency medical attention if you think you have used too much of this medicine.

The first signs of an acetaminophen overdose include loss of appetite, nausea, vomiting, stomach pain, sweating, and confusion or weakness. Later symptoms may include pain in your upper stomach, dark urine, and yellowing of your skin or the whites of your eyes.

Overdose symptoms may also include dizziness, drowsiness, diarrhea, loss of appetite, and seizure (convulsions), or coma.

What should I avoid while taking Q-Gesic (acetaminophen and phenyltoloxamine)?

Acetaminophen and phenyltoloxamine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol while you are taking acetaminophen and phenyltoloxamine. It can increase your risk of liver damage while taking acetaminophen. Do not use any other cold, allergy, pain, or sleep medication without first asking your doctor or pharmacist. Acetaminophen (sometimes abbreviated as "APAP") and antihistamines are contained in many combination medicines. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains acetaminophen, APAP, or an antihistamine.

Q-Gesic (acetaminophen and phenyltoloxamine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have a serious side effect such as:

fast, pounding, or uneven heartbeat;

nausea, stomach pain, low fever, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes); or

easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms.

Less serious side effects may include:

dry eyes, nose, and mouth;

drowsiness or dizziness;

blurred vision;

urinating less than usual; or

feeling restless or excited (especially in children).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Q-Gesic (acetaminophen and phenyltoloxamine)?

Tell your doctor if you regularly use other medicines that make you sleepy (such as cold or allergy medicine, other pain medicines, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by phenyltoloxamine.

There may be other drugs that can interact with acetaminophen and phenyltoloxamine. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Q-Gesic resources

Q-Gesic Side Effects (in more detail)
Q-Gesic Use in Pregnancy & Breastfeeding
Q-Gesic Drug Interactions
Q-Gesic Support Group
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Where can I get more information?

Your pharmacist can provide more information about acetaminophen and phenyltoloxamine.

See also: Q-Gesic side effects (in more detail)