Marvelon (Organon Laboratories Limited)

1. Name Of The Medicinal Product

Marvelon

2. Qualitative And Quantitative Composition

Desogestrel B.P. 150 micrograms

Ethinylestradiol Ph. Eur 30 micrograms

3. Pharmaceutical Form

Tablets

4. Clinical Particulars

4.1 Therapeutic Indications

Oral contraception.

4.2 Posology And Method Of Administration

4.2.1 How to take Marvelon

One tablet is taken daily at the same time,(preferably in the evening) without interruption for 21 days, followed by a break of 7 tablet-free days. Each subsequent pack is started after the 7 tablet-free days have elapsed. Additional contraceptive precautions are not then required.

4.2.2 How to start Marvelon

It is preferable that tablet intake from the first pack is started on the first day of menstruation in which case no extra contraceptive precautions are necessary.

If menstruation has already begun, (that is 2, 3, or 4 days previously), tablet taking should commence on day 5 of the menstrual period. In this case additional contraceptive precautions must be taken for the first 7 days of tablet taking.

If menstruation began more than 5 days previously then the patient should be advised to wait until her next menstrual period before starting to take Marvelon.

Post-Partum Administration

Following childbirth oral contraceptive administration to non-breast feeding mothers should be started 21 days post-partum in which case no additional contraceptive precautions are required.

If intercourse has taken place post-partum, oral contraceptive use should be delayed until the first day of the first menstrual period.

If post-partum administration of Marvelon begins more than 21 days after delivery then additional contraceptive precautions are required for the first 7 days.

N.B. Mothers who are breast feeding should be advised not to use the combined pill since this may reduce the amount of breast-milk, but may be advised instead to use a progestogen-only pill (POP).

After miscarriage or abortion administration should start immediately in which case no additional contraceptive precautions are required.

Changing from a 21 day pill or another 22 day pill to Marvelon:

All tablets in the old pack should be finished. The first Marvelon tablet is taken the next day i.e. no gap is left between taking tablets nor does the patient need to wait for her period to begin. Tablets should be taken as instructed in 'How to take Marvelon'. Additional contraceptive precautions are not required. The patient will not have a period until the end of the first Marvelon pack, but this is not harmful, nor does it matter if she experiences some bleeding on tablet-taking days.

Changing from a combined Every Day Pill (28 day tablets) to Marvelon:

Marvelon should be started after taking the last active tablet from the 'Every Day Pill' pack (i.e. after taking 21 or 22 tablets). The first Marvelon tablet is taken the next day i.e. no gap is left between taking tablets nor does the patient need to wait for her period to begin. One tablet is taken daily at the same time, without interruption for 21 days, followed by a 7 day tablet-free period. Each subsequent pack is started after the 7 day tablet-free period has elapsed. Additional contraceptive precautions are not required. Remaining tablets from the Every Day (ED) pack should be discarded. The patient will not have a period until the end of the first Marvelon pack, but this is not harmful, nor does it matter if she experiences some bleeding on tablet-taking days.

Changing from a Progestogen-only Pill (POP or Mini Pill) to Marvelon:

The first Marvelon tablet should be taken on the first day of the period, even if the patient has already taken a mini pill on that day. One tablet is taken daily at the same time, without interruption for 21 days, followed by a 7 day tablet-free period. Each subsequent pack is started after the 7 day tablet-free period has elapsed. Additional contraceptive precautions are not then required. All the remaining progestogen-only pills in the mini pill pack should be discarded.

If the patient is taking a (mini) pill, then she may not always have a period, especially when she is breast feeding. The first Marvelon tablet should be taken on the day after stopping the mini pill. All remaining pills in the mini pill packet must be discarded. Additional contraceptive precautions must be taken for the first seven days.

ADDITIONAL CONTRACEPTIVE PRECAUTIONS When additional contraceptive precautions are required the patient should be advised either not to have sex, or to use a cap plus spermicide, or for her partner to use a condom. Rhythm methods should not be advised as the pill disrupts the usual cyclical changes associated with the natural menstrual cycle e.g. changes in temperature and cervical mucus.

4.2.3 How to skip a period

To skip a period, a new pack of Marvelon should be started on the day after finishing the current pack (the patient skips the tablet-free days). Tablet-taking should be continued in the usual way. During the use of the second pack she may experience slight spotting or break-through bleeding but contraceptive protection will not be diminished provided there are no tablet omissions. The next pack of Marvelon is started after the usual 7 tablet-free days, regardless of whether the period has completely finished or not.

4.2.4 Advice in case of missed pills

The reliability of Marvelon may be reduced if tablets are forgotten:

If the forgotten tablet is taken within 12 hours, no further precautions are necessary, further tablets should be taken at the usual time.

If one or more tablets are forgotten for more than 12 hours, contraceptive protection will be reduced. The patient should take the last forgotten tablet, even if this means taking two tablets in one day, and then continue to take tablets at the normal time. Additional contraceptive precautions should be taken for the next seven days, and the patient should follow 'the 7-day rule'. (See section 4.4; Special warnings and special precautions for use: Reduced Reliability).

4.2.5 Advice in case of Vomiting or Diarrhoea

If after tablet intake vomiting or diarrhoea occurs, a tablet may not be absorbed properly by the body. If the symptoms disappear within 12 hours of tablet-taking, the patient should take an extra tablet from a spare pack and continue with the rest of the pack as usual. However, if the symptoms continue beyond those 12 hours, additional contraceptive precautions are necessary for any sexual intercourse during the stomach or bowel upset and for the following 7 days (the patient must be advised to follow '7-day rule'). (See section 4.4; Special warnings and special precautions for use: Reduced Reliability).

4.3 Contraindications

• Pregnancy or suspected pregnancy (that cannot yet be excluded) or breast feeding.

• Moderate to severe hypertension

• Hyperlipoproteinaemia

• Arterial thrombosis present or in history (e.g. myocardial infarction, cerebrovascular accident).

• In addition the presence of more than one of the risk factors for arterial disease (See 4.4 Special warnings and special precautions for use; The Pill and Thrombosis).

• History of confirmed venous thromboembolism (VTE); Family history of idiopathic VTE. Other known risk factors for VTE. (See 4.4 Special warnings and special precautions for use; The Pill and Thrombosis).

• Diabetes mellitus with vascular involvement

• Severe liver disease, cholestatic jaundice or hepatitis (viral or non-viral), or a history of these conditions if the results of liver function tests have failed to return to normal, and for 3 months after liver function tests have been found to be normal; a history of jaundice of pregnancy or jaundice due to the use of steroids, Rotor syndrome and Dubin-Johnson syndrome, hepatic cell tumours and porphyria.

• Cholelithiasis

• Known or suspected estrogen-dependent tumours, (See 4.4 Special warnings and special precautions for use: The Pill and Cancer); endometrial hyperplasia; undiagnosed vaginal bleeding.

• Systemic lupus erythematosus or a history of this condition.

• A history during pregnancy or previous use of steroids of:

• severe pruritis • pemphigoid gestationis • jaundice • a manifestation or deterioration of otosclerosis

• Hypersensitivity to any of the components of Marvelon

4.4 Special Warnings And Precautions For Use

Relative Contraindications

If any of the conditions listed below is present, the benefits of COC use must be weighed against the possible risks for each individual woman and discussed with her before she decides to start using it. The patient should be kept under close supervision. In case of aggravation, exacerbation or appearance of any of these conditions or risk factors whilst the patient is taking the Pill, it's use should be discontinued, alternative non-hormonal methods of contraception used (not rhythm or temperature methods) and medical advice sought without delay.

• Disorders of coagulation.

• Other conditions associated with an increased risk of circulatory disease such as latent or overt cardiac failure, renal dysfunction, or a history of these conditions.

• Epilepsy or a history of this condition.

• Migraine or a history of this condition.

• A history of cholelithiasis.

• Presence of any risk factor for estrogen-dependent tumours; estrogen-sensitive gynaecological disorders such as uterine fibromyomata and endometriosis (See below; The Pill and cancer).

• Diabetes mellitus.

• Severe depression or a history of this condition. If this is accompanied by a disturbance in tryptophan metabolism, administration of vitamin B6 might be of therapeutic value.

• Sickle cell haemoglobinopathy, since under certain circumstances, e.g. during infections or anoxia, estrogen-containing preparations may induce thromboembolic process in patients with this condition.

• If the results of liver function tests become abnormal, use should be discontinued.

The Pill and Thrombosis

• Some epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism. These events occur rarely.

• An increased risk of venous thromboembolic disease (VTE) associated with the use of oral contraceptives is well established. The excess risk of VTE is highest during the first year a woman ever uses a combined oral contraceptive. It is smaller than the risk associated with pregnancy, which has been estimated at 60 cases per 100,000 pregnancies. 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 second generation pills is about 15 per 100,000 women per year. 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 for VTE such as obesity.

• Thrombosis has very rarely been reported to occur in other veins or arteries, e.g. hepatic, mesenteric, renal or retinal, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.

• The risk of thromboembolism (venous and/or arterial) increases with:

- age

- smoking (with heavier smoking and increasing age the risk further increases, especially in women over 35 years of age)

- a positive family history (i.e. venous or arterial thromboembolism ever in a sibling or parent at a relatively early age). If a hereditary predisposition is suspected, the woman should be referred to a specialist for advice before deciding about any COC use

- obesity (body mass index over 30kg/m²)

- dyslipoproteinaemia,

- hypertension

- valvular heart disease

- atrial fibrillation

- diabetes

- prolonged immobilisation, major surgery, any surgery to the legs, or major trauma. In these situations it is advisable to discontinue COC use (in the case of elective surgery at least four weeks in advance) and not to resume until two weeks after complete remobilisation.

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

• The increased risk of thromboembolism in the puerperium must be considered.

• Other medical conditions which have been associated with adverse circulatory events include diabetes mellitus, systemic lupus erythematosus, haemolytic uraemic syndrome, chronic inflammatory bowel disease (Crohn's disease or ulcerative colitis) and sickle cell disease.

• An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC.

• Biochemical factors that may be indicative of hereditary or acquired predisposition for venous or arterial thrombosis include Activated Protein C (APC) resistance, hyper homocysteinaemia, antithrombin-III deficiency, protein C deficiency, protein S deficiency, antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant).

• When considering risk/benefit the physician should take into account that adequate treatment of a condition may reduce the associated risk of thrombosis and that the risk associated with pregnancy is higher than that associated with COC use.

• Signs and symptoms of a thrombotic event may include:

• sudden severe pain in the chest, whether or not reaching to the left arm; • sudden breathlessness; • any unusual severe, prolonged headache, especially if it occurs for the first time or gets progressively worse, or is associated with any of the following symptoms:

- sudden partial or complete loss of vision or diplopia - aphasia - vertigo - a bad fainting attack - collapse with or without focal epilepsy - weakness or very marked numbness suddenly affecting one side or one part of the body - motor disturbances - severe pain in the calf of one leg - 'acute' abdomen.

The Pill and Cancer

• The use of estrogen-containing oral contraceptives may promote growth of existing sex steroid dependent tumours. For this reason, the use of these oral contraceptives in patients with such tumours is contraindicated.

• 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).

Estimated cumulative numbers of breast cancers per 10,000 women diagnosed in 5 years of use and up to 10 years after stopping COCs, compared with numbers of breast cancers diagnosed in 10,000 women who had never used COCs

• Malignant hepatic tumours have been reported on rare occasions in long-term users of oral contraceptives. Benign hepatic tumours have also been associated with oral contraceptive usage. A hepatic tumour should be considered in the differential diagnosis when upper abdominal pain, enlarged liver or signs of intra-abdominal haemorrhage occur.

Reduced reliability

When Marvelon is taken according to the directions for use the occurrence of pregnancy is highly unlikely. However, the reliability of oral contraceptives may be reduced under the following circumstances:

Forgotten Tablets

Provided she is less than 12 hours late in taking her tablet the patient should take it as soon as she remembers. Further tablets should be taken at the usual time. Marvelon will still give contraceptive protection during this cycle.

If she is more than 12 hours late in taking one or more tablets then she will not be protected for the next 7 days.

If one or more tablets are forgotten for more than 12 hours, contraceptive protection will be reduced. The patient should take the last forgotten tablet, even if this means taking two tablets in one day, and then continue to take tablets at the normal time. Additional contraceptive precautions should be taken for the next 7 days, and the patient should follow the '7-day rule'.

Vomiting or Diarrhoea

If after tablet intake vomiting or diarrhoea occurs, a tablet may not be absorbed properly by the body. If the symptoms disappear within 12 hours of tablet-taking, the patient should take an extra tablet from a spare pack and continue with the rest of the pack as usual. However, if the symptoms continue beyond those 12 hours, additional contraceptive precautions are necessary for any sexual intercourse during the stomach or bowel upset and for the following 7 days (the patient must be advised to follow '7-day rule').

If the patient is taking certain other medicines

If the patient is taking any of the medicines given in the 'Interactions' section she should be advised to follow the '7-day rule':

THE 7-DAY RULE If any one tablet is forgotten for more than 12 hours If the patient has vomiting or diarrhoea for more than 12 hours: If the patient is taking any of the drugs listed under 'Interactions': The patient should continue to take her tablets as usual and:  Additional contraceptive precautions must be taken for the next 7 days BUT - if these 7 days run beyond the end of the current pack, the next pack must be started as soon as the current one is finished, i.e. no gap should be left between packs. (This prevents an extended break in tablet taking which may increase the risk of the ovaries releasing an egg and thus reducing contraceptive protection). The patient will not have a period until the end of 2 packs but this is not harmful nor does it matter if she experiences some bleeding on tablet taking days.

If after taking Marvelon for several months there is a sudden occurrence of spotting or breakthrough bleeding (not observed in previous cycles) or the absence of withdrawal bleeding, contraceptive effectiveness may be reduced. If withdrawal bleeding fails to occur and none of the above mentioned events has taken place, pregnancy is highly unlikely and oral contraceptive use can be continued until the end of the next pack.( If withdrawal bleeding fails to occur at the end of the second cycle, tablet intake should be discontinued and pregnancy excluded before oral contraceptive use can be resumed.) However, if withdrawal bleeding is absent and any of the above mentioned events has occurred, tablet intake should be discontinued and pregnancy excluded before oral contraceptive use can be resumed.

Medical Examination/consultation

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.

Caution should be observed when prescribing oral contraceptives to young women whose cycles are not yet established.

Chloasma

Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation whilst taking this preparation.

Laboratory Tests

The use of steroids may influence the results of certain laboratory tests. In the literature, at least a hundred different parameters have been reported to possibly be influenced by oral contraceptive use, predominantly by the estrogenic component. Among these are: biochemical parameters of the liver, thyroid, adrenal and renal function, plasma levels of (carrier) proteins and lipid/lipoprotein fractions and parameters of coagulation and fibrinolysis.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Irregular cycles and reduced reliability of oral contraceptives may occur when these preparations are used concomitantly with drugs such as anti-convulsants, barbiturates, antibiotics, (e.g. tetracyclines, ampicillin, rifampicin, etc.), griseofulvin, the herbal remedy St Johns Wort, activated charcoal and certain laxatives.

Special consideration should be given to patients being treated with antibiotics for acne. They should be advised to use a non-hormonal method of contraception, or to use an oral contraceptive containing a progestogen showing minimal androgenicity, which have been reported as helping to improve acne without using an antibiotic.

Oral contraceptives may diminish glucose tolerance and increase the need for insulin or other antidiabetic drugs in diabetics.

4.6 Pregnancy And Lactation

Marvelon is contraindicated for use during pregnancy or suspected pregnancy and in mothers who are breast-feeding.

4.7 Effects On Ability To Drive And Use Machines

No observed effects.

4.8 Undesirable Effects

Adverse Reactions

Various adverse reactions have been associated with oral contraceptive use. The serious reactions are dealt with in more detail. The first appearance of symptoms indicative of any one of these reactions necessitates immediate cessation of oral contraceptive use while appropriate diagnostic and therapeutic measures are undertaken.

• Serious adverse reactions

Some epidemiological studies have suggested an association between the use of COCs and an increased risk of arterial and venous thrombotic and thromboembolic diseases such as myocardial infarction, stroke, deep venous thrombosis, and pulmonary embolism. These events occur rarely.

Thrombosis has very rarely been reported to occur in other veins or arteries, e.g. hepatic, mesenteric, renal or retinal, in COC users. There is no consensus as to whether the occurrence of these events is associated with the use of COCs.

The use of estrogen-containing oral contraceptives may promote growth of existing sex steroid dependent tumours. For this reason, the use of these oral contraceptives in patients with such tumours is contraindicated.

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).

See also section 4.4 Special warnings and special precautions for use; The Pill and Thrombosis, and The Pill and Cancer.

The use of oral contraceptives may sometimes lead to the development of cholestatic jaundice or cholelithiasis.

On rare occasions the use of oral contraceptives may trigger or reactivate systemic lupus erythematosus.

A further rare complication of oral contraceptive use is the occurrence of Sydenhams' chorea which can be reversed by discontinuing the pill. The majority of cases of oral-contraceptive-induced chorea show a pre-existing predisposition which often relates to acute rheumatism.

• Other Adverse Reactions

- Cardiovascular system

rise of blood pressure. If hypertension develops, treatment should be discontinued.

- Genital tract

intermenstrual bleeding, post-medication amenorrhoea, changes in cervical secretion, increase in size of uterine fibromyomata, aggravation of endometriosis and certain vaginal infections, e.g. candidiasis

- Breast

tenderness, pain, enlargement, secretion.

- Gastro-intestinal tract

nausea, vomiting, cholelithiasis, cholestatic jaundice.

- Skin

erythema nodosum, rash, chloasma

- Eyes

discomfort of the cornea if contact lenses are used.

- CNS

headache, migraine, mood changes, depression.

- Metabolic

fluid retention, change in body weight, reduced glucose tolerance.

4.9 Overdose

There have been no reports of serious ill-effects from overdosage even when a considerable number of tablets have been taken by a small child. In general, it is therefore unnecessary to treat overdosage. However, if overdosage is discovered within two or three hours and is large, then gastric lavage can be safely used. There are no antidotes and further treatment should be symptomatic.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Marvelon is an oral contraceptive combination containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol.

Ethinylestradiol is a well known synthetic estrogen.

Desogestrel is a synthetic progestogen. After oral administration it has a strong ovulation-inhibiting activity, a strong progestational and anti-estrogenic activity, no estrogenic activity, very weak androgenic/anabolic activity.

5.2 Pharmacokinetic Properties

After oral administration, desogestrel shows rapid absorption, followed by distribution throughout the body, and subsequent excretion, not resulting in retention of the drug and/or its metabolites. The freely extractable fraction in serum of volunteers contains desogestrel, 3-keto-desogestrel and polar metabolites. The level of the unchanged drug decreases rapidly and the level of the biologically active 3-keto-metabolite is still measurable 24 hours after dosing.

5.3 Preclinical Safety Data

The results of pre-clinical studies do not add to the information included in the other sections of the SmPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

	dl-alpha-tocopherol
	Potato starch
	Povidone
	Stearic acid
	Aerosil
	Lactose

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

3 years

6.4 Special Precautions For Storage

Do not store above 25°C. Store blisters in the original pouches.

6.5 Nature And Contents Of Container

Push-through packs of 21 white tablets each. Tablets are round, biconvex and 6 mm in diameter. They are coded on one side TR5 and on the reverse side Organon*. The pack is PVC/Al blister consisting of aluminium foil with a heat-seal coating and a PVC film. Each blister is packed in a printed aluminium pouch. The pouch is packed in a printed cardboard box together with the package leaflet (1, 3, or 50 pouches per box). Not all pack sizes may be marketed

6.6 Special Precautions For Disposal And Other Handling

See Section 4.2.

7. Marketing Authorisation Holder

Organon Laboratories Ltd

Cambridge Science Park

Milton Road

Cambridge

CB4 OFL,

U.K.

8. Marketing Authorisation Number(S)

PL 0065/0071

9. Date Of First Authorisation/Renewal Of The Authorisation

04 November 1981 / 16 March 2009

10. Date Of Revision Of The Text

May 2011

11 LEGAL CATEGORY

Prescription Only Medicine

RU M0101.071.008

Marvelon/UK/05-11/2

Prevident 5000 Dry Mouth

Generic Name: fluoride topical (FLOR ide TOP i kal)

Brand Names: ACT Fluoride Rinse, ACT Kids Fluoride Rinse, ACT Restoring Mouthwash Cinnamon, ACT Restoring Mouthwash Mint, ACT Restoring Mouthwash Spearmint, ACT Restoring Mouthwash Vanilla Mint, Control Rx, Denta 5000 Plus, Dentagel, Ethedent, Fluoridex, Fluoridex Daily Defense, Fluoridex Daily Defense Enhanced Whitening, Fluorigard, Fluorinse, Gel-Kam, Gel-Kam Dental Therapy Pak, Gel-Kam Dentinbloc, Gel-Kam Sensitivity Therapy, NaFrinse Daily/Acidulated, NaFrinse Daily/Neutral, Nafrinse Solution, NaFrinse Weekly, Neutracare Gel, Neutragard, Neutragard Advanced, Neutral Sodium Fluoride Rinse, Omnii Gel, Omnii Gel Just For Kids, Oral B Anti-Cavity, Perfect Choice, Perio Med, Phos-Flur, Prevident, Prevident 500 Plus Boost, PreviDent 5000 Booster, Prevident 5000 Dry Mouth, Prevident 5000 Plus, Prevident 5000 Sensitive, Prevident Dental Rinse, SF, SF 5000 Plus, Stop, Thera-Flur-N

What is Prevident 5000 Dry Mouth (fluoride topical)?

Fluoride is a substance that strengthens tooth enamel. This helps to prevent dental cavities.

Fluoride topical is used as a medication to prevent tooth decay in patients that have a low level of fluoride topical in their drinking water. Fluoride topical is also used to prevent tooth decay in patients who undergo radiation of the head and/or neck, which may cause dryness of the mouth and an increased incidence of tooth decay.

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

What is the most important information I should know about Prevident 5000 Dry Mouth (fluoride topical)?

Fluoride topical should not be used if the level of fluoride in the drinking water is greater than 0.7 parts per million (ppm).

Before using fluoride topical, tell your dentist and doctor if you are on a low salt or a salt free diet. You may not be able to use fluoride topical, or you may need special tests while you are using it.

Do not eat, drink, or rinse your mouth for 30 minutes after using a fluoride topical. Do not swallow fluoride topical. Spit it out after use. Do not allow a child to swallow fluoride topical or serious overdose symptoms could result.

Overdose symptoms may result if you swallow large amounts of fluoride while using it.

What should I discuss with my healthcare provider before using Prevident 5000 Dry Mouth (fluoride topical)?

Fluoride topical should not be used if the level of fluoride in the drinking water is greater than 0.7 parts per million (ppm).

Before using fluoride topical, tell your dentist and doctor if you are on a low salt or a salt free diet. You may not be able to use fluoride topical, or you may need special tests while you are using it.

If you have gum disease, some forms of fluoride topical may be irritating to your gums. Talk to your dentist or doctor if you have bothersome mouth irritation while using fluoride topical.

Talk to your doctor and dentist before using fluoride topical if you are pregnant. Talk to your doctor and dentist before using fluoride topical if you are breast-feeding. The use of fluoride is particularly important in children to protect against tooth decay. The American Dental Association's Council on Dental Therapeutics recommends the use of fluoride by children up to 13 years of age. The American Academy of Pediatrics recommends fluoride supplementation in children until the age of 16 years old. Do not allow a child to swallow fluoride topical or serious overdose symptoms could result.

How should I use Prevident 5000 Dry Mouth (fluoride topical)?

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

Fluoride topical should be used immediately after brushing or flossing your teeth. For best results, use the medication just before bedtime, unless your doctor tells you otherwise.

Swish this medication in your mouth without swallowing. Then spit it out.

Do not eat, drink, or rinse your mouth for 30 minutes after using fluoride topical. Store fluoride topical at room temperature away from moisture and heat.

What happens if I miss a dose?

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

What happens if I overdose?

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

Overdose symptoms may include nausea, vomiting, stomach pain, diarrhea, drooling, numbness or tingling, loss of feeling anywhere in your body, muscle stiffness, or seizure (convulsions).

Overdose symptoms may result if you swallow large amounts of fluoride while using it.

What should I avoid while using Prevident 5000 Dry Mouth (fluoride topical)?

Do not swallow fluoride topical. Spit it out after use.

Prevident 5000 Dry Mouth (fluoride topical) 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 if you have any of the following side effects:

• 
  

  discolored teeth;

  
  


• 
  

  weakened tooth enamel; or

  
  


• 
  

  any changes in the appearance of your teeth.

  
  

Less serious side effects may include:

• 
  

  stomach upset;

  
  


• 
  

  headache; or

  
  


• 
  

  weakness.

  
  

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 Prevident 5000 Dry Mouth (fluoride topical)?

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

More Prevident 5000 Dry Mouth resources

• Prevident 5000 Dry Mouth Side Effects (in more detail)
• Prevident 5000 Dry Mouth Use in Pregnancy & Breastfeeding
• Prevident 5000 Dry Mouth Support Group
• 0 Reviews for Prevident 5000 Dry Mouth - Add your own review/rating

• Prevident 5000 Dry Mouth Prescribing Information (FDA)


• APF Gel Advanced Consumer (Micromedex) - Includes Dosage Information


• EtheDent Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Gel-Kam Rinse MedFacts Consumer Leaflet (Wolters Kluwer)


• Phos-Flur Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• PreviDent 5000 Sensitive MedFacts Consumer Leaflet (Wolters Kluwer)


• Prevident 5000 Booster Prescribing Information (FDA)


• Prevident 5000 Enamel Protect Prescribing Information (FDA)


• Prevident 5000 Sensitive Prescribing Information (FDA)

Compare Prevident 5000 Dry Mouth with other medications

• Prevention of Dental Caries

Where can I get more information?

• Your pharmacist can provide more information about fluoride topical.

See also: Prevident 5000 Dry Mouth side effects (in more detail)

Mycobutin

1. Name Of The Medicinal Product

Mycobutin.

2. Qualitative And Quantitative Composition

Rifabutin INN

150.0 mg

3. Pharmaceutical Form

Opaque, red-brown, hard gelatin capsules Size N°. 0 containing 150 mg rifabutin in transparent PVC/Al blisters or in amber glass bottles.

The capsules are for oral administration.

4. Clinical Particulars

4.1 Therapeutic Indications

Mycobutin is indicated for:

- the prophylaxis of M. avium intracellulare complex (MAC) infections in patients with HIV disease with CD4 counts lower than 75 cells/mcl.

- the treatment of non-tuberculous mycobacterial disease (such as that caused by MAC and M. xenopi).

- pulmonary tuberculosis.

4.2 Posology And Method Of Administration

Mycobutin can be administered as a single, daily, oral dose at any time independently of meals.

Adults

- prophylaxis of M. avium intracellulare complex (MAC) infections in patients with HIV disease with CD4 counts lower than 75 cells/mcl.:

300 mg (2 capsules) as a single agent.

- treatment of non-tuberculous mycobaterial disease:

450 - 600 mg (3 - 4 capsules) in combination regimens for up to 6 months after negative cultures are obtained.

When Mycobutin is given in association with clarithromycin (or other macrolides) and/or fluconazole (or related compounds) the Mycobutin dosage may need to be reduced to 300 mg (see Section 4.5).

- treatment of pulmonary tuberculosis:

150 - 450 mg (1 - 3 capsules) in combination regimens for at least 6 months.

In accordance with the commonly accepted criteria for the treatment of mycobacterial infections, Mycobutin should always be given in combination with other anti-mycobacterial drugs not belonging to the family of rifamycins.

Children

There are inadequate data to support the use of Mycobutin in children at the present time.

Elderly

No specific recommendations for dosage alterations in the elderly are suggested.

4.3 Contraindications

Mycobutin is contra-indicated in patients with a history of hypersensitivity to rifabutin or other rifamycins (eg rifampicin).

Due to insufficient clinical experience in pregnant and breast-feeding women and in children, Mycobutin should not be used in these patients.

4.4 Special Warnings And Precautions For Use

Before starting Mycobutin prophylaxis, patients should be assessed to ensure that they do not have active disease caused by pulmonary tuberculosis or other mycobacteria.

Prophylaxis against MAC infection may need to be continued throughout the patient's lifetime.

Mycobutin may impart a red-orange colour to the urine and possibly to skin and body secretions. Contact lenses, especially soft, may be permanently stained.

Mild hepatic impairment does not require a dose modification. Mycobutin should be used with caution in cases of severe liver insufficiency. Mild to moderate renal impairment does not require any dosage adjustment.

Severe renal impairment (creatinine clearance below 30 ml/min) requires a dosage reduction of 50%.

It is recommended that white blood cell and platelet counts and liver enzymes be monitored periodically during treatment.

Because of the possibility of occurrence of uveitis, patients should be carefully monitored when rifabutin is given in combination with clarithromycin (or other macrolides) and/or fluconazole (and related compounds). If such an event occurs, the patient should be referred to an ophthalmologist and, if considered necessary, Mycobutin treatment should be suspended.

Uveitis associated with Mycobutin must be distinguished from other ocular complications of HIV.

Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including rifabutin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Rifabutin has been shown to induce the enzymes of the cytochrome P450 3A subfamily and therefore may affect the pharmacokinetic behaviour of drugs metabolised by the enzymes belonging to this subfamily. Upward adjustment of the dosage of such drugs may be required when administered with Mycobutin.

Similarly, Mycobutin might reduce the activity of analgesics, anticoagulants, corticosteroids, cyclosporin, digitalis (although not digoxin), oral hypoglycaemics, narcotics, phenytoin and quinidine.

Clinical studies have shown that Mycobutin does not affect the pharmacokinetics of didanosine (DDI), and isoniazid (however, for the latter refer also to undesirable effects). On the basis of the above metabolic considerations no significant interaction may be expected with ethambutol, theophylline, sulphonamides, pyrazinamide and zalcitabine (DDC).

As p-aminosalicylic acid has been shown to impede GI absorption of rifamycins it is recommended that when it and Mycobutin are both to be administered they be given with an interval of 8 - 12 hours.

The following table provides details of the possible effects of co-administration, on rifabutin and the co-administered drug, and risk-benefit statement.

Coadministered drugs	Effect on rifabutin	Effect on co-administered drug	Comments
ANTIVIRALS
Indinavir	20% increase in AUC.	32% decrease in AUC.
Saquinavir	No data.	40% decrease in AUC.
Ritonavir	4-fold increase in AUC, 2.5-fold increase in Cmax	No data	Due to this multifold increase in rifabutin concentrations and the subsequent risk of side effects, patients requiring both rifabutin and a protease inhibitor, other protease inhibitors should be considered.
Zidovudine	No significant change in kinetics	Approx. 32% decrease in Cmax and AUC.	A large clinical study has shown that these changes are of no clinical relevance.
ANTIFUNGALS
Fluconazole	82% increase in AUC.	No significant change in steady-state plasma concentrations
Itraconazole	No data.	70-75% decrease in Cmax and AUC.	A case report indicates an increase in rifabutin serum levels in the presence of itraconazole.
Ketoconazole/ miconazole	No data.	No data.	Co-administered medications, sucha s ketoconazole, that competitively inhibit the Cyt P450IIIA activity may increase circulating drug levels of rifabutin.
ANTI-PCP (Pneumocystis carinii pneumonia)
Dapsone	No data.	Approximately 27%-40% decrease in AUC.	Study conducted in HIV infected patients (rapid and slow acetylators)
Sulfamethoxazole-Trimethoprim	No significant change in Cmax and AUC.	Approx. 15-20% decrease in AUC.	In another study, only trimethoprim (not sulfamethoxazole had 14% decrease in AUC and 6% in Cmax but were not considered clinically significant.
ANTI-MAC (Mycobacterium avium intracellulare complex)
Clarithromycin	Approx. 77% increase in AUC.	Approx. 50% decrease in AUC.	Study conducted in HIV infected patients
OTHER
Methadone	No data.	No significant effect.	No apparent effect of rifabutin on either peak levels of methadone or systemic exposure based upon AUC. Rifabutin kinetics not evaluated.
Oral contraceptives	No data.	No data.	Contraceptive cover may not be adequate during concomitant therapy with rifabutin, therefore, patients should be advised to use other methods of contraception.
Tacrolimus	No data.	No data.	Rifabutin decreases tacrolimus trough blood levels.

4.6 Pregnancy And Lactation

Due to lack of data in pregnant women, as a precautionary measure, Mycobutin should not be administered to pregnant women or those breast-feeding children even though in experimental animal studies the drug was not teratogenic.

Mycobutin may interact with oral contraceptives (see Section 4.5).

4.7 Effects On Ability To Drive And Use Machines

There have been no reports of adverse effects on ability to drive and use machines.

4.8 Undesirable Effects

The tolerability of Mycobutin in multiple drug regimens, was assessed in both immunocompetent and immunocompromised patients, suffering from tuberculosis and non-tuberculous mycobacteriosis in long term studies with daily dosages up to 600 mg.

Bearing in mind that Mycobutin was often given in these studies as part of a multidrug regimen it is not possible to define with certainty a drug-event relationship. Treatment discontinuation was necessary only in a very few cases. The most commonly reported adverse events, were primarily related to:

- the gastro-intestinal system, such as nausea, vomiting, increase of liver enzymes, jaundice;

- the blood and lymphatic system, such as leucopenia, neutropenia, thrombocytopenia and anemia, where the frequency and severity of haematologic reactions could be increased by combined administration of isoniazid;

- the musculo-skeletal system: arthralgia and myalgia.

Also, fever, rash and rarely other hypersensitivity reactions such as eosinophilia, bronchospasm and shock might occur as has been seen with other antibiotics.

In addition, mild to severe, reversible uveitis has been reported. The risk appears to be low, when Mycobutin is used at 300 mg as monotherapy in MAC prophylaxis, but increases when Mycobutin is administered at higher doses in combination with clarithromycin (or other macrolides) for MAC treatment (see Section 4.4). The possible role of fluconazole (and related compounds) has not been established yet.

Asymptomatic corneal opacities have been reported after long term therapy.

Pseudojaundice (yellow skin discolouration with normal plasma bilirubin) has been reported with high doses of rifabutin. Flu-like syndrome, chest pressure or pain with dyspnoea and rarely hepatitis and haemolysis. Clostridium difficile diarrhoea has been reported rarely.

4.9 Overdose

Gastric lavage and diuretic treatment should be carried out. Supportive care and symptomatic treatment should be administered.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

In vitro activity of rifabutin against laboratory strains and clinical isolates of M. tuberculosis has been shown to be very high. In vitro studies carried out so far have shown that from one-third to half of M.tuberculosis strains resistant to rifampicin are susceptible to rifabutin, indicating that cross-resistance between the two antibiotics is incomplete.

The in vivo activity of rifabutin on experimental infections caused by M. tuberculosis was about 10 times greater than that of rifampicin in agreement with the in vitro findings.

Rifabutin was seen to be active against non-tuberculous (atypical) mycobacteria including M. avium-intracellulare (MAC), in vitro as well as in experimental infections caused by these pathogens in mice with induced immuno-deficiency.

5.2 Pharmacokinetic Properties

In man, rifabutin is rapidly absorbed and maximum plasma concentrations are reached around 2-4 hours after oral administration. The pharmacokinetics of rifabutin is linear after single administration of 300, 450, and 600 mg to healthy volunteers. With these doses, C max is in the range of 0.4-0.7 µg/ml. Plasma concentrations are maintained above the MIC values for M. tuberculosis up to about 30 hours from administration.

Rifabutin is widely distributed in various animal organs with the exception of the brain. In particular, in human lung tissue the concentrations measured up to 24 hours after dosing were about 5-10 times higher than the plasma levels.

The intracellular penetration of rifabutin is very high as demonstrated by intracellular/extracellular concentration ratios which ranged from 9 in neutrophils to 15 in monocytes, both obtained from human sources.

The high intracellular concentration is likely to play a crucial role in sustaining the efficacy of rifabutin against intracellular pathogens such as mycobacteria.

Rifabutin and its metabolites are eliminated mainly by the urinary route. The t_½ of rifabutin in man is approximately 35-40 hours.

5.3 Preclinical Safety Data

Preclinical safety studies of rifabutin indicate a good safety margin in rodents and in monkeys.

In repeated dose studies, target organs were identified at doses producing blood levels higher than those achieved with recommended doses for human therapy. The main target organs are liver and, to a lesser degree, erythrocytes.

Rifabutin did not show any teratogenic, mutagenic or carcinogenic potential.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Microcrystalline cellulose

Sodium lauryl sulphate

Magnesium stearate

Silica gel

6.2 Incompatibilities

None known.

6.3 Shelf Life

24 months at room temperature.

6.4 Special Precautions For Storage

None.

6.5 Nature And Contents Of Container

Transparent PVC/Al blisters in cardboard cartons containing 30 capsules or amber glass bottles containing 30 or 100 capsules.

6.6 Special Precautions For Disposal And Other Handling

There are no special instructions for handling.

Administrative Data

7. Marketing Authorisation Holder

Pfizer Ltd

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

8. Marketing Authorisation Number(S)

PL 00057/1017

9. Date Of First Authorisation/Renewal Of The Authorisation

15th January 2003.

10. Date Of Revision Of The Text

February 2010

Ref: MY_4_0

Indolar SR Capsules 75mg

1. Name Of The Medicinal Product

Indolar* (Indometacin) SR Capsules 75mg.

2. Qualitative And Quantitative Composition

Each capsule contains indometacin 75mg

3. Pharmaceutical Form

Slow release capsule.

4. Clinical Particulars

4.1 Therapeutic Indications

Non-steroidal analgesic and anti-inflammatory agent indicated in active rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, degenerative joint disease of the hip, acute musculo-skeletal disorders and low back pain. Also indicated in periarticular disorders such as bursitis, tendinitis, synovitis, tenosynovitis and capsulitis.

Also indicated in inflammation, pain and oedema following orthopaedic procedures and the treatment of pain and associated symptoms of primary dysmenorrhoea.

4.2 Posology And Method Of Administration

Indolar* SR Capsules should always be given with food or milk to reduce the chance of gastro-intestinal disturbance.

Adults:

One capsule once or twice daily, depending on patients needs and response.

Dosage in dysmenorrhoea: one capsule a day, starting with onset of cramps or bleeding, and continuing for as long as symptoms usually last.

Children:

Safety for use in children has not been established.

Elderly:

Particular care should be taken with the elderly.

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.4).

4.3 Contraindications

Patients with angioneurotic oedema or who have, with aspirin or other non-steroidal anti-inflammatory drugs, experienced acute asthmatic attacks, urticaria or rhinitis.

Active peptic ulcer, a history of recurrent gastro-intestinal lesions, sensitivity to indometacin, to aspirin, to other non-steroidal anti-inflammatory drugs or to any of the other ingredients in the capsule.

Patients who show sensitivity to indometacin or any other ingredient in this product.

Severe heart failure.

4.4 Special Warnings And Precautions For Use

Undesirable effects may be minimised by using the lowest effective dose for the shortest duration necessary to control symptoms (see section 4.2, and GI and cardiovascular risks below).

NSAIDs should only be given with care to patients with a history of gastrointestinal disease.

Caution is required in patients with renal, hepatic or cardiac impairment since the use of NSAIDs may result in deterioration of renal function. The dose should be kept as low as possible and renal function should be monitored in these patients. NSAIDs should be given with care to patients with a history of heart failure or hypertension since oedema has been reported in association with NSAIDs administration.

Caution is required if administered to patients suffering from, or with a previous history of bronchial asthma since NSAIDs have been reported to cause bronchospasm in such patients.

It is reported that a few patients receiving non-steroidal anti-inflammatory drugs manifest borderline elevations in liver function test results. If these persist or worsen, or symptoms of liver disease, a rash or eosinophilia develop, treatment with indometacin should be stopped. Periodic assessment to detect, at an early stage, unwanted effects on peripheral blood (anaemia) and liver function are advisable.

Particular care should be taken with elderly patients who are more susceptible to side-effects from indometacin.

In common with other anti-inflammatory analgesic anti-pyretic agents, indometacin may mask the signs and symptoms of infectious disease and this should be borne in mind in order to avoid delay in starting treatment for infection. Indometacin should be used with caution in patients with an existing, albeit controlled infection.

The use of indometacin may impair female fertility and is not recommended in women attempting to conceive. In women who have difficulties conceiving or who are undergoing investigation of infertility, withdrawal of indometacin should be considered.

Cardiovascular and cerebrovascular effects

Appropriate monitoring and advice are required for patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke).

Patients with uncontrolled hypertension, congestive heart failure, established ischaemic heart disease, peripheral arterial disease, and/or cerebrovascular disease should only be treated with indomethacin after careful consideration. Similar consideration should be made before initiating longer-term treatment of patients with risk factors for cardiovascular disease (e.g. hypertension, hyperlipidaemia, diabetes mellitus, smoking).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Concomitant use of two or more NSAIDs should be avoided.

Use of indometacin with aspirin or other salicylates is not recommended because there is no enhancement of therapeutic effect while the incidence of gastro-intestinal side-effects is increased. Moreover, co-administration of aspirin may decrease the blood concentration of indometacin.

Co-administration of diflunisal increases the plasma level of indometacin by about a third with concomitant decrease in renal clearance. Fatal gastro-intestinal haemorrhage has occurred. The combination should not be used.

Indometacin may decrease the tubular secretion of methotrexate thus potentiating toxicity. Simultaneous use should be undertaken with caution.

Patients receiving anticoagulants should be observed carefully for alteration of prothrombin time even though clinical studies suggest no influence from indometacin on hypoprothrombinaemia induced by anticoagulants.

Indometacin can inhibit platelet aggregation - an effect which disappears within 24 hours of discontinuation; the bleeding time may be prolonged and this effect may be exaggerated in patients with an underlying haemostatic defect.

Diuretics may increase the risk of nephrotoxicity of NSAIDs. Indometacin and triamterene should not be administered together since reversible renal failure may be induced.

Indometacin may reduce the diuretic and antihypertensive effects of thiazides and furosemide in some patients and may cause blocking of the furosemide-induced increase in plasma renin activity.

Co-administration of probenecid may increase plasma levels of indometacin.

Because indometacin may reduce the effect of antihypertensive drugs, patients receiving dual therapy should have the antihypertensive effect of their therapy reassessed.

The risk of gastrointestinal bleeding may be increased by concomitant administration of corticosteroids. A reduction in dosage of these may be possible but should only be effected slowly under supervision.

Indometacin may raise plasma lithium levels and reduce renal lithium clearance in subjects with steady state plasma lithium concentrations. At the onset of such combined therapy, plasma lithium concentration should be monitored more frequently.

When indometacin is taken with antidepressants such as SSRI's or venlafaxine there is an increased risk of bleeding. Indometacin may cause severe drowsiness if taken with haloperidol.

There is a risk of an increase in plasma concentration of indometacin if it is taken with the antiviral ritonavir, if indometacin is taken with the antiviral zidovudine there is a risk of haematological toxicity.

When given with cardiac glycosides, NSAIDs may exacerbate cardiac failure, reduce glomerular filtration rate and increase plasma glycoside levels.

Concomitant administration of ciclosporin may lead to increased risk of nephrotoxicity.

NSAIDs should not be used for 8-12 days after administration of mifepristone as they can reduce its effect.

Animal data indicate that NSAIDs can increase the risk of convulsions associated with quinolone antibiotics. Patients taking NSAIDs and quinolones may have an increased risk of developing convulsions.

Indometainc may enhance the effects of the antidiabetic sulphonylureas and the antiepileptic phenytoin.

There is an increased risk of bleeding if pentoxifylline (oxypentifylline) is taken with indometacin.

There is an increased risk on nephrotoxicity when indometacin is taken concomitantly with tacrolimus.

The dexamethasone suppression test may give false negative results.

4.6 Pregnancy And Lactation

Indometacin can adversely affect the foetus. It is not clear whether the risk is increased the earlier indometacin is used in gestation. However the use of Indolar* SR during pregnancy should if possible be avoided.

Reported adverse effects of indometacin during pregnancy include: transient constriction of the ductus arteriosus, pulmonary hypertension, bronchopulmonary dysplasia, oligohydramnios and possible renal damage. In view of these known effects on the fetal cardiovascular system, use in late pregnancy should be avoided.

Administration of Indolar* SR is not recommended in breast-feeding mothers.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned not to drive or operate machinery if they become dizzy.

4.8 Undesirable Effects

The most common side-effects are gastrointestinal in nature. Nausea, vomiting, constipation or diarrhoea, dyspepsia, epigastric discomfort or abdominal pain have been reported following administration. More rarely anorexia, stomatitis, flatulence, melaena and haematemesis have also been reported.

Ulceration at any point in the gastro-intestinal tract (even with resultant stenosis and obstruction) may also occur accompanied by haemorrhage and perforation (a few fatalities have been reported). Bleeding without obvious ulceration and perforation of pre-existing sigmoid lesions (such as a diverticulum or carcinoma) have also occurred. Increased abdominal pain in patients with ulcerative colitis (or the development of this condition) and regional ileitis have rarely been reported. If gastro-intestinal bleeding does occur, treatment with indometacin should be discontinued.

Occurrence of gastro-intestinal disorders can be reduced by giving indometacin with food, milk or antacids.

Blood dyscrasias, including thrombocytopenia, neutropenia, leucopenia, petechiae, ecchymosis, purpura, aplastic or haemolytic anaemia, agranulocytosis, bone marrow depression and disseminated intravascular coagulation have been reported.

Oedema, increased blood pressure, hypertension, tachycardia, chest pain, arrhythmia, palpitations, congestive cardiac failure, elevation of blood urea and haematuria may also occur.

Hypersensitivity reactions including pruritus, urticaria, angioneurotic oedema, angiitis, erythema nodosum, rash and exfoliative dermatitis have been reported infrequently - as have Stevens Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, hair loss, acute anaphylaxis (including acute loss of blood pressure). Photosensitivity reactions have also been reported.

Acute respiratory distress, including sudden dyspnoea, asthma and pulmonary oedema have been reported on rare occasions. Bronchospasm may be precipitated in patients suffering from, or with a previous history of bronchial asthma or allergic disease.

Non-steroidal anti-inflammatory drugs have been reported to cause nephrotoxicity in various forms and their use may precipitate renal decompensation in those with renal or hepatic dysfunction, diabetes mellitus, advanced age, extracellular volume depletion. Also, there have been reports of acute interstitial nephritis with haematuria, proteinuria and occasionally nephrotic syndrome, renal insufficiency or failure in long-term therapy with indometacin.

Abnormal liver function, hepatitis and jaundice (including some fatalities) have been reported rarely.

Headache, dizziness, light-headedness, fainting, malaise, depression, vertigo and fatigue are not uncommon. Infrequently confusion, anxiety or other psychiatric disorders, drowsiness, convulsions, neuropathy, paraesthesia, hallucinations, involuntary movements, insomnia, aggravation of epilepsy and Parkinsonism may also occur. All are often transient and likely to abate or disappear with reduced or ceased dosage. If headache persists, even after dosage reduction, indometacin should be withdrawn. There have also been reports of peripheral neuropathy.

Optic neuritis, blurred vision and orbital and peri-orbital pain are seen infrequently. Corneal deposits and retinal disturbances have been reported in some patients with rheumatoid arthritis on prolonged therapy with indometacin, and ophthalmic examinations are desirable in patients given prolonged treatment.

Tinnitus or hearing disturbance (rarely deafness) have been reported.

Hyperglycaemia, glycosuria, hyperkalaemia, vaginal bleeding, epistaxis, breast changes (enlargement, tenderness, gynaecomastia), flushing, sweating and ulcerative stomatitis all have been reported rarely.

Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with an increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

4.9 Overdose

Many of the unwanted symptoms associated with indometacin therapy may be seen. Treatment is symptomatic and supportive. Emptying the stomach by induction of vomiting and/or lavage and use of activated charcoal may be appropriate. Antacid therapy may be useful. Close monitoring thereafter is required because intestinal ulceration may develop.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Indometacin is a non-steroidal analgesic and anti-inflammatory agent.

5.2 Pharmacokinetic Properties

Indometacin has a biphasic plasma elimination with the terminal phase showing a half-life ranging between 2 and 12 hours. The following pharmacokinetic particulars were obtained with Indolar* SR 75mg capsules (n = 8).

t½α:	4.0 hours
t½β:	3.9 hours
Tmax :	6.2 hours
Cmax :	2.2 mcg/ml
AUC24 :	31.2 mcg/ml*hour.

5.3 Preclinical Safety Data

No additional data provided. The pre-clinical safety of indometacin is already well documented.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sucrose, corn starch, lactose, povidone, talc, magnesium stearate and polymethacrylates. The capsule shells contain gelatin and the colours titanium dioxide (E171), erythrosine (E127), indigotine (E132) and yellow iron oxide (E172).

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Capsules should be stored in a cool dry place and protected from light.

6.5 Nature And Contents Of Container

Polypropylene securitainers with polyethylene closures, containing 28, 30, 56, 60, 84, 90 or 100 capsules.

6.6 Special Precautions For Disposal And Other Handling

Not applicable.

7. Marketing Authorisation Holder

Sandoz Ltd

Woolmer Way

Bordon

Hampshire

GU35 9QE

8. Marketing Authorisation Number(S)

PL 4416/0066

9. Date Of First Authorisation/Renewal Of The Authorisation

30 January 1994

10. Date Of Revision Of The Text

03/2007

* trade mark

TechneScan PYP

Dosage Form: powder, lyophilized, for solution

Kit for the Preparation of Technetium Tc 99m Pyrophosphate Injection

Rx Only.

Diagnostic–For Intravenous Use

TechneScan PYP Description

TechneScan® PYP® (kit for the preparation of Technetium Tc 99m Pyrophosphate Injection) is a sterile, non-pyrogenic, diagnostic radiopharmaceutical suitable for intravenous administration after reconstitution with sterile sodium pertechnetate Tc 99m injection or sterile 0.9% sodium chloride injection.

Each 10 milliliter reaction vial contains 11.9 milligrams sodium pyrophosphate, 3.2 milligrams (minimum) stannous chloride (SnCl2•2H2O) and 4.4 milligrams (maximum) total tin expressed as stannous chloride (SnCl2•2H2O) in lyophilized form under an atmosphere of nitrogen. Prior to lyophilization the pH is adjusted with hydrochloric acid. The pH of the reconstituted drug is between 4.5 and 7.5. No bacteriostatic preservative is present.

The precise structures of the stannous-pyrophosphate and technetium-stannous-pyrophosphate complexes are not known at this time.

PHYSICAL CHARACTERISTICS

Technetium Tc 99m decays by isomeric transition with a physical half-life of 6.02 hours.1 The principal photon that is useful for detection and imaging is listed in Table 1.

Table 1. Principal Radiation Emission Data1

Radiation	Mean Percent/ Disintegration	Energy (keV)
Gamma-2	89.07	140.5

The specific gamma ray constant for technetium Tc 99m is 0.78 R/mCi-hr at 1 cm. The first half-value thickness of lead (Pb) for technetium Tc 99m is 0.017 cm. A range of values for the relative attenuation of the radiation emitted by this radionuclide that results from interposition of various thicknesses of Pb is shown in Table 2. For example, the use of 0.25 cm of Pb will decrease the external radiation exposure by a factor of about 1000.

Table 2. Radiation Attenuation by Lead Shielding

Shield Thickness (Pb) cm	Coefficient of Attenuation
0.017 0.08 0.16 0.25 0.33	0.5 10-1 10-2 10-3 10-4

To correct for physical decay of this radionuclide, the fractions that remain at selected time intervals after the time of calibration are shown in Table 3.

Table 3. Physical Decay Chart; Technetium Tc 99m, Half-Life 6.02 Hours

*Calibration Time
Hours	Fraction Remaining	Hours	Fraction Remaining
0*	1.000	7	0.447
1	0.891	8	0.398
2	0.794	9	0.355
3	0.708	10	0.316
4	0.631	11	0.282
5	0.562	12	0.251
6	0.501

1

Kocher, David C., Radioactive Decay Data Tables, DOE/TIC-11026, 108 (1981).

TechneScan PYP - Clinical Pharmacology

When injected intravenously, Technetium Tc 99m Pyrophosphate has a specific affinity for areas of altered osteogenesis. It is also concentrated in the injured myocardium, primarily in areas of irreversibly damaged myocardial cells.

One to two hours after intravenous injection of Technetium Tc 99m Pyrophosphate, an estimated 40 to 50 percent of the injected dose had been taken up by the skeleton, and approximately 0.01 to 0.02 percent per gram of acutely infracted myocardium. Within a period of one hour, 10 to 11 percent remains in the vascular system, declining to approximately 2 to 3 percent twenty-four hours post injection. The average urinary excretion was observed to be about 40 percent of the administered dose after 24 hours.

TechneScan PYP also has an affinity for red blood cells. When administered 15 to 30 minutes prior to the intravenous administration of sodium pertechnetate Tc 99m (in vivo red blood cell labeling), approximately 75 percent of the injected radioactivity remains in the blood pool providing excellent images of the cardiac chambers. When the modified in vivo/ in vitro red blood cell labeling method is used, comparable percentages of the injected radioactivity are obtained.

Toxicology data are available upon request.

Indications and Usage for TechneScan PYP

Technetium Tc 99m Pyrophosphate Injection is a skeletal imaging agent used to demonstrate areas of altered osteogenesis, and a cardiac imaging agent used as an adjunct in the diagnosis of acute myocardial infarction.

As an adjunct in the diagnosis of confirmed myocardial infarction (ECG and serum enzymes positive), the incidence of false negative images has been found to be 6 percent. False negative images can also occur if made too early in the evolutionary phase of the infarct or too late in the resolution phase. In a limited study involving 22 patients in whom the ECG was positive and serum enzymes questionable or negative, but in whom the final diagnosis of acute myocardial infarction was made, the incidence of false negative images was 23 percent. The incidence of false positive images has been found to be 7 to 9 percent. False positive images have been reported following coronary by-pass graft surgery, in unstable angina pectoris, old myocardial infarcts and in cardiac contusions.

TechneScan PYP is a blood pool imaging agent which may be used for gated blood pool imaging and for the detection of sites of gastrointestinal bleeding. When administered intravenously 15 to 30 minutes prior to intravenous administration of sodium pertechnetate Tc 99m for in vivo red blood cell labeling, approximately 75 percent of the injected activity remains in the blood pool. The modified in vivo/ in vitro red blood cell labeling method may also be used for blood pool imaging.

Contraindications

None known.

Warnings

Reports indicate impairment of brain images using sodium pertechnetate Tc 99m, which have been preceded by a bone image. The impairment may result in false positives or false negatives. It is recommended, where feasible, that brain imaging precede bone imaging procedures.

Preliminary reports indicate impairment of blood pool images in patients receiving sodium heparin for anticoagulant therapy. This is characterized by a reduction in the amount of injected radioactivity remaining in the blood pool.

TechneScan PYP should be injected by direct venipuncture. Heparinized catheter systems should be avoided.

Precautions

General

TechneScan PYP should not be used more than six hours after preparation.

The components of the kit are sterile and non-pyrogenic. It is essential that the user follow the directions carefully and adhere to strict aseptic procedures during preparation.

The contents of this kit are not radioactive. However, after sodium pertechnetate Tc 99m is added, adequate shielding of the final preparation must be maintained.

The imaging of gastrointestinal bleeding is dependent on such factors as the region of imaging, rate and volume of the bleed, efficacy of labeling of the red blood cells and timeliness of imaging. Due to these factors, images should be taken sequentially over a period of time until a positive image is obtained or clinical conditions warrant the discontinuance of the procedure. The period of time for collecting the images may range up to thirty-six hours.

Any sodium pertechnetate Tc 99m solution which contains an oxidizing agent is not suitable for use in the preparation of Technetium Tc 99m Pyrophosphate Injection.

The contents of the TechneScan PYP reaction vial may be used for the preparation of Technetium Tc 99m Pyrophosphate Injection. TechneScan PYP may also be reconstituted with sterile, nonpyrogenic normal saline containing no preservatives and injected intravenously prior to labeling of red blood cells with sodium pertechnetate Tc 99m using either the in vivo or modified in vivo/in vitro method.

As in the use of any other radioactive material, care should be taken to insure minimum radiation exposure to the patient, consistent with proper patient management, and to insure minimum radiation exposure to occupational workers.

Radiopharmaceuticals should be used only by physicians who are qualified by specific training in the safe use and handling of radionuclides produced by nuclear reactor or particle accelerator and whose experience and training have been approved by the appropriate government agency authorized to license the use of radionuclides.

Bone Imaging

Both prior to and following administration of Technetium Tc 99m Pyrophosphate Injection, patients should be encouraged to drink fluids. Patients should void as often as possible after administration of Technetium Tc 99m Pyrophosphate Injection to minimize background interference from its accumulation in the bladder and to reduce unnecessary exposure to radiation.

Cardiac Imaging

The patient's cardiac condition should be stable before beginning the cardiac imaging procedure.

If not contraindicated by the cardiac status, patients should be encouraged to ingest fluids and to void frequently in order to reduce unnecessary radiation exposure.

Interference from chest wall lesions such as breast tumors and healing rib fractures can be minimized by employing the three recommended projections.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No long term animal studies have been performed to evaluate carcinogenic or mutagenic potential, or whether this drug affects fertility in males or females.

Pregnancy Category C

Animal reproduction studies have not been conducted with Technetium Tc 99m Pyrophosphate Injection. It is also not known whether this drug can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Technetium Tc 99m Pyrophosphate Injection should be given to a pregnant woman only if clearly needed.

Ideally, examinations using radiopharmaceuticals, especially those elective in nature, of a woman of childbearing capability should be performed during the first few (approximately 10) days following the onset of menses.

Nursing Mothers

Technetium Tc 99m is excreted in human milk during lactation, therefore, formula feedings should be substituted for breast feeding.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Adverse Reactions

Several adverse reactions due to the use of Technetium Tc 99m Pyrophosphate Injection have been reported. These were usually flushing, hypotension, fever, chills, nausea, vomiting and dizziness, as well as hypersensitivity reactions such as itching and various skin rashes.

TechneScan PYP Dosage and Administration

Bone and Cardiac Imaging

The recommended adult doses of Technetium Tc 99m Pyrophosphate Injection are:

Indication	Doses as Technetium Tc 99	Fraction of Vial Contents Required
Skeletal Imaging	185 to 555 megabecquerels (5 to 15 mCi)	0.07 to 0.91
Cardiac Imaging	370 to 555 megabecquerels (10 to 15 mCi)	0.26 to 0.45

Technetium Tc 99m Pyrophosphate Injection is injected intravenously over a 10- to 20-second period. For optimal results, bone imaging should be done one to six hours following administration. Cardiac imaging should be done 60 to 90 minutes following administration. The acute myocardial infarct can be visualized from 24 hours to nine days following onset of symptoms, with maximum localization at 48 to 72 hours. Cardiac imaging should be done with a gamma scintillation camera. It is recommended that images be made of the anterior, left anterior oblique and left lateral projections.

The patient dose should be measured by a suitable radioactivity calibration system immediately prior to administration. It is also recommended that the radiochemical purity be checked prior to administration.

Blood Pool Imaging

The recommended adult dose of TechneScan PYP is one-third (0.33) to the entire vial contents, followed by 555 to 740 megabecquerels (15 to 20 millicuries) of sodium pertechnetate Tc 99m. Cardiac imaging should be done 10 minutes following the administration of sodium pertechnetate Tc 99m (in vivo method) or Tc 99m labeled red blood cells (modified in vivo/in vitro method) utilizing a scintillation camera interfaced to an electrocardiographic gating device.

In Vivo Method: TechneScan PYP is reconstituted with sterile, nonpyrogenic normal saline containing no preservatives. The patient dose is administered intravenously 15 to 30 minutes prior to the intravenous administration of 555 to 740 megabecquerels (15 to 20 millicuries) of sodium pertechnetate Tc 99m. TechneScan PYP should be injected by direct venipuncture. Heparinized catheter systems should be avoided.

Modified In Vivo/In Vitro Method Using Acid-Citrate-Dextrose (ACD): TechneScan PYP is reconstituted with sterile, nonpyrogenic normal saline containing no preservatives, and the patient dose is administered intravenously. An intravenous line containing a 3-way stopcock is inserted in a large peripheral vein and kept patent with a continuous drip of sterile, nonpyrogenic normal saline containing no preservatives. Thirty minutes after TechneScan PYP injection, the infusion line and stopcock are cleared by withdrawing and discarding approximately 5 milliliters of whole blood. Immediately following, approximately 5 milliliters of whole blood are withdrawn into a syringe containing 1 milliliter preservative-free acid-citrate-dextrose (ACD) and 555 to 740 megabecquerels (15 to 20 millicuries) of sodium pertechnetate Tc 99m. The stopcock is then turned, residual blood is flushed from the intravenous line, and the normal saline flow is readjusted. The syringe is gently rotated to mix and allowed to incubate at room temperature for 10 minutes prior to injection via the 3-way stopcock.

Modified In Vivo/In Vitro Method Using Heparin: TechneScan PYP is reconstituted with sterile, nonpyrogenic normal saline containing no preservatives, and the patient dose is administered intravenously. An infusion set fitted with a 3-way stopcock is placed in a large peripheral vein, and the intravenous line is heparinized with a saline solution containing 5-10 units preservative-free heparin per milliliter. Thirty minutes after TechneScan PYP injection, 3 milliliters of blood are withdrawn into a syringe containing 555 to 740 megabecquerels (15 to 20 millicuries) of sodium pertechnetate Tc 99m. Anticoagulation of the blood is provided by residual heparin in the intravenous line. The syringe is gently rotated to mix and allowed to incubate at room temperature for 10 minutes prior to injection via the 3-way stopcock.

Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use if contents are turbid.

RADIATION DOSIMETRY

Method of Calculation: The following radiation absorbed dose values were obtained using the Medical Internal Radiation Dose Committee (MIRD) Schema.

Bone and Cardiac Imaging

Maximum Dose: 555 megabecquerels (15 millicuries) administered intravenously. The effective half-life was assumed to be the physical half-life for all calculated values. About 50% of each dose of Technetium Tc 99m Pyrophosphate Injection is retained in skeleton, and about 50% is excreted into the bladder. The estimated absorbed radiation doses to an average patient (70 kg) from an intravenous injection of a maximum dose of 555 megabecquerels (15 millicuries) of Technetium Tc 99m Pyrophosphate Injection are shown in Table 4.

Table 4. Absorbed Radiation Doses (Bone and Cardiac Imaging)

*Dose at point of highest uptake may be a factor of 10 higher.
Tissue	Technetium Tc 99m Pyrophosphate Injection
	mGy/555 MBq	rads/15 mCi
Skeleton*	5.9	0.59
Bone Marrow	4.2	0.42
Kidneys	21.0	2.10
Total Body	1.3	0.13
Bladder
2-hr. void	14.6	1.46
4.8-hr. void	34.5	3.45
Testes
2-hr. void	1.5	0.15
4.8-hr. void	2.3	0.23
Ovaries
2-hr. void	1.4	0.14
4.8-hr. void	2.3	0.23
Heart
Normal	1.1	0.11
Impaired	2.2	0.22

Blood Pool Imaging

The estimated absorbed radiation doses to an average patient (70 kg) from administration of 740 megabecquerels (20 millicuries) of sodium pertechnetate Tc 99m, 30 minutes after the intravenous administration of TechneScan PYP are shown in Table 5.

Table 5. Absorbed Radiation Doses2 (Blood Pool Imaging)*

*Assumes non-resting state, with 75% of the sodium pertechnetate Tc 99m labeling red blood cells and the other 25% remaining as pertechnetate.
**Assumes no initial uptake in spleen.
2 Data supplied by Oak Ridge Associated Universities, Radiopharmaceutical Internal Dose Information Center, 1986.
Tissue	Sodium Pertechnetate Tc 99m 30 min. Post TechneScan PYP Administration
	mGy/740 MBq	rads/20 mCi
Bladder Wall	6.8	0.68
Ovaries	4.6	0.46
Testes	2.6	0.26
Red Marrow	3.8	0.38
Spleen**	3.0	0.30
Blood	10.2	1.02
Total Body	3.0	0.30

How is TechneScan PYP Supplied

Catalog Number 094.

TechneScan PYP is supplied as a lyophilized powder packaged in vials. Each vial contains 11.9 mg sodium pyrophosphate, 3.2 mg (minimum) stannous chloride (SnCl2•2H2O) and 4.4 milligrams (maximum) total tin expressed as stannous chloride (SnCl2•2H2O), sealed under an atmosphere of nitrogen. Prior to lyophilization the pH is adjusted with hydrochloric acid. The pH of the reconstituted drug is between 4.5 and 7.5.

Kits containing 5 vials or 30 vials are available.

Storage

The TechneScan PYP Kit must be maintained in a refrigerator, 2-8°C (36-46°F) until use. The reconstituted vial should be stored at controlled room temperature, 20-25°C (68-77°F).

INSTRUCTIONS FOR PREPARING THE DRUG

Procedural Precautions

All transfer and vial stopper entries must be done using aseptic techniques.

Procedure

Bone and Cardiac Imaging

Note 1: Wear waterproof gloves during the entire preparation procedure and during subsequent patient dose withdrawals from the Reaction Vial.

Note 2: Make all transfers of sodium pertechnetate Tc 99m solution during the preparation procedure with an adequately shielded syringe.

Note 3: Keep the Radioactive Preparation in the lead shield described below (with cap in place) during the useful life of the Radioactive Preparation. Make all withdrawals and injections of the Radioactive Preparation with an adequately shielded syringe.

1. A TechneScan PYP Reaction Vial is removed from the refrigerator and approximately five (5) minutes are allowed for the contents to come to room temperature.


2. Attach radioassay information label with radiation warning symbol to the Reaction Vial and place the vial in a lead Dispensing Shield fitted with a lead cap and having a minimum wall thickness of 1/8 inch. Do not remove Reaction Vial from the Dispensing Shield except, temporarily, for Step 5 below.


3. Sodium pertechnetate Tc 99m solution (1 to 10 milliliters) is added to the Reaction Vial. In choosing the amount of technetium Tc 99m radioactivity to be used in the preparation of the Technetium Tc 99m Pyrophosphate Injection, the labeling efficiency, number of patients, administered radioactive dose, and radioactive decay must be taken into account. The recommended maximum amount of technetium Tc 99m to be added to the Reaction Vial is 3.7 gigabecquerels (100 millicuries).


4. With the Reaction Vial in the Dispensing Shield (with cap in place), shake sufficiently to bring the lyophilized material into solution. Allow to stand for five (5) minutes at room temperature.


5. Using proper shielding, the Reaction Vial should be visually inspected. The resulting solution should be clear and free of particulate matter. If not, the Reaction Vial should not be used.


6. Assay the product in a suitable calibrator and record the time, date of preparation and the activity of the Technetium Tc 99m Pyrophosphate Injection onto the radioassay information label. Store the Reaction Vial in the Dispensing Shield at 15°C to 30°C when not in use and discard after six (6) hours from the time of preparation.

Blood Pool Imaging

1. A TechneScan PYP Reaction Vial is removed from the refrigerator and approximately five (5) minutes are allowed for the contents to come to room temperature.


2. Reconstitute the Reaction Vial with 3 milliliters of sterile, nonpyrogenic normal saline containing no preservatives.


3. Shake the Reaction Vial sufficiently to bring the lyophilized material into solution. Allow to stand for five (5) minutes at room temperature.


4. The Reaction Vial should be visually inspected. The resulting solution should be clear and free of particulate matter. If not, the Reaction Vial should not be used.


5. Store reconstituted Reaction Vial at 15°C to 30°C when not in use and discard after six (6) hours from time of preparation.

This reagent kit is approved for distribution to persons licensed by the U.S. Nuclear Regulatory Commission to use byproduct material identified in Section 35.200 or under an equivalent license of an Agreement State.

St. Louis, MO 63134

Mallinckrodt

A94I0

TECHNESCAN PYP  sodium pyrophosphate and stannous chloride  injection, powder, lyophilized, for solution

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 0019-N094 Route of Administration INTRAVENOUS DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength sodium pyrophosphate (sodium pyrophosphate) Active 11.9 MILLIGRAM  In 1 VIAL stannous chloride dihydrate Inactive 3.2 MILLIGRAM  In 1 VIAL

Product Characteristics Color      Score      Shape Size Flavor Imprint Code Contains

Packaging # NDC Package Description Multilevel Packaging 1 0019-N094-B0 5 VIAL In 1 CELLO PACK contains a VIAL 1 1 VIAL In 1 VIAL This package is contained within the CELLO PACK (0019-N094-B0) 2 0019-N094-D0 30 VIAL In 1 CARTON contains a VIAL 2 1 VIAL In 1 VIAL This package is contained within the CARTON (0019-N094-D0)

Revised: 12/2007Mallinckrodt