Ovranette® 150 / 30 micrograms Coated Tablets

1. Name Of The Medicinal Product

Ovranette^® 150/30 micrograms Coated Tablets.

2. Qualitative And Quantitative Composition

Each tablet contains 0.15mg levonorgestrel and 0.03mg ethinylestradiol.

For excipients see 6.1

3. Pharmaceutical Form

Coated tablets.

White, shiny, sugar coated-tablet with a smooth surface.

4. Clinical Particulars

4.1 Therapeutic Indications

Oral contraception.

Treatment of endometriosis.

Treatment of spasmodic dysmenorrhoea and premenstrual tension.

Treatment of functional uterine bleeding (menorrhagia, metrorrhagia, metropathia haemorrhatica).

Emergency treatment of acute uterine bleeding.

4.2 Posology And Method Of Administration

For oral administration

Dosage and Administration

First treatment cycle: 1 tablet daily for 21 days, starting with the tablet marked number 1, on the first day of the menstrual cycle. Additional contraception (barriers and spermicides) is not required.

Subsequent cycles: Each subsequent course is started when seven tablet-free days have followed the preceding course. A withdrawal bleed should occur during the 7 tablet-free days.

Changing from another 21 day combined oral contraceptive: The first tablet of Ovranette should be taken on the first day immediately after the end of the previous oral contraceptive course. Additional precautions are not required. A withdrawal bleed should not be expected until the end of the first pack.

Changing from an Every Day (ED) 28 day combined oral contraceptive: The first tablet of Ovranette should be taken on the day immediately after the day on which the last active pill in the ED pack has been taken. The remaining tablets in the ED pack should be discarded. Additional precautions are not required. A withdrawal bleed should not be expected until the end of the first pack.

Changing from a Progestogen-only-Pill (POP): The first tablet of Ovranette should be taken on the first day of menstruation even if the POP for that day has already been taken. The remaining tablets in the POP pack should be discarded. Additional precautions are not required.

Post-partum and post-abortum use: After pregnancy, combined oral contraception can be started in non-lactating women 21 days after a vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications. If the pill is started later than 21 days after delivery, then alternative contraception (barriers and spermicides) should be used until oral contraception is started and for the first 7 days of pill-taking. If unprotected intercourse has taken place after 21 days post partum, then oral contraception should not be started until the first menstrual bleed after childbirth. After miscarriage or abortion oral contraception may be started immediately.

Other indications

Endometriosis: Continuous treatment with two tablets daily.

Spasmodic dysmenorrhoea, premenstrual tension: Dosage as for oral contraception.

Functional uterine bleeding: Two tablets are taken daily on a cyclic basis as for oral contraception. In the first one or two cycles it may be necessary to give four tablets, or in exceptional cases, five.

Emergency treatment of acute uterine bleeding: Four tablets are given initially and, if necessary, 4-8 tablets daily.

Elderly: Not applicable

Children: Not applicable

Special Circumstances Requiring Additional Contraception

Missed Pills: If a tablet is delayed, it should be taken as soon as possible, and if it is taken within 12 hours of the correct time, additional contraception is not needed. Further tablets should then be taken at the usual time. If the delay exceeds 12 hours, the last missed pill should be taken when remembered, the earlier missed pills left in the pack and normal pill-taking resumed. If one or more tablets are omitted from the 21 days of pill-taking, addition contraception (barriers and spermicides) should be used for the next 7 days of pill-taking. In addition, if one or more pills are missed during the last 7 days of pill-taking, the subsequent pill-free interval should be disregarded and the next pack started the day after taking the last tablet from the previous pack. In this case, a period should not be expected until the end of the second pack. If the patient does not have a period at the end of the second pack, she must return to her doctor to exclude the possibility of pregnancy.

Gastro-intestinal upset: Vomiting or diarrhoea may reduce the efficacy by preventing full absorption. Additional contraception (barriers and spermicides) should be used during the stomach upset and for the 7 days following the upset. If these 7 days overrun the end of a pack, the next pack should be started without a break. In this case, a period should not be expected until the end of the second pack. If the patient does not have a period at the end of the second pack, she must return to her doctor to exclude the possibility of pregnancy.

Mild laxatives do not impair contraceptive action.

Interaction with other drugs:

Some drugs may reduce the efficacy of oral contraceptives (refer to “4.5. Interaction with other medicaments and other forms of interaction.”). It is, therefore, advisable to use non

4.3 Contraindications

1. Suspected pregnancy

2. History of confirmed venous thromboembolism (VTE). Family history of idiopathic VTE. Other known risk factors for VTE.

3. Arterial thrombotic disorders and a history of these conditions, disorders of lipid metabolism and other conditions in which, in individual cases, there is known or suspected to be a much increased risk of thrombosis.

4. Sickle-cell anaemia

5. Acute or severe chronic liver diseases. Dubin-Johnson syndrome. Rotor syndrome. History, during pregnancy, of idiopathic jaundice or severe pruritis.

6. History of herpes gestationis.

7. Mammary or endometrial carcinoma, or a history of these conditions.

8. Abnormal vaginal bleeding of unknown cause.

9. Deterioration of otosclerosis during pregnancy.

4.4 Special Warnings And Precautions For Use

Warnings:

1. Venous and Arterial Thrombosis and Thromboembolism

Use of COCs is associated with an increased risk of venous and arterial thrombotic and thromboembolic events.

Minimising exposure to oestrogens and progestogens is in keeping with good principles of therapeutics. For any particular oestrogen/progestogen combination, the dosage regimen prescribed should be one that contains the least amount of oestrogen and progestogen that is compatible with a low failure rate and the needs of the patient.

Unless clinically indicated otherwise, new users of COCs should be started on preparations containing less than 50μg of oestrogen.

Venous Thrombosis and Thromboembolism

Use of COCs increases the risk of venous thrombotic and thromboembolic events. Reported events include deep venous thrombosis and pulmonary embolism.

The use of any COC carries an increased risk of venous thrombotic and thromboembolic events compared with no use. The excess risk is highest during the first year a woman ever uses a combined oral contraceptive. This increased risk is less than the risk of venous thrombotic and thromboembolic events associated with pregnancy which is estimated as 60 cases per 100,000 woman-years. Venous thromboembolism is fatal in 1-2% of cases.

Some epidemiological studies have reported a greater risk of VTE for women using combined oral contraceptives containing desogestrel or gestodene (the so-called third generation pills) than for women using pills containing levonorgestrel (the so-called second generation pills).

The spontaneous incidence of VTE in healthy non-pregnant women (not taking any oral contraceptive) is about 5 cases per 100,000 women per year. The incidence in users of the second generation pills (such as Ovranette) is about 15 per 100,000 women per year of use. The incidence in users of third generation pills is about 25 cases per 100,000 women per year of use; this excess incidence has not been satisfactorily explained by bias or confounding. The level of all these risks of VTE increases with age and is likely to be further increased in women with other known risk factors of VTE.

All this information should be taken into account when prescribing this COC. When counselling on the choice of contraceptive method(s) all of the above information should be considered.

The risk of venous thrombotic and thromboembolic events is further increased in women with conditions predisposing for venous thrombosis and thromboembolism. Caution must be exercised when prescribing COCs for such women.

Examples of predisposing conditions for venous thrombosis are:

² or over)

The relative risk of post-operative thromboembolic complications has been reported to be increased two- or four-fold with the use of COCs (see reasons for discontinuation).

Since the immediate post-partum period is associated with an increased risk of thromboembolism, COCs should be started no earlier than day 28 after delivery or second-trimester abortion.

Arterial Thrombosis and Thromboembolism

The use of COCs increases the risk or arterial thrombotic and thromboembolic events. Reported events include myocardial infarction and cerebrovascular events (ischaemic and haemorrhagic stroke).

The risk of arterial thrombotic and thromboembolic events is further increased in women with underlying risk factors.

Caution must be exercised when prescribing COCs for women with risk factors for arterial thrombotic and thromboembolic events.

Examples of risk factors for arterial thrombotic and thromboembolic event are:

²)

COC users with migraine (particularly migraine with aura) may be at increased risk of stroke.

There is no consensus about the possible role of varicose veins and superficial thrombophlebitis in venous thromboembolism

The suitability of a combined oral contraceptive should be judged according to the severity of such conditions in the individual case, and should be discussed with the patient before she decides to take it.

2. The risk of arterial thrombosis associated with combined oral contraceptives increases with age, and this risk is aggravated by cigarette smoking. The use of combined oral contraceptives by women in the older age group, especially those who are cigarette smokers, should therefore be discouraged and alternative methods used.

3. The possibility cannot be ruled out that certain chronic diseases may occasionally deteriorate during the use of combined oral contraceptives. (See 'Precautions').

4. Malignant liver tumours have been reported on rare occasions in long

5. Numerous epidemiological studies have been reported on the risks of ovarian, endometrial, cervical and breast cancer in women using combined oral contraceptives. The evidence is clear that combined oral contraceptives offer substantial protection against both ovarian and endometrial cancer.

An increased risk of cervical cancer in long term users of combined oral contraceptives has been reported in some studies, but there continues to be controversy about the extent to which this is attributable to the confounding effects of sexual behaviour and other factors.

A meta-analysis from 54 epidemiological studies reported that there is a slightly increased relative risk (RR = 1.24) of having breast cancer diagnosed in women who are currently using combined oral contraceptives (COCs). The observed pattern of increased risk may be due to an earlier diagnosis of breast cancer in COC users, the biological effects of COCs or a combination of both. The additional breast cancers diagnosed in current users of COCs or in women who have used COCs in the last ten years are more likely to be localised to the breast than those in women who never used COCs.

Breast cancer is rare among women under 40 years of age whether or not they take COCs. Whilst this background risk increases with age, the excess number of breast cancer diagnoses in current and recent COC users is small in relation to the overall risk of breast cancer (see bar chart).

The most important risk factor for breast cancer in COC users is the age women discontinue the COC; the older the age at stopping, the more breast cancers are diagnosed. Duration of use is less important and the excess risk gradually disappears during the course of the 10 years after stopping COC use such that by 10 years there appears to be no excess.

The possible increase in risk of breast cancer should be discussed with the user and weighed against the benefits of COCs taking into account the evidence that they offer substantial protection against the risk of developing certain other cancers (e.g. ovarian and endometrial cancer).

Reasons for stopping oral contraception immediately:

1. Occurrence of migraine in patients who have never previously suffered from it. Exacerbation of pre

2. Any kind of acute disturbance of vision.

3. Suspicion of thrombosis or infarction including symptoms such as unusual pains in or swelling of the legs, stabbing pains on breathing, persistent cough or coughing blood, pain or tightness in the chest.

4. Six weeks before elective operations, or treatment of varicose veins by sclerotherapy and during immobilisation, e.g. after accidents, etc.

5. Significant rise in blood

6. Jaundice.

7. Clear exacerbation of conditions known to be capable of deteriorating during oral contraception or pregnancy.

8. Pregnancy is a reason for stopping immediately because it has been suggested by some investigations that oral contraceptives taken in early pregnancy may slightly increase the risk of foetal malformations. Other investigations have failed to support these findings. The possibility therefore cannot be excluded, but it is certain that if a risk exists at all, it is very small.

If oral contraception is stopped for any reason and pregnancy is not desired, it is recommended that alternative non-hormonal methods of contraception (such as barriers or spermicides) are used to ensure contraceptive protection is maintained.

Precautions:

1. Assessment of women prior to starting oral contraceptives (and at regular intervals thereafter) should include a personal and family medical history of each woman. Physical examination should be guided by this and by the contraindications (section 4.3) and warnings (section 4.4) for this product. The frequency and nature of these assessments should be based upon relevant guidelines and should be adapted to the individual woman, but should include measurement of blood pressure and, if judged appropriate by the clinician, breast, abdominal and pelvic examination including cervical cytology.

2. Before starting treatment, pregnancy must be excluded.

3. The following conditions require careful observation during medication: a history of severe depressive states, varicose veins, diabetes, hypertension, epilepsy, otosclerosis, multiple sclerosis, porphyria, tetany, disturbed liver function, gall

4. The risk of the deterioration of chloasma, which is often not fully reversible, is reduced by the avoidance of excessive exposure to sunlight.

Menstrual changes:

1. Reduction of menstrual flow: This is not abnormal and it is to be expected in some patients.

2. Missed menstruation: Occasionally withdrawal bleeding may not occur at all. If the tablets have been taken correctly, pregnancy is very unlikely but should be ruled out before a new course of tablets is started.

Intermenstrual bleeding:

Very light “spotting” or heavier “break through bleeding” may occur during tablet-taking, especially in the first few cycles. It appears to be generally of no significance, except where it indicates errors of tablet-taking, or where the possibility of interaction with other drugs exists. However, if irregular bleeding is persistent an organic cause should be considered.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Some drugs accelerate the metabolism of oral contraceptives when taken concurrently and these include barbiturates, phenytoin, phenylbutazone and rifampicin. Other drugs suspected of having the capacity to reduce the efficacy of oral contraceptives include ampicillin and other antibiotics. It is therefore, advisable to use non-hormonal methods of contraception (barriers and spermicides). Please refer to “4.2 Posology and Method of Administration, Interaction with other drugs”.

The response to metyrapone is less pronounced in women taking oral contraceptives.

ACTH function test remains unchanged. Reduction in corticosteriod excretion and elevation or plasma corticosteriods are due to increased cortisol binding capacity of plasma proteins.

Serum protein-bound iodine levels should not be used for evaluation of thyroid function as levels may rise due to increased thyroid hormone binding capacity of plasma proteins.

Erythrocyte sedimentation may be accelerated in absence of any disease due to change in proportion of plasma protein fractions. Increases in plasma copper, iron and alkaline phosphatase have been recorded.

The herbal remedy, St John's Wort (Hypericum perforatum) should not be taken concomitantly with this medicine as it could potentially lead to a loss of contraceptive effect.

4.6 Pregnancy And Lactation

Pregnancy is a reason for stopping administration immediately because it has been suggested by some investigations that oral contraceptives taken in early pregnancy may slightly increase the risk of foetal malformations. Other investigations have failed to support these findings. The possibility therefore cannot be excluded, but it is certain that if a risk exists at all, it is very small. After pregnancy, combined oral contraception can be started in non-lactating women 21 days after vaginal delivery, provided that the patient is fully ambulant and there are no puerperal complications.

Please refer to recommended dosage schedule: Post-partum and post-abortum use.

Administration of oestrogens to lactating women may decrease the quantity or quality of the milk.

4.7 Effects On Ability To Drive And Use Machines

None known.

4.8 Undesirable Effects

See 'Special Warnings and Special Precautions for Use'.

There is an increased risk of venous thromboembolism for all women using a combined oral contraceptive. For information on differences in risk between oral contraceptives, see Section 4.4.

Occasional side-effect may include nausea, vomiting, headaches, breast tenderness, irregular bleeding or missed bleeds, changed body weight or libido, depressive moods, chloasma and altered serum lipid profile.

4.9 Overdose

There have been no reports of serious ill

There are no specific antidotes and further treatment should be symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Ethinylestradiol is a synthetic oestrogen which has actions and uses similar to those of oestradiol, but is much more potent.

Norgestrel is a progestational agent with actions similar to those of progesterone. It is more potent as an inhibitor of ovulation than norethisterone and has androgenic activity.

5.2 Pharmacokinetic Properties

Ethinylestradiol is absorbed by the gastro-intestinal tract. It is only slowly metabolised and excreted in the urine.

Norgestrel is absorbed from the gastrointestinal tract. Metabolites are excreted in the urine and faeces as glucuronide and sulphate conjugates.

5.3 Preclinical Safety Data

Nothing of relevance to the prescriber.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Core: lactose, maize starch, povidone 25, magnesium stearate, talc, purified water.

Coating: sucrose, polyethylene glycol 6000, calcium carbonate, talc, povidone 90, purified water, white wax and wax carnauba.

6.2 Incompatibilities

None known.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store at or below room temperature.

6.5 Nature And Contents Of Container

Aluminium foil and PVC blister packs of 21 tablets.

Cartons containing 1, 3 and 50 blisters.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent

CT13 9NJ

United Kingdom

8. Marketing Authorisation Number(S)

PL 00057/1283

9. Date Of First Authorisation/Renewal Of The Authorisation

11 August 2011

10. Date Of Revision Of The Text

August 2011

Chlor-Trimeton Allergy SR

Generic Name: chlorpheniramine (KLOR fen IR a meen)

Brand Names: AHist, Aller-Chlor, Allergy Relief, C.P.M., Chlo-Amine, Chlor-Mal, Chlor-Trimeton, Chlor-Trimeton Allergy SR, Chlorphen, ChlorTan, Ed Chlor-Tan, Ed ChlorPed, PediaTan, TanaHist-PD, Triaminic Allergy, Wal-finate

What is Chlor-Trimeton Allergy SR (chlorpheniramine)?

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

Chlorpheniramine is used to treat sneezing, itching, watery eyes, and runny nose caused by allergies or the common cold.

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

What is the most important information I should know about Chlor-Trimeton Allergy SR (chlorpheniramine)?

Do not give this medication to a child younger than 4 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not take chlorpheniramine if you are allergic to it.

Ask a doctor or pharmacist before taking chlorpheniramine if you have glaucoma, a stomach ulcer, severe constipation, kidney disease, urination problems, an enlarged prostate, or a thyroid disorder.

Ask a doctor or pharmacist before using any other cold, cough, or allergy medicine. Chlorpheniramine is contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine.

Chlorpheniramine may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine.

What should I discuss with my healthcare provider before taking Chlor-Trimeton Allergy SR (chlorpheniramine)?

Do not take this medication if you are allergic to chlorpheniramine. Do not use chlorpheniramine if you have used an MAO inhibitor such as furazolidone (Furoxone), isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam, Zelapar), or tranylcypromine (Parnate) in the last 14 days. A dangerous drug interaction could occur, leading to serious side effects.

Ask a doctor or pharmacist if it is safe for you to take this medicine if you have:

• 
  

  glaucoma;

  
  


• 
  

  a stomach ulcer;

  
  


• 
  

  severe constipation;

  
  


• 
  

  kidney disease;

  
  


• 
  

  urination problems or an enlarged prostate; or

  
  


• 
  

  a thyroid disorder.

  
  

FDA pregnancy category B. Chlorpheniramine is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Chlorpheniramine 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. Older adults may be more likely to have side effects from this medication.

How should I take Chlor-Trimeton Allergy SR (chlorpheniramine)?

Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Cold or allergy medicine is usually taken only for a short time until your symptoms clear up.

Take this medication with a full glass of water. Take chlorpheniramine with food or milk if it upsets your stomach. Do not crush, chew, break, or open an extended-release tablet or capsule. Swallow it whole. Breaking or opening the pill may cause too much of the drug to be released at one time.

Measure liquid medicine with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.

This medication can cause unusual results with allergy skin tests. Tell any doctor who treats you that you are taking an antihistamine.

Store at room temperature away from moisture and heat.

What happens if I miss a dose?

Since cold or allergy medicine is taken when needed, you may not be on a dosing schedule. If you are taking the medication regularly, take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose?

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

Overdose symptoms may include feeling restless or nervous, nausea, vomiting, stomach pain, dizziness, drowsiness, dry mouth, warmth or tingly feeling, or seizure (convulsions).

What should I avoid while taking Chlor-Trimeton Allergy SR (chlorpheniramine)?

Ask a doctor or pharmacist before using any other cold, cough, or allergy medicine. Chlorpheniramine is contained in many combination medicines. Taking certain products together can cause you to get too much of a certain drug. Check the label to see if a medicine contains an antihistamine.

Avoid becoming overheated or dehydrated during exercise and in hot weather. Chlorpheniramine can decrease perspiration and you may be more prone to heat stroke.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Drinking alcohol can increase certain side effects of chlorpheniramine.

Chlor-Trimeton Allergy SR (chlorpheniramine) 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. Stop taking chlorpheniramine and call your doctor at once if you have a serious side effect such as:

• 
  

  urinating less than usual or not at all;

  
  


• 
  

  confusion, extreme drowsiness;

  
  


• 
  

  severe dizziness, anxiety, restless feeling, nervousness; or

  
  


• 
  

  weak or shallow breathing.

  
  

Less serious side effects may include:

• 
  

  mild dizziness, drowsiness;

  
  


• 
  

  blurred vision;

  
  


• 
  

  dry mouth;

  
  


• 
  

  nausea, stomach pain, constipation;

  
  


• 
  

  problems with memory or concentration; or

  
  


• 
  

  feeling restless or excited (especially in children).

  
  

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

What other drugs will affect Chlor-Trimeton Allergy SR (chlorpheniramine)?

Other cold or allergy medicine, sedatives, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by chlorpheniramine. Tell your doctor if you regularly use any of these medicines.

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

• 
  

  glycopyrrolate (Robinul);

  
  


• 
  

  mepenzolate (Cantil);

  
  


• 
  

  probenecid (Benemid, Probalan);

  
  


• 
  

  rifampin (Rifadin, Rifater, Rifamate, Rimactane);

  
  


• 
  

  zidovudine (Retrovir, AZT);

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  atropine (Atreza, Sal-Tropine), belladonna (Donnatal, and others), benztropine (Cogentin), dimenhydrinate (Dramamine), methscopolamine (Pamine), or scopolamine (Transderm-Scop);

  
  


• 
  

  bladder or urinary medications such as darifenacin (Enablex), flavoxate (Urispas), oxybutynin (Ditropan, Oxytrol), tolterodine (Detrol), or solifenacin (Vesicare);

  
  


• 
  

  bronchodilators such as ipratropium (Atrovent) or tiotropium (Spiriva);

  
  


• 
  

  irritable bowel medications such as dicyclomine (Bentyl), hyoscyamine (Hyomax), or propantheline (Pro-Banthine); or

  
  


• 
  

  salicylates such as aspirin, Backache Relief Extra Strength, Novasal, Nuprin Backache Caplet, Doan's Pills Extra Strength, Pepto-Bismol, Tricosal, and others;

  
  

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

More Chlor-Trimeton Allergy SR resources

• Chlor-Trimeton Allergy SR Side Effects (in more detail)
• Chlor-Trimeton Allergy SR Use in Pregnancy & Breastfeeding
• Drug Images
• Chlor-Trimeton Allergy SR Drug Interactions
• Chlor-Trimeton Allergy SR Support Group
• 0 Reviews for Chlor-Trimeton Allergy SR - Add your own review/rating

• Ahist MedFacts Consumer Leaflet (Wolters Kluwer)


• Aller-Chlor Syrup MedFacts Consumer Leaflet (Wolters Kluwer)


• Chlorpheniramine Maleate/Tannate, Dexchlorpheniramine Maleate Monograph (AHFS DI)


• Ed ChlorPed Suspension Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Pediox-S Suspension MedFacts Consumer Leaflet (Wolters Kluwer)


• QDALL AR Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Chlor-Trimeton Allergy SR with other medications

• Allergic Reactions
• Cold Symptoms
• Hay Fever
• Urticaria

Where can I get more information?

• Your pharmacist can provide more information about chlorpheniramine.

See also: Chlor-Trimeton Allergy SR side effects (in more detail)

Atracurium Besilate 10mg / ml Injection (Hospira UK Ltd)

1. Name Of The Medicinal Product

Atracurium Besilate 10 mg/ml Solution for Injection

2. Qualitative And Quantitative Composition

Atracurium besilate 10 mg/ml (equivalent to atracurium 7.5 mg/ml)

2.5 ml of solution contains 25 mg atracurium besilate

5 ml of solution contains 50 mg atracurium besilate

25 ml of solution contains 250 mg atracurium besilate

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Solution for injection

A clear colourless or faint yellow solution

4. Clinical Particulars

4.1 Therapeutic Indications

Atracurium Besilate Injection is indicated as an adjunct to general anaesthesia during surgery to relax skeletal muscles, and to facilitate endotracheal intubation and mechanical ventilation. It is also indicated to facilitate mechanical ventilation in intensive care unit (ICU) patients.

4.2 Posology And Method Of Administration

Use as an adjunct to general anaesthesia

Atracurium Besilate Injection should only be administered by intravenous injection. Do not give Atracurium Besilate Injection intramuscularly since this may result in tissue irritation and there are no clinical data to support this route of administration.

To avoid distress to the patient, Atracurium Besilate Injection should not be administered before unconsciousness has been induced. Atracurium Besilate Injection should not be mixed in the same syringe, or administered simultaneously through the same needle, with alkaline solutions (e.g. barbiturate solutions).

In common with all neuromuscular blocking agents, monitoring of neuromuscular function is recommended during the use of Atracurium Besilate Injection in order to individualise dosage requirements.

Initial bolus doses for intubation

An initial atracurium besilate dose of 0.3 to 0.6 mg/kg (depending on the duration of full block required), given as an intravenous bolus injection, is recommended. This will provide adequate relaxation for about 15 to 35 minutes.

Endotracheal intubation can usually be accomplished within 90 to 120 seconds of the intravenous injection of 0.5 to 0.6 mg/kg. Maximum neuromuscular blockade is generally achieved approximately 3 to 5 minutes after administration. Spontaneous recovery from the end of full block occurs in about 35 minutes as measured by the restoration of the tetanic response to 95% of normal neuromuscular function.

Although atracurium is potentiated by (approximately 35%) isoflurane or enflurane anaesthesia, the same initial atracurium besilate dose (0.3 to 0.6 mg/kg) may be used for intubation if given prior to the administration of these inhalation agents. However if the initial atracurium dose is administered after steady state anaesthesia with isoflurane or enflurane has been achieved, the dose of atracurium should be reduced by approximately one-third. Smaller dosage reductions may be considered with concomitant halothane anaesthesia since it has only a marginal (approximately 20%) potentiating effect on atracurium.

Maintenance doses

Intermittent IV injection: During prolonged surgical procedures neuromuscular blockade may be maintained with atracurium besilate maintenance doses of 0.1 to 0.2 mg/kg. Generally, under balanced anaesthesia, using maintenance doses of 0.1 mg/kg, the first maintenance dose is required within 20 to 45 minutes of the initial bolus dose, then typically at 15 to 25 minute intervals, however, the need for maintenance doses should be determined by the individual patient's requirements and response. Successive supplementary dosing does not give rise to accumulation of neuromuscular blocking effect.

Use as an infusion: After the initial atracurium bolus dose, neuromuscular blockade may be maintained during prolonged surgical procedures by administering atracurium besilate as a continuous intravenous infusion at a rate of 0.3 to 0.6 mg/kg/hour. The infusion should not be commenced until early spontaneous recovery from the initial atracurium bolus dose is evident.

Atracurium besilate infusion solutions may be prepared by admixing Atracurium Besilate Injection with an appropriate diluent (see below) to give an atracurium besilate concentration of 0.5 mg/ml to 5 mg/ml.

Atracurium Besilate Injection can be administered by infusion during cardiopulmonary bypass surgery at the recommended infusion rates. Induced hypothermia to a body temperature of 25 to 26°C reduces the rate of inactivation of atracurium, and therefore full neuromuscular block may be maintained with approximately half the original infusion rate at these temperatures.

Compatibility with infusion solutions: Atracurium Besilate Injection diluted to 0.5 mg/ml with the following infusion solutions, and stored at 30°C protected from light, was shown to be stable for the times stated below.

Infusion Solution	Period of stability
Sodium Chloride 0.9% Intravenous Infusion	24 hours
Glucose 5% Intravenous Infusion	24 hours
Glucose 4% and Sodium Chloride 0.18% Intravenous Infusion	24 hours
Ringer's Injection USP	24 hours
Compound Sodium Lactate Intravenous Infusion (Hartmann's Solution for Injection)	4 hours

Atracurium Besilate Injection diluted to 5 mg/ml with the following infusion solutions, and stored at 30°C protected from light in 50 ml plastic syringes, was shown to be stable for the times stated below.

Infusion Solution	Period of stability
Sodium Chloride 0.9% Intravenous Infusion	24 hours
Glucose 5% Intravenous Infusion	24 hours
Glucose 4% and Sodium Chloride 0.18% Intravenous Infusion	24 hours
Ringer's Injection USP	24 hours
Compound Sodium Lactate Intravenous Infusion (Hartmann's Solution for Injection)	8 hours

Reversal of neuromuscular blockade

The neuromuscular blockade induced by atracurium can be reversed with an anticholinesterase agent such as neostigmine or pyridostigmine, usually in conjunction with an anticholinergic agent such as atropine or glycopyrronium to prevent the adverse muscarinic effects of the anticholinesterase. Under balanced anaesthesia, reversal can usually be attempted approximately 20 to 35 minutes after the initial atracurium dose, or approximately 10 to 30 minutes after the last atracurium maintenance dose, when recovery of muscle twitch has started. Complete reversal of neuromuscular blockade is usually achieved within 8 to 10 minutes after administration of the reversing agents.

Rare instances of breathing difficulties, possibly related to incomplete reversal, have been reported following attempted pharmacological antagonism of atracurium induced neuromuscular blockade. As with other agents in this class, the tendency for residual neuromuscular block is increased if reversal is attempted at deep levels of blockade or if inadequate doses of reversal agents are employed.

Facilitation of mechanical ventilation in intensive care unit (ICU) patients

After an optional initial bolus dose of 0.3 to 0.6 mg/kg, neuromuscular block may be maintained by administering a continuous atracurium besilate infusion at rates of between 11 and 13 microgram/kg/min (0.65 to 0.78 mg/kg/hr). There may be wide inter-patient variability in dosage requirements and these may increase or decrease with time. Infusion rates as low as 4.5 microgram/kg/min (0.27 mg/kg/hr) or as high as 29.5 microgram/kg/min (1.77 mg/kg/hr) are required in some patients.

The rate of spontaneous recovery from neuromuscular block after infusion of atracurium besilate in ICU patients is independent of the duration of administration.

Spontaneous recovery to a train-of-four ratio >0.75 (the ratio of the height of the fourth to the first twitch in a train-of-four) can be expected to occur in approximately 60 minutes. A range of 32 to 108 minutes has been observed in clinical trials.

Dosage considerations

Use in children: The dosage in children over the age of 1 month is similar to that in adults on a body weight basis, however, large individual variability in the neuromuscular response in paediatric patients indicates that neuromuscular monitoring is essential.

Use in neonates: There are insufficient data to recommend a dose in neonates, however, this patient group is known to have increased sensitivity to non-depolarising muscle relaxants, and as a result it is advisable to reduce doses in this patient group.

Use in the elderly: The standard dose of atracurium may be used in elderly patients, however, it is recommended that it be administered slowly.

Use in patients with reduced renal and/or hepatic function: Standard dosages may be used at all levels of renal or hepatic function, including endstage failure.

Use in patients with cardiovascular disease: In patients with significant cardiovascular disease the initial dose of atracurium should be administered over a period of at least 60 seconds.

See also “Special warnings and special precautions for use”.

4.3 Contraindications

Known or suspected hypersensitivity to the product.

4.4 Special Warnings And Precautions For Use

Atracurium Besilate Injection should be used only by those skilled in the management of artificial respiration and only when facilities are immediately available for endotracheal intubation and for providing adequate ventilation support, including the administration of oxygen under positive pressure and the elimination of carbon dioxide. The clinician must be prepared to assist or control ventilation, and anticholinesterase agents should be immediately available for reversal of neuromuscular blockade.

Atracurium has no known effect on consciousness, pain threshold, or cerebration. In surgery, it should be used only with adequate general anaesthesia.

In common with other neuromuscular blocking agents, the potential for histamine release exists in susceptible patients during administration of atracurium besilate. Caution should be exercised in patients with a history suggestive of an increased sensitivity to the effects of histamine.

Do not give Atracurium Besilate Injection by intramuscular administration.

Atracurium Besilate Injection has an acid pH and therefore should not be mixed with alkaline solutions (e.g. barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same needle. Depending on the resultant pH of such mixtures, Atracurium Besilate Injection may be inactivated and a free acid may be precipitated.

When a small vein is selected as the injection site, Atracurium Besilate Injection should be flushed through the vein with physiological saline after injection. When other anaesthetic drugs are administered through the same indwelling needle or cannula as Atracurium Besilate Injection, it is important that each drug is flushed through with an adequate volume of physiological saline.

Atracurium may have profound effects in patients with myasthenia gravis, Eaton-Lambert syndrome, or other neuromuscular diseases in which potentiation of non-depolarising agents has been noted. A reduced dosage of atracurium and the use of a peripheral nerve stimulator for assessing neuromuscular blockade is especially important in these patients. Similar precautions should be taken in patients with severe electrolyte disorders.

Atracurium does not have significant vagal or ganglion blocking properties in the recommended dosage range. Consequently, atracurium will not counteract the bradycardia produced by many anaesthetic agents or by vagal stimulation during surgery. Therefore, bradycardia during anaesthesia may be more common with atracurium than with other muscle relaxants.

As with other non-depolarising neuromuscular blocking agents, resistance to atracurium may develop in patients suffering from burns. Such patients may require increased doses of atracurium depending on the time elapsed since the burn injury and the extent of the burn.

Atracurium Besilate Injection should be administered over a period of at least 60 seconds to patients who may be unusually sensitive to falls in arterial blood pressure, for example those who are hypovolaemic.

Atracurium Besilate Injection is hypotonic and must not be applied into the infusion line of a blood transfusion.

Monitoring of serial creatine phosphokinase (CPK) values should be considered in asthmatic patients receiving high dose corticosteroids and neuromuscular blocking agents in intensive care units.

Special precautions should be taken in patients with known anaphylactic reactions to curares, as cross-reactivity may be possible with this product.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

As with other non-depolarising neuromuscular blocking agents, the magnitude and/or duration of atracurium's effects may be increased as a result of an interaction with the following agents.

Inhalation anaesthetics: atracurium is potentiated by isoflurane, desflurane, sevoflurane and enflurane anaesthesia, and only marginally potentiated by halothane anaesthesia.

Antibiotics: including the aminoglycosides, polymyxins, spectinomycin, tetracyclines, lincomycin, clindamycin and vancomycin.

Anticonvulsants (acute administration only): phenytoin, carbamazepine.

Antiarrhythmic drugs: local anaesthetics such as lidocaine, procainamide, quinidine.

Beta-blockers: propranolol, oxprenolol

Antirheumatic drugs: chloroquine, d-penicillamine

Calcium channel blockers: diltiazem, nicardipine, nifedipine, verapamil.

Diuretics: frusemide, thiazides, acetazolamide and possibly mannitol.

Ganglion blocking agents: trimetaphan, hexamethonium.

Others: dantrolene, parenteral magnesium sulphate, chlorpromazine, steroids, ketamine, lithium salts and quinine.

Rarely, some of the above drugs may aggravate or unmask latent myasthenia gravis or actually induce a myasthenic syndrome. In these situations a consequent increased sensitivity to atracurium would be expected.

The administration of combinations of non-depolarising neuromuscular blocking agents in conjunction with atracurium may produce a degree of neuromuscular blockade in excess of that which might be expected were an equipotent total dose of atracurium administered. Any synergistic effect may vary between different drug combinations.

A depolarising muscle relaxant such as suxamethonium chloride should not be administered to prolong the neuromuscular blocking effects of non-depolarising blocking agents such as atracurium, as this may result in a prolonged and complex block which can be difficult to reverse with anticholinesterase drugs.

The prior use of suxamethonium reduces the onset (to maximum blockade) by approximately 2 to 3 minutes and may increase the depth of neuromuscular blockade induced by atracurium. Therefore, the initial atracurium dose should be reduced and the reduced dose should not be administered until the patient has recovered from the neuromuscular blocking effects of suxamethonium.

The use of intravenous corticosteroids with neuromuscular blocking agents has been reported to antagonise neuromuscular blockades. In addition, prolonged co-administration of these agents may increase the risk and/or severity of myopathy resulting in prolonged flaccid paralysis following discontinuation of the neuromuscular blocking agent. The myopathy is usually reversible with recovery in several months.

The onset of neuromuscular blockade is likely to be lengthened and the duration of blockade shortened in patients receiving chronic anticonvulsant therapy (e.g. carbamazepine, phenytoin). However, if the anticonvulsants are given acutely, the neuromuscular blocking effects may be increased.

In principle, maintaining neuromuscular monitoring until complete reversal of neuromuscular blockade should permit detection of most interactions. Nevertheless, recurrence of neuromuscular blockade may occur, for example, upon treatment with post surgical antibiotics.

4.6 Pregnancy And Lactation

Pregnancy

Atracurium crosses the placenta but there have been no demonstrated adverse effects in the foetus or newborn infant. Animal studies have indicated that atracurium has no adverse effects on foetal development. As with all neuromuscular blocking agents, the use of atracurium in the first three months of pregnancy should be avoided and it should not be used during the second and third trimesters unless clearly necessary.

Atracurium is suitable for maintenance of muscle relaxation during caesarean section as it does not cross the placenta in clinically significant amounts following recommended doses. In an open study, atracurium besilate (0.3 mg/kg) was administered to 26 pregnant women during delivery by caesarean section. No harmful effects were attributable to atracurium in any of the newborn infants, although small amounts of atracurium were shown to cross the placental barrier. The possibility of respiratory depression in the newborn infant should always be considered following caesarean section during which a neuromuscular blocking agent has been administered.

Anaesthesia during the third trimester of pregnancy exposes the mother to Mendelson syndrome (acid pneumopathy due to gastric acid aspiration). If a muscle relaxant is used at induction of anaesthesia, one should be chosen with a short onset and duration of action and low placental transfer and used in the lowest dose required to induce adequate neuromuscular relaxation. In patients receiving magnesium sulphate, the reversal of neuromuscular blockade may be unsatisfactory and the atracurium dose should be lowered as indicated.

Breastfeeding

Atracurium has a relatively high molecular weight and is highly ionized at physiologic pH, both factors that markedly reduce transfer into milk. In addition, even though milk is slightly more acidic than plasma, any atracurium transferred into milk would be rapidly degraded. Nevertheless, in view of the potential respiratory depressant effect on the neonate, especially if premature, it is recommended that if breastfeeding is started within 24 hours after administration of atracurium, the neonate is closely monitored.

4.7 Effects On Ability To Drive And Use Machines

It is not recommended to use potentially dangerous machinery or drive a car within 24 hours after full recovery from the neuromuscular blocking action of atracurium.

4.8 Undesirable Effects

As with most neuromuscular blocking agents, the potential exists for undesirable effects suggestive of histamine release in susceptible patients. In clinical trials involving 875 patients, reports of skin flushing ranged from 1% at doses up to 0.3 mg/kg, to 29% at doses of 0.6 mg/kg or greater. The incidence of transient hypotension ranged from 1 to 14% respectively for the corresponding dosages. Other undesirable effects reported included bronchospasm, tachycardia and rarely anaphylactoid reactions.

In large scale atracurium surveillance studies, undesirable effects considered possibly or probably related to atracurium were observed in approximately 10% of patients. Localised skin reactions, generalised flushing and hypotension each occurred in approximately 2 to 3% of patients. Hypertension, tachycardia and bradycardia were observed in approximately 1% of patients. Bronchospasm was reported in approximately 0.2% of patients.

The following undesirable effects have been reported for atracurium:

General: Allergic reactions (i.e. anaphylactic or anaphylactoid responses) which in rare instances were severe (e.g. shock, cardiac failure, cardiac arrest), angioneurotic oedema.

Musculoskeletal: Inadequate block, prolonged block.

Cardiovascular: Hypotension, hypertension, vasodilatation (flushing), tachycardia, bradycardia, hypoxaemia.

Respiratory: Dyspnoea, bronchospasm, laryngospasm, wheezing.

Dermatological: Rash, urticaria, generalised erythema, skin flushing, reaction at injection site.

After prolonged administration of atracurium besilate in severely ill patients under intensive care, some incidences of muscle weakness and/or myopathy occurred. Most patients were concomitantly treated with corticosteroids. A causal relationship with atracurium therapy has not been established.

There have been rare reports of seizures in ICU patients who have been receiving atracurium concurrently with several other agents. These patients usually had one or more medical conditions predisposing to seizures (e.g. cranial trauma, cerebral oedema, viral encephalitis, hypoxic encephalopathy, uraemia). In clinical trials, there appears to be no correlation between plasma laudanosine concentration and the occurrence of seizures.

4.9 Overdose

Prolonged muscle paralysis and its consequences are the main signs of overdose.

There is limited experience with atracurium overdosage following parenteral administration. The possibility of iatrogenic overdosage can be minimised by carefully monitoring muscle twitch response to peripheral nerve stimulation. Excessive doses of atracurium are likely to produce symptoms consistent with extensions of the usual pharmacological effects. Overdosage may increase the risk of histamine release and adverse cardiovascular effects, especially hypotension. If cardiovascular support is necessary, this should include proper positioning, fluid administration, and the use of vasopressor agents if necessary. It is essential to maintain a patent airway with assisted positive pressure ventilation until spontaneous respiration is adequate. Full sedation will be required since consciousness is not impaired. The duration of neuromuscular blockade may be prolonged and a peripheral nerve stimulator should be used to monitor recovery. Recovery may be hastened by the administration of an anticholinesterase agent such as neostigmine or pyridostigmine in conjunction with an anticholinergic agent such as atropine, once evidence of spontaneous recovery is present.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Atracurium besilate is a non-depolarising neuromuscular blocking agent (ATC code M03A C04) with an intermediate duration of action, administered intravenously to produce skeletal muscle relaxation.

Non-depolarising neuromuscular blocking agents antagonise the action of the neurotransmitter acetylcholine by competitively binding with cholinergic receptor sites on the motor endplate of the myoneural junction. These effects may be inhibited or reversed by the administration of anticholinesterases such as neostigmine or pyridostigmine.

As with other non-depolarising neuromuscular blocking agents, the time to onset or paralysis is reduced, and the duration of maximum effect prolonged, with increasing atracurium doses.

Once recovery from atracurium's neuromuscular blocking effect begins, it proceeds more rapidly than recovery from tubocurarine, alcuronium, and pancuronium. Regardless of the atracurium dose, the time from start of recovery (from complete block) to complete recovery (as measured by restoration of the tetanic response to 95% of normal) is approximately 30 minutes under balanced anaesthesia, and approximately 40 minutes under halothane, enflurane or isoflurane anaesthesia. Repeated doses have no cumulative effect on recovery rate.

With initial atracurium besilate doses up to 0.5 mg/kg, plasma histamine levels were shown to increase by 15% in a dose dependant way, but haemodynamic changes were minor within this dose range. Following the administration of 0.6 mg/kg of atracurium besilate, histamine levels were shown to increase by 92%, and were shown to correlate with a transient (5 minutes) decrease in blood pressure and a brief (2 to 3 minutes) episode of skin flushing. While these effects are of little clinical significance in most patients, the possibility of substantial histamine release at recommended doses must be considered in sensitive individuals, or in patients in whom substantial histamine release would be especially hazardous (e.g. patients with significant respiratory or cardiovascular disease).

Studies in malignant hyperthermia-susceptible pigs indicated that atracurium besilate does not trigger this syndrome. Clinical studies in patients with a history of malignant hyperthermia revealed the same results.

Atracurium besilate does not appear to affect intraocular pressure, therefore, it is a suitable agent for ophthalmic surgery.

5.2 Pharmacokinetic Properties

The pharmacokinetics of atracurium besilate in humans are essentially linear within the dose range of 0.3 to 0.6 mg/kg. The elimination half-life is approximately 20 minutes. The protein binding of atracurium is approximately 82%. The volume of distribution of atracurium is 0.16 l/kg and plasma clearance of atracurium is about 6.5 ml/min/kg. Some placental transfer occurs in humans. The umbilical venous to maternal venous drug concentration ratios are between 0.03 and 0.33 (mean 0.12+/- 0.04).

The duration of neuromuscular blockade produced by atracurium does not correlate with plasma pseudocholinesterase levels and is not altered by the absence of renal function.This is consistent with the results of in vitro studies which have shown that atracurium is inactivated in plasma via two non-oxidative pathways: ester hydrolysis, catalysed by non-specific esterases; and Hofmann elimination, a non-enzymatic chemical process which occurs at physiological pH and body temperature. The rate of Hofmann elimination, which is the principal route of elimination for atracurium, is increased at a higher pH or at higher temperatures, and reduced at a lower pH or lower temperatures.

Limited clinical experience on long term administration of atracurium besilate show only minimal effects of haemofiltration or haemodialysis on plasma levels of atracurium and its metabolites. The effects of haemoperfusion on plasma levels of atracurium and its metabolites are not known.

5.3 Preclinical Safety Data

Carcinogenicity / Mutagenicity: Carcinogenicity studies have not been performed. Atracurium yielded negative results for gene mutation in bacteria, and chromosomal damage in bone marrow of rats. A positive response in the mouse lymphoma assay was observed only at highly cytotoxic concentrations. This single positive response is not considered to be of clinical relevance.

Reproductive toxicity:. Animal studies have indicated that atracurium has no adverse effect on foetal development.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzenesulphonic acid

Water for Injections

6.2 Incompatibilities

Atracurium Besilate Solution for Injection has an acid pH and therefore should not be mixed with alkaline solutions (e.g. barbiturate solutions) in the same syringe or administered simultaneously during intravenous infusion through the same needle.

6.3 Shelf Life

As packaged for sale – 18 months.

In use – see 4.2 for information on chemical and physical stability following dilution with a number of infusion solutions. However, from a microbiological point of view, the product should be used immediately. If not used immediately, in use storage times and conditions prior to use are the responsibility of the user.

Discard residue immediately after use.

6.4 Special Precautions For Storage

Store in a refrigerator (2°C - 8°C).

Do not freeze.

Keep container in the outer carton.

6.5 Nature And Contents Of Container

2.5 ml: Type I glass ampoule in packs of 5 ampoules.

5 ml: Type I glass ampoule in packs of 5 ampoules.

25 ml: Type I glass vial with rubber stopper in packs of 1 vial.

6.6 Special Precautions For Disposal And Other Handling

Contains no preservative. Discard residue immediately after use.

Do not use if cloudiness or precipitate is observed.

7. Marketing Authorisation Holder

Hospira UK Limited

Queensway

Royal Leamington Spa

Warwickshire

CV31 3RW

UK

8. Marketing Authorisation Number(S)

PL 04515/0099

9. Date Of First Authorisation/Renewal Of The Authorisation

15 October 1996/14 October 2006

10. Date Of Revision Of The Text

April 2008

metformin and saxagliptin

Generic Name: metformin and saxagliptin (met FOR min and SAX a GLIP tin)

Brand Names: Kombiglyze XR

What is metformin and saxagliptin?

Metformin and saxagliptin are oral diabetes medicines that help control blood sugar levels. Metformin works by decreasing glucose (sugar) production in the liver and decreasing absorption of glucose by the intestines. Saxagliptin works by regulating the levels of insulin your body produces after eating.

The combination of metformin and saxagliptin is used to treat type 2 diabetes. This medication is not for treating type 1 diabetes.

Metformin and saxagliptin may also be used for purposes not listed in this medication guide.

What is the most important information I should know about metformin and saxagliptin?

You should not use this medication if you are allergic to metformin (Actoplus Met, Avandamet, Fortamet, Glucophage, Riomet) or saxagliptin (Onglyza), if you have kidney disease, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

If you need to have surgery or any type of x-ray or CT scan using a dye that is injected into your veins, you will need to temporarily stop taking metformin and saxagliptin.

Some people develop lactic acidosis while taking metformin. Early symptoms may get worse over time and this condition can be fatal. Get emergency medical help if you have: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, slow or irregular heart rate, dizziness, or feeling very weak or tired.

What should I discuss with my healthcare provider before taking metformin and saxagliptin?

Some people develop a life-threatening condition called lactic acidosis while taking metformin. You may be more likely to develop lactic acidosis if you have liver or kidney disease, heart attack or congestive heart failure, a severe infection, if you are dehydrated, or if you drink large amounts of alcohol. Do not use this medication if you are allergic to metformin (Actoplus Met, Avandamet, Fortamet, Glucophage, Riomet) or saxagliptin (Onglyza), if you have kidney disease, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

If you need to have surgery or any type of x-ray or CT scan using a dye that is injected into your veins, you will need to temporarily stop taking metformin and saxagliptin. Be sure your caregivers know ahead of time that you are using this medication.

To make sure you can safely take metformin and saxagliptin, tell your doctor if you have any of these other conditions:

• 
  

  liver disease;

  
  


• 
  

  heart disease; or

  
  


• 
  

  if you are over 80 years old;

  
  

Certain oral diabetes medications may increase your risk of serious heart problems. However, not treating your diabetes can damage your heart and other organs. Talk to your doctor about the risks and benefits of treating your diabetes with metformin and saxagliptin. 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. It is not known whether metformin and saxagliptin passes into breast milk or if it could harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I take metformin and saxagliptin?

Take exactly as prescribed by your doctor. Do not take in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. Your blood sugar will need to be checked often, and you may need other blood tests at your doctor's office.

Take metformin and saxagliptin with a meal. Do not crush, chew, or break an extended-release tablet. Swallow it whole. Breaking the pill may cause too much of the drug to be released at one time. Know the signs of low blood sugar (hypoglycemia) and how to recognize them: headache, hunger, weakness, sweating, tremor, irritability, or trouble concentrating.

Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection.

Check your blood sugar carefully during a time of stress or illness, if you travel, exercise more than usual, drink alcohol, or skip meals. These things can affect your glucose levels and your dose needs may also change.

Ask your doctor how to adjust your metformin and saxagliptin dose if needed. Do not change your medication dose or schedule without your doctor's advice.

Metformin and saxagliptin is only part of a complete program of treatment that may also include diet, exercise, weight control, foot care, and eye care. Follow your diet, medication, and exercise routines very closely.

Store at room temperature away from moisture and heat.

See also: Metformin and saxagliptin dosage (in more detail)

What happens if I miss a dose?

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

What happens if I overdose?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. You may have signs of low blood sugar, such as extreme weakness, blurred vision, sweating, trouble speaking, tremors, stomach pain, confusion, and seizure (convulsions). An overdose of metformin may cause lactic acidosis. Get emergency medical help if you have: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting.

What should I avoid while taking metformin and saxagliptin?

Avoid drinking alcohol. It lowers blood sugar and may increase your risk of lactic acidosis.

Metformin and saxagliptin side effects

This medication may cause lactic acidosis (a build-up of lactic acid in the body, which can be fatal). Lactic acidosis can start slowly and get worse over time. Get emergency medical help if you have even mild symptoms of lactic acidosis, such as: muscle pain or weakness, numb or cold feeling in your arms and legs, trouble breathing, stomach pain, nausea with vomiting, slow or irregular heart rate, dizziness, or feeling very weak or tired. Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medicine and call your doctor at once if you have a serious side effect such as:

• 
  

  severe pain in your upper stomach spreading to your back, nausea and vomiting, fast heart rate;

  
  


• 
  

  pain or burning when you urinate; or

  
  


• 
  

  swelling or rapid weight gain.

  
  

Less serious side effects may include:

• 
  

  diarrhea, mild nausea;

  
  


• 
  

  headache; or

  
  


• 
  

  cold symptoms such as runny or stuffy nose, sneezing, sore throat.

  
  

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.

Metformin and saxagliptin Dosing Information

Usual Adult Dose for Diabetes Mellitus Type II:

The dosage of metformin-saxagliptin should be individualized on the basis of the patient's current regimen, effectiveness, and tolerability. Metformin-saxagliptin should generally be administered once daily with the evening meal, with gradual dose titration to reduce the gastrointestinal side effects associated with metformin.

Patients not currently treated with metformin: Metformin-saxagliptin 500 mg-5 mg orally once daily with gradual dose escalation to reduce the gastrointestinal side effects due to metformin.

Patients currently treated with metformin: The dose of metformin-saxagliptin should provide metformin at the dose already being taken, or the nearest therapeutically appropriate dose. Following a switch from metformin immediate-release to metformin extended release, glycemic control should be closely monitored and dosage adjustments made according.

The maximum daily recommended dose is 5 mg for saxagliptin and 2000 mg for metformin extended-release.

Patients who need 2.5 mg saxagliptin and who require a dose of metformin lower than 1000 mg or higher than 1000 mg should use the individual components.

The maximum recommended dose of saxagliptin is 2.5 mg once daily when coadministered with strong cytochrome P450 3A4/5 (CYP450 3A4/5) inhibitors (e.g., ketoconazole, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). For these patients, limit the metformin-saxagliptin dose to 2.5 mg/1000 mg once daily.

What other drugs will affect metformin and saxagliptin?

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

• 
  

  another oral diabetes medication such as glipizide (Glucotrol, Metaglip), glimepiride (Amaryl, Avandaryl, Duetact), glyburide (DiaBeta, Micronase, Glucovance), and others;

  
  


• 
  

  an antibiotic such as clarithromycin (Biaxin), dalfopristin/quinupristin (Synercid), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), telithromycin (Ketek), trimethoprim (Proloprim, Primsol, Bactrim, Cotrim, Septra), or vancomycin (Vancocin, Lyphocin);

  
  


• 
  

  antifungal medication such as clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Nizoral), or voriconazole (Vfend);

  
  


• 
  

  heart or blood pressure medication such as amiloride (Midamor), digoxin (Lanoxin), diltiazem (Cartia, Cardizem), furosemide (Lasix), nifedipine (Nifedical), procainamide (Procan, Pronestyl, Procanbid), quinidine (Quin-G), triamterene (Dyrenium), and others; or

  
  


• 
  

  HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), or ritonavir (Norvir, Kaletra).

  
  

You may be more likely to have hyperglycemia (high blood sugar) if you take metformin and saxagliptin with other drugs that can raise blood sugar, such as:

• 
  

  diuretics (water pills);

  
  


• 
  

  steroids (prednisone and others);

  
  


• 
  

  niacin (Advicor, Niaspan, Niacor, Simcor, Slo-Niacin, and others);

  
  


• 
  

  phenothiazines (Compazine and others);

  
  


• 
  

  thyroid medicine (Synthroid and others);

  
  


• 
  

  birth control pills and other hormones;

  
  


• 
  

  seizure medicines (Dilantin and others); or

  
  


• 
  

  diet pills or medicines to treat asthma, colds or allergies.

  
  

You may be more likely to have hypoglycemia (low blood sugar) if you take metformin and saxagliptin with other drugs that can lower blood sugar, such as:

• 
  

  some nonsteroidal anti-inflammatory drugs (NSAIDs);

  
  


• 
  

  aspirin or other salicylates (including Pepto-Bismol);

  
  


• 
  

  a blood thinner (warfarin, Coumadin and others);

  
  


• 
  

  heart or blood pressure medication (Accupril, Altace, Lotensin, Prinivil, Vasotec, Zestril, and others);

  
  


• 
  

  sulfa drugs (Bactrim, Septra, Sulfatrim, SMX-TMP, and others);

  
  


• 
  

  a monoamine oxidase inhibitor (MAOI); or

  
  


• 
  

  other oral diabetes medications, especially acarbose (Precose), metformin (Glucophage), miglitol (Glyset), pioglitazone (Actos), or rosiglitazone (Avandia).

  
  

These lists are not complete and there are many other medicines that can increase or decrease the effects of metformin and saxagliptin on lowering your blood sugar. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

More metformin and saxagliptin resources

• Metformin and saxagliptin Dosage
• Metformin and saxagliptin Use in Pregnancy & Breastfeeding
• Metformin and saxagliptin Drug Interactions
• Metformin and saxagliptin Support Group
• 1 Review for Metformin and saxagliptin - Add your own review/rating

Compare metformin and saxagliptin with other medications

• Diabetes, Type 2

Where can I get more information?

• Your pharmacist can provide more information about metformin and saxagliptin.

Fluarix 2010-2011 injection

Generic Name: influenza virus vaccine (injection) (in floo ENZ a VYE rus VAK seen)

Brand Names: Afluria 2011-2012, Afluria Preservative-Free 2011-2012, Fluarix 2010-2011, Fluarix 2011-2012, FluLaval 2011-2012, Fluvirin 2011-2012, Fluvirin Preservative-Free 2011-2012, Fluzone 2011-2012, Fluzone High-Dose 2011-2012, Fluzone Intradermal 2011-2012, Fluzone Preservative-Free 2011-2012, Fluzone Preservative-Free Pediatric 2011-2012

What is influenza virus vaccine?

Influenza virus (commonly known as "the flu") is a serious disease caused by a virus. Influenza virus can spread from one person to another through small droplets of saliva that are expelled into the air when an infected person coughs or sneezes. The virus can also be passed through contact with objects the infected person has touched, such as a door handle or other surfaces.

Influenza virus vaccine is used to prevent infection caused by influenza virus. The vaccine is redeveloped each year to contain specific strains of inactivated (killed) flu virus that are recommended by public health officials for that year.

The injectable influenza virus vaccine (flu shot) is a "killed virus" vaccine. Influenza virus vaccine is also available in a nasal spray form, which is a "live virus" vaccine.

Influenza virus vaccine works by exposing you to a small dose of the virus, which helps your body to develop immunity to the disease. Influenza virus vaccine will not treat an active infection that has already developed in the body.

Influenza virus vaccine is for use in adults and children who are at least 6 months old.

Becoming infected with influenza is much more dangerous to your health than receiving this vaccine. Influenza causes thousands of deaths each year, and hundreds of thousands of hospitalizations. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

Like any vaccine, influenza virus vaccine may not provide protection from disease in every person. This vaccine will not prevent illness caused by avian flu ("bird flu").

What is the most important information I should know about this vaccine?

The injectable influenza virus vaccine (flu shot) is a "killed virus" vaccine. Influenza virus vaccine is also available in a nasal spray form, which is a "live virus" vaccine. This medication guide addresses only the injectable form of this vaccine.

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving this vaccine.

Keep track of any and all side effects you have after receiving this vaccine. If you ever need to receive influenza virus vaccine in the future, you will need to tell your doctor if the previous shot caused any side effects.

Like any vaccine, influenza virus vaccine may not provide protection from disease in every person. This vaccine will not prevent illness caused by avian flu ("bird flu").

Influenza virus injectable (killed virus) vaccine will not cause you to become ill with the flu virus that it contains. However, you may have flu-like symptoms at any time during flu season that may be caused by other strains of influenza virus.

Becoming infected with influenza is much more dangerous to your health than receiving this vaccine. However, like any medicine, this vaccine can cause side effects but the risk of serious side effects is extremely low.

What should I discuss with my healthcare provider before receiving this vaccine?

You should not receive this vaccine if you have ever had an allergic reaction to a flu vaccine, or if you have:

• 
  

  an active or uncontrolled neurologic disorder (such as Parkinson's disease, Alzheimer's disease, or epilepsy);

  
  


• 
  

  a history of seizures;

  
  


• 
  

  a history of Guillian-Barre syndrome (within 6 weeks after receiving a vaccine);

  
  


• 
  

  if you are allergic to eggs.

  
  

To make sure you can safely receive this vaccine, tell your doctor if you have any of these other conditions:

• 
  

  a bleeding or blood clotting disorder such as hemophilia or easy bruising;

  
  


• 
  

  a neurologic disorder or disease affecting the brain (or if this was a reaction to a previous vaccine);

  
  


• 
  

  a weak immune system caused by disease, bone marrow transplant, or by using certain medicines or receiving cancer treatments; or

  
  


• 
  

  if you are allergic to latex rubber.

  
  

You can still receive a vaccine if you have a minor cold. In the case of a more severe illness with a fever or any type of infection, wait until you get better before receiving this vaccine.

Vaccines may be harmful to an unborn baby and generally should not be given to a pregnant woman. However, not vaccinating the mother could be more harmful to the baby if the mother becomes infected with a disease that this vaccine could prevent. Your doctor will decide whether you should receive this vaccine, especially if you have a high risk of infection with influenza. It is not known whether influenza virus vaccine passes into breast milk or if it could harm a nursing baby. Do not receive this vaccine without telling your doctor if you are breast-feeding a baby. This vaccine should not be given to a child younger than 6 months old.

How is this vaccine given?

Some brands of this vaccine are made for use in adults and not in children. Your child's doctor can recommend the best influenza virus vaccine for your child.

This vaccine is given as an injection (shot) into a muscle. You will receive this injection in a doctor's office or other clinic setting.

You should receive a flu vaccine every year. Your immunity will gradually decrease over the 12 months after you receive the influenza virus vaccine. Children receiving this vaccine may need a booster shot one month after receiving the first vaccine.

The influenza virus vaccine is usually given in October or November. Some people may need to have their vaccines earlier or later. Follow your doctor's instructions.

Your doctor may recommend treating fever and pain with an aspirin-free pain reliever such as acetaminophen (Tylenol) or ibuprofen (Motrin, Advil, and others) when the shot is given and for the next 24 hours. Follow the label directions or your doctor's instructions about how much of this medicine to give your child.

It is especially important to prevent fever from occurring in a child who has a seizure disorder such as epilepsy.

What happens if I miss a dose?

Since flu shots are usually given only one time per year, you will most likely not be on a dosing schedule. Call your doctor if you forget to receive your yearly flu shot in October or November.

If your child misses a booster dose of this vaccine, call your doctor for instructions.

What happens if I overdose?

An overdose of this vaccine is unlikely to occur.

What should I avoid before or after receiving this vaccine?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Influenza virus injectable vaccine side effects

Influenza virus injectable (killed virus) vaccine will not cause you to become ill with the flu virus that it contains. However, you may have flu-like symptoms at any time during flu season that may be caused by other strains of influenza virus.

You should not receive a booster vaccine if you had a life-threatening allergic reaction after the first shot. Keep track of any and all side effects you have after receiving this vaccine. If you ever need to receive influenza virus vaccine in the future, you will need to tell your doctor if the previous shot caused any side effects. Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Call your doctor at once if you have a serious side effect such as:

• 
  

  severe weakness or unusual feeling in your arms and legs (may occur 2 to 4 weeks after you receive the vaccine);

  
  


• 
  

  high fever;

  
  


• 
  

  seizure (convulsions); or

  
  


• 
  

  unusual bleeding.

  
  

Less serious side effects may include:

• 
  

  low fever, chills;

  
  


• 
  

  mild fussiness or crying;

  
  


• 
  

  redness, bruising, pain, swelling, or a lump where the vaccine was injected;

  
  


• 
  

  headache, tired feeling; or

  
  


• 
  

  joint or muscle pain.

  
  

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 vaccine side effects to the US Department of Health and Human Services at 1-800-822-7967.

What other drugs will affect influenza virus injectable vaccine?

Before receiving this vaccine, tell your doctor if you are using phenytoin (Dilantin), theophylline (Respbid, Slo-Bid, Theodur, Uniphyl), or a blood thinner (warfarin, Coumadin, Jantoven).

Also tell the doctor if you have recently received drugs or treatments that can weaken the immune system, including:

• 
  

  an oral, nasal, inhaled, or injectable steroid medicine;

  
  


• 
  

  medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders, such as azathioprine (Imuran), etanercept (Enbrel), leflunomide (Arava), and others; or

  
  


• 
  

  medicines to treat or prevent organ transplant rejection, such as basiliximab (Simulect), cyclosporine (Sandimmune, Neoral, Gengraf), muromonab-CD3 (Orthoclone), mycophenolate mofetil (CellCept), sirolimus (Rapamune), or tacrolimus (Prograf).

  
  

If you are using any of these medications, you may not be able to receive the vaccine, or may need to wait until the other treatments are finished.

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

More Fluarix 2010-2011 resources

• Fluarix 2010-2011 Side Effects (in more detail)
• Fluarix 2010-2011 Use in Pregnancy & Breastfeeding
• Fluarix 2010-2011 Drug Interactions
• Fluarix 2010-2011 Support Group
• 0 Reviews for Fluarix 2010-2011 - Add your own review/rating

Compare Fluarix 2010-2011 with other medications

• Influenza Prophylaxis

Where can I get more information?

• Your doctor or pharmacist can provide more information about this vaccine. Additional information is available from your local health department or the Centers for Disease Control and Prevention.

See also: Fluarix 2010-2011 side effects (in more detail)