Antimalarial agents

Antimalarials agents are drugs effective in the treatment of malaria. Malaria is an infectious disease caused by the bite of an anopheles mosquito infected with certain protozoans. The best way to prevent malaria is by taking antimalarial drugs prophylactically prior to entering an endemic area.

Antimalarial agents are classified according to their action against different stages of the life cycle of the parasite. Certain antimalarial agents are more effective in the acute attack of malaria, and generally more that one agent will be used simultaneously to avoid resistance. Some antimalarial agents are used as prophylactic agents; they kill the parasite when it enters the host.

See also

• antimalarial combinations
• antimalarial quinolines
• miscellaneous antimalarials

Drug List:

Doxorubicin Hydrochloride for Injection 10 mg and 50 mg

1. Name Of The Medicinal Product

Doxorubicin Hydrochloride for Injection 10 mg and 50 mg

2. Qualitative And Quantitative Composition

Active Constituent		10 mg	50 mg
Doxorubicin	USP	10.0 mg	50.0 mg

3. Pharmaceutical Form

Sterile freeze dried powder for injection.

4. Clinical Particulars

4.1 Therapeutic Indications

Doxorubicin has been used successfully in the treatment of neoplastic conditions such as acute leukaemia, soft tissue and osteogenic sarcomas, breast carcinoma, lymphomas, bronchogenic (lung) carcinoma. It has also been used in the treatment of paediatric malignancy. Doxorubicin is frequently used in combination chemotherapy regimen involving other cytotoxic drugs. Doxorubicin can be used in the treatment of non-metastatic transitional cell carcinoma, carcinoma in situ and papillary tumours of the bladder, by intravesical administration.

4.2 Posology And Method Of Administration

When used as a single agent, the recommended dosage is 60-75 mg/m² body surface area, as a single intravenous injection administered at 21 day intervals. If using body weight to calculate the dose, then dosages of 1.2 – 2.4 mg/kg are recommended.

It has been shown that giving doxorubicin as a single dose every three weeks greatly reduces the distressing toxic effect, mucositis. However, there are some regimens which divide the dose over three successive days (20-25 mg/m² or 0.4-0.8 mg/kg). It is thought that this regimen has greater effectiveness although at a cost of higher toxicity.

Administration of doxorubicin in a weekly regimen has been shown to be as effective as the three weekly regimen. The recommended dosage is 20 mg/m² once a week although objective responses have been seen at 6-12 mg/m². This regimen of weekly dosing also reduces the incidence of cardiotoxicity.

It is particularly important to reduce the dose of doxorubicin if it is used in combination with other drugs with a similar toxicity profile. The recommended lifetime cumulative dose limit is 450-550 mg doxorubicin hydrochloride/m² body surface area.

It is recommended that doxorubicin be slowly administered into the tubing of a freely running intravenous infusion of Sodium Chloride Injection 0.9% or 5% Dextrose Injection. The tubing should be attached to a Butterfly needle inserted preferably into a large vein. The rate of administration is dependent on the size of the vein and the dosage. However the dose should be administered in not less than 3 to 5 minutes. This technique minimises the risk of thrombosis or perivenous extravasation which can lead to severe cellulitis and vesication.

Intravenous infusion is not advised due to the tissue damage that may occur if the infusion infiltrates the tissues. If a central vein catheter is used then infusion of doxorubicin in Sodium Chloride 0.9% Injection is advised.

Local erythematous streaking along the vein as well as facial flushing may be indicative of too rapid administration. A burning or stinging sensation may be indicative of perivenous infiltration and the infusion should be immediately terminated and restarted in another vein. Doxorubicin should not be mixed with heparin since it has been reported that these drugs are incompatible to the extent that a precipitate may form. Until specific compatibility data are available, it is not recommended that doxorubicin be mixed with other drugs.

Intravesical administration

This technique may be used for the treatment of transitional cell carcinoma, papillary bladder tumours and carcinoma in situ. It should not be used for invasive tumours of the bladder which have penetrated the bladder wall.

Many regimens are in use, making interpretation difficult, but the following procedure may be a helpful guide:

1. Patient should be instructed not to drink fluids for 12 hours prior to the examination.

2. Dissolve 50 mg of doxorubicin in 50 ml of normal saline and instil via the catheter into the bladder.

3. The catheter should be removed and the patient instructed to be on one side. At 15 minute intervals the patient should make a quarter turn over a 1 hour period. At the end of this period, the patient may void.

4. The procedure may be repeated at monthly intervals.

Intraarterial administration

Doxorubicin hydrochloride has been administered as an intra-arterial infusion in an attempt to produce local intense activity and reduce systemic toxicity. However it must be recognised that this route of administration is potentially extremely hazardous and can lead to widespread necrosis of perfused tissue unless careful precautions are taken. Intraarterial administration should be undertaken only by experienced professionals.

Paediatric

Adult dosage regimens may be suitable for paediatric cases, but may need to be reduced.

Geriatric

It is recommended that the total cumulative dose of doxorubicin for adults aged 70 or older be restricted to 450 mg/m² body surface area. Adult doses may be suitable for geriatric patients, but may need to be reduced.

Impaired Hepatic Function

Doxorubicin is metabolised by the liver and excreted in bile. Impairment of liver function results in slower excretion of the drug and consequently increased retention and accumulation in the plasma and tissues, resulting in enhanced clinical toxicity.

Doxorubicin dosage must be reduced if hepatic function is impaired according to the following table:

Serum Bilirubin Levels	BSP Retention	Recommended Dose
1.2 – 3.0 mg/100 ml	9 – 15%	50% normal dose
Over 3.0 mg/100 ml	Over 15%	25% normal dose

Impaired Renal Function

Doxorubicin and metabolites are excreted in the urine to a minor degree and there are no clear indications that the pharmacokinetics or toxicity of doxorubicin are altered in patients with impaired renal function.

4.3 Contraindications

Dosage should not be repeated in cases of bone marrow depression or buccal ulceration or buccal burning sensation, which can precede ulceration.

Experienced Physician: Doxorubicin should be administered only under the supervision of a physician who is experienced in the use of cancer chemotherapeutic agents.

4.4 Special Warnings And Precautions For Use

WARNINGS

Cardiac Toxicity: Special attention must be given to the cardiac toxicity exhibited by doxorubicin. This may present as tachycardia or ECG changes including supraventricular tachycardia. Severe cardiac failure may occur suddenly, without premonitory ECG changes.

It is recommended that the cumulative total lifetime dose of doxorubicin (including related drugs such as daunorubicin) should not exceed 450 – 550 mg/sq m body surface area. Above this dosage, the risk of irreversible congestive cardiac failure increases greatly. Total dose should also take account of any previous or concomitant mediastinal irradiation, other anthracycline chemotherapy or concurrent high dose cyclophosphamide, which may also exhibit cardiotoxic effects.

Congestive heart failure and/or cardiomyopathy may be encountered several weeks after discontinuation of doxorubicin therapy and for this reason extreme care should be taken in patients with existing associated heart disease.

Cardiac failure is often not favourably affected by presently known medical or physical therapy for cardiac support. Early clinical diagnosis of drug induced heart failure appears to be essential for successful treatment with digitalis, diuretics, low salt diet and bed rest. Severe cardiac toxicity may occur precipitously without antecedent ECG changes. Base line ECG and periodic follow up ECG during and immediately after active drug therapy is an advisable precaution. Transient ECG changes, such as T-wave flattening, S-T depression and arrhythmias are not considered indications for suspension of doxorubicin therapy. A persistent reduction in the voltage of the QRS wave is presently considered more specifically predictive for cardiac toxicity. If this occurs, the benefit of continued therapy must be carefully evaluated against the risk of producing irreversible cardiac damage.

Bone Marrow Depression: There is a high incidence of bone marrow depression, primarily of leucocytes, requiring careful haematological monitoring. With the recommended dosage schedule, leucopenia is usually transient, reaching its nadir at 10 – 14 days after treatment, with recovery usually occurring by the 21^st day. White blood cell counts as low as 1000/cubic mm are to be expected during treatment with appropriate doses of doxorubicin. Red blood cell and platelet levels should also be monitored, since they may also be depressed.

Haematologic toxicity may require dose reduction or suspension or delay of doxorubicin therapy.

Immunosuppression: Doxorubicin is a powerful but temporary immunosuppressant agent. Appropriate measures should be taken to prevent secondary infection.

Severe Myelosuppression: Persistent severe myelosuppression may result in superinfection or haemorrhage.

Enhanced Toxicity: It has been reported that doxorubicin may enhance the severity of the toxicity of anticancer therapies, such as cyclophosphamide induced haemorrhagic cystitis, mucositis induced by radiotherapy and hepatotoxicity of 6-mercaptopurine.

Infertility: Doxorubicin may cause infertility during the time of drug administration. Although ovulation and menstruation appear to return after termination of therapy, there is no information about the restoration of male fertility.

Hepatic Impairment: Toxicity to recommended doses of doxorubicin is enhanced by hepatic impairment. It is recommended that an evaluation of hepatic function be carried out prior to individual dosing, using conventional clinical laboratory tests such as AST, ALT, alkaline phosphatase, bilirubin and BSP. If required, dosage schedules should be reduced accordingly. (See DOSAGE and ADMINISTRATION).

Extravasation: On intravenous administration of doxorubicin, a stinging or burning sensation signifies extravasation and, even if blood return from aspiration of the infusion needle is good, the injection or infusion should be immediately terminated and restarted in another vein.

Should extravasation occur, stop the infusion immediately and apply ice packs to the injection site. Local injection of dexamethasone or hydrocortisone may be used to minimise local tissue necrosis. Hydrocortisone cream 1% may also be applied locally.

PRECAUTIONS

Initial treatment with doxorubicin requires close observation of the patient and extensive laboratory monitoring.

It is strongly recommended therefore, that patients be hospitalised at least during the first phase of treatment. Blood count and liver function tests should be carried out prior to each doxorubicin treatment.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Not applicable

4.6 Pregnancy And Lactation

Use In Pregnancy

The drug is embryotoxic and teratogenic in rats and embryotoxic and abortifacient in rabbits, and trace amounts of the drug have been found in mouse foetuses and in one aborted human foetus. Although there is no conclusive evidence, there is data which suggests that doxorubicin may harm the foetus. It is therefore recommended that doxorubicin is not administered to women who are pregnant.

Use In Lactation

Doxorubicin is distributed into milk. Experimental data suggests that doxorubicin may harm the infant and should therefore not be administered to mothers who are breast feeding.

4.7 Effects On Ability To Drive And Use Machines

Not known.

4.8 Undesirable Effects

ADVERSE REACTIONS

More Common Reactions

Cardiovascular: Cardiotoxicity i.e. cardiomyopathy, congestive heart failure, supraventricular tachycardia.

Dermatological: Doxorubicin extravasation, skin necrosis, cellulitis, vesication, phlebitis, reversible alopecia, erythematous streaking along the vein proximal to the site of injection, phlebosclerosis. Hair growth returns to normal after cessation of treatment.

Gastrointestinal: Nausea and vomiting, mucositis (stomatitis and oesophagitis), diarrhoea. Mucositis is a frequent and painful complication of doxorubicin treatment. Mucositis most commonly develops 5 to 10 days after treatment, and typically begins as a burning sensation in the mouth and pharynx. It may involve the vagina, rectum and oesophagus, and progress to ulceration with risk of secondary infection and usually subsides in 10 days. Retrospective comparison of the incidence of mucositis suggests that it is less frequent as the intervals between doses increase. Mucositis may be severe in patients who have had previous irradiation to the mucosae.

General: Dehydration, facial flushing (if an injection has been given too rapidly). Administration of doxorubicin may cause red colouration of the urine. Patients should be advised that this is no cause for alarm.

Haematological: Myelosuppression, leucopenia.

Less Common Reactions

Dermatological: Urticarial rash, hyperpigmentation of nailbeds and dermal increases (primarily in children in a few cases), recall of skin reaction due to prior radiotherapy.

General: Chills and fever, anorexia, anaphylaxis

Haematological: Leucopenia, thrombocytopenia, anaemia. Myelosuppression is more common in patients who have had extensive radiotherapy, bone infiltration by tumour, impaired liver function (when appropriate dosage reduction has not been adopted. See DOSAGE: WITH IMPAIRED HEPATIC FUNCTION) and simultaneous treatment with other myelosuppressive agents. The nadir (time from treatment to peripheral blood evidence of maximal myelosuppression) of leucopenia and thrombocytopenia is 10 to 15 days after treatment, and counts return to normal before day 21.

Nervous System: Drowsiness

Ocular: Conjunctivitis.

Renal: Renal damage.

4.9 Overdose

Clinical Features: The symptoms of overdosage are likely to be an extension of doxorubicin's pharmacological action. Single doses of 250 mg and 500 mg of doxorubicin have proved fatal. Such doses may cause acute myocardial degeneration within 24 hours, and severe myelosuppression, the greatest effects of which are seen between 10 and 15 days after administration.

Delayed cardiac failure may occur up to six months after the overdose. Patients should be monitored carefully and if symptoms appear, conventional treatment started.

Management: Symptomatic supportive measures should be instituted. Particular attention should be given to prevention and treatment of possible severe haemorrhage or infections secondary to severe, persistent bone marrow depression. Blood transfusion and reverse barrier nursing may be considered.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Doxorubicin hydrochloride is a cytotoxic anthracycline antibiotic.

Although not completely elucidated, the mechanism of action of doxorubicin is related to its ability to bind to DNA and inhibit nucleic acid synthesis. Cell culture studies have demonstrated rapid cell penetration and perinucleolar chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, mutagenesis and chromosomal aberrations.

The specificity of doxorubicin toxicity appears to be related primarily to proliferative activity of normal tissue. Thus, bone marrow, gastro-intestinal tract and gonads are the main normal tissues damaged.

Doxorubicin is not suitable for oral administration as less than 5% of the drug is absorbed.

5.2 Pharmacokinetic Properties

Pharmacokinetic studies show the intravenous administration of normal or radiolabelled doxorubicin for injection is followed by rapid plasma clearance and significant tissue binding. No information on plasma-protein binding of doxorubicin is available.

The metabolism and disposition of doxorubicin is still to be defined. The drug is metabolised predominantly by the liver to doxorubicinol and several aglycone metabolites. It should be noted that several of the metabolites are cytotoxic. However, it is not certain whether any are more cytotoxic than the parent compound. High levels of metabolites appear rapidly in plasma and undergo a distribution phase with a measurable short initial half-life. Metabolism may be impaired in patients with abnormal liver function.

The disappearance of doxorubicin and its metabolites from the plasma follows a triphasic pharmacokinetic pattern with a mean half-life of the first phase of 12 minutes, of a second phase of 3.3 hours and a prolonged third phase of 29.6 hours.

Urinary excretion of doxorubicin hydrochloride and its metabolites is prolonged and accounts for only 5% of the drug excreted during the first 5 days. Approximately 50% of an administered dose is excreted in bile.

Impairment of liver function results in slower excretion, and consequently, increased retention and accumulation in plasma and tissues. Doxorubicin does not cross the blood brain barrier. However it is known to cross the placenta barrier.

5.3 Preclinical Safety Data

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

6. Pharmaceutical Particulars

6.1 List Of Excipients

Other Constituent	10 mg	50 mg
Lactose monohydrate BP	52.6 mg	263.1 mg

There is no overage included in the above formulations.

6.2 Incompatibilities

Doxorubicin should not be mixed with heparin since it has been reported that these drugs are incompatible to the extent that a precipitate may form. Until specific compatibility data are available, it is not recommended that doxorubicin be mixed with other drugs.

6.3 Shelf Life

36 months.

6.4 Special Precautions For Storage

Store below 25°C and protect from light.

6.5 Nature And Contents Of Container

10 ml or 30 ml clear, Type I conventional glass vials and Onco-Tain^® vials, with 13 mm or 20 mm, 1018 Style, West Type 1816 grey rubber closures, aluminium seal and plastic 'flip-off' tops.

6.6 Special Precautions For Disposal And Other Handling

Doxorubicin is a potent cytotoxic agent which should only be prescribed, prepared and administered by professionals who have been trained in the safe use of the preparation. The following guidelines should be followed when handling, preparing and disposing of doxorubicin.

Preparation

1. Reconstitution of powder, transfer to syringes or infusion bags should be carried out in designated areas, preferably a laminar flow station.

2. Personnel must be adequately protected with suitable clothing, gloves, mask and eye shield.

3. Pregnant women should be excluded from handling cytotoxic agents.

Contamination

1. In the event of contact with the skin or eyes, the affected area should be washed with copious amounts of water or normal saline. A bland cream may be used to treat transient stinging of skin. Medical advice should be sought if the eyes are affected.

2. In the event of spillage treat with 1% Sodium Hypochlorite solution using a cloth/sponge kept in the designate area. Rinse twice with water. Put all cloths into a plastic bag and seal for incineration.

Disposal

All items used during preparation or administration including syringes, containers, absorbent materials, residual solutions should all be placed in a thick plastic bag and incinerated at 700°C.

Preparation of the Injection

The contents of the vial should be reconstituted with Water for Injection BP, Sodium Chloride 0.9%, or Dextrose 5% Injection to a solution concentration of 2 mg per ml.

The reconstituted solution is stable at room temperature, in the vial or in a polypropylene (Terumo) syringe, in the presence or absence of light, for a period of 48 hours. However ,it is recommended that the solution be stored at 2-8°C in a refrigerator, and used within 24 hours, in line with good pharmaceutical practice.

7. Marketing Authorisation Holder

Faulding Pharmaceuticals Plc

Queensway

Royal Leamington Spa

Warwickshire CV31 3RW

United Kingdom

8. Marketing Authorisation Number(S)

PL 4515/0072 - 73

9. Date Of First Authorisation/Renewal Of The Authorisation

26^th July, 2001

10. Date Of Revision Of The Text

7^th December, 2000

Indometacine Sandoz

Indometacine Sandoz may be available in the countries listed below.

Ingredient matches for Indometacine Sandoz

Indometacin

Indometacin is reported as an ingredient of Indometacine Sandoz in the following countries:

• Netherlands

International Drug Name Search

Gris-PEG

Generic Name: griseofulvin (Oral route)

gris-ee-oh-FUL-vin

Commonly used brand name(s)

In the U.S.

• Fulvicin P/G


• Fulvicin-U/F


• Grifulvin V


• Gris-PEG

Available Dosage Forms:

• Tablet


• Capsule


• Suspension

Therapeutic Class: Antifungal

Uses For Gris-PEG

Griseofulvin belongs to the group of medicines called antifungals. It is used to treat fungus infections of the body, feet, groin and thighs, scalp, skin, fingernails, and toenails. This medicine may be taken alone or used along with medicines that are applied to the skin for fungus infections.

Use of griseofulvin for prevention of fungus infection have not been established.

This medicine is available only with your doctor's prescription.

Before Using Gris-PEG

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of griseofulvin in children. However, safety and efficacy have not been established in children up to 2 years of age.

Geriatric

No information is available on the relationship of age to the effects of griseofulvin in geriatric patients.

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Desogestrel


• Dienogest


• Drospirenone


• Estradiol Cypionate


• Estradiol Valerate


• Ethinyl Estradiol


• Ethynodiol Diacetate


• Etonogestrel


• Levonorgestrel


• Medroxyprogesterone Acetate


• Mestranol


• Norelgestromin


• Norethindrone


• Norgestimate


• Norgestrel


• Phenobarbital


• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use this medicine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Actinomycosis (bacterial infection) or


• Blastomycosis (Gilchrist’s disease) or


• Candidiasis (yeast infection) or


• Histoplasmosis (Darling’s disease) or


• Other infections (e.g., bacteria) or


• Sporotrichosis (Rose gardener's disease) or


• Tinea versicolor (Tinea flava)—Griseofulvin will not work in patients with these conditions.

• Liver failure or


• Porphyria (enzyme problem)—Should not be used in patients with these conditions.

• Lupus erythematosus or lupus-like diseases—Use with caution. May make this condition worse.

Proper Use of griseofulvin

This section provides information on the proper use of a number of products that contain griseofulvin. It may not be specific to Gris-PEG. Please read with care.

Keep using this medicine for the full treatment time, even if you feel better after the first few doses. Your infection may not clear up if you stop using the medicine too soon.

Keep yourself clean to help control infection and prevent reinfection.

Griseofulvin is absorbed best when it is taken with a high fat meal, such as a cheeseburger, whole milk, or ice cream. Tell your doctor if you are on a low-fat diet.

Griseofulvin is best taken with or after meals, especially fatty ones (e.g., whole milk or ice cream). This lessens possible stomach upset and helps to clear up the infection by helping your body absorb the medicine better. However, if you are on a low-fat diet, check with your doctor.

For patients taking the oral liquid:

• Use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.

You may swallow the tablets whole or sprinkle the crushed tablets in one tablespoonful of applesauce. Swallow it immediately without chewing.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage forms (microsize capsules, tablets, or suspension):
  
  • Treatment of fungus infections of the feet and nails:
    
    • Adults and teenagers—500 milligrams (mg) every 12 hours.
    
    
    • Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 5 milligrams (mg) per kilogram (kg) (2.3 mg per pound) of body weight every 12 hours, or 10 milligrams (mg) per kilogram (kg) (4.6 mg per pound) of body weight once a day.
    
    
  
  
  • Treatment of fungus infections of the scalp, skin, and groin:
    
    • Adults and teenagers—250 milligrams (mg) every 12 hours or 500 mg once a day.
    
    
    • Children—Dose is based on body weight and must be determined by your doctor. The usual dose is 5 milligrams (mg) per kilogram (kg) (2.3 mg per pound) of body weight every 12 hours, or 10 milligrams (mg) per kilogram (kg) (4.6 mg per pound) of body weight once a day.
    
    
  
  


• For oral dosage form (ultramicrosize tablets):
  
  • Treatment of fungus infections:
    
    • Adults—375 milligrams (mg) per day, taken as a single dose or divided in small doses. Some patients may need 750 mg divided in small doses.
    
    
    • Children 3 years of age and older weighing over 60 pounds—Dose is based on body weight and must be determined by your doctor. The usual dose is 187.5 to 375 mg per day.
    
    
    • Children 3 years of age and older weighing 35 to 60 pounds—Dose is based on body weight and must be determined by your doctor. The usual dose is 125 to 187.5 mg per day.
    
    
    • Children up to 2 years of age—Use and dose must be determined by your doctor.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Precautions While Using Gris-PEG

It is very important that your doctor should check the progress of you or your child at regular visits to make sure that this medicine is working properly and to check for unwanted effects.

If your symptoms do not improve, or if they become worse, check with your doctor. You may need to take this medicine for several weeks or months before your infection gets better.

Using this medicine while you are pregnant may cause serious unwanted effects in your newborn baby. Tell your doctor right away if you think you are pregnant or if you plan to become pregnant while using this medicine.

Serious skin reactions can occur with this medicine. Stop using this medicine and check with your doctor right away if you or your child have blistering, peeling, or loosening of the skin; red skin lesions; severe acne or skin rash; sores or ulcers on the skin; or fever or chills while you are using this medicine.

Stop using this medicine and check with your doctor right away if you or your child have pain or tenderness in the upper stomach; pale stools; dark urine; loss of appetite; nausea; unusual tiredness or weakness; or yellow eyes or skin. These could be symptoms of a serious liver problem.

Griseofulvin has been shown to cause liver and thyroid tumors in some animals. You and your doctor should discuss the good this medicine will do, as well as the risks of taking it.

Birth control pills containing estrogen may not work properly if you take them while you are taking griseofulvin. Unplanned pregnancies may occur. To keep from getting pregnant, use another form of birth control for up to 1 month after your last treatment. Other forms of birth control include condoms, diaphragms, or contraceptive foams or jellies.

Griseofulvin may increase the effects of alcohol. If taken with alcohol it may also cause fast heartbeat, flushing, increased sweating, or redness of the face. If you have these symptoms, do not drink alcoholic beverages while you are taking this medicine, unless you have checked first with your doctor.

This medicine may cause some people to become dizzy, drowsy, or less alert than they are normally. Make sure you know how you react to this medicine before you drive, use machines, or do other things that could be dangerous if you are dizzy or are not alert. If these reactions are especially bothersome, check with your doctor.

Griseofulvin may cause your skin to be more sensitive to sunlight than it is normally. Exposure to sunlight, even for brief periods of time, may cause a skin rash, itching, redness or other discoloration of the skin, or a severe sunburn. When you begin taking this medicine:

• Stay out of direct sunlight, especially between the hours of 10:00 a.m. and 3:00 p.m., if possible.


• Wear protective clothing, including a hat. Also, wear sunglasses.


• Apply a sun block product that has a skin protection factor (SPF) of at least 15. Some patients may require a product with a higher SPF number, especially if they have a fair complexion. If you have any questions about this, check with your doctor.


• Apply a sun block lipstick that has an SPF of at least 15 to protect your lips.


• Do not use a sunlamp or tanning bed or booth.

If you have a severe reaction from the sun, check with your doctor.

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

Gris-PEG Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

• Blistering, peeling, or loosening of the skin


• chills


• cough


• diarrhea


• fever


• itching


• joint or muscle pain


• red, irritated eyes


• sore throat


• sores, ulcers, or white spots in the mouth or on the lips


• unusual tiredness or weakness

Less common

• Confusion


• increased sensitivity of the skin to sunlight


• skin rash, hives, or itching


• soreness or irritation of the mouth or tongue

Rare

• Black, tarry stools


• chest pain


• cloudy urine


• large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs


• numbness, tingling, pain, or weakness in the hands or feet


• painful or difficult urination


• shortness of breath


• swollen glands


• unusual bleeding or bruising


• yellow eyes or skin

Incidence not known

• Abdominal or stomach pain


• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings


• clay-colored stools


• dark urine


• dizziness


• headache


• loss of appetite


• nausea


• unpleasant breath odor


• vomiting of blood

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

• Hives or welts


• redness of the skin

Less common

• Trouble with sleeping

Incidence not known

• Heartburn


• pain or discomfort in the chest, upper stomach, or throat


• sleeplessness


• unable to sleep


• white patches in the mouth or throat or on the tongue


• white patches with diaper rash

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: Gris-PEG side effects (in more detail)

The information contained in the Thomson Reuters Micromedex products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.

The use of the Thomson Reuters Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Reuters Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON REUTERS HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

More Gris-PEG resources

• Gris-PEG Side Effects (in more detail)
• Gris-PEG Use in Pregnancy & Breastfeeding
• Drug Images
• Gris-PEG Drug Interactions
• Gris-PEG Support Group
• 3 Reviews for Gris-PEG - Add your own review/rating

• Gris-PEG Prescribing Information (FDA)


• Gris-PEG Concise Consumer Information (Cerner Multum)


• Gris-PEG Ultramicrosize Tablets MedFacts Consumer Leaflet (Wolters Kluwer)


• Griseofulvin Professional Patient Advice (Wolters Kluwer)


• Griseofulvin Monograph (AHFS DI)


• Griseofulvin Prescribing Information (FDA)


• Grifulvin V Microsize MedFacts Consumer Leaflet (Wolters Kluwer)


• Grisactin 250 Concise Consumer Information (Cerner Multum)

Compare Gris-PEG with other medications

• Dermatophytosis
• Onychomycosis, Fingernail
• Onychomycosis, Toenail
• Tinea Barbae
• Tinea Capitis
• Tinea Corporis
• Tinea Cruris
• Tinea Pedis

Boots Sleepeaze 25 mg Tablets

Boots Sleepeaze 25 mg Tablets

(Diphenhydramine Hydrochloride)

Read all of this leaflet carefully because it contains important information for you.

This medicine is available without prescription to treat minor conditions. However, you still need to take it carefully to get the best results from it.

• Keep this leaflet, you may need to read it again


• Ask your pharmacist if you need more information or advice

What this medicine is for

This medicine contains Diphenhydramine Hydrochloride which belongs to a group of medicines called sedating antihistamines, which help you to sleep.

It can be used to relieve short term sleeplessness.

Before you take this medicine

This medicine can be taken by adults and children aged 16 years and over. However, some people should not take this medicine or should seek the advice of their pharmacist or doctor first.

Do not take:

• 
  If you are allergic to any of the ingredients


• 
  If you have asthma
  


• 
  If you have narrow angle glaucoma (sudden high pressure in the eye)


• 
  If you have a stomach ulcer or obstruction of the gut or bladder


• 
  If you have porphyria (a rare blood disease)


• 
  If you have an intolerance to some sugars, unless your doctor tells you to (this medicine contains lactose)


• 
  If you are pregnant or breastfeeding
  


• 
  If you are a man with prostate problems
  

Talk to your pharmacist or doctor:

• If you have liver problems


• If you have other forms of glaucoma (see above)


• If you have difficulty passing urine


• If you suffer from fits


• If you have a condition called myasthenia gravis

Other important information

Driving and using machines: This medicine causes drowsiness. You should not drive or operate machinery for at least 8 hours after taking the tablets.

Do not drink alcohol (wine, beer, spirits) whilst taking this medicine.

If you take this medicine continuously for a long time (e.g. more than 2 weeks), you may become dependent on it.

If you take other medicines

Before you take these tablets, make sure that you tell your pharmacist about ANY other medicines you might be using at the same time, particularly the following:

• Monoamine oxidase inhibitors (for depression), or other depressant medicines (e.g. hypnotics, sedatives, tranquillizers, tricyclic antidepressants) – do not take this medicine as well, unless your doctor tells you to.

If you are unsure about interactions with any other medicines, talk to your pharmacist. This includes medicines prescribed by your doctor and medicine you have bought for yourself, including herbal and homeopathic remedies.

How to take this medicine

Check the foil is not broken before use. If it is, do not take that tablet.

Adults and children of 16 years and over: Take two tablets 20 minutes before going to bed. Don’t take a third tablet in the same night.

Swallow the tablets with water.

Do not give to children under 16 years.

Do not take more than the amount recommended above.

If symptoms do not go away talk to your doctor.

If you take too many tablets: Talk to a doctor straight away. Take your medicine and this leaflet with you.

Possible side effects

Most people will not have problems, but some may get some. If you are elderly you may be more likely to get some of these side effects.

If you get any of these serious side effects, stop taking the tablets. See a doctor at once:

• Difficulty breathing, swelling of the face, neck, tongue or throat (severe allergic reactions)

These other effects are less serious. If they bother you talk to a pharmacist:

• Blurred vision, dizziness, drowsiness, grogginess (these usually wear off about 8 hours after taking the tablets)


• Dry mouth, feeling sick, difficulty in passing urine


• Headache, difficulty in co-ordinating movement


• Stomach problems, liver problems


• Low blood pressure, fast, slow or irregular heart beat


• Skin rash, sensitivity to light


• Sleep disturbances, tremor, fits, sweating, confusion, depression, nervousness


• Muscle pain and stiffness, pins and needles, hair loss


• Rarely unusual bruising or infections such as sore throats – this may be a sign of very rare changes in the blood

If any side effect becomes severe, or you notice any side effect not listed here, please tell your pharmacist or doctor.

How to store this medicine

Do not store above 25°C.

Store in the original package. Keep the foil in the outer carton.

Keep this medicine in a safe place out of the sight and reach of children, preferably in a locked cupboard.

Use by the date on the end flap of the carton.

What is in this medicine

Each tablet for oral administration contains Diphenhydramine Hydrochloride 25 mg, which is the active ingredient.

As well as the active ingredient, the tablets also contain lactose, maize starch, magnesium stearate.

The pack contains 20 tablets.

Who makes this medicine

Manufactured for

The Boots Company PLC

Nottingham

NG2 3AA

by

Galpharm International Ltd

Upper Cliffe Road

Dodworth Business Park

Dodworth

South Yorkshire

S75 3SP

Marketing Authorisation held by

Galpharm Healthcare Limited

Upper Cliffe Road

Dodworth Business Park

Dodworth

South Yorkshire

S75 3SP

Leaflet prepared June 2007

If you would like any further information about this medicine, please contact

The Boots Company PLC

Nottingham

NG2 3AA

Useful guidelines for a better night’s sleep

In addition to Boots Sleepeaze 25 mg Tablets, the following guidelines may enhance your sleep pattern and help you enjoy the benefits of a good night’s sleep.

• 1. Relax, switch off and unwind from the day. Try to forget the trials and tribulations of the day.
  
  


• 2. Before retiring to bed listen to music, read a book or exercise gently to clear your mind from the day’s stresses. Strenuous exercise should be undertaken earlier on in the day, as this stimulates a rush of adrenaline which may keep you awake.
  
  


• 3. Try to avoid dozing in front of the TV, save your sleep for bedtime. If your dozing is boredom, why not take up an alternative relaxing activity.
  
  


• 4. Do not drink tea or other caffeinated drinks before bedtime, as these will encourage you to visit the lavatory. A hot milky drink or barley water are more suitable.
  
  


• 5. Avoid stimulants such as alcohol and nicotine. It is also advisable to eat before 8 pm, if possible, and avoid fatty foods.
  
  


• 6. Ensure your bed and bedroom are comfortable, not too hot or cold and your room is quiet and dark. Remove all temptations, such as work material from your room.
  
  


• 7. Get into a routine. Experiment by going to bed at the same time and note what time you wake up each day for a week and so identify how many hours sleep you need and adjust these times accordingly.
  
  


• 8. Be patient. An adequate sleep pattern may take some time to establish.

3029aXPil

Mysoline Tablets 50mg

1. Name Of The Medicinal Product

Mysoline 50mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains 50mg primidone.

For full list of excipients see section 6.1

3. Pharmaceutical Form

Tablet

White or virtually white, round, biconvex, uncoated tablets intagliated with a single M on one side and plain on the reverse.

4. Clinical Particulars

4.1 Therapeutic Indications

Mysoline is indicated in the management of grand mal and psychomotor (temporal lobe) epilepsy. It is also of value in the management of focal or Jacksonian seizures, myoclonic jerks and akinetic attacks.

Management of essential tremor.

4.2 Posology And Method Of Administration

Epilepsy: Treatment must always be planned on an individual basis. In many patients it will be possible to use Mysoline alone, but in some, Mysoline will need to be combined with other anticonvulsants or with supporting therapy.

Mysoline is usually given twice daily and may be administered using either the 50 mg or 250 mg strength tablets.

Begin with 125 mg once daily late in the evening. Every 3 days increase the daily dosage by 125 mg until the patient is receiving 500 mg daily. Thereafter, every 3 days increase the daily dosage by 250 mg in adults or 125 mg in children under 9 years - until control is obtained or the maximum tolerated dosage is being given. This may be as much as 1.5 g a day in adults; 1 g a day in children.

Average daily maintenance doses:

	Milligrams
Adults and children over 9 years	750 to 1500
Children 6 to 9 years	750 to 1000
Children 2 to 5 years	500 to 750
Children up to 2 years	250 to 500

The total daily dose is usually best divided and given in two equal amounts, one in the morning and the other in the evening. In certain patients, it may be considered advisable to give a larger dose when the seizures are more frequent. For instance: 1) if the attacks are nocturnal then all or most of the day's dose may be given in the evening; 2) if the attacks are associated with some particular event such as menstruation, a slight increase in the appropriate dose is often beneficial.

Elderly patients: It is advisable to monitor elderly patients with reduced renal function who are receiving primidone.

Patients on other anticonvulsants: Where a patient's attacks are not sufficiently well controlled with other anticonvulsants, or disturbing side effects have arisen, Mysoline may be used to augment or replace existing treatment. First add Mysoline to the current anticonvulsant treatment by the method of gradual introduction described previously. When a worthwhile effect has been achieved and the amount of Mysoline being given has been built up to at least half the estimated requirement, withdrawal of the previous treatment can then be attempted. This should be done gradually over a period of 2 weeks, during which time it may be necessary to increase the Mysoline dosage to maintain control.

Withdrawal of previous treatment should not be too rapid or status epilepticus may occur. Where phenobarbitone formed the major part of the previous treatment, however, both its withdrawal and Mysoline substitution should be made earlier, so as to prevent excessive drowsiness from interfering with accurate assessment of the optimum dosage of Mysoline.

Essential tremor: Initially a dose of 50 mg daily should be introduced. The daily dose should be increased gradually over a 2 to 3 week period until remission of symptoms or the highest dose tolerated up to a maximum of 750 mg daily.

Patients with essential tremor who have not previously been exposed to anticonvulsants, or other drugs known to induce increased hepatic enzyme activity, may experience acute symptoms of tolerance to Mysoline, frequently characterised by vertigo, unsteadiness and nausea. It is, therefore, essential to start such patients at a low dosage (initially 50 mg daily) increasing very slowly up to the maximum tolerated dose or that which produces remission of tremor (up to 750mg daily).

4.3 Contraindications

Patients who exhibit hypersensitivity or an allergic reaction to primidone, to a constituent of the formulation or to phenobarbitone, should not receive the drug. Primidone should not be administered to patients with acute intermittent porphyria.

4.4 Special Warnings And Precautions For Use

Mysoline should be given with caution and may be required in reduced dosage in children, the elderly, debilitated patients or those with impaired renal, hepatic or respiratory function.

Primidone is a potent CNS depressant and is partially metabolised to phenobarbitone. After prolonged administration there is a potential for tolerance, dependence and a withdrawal reaction on abrupt cessation of treatment.

Exceptionally, as with phenytoin and phenobarbitone, megaloblastic anaemia may develop requiring discontinuation of primidone. This condition may respond to treatment with folic acid and/or vitamin B12. There have been isolated reports of other blood dyscrasias.

Primidone has the potential to harm the foetus, see section 4.6 before considering use during pregnancy.

Suicidal ideation and behaviour have been reported in patients treated with anti-epileptic agents in several indications. A meta-analysis of randomised placebo controlled trials of anti-epileptic drugs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for primidone.

Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Both primidone and its major metabolite phenobarbitone are metabolized by, and also induce, liver enzyme activity, principally the CYP 450 3A4 enzyme system..

Agents which inhibit the CYP 450 3A4 enzyme system, such as chloramphenicol, felbamate, nelfinavir*, metronidazole and sodium valproate may result in increased plasma levels of concomitantly administered primidone and its metabolite phenobarbitone.

In addition, St. John's Wort* induces the CYP450 enzyme system and may result in a reduction of plasma levels of concomitantly administered primidone and of its major metabolite phenobarbitone.

Theophylline protein binding may affect phenobarbitone binding, affecting free phenobarbitone levels.

Primidone therapy may also lead to altered pharmacokinetics in concomitantly administered drugs, whose metabolism may be increased and lead to lowered plasma levels and/or a shorter half-life. These drugs include androgens*, beta-antagonists, carbamazepine, cyclosporin, cloazepine, chloramphenicol, corticosteroids/glucocorticosteroids, cyclophosphamide, dicoumarins, digitoxin*, doxycycline, ethosuxamide, etoposide, felbamate, granisetron, lamotrigine, losartan, methadone*, metronidazole, mainserin, montelukast*, nelfinavir*, nimodipine, oral-contraceptives, oxcarbazepine, phenytoin, quinidine, rocuronium, sodium valproate, tiagabine, theophyllines, topiramate, tricyclic antidepressants, vecuronium, warfarin and zonisamide.

Primidone inhibits the glucoronidation of paracetamol* and may increase the hepatotoxicity of paracetamol.

The CNS depressant effect of primidone is additive to those of other CNS depressants such as alcohol, opiates and barbiturates.

The above interactions are potentially clinically significant.

* No formal interaction studies have been performed. The inclusion of the drug is based on reports of their influence or dependence upon enzyme systems influenced by, or of relevance to the metabolic pathways of primidone or its major metabolite, phenobarbitone.

4.6 Pregnancy And Lactation

Pregnancy: Primidone is suspected to have caused serious birth defects when administered during pregnancy. In infants born of epileptic mothers treated with primidone, there have been reports of congenital abnormalities including congenital heart disease, cleft palate and conditions associated with maternal folate deficiency, including spina bifida, microencephaly and anencephaly. Primidone should not be used during pregnancy unless clearly necessary to manage epilepsy in the mother where withdrawal of therapy may cause risks or where alternative anti-epileptic managements are unsuitable.

Withdrawal symptoms may occur in the newly born whose mothers have received primidone during late pregnancy.

Long-term anticonvulsant therapy can be associated with decreased serum folate levels. As folic acid requirements are also increased during pregnancy, regular screening of patients at risk is advised, and treatment with folic acid and Vitamin B12, although controversial, should be considered.

Anticonvulsant therapy in pregnancy has occasionally been associated with coagulation disorders in the neonates. For this reason pregnant patients should be given Vitamin K1 through the last month of pregnancy up to the time of delivery. In the absence of such pretreatment, 10 mg Vitamin K1 may be given to the mother at the time of delivery and 1 mg should be given immediately to the neonate at risk.

Lactation: During breast feeding the baby should be monitored for sedation.

4.7 Effects On Ability To Drive And Use Machines

As with most other anticonvulsants, patients who drive vehicles or operate machinery should be made aware of the possibility of impaired reaction time.

4.8 Undesirable Effects

If adverse effects do appear, the most common side effects are drowsiness and listlessness but these generally occur only in the beginning of treatment.

Visual disturbances, nausea, headache, dizziness, vomiting, nystagmus and ataxia have been reported but are usually transient even when pronounced. On occasions an idiosyncratic reaction may occur which involves these symptoms in an acute and severe form necessitating withdrawal of treatment.

Common ( >1/100)	General	Drowsiness
	Central and peripheral nervous system	Listlessness, ataxia, visual disturbances, nystagmus
	Gastrointestinal	Nausea
Less common (1/100 - 1/1000)	General	Headache, dizziness
	Gastrointestinal	Vomiting
	Dermatological	Allergic reactions particularly affecting the skin can include maculopapular, morbilliform or scarlatiniform rashes.
Rare (< 1/1000)	Central and peripheral nervous system	Personality changes, which may include psychotic reactions.
	Haematological	Megaloblastic anaemia, blood dyscrasias
	Hepatic	Elevations in hepatic enzymes, including gamma-glutamyl transferase (gamma GT) and alkaline phosphatase.
	Musculoskeletal	Arthralgia, osteomalacia. As with phenobarbitone, Dupuytren's contracture has been reported
	Dermatological	Severe reactions such as exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis and lupus erythematosus.

Vitamin D supplementation may be needed during long-term primidone therapy, since vitamin D catabolism may be increased.

Exceptionally, as with phenytoin and phenobarbitone, megaloblastic anaemia may develop requiring discontinuation of primidone. This condition may respond to treatment with folic acid and/or Vitamin B12.

4.9 Overdose

Primidone is metabolised extensively to phenobarbitone and overdosage leads to varying degrees of CNS depression which, depending on the dose ingested, may include ataxia, loss of consciousness, respiratory depression and coma.

Crystalluria may occur in overdosage and could be used as a helpful diagnostic aid where primidone overdosage is suspected.

Depending on the severity of intoxication, therapy should include aspiration of stomach contents, administration of activated charcoal, administration of intravenous fluids, forced alkaline diuresis (striving for a urine pH of 8.0), and general supportive measures. In more life threatening circumstances, haemoperfusion (if the patient is hypotensive) or haemodialysis are effective.

There is no specific antidote.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antiepileptics (barbiturates and derivatives).

Therapeutic classification: N03AA03

The activity of Mysoline is due to the anticonvulsant properties of three active moieties, namely primidone itself and its two major metabolites phenobarbitone and phenylethylmalonamide. The relative contribution of these three moieties to the clinical anticonvulsant effect has not been firmly established. Although the precise mode of action of primidone is unknown, in common with other anticonvulsants, effects on the neuronal membrane particularly with respect to alteration of ionic fluxes are likely to play a fundamental role.

Primidone, as with other anticonvulsants, can induce liver enzymes.

5.2 Pharmacokinetic Properties

Primidone is absorbed rapidly from the gastrointestinal tract, peak plasma levels being attained approximately 3 hours after ingestion. Primidone is well distributed in all organs and tissues: it crosses the blood-brain and placental barriers and is excreted in breast milk. The pharmacokinetics of primidone are complex because of biotransformation into two metabolites, phenobarbitone and phenylethylmalonamide, that have anticonvulsant activity and complex pharmacokinetic properties. Primidone has a plasma half-life of approximately 10 hours which is considerably shorter than those of its principal metabolites.

Primidone and phenylethylmalonamide are bound to plasma proteins to only a small extent, whereas approximately half of phenobarbitone is bound. Approximately 40% of the drug is excreted unchanged in urine.

5.3 Preclinical Safety Data

Primidone is a drug on which extensive clinical experience has been obtained. All relevant information for the prescriber is provided elsewhere in the Summary of Product Characteristics.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Carmellose calcium

Gelatin

Magnesium stearate

Povidone K30

Purified water

Stearic acid

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

5 years.

6.4 Special Precautions For Storage

Store below 25°C.

6.5 Nature And Contents Of Container

HDPE bottle containing 100 tablets, with a white HDPE, tamper-evident, child resistant push-on cap with a white LDPE liner.

6.6 Special Precautions For Disposal And Other Handling

No special requirements.

7. Marketing Authorisation Holder

Acorus Therapeutics Limited

Office Village

Chester Business Park

Chester

Cheshire

CH4 9QZ.

UK

8. Marketing Authorisation Number(S)

PL 20132/0006

9. Date Of First Authorisation/Renewal Of The Authorisation

02/06/2010

10. Date Of Revision Of The Text

02/06/2010

Kemadrin

Pronunciation: proe-SYE-kli-deen
Generic Name: Procyclidine
Brand Name: Kemadrin

Kemadrin is used for:

Treating Parkinson disease. It may also be used for other conditions as determined by your doctor.

Kemadrin is an anticholinergic agent. It works by relaxing smooth muscle, which stops muscle spasms.

Do NOT use Kemadrin if:

• you are allergic to any ingredient in Kemadrin


• you have angle-closure glaucoma

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

Before using Kemadrin:

Some medical conditions may interact with Kemadrin. 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 glaucoma, mental or mood disorders, muscle weakness (eg, myasthenia gravis), ulcerative colitis, (eg, an enlarged prostate), or urination problems


• if you have a blockage of the stomach, esophagus, or urinary tract; kidney or liver problems; high blood pressure; heart or blood vessel disease; an irregular heartbeat; or uncontrolled movements of the hands, mouth, or tongue

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

• Phenothiazines (eg, thioridazine) because the effectiveness may be decreased by Kemadrin

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

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

• Take Kemadrin with food or immediately after finishing a meal.


• If you miss a dose of Kemadrin, 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 Kemadrin.

Important safety information:

• Kemadrin may cause lightheadedness or blurred vision. Do not drive, operate machinery, or do anything else that could be dangerous until you know how you react to Kemadrin. Using Kemadrin alone, with certain other medicines, or with alcohol may lessen your ability to drive or perform other potentially dangerous tasks.


• Kemadrin may cause dizziness, lightheadedness, or fainting. Alcohol, hot weather, exercise, and fever can increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Also, sit or lie down at the first sign of dizziness, lightheadedness, or weakness.


• Do not become overheated in hot weather or during exercise or other activities; heatstroke may occur.


• Use Kemadrin with extreme caution in CHILDREN. Safety and effectiveness have not been confirmed.


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

Possible side effects of Kemadrin:

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; constipation; dilated pupils; dry mouth; giddiness; lightheadedness; loss of appetite; nausea; upset stomach; vomiting.

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); chest pain; confusion; difficult or painful urination; difficulty swallowing; eye pain; fast or pounding heartbeat; mental or mood changes; uncontrolled movements.

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: Kemadrin 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. Symptoms may include dilated pupils; fast breathing; fast heartbeat; hot, dry, or flushed skin.

Proper storage of Kemadrin:

Store Kemadrin 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 Kemadrin out of the reach of children and away from pets.

General information:

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


• Kemadrin 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 Kemadrin. 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 Kemadrin resources

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

• Kemadrin Prescribing Information (FDA)


• Kemadrin Concise Consumer Information (Cerner Multum)


• Kemadrin Monograph (AHFS DI)


• Procyclidine Professional Patient Advice (Wolters Kluwer)

Compare Kemadrin with other medications

• Parkinson's Disease
• Parkinsonian Tremor
• Parkinsonism