Thursday, 29 September 2016

Canesten 100mg Pessary





1. Name Of The Medicinal Product



Canesten 100mg Pessary.


2. Qualitative And Quantitative Composition



Clotrimazole 100mg.



For excipients, see 6.1



3. Pharmaceutical Form



Pessary



4. Clinical Particulars



4.1 Therapeutic Indications



Canesten 100mg Pessaries are recommended for the treatment of candidal vaginitis.



4.2 Posology And Method Of Administration



The pessaries should be inserted into the vagina, as high as possible, using the applicator provided. This is best achieved when lying back with legs bent up.



Adults:



Two pessaries should be inserted daily (preferably at night) for three consecutive days. Alternatively, one pessary may be inserted daily for six days, preferably at night. A second treatment may be carried out if necessary.



There is no separate dosage schedule for the elderly.



Canesten pessaries need moisture in the vagina in order to dissolve completely, otherwise undissolved pieces of the pessary might crumble out of the vagina. Pieces of undissolved pessary may be noticed by women who experience vaginal dryness. To help prevent this it is important that the pessary is inserted as high as possible into the vagina at bedtime.



Generally:



treatment during the menstrual period should not be performed due to the risk of the pessary being washed out by the menstrual flow. The treatment should be finished before the onset of menstruation.



Do not use tampons, intravaginal douches, spermicides or other vaginal products while using this product.



Children:



Not for use in children under 16.



4.3 Contraindications



Hypersensitivity to clotrimazole or any other ingredient in this medicine.



4.4 Special Warnings And Precautions For Use



Medical advice should be sought if this is the first time the patient has experienced symptoms of candidal vaginitis.



Before using Canesten 100mg Pessaries, medical advice must be sought if any of the following are applicable:



- more than two infections of candidal vaginitis in the last six months.



- previous history of a sexually transmitted disease or exposure to partner with sexually transmitted disease.



- pregnancy or suspected pregnancy.



- aged under 16 or over 60 years.



- known hypersensitivity to imidazoles or other vaginal antifungal products.



Canesten 100mg Pessaries should not be used if the patient has any of the following symptoms whereupon medical advice should be sought:



- irregular vaginal bleeding.



- abnormal vaginal bleeding or a blood-stained discharge.



- vulval or vaginal ulcers, blisters or sores.



- lower abdominal pain or dysuria.



- any adverse events such as redness, irritation or swelling associated with the treatment.



- fever or chills.



- nausea or vomiting.



- diarrhoea.



- foul smelling vaginal discharge.



Patients should be advised to consult their physician if the symptoms have not been relieved within one week of using Canesten 100mg Pessaries. The pessaries can be used again if the candidal infection returns after 7 days. However, if the candidal infection recurs more than twice within six months, patients should be advised to consult their physician.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



Laboratory tests have suggested that, when used together, this product may cause damage to latex contraceptives. Consequently the effectiveness of such contraceptives may be reduced. Patients should be advised to use alternative precautions for at least five days after using this product.



Concomitant medication with vaginal clotrimazole and oral tacrolimus (FK-506; immunosuppressant) might lead to increased tacrolimus plasma levels. Patients should thus be closely monitored for signs and symptoms of tacrolimus overdosage, if necessary by determination of the respective plasma levels.



4.6 Pregnancy And Lactation



Data on a large number of exposed pregnancies indicate no adverse effects of Clotrimazole on pregnancy or on the health of the foetus/newborn child. To date, no relevant epidemiological data are available.



Clotrimazole can be used during pregnancy, but only under the supervision of a physician or midwife.



During pregnancy the pessary should be inserted without using an applicator.



4.7 Effects On Ability To Drive And Use Machines



Not applicable.



4.8 Undesirable Effects



As the listed undesirable effects are based on spontaneous reports, assigning accurate frequency of occurrence for each is not possible.



Immune system disorders:



allergic reaction (syncope, hypotension, dyspnea, urticaria, pruritus)



Reproductive system and breast disorders:



genital peeling, pruritus, rash, oedema, discomfort, burning, irritation, pelvic pain



Gastrointestinal disorders:



abdominal pain



4.9 Overdose



In the event of accidental oral ingestion, routine measures such as gastric lavage should be performed only if clinical symptoms of overdose become apparent (e.g. dizziness, nausea or vomiting). It should be carried out only if the airway can be protected adequately.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



ATC Code: G01A F02



Clotrimazole is an imidazole derivative with a broad spectrum of antimycotic activity.



Mechanism of Action



Clotrimazole acts against fungi by inhibiting ergosterol synthesis. Inhibition of ergosterol synthesis leads to structural and functional impairment of the cytoplasmic membrane.



Pharmacodynamic Effects



Clotrimazole has a broad antimycotic spectrum of action in vitro and in vivo, which includes dermatophytes, yeasts, moulds, etc.



The mode of action of clotrimazole is fungistatic or fungicidal depending on the concentration of clotrimazole at the site of infection. In-vitro activity is limited to proliferating fungal elements; fungal spores are only slightly sensitive.



Primarily resistant variants of sensitive fungal species are very rare; the development of secondary resistance by sensitive fungi has so far only been observed in very isolated cases under therapeutic conditions.



5.2 Pharmacokinetic Properties



Pharmacokinetic investigations after vaginal application have shown that only a small amount of clotrimazole (3 – 10% of the dose) is absorbed. Due to the rapid hepatic metabolism of absorbed clotrimazole into pharmacologically inactive metabolites the resulting peak plasma concentrations of clotrimazole after vaginal application of a 500mg dose were less than 10 ng/ml, reflecting that clotrimazole applied intravaginally does not lead to measurable systemic effects or side effects.



5.3 Preclinical Safety Data



There are no pre-clinical data of relevance to the prescriber which are additional to the information included in other sections of the SPC.



6. Pharmaceutical Particulars



6.1 List Of Excipients



Calcium lactate pentahydrate



Maize starch



Crospovidone



Silica, colloidal anhydrous



Lactic acid



Lactose Monohydrate



Magnesium Stearate



Hypromellose



Cellulose, microcrystalline



6.2 Incompatibilities



Not applicable.



6.3 Shelf Life



48 months.



6.4 Special Precautions For Storage



No special precautions for storage



6.5 Nature And Contents Of Container



Six pessaries are packed in a blister pack (foil 25µm PA + 45µm Al soft + 60µm PVC) sealed with aluminium backing foil (foil 20µm Al hard + 7g/m2 HSL sealable to PVC/PVDC). An applicator is also provided.



The pessaries and applicator are enclosed in a cardboard carton.



6.6 Special Precautions For Disposal And Other Handling






1. Pull out plunger A until it stops.



Place pessary into the applicator.



2. Insert applicator containing the pessary carefully as deeply as is comfortable into the vagina. (This is best done with the patient lying on her back with the knees bent up.)



3. Push plunger A until it stops, thereby depositing the pessary into the vagina. Remove the applicator.



4. After use, remove plunger A completely by pulling it out of the applicator B.



Then wash it in warm (not boiling) soapy water, rinse and dry carefully.




 





 



7. Marketing Authorisation Holder



Bayer plc



Bayer House



Strawberry Hill



Newbury, Berkshire



RG14 1JA



Trading as Bayer plc, Consumer Care Division



8. Marketing Authorisation Number(S)



PL 0010/0015R



9. Date Of First Authorisation/Renewal Of The Authorisation



Date of first authorisation: 18 August 1988.



Date of last renewal of authorisation: 17 February 1999.



10. Date Of Revision Of The Text



12/08/2010



LEGAL CATEGORY


P




Normitab




Normitab may be available in the countries listed below.


Ingredient matches for Normitab



Atenolol

Atenolol is reported as an ingredient of Normitab in the following countries:


  • Sri Lanka

International Drug Name Search

levonorgestrel


lee-voe-nor-JES-trel


Commonly used brand name(s)

In the U.S.


  • Next Choice

  • Plan B

  • Plan B One-Step

Available Dosage Forms:


  • Tablet

Therapeutic Class: Contraceptive, Progestin


Pharmacologic Class: Progestin


Uses For levonorgestrel


Levonorgestrel is an emergency contraceptive that is used to prevent pregnancy after unprotected sex or after failure of another birth control method. It works by preventing a woman's egg from fully developing. It may also prevent the attachment of the woman's egg to the wall of the uterus (womb).


No contraceptive method is 100 percent effective. Birth control methods such as having surgery to become sterile or not having sex are more effective. levonorgestrel should not be used as a regular method of birth control. Discuss with your doctor your options for birth control.


levonorgestrel is available only under a special distribution program called Convenient Access, Responsible Education (CARE) program.


Before Using levonorgestrel


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 levonorgestrel, the following should be considered:


Allergies


Tell your doctor if you have ever had any unusual or allergic reaction to levonorgestrel 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 performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of levonorgestrel in teenage females. levonorgestrel may be used for birth control in teenage females but is not recommended before the start of menstruation.


Geriatric


Appropriate studies on the relationship of age to the effects of levonorgestrel have not been performed in the geriatric population. levonorgestrel is not indicated for use in elderly women.


Pregnancy








Pregnancy CategoryExplanation
All TrimestersXStudies in animals or pregnant women have demonstrated positive evidence of fetal abnormalities. This drug should not be used in women who are or may become pregnant because the risk clearly outweighs any possible benefit.

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 levonorgestrel, 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 levonorgestrel 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.


  • Isotretinoin

  • Theophylline

  • Tizanidine

  • Tranexamic Acid

Using levonorgestrel 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.


  • Acitretin

  • Alprazolam

  • Amoxicillin

  • Ampicillin

  • Amprenavir

  • Aprepitant

  • Atazanavir

  • Bacampicillin

  • Betamethasone

  • Bexarotene

  • Bosentan

  • Carbamazepine

  • Colesevelam

  • Cyclosporine

  • Darunavir

  • Delavirdine

  • Doxycycline

  • Efavirenz

  • Etravirine

  • Fosamprenavir

  • Fosaprepitant

  • Fosphenytoin

  • Griseofulvin

  • Lamotrigine

  • Licorice

  • Minocycline

  • Modafinil

  • Mycophenolate Mofetil

  • Mycophenolic Acid

  • Nelfinavir

  • Nevirapine

  • Oxcarbazepine

  • Oxytetracycline

  • Phenobarbital

  • Phenytoin

  • Pioglitazone

  • Prednisolone

  • Primidone

  • Rifabutin

  • Rifampin

  • Rifapentine

  • Ritonavir

  • Rosuvastatin

  • Rufinamide

  • Selegiline

  • St John's Wort

  • Tacrine

  • Telaprevir

  • Tetracycline

  • Topiramate

  • Troglitazone

  • Troleandomycin

  • Voriconazole

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


  • Caffeine

Proper Use of levonorgestrel


To make using emergency contraceptives as safe and reliable as possible, you should understand how and when to use them and what effects may be expected.


levonorgestrel comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.


Plan B® and Plan B® One-Step is available as an over-the-counter medicine for women 17 years of age and older, and is available only with a doctor's prescription for women younger than 17 years of age.


Use levonorgestrel exactly as directed by your doctor. levonorgestrel is for occasional use as an emergency birth control. It should not replace your regular birth control method. You may use levonorgestrel at any time during your monthly period.


If you vomit within 2 hours of taking levonorgestrel, call your doctor right away. Your doctor may prescribe another tablet for you.


Dosing


The dose of levonorgestrel 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 levonorgestrel. 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 emergency contraception:
    • For oral dosage form (Plan B® One-Step tablets):
      • Adults and teenagers 17 years of age and older—One tablet taken as soon as possible not more than 72 hours (3 days) after unprotected sex or after failure of another birth control method.

      • Children younger than 17 years of age—Use and dose must be determined by your doctor.


    • For oral dosage form (Plan B® tablets):
      • Adults and teenagers 17 years of age and older—One tablet taken as soon as possible not more than 72 hours (3 days) after unprotected sex or after failure of another birth control method. A second tablet should be taken 12 hours after the first dose.

      • Children younger than 17 years of age—Use and dose must be determined by your doctor.



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 levonorgestrel


It is very important that your doctor check you closely to make sure levonorgestrel is working properly and does not cause unwanted effects.


Although you are using levonorgestrel to prevent pregnancy, you should know that using levonorgestrel while you are pregnant could harm the unborn baby. Your doctor may give you a pregnancy test before you start using levonorgestrel to make sure you are not pregnant. If you think you have become pregnant while using the medicine, tell your doctor right away.


Call your doctor right away if you have severe lower abdominal or stomach pain 3 to 5 weeks after taking levonorgestrel. You may have a pregnancy outside of the uterus (womb), which is called an ectopic pregnancy. An ectopic pregnancy can be a serious and life-threatening condition. It can also cause problems that may make it harder for you to become pregnant in the future.


You may have some blood spotting a few days after taking levonorgestrel. If the bleeding continues for more than 1 week, check with your doctor right away.


levonorgestrel may make your next monthly period later than expected by a few days. If your next period after taking levonorgestrel is more than 1 week late, check with your doctor right away for a pregnancy test.


levonorgestrel will not protect you from getting HIV/AIDS or other sexually transmitted infections. If this is a concern for you, talk with your doctor.


Your regular birth control method such as birth control pills or patch may not work as well while you are using levonorgestrel. After using levonorgestrel, you must use two forms of birth control. Use birth control pills or patch together with another form of birth control, such as a condom, diaphragm, or contraceptive foam or jelly, during any other times that you have sex in the same monthly period you used levonorgestrel.


Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.


levonorgestrel 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
  • Heavy or light menstrual bleeding

Incidence not known
  • Absent missed or irregular menstrual periods

  • cramps

  • irregular menstruation

  • pain

  • pain in the pelvis

  • stopping of menstrual bleeding

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

  • dizziness

  • headache

  • nausea

  • tenderness of the breasts

  • unusual tiredness or weakness

  • vomiting

Less common
  • Diarrhea

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: levonorgestrel 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 levonorgestrel resources


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


  • Levonorgestrel MedFacts Consumer Leaflet (Wolters Kluwer)

  • Levonorgestrel Professional Patient Advice (Wolters Kluwer)

  • Mirena Prescribing Information (FDA)

  • Mirena Consumer Overview

  • Mirena IUD MedFacts Consumer Leaflet (Wolters Kluwer)

  • Next Choice Prescribing Information (FDA)

  • Plan B Prescribing Information (FDA)

  • Plan B Consumer Overview

  • Plan B One-Step Consumer Overview

  • Plan B One-Step MedFacts Consumer Leaflet (Wolters Kluwer)



Compare levonorgestrel with other medications


  • Abnormal Uterine Bleeding
  • Birth Control
  • Emergency Contraception

Wednesday, 28 September 2016

Ibifen




Ibifen may be available in the countries listed below.


Ingredient matches for Ibifen



Ketoprofen

Ketoprofen is reported as an ingredient of Ibifen in the following countries:


  • Georgia

  • Italy

International Drug Name Search

Lipoblock




Lipoblock may be available in the countries listed below.


Ingredient matches for Lipoblock



Simvastatin

Simvastatin is reported as an ingredient of Lipoblock in the following countries:


  • Japan

International Drug Name Search

Amitriptyline Tablets BP 50mg





1. Name Of The Medicinal Product



AMITRIPTYLINE TABLETS BP 50mg


2. Qualitative And Quantitative Composition



Each tablet contains 50mg Amitriptyline Hydrochloride.



3. Pharmaceutical Form



Tan film-coated tablets.



4. Clinical Particulars



4.1 Therapeutic Indications



1) Symptoms of depressive illness (especially where sedation is required).



2) Relief of nocturnal enuresis in children.



4.2 Posology And Method Of Administration



Posology



Adults: Initially 50-75mg daily in divided doses or as a single dose at night, increasing to 150-200mg daily according to clinical response.



Maintenance dose 50-100mg at night which should be continued for at least three months to lessen chances of relapse.



Adolescents and the Elderly: A lower strength dosage form is recommended for this group of patients. Half the normal maintenance dose may be sufficient to produce a satisfactory clinical response.



Children: For nocturnal enuresis only. A lower strength dosage is recommended for this group of patients.



Method of Administration



For oral administration.



4.3 Contraindications



• hypersensitivity to tricyclic antidepressants or to any of the ingredients in the tablets;



• history of myocardial infarction, arrhythmias, particularly heart block to any degree, congestive heart failure, coronary artery insufficiency;



• mania;



• severe liver disease;



• children under 7 years;



• breast feeding;



• patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken them within the last 14 days.



4.4 Special Warnings And Precautions For Use



The elderly are particularly liable to experience adverse reactions, especially agitation, confusion and postural hypotension.



Behavioural changes may occur in children receiving amitriptyline for the treatment of nocturnal enuresis.



Avoid if possible in patients with narrow angle glaucoma, urinary retention, hepatic insufficiency, blood dyscrasias, symptoms suggestive of prostatic hypertrophy and a history of epilepsy. Even average doses may precipitate an attack of glaucoma in patients with narrow-angle glaucoma.



Patients with cardiovascular disorders, hyperthyroid patients and those receiving thyroid medication or anticholinergic drugs should be closely monitored. The dosage of all medications will need to be carefully adjusted.



When used for the depressive component of schizophrenia, amitriptyline should be used with caution as it may aggravate psychotic symptoms. In manic-depressives, a shift towards the manic phase may occur. Paranoid delusions, with or without associated hostility, may be aggravated. A major tranquilliser should be given concurrently in such cases, or dosage of amitriptyline reduced.



Unless essential, it is inadvisable to combine amitriptyline and electroconvulsive therapy (ECT).



Cardiac arrhythmias and severe hypotension are likely to occur with high dosages or in patients with pre-existing heart disease.



If possible, amitriptyline should be discontinued several days before surgery. If emergency surgery is unavoidable, the anaesthetist should be informed that the patient is being treated with amitriptyline (see section 4.5).



Suicide/suicidal thoughts or clinical worsening



Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.



Suicidal thoughts and behaviours may also develop during early treatment with antidepressants for other disorders, the same precautions observed when treating patients with depression should therefore be followed when treating patients with other disorders.



Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old.



Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.



4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction



Alcohol: Enhances the sedative effect.



Alpha2-adrenoceptor stimulants: Concomitant use of apraclonidine and brimonidine should be avoided.



Altretamine: Risk of severe postural hypotension.



Anaesthetics: Concomitant therapy may increase the risk of arrhythmias and hypotension. If surgery is necessary, the anaesthetist should be informed that a patient is being so treated (see section 4.4).



Analgesics: There is a possibility of increased side effects with nefopam. The risk of CNS toxicity is increased with tramadol. There is a possibility of increased sedation with opioid analgesics.



Anti-arrhythmics: there is an increased risk of ventricular arrhythmias with drugs which prolong the QT interval, including amiodarone (avoid concomitant use), disopyramide, procainamide, propafenone and quinidine.



Antibacterials: Plasma concentrations of some tricyclics are reduced by rifampicin (reduces antidepressant effect). Concomitant use with linezolid may result in CNS excitation and hypertension.



Anticholinergics: Excessive anticholinergic effects may occur when tricyclic antidepressants are combined with anticholinergic drugs. Paralytic ileus, urinary retention or acute glaucoma may be precipitated, especially in elderly patients.



Antidepressants: Concomitant use with MAOIs results in CNS excitation and hypertension. Severe convulsions and fatalities have occurred. Therefore, amitriptyline should not be given with a MAOI, and a minimum of 14 days should elapse between discontinuing a MAOI and starting amitriptyline. After this time, amitriptyline should be used cautiously and dosage increased gradually. Concomitant use of reboxetine should be with caution. The plasma concentrations of some tricyclics are increased by SSRIs. Fluoxetine markedly inhibits Cytochrome P450 II D6, which is involved in the metabolism of a number of tricyclic antidepressants. Patients should be monitored for increased antidepressant plasma levels and toxicity when fluoxetine is used concurrently. Adjustment of the antidepressant dosage may be necessary.



Antiepileptics: Concomitant use of antiepileptics may lower the convulsive threshold. The plasma concentrations of some tricyclics may be reduced (eg by barbiturates, carbamazepine) resulting in reduced antidepressant effect.



Antifungals: Increased serum concentraions have occurred in patients also taking Fluconazole. Serious adverse effects have been reported due to increased amitriptyline plasma concentration.



Antihistamines: Increased anticholinergic and sedative effects. Concomitant use of terfenadine should be avoided due the increased risk of ventricular arrhythmias.



Antihypertensives: In general, the hypotensive effect is enhanced, but the effect of adrenergic neurone blockers (eg guanethidine, debrisoquine, bethanidine) and clonidine may be antagonised. There is an increased risk of hypertension on clonidine withdrawal. It is advisable to review all antihypertensive therapy during treatment with tricyclic antidepressants.



Antipsychotics: Increased risk of ventricular arrhythmias. Avoid concomitant use with pimozide or thioridazine. Concomitant use with antipsychotics may increase plasma concentrations of tricyclic antidepressants and increase the anticholinergic side-effects of phenothiazines and possibly clozapine.



Antivirals: Based on the known metabolism of amitriptyline, the protease inhibitor, ritonavir, may increase the serum levels of amitriptyline. Therefore, careful monitoring of therapeutic and adverse effects is recommended when these drugs are administered concomitantly.



Anxiolytics and hypnotics: Concomitant use enhances the sedative effect. Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients treated with 1g ethchlorvynol and 75mg to 150mg of amitriptyline.



Beta-blockers: There is an increased risk of ventricular arrhythmias associated with concomitant use of sotalol.



Calcium-channel blockers: Diltiazem and verapamil may possibly increase the plasma concentration of amitriptyline.



Disulfiram: Concomitant use may inhibit the metabolism of tricyclics. Delirium has been reported in patients taking amitriptyline with disulfiram.



Diuretics: increased risk of postural hypotension.



Dopaminergics: Concomitant use with entacapone should be avoided. CNS toxicity has been reported with selegiline.



Muscle relaxants: Concomitant use of baclofen enhances its muscle relaxant effect.



Nitrates: Reduced effect of sublingual nitrates (owing to dry mouth).



Oestrogens and progestogens: Oral contraceptives antagonise the antidepressant effect but side-effects may be increased due to increased plasma concentrations of tricyclics.



Sibutramine: Concomitant use is not recommended due to the increased risk of CNS toxicity.



Sympathomimetics: Amitriptyline should not be given with sympathomimetic agents such as adrenaline, ephedrine, isoprenaline, noradrenaline, phenylephrine and phenylpropanolamine due to hypertension and arrhythmias. Local anaesthetics with adrenaline appear to be safe. Methylphenidate may inhibit the metabolism of tricyclics and therefore increase the antidepressant action of amitriptyline.



Ulcer-healing drugs: Plasma concentrations of amitriptyline are increased by cimetidine (inhibition of metabolism).



4.6 Pregnancy And Lactation



The safety of amitriptyline during pregnancy and lactation has not been established. Amitriptyline should not be used during the first and third trimester and the hazards to the foetus, child or mother must be evaluated when considering the possible benefits of amitriptyline therapy during pregnancy. Clinical experience of the use of amitriptyline in pregnancy is limited. Animal studies have shown harmful effects at exceptionally high doses. Withdrawal symptoms, including respiratory depression and agitation have been reported in neonates whose mothers had taken tricyclic antidepressants during the last trimester of pregnancy. Urinary retention in the neonate has also been associated with maternal use of amitriptyline.



Amitriptyline is detectable in breast milk at high doses. Because of the potential for serious adverse reactions in infants from amitriptyline, a decision should be made whether to discontinue breast-feeding or discontinue the drug.



4.7 Effects On Ability To Drive And Use Machines



Amitriptyline may initially impair alertness. Patients should be warned of the performance of potentially hazardous tasks such as driving a car or operating machinery.



4.8 Undesirable Effects



In general, amitriptyline is well tolerated. Not all of the side-effects listed below have been reported with amitriptyline but are included due to the similar pharmacology of other tricyclics. Antidepressant effects of amitriptyline may not become apparent for the first 2-4 weeks of therapy so patients should be closely monitored during this period.



Allergic reactions: Skin rashes, urticaria, photosensitisation, oedema of face and tongue.



Blood and lymphatic system disorders: Bone marrow depression including agranulocytosis, eosinophilia, leucopenia, thrombocytopenia and purpura.



Endocrine disorders: Gynaecomastia, breast enlargement, galactorrhoea, testicular swelling, libido fluctuations, interference with sexual function, syndrome of inappropriate ADH secretion.



Metabolism and nutrition disorders: Elevation or lowering of blood sugar levels. Increased appetite and weight gain may be a drug reaction or due to relief of depression.



Nervous system disorders: Dizziness, fatigue, headache, drowsiness, weakness, disturbed concentration, disorientation, confusional states, insomnia, nightmares, delusions, hallucinations, hypomania, excitement, anxiety, restlessness, peripheral neuropathy, numbness, tingling and paraesthesia of the extremities, inco-ordination, ataxia, tremors, convulsions, altered ECG, extrapyramidal effects, tinnitus. Cases of suicidal ideation and suicidal behaviours have been reported during Amitriptyline therapy or early after treatment discontinuation (see section 4.4). Anticholinergic effects include: dry mouth, hyperpyrexia, blurred vision, accommodation disturbance, increased intra-ocular pressure, mydriasis, constipation, paralytic ileus, urinary retention, urinary tract dilatation.



Cardiovascular disorders: Postural hypotension, hypertension, palpitations, tachycardia, myocardial infarction, heart block and stroke. Arrhythmias and severe hypotension are likely to occur with high doses or overdosage.



Gastrointestinal disorders: Nausea, vomiting, diarrhoea, epigastric distress, anorexia, dysgeusia, stomatitis, parotid swelling, black tongue.



Hepato-biliary disorders: Rarely hepatitis (including altered liver function and jaundice).



Skin and subcutaneous tissue disorders: Increased perspiration and alopecia.



Renal and urinary disorders: Urinary frequency.



Class effects



Epidemiological studies show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this increased risk is unknown.



Abrupt withdrawal after prolonged administration has caused nausea, headache and malaise. Gradual withdrawal has been associated with transient symptoms such as dream and sleep disturbances, irritability and restlessness during the first two weeks of dosage reduction. These are not thought to be signs associated with addiction.



Mania or hypomania have been reported rarely within 2-7 days of stopping therapy with tricyclic antidepressants.



Side-effects in enuresis: As dosages used in enuresis are low compared to those used for depression, side-effects are less frequent. The most common are drowsiness and anticholinergic effects. Infrequently, mild sweating and itching have been reported. Behavioural changes have been observed in children receiving tricyclics for treatment of enuresis.



4.9 Overdose



There is no specific antidote for tricyclic antidepressant poisoning. Patients should be hospitalised and treatment should be symptomatic and based on cardiac (including ECG monitoring) and respiratory support.



Symptoms



Toxicity is due to a combination of anticholinergic (antimuscarinic, atropine-like) effects at autonomic nerve endings and in the brain, cardiac sodium channel blockade and a1 adrenergic receptor blockade. In addition, tricyclic antidepressants block pre-synaptic uptake of amines and the cardiac delayed rectifier potassium channel (Ikr).



Features commonly include: sinus tachycardia, hot dry skin, dry mouth and tongue, dilated pupils, urinary retention and ileus, progressing to ataxia, nystagmus, divergent squint and drowsiness which may lead to deep coma and respiratory depression. Increased tone and hyperreflexia may be present with extensor plantar reflexes. In deep coma all reflexes (including brain-stem reflexes) may be abolished. Convulsions occur in >5% of cases and may herald haemodynamic compromise.



ECG features include prolongation of the PR, QRS and QT intervals, non-specific ST segment and T wave changes and atrioventricular block.



Metabolic acidosis may be present. Hypotension may occur and may be severe.



Hypothermia and rhabdomyolysis may occur in patients who have been unconscious. Occasionally skin blisters may occur.



During recovery confusion, agitation and visual hallucinations may occur.



Features of serotonin toxicity may occur. These include CNS effects (including agitation or coma), autonomic instability (including hyperpyrexia), and neuromuscular excitability (including clonus and raised serum creatine kinase)



This syndrome is more likely to occur if the patient has been exposed to two or more drugs that increase the effect of serotonin in serotonergic synapses (by increasing release, reducing reuptake or metabolism, or stimulating serotonin receptors), either as an acute overdose or if taken regularly, for example - SSRIs, MAOIs, tricyclic antidepressants, venlafaxine, tramadol, triptans, linezolid and St John's Wort; stimulant drugs of abuse (e.g. MDMA (ecstasy), amphetamines, cocaine, cathinone derivatives (mephedrone, etc)).



The cardiovascular and CNS effects in overdose will be potentiated by simultaneous ingestion of alcohol, cardiovascular agents and other psychotropic drugs



Management



Do not give flumazenil to reverse benzodiazepine toxicity in mixed overdoses.



1. Ensure a clear airway and adequate ventilation. Check arterial blood gases and correct any hypoxia. If hypercapnia is present assisted ventilation is indicated.



2. The benefit of gastric decontamination is uncertain. Consider activated charcoal by mouth or naso-gastric tube if the patient presents within 1 hour of ingestion of more than 5mg/kg, provided the airway can be protected.



A second dose of charcoal should be considered after 1 -2 hours in patients with features of toxicity who are able to swallow, or who have been intubated.



3. After cardiac arrest, prolonged resuscitation may be successful and should be continued for at least 1 hour.



4. Observe for at least 6 hours after ingestion. Monitor BP, pulse and cardiac rhythm. Repeat ECGs should be performed. Patients who remain asymptomatic and have a normal ECG by 6 hours are unlikely to develop late complications.



5. Check urea and electrolytes and monitor urine output. Check serum creatine kinase in patients who have been unconscious.



6. If metabolic acidosis persists despite correction of hypoxia and adequate fluid resuscitation consider correction with intravenous sodium bicarbonate. Rapid correction is particularly important if there is prolongation of the QRS or QT intervals.



7. Control convulsions with intravenous diazepam or lorazpam. Give oxygen and correct acid base and metabolic disturbances. Phenytoin is contraindicated in tricyclic overdosage (because in common with TCAs it blocks sodium channels and may increase the risk of cardiac arrhythmias).



8. Correct hypotension by raising the foot of the bed. In severe cases administration of colloid to expand the intravascular volume is required (central venous pressure monitoring may be required). Alkalinisation with sodium bicarbonate may correct hypotension.



9. Agitated adults can be sedated with oral or IV diazepam. If ineffective consider oral or parenteral haloperidol.



10. Glucagon 10mg IV bolus may be given if patients are severely hypotensive.



11. If the patient is hypothermic, rewarm slowly using conventional means.



12. Monitor for rhabdomyolysis if the patient has been unconscious for a considerable time.



13. Forced diuresis, haemodialysis and haemoperfusion are of no value due to the large volume of distribution of tricyclic antidepressants.



14. Other measures as indicated by the patient's clinical condition.



For further information or treatment in children discuss with your local poisons information service: in the UK NPIS 0844 892 0111, in Ireland NPIC (01) 809 2566.



Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Deaths by deliberate or accidental overdosage have occurred with this class of medicament.



5. Pharmacological Properties



5.1 Pharmacodynamic Properties



Amitriptyline hydrochloride is a tricyclic antidepressant.



5.2 Pharmacokinetic Properties



Amitriptyline is readily absorbed from the GI tract, peak plasma levels occurring within ≈ 6 hours of oral administration. Amitriptyline is extensively demethylated in the liver to its primary metabolite, nortriptyline. Paths of metabolism include hydroxylation, N-oxidation and conjugation with glucuronic acid. It is excreted in the urine, mainly in the form of its metabolites, either free or in conjugated form.



5.3 Preclinical Safety Data



There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.



6. Pharmaceutical Particulars



6.1 List Of Excipients



The tablets contain: lactose monohydrate, microcrystalline cellulose (E460), maize starch, colloidal anhydrous silica, magnesium stearate.



The coating contains: hypromellose (E464), macrogol, talc (E553b), titanium dioxide (E171), quinoline yellow (E104), iron oxide (E172).



6.2 Incompatibilities



None known.



6.3 Shelf Life



A three year shelf-life is claimed and our marketed products includes a three year expiry date.



6.4 Special Precautions For Storage



Store below 25°C in a dry place. Protect from light.



6.5 Nature And Contents Of Container



The product containers are rigid injection moulded polypropylene or injection blow-moulded polyethylene containers and snap-on polyethylene lids; in case any supply difficulties should arise the alternative is amber glass containers with screw caps.



The product may also be supplied in blister packs and cartons:



a) Carton: Printed carton manufactured from white folding box board.



b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper aluminium foil with 5-6g/M² PVC and PVdC compatible heat seal lacquer on the reverse side.



Pack sizes: 28s, 30s, 56s, 60s, 84s, 90s, 100s, 112s, 120s, 168s, 180s, 250s, 500s, 1000s



Product may also be supplied in bulk packs, for reassembly purposes only, in polybags contained in tins, skillets or polybuckets filled with suitable cushioning material. Bulk packs are included for temporary storage of the finished product before final packaging into the proposed marketing containers.



Maximum size of bulk packs: 50,000.



6.6 Special Precautions For Disposal And Other Handling



Not applicable.



Administrative Data


7. Marketing Authorisation Holder



Actavis UK Limited



(Trading style: Actavis)



Whiddon Valley



BARNSTAPLE



N Devon EX32 8NS



8. Marketing Authorisation Number(S)



PL 0142/0178



9. Date Of First Authorisation/Renewal Of The Authorisation



17.4.84



Renewed: 29.10.02



10. Date Of Revision Of The Text



22 /02/2011




NB-3




NB-3 may be available in the countries listed below.


Ingredient matches for NB-3



Nicotinamide

Nicotinamide is reported as an ingredient of NB-3 in the following countries:


  • Argentina

International Drug Name Search