Rifater Tablets

1. Name Of The Medicinal Product

Rifater Tablets

2. Qualitative And Quantitative Composition

Rifampicin Ph Eur 120 mg

Isoniazid Ph Eur 50 mg

Pyrazinamide Ph Eur 300 mg

3. Pharmaceutical Form

Tablets

4. Clinical Particulars

4.1 Therapeutic Indications

Rifater is indicated in the treatment of pulmonary tuberculosis.

4.2 Posology And Method Of Administration

Rifater is recommended in the initial intensive phase of the short-course treatment of pulmonary tuberculosis. During this phase, which lasts for 2 months, Rifater should be administered on a daily continuous basis. The concomitant administration of ethambutol or intramuscular streptomycin over the same period of time is advised.

Each Rifater tablet contains isoniazid (INH), pyrazinamide (Z) and rifampicin (RAMP) in such a ratio that the administration of 9-12mg/kg RAMP, 4-5mg/kg INH and 23-30mg/kg Z can be achieved by giving 3 tablets daily to patients weighing less than 40kg, 4 tablets to patients weighing 40-49kg, 5 tablets to patients weighing 50-64kg and 6 tablets to patients weighing 65kg or more.

Rifater should be given as a single dose and preferably on an empty stomach at least 30 minutes before a meal, or 2 hours after a meal to ensure rapid and complete absorption.

Once the initial intensive phase of treatment has been completed treatment can be continued with the combination rifampicin-isoniazid (Rifinah) always on a daily basis.

This regimen, if correctly applied, is 100% effective with very few, if any, relapses. The clinical evidence indicates that these occur generally in the first 6 months after stopping treatment with bacilli fully sensitive to the drugs employed, so that changes in the drugs to be utilised for further treatment are not required. The regimen has been found to be fully effective also in the presence of a bacillary population resistant to isoniazid, to streptomycin or to both drugs.

Children: The ratio of the three drugs in Rifater may not be appropriate in children (eg higher mg/kg doses of INH are usually given in children than in adults). Rifater can be used only in special cases, after careful consideration of the mg/kg dose of each component.

Use in the Elderly: Caution should be exercised in such patients, in view of the possible decrease of the excretory function of the kidney and of the liver.

4.3 Contraindications

Rifater is contra-indicated in patients who are hypersensitive to any one of the components of the combination or any of the excipients. Rifater is contra-indicated in the presence of jaundice.

Rifater use is contraindicated when given concurrently with the combination of saquinavir/ritonavir (see section 4.5 Interactions).

4.4 Special Warnings And Precautions For Use

The precautions for the use of Rifater are the same as those considered when a triple individual administration of rifampicin, isoniazid and pyrazinamide is required. Rifater should only be given under supervision. Each of these drugs has been associated with liver dysfunction.

Rifater should be given under the supervision of a respiratory or other suitably qualified physician.

All tuberculosis patients should have pre-treatment measurements of liver function.

Adults treated for tuberculosis with Rifater should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count and a platelet count (or estimate).

Patients should be seen at least monthly during therapy and should be questioned specifically about symptoms associated with adverse reactions. All patients with abnormalities should have follow-up, including laboratory testing, if necessary.

However, because there is a higher frequency of isoniazid-associated hepatitis among persons older than 35 years of age, a transaminase measurement should be obtained at baseline and at least monthly during therapy in this age group. Other factors associated with an increased risk of hepatitis include daily use of alcohol, chronic liver disease, intravenous drug use and being a black or Hispanic woman.

If the patient has no evidence of pre-existing liver disease and normal pre-treatment liver function, liver function tests need only be repeated if fever, vomiting, jaundice or other deterioration in the patient's condition occur.

Patients with impaired liver function should only be given Rifater in cases of necessity and then with caution and under strict medical supervision. In these patients, careful monitoring of liver function, especially serum glutamic pyruvic transaminase (SGPT) and serum glutamic oxaloacetic transaminase (SGOT) should be carried out prior to therapy and then every two to four weeks during therapy.

If signs of hepatocellular damage or clinically significant changes in hepatic function occur, Rifater should be withdrawn. The need for other forms of antituberculosis therapy and a different regimen should be considered. Urgent advice should be obtained from a specialist in the management of tuberculosis. If Rifater is reintroduced after liver function has returned to normal, liver function should be monitored daily.

Rifampicin

Cautions should be taken in cases of renal impairment if dose> 600 mg/day.

In patients with impaired liver function, elderly patients, malnourished patients and possibly children under two years of age, caution is particularly recommended when instituting therapeutic regimens in which isoniazid is to be used concurrently with rifampicin.

In some cases, hyperbilirubinaemia resulting from competition between rifampicin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels and considering them in conjunction with the patient's clinical condition.

Because of the possibility of immunological reaction including anaphylaxis (see section 4.8 Undesirable effects) occurring with intermittent rifampicin therapy (less than 2 or 3 per week) patients should be closely monitored. Patients should be cautioned against interruption of dosage regimens since these reactions may occur.

Rifampicin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D. Isolated reports have associated porphyria exacerbation with rifampicin administration.

Isoniazid

Use of isoniazid should be carefully monitored in patients with current chronic liver disease or severe renal dysfunction.

Severe and sometimes fatal hepatitis associated with isoniazid therapy may occur and may develop even after many months of treatment. The risk of developing hepatitis is age related. Therefore, patients should be monitored for the prodromal symptoms of hepatitis; such as fatigue, weakness, malaise, anorexia, nausea or vomiting. If these symptoms appear or if signs suggestive of hepatic damage are detected, isoniazid should be discontinued promptly, since continued use of the drug in these cases has been reported to cause a more severe form of liver damage.

Care should be exercised in the treatment of elderly or malnourished patients who may also require Vitamin B6 supplementation with the isoniazid therapy.

Use of isoniazid should be carefully monitored in patients with slow acetylator status, epilepsy, history of psychosis, history of peripheral neuropathy, diabetes, alcohol dependence, HIV infection or porphyria.

Pyrazinamide

Rifater should be used with caution in patients with a history of gout. If hyperuricaemia accompanied by an acute gouty arthritis occurs, the patient should be transferred to a regimen not containing pyrazinamide (e.g. Rifinah 150 or 300).

The possibility of pyrazinamide having an adverse effect on blood clotting time or vascular integrity should be borne in mind in patients with haemoptysis.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Food Interaction

Because isoniazid has some monoamine oxidase inhibiting activity, an interaction with tyramine-containing foods (cheese, red wine) may occur. Diamine oxidase may also be inhibited, causing exaggerated response (e.g. headache, sweating, palpitations, flushing, hypotension) to foods containing histamine (e.g. skipjack, tuna, other tropical fish). Tyramine- and histamine-containing foods should be avoided by patients receiving Rifater.

Interactions with other medicinal products

Cytochrome P-450 enzyme interaction

Rifampicin is known to induce and isoniazid is known to inhibit certain cytochrome P-450 enzymes. In general, the impact of the competing effects of rifampicin and isoniazid on the metabolism of drugs that undergo biotransformation through the affected pathways is unknown. Therefore, caution should be used when prescribing Rifater with drugs metabolised by cytochrome P-450. To maintain optimum therapeutic blood levels, dosages of drugs metabolised by these enzymes may require adjustment when starting or stopping Rifater.

Interactions with Rifampicin

Examples of drugs metabolised by cytochrome P-450 enzymes are:

• Antiarrhythmics (e.g. disopyramide, mexiletine, quinidine, propafenone, tocainide),

• Antiepileptics (e.g. phenytoin),

• Hormone antagonist (antiestrogens e.g. tamoxifen, toremifene, gestinone),

• Antipsychotics (e.g. haloperidol, aripiprazole),

• Anticoagulants (e.g. coumarins),

• Antifungals (e.g. fluconazole, itraconazole, ketoconazole, voriconazole),

• Antivirals (e.g. saquinavir, indinavir, efavirenz, amprenavir, nelfinavir, atazanavir, lopinavir, nevirapine),

• Barbiturates

• Beta-blockers (e.g. bisoprolol, propanolol),

• Anxiolytics and hypnotics (e.g. diazepam, benzodiazepines, zopiclone, zolpidem),

• Calcium channel blockers (e.g. diltiazem, nifedipine, verapamil, nimodipine, isradipine, nicardipine, nisoldipine),

• Antibacterials (e.g. chloramphenicol, clarithromycin, dapsone, doxycycline, fluoroquinolones, telithromycin),

• Corticosteroids

• Cardiac glycosides (digitoxin, digoxin),

• Clofibrate,

• Systemic hormonal contraceptives

• Oestrogen,

• Antidiabetic (e.g. chlorpropamide, tolbutamide, sulfonylureas, rosiglitazone),

• Immunosuppressive agents (e.g. ciclosporin, sirolimus, tacrolimus)

• Irinotecan,

• Thyroid hormone (e.g. levothyroxine),

• Losartan,

• Analgesics (e.g. methadone, narcotic analgesics),

• Praziquantel,

• Progestogens,

• Quinine,

• Riluzole,

• Selective 5-HT3 receptor antagonists (e.g. ondansetron)

• Statins metabolised by CYP 3A4 (e.g. simvastatin),

• Theophylline,

• Tricyclic antidepressants (e.g. amitriptyline, nortriptyline),

• Cytotoxics (e.g. imatinib),

• Diuretics (e.g. eplerenone)

Patients using oral contraceptives should be advised to change to non-hormonal methods of birth control during Rifater therapy. Also diabetes may become more difficult to control.

When rifampicin is given concomitantly with the combination saquinavir/ritonavir, the potential for hepatotoxicity is increased. Therefore, concomitant use of Rifater with saquinavir/ritonavir is contraindicated (see section 4.3 Contraindications).

Other Interactions

Rifampicin may reduce the effect of ACE inhibitors (e.g. enalapril, imidapril), antiemetics (e.g. aprepitant), antineoplastic agents (e.g. imatinib), diuretics (e.g. eplerenone), drugs used in erectile dysfunction (e.g. tadalafil), oral hypoglycemic agents (e.g. nateglinide, repaglinide) and NSAIDS (e.g. etoricoxib).

When the two drugs were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampicin were observed.

Concurrent use of ketoconazole and rifampicin has resulted in decreased serum concentrations of both drugs.

Concomitant antacid administration may reduce the absorption of rifampicin. Daily doses of rifampicin should be given at least 1 hour before the ingestion of antacids.

The potential for hepatotoxicity is increased with an anaesthetic.

When rifampicin is given concomitantly with either halothane or isoniazid, the potential for hepatotoxicity is increased. The concomitant use of rifampicin and halothane should be avoided. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity.

If p-aminosalicylic acid and rifampicin are both included in the treatment regimen, they should be given not less than eight hours apart to ensure satisfactory blood levels.

Interactions with Isoniazid

The following drugs may interact with isoniazid:

• Antiepileptics (e.g. carbamazepine and phenytoin)

There may be an increased risk of distal sensory neuropathy when isoniazid is used in patients taking stavudine.

Concomitant use of zalcitabine with isoniazid has been shown to approximately double the renal clearance if isoniazid in HIV infected patients.

Administration of prednisolone 20mg to 13 slow acetylators and 13 fast acetylators for receiving isoniazid 10mg/kg reduced plasma concentrations of isoniazid by 25% and 40%, respectively. The clinical significance of this effect has not been established.

The effect of acute alcohol intake (serum levels 1g/L maintained for 12 hours) on the metabolism of isoniazid (300mg/d for 2 days) was studies in 10 healthy volunteers in a controlled cross over design. The metabolism of isoniazid and its metabolite, acetyl isoniazid, was not modified by this acute alcohol intake. The metabolism of isoniazid may be increased in chronic alcoholics; however this effect has not been quantified.

Other Interactions

Para-aminosalicylic acid may increase the plasma concentration and elimination half-life of isoniazid by competing for acetylating enzymes.

General anaesthetics may increase the hepatotoxicity of isoniazid.

The absorption of isoniazid is reduced by antacids.

The risk of CNS toxicity is increased when isoniazid is given with cycloserine.

Isoniazid may reduce plasma concentration of ketoconazole and increase plasma concentration of theophylline.

Pyrazinamide

Pyrazinamide antagonizes the effects of probenecid and sulfinpyrazone.

Interference with laboratory and diagnostic tests

Therapeutic levels of rifampicin have been shown to inhibit standard microbiological assays for serum folate and Vitamin B12. Thus alternative assay methods should be considered. Transient elevation of BSP and serum bilirubin has been reported. Rifampicin may impair biliary excretion of contrast media used for visualization of the gallbladder, due to competition for biliary excretion. Therefore, these tests should be performed before the morning dose of rifampicin.

4.6 Pregnancy And Lactation

Pregnancy

Rifampicin

At very high doses in animals rifampicin has been shown to have teratogenic effects. There are no well controlled studies with Rifater in pregnant women. Although rifampicin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampicin, alone or in combination with other antituberculosis drugs, on the human foetus is not known. When administered during the last few weeks of pregnancy, rifampicin may cause post-natal haemorrhages in the mother and infant, for which treatment with Vitamin K1 may be indicated.

Isoniazid

It has been reported that in both rats and rabbits, isoniazid may exert an embryocardial effect when administered orally during pregnancy, although no isoniazid-related congenital anomalies have been found in reproduction studies in mammalian species (mice, rats, rabbits).

Therefore, Rifater should be used in pregnant women or in women of child-bearing potential only if the potential benefit justifies the potential risk to the foetus.

Lactation

Rifampicin, isoniazid and pyrazinamide are excreted in breast milk and infants should not be breast fed by a patient receiving Rifater unless in the physician's judgement the potential benefit to the patient outweighs the potential risk to the infant.

In breast-fed infants whose mothers are taking isoniazid, there is a theoretical risk of convulsions and neuropathy (associated with vitamin B6 deficiency), therefore they should be monitored for early signs of these effects and consideration should be given to treating both mother and infant prophylactically with pyridoxine.

4.7 Effects On Ability To Drive And Use Machines

Isoniazid has been associated with vertigo, visual disorders and psychotic reactions (see section 4.8). Patients should be informed of these, and advised that if affected, they should not drive, operate machinery or take part in any activities where these symptoms may put either themselves or others at risk.

4.8 Undesirable Effects

Rifampicin

Reactions occurring with either daily or intermittent dosage regimens include:

Cutaneous reactions which are mild and self-limiting may appear and do not appear to be hypersensitivity reactions. Typically they consist of flushing and itching with or without a rash. Urticaria and more serious hypersensitivity cutaneous reactions have occurred but are uncommon. Exfoliate dermatitis, pemphigoid reaction, erythema multiforme including Stevens-Johnson syndrome, Lyells syndrome and vasculitis have been reported rarely.

Gastro-intestinal reactions consist of anorexia, nausea, vomiting, abdominal discomfort, and diarrhoea. Pseudomembranous colitis has been reported with rifampicin therapy.

Hepatitis can be caused by rifampicin and liver function tests should be monitored. (See section 4.4. Special warnings and precautions for use).

Central Nervous System: Psychoses have been rarely reported.

Thrombocytopenia with or without purpura may occur, usually associated with intermittent therapy, but is reversible if drug is discontinued as soon as purpura occurs. Cerebral haemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura.

Disseminated intravascular coagulation has also been rarely reported.

Eosinophilia, leucopenia, oedema, muscle weakness and myopathy have been reported to occur in a small percentage of patients treated with rifampicin.

Agranulocytosis has been reported very rarely.

Rare reports of adrenal insufficiency in patients with compromised adrenal function have been observed.

Reactions usually occurring with intermittent dosage regimens and probably of immunological origin include:

• 'Flu Syndrome' consisting of episodes of fever, chills, headache, dizziness, and bone pain appearing most commonly during the 3rd to 6th month of therapy. The frequency of the syndrome varies but may occur in up to 50% of patients given once-weekly regimens with a dose of rifampicin of 25mg/kg or more.

• Shortness of breath and wheezing.

• Decrease in blood pressure and shock.

• Anaphylaxis.

• Acute haemolytic anaemia.

• Acute renal failure usually due to acute tubular necrosis or to acute interstitial nephritis.

If serious complications arise, (renal failure, thrombocytopenia or haemolytic anaemia), Rifater should be stopped and never restarted.

Occasional disturbances of the menstrual cycle have been reported in women receiving long term anti-tuberculosis therapy with regimens containing rifampicin.

Rifampicin may produce a reddish colouration of the urine, sputum, sweat and tears. The patient should be forewarned of this. Soft contact lenses may be permanently stained.

Isoniazid

Severe and sometimes fatal hepatitis may occur with isoniazid therapy. Hypersensitivity reactions including fever and anaphylactic reactions have been reported with isoniazid treatment. Nervous system disorders include vertigo; polyneuritis associated with isoniazid, presenting as paraesthesia, muscle weakness, loss of tendon reflexes etc, is unlikely to occur with the recommended daily dose of Rifater. Various haematological disturbances have been identified during treatment with isoniazid, including eosinophilia, agranulocytosis, thrombocytopenia and anaemia, aplastic anaemia, haemolytic anaemia. High doses of isoniazid can cause convulsions, toxic encephalopathy, optic neuritis and atrophy, memory impairment and toxic psychosis. The possibility that the frequency of seizures may be increased in patients with epilepsy should be borne in mind. Systemic lupus erythromatosus-like syndrome and pellagra have also been reported with isoniazid therapy. Cutaneous reactions (rash, acne, Stevens-Johnson syndrome, exfoliative dermatitis, pemphigus) and gastrointestinal reactions (pancreatitis, constipation, dry mouth, nausea, vomiting, epigastric distress) have been reported.

Other adverse reactions associated with isoniazid therapy are; hyperglycaemia, gynaecomastia and anti-nuclear antibodies

Pyrazinamide

Adverse reactions, other than hepatic reactions, which have been attributed to pyrazinamide are active gout (pyrazinamide has been reported to reduce urate excretion), sideroblastic anaemia, thrombocytopenia with or without purpura, arthralgia, anorexia, nausea and vomiting, dysuria, malaise, fever and aggravation of peptic ulcer. The hepatic reaction is the most common adverse reaction and varies from a symptomless abnormality of hepatic cell function detected only through laboratory liver function tests, through a mild syndrome of fever, malaise and liver tenderness, to more serious reactions such as clinical jaundice and rare cases of acute yellow atrophy and death.

Skin and subcutaneous tissue disorders: Urticaria, pruritus, erythema, rash.

Very rarely, angioedema has been reported.

4.9 Overdose

There is limited overdose information involving rifampicin, isoniazid and pyrazinamide in combination.

Signs and Symptoms

Rifampicin

Nausea, vomiting, abdominal pain, pruritus, headache and increasing lethargy will probably occur within a short time after acute ingestion; unconsciousness may occur when there is severe hepatic disease. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange colouration of the skin, urine, sweat, saliva, tears and faeces will occur, and its intensity is proportional to the amount ingested. Facial or periorbital oedema has also been reported in paediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.

The minimum acute lethal or toxic dose is not well established. However, nonfatal acute overdoses in adults have been reported with doses ranging from 9 to 12 g rifampicin. Fatal acute overdoses in adults have been reported with doses ranging from 14 to 60 g. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal reports. Nonfatal overdoses in paediatrics patients ages 1 to 4 years old of 100 mg/kg for one to two doses have been reported.

Isoniazid

Isoniazid overdosage produces signs and symptoms within 30 minutes to 3 hours after ingestion. Nausea, vomiting, dizziness, slurring of speech, blurring of vision and visual hallucinations (including bright colours and strange designs), are among the early manifestations. With marked overdosage, respiratory distress and CNS depression, progressing rapidly from stupor to profound coma are to be expected, along with severe, intractable seizures. Severe metabolic acidosis, acetonuria and hyperglycaemia are typical laboratory findings.

Pyrazinamide

There is limited information related to pyrazinamide overdose. Liver toxicity and hyperuricemia may occur with overdosage.

Management

In cases of overdosage with Rifater, gastric lavage should be performed as soon as possible. Following evacuation of the gastric contents, the instillation of activated charcoal slurry into the stomach may help absorb any remaining drug from the gastrointestinal tract. Antiemetic medication may be required to control severe nausea and vomiting.

Intensive supportive measures should be instituted, including airway patency and individual symptoms treated as they arise.

Isoniazid

If acute isoniazid overdose is suspected, even in asymptomatic patients, the administration of intravenous pyridoxine (vitamin B6) should be considered. In patients with seizures not controlled with pyridoxine (vitamin B6), anticonvulsant therapy should be administered. Sodium bicarbonate should be given to control metabolic acidosis. Haemodialysis is advised for refractory cases; if this is not available, peritoneal dialysis can be used along with forced diuresis.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Rifampicin, isoniazid and pyrazinamide are all active bactericidal antituberculosis drugs. Rifampicin and isoniazid are particularly active against the rapidly growing extracellular organisms. Pyrazinamide is active against intracellular organisms, particularly in the acid pH environment of macrophages. Rifampicin and isoniazid also have bactericidal activity intracellularly. Rifampicin has activity against slow and intermittently-growing M tuberculosis. Thus, the three agents, rifampicin, isoniazid and pyrazinamide have activity against the three different bacterial populations.

Rifampicin inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase but does not inhibit the mammalian enzyme. Cross-resistance to rifampicin has only been shown after the development of resistance to other rifamycins.

5.2 Pharmacokinetic Properties

Rifampicin

Rifampicin is readily absorbed from the stomach and the duodenum. Peak serum concentrations of the order of 10 µg/ml occur about 2-4 hours after a dose of 10mg/kg body weight on an empty stomach.

In normal subjects the biological half-life of rifampicin in serum averages about 3 hours after a 600mg dose and increases to 5.1 hours after 900mg dose. With repeated administration, the half-life decreases and reaches average values of approximately 2-3 hours. At a dose of up to 600 mg/day the half-life does not differ in patients with renal failure and, consequently, no dosage adjustment is required. The half-life of rifampicin may be decreased when isoniazid is administered concurrently.

After absorption, rifampicin is rapidly eliminated in the bile and an enterohepatic circulation ensues. During this process, rifampicin undergoes progressive deacetylation, so that nearly all the drug in the bile is in this form in about 6 hours. This metabolite retains essentially complete antibacterial activity. Intestinal reabsorption is reduced by deacetylation and elimination is facilitated. Up to 30% of a dose is excreted in the urine with about half of this being unchanged drug. Absorption of rifampicin is reduced when the drug is ingested with food.

Rifampicin is widely distributed throughout the body. It is present in effective concentrations in many organs and body fluids, including cerebrospinal fluid. Rifampicin is about 80% protein bound. Most of the unbound fraction is not ionized and therefore is diffused freely in tissues.

Isoniazid

After oral administration, isoniazid produces peak blood levels within 1 to 2 hours, which decline to 50% or less within 6 hours. Ingestion of isoniazid with food may reduce its absorption. It diffuses readily into all body fluids (cerebrospinal, pleural, and ascitic fluids), tissues, organs and excreta (saliva, sputum and faeces). The drug also passes through the placental barrier and into the milk in concentrations comparable to those in the plasma. From 50 to 70% of a dose of isoniazid is excreted in the urine in 24 hours.

Isoniazid is metabolised primarily by acetylation and dehydrazination. The rate of acetylation is genetically determined. Approximately 50% of Black and Europeans are 'Slow inactivators', the majority of Asians are 'rapid inactivators'.

Pyridoxine deficiency (B₆) is sometimes observed in adults with high doses of isoniazid, probably due to its competition with pyridoxal phosphate of the enzyme apotryptophanase.

Pyrazinamide

Pyrazinamide is well absorbed from the gastrointestinal tract and rapidly distributed throughout the body, with peak plasma levels in 2 hours. It is hydrolysed to pyrazinoic acid and then metabolised to 5-hydroxypyrazinoic acid. Glomerular filtration is the primary route of excretion. It is bactericidal in acid pH, and has intracellular antibacterial activity against M. tuberculosis.

Pharmacokinetic studies in normal volunteers have shown that the three ingredients in Rifater have comparable bioavailability whether they are given together as individual dose forms or as Rifater.

5.3 Preclinical Safety Data

Not applicable

6. Pharmaceutical Particulars

6.1 List Of Excipients

Polyvinylpyrrolidone

Sodium Carboxymethylcellulose

Sodium Lauryl Sulphate

Calcium Stearate

Sucrose

Acacia Gum

Talc

Light Magnesium Carbonate

Kaolin

Titanum Dioxide

Colloidal Silicon Dioxide

Aluminium Hydroxide Gel

Iron Oxide

6.2 Incompatibilities

None stated

6.3 Shelf Life

4 years from date of manufacture

6.4 Special Precautions For Storage

Do not store above 25^oC. Store in the original container.

6.5 Nature And Contents Of Container

PDVC and PVC/PVDC aluminium foil blisters packed in cardboard cartons.

Pack size: 100 tablets

6.6 Special Precautions For Disposal And Other Handling

Not applicable

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

PL 04425/0060

9. Date Of First Authorisation/Renewal Of The Authorisation

27 April 1984/10 May 1995

10. Date Of Revision Of The Text

13 March 2009

LEGAL STATUS

POM

Phisohex

Generic Name: hexachlorophene (Topical application route)

hex-a-KLOR-oh-feen

Commonly used brand name(s)

In the U.S.

• Phisohex

Available Dosage Forms:

• Liquid


• Powder for Suspension


• Foam

Therapeutic Class: Antibacterial Cleansing Agent

Uses For Phisohex

Hexachlorophene is a topical antibacterial cleanser. It is used to clean the skin before surgery to prevent the spread of infection. It works like a detergent to cleanse the skin by killing or preventing the growth of bacteria.

This medicine is available only with your doctor's prescription.

Before Using Phisohex

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Because of hexachlorophene's potential for the risk of increased drug absorption, use in infants and premature babies is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of hexachlorophene in the elderly. However, elderly patients are more likely to have skin diseases, circulation problems, delayed wound healing, and age-related liver, kidney, and heart problems, which may require caution in patients receiving hexachlorophene.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Broken or burned skin—Should not be used in patients with this condition.

• Ichthyosis congenita (genetic skin disorder) or


• Letterer-Siwe disease (a rare disease) or


• Other skin diseases—Use with caution. May increase the risk for serious side effects.

Proper Use of Phisohex

It is very important that you use this medicine only as directed. Do not use more of it, do not use it more often, and do not use it for a longer time than your doctor ordered.

Hexachlorophene should only be used on the skin. Do not swallow it or use it in the eyes, ears, mouth, nose, genital area (sex organs), or anal area. If it does get on these areas, rinse it right away with water.

Follow your doctor's instructions about how to clean and care for your skin before and after you use this medicine. Make sure you understand all of the directions, and ask questions if you find something is not clear.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For topical dosage form (emulsion):
  
  • For cleaning the skin:
    
    • Adults and children—Apply 5 milliliters (mL) to the hands and make it into a lather by adding a small amount of water. Apply to the area to be cleansed, rinse thoroughly with running water, and pat dry.
    
    
    • Infants—Use is not recommended.
    
    
  
  

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Phisohex

Check with your doctor if your skin problem becomes worse. Call your doctor if you develop a constant skin irritation, such as redness, itching or burning, in the area where you used this medicine.

This medicine should not be used on a regular basis on large areas of the body. Follow your doctor's instructions about how long to use this medicine.

This medicine may cause serious and permanent injury when placed in the eyes, ears, mouth, or vagina. Carefully follow all instructions before using this medicine to prevent serious side effects.

Hexachlorophene must not be used to bathe infants on a regular basis unless your doctor tells you otherwise. This may increase risk for more serious side effects.

Do not use this medicine as an occlusive dressing, wet pack, lotion, or tampon. Also, using other skin products that contain alcohol may decrease the effectiveness of hexachlorophene.

Phisohex Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

Incidence not known

• Blistering, crusting, irritation, itching, or reddening of the skin


• cracked, dry, or scaly skin


• increased sensitivity of the skin to sunlight


• redness or other discoloration of the skin


• severe sunburn


• skin rash


• swelling

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Abdominal or stomach cramps


• blurred vision


• cold, clammy skin


• confusion


• convulsions


• decreased urination


• diarrhea


• dizziness


• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly


• dry mouth


• fainting


• fast, weak pulse


• increase in heart rate


• lightheadedness


• loss of appetite


• rapid breathing


• sunken eyes


• sweating


• thirst


• unusual tiredness or weakness


• vomiting


• weight loss


• wheezing


• wrinkled skin

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Phisohex side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Phisohex resources

• Phisohex Side Effects (in more detail)
• Phisohex Use in Pregnancy & Breastfeeding
• Phisohex Drug Interactions
• Phisohex Support Group
• 0 Reviews · Be the first to review/rate this drug

• Phisohex Prescribing Information (FDA)


• pHisoHex Monograph (AHFS DI)


• pHisoHex MedFacts Consumer Leaflet (Wolters Kluwer)

Elimite

permethrin

Dosage Form: cream
Elimite® Cream

(permethrin) 5%*

DESCRIPTION:

Elimite® (permethrin) 5% Cream is a topical scabicidal agent for the treatment of infestation with Sarcoptes scabiei (scabies). It is available in an off-white, vanishing cream base. Elimite® (permethrin) 5% Cream is for topical use only.

Structural formula:

Chemical Name:

The permethrin used is an approximate 1:3 mixture of the cis and trans isomers of the pyrethroid 3-(2,2-dichloroethenyl)-2,2-dimethylcyclopropanecarboxylic acid, (3-phenoxyphenyl) methyl ester. Permethrin has a molecular formula of C21H20CI2O3 and a molecular weight of 391.29. It is a yellow to light orange-brown, low melting solid or viscous liquid.

Active Ingredient: Each gram contains permethrin 50 mg (5%).

Inactive Ingredients: Butylated hydroxytoluene, carbomer 934 P, fractionated coconut oil, glycerin, glyceryl monostearate, isopropyl myristate, lanolin alcohols, mineral oil, polyoxyethylene cetyl ethers, purified water, and sodium hydroxide. Formaldehyde 1 mg (0.1%) is added as a preservative.

CLINICAL PHARMACOLOGY:

Permethrin, a pyrethroid, is active against a broad range of pests including lice, ticks, fleas, mites, and other arthropods. It acts on the nerve cell membrane to disrupt the sodium channel current by which the polarization of the membrane is regulated. Delayed repolarization and paralysis of the pests are the consequences of this disturbance.

Permethrin is rapidly metabolized by ester hydrolysis to inactive metabolites which are excreted primarily in the urine. Although the amount of permethrin absorbed after a single application of the 5% Cream has not been determined precisely, data from studies with 14C-labeled permethrin and absorption studies of the cream applied to patients with moderate to severe scabies indicate it is 2% or less of the amount applied.

INDICATIONS AND USAGE:

Elimite® (permethrin) 5% Cream is indicated for the treatment of infestation with Sarcoptes scabiei (scabies).

CONTRAINDICATIONS:

Elimite® (permethrin) 5% Cream is contraindicated in patients with known hypersensitivity to any of its components, to any synthetic pyrethroid or pyrethrin.

WARNINGS:

If hypersensitivity to Elimite® (permethrin) 5% Cream occurs, discontinue use.

PRECAUTIONS:

General:

Scabies infestation is often accompanied by pruritus, edema, and erythema. Treatment with Elimite® (permethrin) 5% Cream may temporarily exacerbate these conditions.

Information for Patients:

Patients with scabies should be advised that itching, mild burning and/or stinging may occur after application of Elimite® (permethrin) 5% Cream. In clinical trials, approximately 75% of patients treated with Elimite® (permethrin) 5% Cream who continued to manifest pruritus at 2 weeks had cessation by 4 weeks. If irritation persists, they should consult their physician. Elimite® (permethrin) 5% Cream may be very mildly irritating to the eyes. Patients should be advised to avoid contact with eyes during application and to flush with water immediately if Elimite® (permethrin) 5% Cream gets in the eyes.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

Six carcinogenicity bioassays were evaluated with permethrin, three each in rats and mice. No tumorigenicity was seen in the rat studies. However, species-specific increases in pulmonary adenomas, a common benign tumor of mice of high spontaneous background incidence, were seen in the three mouse studies. In one of these studies there was an increased incidence of pulmonary alveolar-cell carcinomas and benign liver adenomas only in female mice when permethrin was given in their food at a concentration of 5000 ppm. Mutagenicity assays, which give useful correlative data for interpreting results from carcinogenicity bioassays in rodents, were negative. Permethrin showed no evidence of mutagenic potential in a battery of in vitro and in vivo genetic toxicity studies.

Permethrin did not have any adverse effect on reproductive function at a dose of 180 mg/kg/day orally in a three-generation rat study.

Pregnancy:

Teratogenic Effects:

Pregnancy Category B: Reproduction studies have been performed in mice, rats, and rabbits (200 to 400 mg/kg/day orally) and have revealed no evidence of impaired fertility or harm to the fetus due to permethrin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers:

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the evidence for tumorigenic potential of permethrin in animal studies, consideration should be given to discontinuing nursing temporarily or withholding the drug while the mother is nursing.

Pediatric Use:

Elimite® (permethrin) 5% Cream is safe and effective in pediatric patients two months of age and older. Safety and effectiveness in infants less than two months of age have not been established.

Geriatric Use:

Clinical studies of Elimite® (permethrin) 5% Cream did not identify sufficient numbers of subjects aged 65 and over to allow a definitive statement regarding whether elderly subjects respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. This drug is known to be substantially excreted by the kidney. However, since topical permethrin is metabolized in the liver and excreted in the urine as inactive metabolites, there does not appear to be an increased risk of toxic reactions in patients with impaired renal function when used as labeled.

ADVERSE REACTIONS:

In clinical trials, generally mild and transient burning and stinging followed application with Elimite® (permethrin) 5% Cream in 10% of patients and was associated with the severity of infestation. Pruritus was reported in 7% of patients at various times post-application. Erythema, numbness, tingling, and rash were reported in 1 to 2% or less of patients (see PRECAUTIONS: General). Other adverse events reported since marketing Elimite® (permethrin) 5% Cream include: headache, fever, dizziness, abdominal pain, diarrhea and nausea and/or vomiting. Although extremely uncommon and not expected when used as directed (see DOSAGE AND ADMINISTRATION), rare occurrences of seizure have been reported. None have been medically confirmed as associated with Elimite® treatment.

OVERDOSAGE:

No instance of accidental ingestion of Elimite® (permethrin) 5% Cream has been reported. If ingested, gastric lavage and general supportive measures should be employed. Excessive topical use (see recommended dosage) may result in increased irritation and erythema.

DOSAGE AND ADMINISTRATION:

Adults and children: Thoroughly massage Elimite® (permethrin) 5% Cream into the skin from the head to the soles of the feet. Scabies rarely infests the scalp of adults, although the hairline, neck, temple, and forehead may be infested in infants and geriatric patients. Usually 30 grams is sufficient for an average adult. The cream should be removed by washing (shower or bath) after 8 to 14 hours. Infants should be treated on the scalp, temple, and forehead. ONE APPLICATION IS GENERALLY CURATIVE.

Patients may experience persistent pruritus after treatment. This is rarely a sign of treatment failure and is not an indication for retreatment. Demonstrable living mites after 14 days indicate that retreatment is necessary.

HOW SUPPLIED:

Elimite® (permethrin) 5% (w/w) Cream is supplied in white laminate tubes with tube head and orifice made of high density polyethylene, and white polypropylene screw caps. Elimite® (permethrin) 5% Cream is available in 60 gm size.

           Elimite® 5% Cream

           60 gm NDC 0023-7915-60.

Note: Store at 15° to 25°C (59° to 77°F).

Rx only

*w/w

Manufactured for: ALLERGAN

Revised June 2004

Allergan, Inc.

Irvine, CA 92612 U.S.A.

by DSM Pharmaceuticals, Inc.

Greenville, NC 27834

©2004, Allergan, Inc.

® Marks owned by Allergan, Inc.

71655US11P

Principal Display Panel

PDP for the tube:

60 g NDC 0023-7915-60

Elimite® CREAM

(PERMETHRIN) 5%*

Manufactured for Allergan, Inc.

Irvine, CA 92612, U.S.A.

by DSM Pharmaceuticals, Inc.

Greenville, NC 27834

©2005 Allergan, Inc.

® Marks owned by Allergan, Inc.

*W/W

FOR EXTERNAL USE ONLY.

NOT FOR USE IN EYES.

Rx Only

PDP for the carton:

60 g NDC 0023-7915-60

Elimite® CREAM

(PERMETHRIN) 5%*

*W/W

FOR EXTERNAL USE ONLY.

NOT FOR USE IN EYES.

Rx Only

Elimite  permethrin  cream

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0023-7915 Route of Administration CUTANEOUS DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength permethrin (permethrin) permethrin 50 mg  in 1 g

Inactive Ingredients Ingredient Name Strength butylated hydroxytoluene   carbomer 934   medium-chain triglycerides   glycerin   glyceryl monostearate   isopropyl myristate   lanolin alcohols   mineral oil   water   sodium hydroxide   Formaldehyde

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0023-7915-60 1 TUBE In 1 CARTON contains a TUBE 1 60 g In 1 TUBE This package is contained within the CARTON (0023-7915-60) 2 0023-7915-30 1 TUBE In 1 CARTON contains a TUBE 2 30 g In 1 TUBE This package is contained within the CARTON (0023-7915-30)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA019855	12/01/1989	12/31/2009

Labeler - Allergan, Inc. (144796497)

Establishment
Name	Address	ID/FEI	Operations
Allergan, Inc.		144796497	MANUFACTURE

Revised: 12/2009Allergan, Inc.

More Elimite resources

• Elimite Side Effects (in more detail)
• Elimite Dosage
• Elimite Use in Pregnancy & Breastfeeding
• Elimite Support Group
• 1 Review for Elimite - Add your own review/rating

• Elimite Concise Consumer Information (Cerner Multum)


• Elimite Topical Advanced Consumer (Micromedex) - Includes Dosage Information


• Elimite Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Acticin Concise Consumer Information (Cerner Multum)

Compare Elimite with other medications

• Head Lice
• Lice
• Scabies

Percocet

Generic Name: oxycodone and acetaminophen (Oral route)

a-seet-a-MIN-oh-fen, ox-i-KOE-done hye-droe-KLOR-ide

Oral route(Tablet)

Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4000 mg/day, and often involve more than one acetaminophen-containing product .

Commonly used brand name(s)

In the U.S.

• Endocet


• Magnacet


• Narvox


• Percocet


• Perloxx


• Primalev


• Roxicet


• Roxilox


• Tylox


• Xolox

Available Dosage Forms:

• Tablet


• Solution


• Capsule

Therapeutic Class: Opioid/Acetaminophen Combination

Chemical Class: Oxycodone

Uses For Percocet

Oxycodone and acetaminophen combination is used to relieve moderate to moderately severe pain.

Acetaminophen is used to relieve pain and reduce fever in patients. It does not become habit-forming when taken for a long time. But acetaminophen may cause other unwanted effects when taken in large doses, including liver damage.

Oxycodone belongs to the group of medicines called narcotic analgesics (pain medicines). It acts on the central nervous system (CNS) to relieve pain.

When oxycodone is used for a long time, it may become habit-forming, causing mental or physical dependence. However, people who have continuing pain should not let the fear of dependence keep them from using narcotics to relieve their pain. Mental dependence (addiction) is not likely to occur when narcotics are used for this purpose. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

This medicine is available only with your doctor's prescription.

Before Using Percocet

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of oxycodone and acetaminophen combination in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of oxycodone and acetaminophen combination in the elderly. However, elderly patients are more likely to have age-related kidney or liver problems, which may require caution and an adjustment in the dose for patients receiving oxycodone and acetaminophen combination.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Naltrexone

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acetophenazine


• Adinazolam


• Alfentanil


• Alprazolam


• Amobarbital


• Anileridine


• Aprobarbital


• Atazanavir


• Brofaromine


• Bromazepam


• Brotizolam


• Buprenorphine


• Buspirone


• Butabarbital


• Butalbital


• Butorphanol


• Carisoprodol


• Chloral Hydrate


• Chlordiazepoxide


• Chlorpromazine


• Chlorzoxazone


• Clarithromycin


• Clobazam


• Clonazepam


• Clorazepate


• Clorgyline


• Codeine


• Dantrolene


• Desflurane


• Dexmedetomidine


• Dezocine


• Diazepam


• Diphenhydramine


• Doxylamine


• Enflurane


• Erythromycin


• Escitalopram


• Estazolam


• Eszopiclone


• Ethchlorvynol


• Ethopropazine


• Fentanyl


• Flumazenil


• Flunitrazepam


• Fluphenazine


• Flurazepam


• Fluvoxamine


• Fospropofol


• Furazolidone


• Halazepam


• Halothane


• Hydrocodone


• Hydromorphone


• Hydroxyzine


• Indinavir


• Iproniazid


• Isocarboxazid


• Isoflurane


• Itraconazole


• Ketamine


• Ketazolam


• Ketoconazole


• Lazabemide


• Levorphanol


• Linezolid


• Lorazepam


• Lormetazepam


• Medazepam


• Meperidine


• Mephenesin


• Mephobarbital


• Meprobamate


• Mesoridazine


• Metaxalone


• Methdilazine


• Methocarbamol


• Methohexital


• Midazolam


• Moclobemide


• Morphine


• Morphine Sulfate Liposome


• Nalbuphine


• Nefazodone


• Nelfinavir


• Nialamide


• Nitrazepam


• Nitrous Oxide


• Nordazepam


• Opium


• Oxazepam


• Oxycodone


• Oxymorphone


• Pargyline


• Pentazocine


• Pentobarbital


• Perphenazine


• Phenelzine


• Phenobarbital


• Prazepam


• Procarbazine


• Prochlorperazine


• Promazine


• Promethazine


• Propiomazine


• Propofol


• Propoxyphene


• Quazepam


• Ramelteon


• Rasagiline


• Remifentanil


• Ritonavir


• Saquinavir


• Secobarbital


• Selegiline


• Sertraline


• Sevoflurane


• Sodium Oxybate


• Sufentanil


• Tapentadol


• Telithromycin


• Temazepam


• Thiethylperazine


• Thiopental


• Thioridazine


• Toloxatone


• Tranylcypromine


• Triazolam


• Trifluoperazine


• Triflupromazine


• Trimeprazine


• Zaleplon


• Zolpidem

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol


• Carbamazepine


• Isoniazid


• Miconazole


• Phenytoin


• Rifampin


• St John's Wort


• Voriconazole


• Warfarin


• Zidovudine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Using this medicine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Cabbage

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Addison's disease (adrenal gland problem) or


• Alcohol abuse, history of or


• Brain tumor, history of or


• Chronic obstructive pulmonary disease (COPD) or


• CNS depression or


• Cor pulmonale (serious heart condition) or


• Drug dependence, especially with narcotics, or history of or


• Enlarged prostate (BPH, prostatic hypertrophy) or


• Head injuries, history of or


• Hypothyroidism (an underactive thyroid) or


• Hypovolemia (low blood volume) or


• Kyphoscoliosis (curvature of the spine with breathing problems) or


• Mental illness or


• Problems with passing urine—Use with caution. May increase risk for more serious side effects.

• Asthma, severe or


• Hypercarbia (high carbon dioxide in the blood), severe or


• Paralytic ileus (bowels stop working and may be blocked) or


• Respiratory depression (very slow breathing)—Should not be used in patients with these conditions.

• Hypotension (low blood pressure) or


• Pancreatitis (inflammation of the pancreas) or


• Seizures, history of or


• Stomach problems—Use with caution. May make these conditions worse.

• Kidney disease or


• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Proper Use of oxycodone and acetaminophen

This section provides information on the proper use of a number of products that contain oxycodone and acetaminophen. It may not be specific to Percocet. Please read with care.

Take this medicine only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for elderly patients, who may be more sensitive to the effects of pain medicines. If too much of this medicine is taken for a long time, it may become habit-forming and cause mental or physical dependence. Also, large amounts of acetaminophen may cause liver damage if taken for a long time.

Measure the oral liquid using the patient cup that comes with the package.

Carefully check the labels of all other medicines you are using, because they may also contain acetaminophen. It is not safe to use more than 4 grams (4,000 milligrams) of acetaminophen in one day (24 hours).

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For moderate to moderately severe pain:
  
  • For oral dosage form (capsules):
    
    • Adults—One capsule every 6 hours as needed.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (solution):
    
    • Adults—5 milliliters (mL) or one teaspoonful every 6 hours as needed. However, the dose is usually not more than 60 mL (12 teaspoonfuls) per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (tablets):
    
    • Adults—One tablet every 6 hours as needed. However, the dose is usually not more than 6 to 12 tablets per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Flush any unused capsules, liquid, or tablets down the toilet.

Precautions While Using Percocet

It is very important that your doctor check your progress while you are taking this medicine. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

It is against the law and dangerous for anyone else to use your medicine. Keep your unused tablets in a safe and secure place. People who are addicted to drugs might want to steal this medicine.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that can make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for allergies or colds; sedatives, tranquilizers, or sleeping medicine; other prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Also, there may be a greater risk of liver damage if you drink three or more alcoholic beverages while you are taking acetaminophen. Do not drink alcoholic beverages, and check with your doctor before taking any of these medicines while you are using this medicine.

This medicine may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose. Call your doctor for instructions.

Dizziness, lightheadedness, or fainting may occur when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem. Also, lying down for a while may relieve the dizziness or lightheadedness.

This medicine may make you dizzy, drowsy, or lightheaded. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Check with your doctor right away if you have pain or tenderness in the upper stomach; pale stools; dark urine; loss of appetite; nausea; unusual tiredness or weakness; or yellow eyes or skin. These could be symptoms of a serious liver problem.

This medicine may cause a serious type of allergic reaction called anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Stop using this medicine and call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; or any swelling of your hands, face, or mouth while you are using this medicine.

Using narcotics for a long time can cause severe constipation. To prevent this, your doctor may direct you to take laxatives, drink a lot of fluids, or increase the amount of fiber in your diet. Be sure to follow the directions carefully, because continuing constipation can lead to more serious problems.

If you have been using this medicine regularly for several weeks or longer, do not change your dose or suddenly stop using it without checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as abdominal or stomach cramps, anxiety, fever, irritability, nausea, restlessness, runny nose, sweating, tremors, or trouble with sleeping.

Using this medicine while you are pregnant may cause serious unwanted effects in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.

Before you have any medical tests, tell the medical doctor in charge that you are taking this medicine. The results of some tests may be affected by this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines, especially those containing acetaminophen (Tylenol (R)), and herbal or vitamin supplements.

Percocet Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Abdominal or stomach pain


• black, tarry stools


• chills


• dark urine


• dizziness


• fever


• headache


• itching


• light-colored stools


• loss of appetite


• nausea


• rash


• unpleasant breath odor


• unusual tiredness or weakness


• vomiting of blood


• yellow eyes or skin

Rare

• Cough or hoarseness


• fever with or without chills


• general feeling of tiredness or weakness


• lower back or side pain


• painful or difficult urination


• sore throat


• sores, ulcers, or white spots on the lips or in the mouth


• unusual bleeding or bruising

Incidence not known

• Back, leg, or stomach pains


• bleeding gums


• bloating


• blood in the urine or stools


• blue lips and fingernails


• blurred vision


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• chest pain or discomfort


• clay-colored stools


• cloudy urine


• clumsiness


• confusion


• constipation


• coughing that sometimes produces a pink frothy sputum


• decrease in the frequency of urination


• decrease in urine volume


• decreased awareness or responsiveness


• decreased frequency or amount of urine


• decreased urination


• difficult or labored breathing


• difficult or painful urination


• difficult, fast, noisy breathing, sometimes with wheezing


• difficulty in passing urine (dribbling)


• difficulty with swallowing


• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position


• drowsiness


• dry mouth


• extremely shallow or slow breathing


• fainting


• fast or deep breathing


• fast, slow, irregular, pounding, or racing heartbeat or pulse


• feeling of warmth


• general body swelling


• greatly decreased frequency of urination or amount of urine


• hives or welts


• increase in heart rate


• increased blood pressure


• increased sweating


• increased thirst


• indigestion


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• lightheadedness


• low body temperature


• muscle aches


• muscle tremors


• muscle weakness


• nervousness


• noisy breathing


• nosebleeds


• numbness or tingling in the hands, feet, or lips


• pains in the stomach, side, or abdomen, possibly radiating to the back


• pale skin


• pinpoint red spots on the skin


• pounding in the ears


• puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue


• rapid, deep breathing


• rapid, shallow breathing


• redness of the face, neck, arms, and occasionally, upper chest


• redness of the skin


• restlessness


• seizures


• severe constipation


• severe sleepiness


• severe vomiting


• shivering


• shortness of breath


• skin blisters


• skin rash


• sleepiness


• slow or irregular breathing


• sore throat


• stomach cramps


• stomach pain, continuing


• sudden decrease in the amount of urine


• sunken eyes


• sweating


• swelling in the legs and ankles


• swelling of the face, fingers, or lower legs


• thirst


• tightness in the chest


• tiredness


• troubled breathing


• unpleasant breath odor


• upper right abdominal or stomach pain


• vomiting


• vomiting of blood


• weak or feeble pulse


• weakness or heaviness of the legs


• weight gain


• wheezing


• wrinkled skin

Get emergency help immediately if any of the following symptoms of overdose occur:

Symptoms of overdose

• Bluish lips or skin


• change in consciousness


• cold, clammy skin


• extreme sleepiness


• general feeling of discomfort or illness


• loss of consciousness


• no blood pressure or pulse


• not breathing


• stopping of heart


• unconsciousness

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Relaxed and calm

Incidence not known

• Acid or sour stomach


• agitation


• anxiety


• bad or unusual or unpleasant (after) taste


• belching


• change in taste


• cold sweats


• constricted, pinpoint, or small pupils (black part of the eye)


• continuing ringing or buzzing or other unexplained noise in the ears


• cool, pale skin


• depression


• diarrhea


• difficulty with moving


• disturbed color perception


• double vision


• excess air or gas in the stomach or intestines


• false or unusual sense of well-being


• flushed, dry skin


• fruit-like breath odor


• full feeling


• general feeling of discomfort or illness


• halos around lights


• hearing loss


• heartburn


• increased hunger


• increased thirst


• increased urination


• indigestion


• joint pain


• lack or loss of strength


• muscle cramps or spasms


• muscle pain or stiffness


• nervousness


• night blindness


• nightmares


• overbright appearance of lights


• passing gas


• rash


• red eye


• seeing, hearing, or feeling things that are not there


• seizures


• severe sleepiness


• shakiness


• sleepiness or unusual drowsiness


• sleeplessness


• slurred speech


• stomach discomfort, upset, or pain


• stomach fullness


• sweating


• swollen joints


• thirst


• trouble sleeping


• troubled breathing


• tunnel vision


• unable to sleep


• unexplained weight loss


• unusual drowsiness, dullness, tiredness, weakness, or feeling of sluggishness

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Percocet side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Percocet resources

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

Compare Percocet with other medications

• Pain

Fortesta Gel

Pronunciation: tes-TOS-ter-one
Generic Name: Testosterone
Brand Name: Fortesta

Children who have been exposed to Fortesta Gel have developed symptoms such as enlarged genitals; increased pubic hair, erections, or sex drive; aggressive behavior; and increased bone age. Contact the child's doctor right away if any of these symptoms occur. Children should avoid contact with unwashed or unclothed application sites in men who use Fortesta Gel.

Closely follow the recommended instructions for use of Fortesta Gel.

Fortesta Gel is used for:

Treating symptoms of low testosterone in adult men when the body does not make any testosterone or not enough testosterone (hypogonadism). It may also be used for other conditions as determined by your doctor.

Fortesta Gel is an androgen hormone. It works by replacing or supplementing the testosterone that is naturally made in the body.

Do NOT use Fortesta Gel if:

• you are allergic to any ingredient in Fortesta Gel


• you are pregnant, may become pregnant, or are breast-feeding


• you have known or suspected breast or prostate cancer

Contact your doctor or health care provider right away if any of these apply to you.

Before using Fortesta Gel:

Some medical conditions may interact with Fortesta Gel. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you have heart problems (eg, congestive heart failure), high cholesterol levels, swelling or fluid buildup (edema), lung problems, or sleep apnea (long pauses in breathing while you sleep)


• if you have cancer, diabetes, an enlarged prostate, benign prostatic hypertrophy (BPH), kidney or liver problems, high blood calcium levels, or you are overweight


• if you are using insulin

Some MEDICINES MAY INTERACT with Fortesta Gel. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Corticosteroids (eg, prednisone) or corticotropin (ACTH) because they may increase the risk of Fortesta Gel's side effects


• Anticoagulants (eg, warfarin) because the risk of their side effects may be increased by Fortesta Gel

This may not be a complete list of all interactions that may occur. Ask your health care provider if Fortesta Gel may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Fortesta Gel:

Use Fortesta Gel as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Fortesta Gel comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Fortesta Gel refilled.


• You will need to prime this product before the first use. To prime it, with the canister in the upright position, depress the pump 8 times and appropriately discard the gel that is pumped out.


• Apply Fortesta Gel with one finger and gently rub it evenly onto clean, dry skin of the front and inner thighs. Make sure that your shorts or pants will be able to cover the application site.


• Do not apply Fortesta Gel to the genitals or other parts of the body. Avoid applying Fortesta Gel to the thigh adjacent to the scrotum. Do not apply it over open sores, wounds, or irritated skin.


• It is best to apply Fortesta Gel at the same time every day in the morning after showering or bathing, unless directed otherwise by your doctor.


• Do not allow another person to apply Fortesta Gel for you.


• Wash your hands with soap and water immediately after using Fortesta Gel.


• Allow Fortesta Gel to dry for a few minutes before dressing.


• After Fortesta Gel has dried, cover the application site (eg, with shorts or pants) to prevent others from coming into contact with Fortesta Gel. If direct skin-to-skin contact with another person is expected, wash the application site well with soap and water to remove the medicine.


• For best results, wait at least 2 hours after applying Fortesta Gel before you shower or swim. Showering or swimming just 1 hour after applying Fortesta Gel may be permitted if done very infrequently.


• If you miss a dose of Fortesta Gel, use it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Fortesta Gel.

Important safety information:

• Fortesta Gel may cause dizziness. This effect may be worse if you take it with alcohol or certain medicines. Use Fortesta Gel with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Do NOT change your dose or use more than the recommended dose without checking with your doctor.


• Patients who use androgens (such as testosterone) may have an increased risk of prostate cancer. Check with your doctor if you have questions about your risk of prostate cancer while you use Fortesta Gel.


• Do not allow others, especially children and women, to come into contact with the medicine, the application site, or any unwashed clothing that may have touched the application site. If someone else comes into contact with Fortesta Gel, have them wash the area with soap and water right away.


• Contact your doctor right away if a child you are in close contact with develops enlarged genitals, pubic hair, or increased sex drive, or if your female partner develops a change in hair distribution, an increase in acne, or any masculine signs.


• Fortesta Gel is flammable. Avoid fire, an open flame, or smoking after application until Fortesta Gel has dried.


• Do not switch between other topical testosterone products and Fortesta Gel without talking to your doctor.


• Tell your doctor or dentist that you take Fortesta Gel before you receive any medical or dental care, emergency care, or surgery.


• Fortesta Gel may interfere with certain lab tests. Be sure your doctor and lab personnel know you are using Fortesta Gel.


• Diabetes patients - Fortesta Gel may affect your blood sugar. Check blood sugar levels closely. Ask your doctor before you change the dose of your diabetes medicine.


• Large doses of Fortesta Gel may lower your sperm count. Discuss any questions or concerns with your doctor.


• Lab tests, including liver function, hematocrit, blood cholesterol, prostate-specific antigen (PSA), and blood testosterone, may be performed while you use Fortesta Gel. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.


• Use Fortesta Gel with caution in the ELDERLY; they may be more sensitive to its effects, especially an enlarged prostate or prostate cancer.


• Fortesta Gel should be used with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in these children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: Fortesta Gel is not approved for use in women. Fortesta Gel may cause harm to the fetus. Do not use Fortesta Gel if you are pregnant. If you think you may be pregnant, contact your doctor right away. It is not known if Fortesta Gel is found in breast milk. Do not breast-feed while using Fortesta Gel.

Possible side effects of Fortesta Gel:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Abnormal dreams; acne; change in sex drive; dizziness; headache; skin redness or irritation at the application site.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); breast tenderness or enlargement; calf pain, swelling, or redness; change in the size or shape of the testicles; dark urine; excessive daytime sleepiness; frequent, prolonged, or painful erections; interrupted breathing while sleeping; loss of appetite; memory problems; migraine; mood or mental changes (eg, anxiety, depression, hostility, suicidal thoughts); nausea; new or worsening urination problems (eg, frequent urination, inability to urinate, weak urine stream); pale stools; severe headache; shortness of breath; skin discoloration; stomach pain; swelling of the hands, ankles, or legs; trouble sleeping or other sleep changes; unexplained or unusual weight gain; unusual tiredness or weakness; vomiting; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Fortesta side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include confusion; one-sided weakness; slurred speech; vision changes.

Proper storage of Fortesta Gel:

Store Fortesta Gel between 68 and 77 degrees F (20 and 25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Do not freeze. Store away from heat, moisture, and light. Keep Fortesta Gel out of the reach of children and away from pets.

General information:

• If you have any questions about Fortesta Gel, please talk with your doctor, pharmacist, or other health care provider.


• Fortesta Gel is to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Fortesta Gel. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Fortesta resources

• Fortesta Side Effects (in more detail)
• Fortesta Use in Pregnancy & Breastfeeding
• Fortesta Drug Interactions
• Fortesta Support Group
• 2 Reviews for Fortesta - Add your own review/rating

Compare Fortesta with other medications

• Hypogonadism, Male

Antidepressants

Antidepressants are drugs that treat depression and improve the symptoms. The main types of antidepressants are tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors and other atypical antidepressants. All types of antidepressant drugs may take more than two weeks to show any benefits, although their pharmacological effects are produced immediately.

See also

• miscellaneous antidepressants
• monoamine oxidase inhibitors
• phenylpiperazine antidepressants
• selective serotonin reuptake inhibitors
• serotonin-norepinephrine reuptake inhibitors
• tetracyclic antidepressants
• tricyclic antidepressants

Drug List:

Hydrocortisone Butyrate Solution

Dosage Form: topical solution
Hydrocortisone Butyrate Solution, 0.1%



For Dermatological Use Only

DESCRIPTION

Hydrocortisone Butyrate Solution, 0.1% contains the topical corticosteroid hydrocortisone butyrate, a non-fluorinated hydrocortisone ester. It has the chemical name: pregn-4-ene-3,20-dione, 11,21 - dihydroxy-17-[(1-oxobutyl)oxy]-, (11β-;

the molecular formula: C25H36O6;

the molecular weight: 432.54;

and the CAS registry number: 13609-67-1.

Its structural formula is:

Each mL of Hydrocortisone Butyrate Solution, 0.1% contains 1.0 mg of hydrocortisone butyrate in a vehicle consisting of isopropyl alcohol (50%), glycerin, povidone, citric acid, sodium citrate and purified water.

CLINICAL PHARMACOLOGY

Topical corticosteroids share anti-inflammatory, anti-pruritic and vasoconstrictive actions. The mechanism of anti-inflammatory activity of the topical corticosteroids is unclear. Various laboratory methods, including vasoconstrictor assays, are used to compare and predict potencies and/or clinical efficacies of the topical corticosteroids. There is some evidence to suggest that a recognizable correlation exists between vasoconstrictor potency and therapeutic efficacy in man.

PHARMACOKINETICS

The extent of percutaneous absorption of topical corticosteroids is determined by many factors including the vehicle, the integrity of the epidermal barrier, and the use of occlusive dressings.

Topical corticosteroids can be absorbed from normal intact skin. Inflammation and/or other disease processes in the skin increase percutaneous absorption. Occlusive dressings substantially increase the percutaneous absorption of topical corticosteroids.

Once absorbed through the skin, topical corticosteroids are handled through pharmacokinetic pathways similar to systemically administered corticosteroids. Corticosteroids are bound to plasma proteins in varying degrees. Corticosteroids are metabolized primarily in the liver and are then excreted by the kidneys. Some of the topical corticosteroids and their metabolites are also excreted into the bile.

INDICATIONS AND USAGE

Hydrocortisone Butyrate Solution, 0.1% is indicated for the relief of the inflammatory and pruritic manifestations of seborrheic dermatoses.

CONTRAINDICATIONS

Topical corticosteroids are contraindicated in those patients with a history of hypersensitivity to any of the components of the preparation.

PRECAUTIONS

General

Systemic absorption of topical corticosteroids has produced reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Conditions which augment systemic absorption include the application of the more potent steroids, use over large surface areas, prolonged use, and the addition of occlusive dressings.

Therefore, patients receiving a large dose of a potent topical steroid applied to a large surface area or under an occlusive dressing should be evaluated periodically for evidence of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests.

If HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce the frequency of application, or to substitute a less potent steroid.

Recovery of HPA axis function is generally prompt and complete upon discontinuation of the drug.

Infrequently, signs and symptoms of steroid withdrawal may occur, requiring supplemental systemic corticosteroids.

Children may absorb proportionally larger amounts of topical corticosteroids and thus be more susceptible to systemic toxicity.

(See PRECAUTIONS - PEDIATRIC USE).

If irritation develops, topical corticosteroids should be discontinued and appropriate therapy instituted.

In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be instituted. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection has been adequately controlled.

Information for the Patient

Patients using topical corticosteroids should receive the following information and instructions:

1. This medication is to be used as directed by the physician. It is for external use only. Avoid contact with the eyes.

2. Patients should be advised not to use this medication for any disorder other than for which it was prescribed.

3. The treated skin area should not be bandaged or otherwise covered or wrapped as to be occlusive unless directed by the physician.

4. Patients should report any signs of local adverse reactions especially under occlusive dressing.

5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute occlusive dressings.

Laboratory Tests

The following tests may be helpful in evaluating the HPA axis suppression:

Urinary free cortisol test

ACTH stimulation test

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids.

Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed negative results.

Pregnancy Category C

Corticosteroids are generally teratogenic in laboratory animals when administered systemically at relatively low dosage levels. The more potent corticosteroids have been shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from topically applied corticosteroids. Therefore, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Drugs of this class should not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time.

Nursing Mothers

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids are secreted into breast milk, in quantities not likely to have a deleterious effect on the infant. Nevertheless, caution should be exercised when topical corticosteroids are administered to a nursing woman.

Pediatric Use

Pediatric patients may demonstrate greater susceptibility to topical corticosteroid-induced HPA axis suppression and Cushing's syndrome than mature patients because of a larger skin surface area to body weight ratio.

Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing's syndrome, and intracranial hypertension have been reported in children receiving topical corticosteroids.

Manifestations of adrenal suppression in children include linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema.

Administration of topical corticosteroids to children should be limited to the least amount compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may interfere with the growth and development of children.

ADVERSE REACTIONS

The following local adverse reactions are reported infrequently with topical corticosteroids but may occur more frequently with the use of occlusive dressings. These reactions are listed in an approximate decreasing order of occurrence: burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, miliaria.

OVERDOSAGE

Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. (See PRECAUTIONS.)

DOSAGE AND ADMINISTRATION

Hydrocortisone Butyrate Solution, 0.1% should be applied to the affected area as a thin film two or three times daily depending on the severity of the condition.

HOW SUPPLIED

Hydrocortisone Butyrate Solution, 0.1% is supplied in tubes containing:

60 mL          NDC 43478-273-61

STORAGE

Store at controlled temperature between 41° - 77°F (5° - 25°C).

Manufactured for Rouses Point Pharmaceuticals, LLC

Cranford, NJ 07016

By Ferndale Laboratories, Inc.

Ferndale, MI 48220

PRINCIPAL DISPLAY PANEL

NDC 43478-273-61

HYDROCORTISONE BUTYRATE  hydrocortisone butyrate  solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 43478-273 Route of Administration TOPICAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HYDROCORTISONE BUTYRATE (HYDROCORTISONE) HYDROCORTISONE BUTYRATE 1 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength ISOPROPYL ALCOHOL   ANHYDROUS CITRIC ACID   SODIUM CITRATE   GLYCERIN   POVIDONE   WATER

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 43478-273-61 1 BOTTLE In 1 CARTON contains a BOTTLE 1 60 mL In 1 BOTTLE This package is contained within the CARTON (43478-273-61)

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA019116	02/24/2010

Labeler - Rouses Point Pharm (849346924)

Registrant - Triax Pharmaceuticals, LLC (194481409)

Establishment
Name	Address	ID/FEI	Operations
Ferndale Laboratories, Inc.		005320536	MANUFACTURE, ANALYSIS

Establishment
Name	Address	ID/FEI	Operations
Pharmacia & Upjohn Co., Inc.		007702681	API MANUFACTURE

Revised: 03/2010Rouses Point Pharm

More Hydrocortisone Butyrate Solution resources

• Hydrocortisone Butyrate Solution Use in Pregnancy & Breastfeeding
• Hydrocortisone Butyrate Solution Drug Interactions
• Hydrocortisone Butyrate Solution Support Group
• 15 Reviews for Hydrocortisone Butyrate - Add your own review/rating

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• Anal Itching
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• Dermatitis
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• Gingivitis
• Hemorrhoids
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