Clomid

1. Name Of The Medicinal Product

Clomid™ 50mg Tablets

2. Qualitative And Quantitative Composition

Clomifene Citrate 50mg

3. Pharmaceutical Form

Tablet

4. Clinical Particulars

4.1 Therapeutic Indications

Clomid 50mg Tablets (Clomifene Citrate BP) is indicated for the treatment of ovulatory failure in women desiring pregnancy. Clomid 50mg Tablets is indicated only for patients in whom ovulatory dysfunction is demonstrated. Other causes of infertility must be excluded or adequately treated before giving Clomid 50mg Tablets.

4.2 Posology And Method Of Administration

Route of Administration

Oral

Adults Only:

The recommended dose for the first course of Clomid 50mg Tablets (Clomifene Citrate BP) is 50mg (1 tablet) daily for 5 days. Therapy may be started at any time in the patient who has had no recent uterine bleeding. If progestin-induced bleeding is planned, or if spontaneous uterine bleeding occurs before therapy, the regimen of 50mg daily for 5 days should be started on or about the fifth day of the cycle. When ovulation occurs at this dosage, there is no advantage to increasing the dose in subsequent cycles of treatment.

If ovulation appears not to have occurred after the first course of therapy, a second course of 100mg daily (two 50mg tablets given as a single daily dose) for 5 days should be given. This course may be started as early as 30 days after the previous one. Increase of the dosage or duration of therapy beyond 100mg/day for 5 days should not be undertaken.

The majority of patients who are going to respond will respond to the first course of therapy, and 3 courses should constitute an adequate therapeutic trial. If ovulatory menses have not yet occurred, the diagnosis should be re-evaluated. Treatment beyond this is not recommended in the patient who does not exhibit evidence of ovulation.

Long-term cyclic therapy.

Not recommended.

The relative safety of long-term cyclic therapy has not been conclusively demonstrated and, since the majority of patients will ovulate following 3 courses, long-term cyclic therapy is not recommended, i.e. beyond a total of about 6 cycles (including 3 ovulatory cycles).

Special Populations

Special care with lower dosage or duration of treatment is particularly recommended if unusual sensitivity to pituitary gonadotrophin is suspected, such as in patients with polycystic ovary syndrome (See Section 5.1).

4.3 Contraindications

Pregnancy: See 4.6

Liver disease: Clomid 50mg Tablets (Clomifene Citrate BP) therapy is contraindicated in patients with liver disease or a history of liver dysfunction.

Abnormal uterine bleeding: Clomid 50mg Tablets is contraindicated in patients with hormone-dependent tumours or in patients with abnormal uterine bleeding of undetermined origin.

Ovarian cyst: Clomid 50mg Tablets should not be given in the presence of an ovarian cyst, except polycystic ovary, since further enlargement of the cyst may occur. Patients should be evaluated for the presence of ovarian cyst prior to each course of treatment.

4.4 Special Warnings And Precautions For Use

Warnings:

General: Good levels of endogenous oestrogen (as estimated from vaginal smears, endometrial biopsy, assay of urinary oestrogen, or endometrial bleeding in response to progesterone) provide a favourable prognosis for ovulatory response induced by Clomid 50mg Tablets. A low level of oestrogen, although clinically less favourable, does not preclude successful outcome of therapy. Clomid 50mg Tablets therapy is ineffective in patients with primary pituitary or primary ovarian failure. Clomid 50mg Tablets therapy cannot be expected to substitute for specific treatment of other causes of ovulatory failure, such as thyroid or adrenal disorders. For hyperprolactinaemia there is other preferred specific treatment. Clomid 50mg Tablets is not first line treatment for low weight related amenorrhoea, with infertility, and has no value if a high FSH blood level is observed following an early menopause.

Ovarian Hyperstimulation Syndrome: Ovarian Hyperstimulation Syndrome (OHSS) has been reported in patients receiving Clomid 50mg Tablets therapy for ovulation induction. In some cases, OHSS occurred following the cyclic use of Clomid 50mg Tablets therapy or when Clomid 50mg Tablets was used in combination with gonadotropins. The following symptoms have been reported in association with this syndrome during Clomid 50mg Tablets therapy: pericardial effusion, anasarca, hydrothorax, acute abdomen, renal failure, pulmonary oedema, ovarian haemorrhage, deep venous thrombosis, torsion of the ovary and acute respiratory distress. If conception results, rapid progression to the severe form of the syndrome may occur.

To minimise the hazard of the abnormal ovarian enlargement associated with Clomid 50mg Tablets therapy, the lowest dose consistent with expectation of good results should be used. The patient should be instructed to inform the physician of any abdominal or pelvic pain, weight gain, discomfort or distension after taking Clomid 50mg Tablets. Maximal enlargement of the ovary may not occur until several days after discontinuation of the course of Clomid 50mg Tablets. Some patients with polycystic ovary syndrome who are unusually sensitive to gonadotropin may have an exaggerated response to usual doses of Clomid 50mg Tablets.

The patient who complains of abdominal or pelvic pain, discomfort, or distension after taking Clomid 50mg Tablets should be examined because of the possible presence of an ovarian cyst or other cause. Due to fragility of enlarged ovaries in severe cases, abdominal and pelvic examination should be performed very cautiously. If abnormal enlargement occurs Clomid 50mg Tablets should not be given until the ovaries have returned to pre-treatment size. Ovarian enlargement and cyst formation associated with Clomid 50mg Tablets therapy usually regress spontaneously within a few days or weeks after discontinuing treatment. Most of these patients should be managed conservatively. The dosage and/or duration of the next course of treatment should be reduced.

Visual Symptoms: Patients should be advised that blurring or other visual symptoms such as spots or flashes (scintillating scotomata) may occasionally occur during or shortly after therapy with Clomid 50mg Tablets. These visual disturbances are usually reversible; however, cases of prolonged visual disturbance have been reported including after Clomid 50mg Tablet discontinuation. The visual disturbances may be irreversible especially with increased dosage or duration of therapy. The significance of these visual symptoms is not understood. If the patient has any visual symptoms, treatment should be discontinued and ophthalmologic evaluation performed. Patients should be warned that visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting.

Precautions:

Multiple Pregnancy: There is an increased chance of multiple pregnancy when conception occurs in relationship to Clomid 50mg Tablets therapy. The potential complications and hazards of multiple pregnancy should be discussed with the patient. During the clinical investigation studies, the incidence of multiple pregnancy was 7.9% (186 of 2369 Clomid 50mg Tablets associated pregnancies on which outcome was reported). Among these 2369 pregnancies, 165 (6.9%) twin, 11 (0.5%) triplet, 7 (0.3%) quadruplet and 3 (0.13%) quintuplet. Of the 165 twin pregnancies for which sufficient information was available, the ratio of monozygotic twins was 1:5.

Ectopic Pregnancy: There is an increased chance of ectopic pregnancy (including tubal and ovarian sites) in women who conceive following Clomid 50mg Tablets therapy. Multiple pregnancies, including simultaneous intrauterine and extrauterine pregnancies, have been reported.

Uterine Fibroids: Caution should be exercised when using Clomid 50mg Tablets in patients with uterine fibroids due to potential for further enlargement of the fibroids.

Pregnancy Wastage and Birth Anomalies: The overall incidence of reported birth anomalies from pregnancies associated with maternal Clomid 50mg Tablets ingestion (before or after conception) during the investigational studies was within the range of that reported in the published references for the general population. Among the birth anomalies spontaneously reported in the published literature as individual cases, the proportion of neural tube defects has been high among pregnancies associated with ovulation induced by Clomid 50mg Tablets, but this has not been supported by data from population based studies.

The physician should explain so that the patient understands the assumed risk of any pregnancy whether the ovulation was induced with the aid of Clomid 50mg Tablets or occurred naturally.

The patient should be informed of the greater pregnancy risks associated with certain characteristics or conditions of any pregnant woman: e.g. age of female and male partner, history of spontaneous abortions, Rh genotype, abnormal menstrual history, infertility history (regardless of cause), organic heart disease, diabetes, exposure to infectious agents such as rubella, familial history of birth anomaly, and other risk factors that may be pertinent to the patient for whom Clomid 50mg Tablets is being considered. Based upon the evaluation of the patient, genetic counselling may be indicated.

Population based reports have been published on possible elevation of risk of Down's Syndrome in ovulation induction cases and of increase in trisomy defects among spontaneously aborted foetuses from subfertile women receiving ovulation inducing drugs (no women with Clomid 50mg Tablets alone and without additional inducing drug). However, as yet, the reported observations are too few to confirm or not confirm the presence of an increased risk that would justify amniocentesis other than for the usual indications because of age and family history.

The experience from patients of all diagnosis during clinical investigation of Clomid 50mg Tablets shows a pregnancy (single and multiple) wastage or foetal loss rate of 21.4% (abortion rate of 19.0%), ectopic pregnancies, 1.18%, hydatidiform mole, 0.17%, foetus papyraceous, 0.04% and of pregnancies with one or more stillbirths, 1.01%.

Clomid 50mg Tablets therapy after conception was reported for 158 of the 2369 delivered and reported pregnancies in the clinical investigations. Of these 158 pregnancies 8 infants (born of 7 pregnancies) were reported to have birth defects.

There was no difference in reported incidence of birth defects whether Clomid 50mg Tablets was given before the 19th day after conception or between the 20th and 35th day after conception. This incidence is within the anticipated range of general population.

Ovarian Cancer: There have been rare reports of ovarian cancer with fertility drugs; infertility itself is a primary risk factor. Epidemiological data suggest that prolonged use of Clomid 50mg Tablets may increase this risk. Therefore the recommended duration of treatment should not be exceeded (see section 4.2).

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

None stated.

4.6 Pregnancy And Lactation

Clomid 50mg Tablets is not indicated during pregnancy. Although there is no evidence that Clomid 50mg Tablets has a harmful effect on the human foetus, there is evidence that Clomid 50mg Tablets has a deleterious effect on rat and rabbit foetuses when given in high doses to the pregnant animal. To avoid inadvertent Clomid 50mg Tablets administration during early pregnancy, appropriate tests should be utilised during each treatment cycle to determine whether ovulation occurs. The patient should have a pregnancy test before the next course of Clomid 50mg Tablets therapy.

It is not known whether Clomifene citrate is excreted in human milk. Clomifene may reduce lactation.

4.7 Effects On Ability To Drive And Use Machines

Patients should be warned that visual symptoms may render such activities as driving a car or operating machinery more hazardous than usual, particularly under conditions of variable lighting. (See 'Warnings')

4.8 Undesirable Effects

Symptoms/Signs/Conditions: Adverse effects appeared to be dose—related, occurring more frequently at the higher dose and with the longer courses of treatment used in investigational studies. At recommended dosage, adverse effects are not prominent and infrequently interfere with treatment.

During the investigational studies, the more commonly reported adverse effects included ovarian enlargement (13.6%), vasomotor flushes (10.4%), abdominal-pelvic discomfort (distention, bloating) (5.5%), nausea and vomiting (2.2%), breast discomfort (2.1%), visual symptoms (1.5%), headache (1.3%) and intermenstrual spotting or menorrhagia (1.3%).

Ovarian enlargement: At recommended dosage, abnormal ovarian enlargement is infrequent although the usual cyclic variation in ovarian size may be exaggerated. Similarly, cyclic ovarian pain (mittelschmerz) may be accentuated. With higher or prolonged dosage, more frequent ovarian enlargement and cyst formation may occur, and the luteal phase of the cycle may be prolonged.

Rare instances of massive ovarian enlargement are recorded. Such an instance has been described in a patient with polycystic ovary syndrome whose Clomid 50mg Tablets therapy consisted of 100mg daily for 14 days. Abnormal ovarian enlargement usually regresses spontaneously; most of the patients with this condition should be treated conservatively.

Eye/Visual Symptoms: Symptoms described usually as “blurring” or spots or flashes (scintillating scotomata) increase in incidence with increasing total dose.

These symptoms appear to be due to intensification and prolongation of after-images. After-images as such have also been reported. Symptoms often first appear or are accentuated with exposure to bright-light environment. Ophthalmologically definable scotomata, phosphenes and reduced visual acuity have been reported.

There are rare reports of cataracts and optic neuritis.

These visual disturbances are usually reversible. However, cases of prolonged visual disturbance have been reported, including after Clomid 50mg Tablets have been discontinued. The visual disturbances may be irreversible, especially with increased dosage or duration of therapy.

Genitourinary: There are reports of new cases of endometriosis and exacerbation of pre-existing endometriosis during Clomid 50mg Tablets therapy.

Multiple pregnancies, including simultaneous intrauterine and extrauterine pregnancies, have been reported. There is an increased chance of ectopic pregnancy in women who conceive following Clomid 50mg Tablets therapy.

Tumours/neoplasms: Isolated reports have been received on the occurrence of endocrine-related or dependent neoplasms or their aggravation. Ovarian cancer: see section 4.4.

Central nervous system: Convulsions have been reported; patients with a history of seizures may be predisposed. In investigational patients, CNS symptoms/signs, conditions of dizziness, light-headedness/vertigo (0.9%), nervous tension/insonmia (0.8%) and fatigue/depression (0.7%) were reported. After prescription availability, there were isolated additional reports of these conditions and also reports of other conditions such as syncope/fainting, cerebrovascular accident, cerebral thrombosis, psychotic reactions including paranoid psychosis, neurologic impairment, disorientation and speech disturbance.

Dermatoses: Dermatitis and rash were reported by investigational patients. Conditions such as rash and urticaria were the most common ones reported after prescription availability but also reported were conditions such as allergic reaction, erythema multiforme, ecchymosis and angioneurotic oedema. Hair thinning (alopecia) has been reported very rarely.

Liver function: Bromsulphalein (BSP) retention of greater than 5% was reported in 32 of 141 patients in whom it was measured, including 5 of 43 patients who took approximately the dose of Clomid 50mg Tablets now recommended. Retention was usually minimal unless associated with prolonged continuous Clomid 50mg Tablets administration or with apparently unrelated liver disease. Other liver function tests were usually normal. In a later study in which patients were given 6 consecutive monthly courses of Clomid 50mg Tablets (50 or 100mg daily for 3 days) or matching placebo, BSP tests were done on 94 patients. Values in excess of 5% retention were recorded in 11 patients, 6 of whom had taken drug and 5 placebo.

In a separate report, one patient taking 50mg of Clomid 50mg Tablets daily developed jaundice on the 19th day of treatment; liver biopsy revealed bile stasis without evidence of hepatitis.

4.9 Overdose

Toxic effects of acute overdosage of Clomid 50mg Tablets have not been reported but the number of overdose cases recorded is small. In the event of overdose, appropriate supportive measures should be employed.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: ovulation stimulants, synthetic

ATC code: G03BG02

Mechanism of action:

The ovulatory response to cyclic Clomid 50mg Tablets therapy is mediated through increased output of pituitary gonadotrophins, which in turn stimulates the maturation and endocrine activity of the ovarian follicle.

Pharmacodynamic effects:

Clomid 50mg Tablets is a triarylethylene compound (related to chlorotrianisene and triparanol). It is a non-steroidal agent which stimulates ovulation in a high percentage of appropriately selected anovulatory women.

5.2 Pharmacokinetic Properties

Orally administered ¹⁴C labelled Clomifene citrate was readily absorbed when administered to humans. Cumulative excretion of the ¹⁴C label by way of urine and faeces averaged about 50% of the oral dose after 5 days in 6 subjects, with mean urinary excretion of 7.8% and mean faecal excretion of 42.4%. A mean rate of excretion of 0.73% per day of the ¹⁴C dose after 31 days to 35 days and 0.45% per day of the ¹⁴C dose after 42 days to 45 days was seen in faecal and urine samples collected from 6 subjects for 14 to 53 days after Clomifene citrate ¹⁴C administration. The remaining drug/metabolites may be slowly excreted from a sequestered enterohepatic recirculation pool.

5.3 Preclinical Safety Data

Carcinogenicity

Prolonged use of Clomid 50mg Tablets may increase the risk of developing ovarian cancer.

Long term toxicity studies in animals have not been performed to evaluate the carcinogenic potential of Clomid 50mg Tablets.

Mutagenicity

Mutagenic potential of Clomid 50mg Tablets has not been evaluated.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sucrose

Lactose

Soluble starch

Maize starch

Magnesium stearate

Iron oxide yellow E172

Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Store in original container, do not store above 25°C.

6.5 Nature And Contents Of Container

Blister pack:

Base: 250 micron PVC

Foil: 20 micron hard-tempered aluminium

(in cardboard cartons)

Pack sizes: 30 tablets.

6.6 Special Precautions For Disposal And Other Handling

None.

7. Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

8. Marketing Authorisation Number(S)

PL 04425/5900R

9. Date Of First Authorisation/Renewal Of The Authorisation

Licence renewed: 29th September 1995.

10. Date Of Revision Of The Text

16 August 2010

LEGAL CLASSIFICATION

POM

Fluorometholone

Pronunciation: flure-oh-METH-oh-lone
Generic Name: Fluorometholone
Brand Name: Examples include Fluor-Op and FML Forte

Fluorometholone is used for:

Treating inflammation (swelling, warmth, redness, pain) of the eyes and eyelids.

Fluorometholone is a corticosteroid. Exactly how Fluorometholone works is unknown.

Do NOT use Fluorometholone if:

• you are allergic to any ingredient in Fluorometholone


• you have a viral infection of the eye (eg, herpes), a fungal or tuberculosis infection of the eye, certain untreated eye infections (eg, infections producing pus or discharge), or vaccinia or chickenpox infection

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

Before using Fluorometholone:

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

• if you are pregnant, plan 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 thinning of the eye tissues (eg, cornea, sclera), other eye problems (eg, glaucoma, cataracts, nerve damage), or diabetes


• if you have recently had cataract surgery

Some MEDICINES MAY INTERACT with Fluorometholone. Because little, if any, of Fluorometholone is absorbed into the blood, the risk of it interacting with another medicine is low.

This may not be a complete list of all interactions that may occur. Ask your health care provider if Fluorometholone 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 Fluorometholone:

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

• Shake well before each use.


• To use Fluorometholone, first, wash your hands. Tilt your head back. Using your index finger, pull the lower eyelid away from the eye to form a pouch. Drop the medicine into the pouch and gently close your eyes. Immediately use your finger to apply pressure to the inside corner of the eye for 1 to 2 minutes. Do not blink. Remove excess medicine around your eye with a clean tissue, being careful not to touch your eye. Wash your hands to remove any medicine that may be on them. To prevent germs from contaminating your medicine, do not touch the applicator tip to any surface, including your eye. Keep the container tightly closed.


• Do not wear soft contact lenses while you are using Fluorometholone. Sterilize contact lenses according to the manufacturer's directions and check with your doctor before using them.


• If your doctor prescribed more than 1 eye medicine, find out the best order for using each medicine.


• If you miss a dose of Fluorometholone, use 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 use 2 doses at once.

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

Important safety information:

• Fluorometholone may cause blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Fluorometholone.


• If your condition does not improve within 2 days or if it becomes worse, check with your doctor.


• LAB TESTS, including eye pressure, may be performed to monitor your progress or to check for side effects. Be sure to keep all doctor and lab appointments.


• Use Fluorometholone with extreme caution in CHILDREN younger than 2 years of age. Safety and effectiveness in this age group have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, discuss with your doctor the benefits and risks of using Fluorometholone during pregnancy. It is unknown if Fluorometholone is excreted in breast milk after use in the eye. If you are or will be breast-feeding while you are using Fluorometholone, check with your doctor or pharmacist to discuss the risks to your baby.

Possible side effects of Fluorometholone:

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; taste changes; temporary burning or stinging.

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

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); changes in vision; continuing blurred vision; discharge from eyes; eye pain, itching, redness, swelling, irritation, or sores not present when you began using Fluorometholone.

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.

See also: Fluorometholone 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 Fluorometholone:

Store Fluorometholone below 77 degrees F (25 degrees C). Store away from heat, moisture, and light. Do not freeze. Do not store in the bathroom. Keep Fluorometholone out of the reach of children and away from pets.

General information:

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


• Fluorometholone 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 Fluorometholone. 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

Copyright © 2012 Wolters Kluwer Health, Inc.

More Fluorometholone resources

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

• Flarex Concise Consumer Information (Cerner Multum)


• Flarex Prescribing Information (FDA)


• Fluor-Op Prescribing Information (FDA)

Compare Fluorometholone with other medications

• Eye Dryness/Redness
• Eye Redness/Itching
• Eyelash Hypotrichosis

Efudex Occlusion Pack

Generic Name: fluorouracil topical (flore oh YER a sill)

Brand Names: Carac, Efudex, Efudex Occlusion Pack, Fluoroplex

What is Efudex Occlusion Pack (fluorouracil topical)?

Fluorouracil interferes with the growth of skin cells. Fluorouracil works by causing the death of cells which are growing fastest, such as abnormal skin cells.

Fluorouracil topical is used to treat scaly overgrowths of skin (actinic or solar keratoses). Fluorouracil topical may also be used in the treatment of superficial basal cell carcinoma.

Fluorouracil topical may also be used for purposes other than those listed in this medication guide.

What is the most important information I should know about Efudex Occlusion Pack (fluorouracil topical)?

Do not use fluorouracil topical on skin that is irritated, peeling, or infected or on open wounds. Wait until these conditions have fully healed before using fluorouracil topical. Fluorouracil topical is in the FDA pregnancy category X. This means that it is known to harm an unborn baby. Miscarriage and birth defects have been reported when fluorouracil topical was applied to mucous membrane areas by pregnant women. Do not use fluorouracil topical if you are pregnant or planning a pregnancy. Discuss with your doctor appropriate forms of birth control before starting treatment with fluorouracil topical.

Fluorouracil topical is available in a number of strengths and forms (creams and solutions). It is very important that you use the correct form and strength. Contact your doctor or pharmacist if you have questions regarding which product to use.

Avoid exposure to sunlight or artificial UV rays (e.g., sun lamps) during and immediately following treatment with fluorouracil topical. Use a sunscreen with a minimum sun protection factor (SPF) 15 and wear protective clothing when sun exposure is unavoidable. Individuals with fair skin may require a sunscreen with a higher SPF rating.

What should I discuss with my healthcare provider before using Efudex Occlusion Pack (fluorouracil topical)?

Before using fluorouracil topical, tell your doctor if you:

• 
  

  have ever had an allergic reaction to another form of fluorouracil topical (Carac, Efudex, Fluoroplex) or injectable fluorouracil (Adrucil, 5-FU); or

  
  


• 
  

  have dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.

  
  

You may not be able to use fluorouracil topical, or you may require a dosage adjustment or special monitoring during treatment if you have any of the conditions listed above.

Fluorouracil topical is in the FDA pregnancy category X. This means that it is known to harm an unborn baby. Miscarriage and birth defects have been reported when fluorouracil topical was applied to mucous membrane areas by pregnant women. Do not use fluorouracil topical if you are pregnant or planning a pregnancy. Discuss with your doctor appropriate forms of birth control before starting treatment with fluorouracil topical. It is not known whether fluorouracil topical passes into breast milk. Do not use fluorouracil topical without first talking to your doctor if you are breast-feeding a baby. The safety and effectiveness of fluorouracil topical in patients younger than 18 years of age have not been established.

How should I use Efudex Occlusion Pack (fluorouracil topical)?

Use fluorouracil topical exactly as directed by your doctor. If you do not understand these directions, ask your pharmacist, nurse, or doctor to explain them to you.

Fluorouracil topical is available in a number of strengths and forms (creams and solutions). It is very important that you use the correct form and strength. Contact your doctor or pharmacist if you have questions regarding which product to use.

Clean the area where you will apply fluorouracil topical. Rinse well and dry the area with a towel and wait ten minutes before applying the medication.

Wash your hands before and immediately after applying this medication, unless it is being used to treat a hand condition.

Apply fluorouracil topical to the affected area with the finger tips or a non-metal applicator, smoothing it gently onto the affected skin. Use enough to cover the entire area with a thin film.

Fluorouracil topical should not be applied on the eyelids or in the eyes, nose, or mouth. Use caution when applying fluorouracil topical around the eyes, nose, or mouth. Do not use fluorouracil topical on skin that is irritated, peeling, or infected or on open wounds. Wait until these conditions have fully healed before using fluorouracil topical.

Do not cover the area after applying fluorouracil topical. This could cause too much medicine to be absorbed by the body and could be harmful. If a covering is needed, ask your doctor if a porous gauze dressing may be used.

A moisturizer or sun screen may be applied 2 hours after fluorouracil topical has been applied. Do not use any other skin products including creams, lotions, medications, or cosmetics unless instructed by your doctor.

The reaction of the skin treated with fluorouracil topical may be unsightly during treatment, and sometimes, for several weeks after completion of therapy.

Store fluorouracil topical at room temperature away from moisture and heat.

What happens if I miss a dose?

Apply the missed dose as soon as you remember. However, if it is almost time for the next dose, skip the dose you missed and apply only the next regularly scheduled dose. Do not apply a double dose of this medication.

What happens if I overdose?

An overdose of fluorouracil topical is unlikely to occur. If you do suspect an overdose, or if fluorouracil topical has been ingested, call a poison control center or an emergency room for advice.

What should I avoid while using Efudex Occlusion Pack (fluorouracil topical)?

Do not use other prescription or over-the-counter skin products without first talking to your doctor during treatment with fluorouracil topical. They may interfere with the treatment or increase irritation of the skin. Avoid exposure to sunlight or artificial UV rays (e.g., sun lamps) during and immediately following treatment with fluorouracil topical. Use a sunscreen with a minimum sun protection factor (SPF) 15 and wear protective clothing when sun exposure is unavoidable. Individuals with fair skin may require a sunscreen with a higher SPF rating.

Efudex Occlusion Pack (fluorouracil topical) side effects

Serious side effects are not likely to occur. Stop using fluorouracil topical and seek emergency medical attention if you experience an allergic reaction (shortness of breath; closing of your throat; swelling of your lips, face, or tongue; or hives).

Fluorouracil topical may cause skin irritation, dryness, scaling or peeling (exfoliation), rash, and other local reactions. Eye irritation has also been reported. If these side effects are excessive or worsen with continued treatment, contact your doctor.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

What other drugs will affect Efudex Occlusion Pack (fluorouracil topical)?

Do not use other prescription or over-the-counter skin products without first talking to your doctor during treatment with fluorouracil topical. They may interfere with treatment or increase irritation to the skin.

Drugs other than those listed here may also interact with fluorouracil topical. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines.

More Efudex Occlusion Pack resources

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

• Carac Cream MedFacts Consumer Leaflet (Wolters Kluwer)


• Carac Prescribing Information (FDA)


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


• Efudex Prescribing Information (FDA)


• Fluoroplex Prescribing Information (FDA)

Compare Efudex Occlusion Pack with other medications

• Actinic Keratosis
• Basal Cell Carcinoma
• Skin Cancer

Where can I get more information?

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

See also: Efudex Occlusion Pack side effects (in more detail)

Galenphol Linctus

1. Name Of The Medicinal Product

Galenphol Linctus

Care Pholcodine 5mg/5ml Oral Solution Sugar Free

2. Qualitative And Quantitative Composition

Pholcodine 5.0mg (Per 5ml Dose)

For excipients, see 6.1.

3. Pharmaceutical Form

Oral liquid

A viscous red coloured liquid.

4. Clinical Particulars

4.1 Therapeutic Indications

Used for the relief of an unproductive dry cough.

4.2 Posology And Method Of Administration

For oral administration

Adult and children over 12 years:

Two or three 5ml spoonfuls three or four times daily.

Not more than 4 doses should be given in any 24 hours

Elderly:

Adult dose is appropriate.

Do not exceed the stated dose.

Keep out of the sight and reach of children.

4.3 Contraindications

Liver failure.

Should not be administered to patients in or at risk of developing respiratory failure or during an attack of asthma.

Patients receiving monoamine oxidase inhibitors or within 2 weeks of cessation of their use.

Patients with chronic bronchitis, COPD, bronchiolitis or bronchiectasis due to sputum retention.

Known hypersensitivity to any of the ingredients.

Children under 12 years of age.

4.4 Special Warnings And Precautions For Use

Should be used with caution in patients with renal, hepatic or respiratory disease, including a history of asthma. Galenphol and other cough suppressants may cause sputum retention and this may be harmful in patients with chronic bronchitis and bronchiectasis.

Ask a doctor before use if you suffer from a chronic or persistent cough, if you have asthma, are suffering from an acute asthma attack or where cough is accompanied by excessive secretions.

Use of pholcodine with alcohol or other CNS depressants may increase the effects on the CNS and cause toxicity in relatively smaller doses.

This medicine contains 1.2 vol% ethanol, i.e. up to 144 mg per 15 ml dose, equivalent to 4 ml beer or 2 ml wine. Harmful for those suffering from alcoholism. To be taken into account in pregnant or breastfeeding women, children and high risk groups such as patients with liver disease or epilepsy.

It also contains sodium hydroxybenzoates and amaranth dye which may cause allergic reactions (possibly delayed).

Do not exceed the stated dose.

Do not take with other cough and cold medicines.

If symptoms persist consult your doctor.

Do not give to children under 12 years.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Monoamine oxidase inhibitors: Galenphol should not be used within 14 days of treatment.

Interaction with neuromuscular blocking agents (anaphylaxis) has been reported.

The reduction of blood pressure caused by antihypertensives may accentuate the hypotensive effects of pholcodine. Diuretics may have the same effect.

Pholcodine may enhance the sedative effect of central nervous system depressants including alcohol, barbiturates, hypnotics, narcotic analgesics, sedatives and tranquillisers (phenothiazines and tricyclic antidepressants).

4.6 Pregnancy And Lactation

No data available on the use of Galenphol in pregnancy or lactation.

Galenphol should be avoided during pregnancy unless considered necessary by the physician and should be avoided during the first trimester. Opioid administration near term in the third trimester may cause respiratory depression in the newborn, withdrawal effects in neonates of dependent mothers, gastric stasis and risk of inhalation pneumonia in the mother during labour.

Pholcodine has been detected in human milk but in amounts usually too small to be harmful; however mothers may vary considerably in their capacity to metabolise pholcodine with a risk of morphine overdose in the infant.

4.7 Effects On Ability To Drive And Use Machines

Using the dose recommended, it is not considered to be a hazard, however, the use of pholcodine may cause sedation, dizziness and nausea. If affected, driving or operation of machinery would not be advised.

4.8 Undesirable Effects

The following side effects may be associated with the use of pholcodine:

Occasional drowsiness, dizziness, excitation, confusion, sputum retention, vomiting, gastrointestinal disturbances (nausea and constipation) and skin reactions including rash.

Immune system disorders have been noted including hypersensitivity reactions and anaphylaxis.

4.9 Overdose

It is thought to be of low toxicity, but the effects in overdosage will be potentiated by simultaneous ingestion of alcohol and psychotropic drugs.

Symptoms of overdose include respiratory depression, nausea, drowsiness, restlessness, excitement and ataxia. Treatment should be symptomatic to maintain vital functions. Respiratory distress should be treated by supportive means. Airways protective gastric lavage may be used.

In severe cases a narcotic antagonist such as naloxone may be considered. Naloxone has been used successfully to reverse central or peripheral opioid effects in children (0.01mg/kg body weight). Other treatment option is activated charcoal (1g/kg body weight) if more than 4mg/kg has been ingested within 1 hour, provided the airway can be protected.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

R05D A08 - Opium alkaloids and derivatives.

Galenphol contains pholcodine which is a centrally acting cough suppressant. It has none of the other properties of opiate agents.

5.2 Pharmacokinetic Properties

None stated.

5.3 Preclinical Safety Data

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Citric acid monohydrate

Nipasept sodium [containing Sodium Methyl Parahydroxybenzoate (E219), Sodium Ethyl Parahydroxybenzoate (E215) & Sodium Propyl Parahydroxybenzoate (E217)

Alcohol 96%

Amaranth (E123)

Blanose cellulose gum (7HOF)

Saccharin sodium

Menthol

Condensed milk flavour (F12516)

Aniseed flavour (545008E)

Glycerol

Purified water

6.2 Incompatibilities

None stated.

6.3 Shelf Life

Two years from the date of manufacture.

6.4 Special Precautions For Storage

Store in a cool place.

6.5 Nature And Contents Of Container

200ml amber glass bottles with 28mm tamper evident child resistant closure with EPE/Saranex liner.

Amber HDPE 2 litre Winchester with a polypropylene cap.

6.6 Special Precautions For Disposal And Other Handling

None stated.

ADMINISTRATION DETAILS

7. Marketing Authorisation Holder

Thornton & Ross Ltd

Linthwaite

Huddersfield

HD7 5QH

United Kingdom

8. Marketing Authorisation Number(S)

PL 00240/0101

9. Date Of First Authorisation/Renewal Of The Authorisation

30 August 2002

10. Date Of Revision Of The Text

08/08/2011

Factive

Generic Name: Gemifloxacin Mesylate
Class: Quinolones
VA Class: AM900
Chemical Name: (Z - 7 - [3 - (Aminomethyl) - 4 - (methoxyimino) - 1 - pyrrolidinyl] - 1 - cyclopropyl - 6 - fluoro - 1,4 - dihydro - 4 - oxo - 1,8 - naphthyridine - 3 - carboxylic acid monomethanesulfonate
Molecular Formula: C₁₈H₂₀FN₅O₄•CH₄O₃S
CAS Number: 204519-65-3

• 
  

  Fluoroquinolones, including gemifloxacin, are associated with an increased risk of tendinitis and tendon rupture in all age groups.^{1 55 56} This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.^{1 55 56} (See Tendinopathy and Tendon Rupture under Cautions.)

  
  

REMS:

FDA approved a REMS for gemifloxacin mesylate to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page () or the ASHP REMS Resource Center ().

Introduction

Antibacterial; naphthyridine derivative; fluoroquinolone.^{1 4 12 23}

Uses for Factive

Respiratory Tract Infections

Treatment of acute bacterial exacerbations of chronic bronchitis caused by susceptible Streptococcus pneumoniae, Haemophilus influenzae, H. parainfluenzae, or Moraxella catarrhalis.^{1 2 3 28}

Treatment of mild to moderate community-acquired pneumonia (CAP) caused by susceptible S. pneumoniae (including multidrug-resistant strains), H. influenzae, M. catarrhalis, Mycoplasma pneumoniae, Chlamydophila pneumoniae (formerly Chlamydia pneumoniae), or Klebsiella pneumoniae.^{1 29 43}

Select regimen for empiric treatment of CAP based on most likely pathogens and local susceptibility patterns; after pathogen is identified, modify to provide more specific therapy (pathogen-directed therapy).⁶ Do not use a fluoroquinolone alone for empiric treatment of CAP in inpatients requiring treatment in an intensive care unit (ICU).⁶

For empiric outpatient treatment of CAP in previously healthy adults without risk factors for drug-resistant S. pneumoniae (DRSP), IDSA and ATS recommend monotherapy with a macrolide (azithromycin, clarithromycin, erythromycin) or, alternatively, doxycycline.⁶ If risk factors for DRSP are present (e.g., chronic heart, lung, liver, or renal disease, diabetes mellitus, alcoholism, malignancy, asplenia, immunosuppression, history of anti-infective treatment within the last 3 months), IDSA and ATS recommend monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam active against S. pneumoniae (high-dose amoxicillin or fixed combination of amoxicillin and clavulanic acid or, alternatively, ceftriaxone, cefpodoxime, or cefuroxime) given in conjunction with a macrolide or doxycycline.⁶

For empiric inpatient treatment of CAP in non-ICU patients, IDSA and ATS recommend adults receive monotherapy with a fluoroquinolone with enhanced activity against S. pneumoniae (gemifloxacin, levofloxacin, moxifloxacin) or, alternatively, a combination regimen that includes a β-lactam (usually cefotaxime, ceftriaxone, or ampicillin) given in conjunction with a macrolide (azithromycin, clarithromycin, erythromycin) or doxycycline.⁶ For empiric inpatient treatment of CAP in ICU patients when Pseudomonas and oxacillin-resistant (methicillin-resistant) Staphylococcus aureus are not suspected, IDSA and ATS recommend a combination regimen that includes a β-lactam (cefotaxime, ceftriaxone, fixed combination of ampicillin and sulbactam) given in conjunction with either azithromycin or a fluoroquinolone (gemifloxacin, levofloxacin, moxifloxacin).⁶

Factive Dosage and Administration

Administration

Oral Administration

Administer orally once daily without regard to meals.^{1 14}

Take with copious amounts (≥100 mL) of fluids to prevent formation of highly concentrated urine.¹

Tablets should be swallowed intact and should not be chewed or crushed.^{1 23}

Dosage

Available as gemifloxacin mesylate; dosage expressed in terms of gemifloxacin.¹

Adults

Respiratory Tract Infections

Acute Exacerbations of Chronic Bronchitis

Oral

320 mg once daily for 5 days.¹

Mild to Moderate Community-acquired Pneumonia (CAP)

Oral

Known or suspected to be caused by S. pneumoniae, H. influenzae, M. pneumoniae, or C. pneumoniae: 320 mg once daily for 5 days.¹

Known or suspected to be caused by multidrug-resistant S. pneumoniae, K. pneumoniae, or M. catarrhalis: 320 mg once daily for 7 days.¹

Manufacturer recommends that results of initial sputum cultures be used to guide clinical decisions regarding use of a 5- or 7-day regimen.¹ IDSA and ATS state that CAP should be treated for a minimum of 5 days and patients should be afebrile for 48–72 hours before discontinuing anti-infective therapy.⁶

Prescribing Limits

Adults

Do not exceed recommended dosage or duration of therapy.¹

Special Populations

Hepatic Impairment

Dosage adjustments not required in adults with mild, moderate, or severe hepatic impairment (Child Pugh class A, B, or C).¹

Renal Impairment

Reduce dosage to 160 mg once daily in adults with Cl_cr ≤40 mL/minute, including those on hemodialysis or CAPD.¹

Gemifloxacin partially removed by hemodialysis;¹ administer dose after hemodialysis.²³

Geriatric Patients

No dosage adjustments except those related to renal impairment.¹ (See Renal Impairment under Dosage and Administration.)

Cautions for Factive

Contraindications

• 
  

  Known hypersensitivity to gemifloxacin, other fluoroquinolones, or any ingredient in the formulation.¹

  
  

Warnings/Precautions

Warnings

Tendinopathy and Tendon Rupture

Fluoroquinolones, including gemifloxacin, are associated with increased risk of tendinitis and tendon rupture in all age groups.^{1 55 56} This risk is further increased in older adults (usually those >60 years of age), individuals receiving concomitant corticosteroids, and kidney, heart, or lung transplant recipients.^{1 55 56} (See Geriatric Use under Cautions.)

Other factors that may independently increase risk of tendon rupture include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis.^{1 55 56} Tendinitis and tendon rupture have been reported in patients receiving fluoroquinolones who did not have any of these risk factors.¹

Fluoroquinolone-associated tendinitis and tendon rupture most frequently involve the Achilles tendon and may require surgical repair.¹ Tendinitis and tendon rupture in the rotator cuff (shoulder), hand, biceps, thumb, and other tendon sites also reported.¹

Tendon rupture can occur during or following fluoroquinolone therapy and has been reported up to several months after completion of therapy.¹

Discontinue if pain, swelling, inflammation, or rupture of a tendon occurs.^{1 55 56} Advise patients to rest and refrain from exercise and contact a clinician at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon; weakness or inability to use a joint).^{1 55 56} (See Advice to Patients.)

Prolongation of QT Interval

Prolonged QT interval and increased risk of ventricular arrhythmias, including torsades de pointes, reported with some fluoroquinolones, including gemifloxacin.^{1 24}

Do not exceed usual recommended dosage since this may increase risk of prolonged QT interval, especially in those with renal or hepatic impairment.¹

Avoid use in patients with a history of prolonged QT interval, in those with uncorrected electrolyte disorders (e.g., hypokalemia, hypomagnesemia), and in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.¹

Use with caution in patients receiving drugs that prolong QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants) and in those with ongoing proarrhythmic conditions, such as clinically important bradycardia or acute myocardial ischemia.¹

Musculoskeletal Effects

Fluoroquinolones, including gemifloxacin, cause arthropathy and osteochondrosis in immature animals of various species;^{1 12 45 46 47 48 49 52 53} relevance of these adverse effects in immature animals to use in humans unknown.^{50 51} Safety and efficacy of gemifloxacin not established in children and adolescents <18 years of age (see Pediatric Use under Cautions) or in pregnant or lactating women (see Pregnancy and see Lactation under Cautions).¹

CNS Effects

Seizures, toxic psychoses, and increased intracranial pressure and CNS stimulation, which may lead to tremor, restlessness, anxiety, lightheadedness, confusion, hallucinations, paranoia, depression, insomnia, and rarely, suicidal thoughts or acts, have been reported with fluoroquinolones.¹

Use with caution in patients with known or suspected CNS disorders (e.g., seizure disorders) or other risk factors that predispose to seizures.¹

If nervous system effects occur, discontinue gemifloxacin and institute appropriate measures.¹

Peripheral Neuropathy

Sensory or sensorimotor axonal polyneuropathy affecting small and/or large axons resulting in paresthesias, hypoesthesias, dysesthesias, and weakness have been reported rarely in patients receiving quinolones.¹

Superinfection/Clostridium difficile-associated Diarrhea and Colitis (CDAD)

Possible emergence and overgrowth of nonsusceptible organism.¹ Institute appropriate therapy if superinfection occurs.¹

Treatment with anti-infectives alters normal colon flora and may permit overgrowth of Clostridium difficile.^{1 31 32 33 34 35} C. difficile-associated diarrhea and colitis (CDAD; also known as antibiotic-associated diarrhea and colitis or pseudomembranous colitis) has been reported with nearly all anti-infectives, including gemifloxacin, and may range in severity from mild diarrhea to fatal colitis.^{1 37 41 42} Outbreaks of severe CDAD caused by fluoroquinolone-resistant C. difficile have been reported with increasing frequency over the past several years.^{36 37 38 39 41} Hypertoxin-producing strains of C. difficile are associated with increased morbidity and mortality since they may be refractory to anti-infectives and colectomy may be required.¹

Consider CDAD if diarrhea develops during or after therapy and manage accordingly.^{1 31 32 33 34 35 40} Careful medical history is necessary since CDAD has been reported to occur as late as 2 months or longer after anti-infective therapy is discontinued.¹

If CDAD is suspected or confirmed, discontinuance of gemifloxacin may be needed.¹ Some mild cases of CDAD may respond to discontinuance alone.^{31 32 33 34 35} Manage moderate to severe cases with fluid, electrolyte, and protein supplementation, appropriate anti-infective therapy active against C. difficile (e.g., oral metronidazole or vancomycin), and surgical evaluation when clinically indicated.^{1 31 32 33 34 35}

Sensitivity Reactions

Hypersensitivity Reactions

Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions reported in patients receiving fluoroquinolones.¹ These reactions may occur with first dose.¹

Some reactions have been accompanied by cardiovascular collapse, hypotension or shock, seizures, loss of consciousness, tingling, angioedema (e.g., edema or swelling of the tongue, larynx, throat, or face), airway obstruction (e.g., bronchospasm, shortness of breath, acute respiratory distress), urticaria, pruritus, and other severe skin reactions.¹

Discontinue gemifloxacin at first appearance of rash, jaundice, or any other sign of hypersensitivity.^{1 23} Institute appropriate therapy as indicated (e.g., epinephrine, corticosteroids, maintenance of an adequate airway and oxygen).¹

Photosensitivity Reactions

Moderate to severe photosensitivity/phototoxicity reactions reported rarely with fluoroquinolones, including gemifloxacin.¹

Phototoxicity may manifest as exaggerated sunburn reactions (e.g., burning, erythema, exudation, vesicles, blistering, edema) on areas exposed to sun or artificial ultraviolet (UV) light (usually the face, neck, extensor surfaces of forearms, dorsa of hands).¹

Relative potential of the various fluoroquinolones to cause photosensitivity/phototoxicity unclear.¹ Factors that contribute to susceptibility to this adverse effect during fluoroquinolone therapy include patient's skin pigmentation, frequency and duration of exposure to sun and UV light, use of protective clothing and sunscreen, concomitant use of other drugs, and dosage and duration of fluoroquinolone therapy.¹

Avoid unnecessary or excessive exposure to sunlight or artificial UV light (tanning beds, UVA/UVB treatment) while receiving gemifloxacin.¹ If patient needs to be outdoors, they should wear loose-fitting clothing that protects skin from sun exposure and use other sun protection measures (sunscreen).¹

Discontinue gemifloxacin if photosensitivity or phototoxicity (sunburn-like reaction, skin eruption) occurs.¹

General Precautions

Selection and Use of Anti-infectives

When prescribing a fluoroquinolone, consider potential benefits and risks for the individual patient.^{55 56} Most patients tolerate the drugs, but serious adverse reactions (e.g., CNS effects, QT prolongation, C. difficile-associated diarrhea and colitis, damage to liver, kidneys, or bone marrow, alterations in glucose homeostatis) may occur rarely.^{55 56}

To reduce development of drug-resistant bacteria and maintain effectiveness of gemifloxacin and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.¹

When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.¹ In the absence of such data, consider local epidemiology and susceptibility patterns when selecting anti-infectives for empiric therapy.¹

Dermatologic Reactions

Rash (maculopapular, urticarial) reported;^{1 5 12} usually resolves within 14 days.¹

Rash reported most frequently in patients <40 years of age (especially women), in women receiving hormone replacement therapy, and in patients who received gemifloxacin for >7 days (although this was not evident in men ≥40 years of age).¹

Discontinue gemifloxacin at first appearance of rash.¹

Specific Populations

Pregnancy

Category C.¹

Lactation

Distributed into milk in rats.¹ Do not use in nursing women unless possible benefits outweigh potential risks.¹

Pediatric Use

Safety and efficacy not established in children or adolescents <18 years of age.¹ Like other fluoroquinolones, gemifloxacin causes arthropathy and osteochondrosis in juvenile animals.¹ (See Musculoskeletal Effects under Cautions.)

AAP states use of fluoroquinolones may be justified in children <18 years of age in special circumstances after careful assessment of the risks and benefits for the individual patient and after these benefits and risks have been explained to the parents or caregivers.²⁶

Geriatric Use

No overall differences in safety or efficacy relative to younger adults.¹

Risk of severe tendon disorders, including tendon rupture, is increased in older adults (usually those >60 years of age).^{1 55 56} This risk is further increased in those receiving concomitant corticosteroids.^{1 55 56} (See Tendinopathy and Tendon Rupture under Cautions.) Use caution in geriatric adults, especially those receiving concomitant corticosteroids.¹

Risk of QT interval prolongation may be increased in geriatric patients.¹ (See Prolongation of QT Interval under Cautions.)

Consider age-related decreases in renal function when selecting dosage.¹ (See Renal Impairment under Dosage and Administration.)

Hepatic Impairment

Serum concentrations and AUC may be increased; dosage adjustments not considered necessary.¹

Renal Impairment

Decreased renal clearance and prolonged half-life; reduce dosage in those with Cl_cr ≤40 mL/minute.¹ (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

GI effects (diarrhea, nausea, abdominal pain, vomiting); rash; headache; dizziness.¹

Interactions for Factive

Does not inhibit and is not metabolized by CYP isoenzymes.¹ Pharmacokinetic interactions with drugs metabolized by CYP isoenzymes unlikely.¹

Drugs that Prolong QT Interval

Potential pharmacologic interaction (additive effect on QT interval prolongation).¹ Avoid use in patients receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents.¹ Use with caution in patients receiving other drugs that prolong QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).¹ (See Prolongation of QT Interval under Cautions.)

Specific Drugs

Drug	Interaction	Comments
Antacids (aluminum- or magnesium-containing)	Decreased absorption of gemifloxacin1	Administer antacids containing aluminum or magnesium at least 3 hours before or 2 hours after gemifloxacin1
Antacids (calcium-containing); calcium supplements	No clinically important pharmacokinetic interactions 1
Anticoagulants, oral (warfarin)	Increased PT, INR, and/or bleeding reported1	Closely monitor PT, INR, or other suitable coagulation test1 Consider that infectious disease and its accompanying inflammatory process, age, and general patient status also are risk factors for increased anticoagulation activity1
Cimetidine	Slightly increased gemifloxacin concentrations1	Not considered clinically important1
Corticosteroids	Increased risk of tendinitis or tendon rupture, especially in patients >60 years of age1 55 56
Didanosine	Decreased absorption of gemifloxacin with buffered didanosine preparations1	Administer buffered didanosine (pediatric oral solution admixed with antacid) at least 3 hours before or 2 hours after gemifloxacin1
Digoxin	No evidence of effect on digoxin pharmacokinetics1
Hormonal contraceptives	Possible decreased gemifloxacin concentrations;1 no evidence of effect on pharmacokinetics of ethinyl estradiol/levonorgestrel oral contraceptives1	Not considered clinically important1
Iron preparations	Decreased absorption of gemifloxacin1 15	Administer ferrous sulfate and dietary supplements containing iron at least 3 hours before or 2 hours after gemifloxacin1 15
Multivitamins and mineral supplements	Decreased absorption of gemifloxacin1	Administer supplements containing zinc, magnesium, or iron at least 3 hours before or 2 hours after gemifloxacin1
Omeprazole	Possible increased gemifloxacin concentrations1	Not considered clinically important1
Probenecid	Increased gemifloxacin concentrations1
Sucralfate	Decreased absorption of gemifloxacin1 15	Administer gemifloxacin at least 2 hours before sucralfate1 15
Theophylline	No evidence of effect on theophylline pharmacokinetics 1

Factive Pharmacokinetics

Absorption

Bioavailability

71%.¹

Rapidly absorbed from GI tract;^{1 21 30} peak plasma concentrations attained within 0.5 –2 hours.^{1 21 30}

Food

Administration of 320-mg dose with a standard high-fat breakfast (2 eggs cooked in butter, 2 strips of bacon, hash brown potatoes, 2 slices of toast with butter, 300 mL whole milk) reduces peak plasma concentration and AUC by 12 and 3%, respectively;¹⁴ this reduction in systemic exposure not considered clinically important.^{1 14}

Distribution

Extent

Widely distributed into body tissues and fluids, including lung tissue and fluids.¹

Distributed into milk in rats.¹

Plasma Protein Binding

60–70%.¹

Elimination

Metabolism

Metabolized to a limited extent in liver.¹ Not metabolized by CYP isoenzymes.¹

Elimination Route

Eliminated by renal and nonrenal mechanisms.¹

36% of a dose eliminated in urine and 61% excreted in feces as unchanged drug and metabolites.¹

Half-life

7 hours (range 4–12 hours).^{1 21 30}

Special Populations

Pharmacokinetics in geriatric patients similar to that in younger adults.¹

Adults with hepatic impairment: Peak plasma concentrations increased 25% in those with mild to moderate hepatic impairment (Child-Pugh class A or B) and increased 41% in those with severe hepatic impairment (Child-Pugh class C); no substantial change in plasma half-life.¹ Increased serum concentrations not considered clinically important.¹

Adults with renal impairment: Decreased clearance and prolonged half-life.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹ Protect from light.¹

Actions and Spectrum

• 
  

  Usually bactericidal.¹

  
  


• 
  

  Like other fluoroquinolones, gemifloxacin inhibits bacterial DNA gyrase and topoisomerase IV.^{1 4 12} Unlike some fluoroquinolones, gemifloxacin targets both enzymes in susceptible S. pneumoniae.^{1 12}

  
  


• 
  

  Spectrum of activity includes gram-positive aerobic bacteria, some gram-negative aerobic bacteria, and some other organisms (e.g., Chlamydia, Mycoplasma).^{1 4 12 22}

  
  


• 
  

  More active in vitro than some other fluoroquinolones against S. pneumoniae,^{4 12 13 22 23} but less active than ciprofloxacin in vitro against many Enterobacteriaceae and Pseudomonas aeruginosa.^{4 12}

  
  


• 
  

  Gram-positive aerobes: Active in vitro and in clinical infections against S. pneumoniae (including penicillin-resistant and multidrug-resistant strains).¹ Also active in vitro against Staphylococcus aureus (oxacillin-susceptible [methicillin-susceptible] strains only) and S. pyogenes (group A β-hemolytic streptococci).¹

  
  


• 
  

  Gram-negative aerobes: Active in vitro and in clinical infections against H. influenzae,¹ H. parainfluenzae,¹ K. pneumoniae,¹ and M. catarrhalis.¹ Also active in vitro against some strains of Acinetobacter, K. oxytoca, Legionella pneumophila, and Proteus vulgaris.¹

  
  


• 
  

  Other organisms: Active in vitro and in clinical infections against C. pneumoniae ¹ and M. pneumoniae.¹ Has some activity against Mycobacterium tuberculosis in vitro, but is considerably less active against mycobacteria than some other fluoroquinolones (e.g., ciprofloxacin, ofloxacin, levofloxacin).²⁷

  
  


• 
  

  Some cross-resistance occurs between gemifloxacin and other fluoroquinolones.¹

  
  

Advice to Patients

• 
  

  Advise patients that antibacterials (including gemifloxacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).¹

  
  


• 
  

  Importance of completing full course of therapy, even if feeling better after a few days.¹

  
  


• 
  

  Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with gemifloxacin or other antibacterials in the future.¹

  
  


• 
  

  May be taken without regard to meals,¹ but should be taken with copious amounts (≥100 mL) of fluids to prevent formation of highly concentrated urine.¹

  
  


• 
  

  Importance of taking gemifloxacin at least 2 hours before or 3 hours after multivitamins containing iron, magnesium, or zinc; aluminum- or magnesium-containing antacids; or buffered didanosine (pediatric oral solution admixed with antacid).¹ Importance of taking gemifloxacin at least 2 hours before sucralfate.¹

  
  


• 
  

  Increased risk of tendinitis and tendon rupture in all age groups and further increased risk in adults >60 years of age, individuals receiving corticosteroids, and kidney, heart, or lung transplant recipients.^{1 55 56} Importance of resting and refraining from exercise at the first sign of tendinitis or tendon rupture (e.g., pain, swelling, or inflammation of a tendon; weakness or inability to use a joint), discontinuing the drug, and contacting a clinician regarding changing to an anti-infective that is not a fluoroquinolone.^{1 55 56} (See Tendinopathy and Tendon Rupture under Cautions.)

  
  


• 
  

  Potential for gemifloxacin to cause dizziness and lightheadedness; need for caution when operating machinery or driving a motor vehicle until effects of drug on individual are known.¹

  
  


• 
  

  Importance of informing clinician if medical history includes palpitations, seizures, or fainting spells or if any of these occur during therapy.¹

  
  


• 
  

  Advise patient that gemifloxacin has been associated with rash or hives and that rash occurs most frequently in patients <40 years of age (especially women), in postmenopausal women receiving hormone replacement therapy, and in patients who receive gemifloxacin for >5 days (especially when given for >7 days).¹ Importance of discontinuing gemifloxacin and informing clinician if rash occurs.¹

  
  


• 
  

  May be associated with hypersensitivity reactions (including anaphylactic reactions), even following the first dose.¹ Importance of immediately discontinuing gemifloxacin and informing clinician at the first sign of rash, jaundice, or any other sign of hypersensitivity.¹

  
  


• 
  

  Risk of photosensitivity/phototoxicity reactions following exposure to sun or UV light while receiving fluoroquinolones.¹ Importance of avoiding or minimizing exposure to sunlight or artificial UV light (e.g., tanning beds, UVA/UVB treatment) and using protective measures (e.g., wearing loose-fitting clothes, sunscreen) if outdoors during gemifloxacin therapy.¹ Discontinue gemifloxacin and inform a clinician if a sunburn-like reaction or skin eruption occurs.

  
  


• 
  

  Advise patient that gemifloxacin may prolong QT interval and should be avoided in those receiving class IA (e.g., quinidine, procainamide) or class III (e.g., amiodarone, sotalol) antiarrhythmic agents and used with caution in those receiving drugs that prolong QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).¹

  
  


• 
  

  Importance of informing clinician of personal or family history of QT interval prolongation or proarrhythmic conditions (e.g., recent hypokalemia, bradycardia, recent myocardial ischemia).¹

  
  


• 
  

  Advise patients that seizures have been reported and importance of informing clinician about any history of convulsions, seizures, or epilepsy before taking gemifloxacin.¹

  
  


• 
  

  Advise patients of risk of other CNS problems (e.g., tremors, restlessness, confusion, hallucinations).¹

  
  


• 
  

  Advise patients that diarrhea is a common problem caused by anti-infectives and usually ends when the drug is discontinued.¹ Importance of contacting a clinician if watery and bloody stools (with or without stomach cramps and fever) occur during or as late as 2 months or longer after the last dose.¹

  
  


• 
  

  Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, especially drugs that may affect QT interval (e.g., cisapride [available in the US only under a limited-access protocol], erythromycin, antipsychotic agents, tricyclic antidepressants).¹ Importance of informing clinicians of concomitant therapy with warfarin or its derivatives.¹

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of advising patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

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

Gemifloxacin Mesylate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	320 mg (of gemifloxacin)	Factive ()	Oscient

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Factive 320MG Tablets (CORNERSTONE BIOPHARMA): 5/$219.99 or 15/$629.98

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 October 27, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Oscient Pharmaceuticals. Factive (gemifloxacin mesylate) tablets prescribing information. Waltham, MA; 2008 Oct

2. File T, Schlemmer B, Garau J et al. Gemifloxacin versus amoxicillin/clavulanate in the treatment of acute exacerbations of chronic bronchitis. J Chemother. 2000; 12:314-25. [PubMed 10949981]

3. Wilson R, Schentag JJ, Ball P et al. A comparison of gemifloxacin and clarithromycin in acute exacerbations of chronic bronchitis and long-term clinical outcomes. Clin Ther. 2002; 24:639-52. [IDIS 485250] [PubMed 12017408]

4. Lowe MN, Lamb HM. Gemifloxacin. Drugs. 2000; 59:1137-47. [PubMed 10852645]

5. File TM, Schlemmer B, Garau J et al. Efficacy and safety of gemifloxacin in the treatment of community-acquired pneumonia: a randomized, double-blind comparison with trovafloxacin. J Antimicrob Chemother. 2001; 48:67-74. [IDIS 467735] [PubMed 11474633]

6. Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007; 44 Suppl 2:S27-72. [PubMed 17278083]

7. Heffelfinger JD, Dowell SF, Jorgensen JH et al. Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the drug-resistance streptococcus pneumoniae therapeutic working group. Arch Intern Med. 2000; 160:1399-1408. [IDIS 448719] [PubMed 10826451]

9. Bishai W. Current issues on resistance, treatment guidelines, and the appropriate use of fluoroquinolones for respiratory tract infections. Clin Ther. 2002; 24:838-50. [IDIS 483635] [PubMed 12117077]

10. Schering-Plough. Avelox (moxifloxacin hydrochloride) tablets and Avelox I.V. (moxifloxacin hydrochloride in sodium chloride injection) prescribing information. Kenilworth, NJ; 2008 Oct.

12. Zhanel GG, Ennis K, Vercaigne L et al. A critical review of the fluoroquinolones: focus on respiratory tract infections. Drugs. 2002; 62:13-59. [PubMed 11790155]

13. Ball P. Quinolone generations: natural history or natural selection?. J Antimicrob Chemother. 2000; 46:17-24. [IDIS 450996] [PubMed 10997595]

14. Allen A, Bygate E, Clark D et al. The effect of food on the bioavailability of oral gemifloxacin in healthy volunteers. Int J Antimicrob Agents. 2000; 16:45-50. [PubMed 11185412]

15. Allen A, Bygate E, Faessel H et al. The effect of ferrous sulphate and sucralfate on the bioavailability of oral gemifloxacin in healthy volunteers. Int J Antimicrob Agents. 2000; 16:283-9.

16. Allen A, Vousden M, Porter A et al. Effect of Maalox on the bioavailability of oral gemifloxacin in healthy volunteers. Chemotherapy. 1999; 45:504-11. [IDIS 439831] [PubMed 10567782]

17. Davy M, Allen A, Bird N et al. Lack of effect of gemifloxacin on the steady-state pharmacokinetics of theophylline in healthy volunteers. Chemotherapy. 1999; 45:478-84. [IDIS 439827] [PubMed 10567778]

18. Vousden M, Allen A, Lewis A et al. Lack of pharmacokinetic interaction between gemifloxacin and digoxin in healthy elderly volunteers. Chemotherapy. 1999; 45:485-90. [IDIS 439828] [PubMed 10567779]

19. Davy M, Bird N, Rost KL et al. Lack of effect of gemifloxacin on the steady-state pharmacodynamics of warfarin in healthy volunteers. Chemotherapy. 1999; 45:491-5. [IDIS 439829] [PubMed 10567780]

20. Allen A, Vousden M, Lewis A et al. Effect of omeprazole on the pharmacokinetics of oral gemifloxacin in healthy volunteers. Chemotherapy. 1999; 45:496-503. [IDIS 439830] [PubMed 10567781]

21. Allen A, Bygate E, Vousden M et al. Multiple-dose pharmacokinetics and tolerability of gemifloxacin administered orally to healthy volunteers. Antimicrob Agents Chemother. 2001; 45:540-5. [IDIS 458566] [PubMed 11158752]

22. Boswell FJ, Andrews JM, Jevons G et al. Comparison of the in vitro activities of several new fluoroquinolones against respiratory pathogens and their abilities to select fluoroquinolone resistance. J Antimicrob Chemother. 2002; 50:495-502. [PubMed 12356793]

23. Genesoft, Inc, South San Francisco, CA: Personal communication.

24. Ortho-McNeil Pharmaceutical. Levaquin (levofloxacin) tablets, oral solution, injection for intravenous use, and injection in 5% dextrose for intravenous use prescribing information. Raritan, NJ; 2008 Oct.

26. American Academy of Pediatrics. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2006.

27. Ruiz-Serrano MJ, Alcala L, Martinez L et al. In vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs. Antimicrob Agents Chemother. 2000; 44:2567-8.

28. Sethi S, Fogarty C, Fulambarker A. A randomized, double-blind study comparing 5 days oral gemifloxacin with 7 days of levofloxacin in patients with acute exacerbation of chronic bronchitis. Respir Med. 2004; 98:697-707. [PubMed 15303633]

29. Leophonte P, File T, Feldman C. Gemifloxacin once daily for 7 days compared to amoxicillin/clavulanic acid thrice daily for 10 days for the treatment of community-acquired pneumonia of suspected pneumococcal origin. Respir Med. 2004; 98:708-20. [PubMed 15303634]

30. Allen A, Bygate E, Oliver S et al. Pharmacokinetics and tolerability of gemifloxacin (SB-265805) after administration of single oral doses to healthy volunteers. Antimicrob Agents Chemother. 2000; 44:1604-8. [PubMed 10817716]

31. Johnson S, Gerding DN. Clostridium difficile-associated diarrhea. Clin Infect Dis. 1998; 26:1027-36. [IDIS 407733] [PubMed 9597221]

32. Gerding DN, Johnson S, Peterson LR et al for the Society for Healthcare Epidemiology of America. Position paper on Clostridium difficile-associated diarrhea and colitis. Infect Control Hosp Epidemiol. 1995; 16:459-77. [PubMed 7594392]

33. Fekety R for the American College of Gastroenterology Practice Parame