Acticin

Generic Name: permethrin topical (per METH rin)

Brand Names: Elimite, Lice Bedding Spray, Nix Complete Lice Treatment System, Nix Cream Rinse, Nix Lice Control, RID Home Lice Control Spray for Surfaces

What is Acticin (permethrin topical)?

Permethrin is an anti-parasite medication.

Permethrin topical (for the skin) is used to treat head lice and scabies.

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

What is the most important information I should know about Acticin (permethrin topical)?

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

Do not take this medication by mouth. It is for use only on the skin, hair, fabrics, or other surfaces. Do not apply permethrin topical to open cuts or wounds. Do not use this medication if you are allergic to permethrin or to chrysanthemums. For the most complete treatment of lice or scabies and to prevent reinfection, you must treat your environment (clothing, bedding, pillows, furniture, hats, hair brushes and accessories, etc) at the same time you treat your body.

Avoid sexual or intimate contact with others until your lice or scabies infection has cleared up. Avoid sharing hair brushes, combs, hair accessories, hats, clothing, bed linens, and other articles of personal use. Lice and scabies infections are highly contagious.

What should I discuss with my healthcare provider before using Acticin (permethrin topical)?

Do not use this medication if you are allergic to permethrin or to chrysanthemums. FDA pregnancy category B. Permethrin topical is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Permethrin can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby. Do not use this medication on an infant younger than 2 months without the advice of a doctor.

How should I use Acticin (permethrin topical)?

Do not take this medication by mouth. It is for use only on the skin, hair, fabrics, or other surfaces.

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

You may need to shake the medication before each use. Follow the directions on the medicine label. Do not apply permethrin topical to open cuts or wounds.

To treat scabies:

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  Make sure your skin is clean and dry. Apply a thin layer of permethrin topical to all body parts from the neck down to the soles of the feet. Rub in completely. Leave the medication on for 8 to 14 hours, then wash it off completely.

  
  


• When using permethrin topical on an infant, also apply the medication to the scalp, temples, and forehead. Avoid applying close to the eyes, nose, mouth, or genitals.


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  If your condition does not clear up within 14 days after applying permethrin topical, use another application.

  
  

To treat head lice:

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  When using the shampoo, apply it to dry hair only. Cover all hair completely and leave the shampoo in for 10 minutes. Then work into a lather using warm water and rinse out thoroughly.

  
  


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  When using the cream rinse, wash your hair using shampoo only (no conditioner or 2-in-1 shampoo). Rinse thoroughly and towel dry the hair, leaving it damp. Apply enough of the cream rinse to completely saturate all hair. Leave the cream rinse in your hair for 10 minutes.

  
  


• Use a towel or washcloth to protect your eyes while the medication is left in your hair.


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  Use a second application if lice are still seen 7 days after your first treatment.

  
  


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  You may also use a nit comb to remove lice eggs from the hair. Your hair should be slightly damp while using a nit comb. Work on only one section of hair at a time, combing through 1- to 2-inch strands from the scalp to the ends.

  
  


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  Rinse the nit comb often during use. Place removed nits into a sealed plastic bag and throw it into the trash to prevent re-infestation.

  
  


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  Check the scalp again daily to make sure all nits have been removed.

  
  

To treat pubic lice (crabs):

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  Wash and dry the treatment area. Apply permethrin topical to all pubic hair and any surrounding hairs on the thighs and around the anus.

  
  


• 
  

  Avoid getting this medication inside the rectum or vagina.

  
  


• 
  

  Leave the medication in for 10 minutes. Then work into a lather using warm water and rinse out thoroughly.

  
  


• 
  

  You may also use a nit comb to remove lice eggs from pubic hair (hair should be slightly damp).

  
  


• 
  

  All sexual partners should also be treated to prevent re-infestation of crabs.

  
  

To prevent reinfection, wash all clothing, hats, bed clothes, bed linens, and towels in hot water and dry in high heat. Dry-clean any non-washable clothing. Hair brushes, combs, and hair accessories should be soaked in hot water for at least 10 minutes.

Use permethrin surface spray to disinfect non-washable items such as:

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  furniture;

  
  


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  mattresses and pillows;

  
  


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  stuffed toys;

  
  


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  hats, gloves, and scarves;

  
  


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  headphones or headbands;

  
  


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  the inside of a bike helmet; or

  
  


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  seats and carpets inside your car.

  
  

Stuffed toys or pillows that cannot be washed should be sealed in air-tight plastic bags for 4 weeks.

Vacuum all rugs and carpets and throw away the vacuum cleaner bag.

For the most complete treatment of lice or scabies, you must treat your environment (clothing, bedding, etc) at the same time you treat your body. Store permethrin topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Since permethrin topical is usually needed only once, you are not likely to be on a dosing schedule. Wait at least 7 days before using a second application.

What happens if I overdose?

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

Symptoms of a permethrin topical overdose are unknown.

What should I avoid while using Acticin (permethrin topical)?

Avoid getting this medication in your mouth or eyes. If it does get into any of these areas, rinse with water.

Do not use other medicated skin products unless your doctor has told you to.

Avoid sexual or intimate contact with others until your lice or scabies infection has cleared up. Avoid sharing hair brushes, combs, hair accessories, hats, clothing, bed linens, and other articles of personal use. Lice and scabies infections are highly contagious.

Acticin (permethrin topical) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have severe burning, stinging, redness, or swelling after applying permethrin topical.

Less serious side effects may include:

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  itching or mild skin rash;

  
  


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  mild burning, stinging, or redness; or

  
  


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  numbness or tingling where the medication was applied.

  
  

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

What other drugs will affect Acticin (permethrin topical)?

It is not likely that other drugs you take orally or inject will have an effect on topically applied permethrin. But many drugs can interact with each other. Tell your doctor about all your prescription and over-the-counter medications, vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start a new medication without telling your doctor.

More Acticin resources

• Acticin Side Effects (in more detail)
• Acticin Use in Pregnancy & Breastfeeding
• Acticin Support Group
• 0 Reviews for Acticin - Add your own review/rating

• Acticin Cream MedFacts Consumer Leaflet (Wolters Kluwer)


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


• Elimite Prescribing Information (FDA)

Compare Acticin with other medications

• Head Lice
• Lice
• Scabies

Where can I get more information?

• Your pharmacist has additional information about permethrin topical written for health professionals that you may read.

See also: Acticin side effects (in more detail)

Pierre Fabre Pharmaceuticals Inc

Address Pierre Fabre Pharmaceuticals Inc, 9 Campus drive NJ 07054 Contact Details Phone: (973) 898-1042 Website: http://www.pfpharmausa.com/

Lysodren 500 mg tablets

1. Name Of The Medicinal Product

Lysodren 500 mg tablets

2. Qualitative And Quantitative Composition

Each tablet contains 500 mg of mitotane.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Tablet.

White, biconvex, round, scored tablets.

4. Clinical Particulars

4.1 Therapeutic Indications

Symptomatic treatment of advanced (unresectable, metastatic or relapsed) adrenal cortical carcinoma.

The effect of Lysodren on non-functional adrenal cortical carcinoma is not established.

4.2 Posology And Method Of Administration

Treatment should be initiated and followed by a suitably experienced specialist.

Posology

Treatment in adults should be started with 2 - 3 g mitotane per day and increased progressively (e.g. at two

If it is urgent to control Cushing's symptoms in highly symptomatic patients, higher starting doses between 4 - 6 g daily could be necessary and daily dose increased more rapidly (e.g. every week). A starting dose higher than 6 g/day is generally not recommended.

Dose adjustments, monitoring and discontinuation

Dose adjustment is aimed to reach a therapeutic window (mitotane plasma levels between 14 and 20 mg/l) which ensures optimal use of Lysodren with acceptable safety. Indeed, neurologic toxicity has been associated with levels above 20 mg/l and therefore this threshold should not be reached. Weaker evidence has suggested that mitotane plasma levels above 14 mg/l may result in enhanced efficacy. Mitotane plasma levels higher than 20 mg/l may be associated with severe undesirable effects and offer no further benefit in terms of efficacy. Mitotane plasma levels should therefore be monitored in order to adjust the Lysodren dose and to avoid reaching toxic levels.

Dosing should be individually adjusted based on mitotane plasma levels monitoring and clinical tolerance until mitotane plasma levels reach the therapeutic window 14 – 20 mg/l. The target plasma concentration is usually reached within a period of 3 to 5 months.

Mitotane plasma levels should be assessed after each dose adjustment and at frequent (e.g. every two weeks) intervals, until the optimal maintenance dose is reached. Monitoring should be more frequent (e.g. every week) when a high starting dose has been used. It should be taken into account that dose adjustments do not produce immediate changes in plasma levels of mitotane (section 4.4). In addition, because of tissue accumulation, mitotane plasma levels should be monitored regularly (e.g. monthly) once the maintenance dose has been reached.

Regular monitoring (e.g. every two months) of mitotane plasma levels is also necessary after interruption of treatment. Treatment can be resumed when mitotane plasma levels will be ranged between 14

If serious adverse reactions occur, such as neurotoxicity, treatment with mitotane may need to be transiently interrupted. In case of mild toxicity, the dose should be reduced until the maximum tolerated dose is attained.

Treatment with Lysodren should be continued as long as clinical benefits are observed. If no clinical benefits are observed after 3 months at optimal dose, treatment should be permanently discontinued.

Special populations

Paediatric patients

The experience in children is limited.

The paediatric posology of mitotane has not been well characterised but appears equivalent to that of adults after correction for body surface.

Treatment should be initiated at 1.5 to 3.5 g/m²/day in children and adolescents with the objective of reaching 4 g/m²/day. Mitotane plasma levels should be monitored as for adults, with particular attention when plasma levels reach 10 mg/l as a quick increase in plasma levels may be observed. Dose may be reduced after 2 or 3 months according to the mitotane plasma levels or in case of serious toxicity.

Hepatic impairment

Since mitotane is mainly metabolised through the liver, mitotane plasma levels are expected to increase if liver function is impaired. There is no experience in the use of mitotane in patients with hepatic impairment, so data are insufficient to give a dose recommendation in this group. The use of mitotane in patients with severe hepatic impairment is not recommended. In patients with mild or moderate hepatic impairment, caution should be exercised and monitoring of liver biochemistry should be performed. Monitoring of mitotane plasma levels is specially recommended in these patients (see section 4.4).

Renal impairment

There is no experience in the use of mitotane in patients with renal impairment, so data are insufficient to give a dose recommendation in this group. The use of mitotane in patients with severe renal impairment is not recommended and, in cases of mild to moderate renal impairment, caution should be exercised. Monitoring of mitotane plasma levels is specially recommended in these patients (see section 4.4).

Elderly patients (

There is no experience on the use of mitotane in elderly patients, so data are insufficient to give a dose recommendation in this group. Caution should be exercised and frequent monitoring of mitotane plasma levels is highly recommended.

Method of administration

The total daily dose may be divided in two or three doses according to patient's convenience. Tablets should be taken with water during meals containing fat-rich food (see section 4.5). Patients should be advised not to use any tablets showing signs of deterioration, and caregivers to wear disposable gloves when handling the tablets.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients

Lactation (see section 4.6)

Concomitant use with spironolactone (see section 4.5)

4.4 Special Warnings And Precautions For Use

Before the initiation of the treatment: Large metastatic masses should be surgically removed as far as possible before starting mitotane treatment, in order to minimise the risk of infarction and haemorrhage in the tumour due to a rapid cytotoxic effect of mitotane.

Risk of adrenal insufficiency: All patients with non functional tumour and 75% of patients with functional tumour show signs of adrenal insufficiency. Therefore, steroid replacement may be necessary in these patients. Since mitotane increases plasma levels of steroid binding proteins, free cortisol and corticotropin (ACTH) determinations are necessary for optimal dosing of steroid substitution (see section 4.8).

Shock, severe trauma or infection: Mitotane should be temporarily discontinued immediately following shock, severe trauma or infection, since adrenal suppression is its prime action. Exogenous steroids should be administered in such circumstances, since the depressed adrenal gland may not immediately start to secrete steroids. Because of an increased risk of acute adrenocortical insufficiency, patients should be instructed to contact their physician immediately if injury, infection, or any other concomitant illness occurs. Patients should carry with them the Lysodren Patient Card provided with the package leaflet indicating that they are prone to adrenal insufficiency and that, in case of emergency care, adequate precautionary measures should be taken.

Monitoring of plasma levels: Mitotane plasma levels should be monitored in order to adjust the mitotane dose, particularly if high starting doses are considered necessary. Dose adjustments may be necessary to achieve the desired therapeutic levels in the window between 14 and 20 mg/l and avoid specific adverse reactions (see section 4.2).

Hepatic or renal impairment: There are insufficient data to support the use of mitotane in patients with severe hepatic or renal impairment. In patients with mild or moderate hepatic or renal impairment, caution should be exercised and monitoring of mitotane plasma levels is particularly recommended (see section 4.2).

Mitotane tissue accumulation: Fat tissue can act as a reservoir for mitotane, resulting in a prolonged half-life and potential accumulation of mitotane. Consequently, despite a constant dose, mitotane levels may increase. Therefore, monitoring of mitotane plasma levels (e.g. every two months) is also necessary after interruption of treatment, as prolonged release of mitotane can occur. Caution and close monitoring of mitotane plasma levels are highly recommended when treating overweight patients.

Central nervous system disorders: Long-term continuous administration of high doses of mitotane may lead to reversible brain damage and impairment of function. Behavioural and neurological assessments should be made at regular intervals, especially when mitotane plasma levels exceed 20 mg/l (see section 4.8).

Bleeding time: Prolonged bleeding time has been reported in patients treated with mitotane and this should be taken into account when surgery is considered (see section 4.8).

Warfarin and coumarin-like anticoagulants: Physicians should closely monitor patients for a change in anticoagulant dose requirements when administering mitotane to patients on coumarin-like anticoagulants (see section 4.5).

Substances metabolised through cytochrome P450: Mitotane is a hepatic enzyme inducer and it should be used with caution in case of concomitant use of medicinal products influenced by hepatic enzyme induction (see section 4.5).

Women of childbearing potential: Women of childbearing potential must use effective contraception during treatment with mitotane (see section 4.6).

Paediatric patients: In children and adolescents, neuro-psychological retardation can be observed during mitotane treatment. In such cases, thyroid function should be investigated in order to identify a possible thyroid impairment linked to mitotane treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Spironolactone: Mitotane must not be given in combination with spironolactone, since this active substance may block the action of mitotane (see section 4.3).

Warfarin and coumarin-like anticoagulants: Mitotane has been reported to accelerate the metabolism of warfarin through hepatic microsomal enzyme induction, leading to an increase in dose requirements for warfarin. Therefore, physicians should closely monitor patients for a change in anticoagulant dose requirements when administering mitotane to patients on coumarin

Substances metabolised through cytochrome P450: Mitotane has been shown to have an inductive effect on cytochrome P450 enzymes. Therefore, the plasma concentrations of the substances metabolised via cytochrome P450 may be modified. In the absence of information on the specific P450 isoenzymes involved, caution should be taken when co-prescribing active substances metabolised by this route such as, among others, anticonvulsants, rifabutin, rifampicin, griseofulvin and St. John's wort (Hypericum perforatum).

Medicinal products active on central nervous system: Mitotane can cause central nervous system undesirable effects at high concentrations (see section 4.8). Although no specific information on pharmacodynamic interactions in the central nervous system is available, this should be borne in mind when co-prescribing medicinal products with central nervous system depressant action.

Fat-rich food: Data with various mitotane formulations suggest that administration with fat-rich food enhances absorption of mitotane.

Hormone binding protein: Mitotane has been shown to increase plasma levels of hormone binding proteins (e.g. sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG)). This should be taken into account when interpreting the results of hormonal assays and may result in gynaecomastia.

4.6 Pregnancy And Lactation

Pregnancy

Data on a limited number of exposed pregnancies indicate abnormalities on the adrenals of the foetus after exposure to mitotane. Animal reproduction studies have not been conducted with mitotane. Animal studies with similar substances have shown reproductive toxicity (see section 5.3). Lysodren should be given to a pregnant woman only if clearly needed and if the clinical benefit clearly outweighs any potential risk to the foetus.

Women of childbearing potential must use effective contraception during treatment and after discontinuation of treatment as long as mitotane plasma levels are detectable. The prolonged elimination of mitotane from the body after discontinuation of Lysodren should be considered.

Lactation

Due to the lipophilic nature of mitotane, it is likely to be excreted in breast milk. Breast

4.7 Effects On Ability To Drive And Use Machines

Lysodren has a major influence on the ability to drive and use machines. Ambulatory patients should be warned not to drive or use machines.

4.8 Undesirable Effects

Safety data are based on literature (mainly retrospective studies). More than 80 % of patients treated with mitotane have shown at least one type of undesirable effect. Adverse reactions listed below are classified according to frequency and system organ class. Frequency groupings are defined according to the following convention: Very common (

Table 1: Frequency of adverse reactions identified from literature data

	Adverse reaction
System Organ Class	Very common	Common	Not Known
Investigations	Elevated liver enzymes Plasma cholesterol increased Plasma triglycerides increased		Blood uric acid decreased
Blood and lymphatic system disorders	Leucopoenia Bleeding time prolonged	Anaemia Thrombocytopenia
Nervous system disorders	Ataxia Paresthesia Vertigo Sleepiness	Mental impairment Polyneuropathy Movement disorder Dizziness Headache
Eye disorders			Maculopathy Retinal toxicity Diplopia Lens opacity Visual impairment Vision blurred
Gastrointestinal disorders	Mucositis Vomiting Diarrhoea Nausea Epigastric discomfort		Salivary hypersecretion
Renal and urinary disorders			Haemorrhagic cystitis Haematuria Proteinuria
Skin and subcutaneous tissue disorders	Skin rash
Muscoloskeletal and connective tissue disorders	Myasthenia
Endocrine disorders	Adrenal insufficiency		Thyroid impairment
Metabolism and nutrition disorders	Anorexia Hypercholesterolemia Hypertriglyceridaemia		Hypouricaemia
Infections and infestations			Opportunistic mycosis
Vascular disorders			Hypertension Orthostatic hypotension Flushing
General disorders and administration site conditions	Asthenia		Hyperpyrexia Generalised aching
Hepatobiliary disorders		Autoimmune hepatitis	Liver damage (hepatocellular/cholestatic/mixed)
Reproductive system and breast disorders	Gynaecomastia
Psychiatric disorders	Confusion

Gastrointestinal disorders are the most frequently reported (10 to 100 % of patients) and are reversible when the dose is reduced. Some of these effects (anorexia) may constitute the hallmark of initial central nervous system impairment.

Nervous system undesirable effects occur in approximately 40 % of patients. Other undesirable central nervous effects have been reported in literature such as memory defects, aggressiveness, central vestibular syndrome, dysarthria, or Parkinson syndrome. Serious undesirable effects appear linked to the cumulative exposure to mitotane and are most likely to occur when mitotane plasma levels are at 20 mg/l or above. At high doses and after prolonged utilization, brain function impairment can occur. Nervous system undesirable effects appear reversible after cessation of mitotane treatment and decrease in plasma levels (see section 4.4).

Skin rashes which have been reported in 5 to 25 % of patients do not seem to be dose related.

Leucopoenia has been reported in 8 to 12 % of patients. Prolonged bleeding time appears a frequent finding (90 %): although the exact mechanism of such an effect is unknown and its relation with mitotane or with the underlying disease is uncertain, it should be taken into account when surgery is considered.

The activity of liver enzymes (gamma-GT, aminotransferase, alkaline phosphatase) is commonly increased. Autoimmune hepatitis has been reported in 7 % of patients with no other information on mechanism. Liver enzymes levels normalize when the mitotane dose is decreased. A case of cholestatic hepatitis has been reported. Therefore, the possibility of mitotane-induced liver damage cannot be excluded.

Paediatric patients

Neuro-psychological retardation may be observed during mitotane treatment. In such cases, thyroid function should be investigated in order to identify a possible thyroid impairment linked to mitotane treatment. Hypothyroidism and growth retardation may be also observed.

4.9 Overdose

Mitotane overdose may lead to central nervous system impairment especially if mitotane plasma levels are above 20 mg/l. No proven antidotes have been established for mitotane overdose. The patient should be followed closely, taking into account that impairment is reversible, but given the long half

It is recommended to increase frequency of mitotane plasma level monitoring (e.g. every two weeks) in patients at risk of overdose (e.g. in case of renal or hepatic impairment, obese patients or patients with a recent weight loss).

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Other antineoplastic agents, ATC code: L01XX23

Mechanism of action

Mitotane is an adrenal cytotoxic active substance, although it can apparently also cause adrenal inhibition without cellular destruction. Its biochemical mechanism of action is unknown. Available data suggest that mitotane modifies the peripheral metabolism of steroids and that it also directly suppresses the adrenal cortex. The administration of mitotane alters the extra-adrenal metabolism of cortisol in humans, leading to a reduction in measurable 17-hydroxy corticosteroids, even though plasma levels of corticosteroids do not fall. Mitotane apparently causes increased formation of 6-beta-hydroxy cholesterol.

Clinical efficacy

Mitotane has not been studied in a comprehensive clinical development program. Available clinical information comes mainly from published data in patients with inoperable or metastatic adrenal carcinoma. In terms of overall survival, four studies conclude that mitotane treatment does not increase the survival rate whereas five find an increase in the survival rate. Among the latter, three studies find such an increase only in patients in whom mitotane plasma is above 14 mg/l. In terms of total or partial tumour and/or metastasis regression, eleven studies have shown some degree of improvement and sometimes occasional prolonged remissions. However, in several studies, the objective criteria for evaluating tumour response are missing or not reported. There are nevertheless some studies which provide accurate information on tumour regression or disappearance and demonstrate that the threshold of 14 mg/l appears necessary to induce an objective tumour regression. In addition, mitotane induces a state of adrenal insufficiency which leads to the disappearance of Cushing syndrome in patients with secreting adrenal carcinoma and necessitates substitution hormonotherapy.

Paediatric patients

Clinical information comes mainly from a prospective trial (n= 24 patients) in children and adolescents aged at diagnosis from 5 months to 16 years (median age: 4 years) who had an unresectable primary tumour or who presented a tumour recurrence or a metastasic disease; most of the children (75%) presented with endocrine symptoms. Mitotane was given alone or combined with chemotherapy with various agents. Overall, the disease-free interval was 7 months (2 to 16 months). There were recurrences in 40% of children; the survival rate at 5 years was 49%.

5.2 Pharmacokinetic Properties

Absorption

In a study performed in 8 patients with adrenal carcinoma treated with 2 to 3 g daily of mitotane, a highly significant correlation was found between plasma mitotane concentration and the total mitotane dose. The target plasma mitotane concentration (14 mg/l) was reached in all patients within 3 to 5 months and the total mitotane dose ranged between 283 and 387 g (median value: 363 g). The threshold of 20 mg/l was reached for cumulative amounts of mitotane of approximately 500 g. In another study, 3 patients with adrenal carcinoma received Lysodren according to a precise protocol allowing fast introduction of a high dose if the product was well tolerated: 3 g (as 3 intakes) on day 1, 4.5 g on day 2, 6 g on day 3, 7.5 g on day 4 and 9 g on day 5. This dose of Lysodren was continued or decreased in function of side effects and plasma mitotane levels. There was a positive linear correlation between the cumulative dose of Lysodren and the plasma levels of mitotane. In two of the 3 patients, plasma levels of more than 14 mg/l were achieved within 15 days and in one of them levels above 20 mg/l were achieved within approximately 30 days. In addition, in both studies, in some patients, the plasma mitotane levels continued to rise despite maintenance or a decrease of the daily dose of mitotane.

Distribution

Autopsy data from patients show that mitotane is found in most tissues of the body, with fat as the primary site of storage.

Metabolism

Metabolism studies in man have identified the corresponding acid, 1,1-(o,p'-dichlorodiphenyl) acetic acid (o,p'-DDA), as the major circulating metabolite, together with smaller quantities of the 1,1-(o,p'-dichlorodiphenyl)-2,2 dichloroethene (o,p'-DDE) analogue of mitotane. No unchanged mitotane has been found in bile or in urine, where o,p'-DDA predominates, together with several of its hydroxylated metabolites. For induction with cytochrome P450, see section 4.5.

Excretion

After intravenous administration, 25% of the dose was excreted as metabolites within 24 hours. Following discontinuation of mitotane treatment, it is slowly released from storage sites in fat, leading to reported terminal plasma half-lives ranging from 18 to 159 days.

5.3 Preclinical Safety Data

Non-clinical data on the general toxicity of mitotane is limited.

Reproductive toxicity studies have not been performed with mitotane. However, dichlorodiphenyltrichlorethane (DDT) and other polychlorinated biphenyl analogues are known to have deleterious effects on fertility, pregnancy and development, and mitotane could be expected to share these properties.

The genotoxic and carcinogenic potential of mitotane has not been investigated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Maize starch

Microcrystalline cellulose (E 460)

Macrogol 3350

Silica colloidal anhydrous

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years.

After opening: 1 year.

6.4 Special Precautions For Storage

Store in the original container.

6.5 Nature And Contents Of Container

Square opaque white HDPE bottle containing 100 tablets.

Pack size of 1 bottle.

6.6 Special Precautions For Disposal And Other Handling

This medicinal product should not be handled by persons other than the patient and his/her caregivers, and especially not by pregnant women. Caregivers should wear disposable gloves when handling the tablets.

Any unused product or waste material should be disposed of in accordance with local requirements for cytotoxic medicinal products.

7. Marketing Authorisation Holder

Laboratoire HRA Pharma

15 rue Béranger

75003 Paris

France

8. Marketing Authorisation Number(S)

EU/1/04/273/001

9. Date Of First Authorisation/Renewal Of The Authorisation

Date of first autorisation : 28/04/2004

Date of last renewal : 28/04/2009

10. Date Of Revision Of The Text

Detailed information on this medicinal product is available on the website of the European Medicines Agency (EMEA) http://www.emea.europa.eu/

Antepsin Suspension

1. Name Of The Medicinal Product

Antepsin 1g/5ml Oral Suspension

2. Qualitative And Quantitative Composition

Each 5 mL dose contains 1 gram sucralfate.

For excipients, see section 6.1

3. Pharmaceutical Form

Oral Suspension

White to off-white viscous suspension with an odour of aniseed/caramel.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of duodenal ulcer, gastric ulcer, chronic gastritis, and the prophylaxis of gastrointestinal haemorrhage from stress ulceration in seriously ill patients.

4.2 Posology And Method Of Administration

For oral administration.

Duodenal ulcer, gastric ulcer, chronic gastritis:

Adults: The usual dose is 2 grams twice daily to be taken on rising and at bedtime, or 1 gram 4 times a day to be taken 1 hour before meals and at bedtime. Maximum daily dose: 8 grams.

Four to six weeks' treatment is usually needed for ulcer healing, but up to twelve weeks may be necessary in resistant cases.

Antacids may be used as required for relief of pain, but should not be taken half an hour before or after Antepsin.

Children and Elderly: see below

Prophylaxis of gastrointestinal haemorrhage from stress ulceration:

Adults: The usual dose is 1 gram six times a day. A maximum dose of 8 grams daily should not be exceeded. Antacids may be used as required for relief of pain, but should not be taken half an hour before or after Antepsin.

Elderly: There are no special dosage requirements for elderly patients but as with all medicines, the lowest effective dose should be used.

Children: Safety and effectiveness in children has not been established.

4.3 Contraindications

Contraindicated in individuals who are hypersensitive to any of the ingredients of Antepsin.

4.4 Special Warnings And Precautions For Use

The product should only be used with caution in patients with renal dysfunction, due to the possibility of increased aluminium absorption.

In patients with severe renal impairment or on dialysis, Antepsin should be used with extreme caution and only for short-term treatment. The concomitant use of other aluminium containing medications is not recommended in view of the enhanced potential for aluminium absorption and toxicity. Antepsin may also cause allergic reactions (possibly delayed).

Bezoars (an insoluble mass formed with the gastric lumen) have been reported occasionally in patients taking Antepsin Suspension. The majority of these patients had underlying conditions that may predispose to bezoar formation such as delayed gastric emptying, or were receiving concomitant enteral feeding (see under Interactions). Bezoars have been reported after administration of Antepsin Suspension to severely ill patients in ITU, especially in premature infants in whom the use of sucralfate is not recommended.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant administration of Antepsin may reduce the bioavailability of certain drugs including tetracycline, ciprofloxacin, norfloxacin, ketoconazole, digoxin, warfarin, phenytoin, theophylline, thyroxine, quinidine and H₂ antagonists. The bioavailability of these agents may be restored by separating the administration of these agents from Antepsin by two hours. This interaction appears to be non systemic in origin presumably resulting from these agents being bound by Antepsin in the gastrointestinal tract. Because of the potential of Antepsin to alter the absorption of some drugs from the gastrointestinal tract, the separate administration of Antepsin from that of other agents should be considered when alterations in bioavailability are felt to be critical for concomitantly administered drugs.

The administration of Antepsin Suspension and enteral feeds by nasogastric tube should be separated by one hour in patients receiving Antepsin Suspension for the prophylaxis of stress ulceration. In rare cases bezoar formation has been reported when Antepsin and enteral feeds have been given too closely together.

4.6 Pregnancy And Lactation

Pregnancy:

Teratogenicity studies in mice, rats and rabbits at doses up to 50 times the human dose have revealed no evidence of harm to the foetus. Safety in pregnant women has not been established and Antepsin should be used during pregnancy only if clearly needed.

Lactation:

It is not known whether this drug is excreted in human milk. Caution should be exercised when Antepsin is administered to breast-feeding women.

4.7 Effects On Ability To Drive And Use Machines

Do not drive if you feel dizzy or drowsy.

4.8 Undesirable Effects

Adverse reactions to Antepsin in clinical trials were minor and only rarely led to discontinuation of the drug. Adverse events seen during use of Antepsin have included constipation, diarrhoea, nausea, vomiting, gastric discomfort, indigestion, flatulence, dry mouth, rash, back pain, dizziness, headache, vertigo, drowsiness and hypersensitivity reactions including pruritus, oedema, urticaria and shortness of breath.

4.9 Overdose

There is no experience in humans with overdose. Acute oral toxicity studies in animals, however, using doses up to 12 g/kg body weight, could not find a lethal dose. Risks associated with overdose, should, therefore, be minimal.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Alimentary tract and metabolism, ATC code: A02B X02

The action of Antepsin is non-systemic as the drug is only minimally absorbed from the gastro-intestinal tract. The small amounts that are absorbed are excreted primarily in the urine. Antepsin exerts a generalised cytoprotective effect by preventing gastro-intestinal mucosal injury.

Studies in humans and animal models show that Antepsin forms an ulcer adherent complex with the proteinaceous exudate of the ulcer site. This property enables Antepsin to form a protective barrier over the ulcer lesion giving sustained protection against the penetration and action of gastric acid, pepsin and bile.

Studies both in humans and animals demonstrate that Antepsin protects the gastric mucosa against various irritants such as alcohol, acetylsalicyclic acid and sodium taurocholate.

Antepsin also directly inhibits pepsin activity and absorbs bile salts. It has only weak antacid activity. It does not alter gastric emptying time, nor normal digestive function. Antepsin has no demonstrated pharmacological effect on the cardiovascular or central nervous systems.

5.2 Pharmacokinetic Properties

Sucralfate is only minimally absorbed from the gastro-intestinal tract. The small amounts that are absorbed are excreted primarily in the urine. Absorption of aluminium from sucralfate may be increased in patients on dialysis or with renal dysfunction (see also “other special warnings and precautions”).

5.3 Preclinical Safety Data

There was no evidence of carcinogenesis in mice and rats receiving oral sucralfate in dosages of up to 1 g/kg daily (12 times the usual human dosage) for 2 years. In animal studies there was no effect evidence of impaired fertility. The effect of sucralfate on human fertility is not known.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Saccharin sodium

Sodium dihydrogen phosphate dihydrate Ph.Eur.

Purified water

Glycerol

Sodium propyl hydroxybenzoate (E217)

Sodium methyl hydroxybenzoate (E219)

Xanthan gum

Aniseed flavour

Caramel flavour

6.2 Incompatibilities

Not applicable

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Store below 25^oC.

6.5 Nature And Contents Of Container

Glass bottle (pack size 250 mL)

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Chugai Pharma UK Ltd.

Mulliner House

Flanders Road

Turnham Green

London

W4 1NN

UK

8. Marketing Authorisation Number(S)

PL 12185/0010

9. Date Of First Authorisation/Renewal Of The Authorisation

29/09/2005

10. Date Of Revision Of The Text

5 November 2007

tramadol

TRAM-a-dol

Commonly used brand name(s)

In the U.S.

• ConZip


• FusePaq Synapryn


• Rybix ODT


• Ryzolt


• Ultram


• Ultram ER

Available Dosage Forms:

• Capsule, Extended Release


• Tablet, Extended Release


• Tablet, Disintegrating


• Tablet


• Suspension

Therapeutic Class: Analgesic

Chemical Class: Opioid

Uses For tramadol

Tramadol is used to relieve moderate to moderately severe pain, including pain after surgery. The extended-release or long-acting tablets are used for chronic ongoing pain.

Tramadol belongs to the group of medicines called opioid analgesics. It acts in the central nervous system (CNS) to relieve pain. When tramadol is used for a long time, it may become habit-forming (causing mental or physical dependence). Physical dependence may lead to side effects when you stop taking the medicine.

tramadol is available only with your doctor's prescription.

Before Using tramadol

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 tramadol, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to tramadol 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 Rybix™ ODT, Ryzolt™, and Ultram® tablets in children younger than 16 years of age. Safety and efficacy have not been established.

Appropriate studies have not been performed on the relationship of age to the effects of Ultram® ER extended-release tablets 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 tramadol in the elderly. However, elderly patients are more likely to have unwanted side effects (e.g., constipation; lightheadedness, dizziness, or fainting; stomach upset; weakness) and age-related liver, kidney, or heart problems, which may require caution and an adjustment in the dose for patients receiving tramadol.

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 tramadol, 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 tramadol 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.

• Rasagiline


• Selegiline

Using tramadol 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


• Amitriptyline


• Amoxapine


• Bromperidol


• Carbamazepine


• Chlorpromazine


• Chlorprothixene


• Citalopram


• Clobazam


• Clomipramine


• Clorgyline


• Clovoxamine


• Clozapine


• Cyclobenzaprine


• Desipramine


• Desvenlafaxine


• Dothiepin


• Doxepin


• Duloxetine


• Escitalopram


• Ethopropazine


• Femoxetine


• Fluoxetine


• Flupenthixol


• Fluphenazine


• Fluvoxamine


• Haloperidol


• Imipramine


• Isocarboxazid


• Ketamine


• Linezolid


• Lofepramine


• Loxapine


• Melperone


• Mesoridazine


• Methotrimeprazine


• Milnacipran


• Mirtazapine


• Moclobemide


• Molindone


• Nortriptyline


• Olanzapine


• Paroxetine


• Penfluridol


• Perphenazine


• Phenelzine


• Pimozide


• Pipotiazine


• Prochlorperazine


• Promazine


• Promethazine


• Propiomazine


• Protriptyline


• Remoxipride


• Risperidone


• Sertraline


• Sulpiride


• Tapentadol


• Thiethylperazine


• Thioridazine


• Thiothixene


• Tranylcypromine


• Trifluoperazine


• Triflupromazine


• Trimeprazine


• Trimipramine


• Venlafaxine


• Vilazodone


• Zuclopenthixol

Using tramadol 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.

• Digoxin


• Quinidine


• Warfarin

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 tramadol 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 tramadol, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

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

• Alcohol abuse, history of or


• CNS depression or


• Depression, history of or


• Drug abuse, history of or


• Head injury or


• Hormonal problems or


• Increased pressure in the head or


• Infections of the central nervous system (CNS) or


• Mental illness, history of or


• Phenylketone allergy, history of or


• Respiratory depression (hypoventilation or slow breathing) or


• Seizures or epilepsy, history of or


• Stomach problems, severe—Use with caution. The chance of serious side effects may be increased.

• Breathing or lung problems (e.g., asthma, hypercapnia), severe—Should not be used in patients with this condition.

• Kidney disease or


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

• Phenylketonuria (PKU)—The orally disintegrating tablet contains phenylalanine, which can make this condition worse.

Proper Use of tramadol

Take tramadol 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.

If you think that tramadol is not working as well after you have been taking it for a few weeks, do not increase the dose. Instead, check with your doctor.

If you are using the disintegrating tablet, make sure your hands are dry before you handle the tablet. Do not open the blister pack that contains the tablet until you are ready to take it. Remove the tablet from the blister pack by peeling back the foil, then taking the tablet out. Do not push the tablet through the foil. Do not break, crush, or chew it. Place the tablet in your mouth. It should melt quickly. After the tablet has melted, swallow or take a sip of water.

Swallow the extended-release tablets whole with liquids. Do not break, crush, or chew it.

Dosing

The dose of tramadol 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 tramadol. 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 chronic pain:
  
  • For oral dosage form (extended-release tablets):
    
    • Adults—At first, 100 milligrams (mg) once a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 300 mg per day.
    
    
    • Children—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (tablets):
    
    • Adults and teenagers 16 years of age and older—At first, 50 to 100 milligrams (mg) every four to six hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
    
    
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
    
    
  
  

• For moderate to severe pain:
  
  • For oral dosage form (disintegrating tablets):
    
    • Adults and teenagers 16 years of age and older—At first, 50 to 100 milligrams (mg) every four to six hours as needed. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
    
    
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
    
    
  
  
  • For oral dosage form (tablets):
    
    • Adults and teenagers 16 years of age and older—At first, 25 milligrams (mg) per day, taken every morning. Your doctor may increase your dose as needed. However, the dose is usually not more than 400 mg per day.
    
    
    • Children younger than 16 years of age—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of tramadol, 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.

Precautions While Using tramadol

It is very important that your doctor check your progress at regular visits to make sure the medicine is working properly and to check for any unwanted effects.

tramadol will add to the effects of alcohol and other CNS depressants (medicine that makes you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Do not drink alcoholic beverages, and check with your doctor or dentist before taking any of these medicines while you are using tramadol.

Make sure your doctor knows about all the other medicines you are using. tramadol may increase your risk for seizures. (convulsions) and may cause a serious condition called serotonin syndrome.

tramadol can increase thoughts of suicide. Tell your doctor right away if you start to feel more depressed or have thoughts about hurting yourself. Report any unusual thoughts or behaviors that trouble you, especially if they are new or get worse quickly. Make sure your caregiver knows if you have trouble sleeping, get upset easily, have a big increase in energy, or start to act reckless. Tell your doctor if you have any sudden or strong feelings, such as feeling nervous, angry, restless, violent, or scared. Let your doctor know if you or anyone in your family has bipolar disorder (manic-depressive disorder) or has tried to commit suicide.

tramadol may cause serious allergic reactions, including anaphylaxis. Anaphylaxis can be life-threatening and requires immediate medical attention. Call your doctor right away if you have a rash; itching; hoarseness; trouble breathing; trouble swallowing; swelling of your hands, face, or mouth; or chest pain while you are using tramadol.

tramadol may cause some people to become drowsy, dizzy, lightheaded, or less alert than they are normally. Make sure you know how you react to tramadol before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

Make sure your doctor knows if you are pregnant, may be pregnant, or planning to become pregnant.

Dizziness, lightheadedness, or fainting may occur, especially when you get up suddenly from a lying or sitting position. Getting up slowly may help lessen this problem.

Nausea or vomiting may occur, especially after the first couple of doses. This effect may go away if you lie down for awhile. However, if nausea or vomiting continues, check with your doctor. Lying down for a while may also help relieve some other side effects, such as dizziness or lightheadedness that may occur.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the doctor or dentist in charge that you are taking tramadol. Taking tramadol together with medicines that are used during surgery or dental or emergency treatments may cause increased side effects.

If you think you or someone else may have taken an overdose of tramadol, get emergency help at once. Signs of an overdose include convulsions (seizures); difficult or troubled breathing; irregular, fast or slow, or shallow breathing; pale or blue lips, fingernails, or skin; pinpoint pupils of the eyes, or shortness of breath.

Do not stop suddenly taking tramadol without first 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 a possible worsening of your condition and reduce the possibility of withdrawal symptoms such as anxiety, diarrhea, headache, nausea, shivering, sweating, tremors, or trouble with sleeping.

tramadol 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:

Less common or rare

• Abdominal or stomach fullness


• abnormal or decreased touch sensation


• blisters under the skin


• bloating


• blood in the urine


• blood pressure increased


• blurred vision


• change in walking and balance


• chest pain or discomfort


• chills


• convulsions (seizures)


• darkened urine


• difficult urination


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


• fainting


• fast heartbeat


• frequent urge to urinate


• gaseous abdominal or stomach pain


• heart rate increased


• indigestion


• irregular heartbeat


• loss of memory


• numbness and tingling of the face, fingers, or toes


• numbness, tingling, pain, or weakness in the hands or feet


• pain in the arms, legs, or lower back, especially pain in the calves or heels upon exertion


• pain or discomfort in the arms, jaw, back, or neck


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


• pale bluish-colored or cold hands or feet


• recurrent fever


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


• severe cramping


• severe nausea


• severe redness, swelling, and itching of the skin


• shortness of breath


• sweats


• trembling and shaking of the hands or feet


• trouble performing routine tasks


• weak or absent pulses in the legs


• yellow eyes or skin

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

Symptoms of overdose

• Change in consciousness


• decreased awareness or responsiveness


• difficulty with breathing


• lack of muscle tone


• lightheadedness


• loss of consciousness


• pinpointed pupils of the eyes


• severe sleepiness


• shortness of breath


• slow or irregular heartbeat


• unusual tiredness

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

• Abdominal or stomach pain


• agitation


• anxiety


• constipation


• cough


• diarrhea


• discouragement


• drowsiness


• dry mouth


• feeling of warmth


• feeling sad or empty


• feeling unusually cold


• fever


• general feeling of discomfort or illness


• headache


• heartburn


• irritability


• itching of the skin


• joint pain


• loss of appetite


• loss of interest or pleasure


• loss of strength or weakness


• muscle aches and pains


• nausea


• nervousness


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


• restlessness


• runny nose


• shivering


• skin rash


• sleepiness or unusual drowsiness


• sore throat


• stuffy nose


• sweating


• tiredness


• trouble concentrating


• unusual feeling of excitement


• weakness

Less common or rare

• Abnormal dreams


• appetite decreased


• back pain


• bladder pain


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


• bloody or cloudy urine


• body aches or pain


• change in hearing


• clamminess


• cold flu-like symptoms


• confusion


• cough producing mucus


• cracked, dry, or scaly skin


• decreased interest in sexual intercourse


• difficult, burning, or painful urination


• difficulty with moving


• disturbance in attention


• ear congestion


• ear drainage


• earache or pain in ear


• excessive gas


• fall


• false or unusual sense of well-being


• feeling hot


• feeling jittery


• flushing or redness of the skin


• general feeling of bodily discomfort


• goosebumps


• headache, severe and throbbing


• hoarseness


• hot flashes


• inability to have or keep an erection


• itching, pain, redness, swelling, tenderness, or warmth on the skin


• joint sprain


• joint stiffness


• joint swelling


• loss in sexual ability, desire, drive, or performance


• loss of voice


• lower back or side pain


• muscle aching or cramping


• muscle injury


• muscle pain or stiffness


• muscle spasms or twitching


• nasal congestion


• neck pain


• night sweats


• pain


• pain in the limbs


• pain or tenderness around the eyes and cheekbones


• pain, swelling, or redness in the joints


• skin discoloration


• swelling


• swelling of the hands, ankles, feet, or lower legs


• tightness of the chest


• trouble in holding or releasing urine


• trouble with sleeping


• troubled breathing


• weight increased or decreased

After you stop using tramadol, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Gooseflesh


• high blood pressure


• increased sweating


• increased yawning


• shivering or trembling


• unusually large pupils

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: tramadol side effects (in more detail)

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More tramadol resources

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

• ConZip Prescribing Information (FDA)


• ConZip Extended-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Rybix ODT Prescribing Information (FDA)


• Rybix ODT Orally Disintegrating Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Ryzolt Prescribing Information (FDA)


• Ryzolt Consumer Overview


• Ryzolt Extended-Release Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Tramadol MedFacts Consumer Leaflet (Wolters Kluwer)


• Tramadol Hydrochloride Monograph (AHFS DI)


• Ultram Prescribing Information (FDA)


• Ultram Consumer Overview


• Ultram ER Prescribing Information (FDA)

Compare tramadol with other medications

• Anxiety
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• Syringomyelia
• Vulvodynia

Azulfidine EN-tabs

Generic Name: sulfasalazine (SUL fa SAL a zeen)

Brand Names: Azulfidine, Azulfidine EN-tabs, Sulfazine

What is sulfasalazine oral?

Sulfasalazine affects a substance in the body that causes inflammation, tissue damage, and diarrhea.

Sulfasalazine is used to treat moderate to severe ulcerative colitis. It is also used to treat rheumatoid arthritis in children and adults who have received other arthritis medications without successful treatment of symptoms.

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

What is the most important information I should know about sulfasalazine oral?

You should not use this medication if you have porphyria, a blockage in your bladder or intestines, or if you are allergic to sulfasalazine, sulfa drugs, aspirin, or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others).

Before using sulfasalazine, tell your doctor if you have asthma, kidney or liver disease, or glucose-6-phosphate dehydrogenase (G6PD) deficiency.

Also tell your doctor about all other medications you use, especially digoxin (digitalis, Lanoxin), folic acid (Folicin, FA-8), or vitamin or mineral supplements that contain folic acid.

Do not crush, break, or chew a sulfasalazine tablet. Swallow the pill whole. The enteric-coated tablet has a special coating to protect your stomach. Breaking the pill could damage this coating. For best results, keep using the medication as directed. Sulfasalazine will not cure ulcerative colitis, but it can reduce the number of attacks you have. If you are treating arthritis, do not stop using any of your other arthritis medications until your doctor tells you to.

What should I discuss with my healthcare provider before taking sulfasalazine oral?

You should not use this medication if you are allergic to sulfasalazine, or if you have:

• 
  

  a blockage in your bladder or intestines;

  
  


• 
  

  porphyria (a genetic enzyme disorder that causes symptoms affecting the skin or nervous system);

  
  


• 
  

  if you are allergic to sulfa drugs (such as Bactrim, Septra, Cotrim, and others); or

  
  


• 
  

  if you are allergic to aspirin or other salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others).

  
  

Before using sulfasalazine, tell your doctor if you are allergic to any drugs, or if you have:

• 
  

  asthma;

  
  


• 
  

  glucose-6-phosphate dehydrogenase (G6PD) deficiency;

  
  


• 
  

  kidney disease; or

  
  


• 
  

  liver disease.

  
  

If you have any of these conditions, you may need a dose adjustment or special tests to safely take sulfasalazine.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Sulfasalazine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take sulfasalazine oral?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Take this medication after a meal. Do not crush, break, or chew a sulfasalazine tablet. Swallow the pill whole. The enteric-coated tablet has a special coating to protect your stomach. Breaking the pill could damage this coating. For best results, keep using the medication as directed. Sulfasalazine will not cure ulcerative colitis, but it can reduce the number of attacks you have. If you are treating arthritis, do not stop using any of your other arthritis medications until your doctor tells you to. Your symptoms may not improve right away when you start taking sulfasalazine, and you may still need your other medications for awhile.

To be sure this medication is not causing harmful effects, your liver and kidney function may need to be checked with blood and urine tests on a regular basis. Do not miss any scheduled appointments.

Store sulfasalazine at room temperature away from moisture and heat.

What happens if I miss a dose?

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

What happens if I overdose?

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

Overdose symptoms may include nausea, vomiting, stomach pain, drowsiness, or seizure (convulsions).

What should I avoid while taking sulfasalazine oral?

Follow your doctor's instructions about any restrictions on food, beverages, or activity while you are using sulfasalazine.

Sulfasalazine oral side effects

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

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  fever, sore throat, or other flu symptoms;

  
  


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  pale skin, easy bruising;

  
  


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  dark urine, jaundice (yellowing of the skin or eyes);

  
  


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  pain or burning when you urinate;

  
  


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  urinating less than usual or not at all;

  
  


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  the appearance of a whole tablet in your stool; or

  
  


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  fever, sore throat, and headache with a severe blistering, peeling, and red skin rash.

  
  

Less serious side effects may include:

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  mild nausea, vomiting, diarrhea, upset stomach;

  
  


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  loss of appetite;

  
  


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  headache, ringing in your ears;

  
  


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  dizziness, spinning sensation;

  
  


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  white patches or sores inside your mouth or on your lips;

  
  


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  sleep problems (insomnia); or

  
  


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  mild itching or skin rash.

  
  

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect sulfasalazine oral?

Before taking sulfasalazine, tell your doctor if you are using any of the following drugs:

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  digoxin (digitalis, Lanoxin);

  
  


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  folic acid (Folicin, FA-8); or

  
  


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  vitamin or mineral supplements that contain folic acid.

  
  

This list is not complete and there may be other drugs that can interact with sulfasalazine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

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• sulfasalazine Oral, Rectal Advanced Consumer (Micromedex) - Includes Dosage Information

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Where can I get more information?

• Your pharmacist can provide more information about sulfasalazine.

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