Hot PLR Content Directory Singapore: May 2012

Thursday, 31 May 2012

Vicks Vitamin C Drops

Generic Name: ascorbic acid (vitamin C) (as KORE bik AS id)

Brand Names: Acerola, Ascorbic Acid Quick Melts, C-Time, C/Rose Hips, Cecon, Cemill 1000, Cemill 500, Ester-C, N Ice with Vitamin C, Sunkist Vitamin C, Vicks Vitamin C Drops, Vitamin C, Vitamin C TR, Vitamin C with Rose Hips

What is ascorbic acid?

Ascorbic acid (vitamin C) occurs naturally in foods such as citrus fruit, tomatoes, potatoes, and leafy vegetables. Ascorbic acid is important for bones and connective tissues, muscles, and blood vessels. Vitamin C also helps the body absorb iron, which is needed for red blood cell production.

Ascorbic acid is used to treat and prevent vitamin C deficiency.

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

What is the most important information I should know about ascorbic acid?

You should not use this medication if you have ever had an allergic reaction to ascorbic acid.

Ask a doctor or pharmacist about using ascorbic acid if you have kidney disease or a history of kidney stones, liver disease (especially cirrhosis), or an enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency (G6PD).

It is not known whether ascorbic acid is harmful to an unborn baby or a nursing baby. Some vitamins and minerals are needed during pregnancy or for breast milk production, but some may be harmful if taken in large doses. Do not take ascorbic acid without telling your doctor if you are pregnant or breast-feeding.

Ascorbic acid can be harmful to the kidneys, and this effect is increased when ascorbic acid is used together with other medicines that can harm the kidneys. Before taking ascorbic acid, tell your doctor if you are receiving chemotherapy, or using medicines to treat a bowel disorder, medication to prevent organ transplant rejection, antiviral medications, pain or arthritis medicines, or any injected antibiotics. You may need dose adjustments or special tests when taking any of these medications together with ascorbic acid.

Before taking ascorbic acid, tell your doctor about all other medications you take.

Stop using ascorbic acid and call your doctor at once if you have severe pain in your lower back or side, blood in your urine, pain when you urinate, severe or ongoing diarrhea, or feel like you might pass out.

What should I discuss with my healthcare provider before taking ascorbic acid?

You should not use this medication if you have ever had an allergic reaction to ascorbic acid.

Ask a doctor or pharmacist about using ascorbic acid if you have:

kidney disease or a history of kidney stones;

liver disease (especially cirrhosis); or

an enzyme deficiency called glucose-6-phosphate dehydrogenase deficiency (G6PD).

It is not known whether ascorbic acid is harmful to an unborn baby. Some vitamins and minerals can harm an unborn baby if taken in large doses. You may need to use a prenatal vitamin specially formulated for pregnant women. Do not take ascorbic acid without telling your doctor if you are pregnant. Ascorbic acid can pass into breast milk, but it is not known whether it would be harmful to a nursing baby. Some vitamins and minerals are needed for breast milk production, but some may harm a nursing baby. Do not take ascorbic acid without telling your doctor if you are breast-feeding a baby.

How should I take ascorbic acid?

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

The recommended dietary allowance of ascorbic acid increases with age, and whether you are pregnant or breast-feeding. Follow your doctor's instructions. You may also consult the National Academy of Sciences "Dietary Reference Intake" or the U.S. Department of Agriculture's "Dietary Reference Intake" (formerly "Recommended Daily Allowances" or RDA) listings for more information.

Take the ascorbic acid regular tablet or capsule with a full glass (8 ounces) of water.

The ascorbic acid chewable tablet must be chewed before swallowing. Ascorbic acid gum may be chewed over a long period and then spit out and thrown away.

Remove the disintegrating tablet from the package using dry hands, and place the tablet in your mouth. It will begin to dissolve right away. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. Swallow several times as the tablet dissolves.

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.

Dissolve the powder form of ascorbic acid in a small amount of water or other liquid. Follow the directions on the package label about what types of liquid you may use. Stir the mixture and drink all of it right away. To make sure you get the entire dose, add a little more water to the same glass, swirl gently and drink right away.

Store ascorbic acid at room temperature away from moisture and heat.

What happens if I miss a dose?

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

What happens if I overdose?

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

An overdose of ascorbic acid is not likely to cause life-threatening symptoms.

What should I avoid while taking ascorbic acid?

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

Smoking can make ascorbic acid less effective.

Ascorbic acid 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 using ascorbic acid and call your doctor at once if you have a serious side effect such as:

severe pain in your lower back or side;

blood in your urine;

pain when you urinate;

severe or ongoing diarrhea; or

feeling like you might pass out.

Less serious side effects may include:

heartburn, stomach cramps;

nausea, vomiting, diarrhea;

headache, dizziness;

flushing (warmth, redness, or tingling under your skin);

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 ascorbic acid?

You may need dose adjustments or special tests when taking any of these medications together with ascorbic acid.

The following drugs can interact with ascorbic acid. Tell your doctor if you are using any of these:

aspirin or acetaminophen (Tylenol);

fluphenazine (Permitil);

indinavir (Crixivan);

levodopa (Atamet, Larodopa, Parcopa, Sinemet);

nicotine patches (Nicoderm, Habitrol, Commit);

antacids that contain aluminum (such as Amphojel, Maalox, Mylanta, Rulox, and others);

an antibiotic such as demeclocycline (Declomycin), doxycycline (Adoxa, Doryx, Oracea, Vibramycin), minocycline (Dynacin, Minocin, Solodyn, Vectrin), or tetracycline (Brodspec, Panmycin, Sumycin, Tetracap); or

a barbiturate such as butabarbital (Butisol), secobarbital (Seconal), pentobarbital (Nembutal), or phenobarbital (Solfoton);

birth control pills or hormone replacement therapy, including Premarin, Estratest, Vivelle, Climara, Estring, Estrace, and others; or

a blood thinner such as warfarin (Coumadin).

This list is not complete and there may be other drugs that can interact with ascorbic acid. 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 Vicks Vitamin C Drops resources

Vicks Vitamin C Drops Side Effects (in more detail)
Vicks Vitamin C Drops Use in Pregnancy & Breastfeeding
Vicks Vitamin C Drops Drug Interactions
Vicks Vitamin C Drops Support Group
0 Reviews for Vicks Vitamin C - Add your own review/rating

Ascorbic Acid Monograph (AHFS DI)

ascorbic acid Advanced Consumer (Micromedex) - Includes Dosage Information

Ascorbic Acid MedFacts Consumer Leaflet (Wolters Kluwer)

Acerola Natural MedFacts for Consumers (Wolters Kluwer)

Acerola Natural MedFacts for Professionals (Wolters Kluwer)

Cecon Solution MedFacts Consumer Leaflet (Wolters Kluwer)

Cenolate Injection MedFacts Consumer Leaflet (Wolters Kluwer)

Cevi-Bid Controlled-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Vicks Vitamin C Drops with other medications

Dietary Supplementation
Scurvy
Urinary Acidification

Where can I get more information?

Your doctor, pharmacist, or health care provider may have more information about ascorbic acid.

See also: Vicks Vitamin C side effects (in more detail)

Tuesday, 29 May 2012

Progestins

Class: Contraceptives
ATC Class: G03FA10
VA Class: HS200
CAS Number: 54048-10-1
Brands: Implanon, Micronor, Mirena, Next Choice, Nor-QD, Plan B One-Step

Introduction

Contraceptives containing synthetic progestinic steroids.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ^a

Uses for Progestins

Contraception

Prevention of conception in women.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ^a

Predominantly used by women who are breastfeeding and in those who do not tolerate estrogens or in whom estrogens are contraindicated.^b

Levonorgestrel-releasing intrauterine system (Mirena): Intended for women who have had ≥1 child; are in a stable, mutually monogamous relationship; have no history of pelvic inflammatory disease (PID); and have no history of ectopic pregnancy or any condition that would predispose to ectopic pregnancy.¹¹⁷

Postcoital (Emergency) Contraception

Prevention of conception after unprotected intercourse (including known or suspected contraceptive failure) as an emergency contraceptive (“morning-after” pills). ¹⁰¹ ¹⁰² ¹⁰⁶ ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹ ¹³⁰ ¹³² Postcoital (emergency) contraceptive regimens are not as effective as most other forms of long-term contraception and should not be used as routine forms of contraception.¹⁰⁶ ¹²⁶ ¹²⁷ ¹³²

An emergency contraceptive regimen employing a progestin alone (levonorgestrel) appears to be more effective and better tolerated than a common estrogen-progestin emergency contraceptive (“Yuzpe”) regimen when the regimens are initiated within 72 hours of unprotected intercourse, and therefore, generally is preferred when readily available.¹⁰¹ ¹⁰² ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹

Progestins Dosage and Administration

Administration

Administer norethindrone orally.¹¹⁹ ¹²⁰

Administer levonorgestrel orally or as an intrauterine system.¹⁰⁶ ¹¹⁷ ¹³²

Administer etonogestrel implant by sub-Q insertion.¹²⁵

Oral Administration

Contraception

Take as near as possible to the same time each day (i.e., at regular 24-hour intervals) and continue daily without interruption to ensure maximum contraceptive efficacy.¹¹⁹ ¹²⁰

If vomiting occurs soon after a dose, use a back-up method of contraception (e.g., condoms, foam, sponges) for 48 hours.¹¹⁹ ¹²⁰

Available in a mnemonic dispensing package designed to aid the user in complying with the prescribed dosing regimen.¹¹⁹ ¹²⁰

Postcoital (Emergency) Contraception

Plan B One-Step, Next Choice: Administer as soon as possible but preferably within 72 hours following unprotected sex.¹⁰⁶ ¹³²

Most data support administration of the first dose up to 120 hours† after unprotected intercourse if necessary,¹²⁶ ¹²⁷ ¹²⁸ but efficacy decreases as initiation of contraception becomes more remote from unprotected intercourse.¹⁰¹ ¹⁰² ¹⁰³ ¹²⁶ ¹²⁷ ¹²⁸

May be used at any time during the menstrual cycle.¹⁰⁶ ¹³² Efficacy not established if administered >120 hours after unprotected sex.¹²⁶ ¹²⁷

Plan B One-Step: If vomiting occurs within 2 hours after administration, consider repeating the dose.¹³²

Next Choice: If vomiting occurs within 1 hour after administration, the woman should contact her healthcare provider to discuss repeating the dose.¹⁰⁶

Food not effective in reducing adverse GI effects (i.e., nausea).¹²⁶ ¹²⁷

Sub-Q Administration

Insert etonogestrel implant (Implanon) subdermally in the inner aspect of the upper arm about 6–8 cm above the elbow crease.¹²⁵ Consult manufacturer’s labeling for proper method of administration and associated precautions.¹²⁵

Intrauterine Administration

Insert levonorgestrel-releasing intrauterine system (Mirena) into the uterine cavity under strict aseptic conditions.¹¹⁷ (See Intrauterine Device Considerations under Cautions.) Consult manufacturer’s labeling for proper methods of inserting and removing the intrauterine system and for associated precautions.¹¹⁷

Dosage

When switching contraceptive methods, initiate new therapy in a manner that ensures continuous contraceptive coverage based on the mechanism of action of both methods.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Adults

Contraception

Oral

Norethindrone: 0.35 mg daily.¹¹⁹ ¹²⁰ Take 1 tablet each day and continue daily without interruption.¹¹⁹ ¹²⁰ Start on the first day of the menstrual cycle.¹¹⁹ ¹²⁰ If the first dose is taken on another day, use back-up method of contraception (e.g., condom, spermicide) for each sexual encounter for the next 48 hours.¹¹⁹ ¹²⁰

Women switching from estrogen-progestin oral contraceptives: Start norethindrone on the day after the last hormonally active tablet.¹¹⁹ ¹²⁰

Women may start using norethindrone tablets on the next day after a miscarriage or an abortion.¹¹⁹ ¹²⁰

Women whose infants are only partially breast-fed may begin norethindrone 3 weeks after delivery.¹¹⁹ ¹²⁰ Women who are exclusively breast-feeding their infants may begin 6 weeks after delivery.¹¹⁹ ¹²⁰

When a dose is taken >3 hours late or if one or more consecutive doses are missed, take the missed dose as soon as remembered, then resume regular schedule; use a back-up method of contraception (e.g., condom, spermicide) for 48 hours.¹¹⁹ ¹²⁰ If unsure of what drug regimen to take as a result of missed tablets, use a back-up method of contraception for each sexual encounter and take one tablet daily until clinician contacted.¹¹⁹ ¹²⁰

Sub-Q

Etonogestrel contraceptive implant (Implanon): One 68-mg implant every 3 years.¹²⁵

To initiate therapy in women who did not use hormonal contraception in the preceding month, insert the contraceptive implant on or before day 5 of the cycle; a back-up method of contraception is not needed.¹²⁵

Women switching from estrogen-progestin oral contraceptives, contraceptive transdermal system, or vaginal contraceptive ring: Insert the contraceptive implant within 7 days of the last hormonally active tablet, removal of a transdermal patch, or removal of the vaginal ring; a back-up method of contraception is not needed.¹²⁵

Women switching from progestin-only oral contraceptives: Insert the contraceptive implant on any day of the month (without skipping any day between receiving the last progestin oral contraceptive and the initial administration of the implant); a back-up method of contraception is not needed.¹²⁵

Women switching from a progestin-only contraceptive injection: Insert the contraceptive implant on the same day as the next contraceptive injection would have been due; a back-up method of contraception is not needed.¹²⁵

Women switching from a progestin-containing intrauterine device: Insert the contraceptive implant on the same day as the intrauterine device is removed; a back-up method of contraception is not needed.¹²⁵

The contraceptive implant can be inserted immediately after a first-trimester abortion.¹²⁵ If therapy with the contraceptive insert is not initiated within 5 days of a first-trimester abortion, follow the instructions for women who did not use hormonal contraception in the preceding month.¹²⁵

The contraceptive implant can be inserted 21–28 days after a second-trimester abortion.¹²⁵

The contraceptive implant can be inserted 21–28 days postpartum in women who are not exclusively breast-feeding; a back-up method of contraception is not needed.¹²⁵ The implant can be inserted after the fourth postpartum week in women who are exclusively breast-feeding their infant.¹²⁵ If implant insertion occurs >4 weeks postpartum, use back-up method of contraception for 7 days.¹²⁵

Remove implant 3 years after insertion.¹²⁵ At time of implant removal, may insert another implant to continue therapy.¹²⁵

Intrauterine

Levonorgestrel-releasing intrauterine contraceptive system (Mirena): One system containing 52 mg every 5 years.¹¹⁷

To initiate therapy, insert the intrauterine contraceptive system within 7 days of menses onset.¹¹⁷

The intrauterine contraceptive system can be inserted immediately after a first-trimester abortion; delay insertion until involution of the uterus is complete after a second-trimester abortion.¹¹⁷

The intrauterine contraceptive system should not be inserted until 6 weeks postpartum or after involution of the uterus is complete.¹¹⁷

Remove the intrauterine contraceptive system after 5 years of use (contraceptive efficacy >5 years not established).¹¹⁷ At time of system removal, may insert another intrauterine contraceptive system to continue therapy; removal and replacement with a new system can be done at any time during the menstrual cycle.¹¹⁷

For women with regular menstrual cycles who wish to initiate an alternative contraceptive method, remove the intrauterine system during the first 7 days of a menstrual cycle and start new method.¹¹⁷ For those with irregular cycles or amenorrhea or for those in whom the system is removed after the seventh day of the menstrual cycle, initiate the new contraceptive method at least 7 days before removal of the intrauterine system.¹¹⁷

Postcoital (Emergency) Contraception

Oral

Plan B One-Step: Single 1.5-mg dose taken as soon as possible within 72 hours of unprotected intercourse.¹³²

Next Choice: 0.75-mg dose taken as soon as possible within 72 hours of unprotected intercourse, followed by a second 0.75-mg dose 12 hours later.¹⁰¹ ¹⁰² ¹⁰⁶

If necessary, the first dose can be administered up to120 hours† after unprotected intercourse,¹²⁶ ¹²⁷ ¹²⁸ but efficacy decreases the longer initiation of contraception is delayed.¹⁰¹ ¹⁰² ¹⁰³ ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹

Repeated postcoital (emergency) contraception use indicates need for counseling about other contraceptive options.¹²⁶ ¹³¹ Safety of recurrent use not established but risk appears low, even within same menstrual cycle.¹²⁶ ¹³¹ Consider possibility that risk of adverse effects may be increased with frequently repeated postcoital contraception.¹³¹

FDA has approved Plan B One-Step for OTC status for women ≥17 years of age.¹³² Plan B One-Step and Next Choice are prescription-only preparations for women <17 years of age.¹⁰⁶ ¹³²

Cautions for Progestins

Contraindications

Known or suspected pregnancy.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²

Undiagnosed vaginal bleeding.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Known or suspected breast cancer.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Benign or malignant liver tumor.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Liver disease.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Current or past history of thrombosis or thromboembolic disorders.¹²⁵

Levonorgestrel-releasing intrauterine contraceptive system also is contraindicated in women with uterine abnormalities that distort the uterine cavity (e.g., fibroids), PID or history of PID (unless there has been a subsequent intrauterine pregnancy), postpartum endometritis or infected abortion in the past 3 months, untreated acute cervicitis or vaginosis, conditions associated with immune compromise (e.g., HIV, leukemia, IV drug abuse), a previously inserted IUD still in place, genital actinomycosis, history of ectopic pregnancy or predisposition for ectopic pregnancy, known or suspected uterine or cervical neoplasia, abnormal Papanicolaou test (Pap smear), and in women with multiple sexual partners or whose partners have multiple sexual partners.¹¹⁷

Postcoital (emergency) contraception: Manufacturer states that not known whether the conditions for contraindications of progestin-only oral contraceptives apply to the postcoital contraceptive regimen.¹⁰⁶ Most experts state that there currently is no real contraindication to postcoital (emergency) contraception with the recommended levonorgestrel regimens and that the benefits generally outweigh any theoretical or proven risk.¹²⁶ ¹²⁷ ¹³¹

Hypersensitivity to the drug or any ingredient in the formulation.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Warnings/Precautions

Warnings

Ectopic Pregnancy

Consider the possibility of ectopic pregnancy if pregnancy or severe abdominal pain occurs in women using progestin contraception, including those using postcoital (emergency) regimens.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³² Current evidence does not support increased risk of ectopic pregnancy after use of levonorgestrel for postcoital (emergency) contraception in the general population; rather, preventing pregnancy overall actually reduces absolute risk.¹²⁶ ¹²⁷ Postcoital contraception with levonorgestrel can be used in women with history of ectopic pregnancy.¹⁰⁶ ¹³¹ ¹³²

Ovarian Follicles

Possible delayed atresia of ovarian follicles, resulting in follicular enlargement.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Follicular enlargement generally is asymptomatic or associated with mild abdominal pain and resolves spontaneously; in rare cases, surgery may be required.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Bleeding Irregularities

Possible breakthrough bleeding or irregular vaginal bleeding.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Perform adequate diagnostic tests in patients with undiagnosed vaginal bleeding.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Rule out pregnancy in patients with amenorrhea.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ If pregnancy occurs, discontinue therapy.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Postcoital (emergency) contraception: Irregular vaginal bleeding also possible with postcoital contraceptive regimens;¹⁰⁶ ¹²⁶ ¹³² rule out pregnancy if menses is delayed >7 days after anticipated onset.¹⁰⁶ ¹³²

Carcinoma of Breast and Reproductive Organs

Insufficient data to determine whether use of progestin-only contraceptives is associated with an increased risk of breast cancer or cervical carcinoma.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ (See Contraindications under Cautions.)

Hepatic Effects

Insufficient data to determine whether use of progestin-only contraceptives is associated with increased risk of hepatocellular carcinoma.¹¹⁹ ¹²⁰ (See Contraindications and also see Hepatic Impairment under Cautions.)

Implant Considerations

Carefully follow recommended procedures for insertion and removal of implant to minimize potential for complications.¹²⁵

If infection develops at insertion site, initiate appropriate treatment; if infection persists, remove the implant.¹²⁵

Intrauterine Device Considerations

Evaluate women for suitability (i.e., exclude pregnancy; evaluate for genital infections, risk for ectopic pregnancy, and/or PID) prior to insertion of levonorgestrel-releasing intrauterine device.¹¹⁷ Insert the device under strict aseptic conditions.¹¹⁷

Possible complications include intrauterine pregnancy with the device in place; if this occurs, remove device to reduce possibility of complications to the woman (e.g., septicemia, septic shock, death) and fetus (e.g., miscarriage, sepsis, premature labor, premature delivery).¹¹⁷ Long-term effects unknown if pregnancy is continued with the intrauterine device in place.¹¹⁷ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Sepsis following insertion of the device reported rarely.¹¹⁷ Increased risk of infective endocarditis in women with valvular or congenital heart disease and in those with surgically constructed systemic-pulmonary shunts; prophylactic anti-infective therapy recommended at time of insertion for women with congenital heart disease.¹¹⁷

Other complications include penetration or embedment of the device in the myometrium and perforation of the uterus or cervix.¹¹⁷

Fetal/Neonatal Morbidity and Mortality

Congenital abnormalities reported infrequently in neonates born to women with a levonorgestrel-releasing intrauterine device in place during the pregnancy.¹¹⁷

Thromboembolic Disorders

Thromboembolic events (i.e., pulmonary embolism, stroke) reported in patients using etonogestrel implant (Implanon).¹²⁵

General Precautions

Physical Examination and Follow-up

Annual medical history and physical examination advised with long-term progestin therapy.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Physical examination may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician.¹¹⁹ ¹²⁰ Complete medical examination should be performed prior to initiating therapy with etonogestrel implant or levonorgestrel-releasing intrauterine system.¹¹⁷ ¹²⁵ Exercise particular care in women with family history of breast cancer or those who have breast nodules.¹²⁵

Metabolic Effects

Slight deterioration in glucose tolerance and increases in plasma insulin reported.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Monitor prediabetic and diabetic patients.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Altered lipid metabolism (decreased HDL, HDL₂, apolipoprotein A-I and A-II; increased hepatic lipase) noted; no change in total cholesterol, LDL, VLDL, or HDL₃ observed.¹¹⁹ ¹²⁰ Closely monitor women with hyperlipidemia.¹²⁵

Ocular Effects

Obtain ophthalmologist assessment for contact lens wearers who develop visual disturbances or changes in lens tolerance.¹²⁵

Depression

Exercise caution in women with a history of depression; discontinue if severe depression recurs during use.¹²⁵

Headache

Discontinue contraceptive and evaluate cause if migraine occurs or is exacerbated, or when new headache pattern develops that is recurrent, persistent, or severe.¹¹⁹ ¹²⁰

HIV and STDs

Does not protect against HIV infection or other sexually transmitted diseases (STDs).¹⁰⁶ ¹²⁷ ¹³¹ ¹³²

Specific Populations

Pregnancy

Levonorgestrel-releasing intrauterine contraceptive system (Mirena): Category X.¹¹⁷

Rule out pregnancy prior to initiating therapy.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Rule out pregnancy in patients with amenorrhea.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ If pregnancy occurs, discontinue therapy.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Postcoital (emergency) contraception: No need to rule out pregnancy with postcoital contraceptive regimens.¹²⁶ ¹²⁷ ¹²⁸ Postcoital contraceptive regimens (i.e., levonorgestrel, estrogen-progestins regimens) do not exhibit abortifacient properties¹²⁶ ¹²⁷ ¹²⁸ and do not interrupt pregnancy once endometrial implantation has occurred.¹⁰⁶ ¹²⁶ ¹²⁷ ¹²⁸ ¹³² No known harm to pregnant woman, course of pregnancy, or fetus from postcoital contraceptive regimens.¹²⁶ ¹²⁷ ¹²⁸ ¹³¹

Most studies have revealed no effects on fetal development associated with long-term use of oral progestin contraceptives.¹⁰⁶ ¹¹⁹ ¹²⁰ ¹²⁶ ¹²⁷ ¹²⁸

Lactation

Small amounts of progestins are distributed into milk.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Adverse effects, such as jaundice, reported rarely in infants.¹²⁰

Postcoital (emergency) contraception: Nursing can continue during postcoital contraceptive regimens.¹⁰⁶ ¹³¹

Pediatric Use

Safety and efficacy of progestin contraceptives have been established in women of reproductive age.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³² Safety and efficacy are expected to be identical for postpubertal adolescents <16 years of age and users ≥16 years of age.¹⁰⁶ ¹¹⁹ ¹²⁰ ¹²⁵ ¹²⁸ Not indicated before menarche.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²

Geriatric Use

Progestin contraceptives have not been evaluated in women >65 years of age and are not indicated in this population.¹¹⁷ ¹²⁵

Hepatic Impairment

Steroid hormones (including oral contraceptives) may be poorly metabolized in patients with hepatic dysfunction; use with caution in those individuals.¹²⁵ (See Contraindications under Cautions.)

Postcoital (emergency) contraception: No precautions appear necessary with short-term postcoital contraceptive regimens; benefits outweigh any theoretical or known risk.¹²⁶ ¹³¹

Common Adverse Effects

Norethindrone tablets: Bleeding irregularities (e.g., frequent or irregular bleeding), headache, breast tenderness, nausea, dizziness.¹¹⁹ ¹²⁰

Levonorgestrel tablets: Nausea, abdominal pain, fatigue, headache, menstrual changes (e.g., heavier or lighter menstrual bleeding), dizziness, breast tenderness.¹⁰⁶ ¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹ ¹³² Postcoital (emergency) contraceptive regimens better tolerated with levonorgestrel than with estrogen-progestins.¹²⁶ ¹²⁷ ¹²⁸ ¹²⁹

Etonogestrel implants: Bleeding irregularities (e.g., frequent, heavy, or prolonged bleeding, spotting).¹²⁵

Levonorgestrel-releasing intrauterine system: Abdominal pain, leukorrhea, headache, vaginitis, back pain, breast pain, acne, depression, hypertension, upper respiratory infection, nausea, nervousness, dysmenorrhea, weight increase, skin disorder, decreased libido, abnormal Pap smear, sinusitis.¹¹⁷

Interactions for Progestins

Specific Drugs

Drug	Interaction
Anticonvulsants (carbamazepine, felbamate, oxcarbazepine, phenytoin, topiramate)	Possible reduced contraceptive efficacy¹⁰⁶ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²
Antifungal agents, azole	Possible increased plasma concentrations of contraceptive steroids with itraconazole or ketoconazole¹²⁵
Anti-infective agents	Interaction unlikely with most anti-infective agents¹⁰⁶ ¹¹⁹
Antiretroviral agents	Possible changes in pharmacokinetics of orally administered progestins with some HIV protease inhibitors¹²⁰ ¹²⁵ ¹³² ^c
Barbiturates	Possible reduced contraceptive efficacy¹⁰⁶ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²
Bosentan	Possible reduced contraceptive efficacy¹³²
Griseofulvin	Possible reduced contraceptive efficacy¹²⁵ ¹³²
Modafinil	Possible reduced contraceptive efficacy¹²⁵
Rifampin	Possible reduced contraceptive efficacy¹⁰⁶ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²
St. John’s wort (Hypericum perforatum)	Possible reduced contraceptive efficacy¹²⁰ ¹²⁵ ¹³²

Progestins Pharmacokinetics

Absorption

Bioavailability

Levonorgestrel: Rapidly absorbed following oral administration with peak plasma concentrations achieved in 1.6–1.7 hours.¹⁰⁶ ¹³² Bioavailability is about 100%.¹⁰⁶

Norethindrone: Rapidly absorbed following oral administration with peak plasma concentrations achieved in 1–2 hours.¹¹⁹ ¹²⁰

Etonogestrel: Approximately 100% bioavailable following sub-Q administration.¹²⁵ Following sub-Q insertion of etonogestrel implant, the drug is released at a rate of 60–70 mcg/day at week 5–6, 35–45 mcg/day at the end of year one, 30–40 mcg/day at the end of year two, and 25–30 mcg/day at the end of year three.¹²⁵ Peak serum concentrations achieved in a few weeks following insertion of the implant.¹²⁵

Levonorgestrel: Following insertion of a levonorgestrel-containing intrauterine system, drug is released into the uterine cavity at a rate of 20 mcg/day; rate of drug release decreases over time to about 10 mcg/day after 5 years of use.¹¹⁷

Food

Effect of food on oral bioavailability not studied.¹⁰⁶ ¹²⁰ ¹³²

Distribution

Extent

Distributed into human milk.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Plasma Protein Binding

Levonorgestrel: 50% bound to albumin and 47.5% bound to sex hormone binding globulin (SHBG).¹⁰⁶ ¹¹⁷

Norethindrone: 61% bound to albumin and 36% bound to SHBG.¹²⁰

Etonogestrel: 66% bound to albumin and 32% bound to SHBG.¹²⁵

Elimination

Metabolism

Etonogestrel is metabolized in the liver by CYP3A4.¹²⁵

Norethindrone is metabolized mainly by reduction, followed by sulfate and glucuronide conjugation.¹²⁰

Elimination Route

Progestins are excreted in urine and feces, principally as metabolites and glucuronide and sulfate conjugates.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²

Half-life

Levonorgestrel (single oral dose): 24.4–27.5 hours.¹⁰⁶ ¹³²

Norethindrone (single oral dose): Approximately 8 hours.¹²⁰

Etonogestrel: Approximately 25 hours.¹²⁵

Stability

Storage

Oral

Tablets

Levonorgestrel: 20–25°C.¹⁰⁶ ¹³²

Norethindrone: 25°C (may be exposed to 15–30°C).¹¹⁹ ¹²⁰

Implant

Etonogestrel implant (Implanon): 25°C (may be exposed to 15–30°C).¹²⁵ Protect from light; avoid direct sunlight.¹²⁵

Intrauterine System

Levonorgestrel-releasing intrauterine system (Mirena): 25°C (may be exposed to 15–30°C).¹¹⁷ System is supplied sterile; do not resterilize or use device if inner package is damaged or opened.¹¹⁷

ActionsActions

Progestin contraceptives produce contraceptive effects by suppressing ovulation, thickening cervical mucus (thus inhibiting sperm migration into the uterus), lowering mid-cycle LH and FSH peaks, slowing ovum movement through the fallopian tubes, and/or alteration of the endometrium.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹²⁶ ¹²⁷ ^a

Progestin contraceptives administered after intercourse (postcoital) produce contraceptive effects by inhibiting or delaying ovulation.¹⁰⁶ ¹²⁶ ¹³² Recent evidence suggests that any endometrial effects are insufficient to prevent implantation.¹²⁶ ¹²⁷ Effects on ovulation alone cannot explain efficacy of postcoital (emergency) contraceptive; interference of sperm transport or penetration and/or impairment of corpus luteum function proposed as contributing factors.¹²⁶ ¹²⁷ Only effective before pregnancy is established; not effective after implantation of a fertilized ovum.¹⁰⁶ ¹²⁶ ¹²⁷ ¹²⁸ ¹³²

Advice to Patients

Importance of reading the manufacturer’s patient information.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²

Importance of taking progestin-only oral contraceptives at the same time each day, without interruption (including during all bleeding episodes).¹¹⁹ ¹²⁰

Importance of using a backup method of contraception (e.g., condoms, spermicides) for each sexual encounter during the next 48 hours when a progestin-only oral contraceptive dose is ≥3 hours late.¹¹⁹ ¹²⁰

Next Choice postcoital (emergency) contraception: Importance of scheduling the initial dose as conveniently as possible (preferably no later than 72 hours after intercourse if possible) and of taking the second dose 12 hours after the initial dose.¹⁰⁶

Postcoital (emergency) contraception: Therapy can be initiated up to 120 hours† after intercourse if necessary, but advise of decreased efficacy as time from intercourse to initiation of contraception increases.¹²⁶ ¹²⁷ ¹²⁸

Postcoital (emergency) contraception: Importance of consulting clinician about alternative methods of contraception if postcoital contraception is used repeatedly.¹²⁷ ¹³¹

Importance of informing women that progestin-only contraceptives, like all nonbarrier contraceptive methods, do not protect against HIV infection or other sexually transmitted diseases.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ ¹³²

Importance of advising patients of anticipated menstrual effects.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Importance of women informing a clinician if prolonged (i.e., >8 days) or unusually heavy bleeding, amenorrhea, or severe abdominal pain occurs.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ Plan to breast-feed not relevant for postcoital (emergency) contraceptive regimens.¹²⁶ ¹²⁷ ¹²⁸

Importance of women informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as concomitant illnesses.¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵

Importance of informing patients of other important precautionary information.¹⁰⁶ ¹¹⁷ ¹¹⁹ ¹²⁰ ¹²⁵ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

FDA has approved Plan B One-Step for OTC status for women ≥17 years of age; the contraceptive remains a prescription-only preparation for women <17 years of age.¹³² A commercial version of Plan B One-Step in a package that meets the prescription and OTC labeling requirements is available.¹³² Next Choice is a prescription-only preparation for women <17 years of age.¹⁰⁶

The manufacturer (Wyeth) of levonorgestrel for sub-Q implantation (Norplant) ceased production of the implants and, because of ongoing shortages with product component supplies, has no plans to reintroduce them in the US.^a The implant has not been available since August 2000.¹⁰⁹ ¹¹⁰

Etonogestrel
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Implant	68 mg	Implanon	Organon

Levonorgestrel
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Intrauterine	Intrauterine System	52 mg	Mirena	Berlex
Oral	Tablets	0.75 mg	Next Choice (available in pack of 2 tablets)	Watson
		1.5 mg	Plan B One Step	Duramed

Norethindrone (Norethisterone)
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets	0.35 mg	Micronor	Ortho-McNeil
			Nor-Q.D.	Watson

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 05/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Prometrium 100MG Capsules (ABBOTT): 30/$68.99 or 90/$184.98

Prometrium 200MG Capsules (ABBOTT): 30/$121.99 or 90/$335.97

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 01, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 2081

Saturday, 26 May 2012

Entuss Liquid

Pronunciation: hye-droe-KOE-done/poe-TASS-ee-um gwye-a-kole-SUL-foe-nate
Generic Name: Hydrocodone/Potassium Guaiacolsulfonate
Brand Name: Examples include Entuss and Mintuss NX

Entuss Liquid is used for:

Relieving cough and throat and airway irritation due to colds, flu, or hay fever. It may also be used for other conditions as determined by your doctor.

Entuss Liquid is a cough suppressant and expectorant combination. It works by loosening mucus and lung secretions in the chest, and making coughs more productive. The cough suppressant works in the brain to help decrease the cough reflex to reduce a dry cough.

Do NOT use Entuss Liquid if:

you are allergic to any ingredient in Entuss Liquid or any other codeine or morphine-related medicine (eg, oxycodone)

you are taking sodium oxybate (GHB)

you have increased pressure in the brain, trouble breathing, or diarrhea due to antibiotic use

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

Before using Entuss Liquid:

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

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

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

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

if you have a history of glaucoma, an enlarged prostate gland or other prostate problems, heart problems, diabetes, high blood pressure, blood vessel problems, stroke, adrenal gland problems, or an underactive thyroid

if you have a history of stomach problems, bowel problems (eg, chronic inflammation or ulceration of the bowel), or gallbladder problems (eg, gallstones), or if you have had recent abdominal surgery

if you have breathing or lung problems (eg, asthma, chronic bronchitis, emphysema), or chronic obstructive pulmonary disease (COPD), or if cough occurs with large amounts of mucus

if you have recently had any head injury, brain injury or tumor, infection of the brain or nervous system, epilepsy, or seizures

if you have a history of alcohol abuse, drug abuse, or suicidal thoughts or behavior

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

Cimetidine because it may increase the risk of Entuss Liquid's side effects

Barbiturates (eg, phenobarbital) or sodium oxybate (GHB) because the risk of severe drowsiness or breathing problems may be increased

Naltrexone because it may decrease Entuss Liquid's effectiveness

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

How to use Entuss Liquid:

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

Take Entuss Liquid by mouth with or without food.

Drinking extra fluids while you are taking Entuss Liquid is recommended. Check with your doctor for instructions.

Use a measuring device marked for medicine dosing. Ask your pharmacist for help if you are unsure of how to measure your dose.

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

Ask your health care provider any questions you may have about how to use Entuss Liquid.

Important safety information:

Entuss Liquid may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Entuss Liquid with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor.

If your symptoms do not get better within 5 to 7 days or if they get worse, check with your doctor.

Tell your doctor or dentist that you take Entuss Liquid before you receive any medical or dental care, emergency care, or surgery.

Entuss Liquid may interfere with certain lab tests. Be sure your doctor and lab personnel know you are taking Entuss Liquid.

Use Entuss Liquid with caution in the ELDERLY; they may be more sensitive to its effects.

Entuss Liquid should be used with extreme caution in CHILDREN younger than 6 years old; safety and effectiveness in these children have not been confirmed.

PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Entuss Liquid while you are pregnant. It is not known if Entuss Liquid is found in breast milk. Do not breast-feed while taking Entuss Liquid.

When used for long periods of time or at high doses, Entuss Liquid may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Entuss Liquid stops working well. Do not take more than prescribed.

When used for longer than a few weeks or at high doses, some people develop a need to continue taking Entuss Liquid. This is known as DEPENDENCE or addiction.

If you suddenly stop taking Entuss Liquid, you may experience WITHDRAWAL symptoms including anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping.

Possible side effects of Entuss Liquid:

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

Constipation; dizziness; drowsiness; excitability; headache; nausea; nervousness or anxiety; trouble sleeping; weakness.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); anxiety; change in amount of urine; difficulty urinating; hearing change or loss; mental or mood changes; severe drowsiness.

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

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include blurred vision; confusion; hallucinations; seizures; severe dizziness, lightheadedness, or headache; severe drowsiness; unusually fast, slow, or irregular heartbeat; vomiting.

Proper storage of Entuss Liquid:

Store Entuss Liquid at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Entuss Liquid out of the reach of children and away from pets.

General information:

If you have any questions about Entuss Liquid, please talk with your doctor, pharmacist, or other health care provider.

Entuss Liquid is to be used only by the patient for whom it is prescribed. Do not share it with other people.

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

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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Entuss resources

Entuss Use in Pregnancy & Breastfeeding
Entuss Drug Interactions
Entuss Support Group
0 Reviews · Be the first to review/rate this drug

Friday, 25 May 2012

Vfend Tablets

Pronunciation: VOR-i-KON-a-zole
Generic Name: Voriconazole
Brand Name: Vfend

Vfend is used for:

Treating certain fungal infections.

Vfend is an azole antifungal. It works by blocking fungal cell wall growth, resulting in the death of the fungus.

Do NOT use Vfend if:

you are allergic to any ingredient in Vfend

you have galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption

you have untreated low blood calcium, magnesium, or potassium levels

you are taking astemizole, a barbiturate (eg, phenobarbital), cabazitaxel, carbamazepine, cisapride, crizotinib, dronedarone, an ergot alkaloid (eg, ergotamine), erythromycin, everolimus, fluconazole, lurasidone, pimozide, quinidine, rifabutin, rifampin, rivaroxaban, sirolimus, St. John's wort, terfenadine, or ticagrelor

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

Before using Vfend:

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

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

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

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

if you are allergic to other azole antifungals (eg, fluconazole, itraconazole)

if you have a history of heart problems (eg, cardiomyopathy, irregular heartbeat); an abnormal electrocardiogram (ECG) (a type of heart test); or low blood calcium, magnesium, or potassium levels

if you have liver problems (eg, cirrhosis), kidney problems, pancreas problems, a weakened immune system, or a blood disease (eg, blood or bone marrow cancer)

if you have trouble digesting dairy products or lactose

if you have ever been on chemotherapy or have had a stem cell transplant

if you have taken fluconazole within the last 24 hours

if you are taking ritonavir. Vfend should not be taken with certain doses of ritonavir

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

Medicines that may harm the kidney because the risk of kidney side effects may be increased. Ask your doctor or pharmacist if you are unsure if any of your medicines might affect the kidney

Medicines that may increase the risk of a certain type of irregular heartbeat (prolonged QT interval). Check with your doctor or pharmacist if you are unsure if any of your medicines may increase the risk of this type of irregular heartbeat

Many other prescription and nonprescription medicines (eg, used for aches and pains, anxiety, birth control, blood flow problems, blood thinning, cancer, diabetes, drug dependence, heartburn or reflux, high blood pressure, high cholesterol, HIV, immune system suppression, infections, irregular heartbeat or other heart problems, mental or mood problems, pain, seizures, stomach or bowel problems), multivitamin products, or herbal or dietary supplements (eg, herbal teas, coenzyme Q10, garlic, ginseng, ginkgo, St. John's wort) may interact with Vfend. Ask your doctor or pharmacist if you are unsure if any of your medicines might interact with Vfend

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

How to use Vfend:

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

An extra patient leaflet is available with Vfend. Talk to your pharmacist if you have questions about this information.

Take Vfend by mouth on an empty stomach at least 1 hour before or 1 hour after eating.

To clear up your infection completely, take Vfend for the full course of treatment. Keep taking it even if you feel better in a few days.

If you miss a dose of Vfend, take it as soon as possible. If it is more than 6 hours after the missed dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

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

Important safety information:

Vfend may cause blurred vision or sensitivity to light. These effects may be worse if you take it with alcohol or certain medicines. Use Vfend with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

Avoid driving at night while you are using Vfend.

Vfend may cause you to become sunburned more easily. Avoid the sun, sunlamps, or tanning booths until you know how you react to Vfend. Use a sunscreen or wear protective clothing if you must be outside for more than a short time.

Certain types of skin cancers (eg, melanoma, squamous cell) have been reported in patients who became sensitive to sunlight while taking Vfend for a long period of time. Contact your doctor if you notice a change in the appearance of a mole or other unusual skin change or growth. Discuss any questions or concerns with your doctor.

Vfend may make your eyes more sensitive to sunlight. It may help to wear sunglasses. Avoid strong, direct sunlight.

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

If your symptoms do not improve within a few days or if they become worse, check with your doctor.

Women who may become pregnant should use effective birth control (eg, birth control pills) while taking Vfend. Talk with your doctor if you have questions about effective birth control.

Lab tests, including eye exams, liver and kidney function, and pancreas function, may be performed while you use Vfend. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

Vfend should be used with extreme caution in CHILDREN younger than 12 years old; safety and effectiveness in these children have not been confirmed.

PREGNANCY and BREAST-FEEDING: Vfend may cause harm to the fetus. Do not become pregnant while you are using it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Vfend while you are pregnant. It is not known if Vfend is found in breast milk. Do not breast-feed while taking Vfend.

Possible side effects of Vfend:

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

Blurred vision; headache; nausea; sensitivity to light; sensitivity to the sun; vomiting.

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

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; black, tarry stools; bone pain; calf or leg pain, redness, swelling, or tenderness; change in the appearance of a mole; chest, jaw, or arm pain; confusion; decreased urination; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; flushing; hallucinations; mental or mood changes (eg, depression); mouth sores; one-sided weakness; red, swollen, peeling, or blistered skin; seizures; severe or persistent dizziness or headache; shortness of breath; speech changes; sudden, severe nausea or vomiting; suicidal thoughts or actions; swelling of the arms or legs; symptoms of liver problems (eg, yellowing of the skin or eyes; dark urine; pale stools; severe or persistent nausea, vomiting, or stomach pain; loss of appetite; itching); symptoms of pancreatitis (eg, severe stomach or back pain, with or without nausea or vomiting); unusual bruising or bleeding; unusual skin change or skin growth; unusual sweating or weakness; unusual tiredness; unusual vaginal bleeding; vision changes (eg, color vision change, persistent or severe blurred vision or sensitivity to light).

See also: Vfend side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.

Proper storage of Vfend:

Store Vfend at room temperature, between 59 and 86 degrees F (15 and 30 degrees C). Store away from heat, moisture, and light. Do not store in the bathroom. Keep Vfend out of the reach of children and away from pets.

General information:

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

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

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

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

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

Issue Date: February 1, 2012

Database Edition 12.1.1.002

More Vfend resources

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

Compare Vfend with other medications

Aspergillosis, Invasive
Blastomycosis
Candida Infections, Systemic
Coccidioidomycosis, Meningitis
Cutaneous Fungal Infection
Esophageal Candidiasis
Eumycetoma
Fungal Infection, Internal and Disseminated
Fungal Meningitis
Fungal Pneumonia
Fusariosis
Ocular Fungal Infection
Pseudoallescheriosis
Systemic Fungal Infection

Monday, 21 May 2012

Gemcitabine 38mg / ml powder for solution for infusion

1. Name Of The Medicinal Product

Gemcitabine 38mg/ml powder for solution for infusion

2. Qualitative And Quantitative Composition

One ml of the reconstituted solution for infusion (see section 6.6) contains 38mg gemcitabine (as hydrochloride).

200 mg vial:

Each vial contains 200mg of gemcitabine (as hydrochloride).

Contains approximately 0.15mmol (3.56mg) sodium per 200mg vial.

1 g vial:

Each vial contains 1g of gemcitabine (as hydrochloride).

Contains approximately 0.77mmol (17.81mg) sodium per 1g vial.

2 g vial:

Each vial contains 2g of gemcitabine (as hydrochloride).

Contains approximately 1.54mmol (35.62mg) sodium per 2g vial.

For a full list of excipients, see section 6.1.

3. Pharmaceutical Form

Powder for solution for infusion.

White or almost white compact aggregate. After reconstitution in sodium chloride 0.9% the solution is clear to pale opalescent and colourless to pale yellow.

The pH of the reconstituted solution in sodium chloride 0.9% solution is 3.0 ± 0.3.

The osmolarity of the reconstituted solution (38mg/ml of gemcitabine (as hydrochloride) in sodium chloride 0.9% solution) is 775 mOsm/l.

4. Clinical Particulars

4.1 Therapeutic Indications

Gemcitabine is indicated for the treatment of locally advanced or metastatic bladder cancer in combination with cisplatin.

Gemcitabine is indicated for treatment of patients with locally advanced or metastatic adenocarcinoma of the pancreas.

Gemcitabine, in combination with cisplatin is indicated as first line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine monotherapy can be considered in elderly patients or those with performance status 2.

Gemcitabine is indicated for the treatment of patients with locally advanced or metastatic epithelial ovarian carcinoma, in combination with carboplatin, in patients with relapsed disease following a recurrence-free interval of at least 6 months after platinum-based, first-line therapy.

Gemcitabine, in combination with paclitaxel, is indicated for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/neoadjuvant chemotherapy. Prior chemotherapy should have included an anthracycline unless clinically contraindicated.

4.2 Posology And Method Of Administration

Gemcitabine should only be prescribed by a physician qualified in the use of anti-cancer chemotherapy.

Recommended posology

Bladder cancer

Combination use

The recommended dose for gemcitabine is 1000mg/m², given by 30² on Day 1 following gemcitabine or day 2 of each 28

Pancreatic cancer

The recommended dose of gemcitabine is 1000mg/m², given by 30

Non small cell lung cancer

Monotherapy

The recommended dose of gemcitabine is 1000mg/m², given by 30

Combination use

The recommended dose for gemcitabine is 1250mg/m² body surface area given as a 30

Cisplatin has been used at doses between 75-100mg/m² once every 3 weeks.

Breast cancer

Combination use

Gemcitabine in combination with paclitaxel is recommended using paclitaxel (175mg/m²) administered on Day 1 over approximately 3²) as a 30⁶/l) prior to initiation of gemcitabine + paclitaxel combination.

Ovarian cancer

Combination use

Gemcitabine in combination with carboplatin is recommended using gemcitabine 1000mg/m² administered on Days 1 and 8 of each 21

Monitoring for toxicity and dose modification due to toxicity

Dose modification due to non haematological toxicity

Periodic physical examination and checks of renal and hepatic function should be made to detect non-haematological toxicity. Dosage reduction with each cycle or within a cycle may be applied based upon the grade of toxicity experienced by the patient. In general, for severe (Grade 3 or 4) non-haematological toxicity, except nausea/vomiting, therapy with gemcitabine should be withheld or decreased depending on the judgement of the treating physician. Doses should be withheld until toxicity has resolved in the opinion of the physician.

For cisplatin, carboplatin, and paclitaxel dosage adjustment in combination therapy, please refer to the corresponding Summary of Product Characteristics.

Dose modification due to haematological toxicity

Initiation of a cycle

For all indications, the patient must be monitored before each dose for platelet and granulocyte counts. Patients should have an absolute granulocyte count of at least 1,500 (x 10⁶/l) and platelet account of 100,000 (x 10⁶/l) prior to the initiation of a cycle.

Within a cycle

Dose modifications of gemcitabine within a cycle should be performed according to the following tables:

Dose modification of gemcitabine within a cycle for bladder cancer, NSCLC and pancreatic cancer, given in monotherapy or in combination with cisplatin
Absolute granulocyte count (x 10⁶/l)	Platelet count (x 10⁶/l)	Percentage of standard dose of gemcitabine (%)
> 1,000 and	> 100,000	100
500-1,000 or	50,000-100,000	75
<500 or	< 50,000	Omit dose *

*Treatment omitted will not be re-instated within a cycle before the absolute granulocyte count reaches at least 500 (x10⁶/l) and the platelet count reaches 50,000 (x10⁶/l).

Dose modification of gemcitabine within a cycle for breast cancer, given in combination with paclitaxel
Absolute granulocyte count (x 10⁶/l)	Platelet count (x 10⁶/l)	Percentage of standard dose of gemcitabine (%)
	>75,000	100
1,000- <1,200 or	50,000-75,000	75
700- <1,000 and		50
<700 or	<50,000	Omit dose*

*Treatment omitted will not be re-instated within a cycle. Treatment will start on day 1 of the next cycle once the absolute granulocyte count reaches at least 1,500 (x10⁶/l) and the platelet count reaches 100,000 (x10⁶/l).

Dose modification of gemcitabine within a cycle for ovarian cancer, given in combination with carboplatin
Absolute granulocyte count (x 10⁶/l)	Platelet count (x 10⁶/l)	Percentage of standard dose of gemcitabine (%)
> 1,500 and		100
1000-1,500 or	75,000-100,000	50
<1000 or	< 75,000	Omit dose*

Dose modifications due to haematological toxicity in subsequent cycles, for all indications

The gemcitabine dose should be reduced to 75% of the original cycle initiation dose, in the case of the following haematological toxicities:

• Absolute granulocyte count < 500 x 10⁶/l for more than 5 days

• Absolute granulocyte count < 100 x 10⁶/l for more than 3 days

• Febrile neutropaenia

• Platelets < 25,000 x 10⁶/l

• Cycle delay of more than 1 week due to toxicity

Method of administration

The medicinal product is tolerated well during infusion and may be administered ambulant. If extravasation occurs, generally the infusion must be stopped immediately and started again in another blood vessel. The patient should be monitored carefully after the administration.

For instructions on reconstitution, see section 6.6

Special populations

Patients with renal or hepatic impairment

Gemcitabine should be used with caution in patients with hepatic or renal insufficiency as there is insufficient information from clinical studies to allow for clear dose recommendations for these patient populations (see sections 4.4 and 5.2).

Elderly population(> 65 years)

Gemcitabine has been well tolerated in patients over the age of 65. There is no evidence to suggest that dose adjustments, other than those already recommended for all patients, are necessary in the elderly (see section 5.2).

Paediatric population (< 18 years)

Gemcitabine is not recommended for use in children under 18 years of age due to insufficient data on safety and efficacy.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients.

Breast-feeding (see section 4.6).

4.4 Special Warnings And Precautions For Use

Prolongation of the infusion time and increased dosing frequency have been shown to increase toxicity.

Haematological toxicity

Gemcitabine can suppress bone marrow function as manifested by leucopaenia, thrombocytopaenia and anaemia.

Patients receiving gemcitabine should be monitored prior to each dose for platelet, leucocyte and granulocyte counts. Suspension or modification of therapy should be considered when drug-induced bone marrow depression is detected (see section 4.2). However, myelosuppression is short lived and usually does not result in dose reduction and rarely in discontinuation.

Peripheral blood counts may continue to deteriorate after gemcitabine administration has been stopped. In patients with impaired bone marrow function, the treatment should be started with caution. As with other cytotoxic treatments, the risk of cumulative bone-marrow suppression must be considered when gemcitabine treatment is given together with other chemotherapy.

Hepatic insufficiency

Administration of gemcitabine in patients with concurrent liver metastases or a pre-existing medical history of hepatitis, alcoholism or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.

Laboratory evaluation of renal and hepatic function (including virological tests) should be performed periodically.

Gemcitabine should be used with caution in patients with hepatic insufficiency or with impaired renal function as there is insufficient information from clinical studies to allow clear dose recommendation for this patient population (see section 4.2).

Concomitant radiotherapy

Concomitant radiotherapy (given together or

Live vaccinations

Yellow fever vaccine and other live attenuated vaccines are not recommended in patients treated with gemcitabine (see section 4.5).

Cardiovascular

Due to the risk of cardiac and/or vascular disorders with gemcitabine, particular caution must be exercised with patients presenting a history of cardiovascular events.

Pulmonary

Pulmonary effects, sometimes severe (such as pulmonary oedema, interstitial pneumonitis or adult respiratory distress syndrome (ARDS)) have been reported in association with gemcitabine therapy. The aetiology of these effects is unknown. If such effects develop, consideration should be made to discontinuing gemcitabine therapy. Early use of supportive care measure may help ameliorate the condition.

Renal

Clinical findings consistent with the haemolytic uraemic syndrome (HUS) were rarely reported in patients receiving gemcitabine (see section 4.8). Gemcitabine should be discontinued at the first signs of any evidence of microangiopathic haemolytic anaemia, such as rapidly falling haemoglobin with concomitant thrombocytopaenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen, or LDH. Renal failure may not be reversible with discontinuation of therapy and dialysis may be required.

Fertility

In fertility studies gemcitabine caused hypospermatogenesis in male mice (see section 5.3). Therefore, men being treated with gemcitabine are advised not to father a child during and up to 6 months after treatment and to seek further advice regarding cryoconservation of sperm prior to treatment because of the possibility of infertility due to therapy with gemcitabine (see section 4.6).

Sodium

Vial of 200mg gemcitabine contains 3.56mg (<1mmol) sodium.

Vial of 1g gemcitabine contains 17.81mg (< 1mmol) sodium.

Vial of 2g gemcitabine contains 35.62mg (1.54mmol) sodium.

This should be taken into consideration by patients on a controlled sodium diet.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No specific interaction studies have been performed (see section 5.2)

Radiotherapy

Concurrent (given together or ² was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non-small cell lung cancer, significant toxicity in the form of severe, and potentially life threatening mucositis, especially oesophagitis, and pneumonitis was observed, particularly in patients receiving large volumes of radiotherapy [median treatment volumes 4,795 cm³]. Studies done subsequently have suggested that it is feasible to administer gemcitabine at lower doses with concurrent radiotherapy with predictable toxicity, such as a phase II study in non-small cell lung cancer, where thoracic radiation doses of 66 Gy were applied concomitantly with an administration with gemcitabine (600mg/m², four times) and cisplatin (80mg/m² twice) during 6 weeks. The optimum regimen for safe administration of gemcitabine with therapeutic doses of radiation has not yet been determined in all tumour types.

Non-concurrent (given>7 days apart)- Analysis of the data does not indicate any enhanced toxicity when gemcitabine is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that gemcitabine can be started after the acute effects of radiation have resolved or at least one week after radiation.

Radiation injury has been reported on targeted tissues (e.g. oesophagitis, colitis, and pneumonitis) in association with both concurrent and non-concurrent use of gemcitabine.

Others

Yellow fever and other live attenuated vaccines are not recommended due to the risk of systemic, possibly fatal, disease, particularly in immunosuppressed patients.

4.6 Pregnancy And Lactation

Pregnancy

There are no adequate data from the use of gemcitabine in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Based on results from animal studies and the mechanism of action of gemcitabine, this substance should not be used during pregnancy unless clearly necessary. Women should be advised not to become pregnant during treatment with gemcitabine and to warn their attending physician immediately, should this occur after all.

Breast-feeding

It is not known whether gemcitabine is excreted in human milk and adverse effects on the suckling child cannot be excluded. Breast-feeding must be discontinued during gemcitabine therapy.

Fertility

4.7 Effects On Ability To Drive And Use Machines

No studies on the effects on the ability to drive and use machines have been performed. However, gemcitabine has been reported to cause mild to moderate somnolence, especially in combination with alcohol consumption. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.

4.8 Undesirable Effects

The most commonly reported adverse drug reactions associated with gemcitabine treatment include: nausea with or without vomiting, raised liver transaminases (AST/ALT) and alkaline phosphatase, reported in approximately 60% of patients; proteinuria and haematuria reported in approximately 50% patients; dyspnoea reported in 10

The frequency and severity of the adverse reactions are affected by the dose, infusion rate and intervals between doses (see section 4.4). Dose

Clinical trial data

Frequencies are defined as: Very common (

The following table of undesirable effects and frequencies is based on data from clinical trials. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

System Organ Class	Frequency grouping
Blood and lymphatic system disorders	Very common • Leucopaenia (Neutropaenia Grade 3 = 19.3 %; Grade 4 = 6 %). Bone-marrow suppression is usually mild to moderate and mostly affects the granulocyte count (see section 4.2) • Thrombocytopaenia • Anaemia Common • Febrile neutropaenia Very rare • Thrombocytosis
Immune system disorders	Very Rare • Anaphylactoid reaction
Metabolism and nutrition disorders	Common • Anorexia
Nervous system disorders	Common • Headache • Insomnia • Somnolence
Cardiac disorders	Rare • Myocardial infarct
Vascular disorders	Rare • Hypotension
Respiratory, thoracic and mediastinal disorders	Very common • Dyspnoea –usually mild and passes rapidly without treatment Common • Cough • Rhinitis Uncommon • Interstitial pneumonitis (see section 4.4) • Bronchospasm –usually mild and transient but may require parenteral treatment
Gastrointestinal disorders	Very common • Vomiting • Nausea Common • Diarrhoea • Stomatitis and ulceration of the mouth • Constipation
Hepatobiliary disorders	Very common • Elevation of liver transaminases (AST and ALT) and alkaline phosphatase Common • Increased bilirubin Rare • Increased gamma-glutamyl transferase (GGT)
Skin and subcutaneous tissue disorders	Very common • Allergic skin rash frequently associated with pruritus • Alopecia Common • Itching •Sweating Rare • Ulceration • Vesicle and sore formation • Scaling Very rare • Severe skin reactions, including desquamation and bullous skin eruptions
Musculoskeletal and connective tissue disorders	Common • Back pain • Myalgia
Renal and urinary disorders	Very Common • Haematuria • Mild proteinuria
General disorders and administration site conditions	Very common • Influenza-like symptoms - the most common symptoms are fever, headache, chills, myalgia, asthenia and anorexia. Cough, rhinitis, malaise, perspiration and sleeping difficulties have also been reported. • Oedema/peripheral oedema-including facial oedema. Oedema is usually reversible after stopping treatment Common • Fever • Asthenia • Chills Rare • Injection site reactions-mainly mild in nature
Injury, poisoning, and procedural Complications	Radiation toxicity (see section 4.5).

Postmarketing experience (spontaneous reports) frequency not known (can't be estimated from the available data)

Nervous system disorders

Cerebrovascular accident

Cardiac disorders

Arrythmias, predominantly supraventricular in nature

Heart failure

Vascular disorders

Clinical signs of peripheral vasculitis and gangrene

Respiratory, thoracic and mediastinal disorders

Pulmonary oedema

Adult respiratory distress syndrome (see section 4.4)

Gastrointestinal disorders

Ischaemic colitis

Hepatobiliary disorders

Serious hepatotoxicity, including liver failure and death

Skin and subcutaneous tissue disorders

Severe skin reactions, including desquamation and bullous skin eruptions, Lyell's Syndrome, Steven-Johnson Syndrome

Renal and urinary disorders

Renal failure (see section 4.4)

Haemolytic uraemic syndrome (see section 4.4)

Injury, poisoning and procedural complications

Radiation recall

Combination use in breast cancer

The frequency of grade 3 and 4 haematological toxicities, particularly neutropaenia, increases when gemcitabine is used in combination with paclitaxel. However, the increase in these adverse reactions is not associated with an increased incidence of infections or haemorrhagic events. Fatigue and febrile neutropaenia occur more frequently when gemcitabine is used in combination with paclitaxel. Fatigue, which is not associated with anaemia, usually resolves after the first cycle.

Grade 3 and 4 Adverse Events Paclitaxel versus gemcitabine plus paclitaxel
	Number (%) of Patients
Paclitaxel arm (N=259)	Gemcitabine plus Paclitaxel arm (N=262)
Grade 3	Grade 4	Grade 3	Grade 4
Laboratory
Anaemia	5 (1.9)	1 (0.4)	15 (5.7)	3 (1.1)
Thrombocytopaenia	0	0	14 (5.3)	1 (0.4)
Neutropaenia	11 (4.2)	17 (6.6)*	82 (31.3)	45 (17.2)*
Non-laboratory
Febrile neutropaenia	3 (1.2)	0	12 (4.6)	1(0.4)
Fatigue	3 (1.2)	1 (0.4)	15 (5.7)	2 (0.8)
Diarrhoea	5 (1.9)	0	8 (3.1)	0
Motor neuropathy	2(0.8)	0	6(2.3)	1(0.4)
Sensory neuropathy	9(3.5)	0	14(5.3)	1(0.4)

*Grade 4 neutropaenia lasting for more than 7 days occurred in 12.6% of patients in the combination arm and 5.0% of patients in the paclitaxel arm.

Combination use in bladder cancer

Grade 3 and 4 Adverse Events MVAC versus Gemcitabine plus cisplatin
	Number (%) of Patients
MVAC (methotrexate, vinblastine, doxorubicin and cisplatin) arm (N=196)	Gemcitabine plus cisplatin arm (N=200)
Grade 3	Grade 4	Grade 3	Grade 4
Laboratory
Anaemia	30(16)	4(2)	47(24)	7(4)
Thrombocytopaenia	15(8)	25(13)	57(29)	57(29)
Non-laboratory
Nausea and vomiting	37(19)	3(2)	44(22)	0(0)
Diarrhoea	15(8)	1(1)	6(3)	0(0)
Infection	19(10)	10(5)	4(2)	1(1)
Stomatitis	34(18)	8(4)	2(1)	0(0)

Combination use in ovarian cancer

Grade 3 and 4 Adverse Events Carboplatin versus Gemcitabine plus carboplatin
	Number (%) of Patients
Carboplatin arm (N=174)	Gemcitabine plus carboplatin arm (N=175)
Grade 3	Grade 4	Grade 3	Grade 4
Laboratory
Anaemia	10(5.7)	4(2.3)	39(22.3)	9(5.1)
Neutropaenia	19(10.9)	2(1.1)	73(41.7)	50(28.6)
Thrombocytopaenia	18(10.3)	2(1.1)	53(30.3)	8(4.6)
Leucopaenia	11(6.3)	1(0.6)	84(48.0)	9(5.1)