pseudoephedrine

soo-doe-e-FED-rin

Commonly used brand name(s)

In the U.S.

• 12 Hour Cold Maximum Strength


• Biofed


• Cenafed


• Chlor-Trimeton Nasal Decongestant


• Contac 12-Hour


• Dimetapp Decongestant


• Efidac 24 Pseudoephedrine


• ElixSure Congestion Children's


• Genaphed


• Pediacare Decongestant Infants


• Simply Stuffy


• Sudafed

Available Dosage Forms:

• Capsule, Extended Release


• Tablet, Chewable


• Tablet, Extended Release


• Solution


• Syrup


• Liquid


• Tablet


• Capsule


• Capsule, Liquid Filled


• Suspension

Therapeutic Class: Decongestant

Pharmacologic Class: Alpha-Adrenergic Agonist

Uses For pseudoephedrine

Pseudoephedrine is used to relieve nasal or sinus congestion caused by the common cold, sinusitis, and hay fever and other respiratory allergies. It is also used to relieve ear congestion caused by ear inflammation or infection.

Some of these preparations are available only with your doctor's prescription.

Do not give any over-the-counter (OTC) cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects .

Before Using pseudoephedrine

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 pseudoephedrine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to pseudoephedrine 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

Pseudoephedrine may be more likely to cause side effects in infants, especially newborn and premature infants, than in older children and adults.

Do not give any over-the-counter (OTC) cough and cold medicine to a baby or child under 4 years of age. Using these medicines in very young children might cause serious or possibly life-threatening side effects .

Geriatric

Many medicines have not been studied specifically in older people. Therefore, it may not be known whether they work exactly the same way they do in younger adults or if they cause different side effects or problems in older people. There is no specific information comparing use of pseudoephedrine in the elderly with use in other age groups.

Breast Feeding

Studies in women suggest that this medication poses minimal risk to the infant when used during 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 pseudoephedrine, 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 pseudoephedrine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Clorgyline


• Dihydroergotamine


• Furazolidone


• Iproniazid


• Isocarboxazid


• Linezolid


• Moclobemide


• Nialamide


• Pargyline


• Phenelzine


• Procarbazine


• Rasagiline


• Selegiline


• Toloxatone


• Tranylcypromine

Using pseudoephedrine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Guanethidine


• Methyldopa


• Midodrine

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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

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

• Type 2 diabetes mellitus—Use of pseudoephedrine may cause an increase in blood glucose levels

• Enlarged prostate or


• Glaucoma, or a predisposition to glaucoma or


• Heart disease or blood vessel disease or


• High blood pressure—Pseudoephedrine may make the condition worse

• Overactive thyroid—Use of pseudoephedrine may make the condition worse

Proper Use of pseudoephedrine

For patients taking pseudoephedrine extended-release capsules:

• Swallow the capsule whole. However, if the capsule is too large to swallow, you may mix the contents of the capsule with jam or jelly and swallow without chewing.


• Do not crush or chew before swallowing.

For patients taking pseudoephedrine extended-release tablets:

• Swallow the tablet whole.


• Do not break, crush, or chew before swallowing.

To help prevent trouble in sleeping, take the last dose of pseudoephedrine for each day a few hours before bedtime. If you have any questions about this, check with your doctor.

Take pseudoephedrine only as directed. Do not take more of it, do not take it more often, and do not take it for a longer period of time than recommended on the label (usually 7 days), unless otherwise directed by your doctor. To do so may increase the chance of side effects.

Dosing

The dose of pseudoephedrine 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 pseudoephedrine. 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 nasal or sinus congestion:
  
  • For regular (short-acting) oral dosage form (capsules, oral solution, syrup, or tablets):
    
    • Adults and children 12 years of age and older—60 milligrams (mg) every four to six hours. Do not take more than 240 mg in twenty-four hours.
    
    
    • Children 6 to 12 years of age—30 mg every four to six hours. Do not take more than 120 mg in twenty-four hours.
    
    
    • Children 4 to 6 years of age—15 mg every four to six hours. Do not take more than 60 mg in twenty-four hours.
    
    
    • Children and infants up to 4 years of age—Use is not recommended .
    
    
  
  
  • For long-acting oral dosage form (extended-release capsules or extended-release tablets):
    
    • Adults and children 12 years of age and older—120 mg every 12 hours, or 240 mg every 24 hours. Do not take more than 240 mg in 24 hours.
    
    
    • Infants and children up to 12 years of age—Use is not recommended .
    
    
  
  

Missed Dose

If you miss a dose of pseudoephedrine, 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.

Precautions While Using pseudoephedrine

If symptoms do not improve within 7 days or if you also have a high fever, check with your doctor since these signs may mean that you have other medical problems.

pseudoephedrine 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 as soon as possible if any of the following side effects occur:

Rare - more common with high doses

• Convulsions (seizures)


• hallucinations (seeing, hearing, or feeling things that are not there)


• irregular or slow heartbeat


• shortness of breath or troubled breathing

Symptoms of overdose

• Convulsions (seizures)


• fast breathing


• hallucinations (seeing, hearing, or feeling things that are not there)


• increase in blood pressure


• irregular heartbeat (continuing)


• shortness of breath or troubled breathing (severe or continuing)


• slow or fast heartbeat (severe or continuing)


• unusual nervousness, restlessness, or excitement

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

• Nervousness


• restlessness


• trouble in sleeping

Less common

• Difficult or painful urination


• dizziness or light-headedness


• fast or pounding heartbeat


• headache


• increased sweating


• nausea or vomiting


• trembling


• unusual paleness


• weakness

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: pseudoephedrine side effects (in more detail)

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More pseudoephedrine resources

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

• Pseudoephedrine MedFacts Consumer Leaflet (Wolters Kluwer)


• Pseudoephedrine Monograph (AHFS DI)


• Dimetapp Decongestant Drops MedFacts Consumer Leaflet (Wolters Kluwer)


• Drixoral Non-Drowsy Sustained-Release Capsules MedFacts Consumer Leaflet (Wolters Kluwer)


• Entex Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• Entex Consumer Overview


• Sudafed Consumer Overview


• Tylenol Simply Stuffy Liquid MedFacts Consumer Leaflet (Wolters Kluwer)

Compare pseudoephedrine with other medications

• Nasal Congestion

Trimethoprim 200 mg tablets

1. Name Of The Medicinal Product

Trimethoprim 200mg Tablets

2. Qualitative And Quantitative Composition

Each tablet contains Trimethoprim 200mg

For a full list of excipients see section 6.1.

3. Pharmaceutical Form

Tablet: White coloured flat bevelled edged tablets engraved with 'MT200'.

Slight characteristic odour.

4. Clinical Particulars

4.1 Therapeutic Indications

Treatment of susceptible infections caused by trimethoprim sensitive organisms including most gram-positive and gram-negative aerobic organisms, including Haemophilus influenzae, Streptococcus pneumoniae, Klebsiella pneumonia, Staphylococcus aureus, Eschersichia coli, Enterobacter, Proteus and Streptococcus faecalis.

Exceptions include anaerobic bacteria. Mycobacterium tuberculosis, neisseria gonorrhoeae, pseudomonas aeruginosa and treponema pallidum.

Prophylaxis of recurrent urinary tract infections.

Consideration should be given to official guidance on the appropriate use of antibacterial agents

4.2 Posology And Method Of Administration

Posology

Acute infections:

Treatment should continue for a period of between three days (e.g. uncomplicated bacterial cystitis in women) and two weeks according to the nature and severity of infection. The first dose can be doubled.

• Adults and children over 12 years: 200mg twice daily.

• Children 6-12 years: 100mg twice daily.

• Children under 6 years of age: Not recommended; a more suitable dosage form should be used in this age group.

• Elderly: Dosage is dependent upon kidney function; see special dosage schedule.

Long-term treatment and prophylactic therapy:

• Adults and children over 12 years: 100mg at night.

• Children 6-12 years: 50mg at night. Where a single daily dose is required, dosage at bedtime may maximise urinary concentrations. The approximate dosage in children is 2mg trimethoprim per kg body weight per day.

• Elderly: Dosage is dependent upon kidney function; see special dosage schedule

Advised dosage schedule where there is reduced kidney function:

Creatinine Clearance	Plasma creatinine (micromol/l)	Dosage advised
Over 0.45	Men <250 Women <175	Normal
0.25 - 0.45	Men 250-600	Normal for 3 days then half
Women 175-400	dose
Under 0.25	Men >600 Women >400	Half the normal dose

Trimethoprim is removed by dialysis. However, it should not be administered to dialysis patients unless plasma concentrations can be estimated regularly.

Route of administration: oral

4.3 Contraindications

Hypersensitivity to trimethoprim or any of the excipients. Pregnancy. Severe hepatic insufficiency. Severe renal insufficiency where blood levels cannot be regularly monitored. Megaloblastic anaemia and other blood dyscrasias.Trimethoprim should not be administered to premature infants or children under 4 months of age.

4.4 Special Warnings And Precautions For Use

Administer with care to patients with impaired renal function. Regular haematological examination should be performed during long-term therapy.

Caution should be exercised in the administration of trimethoprim to patients with actual or potential folate deficiency (e.g. the elderly) and administration of folate supplement should be considered.

Although an effect on folate metabolism is possible, interference with haematopoiesis rarely occurs at the recommended dose. If any such change is seen, folinic acid should reverse the effect. Elderly people may be more susceptible and a lower dose may be advisable.

In patients with renal impairment, care should be taken to avoid accumulation.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorbtion should not take this medicine.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Special care is necessary patients receiving pyrimethamine therapy in addition to trimethoprim. Increased antifolate effect when trimethoprim is given with pyrimetamine.

Bone marrow depressants - trimethoprim may increase the potential for bone marrow aplasia.

Rifampicin may increase the elimination and shorten the elimination half-life of trimethoprim.

Phenytoin and digoxin - the patient should be carefully controlled as trimethoprim may increase the elimination half-life of phenytoin and digoxin.

Trimethoprim may potentiate the anticoagulant effect of warfarin

Ciclosporin may increase the nephrotoxicity of trimethoprim.

4.6 Pregnancy And Lactation

Trimethoprim is contraindicated during pregnancy (see section 4.3).

Although trimethoprim is excreted in breast milk, it is not necessarily contraindicated for short-term therapy during lactation.

4.7 Effects On Ability To Drive And Use Machines

None known

4.8 Undesirable Effects

Blood and lymphatic system disorders

Trimethoprim therapy may affect haematopoiesis

Immune system disorders

Photosensitivity and allergic reactions including urticaria, angioedema and anaphylaxis

Nervous system disorders

Headache, Aseptic meningitis

Gastrointestinal disorders

Gastro-intestinal disturbances including nausea and vomiting

Skin and subcutaneous tissue disorders

Pruritis, skin rashes.

More severe skin sensitivity reactions such as erythema multiforme, Stevens-Johnson Syndrome and ToxicEpidermal Necrolysis have been reported rarely.

Musculoskeletal and connective tissue disorders

Myalgia

4.9 Overdose

Treat symptomatically, gastric lavage and forced diuresis may be used. Depression of haematopoiesis by trimethoprim may be countered by intramuscular injections of calcium folinate.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic Group: Systemic antibacterial. ATC Code: J01EA01

Mechanism of action: Trimethoprim is a dihydrofolate reductase inhibitor which affects the nucleoprotein metabolism of micro-organisms by interference in the folic-folinic acid systems.

Trimethoprim is effective in vitro against a wide range of Gram-positive and aerobic Gram-negative organisms, including enterobacteria Escherica coli, Proteus, Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus faecalis, Haemophilus influenzae and Staphylococcus aureus.

It is not effective against Anaerobes, Pseudomonas aeruginosa, Treponema pallidum, Mycobacteria, Nocardia species, Neisseria species and Brucella abortus.

5.2 Pharmacokinetic Properties

Trimethoprim is rapidly and almost completely absorbed from the gastrointestinal tract and peak concentrations in the circulation occur about 1-4 hours after an oral dose. Peak plasma concentrations of about 1μg/ml have been reported after a single dose of 100mg. Approximately 40-70% is bound to plasma proteins. The half life is approximately 8-10 hours. About 40-60% of a dose is excreted unchanged in the urine within 24 hours, together with metabolites; hence, patients with impairment of renal function such as the elderly may require a reduction in dosage due to accumulation. It appears in breast milk.

5.3 Preclinical Safety Data

There is no pre-clinical data of relevance to the prescriber additional to that included in other sections of the SmPC.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Lactose

Povidone 25cps

Crospovidone

Sodium starch glycollate

Magnesium stearate

6.2 Incompatibilities

None known

6.3 Shelf Life

36 months

6.4 Special Precautions For Storage

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

6.5 Nature And Contents Of Container

High density polystyrene with polythene lids and/or polypropylene containers with polythene lids and polyurethane or polythene inserts.

Blister pack - 25 micron PVC glass-clear/bluish rigid PVC (pharmaceutical grade) 20 micron hard-tempered aluminium foil coated on the pull side with 6-7gsm heat seal lacquer and printed on the bright side.

Pack sizes: 50, 100, 500, 1000, 5000 (Bulk pack), 6, 14 & 28 (blister pack)

Not all pack sizes may be marketed.

6.6 Special Precautions For Disposal And Other Handling

No special requirements

7. Marketing Authorisation Holder

Milpharm Limited,

Ares,

Odyssey Business Park,

West End Road,

South Ruislip HA4 6QD,

United Kingdom

8. Marketing Authorisation Number(S)

PL 16363/0024

9. Date Of First Authorisation/Renewal Of The Authorisation

8 March 2001

10. Date Of Revision Of The Text

01/11/2011

Aralen Phosphate

Generic Name: Chloroquine Phosphate
Class: Antimalarials
VA Class: AP101
CAS Number: 50-63-5

Introduction

Antimalarial; 4-aminoquinoline derivative.¹³⁶

Uses for Aralen Phosphate

Malaria

Prevention (prophylaxis) of malaria caused by Plasmodium malariae, P. ovale, chloroquine-susceptible P. vivax, or chloroquine-susceptible P. falciparum.^{136 174 176 178} Recommended by CDC and others as drug of choice for prevention of malaria caused by susceptible Plasmodium; should be used whenever malaria prophylaxis is indicated in individuals traveling to malarious areas where chloroquine-resistant P. falciparum malaria has not been reported.^{140 147 148 149 162 163 164 166 174 175 176 177 178} (See Chloroquine-resistant Plasmodium under Cautions.)

Treatment of uncomplicated malaria caused by susceptible P. falciparum.¹⁹¹ Recommended by CDC and others as the drug of choice for treatment of uncomplicated P. falciparum malaria acquired in areas where chloroquine resistance has not been reported.^{174 183 191} (See Chloroquine-resistant Plasmodium under Cautions.)

Treatment of uncomplicated malaria caused by P. malariae, P. ovale, or chloroquine-susceptible P. vivax.^{136 174 183 191} Recommended by CDC and others as the drug of choice for treatment of uncomplicated malaria caused by these Plasmodium;^{174 183 191} do not use for P. vivax malaria acquired in Papua New Guinea or Indonesia.^{183 191} (See Chloroquine-resistant Plasmodium under Cautions.)

Active only against the asexual erythrocytic forms of Plasmodium (not exoerythrocytic stages) and cannot prevent delayed primary attacks or relapse of P. ovale or P. vivax malaria or provide a radical cure; primaquine usually also indicated to eradicate hypnozoites and prevent relapse in patients exposed to or being treated for P. ovale or P. vivax malaria.^{176 183}

Detailed recommendations regarding prevention of malaria available from CDC 24 hours a day from the voice information service (877-394-8747) or at .¹⁷⁶

Assistance with diagnosis or treatment of malaria available from CDC Malaria Hotline at 770-488-7788 from 8:00 a.m. to 4:30 p.m. Eastern Standard Time or CDC Emergency Operation Center at 770-488-7100 after hours, on weekends, and holidays.¹⁹¹

Extraintestinal Amebiasis

Has been used for treatment of extraintestinal amebiasis¹³⁶ (including liver abscess) caused by Entamoeba histolytica.

Ineffective for treatment of intestinal amebiasis.^a

A nitroimidazole derivative (metronidazole, tinidazole) followed by a luminal amebicide (iodoquinol, paromomycin, diloxanide furoate) is usual regimen of choice for mild to moderate or severe intestinal disease and for amebic hepatic abscess.^{174 178}

Rheumatoid Arthritis

Has been used for treatment of rheumatoid arthritis† in patients whose symptoms progress despite an adequate regimen of nonsteroidal anti-inflammatory agents (NSAIAs).^a

No longer a recommended disease-modifying antirheumatic drug (DMARD).^a Other DMARDs generally preferred,^{105 106} especially since risk of severe and sometimes irreversible toxicity must be considered if chloroquine is used for prolonged periods in treatment of rheumatoid arthritis. (See Cautions.)^a

Lupus Erythematosus

Has been used as an adjunct to topical corticosteroid therapy in treatment of discoid lupus erythematosus† and as an adjunct to systemic corticosteroid and/or salicylate therapy in treatment of systemic lupus erythematosus†.^a

If used for prolonged periods in the treatment of lupus erythematosus, the risk of serious and sometimes irreversible toxicity should be considered.^a (See Cautions.)

Porphyria Cutanea Tarda and Polymorphous Light Eruptions

Has been used with some success in treatment of porphyria cutanea tarda†.^{185 186 187} (See Patients with Psoriasis or Porphyria under Cautions.)

Has been effective in some cases when used in treatment of polymorphous light eruptions†.

Sarcoidosis

Has been used with some success in the treatment of sarcoidosis†.^{188 189}

Aralen Phosphate Dosage and Administration

Administration

Administer orally.¹³⁶

Oral Administration

Administration with meals may minimize adverse GI effects.^a

Because tablets have a bitter taste, they have been pulverized and mixed with chocolate or cherry syrup for administration in children or, alternatively, enclosed in gelatin capsules for mixing in food or drink.^a Outside the US, the drug is available in many countries as an oral suspension for use in children.¹⁷⁶ However, the chloroquine concentration varies depending on the specific oral suspension, and parents should be instructed how to calculate the appropriate volume to be administered based on the child's body weight.¹⁷⁶

For prevention of malaria, chloroquine is given once weekly and should be administered on the same day each week.^{136 148 163 166} If intolerable adverse GI effects occur despite administration with meals, the usual weekly dose can be divided into 2 doses and administered on separate days during the week.^a

Dosage

Available as chloroquine phosphate;¹³⁶ dosage usually expressed in terms of chloroquine.¹³⁶ Each 100 mg of chloroquine phosphate is equivalent to 60 mg of chloroquine.¹³⁶

Dosage of chloroquine in children should be calculated in proportion to adult dosage based on body weight.¹³⁶

Pediatric Patients

Malaria

Prevention of Malaria in Areas without Chloroquine-resistant Plasmodium

Oral

5 mg/kg (8.3 mg/kg of chloroquine phosphate) once weekly on the same day each week.^{136 163 174 176}

Initiate prophylaxis 1–2 weeks prior to entering a malarious area and continue for 4 weeks after leaving the area.¹⁷⁶

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of chloroquine prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.^{174 176}

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

An initial dose of 10 mg/kg of chloroquine (16.7 mg/kg of chloroquine phosphate) followed by 5-mg/kg doses (8.3 mg/kg of chloroquine phosphate) given at 6, 24, and 48 hours after the initial dose.^{174 183 191}

Adults

Malaria

Prevention of Malaria in Areas without Chloroquine-resistant Plasmodium

Oral

300 mg (500 mg of chloroquine phosphate) once weekly.^{136 163 174 176}

Initiate prophylaxis 1–2 weeks prior to entering a malarious area and continue for 4 weeks after leaving the area.¹⁷⁶

Terminal prophylaxis with primaquine may be indicated during the final 2 weeks of chloroquine prophylaxis if exposure occurred in areas where P. ovale or P. vivax are endemic.^{174 176}

Treatment of Uncomplicated Chloroquine-susceptible Malaria

Oral

An initial dose of 600 mg of chloroquine (1 g of chloroquine phosphate) followed by 300-mg doses (500 mg of chloroquine phosphate) given at 6, 24, and 48 hours after the initial dose.¹⁹¹

Prophylaxis of P. ovale or P. vivax When Primaquine Is Deferred during Pregnancy

Oral

300 mg (500 mg of chloroquine phosphate) once weekly for the duration of the pregnancy.¹⁸³ Given after the usual treatment regimen and continued until primaquine can be given to provide a radical cure after delivery.¹⁸³

Extraintestinal Amebiasis

Oral

600 mg of chloroquine (1 g of chloroquine phosphate) once daily for 2 days, followed by 300 mg (500 mg of chloroquine phosphate) once daily for at least 2–3 weeks; usually used in conjunction with an intestinal amebicide.¹³⁶

Rheumatoid Arthritis†

Oral

150 mg (250 mg of chloroquine phosphate) daily. After remission or maximum improvement occurs, dosage should be reduced.^a

A response may not occur until after >4–6 weeks of therapy.^a Some clinicians recommend that the drug be continued for 4 months before being considered ineffective for treatment of rheumatoid arthritis.^a

Lupus Erythematosus†

Oral

150 mg (250 mg of chloroquine phosphate) daily.^a

When used in conjunction with topical corticosteroids in treatment of discoid lupus erythematosus, skin lesions may regress within 3–4 weeks and new lesions may not appear.^a When systemic and cutaneous manifestations of lupus erythematosus subside, reduce chloroquine dosage gradually over several months, and discontinue as soon as possible.^a

Prescribing Limits

Pediatric Patients

Malaria

Prevention of Malaria in Areas Without Chloroquine-resistant Plasmodium

Oral

Maximum dosage of 300 mg (500 mg of chloroquine phosphate) daily, regardless of weight.^{136 174 176}

Cautions for Aralen Phosphate

Contraindications

• 
  

  Hypersensitivity to chloroquine or other 4-aminoquinoline derivatives.¹³⁶

  
  


• 
  

  Retinal or visual field changes attributable to 4-aminoquinoline derivatives or to any other etiology.¹³⁶ After weighing the possible benefits and risks to the patient, some clinicians may elect to use chloroquine in these patients for treatment of acute attacks of malaria caused by susceptible Plasmodium.¹³⁶

  
  

Warnings/Precautions

Warnings

Chloroquine-resistant Plasmodium

For prevention of malaria, use only in individuals traveling to malarious areas where chloroquine-resistant P. falciparum malaria has not been reported.^{136 140 147 148 149 162 163 164 166 174 175 176 177 178} Malaria-related deaths have been reported in US citizens using chloroquine-containing regimens (i.e., chloroquine alone or in conjunction with proguanil) for malaria prevention in countries with chloroquine-resistant P. falciparum.¹¹⁸

For prevention or treatment of malaria, consider that chloroquine-resistant P. falciparum have been reported in many areas where malaria occurs.^{140 143 144 174 176 183}

Consider that chloroquine-resistant P. vivax has been reported with a high incidence in Papua New Guinea and Indonesia and rarely in Burma (Myanmar), India, and Central and South America.^{183 191} A treatment regimen effective against chloroquine-resistant P. vivax should be used in those who acquire P. vivax malaria in Papua New Guinea or Indonesia.^{174 183 191}

Malaria patients who do not respond to chloroquine should be switched to a treatment recommended for chloroquine-resistant P. falciparum (e.g., quinine sulfate with doxycycline, tetracycline or clindamycin; fixed combination of atovaquone and proguanil; fixed combination of artemether and lumefantrine) or chloroquine-resistant P. vivax (e.g., quinine sulfate with doxycycline or tetracycline in conjunction with primaquine; mefloquine in conjunction with primaquine; fixed combination of atovaquone and proguanil in conjunction with primaquine).^{183 191}

Ocular Effects

Dose-related retinopathy reported, which may progress even after the drug is discontinued.¹³⁶ Retinal changes may be reversible if detected early, but usually are permanent and may rarely result in blindness.¹³⁶

Whenever long-term therapy is contemplated, perform initial (base line) and periodic ophthalmologic examinations, including visual acuity, slit-lamp, funduscopic, and visual field tests.¹³⁶

Discontinue drug immediately and closely observe patient for possible progression if there is any indication of abnormalities in visual acuity or visual field, abnormalities in the retinal macular area (such as pigmentary changes or loss of foveal reflex), or if any other visual symptoms (e.g., light flashes and streaks) occur which are not fully explainable by difficulties of accommodation or corneal opacities.¹³⁶

Neuromuscular Effects

Skeletal muscle myopathy or neuromyopathy occur rarely; neuromyopathy is manifested as slowly progressing weakness which first affects proximal muscles of lower extremities.¹³⁶

Patients receiving prolonged therapy should be questioned and examined periodically for evidence of muscular weakness; knee and ankle reflexes should be tested.¹³⁶

Discontinue chloroquine if muscular weakness occurs.¹³⁶

Patients with Psoriasis or Porphyria

May exacerbate psoriasis and precipitate a severe attack in patients with the disease.¹³⁶ Use in psoriasis patients only if potential benefits outweigh the risks.¹³⁶

May exacerbate porphyria.¹³⁶ Use in patients with porphyria only if potential benefits outweigh the risks.¹³⁶

General Precautions

Hematologic Effects

Aplastic anemia, reversible agranulocytosis, thrombocytopenia, and neutropenia reported rarely.¹³⁶

Periodically monitor CBCs in patients receiving prolonged treatment.¹³⁶ Consider discontinuing chloroquine if any severe blood disorder occurs which is not attributable to the disease being treated.¹³⁶

Use with caution in patients with G-6-PD deficiency.¹³⁶

Otic Effects

Nerve-type deafness, tinnitus, and reduced hearing reported rarely in patients with pre-existing auditory damage.¹³⁶

Use with caution in patients with preexisting auditory damage.¹³⁶ Discontinue chloroquine immediately and closely observe patient if any hearing defects occur.¹³⁶

CNS Effects

Seizures may occur; advise patients with a history of epilepsy about the risk.¹³⁶

Specific Populations

Pregnancy

Category C.^c

Avoid use during pregnancy unless the clinician determines that the benefits of prevention or treatment of malaria outweigh the risks.¹³⁶

Has been used for prophylaxis and treatment of malaria in pregnant women without evidence of adverse effects on the fetus.¹⁷⁶

CDC states that the benefits of chloroquine prophylaxis in pregnant women exposed to malaria outweigh the potential risks to the fetus.¹⁷⁶

Because malaria infection in pregnant women is associated with high risks of maternal and perinatal morbidity and mortality (e.g., miscarriage, premature delivery, low birth weight, congenital infection and/or perinatal death), CDC recommends prompt chloroquine treatment in pregnant women with uncomplicated malaria caused by P. malariae, P. ovale, chloroquine-susceptible P. falciparum, or chloroquine-susceptible P. vivax.¹⁸³

Because use of primaquine should be deferred during pregnancy, CDC recommends that pregnant women being treated for P. ovale or P. vivax malaria receive chloroquine prophylaxis for the duration of the pregnancy (after the initial chloroquine treatment regimen) until primaquine can be given after delivery to provide a radical cure.^{183 191}

Lactation

Distributed into milk.^{122 123 124} Discontinue nursing or the drug.¹³⁶

Amount of drug present in human milk does not appear to be harmful to nursing infants, but is insufficient to provide adequate protection against malaria in these infants.¹⁷⁶ When chemoprophylaxis is necessary in such infants, they should receive recommended dosages of the appropriate antimalarial agent(s).¹⁷⁶

Pediatric Use

Pediatric patients are especially sensitive to 4-aminoquinoline derivatives.¹³⁶ Fatalities have been reported following accidental ingestion of relatively small doses.¹³⁶

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.¹³⁶

Substantially eliminated by kidneys; risk of toxicity may be greater in patients with impaired renal function.¹³⁶ Select dosage with caution and assess renal function periodically since geriatric patients are more likely to have renal impairment.¹³⁶

Hepatic Impairment

Concentrates in the liver; use with caution in patients with hepatic disease or alcoholism and in those receiving known hepatotoxic drugs.¹³⁶

Common Adverse Effects

Ocular effects; skeletal muscle myopathy or neuromyopathy; GI effects (anorexia, nausea, vomiting, diarrhea, abdominal cramps); dermatologic effects (pleomorphic skin eruptions, skin and mucosal pigmentary changes).¹³⁶

Interactions for Aralen Phosphate

Specific Drugs

Drug	Interaction	Comments
Ampicillin	Possible reduced bioavailability of ampicillin136	Administer chloroquine at least 2 hours before or after ampicillin136
Antacids	Possible reduced GI absorption of chloroquine136	Administer chloroquine at least 4 hours before or after antacids136
Cimetidine	Possible inhibition of chloroquine metabolism resulting in increased concentrations of the antimalarial136	Avoid concomitant use136
Cyclosporine	Possible increased cyclosporine concentrations136	Closely monitor serum cyclosporine concentrations; if necessary, discontinue chloroquine136
Praziquantel	Possible decreased praziquantel concentrations184
Rabies vaccine	Possible interference with immune response to intradermally administered human diploid-cell rabies vaccine (HDCV) (no longer commercially available in the US)116 117 176 182	Complete preexposure intradermal vaccination with HDCV (no longer commercially available in the US) before initiating chloroquine malaria prophylaxis or administer the vaccine IM in those receiving chloroquine 176 182
Sulfadoxine and pyrimethamine	Possible increased incidence and severity of adverse effects when used concomitantly with chloroquine compared with use of sulfadoxine and pyrimethamine alone190

Aralen Phosphate Pharmacokinetics

Absorption

Bioavailability

Rapidly and almost completely absorbed from GI tract following oral administration;^{a 136} peak plasma concentrations generally attained within 1–2 hours.^a

Food

Bioavailability of chloroquine is greater when administered with food;^a rate of absorption is unaffected but peak plasma concentrations and AUCs are higher.^a

Distribution

Extent

Widely distributed into body tissues.^a

Chloroquine binds to melanin-containing cells in the eyes and skin; skin concentrations of the drug are considerably higher than plasma concentrations.^a Also concentrates in erythrocytes and binds to platelets and granulocytes.^a

Crosses placenta in mice.¹³⁶ Distributed into milk.^{122 123 124}

Plasma Protein Binding

50–65%.¹⁰⁴

Elimination

Metabolism

Partially metabolized; the major metabolite is desethylchloroquine.^{122 123 124 136 147} Desethylchloroquine also has antiplasmodial activity, but is slightly less active than chloroquine.¹¹⁴

Elimination Route

Chloroquine and its metabolites are slowly excreted by the kidneys; unabsorbed drug is excreted in feces.^a

Up to 70% of a dose is excreted unchanged in urine and up to 25% of dose may be excreted in urine as desethylchloroquine.^a Small amounts of chloroquine may be present in urine for weeks, months, and occasionally years after the drug is discontinued.^a

Half-life

Usually 72–120 hours.^a

Serum concentrations decline in a biphasic manner and terminal half-life increases with increasing doses.^a Terminal half-life is 3.1 hours after a single 250-mg oral dose, 42.9 hours after a single 500-mg oral dose, and 312 hours after a single 1-g oral dose.^a

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C) in tight container.¹³⁶

Actions and SpectrumActions

• 
  

  A blood schizonticidal agent active against asexual erythrocytic forms of most strains of Plasmodium malariae, P. ovale, P. vivax, and many strains of P. falciparum.^a Not active against preerythrocytic or exoerythrocytic forms of plasmodia.^a Gametocytocidal for P. malariae and P. vivax, but has no direct activity against the gametocytes of P. falciparum.^a

  
  


• 
  

  Chloroquine-resistant P. falciparum also are resistant to hydroxychloroquine and may be cross-resistant to pyrimethamine or quinine.^a Chloroquine-resistant P. falciparum may be susceptible to quinine or the fixed combination of sulfadoxine and pyrimethamine, but P. falciparum resistant to both chloroquine and sulfadoxine and pyrimethamine are widespread in certain areas.¹⁷⁶

  
  


• 
  

  Active in vitro against the trophozoite form of Entamoeba histolytica.^a Acts as a tissue amebicide.^a

  
  


• 
  

  Has anti-inflammatory activity; mechanism(s) of action in the treatment of rheumatoid arthritis and lupus erythematosus has not been determined.^a

  
  

Advice to Patients

• 
  

  Importance of keeping chloroquine out of reach of children since they are especially sensitive to 4-aminoquinoline derivatives.¹³⁶

  
  


• 
  

  Advise patients with a history of epilepsy about the risk of seizures.¹³⁶

  
  


• 
  

  Necessity of taking protective measures to reduce contact with mosquitoes (protective clothing, insect repellents, mosquito nets, remaining in air-conditioned or well-screened areas).^{140 162 163 164 165 166 176}

  
  


• 
  

  Possibility of contracting malaria during travel, regardless of prophylactic regimen used.^{140 162 163 164 165 166 176}

  
  


• 
  

  Importance of seeking medical attention as soon as possible if febrile illness develops during or after return from a malaria-endemic area and of informing clinician of possible malaria exposure.^{162 163 166 176}

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹³⁶

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹³⁶

  
  


• 
  

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

  
  

Preparations

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

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Chloroquine Phosphate

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	150 mg (of chloroquine)*	Chloroquine Phosphate Tablets	Global, West-Ward
		300 mg (of chloroquine)*	Aralen Phosphate	Sanofi-Aventis
			Chloroquine Phosphate Tablets	West-Ward

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Aralen 500MG Tablets (SANOFI-AVENTIS U.S.): 25/$190 or 75/$545.96

Chloroquine Phosphate 250MG Tablets (WEST-WARD): 30/$70.99 or 90/$203.98

Chloroquine Phosphate 500MG Tablets (WEST-WARD): 7/$36.99 or 21/$108.97

Disclaimer

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

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

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions January 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

101. Trigg PI, Wensdorfer WH, Sheth UK et al. Intramuscular chloroquine in children. Lancet. 1984; 2:288. [IDIS 188799] [PubMed 6146836]

104. White NJ. Clinical pharmacokinetics of antimalarial drugs. Clin Pharmacokinet. 1985; 10:187-215. [IDIS 202191] [PubMed 3893840]

105. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002; 46:328-46. [IDIS 476480] [PubMed 11840435]

106. Anon. Drugs for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64. [PubMed 10887424]

107. Chow AW, Jewesson PJ. Pharmacokinetics and safety of antimicrobial agents during pregnancy. Rev Infect Dis. 1985; 7:287-313. [IDIS 200121] [PubMed 3895351]

108. Public Health Laboratory Service Malaria Reference Laboratory. Prevention of malaria in pregnancy and early childhood. BMJ. 1984; 289:1296-7. [IDIS 192762] [PubMed 6437523]

109. Wolfe MS, Cordero JF. Safety of chloroquine in chemosuppression of malaria during pregnancy. BMJ. 1985; 290:1466-7. [IDIS 201367] [PubMed 3922534]

114. Verdier F, LeBras J, Clavier F et al. Blood levels and in vitro activity of desethylchloroquine against Plasmodium falciparum. Lancet. 1984; 1:1186-7. [IDIS 185836] [PubMed 6144914]

115. Akintonwa A, Odutola TA, Edeki T et al. Hemodialysis clearance of chloroquine in uremic patients. Ther Drug Monit. 1986; 8:285-7. [IDIS 220380] [PubMed 3750371]

116. Taylor DN, Wasi C, Bernard K. Chloroquine prophylaxis associated with a poor antibody response to human diploid cell rabies vaccine. Lancet. 1984; 1:1405. [IDIS 186824] [PubMed 6145850]

117. Pappaioanou M, Fishbein DB, Dreesen DW et al. Antibody response to preexposure human diploid-cell rabies vaccine given concurrently with chloroquine. N Engl J Med. 1986; 314:280-4. [IDIS 209991] [PubMed 3510393]

118. Centers for Disease Control and Prevention. Malaria deaths following inappropriate malaria chemoprophylaxis—United States, 2001. MMWR Morb Mortal Wkly Rep. 2001; 50:597-9. [PubMed 11476528]

119. Ratliff NB, Estes ML, Myles JL et al. Diagnosis of chloroquine cardiomyopathy by endomyocardial biopsy. N Engl J Med. 1987; 316:191-3. [IDIS 224846] [PubMed 3796692]

120. Piette JC, Guillevin L, Chapelon C et al. Chloroquine cardiotoxicity. N Engl J Med. 1987; 317:710-1. [IDIS 233346] [PubMed 3627179]

121. Centers for Disease Control and Prevention. Local transmission of Plasmodium vivax malaria—Virginia, 2002. MMWR Morb Mortal Wkly Rep. 2002; 51:921-3. [IDIS 488503] [PubMed 12403407]

122. Edstein MD, Veenendaal JR, Newman K et al. Excretion of chloroquine, dapsone and pyrimethamine in human milk. Br J Clin Pharmacol. 1986; 22:733-5. [IDIS 224280] [PubMed 3567020]

123. Ogunbona FA, Onyeji CO, Bolaji OO et al. Excretion of chloroquine and desethylchloroquine in human milk. Br J Clin Pharmacol. 1987; 23:473-6. [IDIS 228665] [PubMed 3580253]

124. Ette EI, Essien EE, Ogonor JI et al. Chloroquine in human milk. J Clin Pharmacol. 1987; 27:499-502. [IDIS 233119] [PubMed 3655001]

125. Jaeger A, Saunder P, Kopferschmitt J et al. Clinical features and management of poisoning due to antimalarial drugs. Med Toxicol Adverse Drug Exp. 1987; 2:242-73. [IDIS 233506] [PubMed 3306266]

126. Ellenhorn MJ, Barceloux DG. Medical toxicology: diagnosis and treatment of human poisoning. New York: Elsevier; 1988:341-7.

127. Riou B, Barriot P, Rimailho A et al. Treatment of severe chloroquine poisoning. N Engl J Med. 1988; 318:1-6. [IDIS 236482] [PubMed 3336379]

133. Krogstad DJ, Herwaldt BL. Chemoprophylaxis and treatment of malaria. N Engl J Med. 1988; 319:1538-40. [IDIS 248326] [PubMed 3185677]

134. White NJ, Miller KD, Churchill FC et al. Chloroquine treatment of severe malaria in children: pharmacokinetics, toxicity, and new dosage recommendations. N Engl J Med. 1988; 319:1493-500. [IDIS 248321] [PubMed 3054558]

136. Sanofi-Synthelabo. Aralen (chloroquine phosphate) prescribing information. New York, NY; 2003 Jun.

140. Anon. Advice for travelers. Med Lett Treat Guid. 2006; 45:25-34.

142. Centers for Disease Control. Revised dosing regimen for malaria prophylaxis with mefloquine. MMWR Morb Mortal Wkly Rep. 1990; 39:630.

143. Whitby M, Wood G, Veenendaal JR et al. Chloroquine-resistant Plasmodium vivax. Lancet. 1989; 2:1395. [IDIS 261420] [PubMed 2574333]

144. World Health Organization. WHO Drug Information. 1990; 4:9-15.

147. Panisko DM, Keystone JS. Treatment of malaria: 1990. Drugs. 1990; 39:160-89. [PubMed 2183998]

148. White NJ. Drug treatment and prevention of malaria. Eur J Clin Pharmacol. 1988; 34:1-14. [IDIS 242316] [PubMed 3282892]

149. White NJ. Antiparasitic drugs in children. Clin Pharmacokinet. 1989; 17(Suppl 1):138-55. [PubMed 2692937]

151. Centers for Disease Control. Change of dosing regimen for malaria prophylaxis with mefloquine. MMWR Morb Mortal Wkly Rep. 1991; 40:72-3. [IDIS 277075] [PubMed 1898981]

152. Anon. Treatment of severe Plasmodium falciparum malaria with quinidine gluconate: discontinuation of parenteral quinine from CDC drug service. MMWR Morb Mortal Wkly Rep. 1991; 40:240. [PubMed 1848916]

154. Collignon P. Chloroquine resistance in Plasmodium vivax. J Infect Dis. 1991; 164:222-3. [IDIS 284165] [PubMed 2056216]

161. Schwartz IK, Lackritz EM, Patchen LC. Chloroquine-resistant Plasmodium vivax from Indonesia. N Engl J Med. 1991; 324:927. [IDIS 279271] [PubMed 2000121]

162. Wyler DJ. Malaria chemoprophylaxis for the traveler. N Engl J Med. 1993; 329:31-7. [IDIS 316065] [PubMed 8505942]

163. World Health Organization. International travel and health: vaccination requirements and health advice. Geneva: World Health Organization; 2001. From WHO web site.

164. Wyler DJ. Malaria: overview and update. Clin Infect Dis. 1993; 16:449-58. [IDIS 312108] [PubMed 8513046]

165. Bradley D. Prophylaxis against malaria for travelers from the United Kingdom. BMJ. 1993; 306:1247-52. [IDIS 313802] [PubMed 8499856]

166. World Health Organization. WHO model prescribing information: drugs used in parasitic diseases. Geneva, Switzerland: WHO; 1992:62-77.

167. Meeran K, Jacobs MG, Scott J et al. Chloroquine poisoning: rapidly fatal without treatment. BMJ. 1993; 307:49-50. [IDIS 317216] [PubMed 8343674]

168. Wilkinson R, Mahatane J, Wade P et al. Chloroquine poisoning. BMJ. 1993; 307:504. [IDIS 319240] [PubMed 8400953]

169. Laurenson IF, Naraqi S, Lalloo DG et al. Chloroquine overdose in Papua New Guinea. BMJ. 1993; 307:564-5. [PubMed 8400996]

170. Kivistö KT, Neuvonen PJ. Activated charcoal for chloroquine poisoning. BMJ. 1993; 307:1068. [IDIS 321971] [PubMed 8305074]

171. Mirochnick M, Barnett E, Clarke DF et al. Stability of chloroquine in an extemporaneously prepared suspension stored at three temperatures. Ped Infect Dis J. 1994; 13:827-8.

174. Anon. Drugs for parasitic infections. From the Medical Letter website. Aug 2008.

175. Lobel HO, Kozarsky PE. Update on prevention of malaria for travelers. JAMA. 1997; 278:1767-71. [IDIS 395515] [PubMed 9388154]

176. Centers for Disease Control and Prevention. Health information for international travel, 2010. Atlanta, GA: US Department of Health and Human Services; 2010. Updates available from CDC website.

177. Wolfe MS. Protection of travelers. Clin Infect Dis. 1997; 25:177-86. [IDIS 392200] [PubMed 9332506]

178. Committee on Infectious Diseases, American Academy of Pediatrics. Red book: 2003 report of the Committee on Infectious Diseases. 26th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2003:192-4,414-9.

180. Baguet JP, Tremel F, Fabre M. Chloroquine cardiomyopathy with conduction disorders. Heart. 1999; 81:221-3. [IDIS 423686] [PubMed 9922366]

181. Reuss-Borst M, Berner B, Wulf G et al. Complete heart block as a rare complication of treatment with chloroquine. J Rheumatol. 1999; 26:1394-5. [IDIS 429747] [PubMed 10381062]

182. Centers for Disease Control and Prevention. Human rabies prevention—United States, 1999: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 1999; 48(No. RR-1):1-21.

183. Centers for Disease Control and Prevention. CDC treatment guidelines: Treatment of malaria (guidelines for clinicians). 2007 Mar. From the CDC website.

184. Bayer. Biltricide (praziquantel) tablets prescribing information. West Haven, CT; 2004 Aug.

185. Sarkany RP. The management of porphyria cutanea tarda. Clin Exp Dermatol. 2001; 26:225-32. [PubMed 11422163]

186. Wallace DJ. The use of chloroquine and hydroxychloroquine for non-infectious conditions other than rheumatoid arthritis or lupus: a critical review. Lupus. 1996;5 (Suppl 1):S59-64.

187. Badminton MN, Elder GH. Management of acute and cutaneous porphyrias. Int J Clin Pract. 2002; 56:272-8. [IDIS 482137] [PubMed 12074210]

188. Baltzan M, Mehta S, Kirkham TH et al. Randomized trial of prolonged chloroquine therapy in advanced pulmonary sarcoidosis. Am J Respir Crit Care Med. 1999; 160:192-7. [IDIS 432954] [PubMed 10390399]

189. Fazzi P. Pharmacotherapeutic management of pulmonary sarcoidosis. Am J Respir Med. 2003; 2:311-20. [PubMed 14719997]

190. Roche Laboratories. Fansidar (sulfadoxine and pyrimethamine) tablets prescribing information. Nutley, NJ; 2004 Aug.

191. Centers for Disease Control and Prevention. Guidelines for treatment of malaria in the United States (based on drugs currently available for use in the United States). From the CDC website. Accessed 2009 Jul 1.

a. AHFS Drug Information 2004. McEvoy GK, ed. Chlorquine Hydrochloride and Chloroquine Phosphate. Bethesda, MD: American Society of Health-System Pharmacists; 2004:822-7.

c. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 6th ed. Philadelphia; PA: Lippincott Wiliams & Wilkins; 2002:239-41.

More Aralen Phosphate resources

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

• Aralen Phosphate Advanced Consumer (Micromedex) - Includes Dosage Information


• Aralen Phosphate Concise Consumer Information (Cerner Multum)


• Chloroquine Prescribing Information (FDA)


• Chloroquine Professional Patient Advice (Wolters Kluwer)


• Chloroquine MedFacts Consumer Leaflet (Wolters Kluwer)

Compare Aralen Phosphate with other medications

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Allerfrim

Generic Name: pseudoephedrine and triprolidine (try PROE li deen and soo doe e FED rin)

Brand Names: A-Phedrin, Allerfrim, Allerphed, Altafed, Aphedrid, Aprodine, Biofed-PE, Genac, Histafed, Pediatex TD, Tripohist D, Vi-Sudo, Zymine-D

What is Allerfrim (pseudoephedrine and triprolidine)?

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

Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).

The combination of pseudoephedrine and triprolidine is used to treat sneezing, cough, runny or stuffy nose, itchy or watery eyes, hives, skin rash, itching, and other symptoms of allergies and the common cold.

Pseudoephedrine and triprolidine may also be used for other purposes not listed in this medication guide.

What is the most important information I should know about Allerfrim (pseudoephedrine and triprolidine)?

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Do not use any other over-the-counter cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant. Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body. Pseudoephedrine and triprolidine can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

What should I discuss with my healthcare provider before taking Allerfrim (pseudoephedrine and triprolidine)?

Do not use a cough or cold medicine if you have used an MAO inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), rasagiline (Azilect), selegiline (Eldepryl, Emsam), or tranylcypromine (Parnate) within the past 14 days. Serious, life-threatening side effects can occur if you take cough or cold medicine before the MAO inhibitor has cleared from your body.

Ask a doctor or pharmacist if it is safe for you to take pseudoephedrine and triprolidine if you have:

• kidney disease;


• 
  

  diabetes;

  
  


• 
  

  glaucoma;

  
  


• 
  

  heart disease or high blood pressure;

  
  


• 
  

  diabetes;

  
  


• 
  

  a thyroid disorder;

  
  


• 
  

  an enlarged prostate; or

  
  


• 
  

  problems with urination.

  
  

This medication may be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. Pseudoephedrine and triprolidine can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

Artificially-sweetened liquid forms of cold medicine may contain phenylalanine. This would be important to know if you have phenylketonuria (PKU). Check the ingredients and warnings on the medication label if you are concerned about phenylalanine.

How should I take Allerfrim (pseudoephedrine and triprolidine)?

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

Do not give this medication to a child younger than 2 years old. Always ask a doctor before giving a cough or cold medicine to a child. Death can occur from the misuse of cough and cold medicines in very young children. Take this medicine with a full glass of water. Do not crush, chew, or break an extended-release tablet. Swallow the pill whole. It is specially made to release medicine slowly in the body. Breaking or opening the pill would cause too much of the drug to be released at one time.

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

Talk with your doctor if your symptoms do not improve after 7 days of treatment, or if you have a fever with a headache, cough, or skin rash.

If you need to have any type of surgery, tell the surgeon ahead of time if you have taken a cold medicine within the past few days.

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

Store the medication at room temperature away from moisture and heat.

What happens if I miss a dose?

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

What happens if I overdose?

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

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

What should I avoid while taking Allerfrim (pseudoephedrine and triprolidine)?

This medication can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert. Avoid drinking alcohol. It can increase some of the side effects of this medication.

Avoid taking diet pills, caffeine pills, or other stimulants (such as ADHD medications) without your doctor's advice. Taking a stimulant together with a decongestant can increase your risk of unpleasant side effects.

Do not use any other over-the-counter cold, allergy, or sleep medication without first asking your doctor or pharmacist. If you take certain products together you may accidentally take too much of a certain drug. Read the label of any other medicine you are using to see if it contains an antihistamine or decongestant.

Allerfrim (pseudoephedrine and triprolidine) side effects

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

• 
  

  fast, pounding, or uneven heartbeat;

  
  


• 
  

  confusion, hallucinations, unusual thoughts or behavior;

  
  


• 
  

  severe dizziness, anxiety, restless feeling, or nervousness;

  
  


• 
  

  increased blood pressure (severe headache, blurred vision, trouble concentrating, chest pain, numbness, seizure);

  
  


• 
  

  confusion, hallucinations, unusual thoughts or behavior;

  
  


• 
  

  easy bruising or bleeding, unusual weakness, fever, chills, body aches, flu symptoms; or

  
  


• 
  

  urinating less than usual or not at all.

  
  

Less serious side effects may include:

• 
  

  blurred vision;

  
  


• 
  

  dry mouth;

  
  


• 
  

  nausea, stomach pain, constipation;

  
  


• 
  

  mild loss of appetite, stomach upset;

  
  


• 
  

  warmth, tingling, or redness under your skin;

  
  


• 
  

  sleep problems (insomnia);

  
  


• 
  

  restless or excitability (especially in children);

  
  


• 
  

  skin rash or itching;

  
  


• 
  

  dizziness, drowsiness;

  
  


• 
  

  problems with memory or concentration; or

  
  


• 
  

  ringing in your ears.

  
  

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

What other drugs will affect Allerfrim (pseudoephedrine and triprolidine)?

Tell your doctor if you regularly use other medicines that make you sleepy (such as narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression, or anxiety). They can add to sleepiness caused by pseudoephedrine and triprolidine.

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

• 
  

  medicines to treat high blood pressure;

  
  


• 
  

  a diuretic (water pill);

  
  


• 
  

  medication to treat irritable bowel syndrome;

  
  


• 
  

  bladder or urinary medications such as oxybutynin (Ditropan, Oxytrol) or tolterodine (Detrol);

  
  


• 
  

  aspirin or salicylates (such as Disalcid, Doan's Pills, Dolobid, Salflex, Tricosal, and others);

  
  


• 
  

  a beta-blocker such as atenolol (Tenormin, Tenoretic), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others; or

  
  


• 
  

  antidepressants such as amitriptyline (Elavil), clomipramine (Anafranil), imipramine (Janimine, Tofranil), and others.

  
  

This list is not complete and there may be other drugs that can interact with pseudoephedrine and triprolidine. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

More Allerfrim resources

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

• Allerfrim Liquid MedFacts Consumer Leaflet (Wolters Kluwer)


• Actifed MedFacts Consumer Leaflet (Wolters Kluwer)


• Actifed Consumer Overview


• Tripohist D Prescribing Information (FDA)

Compare Allerfrim with other medications

• Cold Symptoms
• Hay Fever

Where can I get more information?

• Your pharmacist can provide more information about pseudoephedrine and triprolidine.

See also: Allerfrim side effects (in more detail)

Anodesyn Ointment

1. Name Of The Medicinal Product

Anodesyn Ointment

Care Haemorrhoid Relief Ointment

Sainsburys Haemorrhoid Relief Ointment

Tesco Haemorrhoid Relief Ointment

2. Qualitative And Quantitative Composition

Allantoin 0.5% w/w.

Lidocaine Hydrochloride 0.5% w/w.

For excipients, see 6.1

3. Pharmaceutical Form

A soft white translucent ointment.

4. Clinical Particulars

4.1 Therapeutic Indications

For the symptomatic relief of pain and irritation associated with external haemorrhoids.

4.2 Posology And Method Of Administration

Route of administration: For external application.

Adults & the elderly.

For external piles, wash the affected area with tepid water, dry and apply the ointment with gauze or lint.

Repeat as required, do not use for more than 7 days unless advised by your doctor.

Children.

Not recommended for children.

4.3 Contraindications

Hypersensitivity to any of the ingredients, especially lidocaine.

4.4 Special Warnings And Precautions For Use

Anodesyn Ointment / Care Haemorrhoid Relief Ointment / Sainsburys Haemorrhoid Relief Ointment/Tesco Haemorrhoid Relief Ointment is intended for use for short periods and should not be used for longer than 7 days without medical advice. Patients should be instructed to seek medical advice if they experience persistent pain or bleeding from the anus, especially where associated with a change in bowel habit, if the stomach is distended or if they are losing weight.

Avoid contact with the eyes.

The label will state:

Keep all medicines out of the reach and sight of children.

If symptoms persist for more than 7 days consult your doctor.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

No clinically significant drug interactions known.

4.6 Pregnancy And Lactation

The safety of Anodesyn Ointment / Care Haemorrhoid Relief Ointment / Sainsburys Haemorrhoid Relief Ointment/Tesco Haemorrhoid Relief Ointment in pregnancy and lactation has not been assessed, but it is thought unlikely to constitute a hazard, though caution should be exercised during the first trimester.

Lidocaine crosses the placenta and is distributed into breast milk.

4.7 Effects On Ability To Drive And Use Machines

No or negligible influence.

4.8 Undesirable Effects

Hypersensitivity to any of the ingredients, especially lidocaine.

4.9 Overdose

Accidental ingestion may result in anaesthesia of the upper respiratory tract, nausea, vomiting and abdominal discomfort. Ingestion of very large quantities could result in CNS and cardiovascular toxicity. Treatment should be symptomatic and supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

C05A X - Other antihaemorrhoidals for topical use

Lidocaine has a local anaesthetic action, relieving pain and discomfort in the affected areas.

Allantoin is claimed to promote healing.

5.2 Pharmacokinetic Properties

No data available.

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

White Soft Paraffin

Wool Fat

Purified Water

6.2 Incompatibilities

Not applicable.

6.3 Shelf Life

Three years.

6.4 Special Precautions For Storage

Store at or below 25°C.

6.5 Nature And Contents Of Container

A collapsible 25g aluminium tube, internally lacquered with a latex welt and HPDE screw cap. Supplied with a nozzle and packed in a carton.

6.6 Special Precautions For Disposal And Other Handling

None stated

7. Marketing Authorisation Holder

Thornton & Ross Limited

Linthwaite

Huddersfield

West Yorkshire

HD7 5QH

United Kingdom

8. Marketing Authorisation Number(S)

PL 00240/0072

9. Date Of First Authorisation/Renewal Of The Authorisation

2 December 2002 / 29 September 2003

10. Date Of Revision Of The Text

23/1/2008

11 DOSIMETRY (IF APPLICABLE)

Not Applicable

12 INSTRUCTIONS FOR PREPARATION OF RADIOPHARMACEUTICALS (IF APPLICABLE)

Not Applicable

Ismo

isosorbide mononitrate

Dosage Form: tablets

Ismo Description

Isosorbide mononitrate is 1,4:3,6-dianhydro-D-glucitol, 5-nitrate, an organic nitrate whose structural formula is:

and whose molecular weight is 191.14. The organic nitrates are vasodilators, active on both arteries and veins. Each Ismo® tablet contains 20 mg of isosorbide mononitrate. The inactive ingredients in each tablet are colloidal silicon dioxide, D&C Yellow 10 Aluminum Lake, FD&C Yellow 6 Aluminum Lake, hydroxypropyl methylcellulose, lactose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 20, povidone, sodium starch glycolate, titanium dioxide and hydroxypropyl cellulose.

Ismo - Clinical Pharmacology

Isosorbide mononitrate is the major active metabolite of isosorbide dinitrate (ISDN), and most of the clinical activity of the dinitrate is attributable to the mononitrate.

The principal pharmacological action of isosorbide mononitrate, due to its nitric oxide metabolite, is direct relaxation of vascular smooth muscle. The result is dilatation of peripheral arteries and veins, especially the latter. Dilation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload). Dilatation of the coronary arteries also occurs. The relative importance of preload reduction, afterload reduction, and coronary dilatation remains undefined.

Pharmacodynamics

Dosing regimens for most chronically used drugs are designed to provide plasma concentrations that are continu-ously greater than a minimally effective concentration. This strategy is inappropriate for organic nitrates. Several well-controlled clinical trials have used exercise testing to assess the antianginal efficacy of continuously delivered nitrates. In the large majority of these trials, active agents were indistinguishable from placebo after 24 hours (or less) of continuous therapy. Attempts to overcome tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their antianginal efficacy been restored. The drug-free interval sufficient to avoid tolerance to isosorbide mononitrate has not been completely defined. In the only regimen of twice-daily isosorbide mononitrate that has been shown to avoid development of tolerance, the two doses of Ismo tablets are given 7 hours apart, so there is a gap of 17 hours between the second dose of each day and the first dose of the next day. Taking account of the relatively long half-life of isosorbide mononitrate this result is consistent with those obtained for other organic nitrates. The same twice-daily regimen of Ismo tablets successfully avoided significant rebound/withdrawal effects. The incidence and magnitude of such phenomena have appeared, in studies of other nitrates, to be highly dependent upon the schedule of nitrate administration.

Pharmacokinetics

In humans, isosorbide mononitrate is not subject to first pass metabolism in the liver. The absolute bioavailability of isosorbide mononitrate from Ismo tablets is nearly 100%. Maximum serum concentrations of isosorbide mononitrate are achieved 30 to 60 minutes after ingestion of Ismo. The volume of distribution of isosorbide mononitrate is approximately 0.6 L/kg, and less than 4% is bound to plasma proteins. It is cleared from the serum by denitration to isosorbide; glucuronidation to the mononitrate glucuronide; and denitration/hydration to sorbitol. None of these metabolites is vasoactive. Less than 1% of administered isosorbide mononitrate is eliminated in the urine. The overall elimination half-life of isosorbide mononitrate is about 5 hours; the rate of clearance is the same in healthy young adults , in patients with various degrees of renal, hepatic, or cardiac dysfunction, and in the elderly. In a single-dose study, the pharmacokinetics of isosorbide mononitrate were dose-proportional up to at least 60 mg.

Clinical Trials

Controlled trials of single doses of Ismo tablets have demonstrated that antianginal activity is present about 1 hour after dosing, with peak effect seen from 1 to 4 hours after dosing. In placebo-controlled trials lasting 2 to 3 weeks, Ismo tablets were administered twice daily, in asymmetric regimens (with interdosing intervals of 7 and 17 hours) designed to avoid tolerance. One trial tested doses of 10 mg and 20 mg; one trial tested doses of 20 mg, 40 mg, and 60 mg; and three trials tested only doses of 20 mg. In each trial, the subjects were persons with known chronic stable angina, and the primary measure of efficacy was exercise tolerance on a standardized treadmill test. After initial dosing and for at least 3 weeks, exercise tolerance in patients treated with Ismo 20 mg tablets was significantly greater than that seen in patients treated with placebo, although there was some attenuation of effect with time. Treatment with Ismo tablets was superior to placebo for at least 12 hours after the first dose (i.e., 5 hours after the second dose) of each day. Significant tolerance and rebound phenomena were not observed. The 10-mg dose was not unequivocally superior to placebo, while the effect of the 40-mg dose was similar to that of the 20-mg dose. The 60-mg dose appeared to be less effective, and it was associated with a rebound phenomenon (early-morning worsening).

Indications and Usage for Ismo

Ismo tablets are indicated for the prevention of angina pectoris due to coronary artery disease. The onset of action of oral isosorbide mononitrate is not sufficiently rapid for this product to be useful in aborting an acute anginal episode.

Contraindications

Allergic reactions to organic nitrates are extremely rare, but they do occur. Isosorbide mononitrate is contraindicated in patients who are allergic to it.

Warnings

Amplification of the vasodilatory effects of Ismo by sildenafil can result in severe hypotension. The time course and dose dependence of this interaction have not been studied. Appropriate supportive care has not been studied, but it seems reasonable to treat this as a nitrate overdose, with elevation of the extremities and with central volume expansion.

The benefits of isosorbide mononitrate in patients with acute myocardial infarction or congestive heart failure have not been established. Because the effects of isosorbide mononitrate are difficult to terminate rapidly, this drug is not recommended in these settings. If isosorbide mononitrate is used in these conditions, careful clinical or hemo-dynamic monitoring must be used to avoid the hazards of hypotension and tachycardia.

Precautions

General

Severe hypotension, particularly with upright posture, may occur with even small doses of isosorbide mononitrate. This drug should therefore be used with caution in patients who may be volume depleted or who, for whatever reason, are already hypotensive. Hypotension induced by isosorbide mononitrate may be accompanied by paradoxical bradycardia and increased angina pectoris. Nitrate therapy may aggravate the angina caused by hypertrophic cardiomyopathy. In industrial workers who have had long-term exposure to unknown (presumably high) doses of organic nitrates, tolerance clearly occurs. Chest pain, acute myocardial infarction, and even sudden death have occurred during temporary withdrawal of nitrates from these workers, demonstrating the existence of true physical dependence. The importance of these observations to the routine, clinical use of oral isosorbide mononitrate is not known.

Information for Patients

Patients should be told that the antianginal efficacy of Ismo tablets can be maintained by carefully following the prescribed schedule of dosing (two doses taken 7 hours apart). For most patients, this can be accomplished by taking the first dose on awakening and the second dose 7 hours later. As with other nitrates, daily headaches sometimes accompany treatment with isosorbide mononitrate. In patients who get these headaches, the headaches are a marker of the activity of the drug. Patients should resist the temptation to avoid headaches by altering the schedule of their treatment with isosorbide mononitrate, since loss of headache may be associated with simultaneous loss of antianginal efficacy. Aspirin and/or acetaminophen, on the other hand, often successfully relieve isosorbide mononitrate-induced headaches with no deleterious effect on isosorbide mononitrate’s antianginal efficacy. Treatment with isosorbide mononitrate may be associated with lightheadedness on standing, especially just after rising from a recumbent or seated position. This effect may be more frequent in patients who have also consumed alcohol.

Drug Interactions:

The vasodilating effects of isosorbide mononitrate may be additive with those of other vasodilators. Alcohol, in particular, has been found to exhibit additive effects of this variety. Marked symptomatic orthostatic hypotension has been reported when calcium channel blockers and organic nitrates were used in combination. Dose adjustments of either class of agents may be necessary.

Carcinogenesis, Mutagenesis, Impairment of Fertility:

No carcinogenic effects were observed in mice exposed to oral isosorbide mononitrate for 104 weeks at doses of up to 900 mg/kg/day (102 X the human exposure comparing body surface area). Rats treated with 900 mg/kg/day for 26 weeks (225 X the human exposure comparing body surface area) and 500 mg/kg/day for the remaining 95 to 111 weeks (males and females, respectively) showed no evidence of tumors. No mutagenic activity was seen in a variety of in vitro and in vivo assays. No adverse effects on fertility were observed when isosorbide mononitrate was administered to male and female rats at doses of up to 500 mg/kg/day (125 X the human exposure comparing body surface area).

Pregnancy Category C

Isosorbide mononitrate has been shown to be associated with stillbirths and neonatal death in rats receiving 500 mg/kg/day of isosorbide mononitrate (125 X the human exposure comparing body surface area). At 250 mg/kg/day, no adverse effects on reproduction and development were reported. In rats and rabbits receiving isosorbide mononitrate at up to 250 mg/kg/day, no developmental abnormalities, fetal abnormalities, or other effects upon reproductive performance were detected; these doses are larger than the maximum recommended human dose by factors between 70 (body-surface-area basis in rabbits) and 310 (body-weight basis, either species). In rats receiving 500 mg/kg/day, there were small but statistically significant increases in the rates of prolonged gestation, prolonged parturition, stillbirth, and neonatal death; and there were small but statistically significant decreases in birth weight, live litter size, and pup survival.

There are no adequate and well-controlled studies in pregnant women. Isosorbide mononitrate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers:

It is not known whether isosorbide mononitrate is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isosorbide mononitrate is administered to a nursing woman.

Pediatric Use:

Safety and effectiveness of isosorbide mononitrate in pediatric patients have not been established.

Geriatric Use

Clinical studies of Ismo® did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, although age, renal, hepatic or cardiac dysfunction do not appear to have a clinically significant effect on the clearance of Ismo®.

Adverse Reactions

The table below shows the frequencies of the adverse reactions observed in more than 1% of the subjects (a) in 6 placebo-controlled domestic studies in which patients in the active-treatment arm received 20 mg of isosorbide mononitrate twice daily, and (b) in all studies in which patients received isosorbide mononitrate in a variety of regimens. In parentheses, the same table shows the frequencies with which these adverse reactions led to discontinuation of treatment. Overall, 11% of the patients who received isosorbide mononitrate in the six controlled U.S. studies discontinued treatment because of adverse reactions. Most of these discontinued because of headache. “Dizziness” and nausea were also frequently associated with withdrawal from these studies.

Frequency of Adverse Reactions (Discontinuations)*
* Some individuals discontinued for multiple reasons.
	6 Controlled Studies		92 Clinical Studies
Dose	Placebo	20 mg	(varied)
Patients	204	219	3344
Headache	9% (0%)	38% (9%)	19% (4.3%)
Dizziness	1% (0%)	5% (1%)	3% (0.2%)
Nausea, Vomiting	<1% (0%)	4% (3%)	2% (0.2%)

Other adverse reactions, each reported by fewer than 1% of exposed patients, and in many cases of uncertain relation to drug treatment, were::

Cardiovascular: angina pectoris, arrhythmias, atrial fibrillation, hypotension, palpitations, postural hypotension, premature ventricular contractions, supraventricular tachycardia, syncope.

Dermatologic: pruritus, rash.

Gastrointestinal: abdominal pain, diarrhea, dyspepsia, tenesmus, tooth disorder, vomiting.

Genitourinary: dysuria, impotence, urinary frequency.

Miscellaneous: asthenia, blurred vision, cold sweat, diplopia, edema, malaise, neck stiffness, rigors.

Musculoskeletal: arthralgia.

Neurological: agitation, anxiey, confusion, dyscoordination, hypoesthesia, hypokinesia, increased appetite, insomnia, nervousness, nightmares.

Respiratory: bronchitis, pneumonia, upper-respiratory tract infection.

Extremely rarely, ordinary doses of organic nitrates have caused methemoglobinemia in normal-seeming patients; for futher discussion of its diagnosis and treatment see under OVERDOSAGE.

Overdosage

Hemodynamic Effects

The ill effects of isosorbide mononitrate overdose are generally the results of isosorbide mononitrate’s capacity to induce vasodilatation, venous pooling, reduced cardiac output, and hypotension. These hemodynamic changes may have protean manifestations, including increased intracranial pressure, with any or all of persistent throbbing headache, confusion, and moderate fever; vertigo; palpitations; visual disturbances; nausea and vomiting (possibly with colic and even bloody diarrhea); syncope (especially in the upright posture); air hunger and dyspnea, later followed by reduced ventilatory effort; diaphoresis, with the skin either flushed or cold and clammy; heart block and bradycardia; paralysis; coma; seizures and death.

Laboratory determinations of serum levels of isosorbide mononitrate and its metabolites are not widely available, and such determinations have, in any event, no established role in the management of isosorbide mononitrate overdose. There are no data suggesting what dose of isosorbide mononitrate is likely to be life-threatening in humans. In rats and mice, there is significant lethality at doses of 2000 mg/kg and 3000 mg/kg, respectively. No data are available to suggest physiological maneuvers (e.g., maneuvers to change the pH of the urine) that might accelerate elimination of isosorbide mononitrate. In particular, dialysis is known to be ineffective in removing isosorbide mononitrate from the body. No specific antagonist to the vasodilator effects of isosorbide mononitrate is known, and no intervention has been subject to controlled study as a therapy of isosorbide mononitrate overdose. Because the hypotension associated with isosorbide mononitrate overdose is the result of venodilatation and arterial hypovolemia, prudent therapy in this situation should be directed toward an increase in central fluid volume. Passive elevation of the patient’s legs may be sufficient, but intravenous infusion of normal saline or similar fluid may also be necessary. The use of epinephrine or other arterial vasoconstrictors in this setting is likely to do more harm than good. In patients with renal disease or congestive heart failure, therapy resulting in central volume expansion is not without hazard. Treatment of isosorbide mononitrate overdose in these patients may be subtle and difficult, and invasive monitoring may be required.

Methemoglobinemia

Methemoglobinemia has been reported in patients receiving other organic nitrates, and it probably could also occur as a side effect of isosorbide mononitrate. Certainly nitrate ions liberated during metabolism of isosorbide mononitrate can oxidize hemoglobin into methemoglobin. Even in patients totally without cytochrome b5 reductase activity, however, and even assuming that the nitrate moiety of isosorbide mononitrate is quantitatively applied to oxidation of hemoglobin, about 2 mg/kg of isosorbide mononitrate should be required before any of these patients manifests clinically significant (≥10%) methemoglobinemia. In patients with normal reductase function, significant production of methemoglobin should require even larger doses of isosorbide mononitrate. In one study in which 36 patients received 2 to 4 weeks of continuous nitroglycerin therapy at 3.1 to 4.4 mg/hr (equivalent, in total administered dose of nitrate ions, to 7.8 to 11.1 mg of isosorbide mononitrate per hour), the average methemoglobin level measured was 0.2%; this was comparable to that observed in parallel patients who received placebo. Notwithstanding these observations, there are case reports of significant methemoglobinemia in association with moderate overdoses of organic nitrates. None of the affected patients had been thought to be unusually susceptible.

Methemoglobin levels are available from most clinical laboratories. The diagnosis should be suspected in patients who exhibit signs of impaired oxygen delivery despite adequate cardiac output and adequate arterial pO2. Classically, methemoglobinemic blood is described as chocolate brown, without color change on exposure to air. When methemoglobinemia is diagnosed, the treatment of choice is methylene blue, 1 to 2 mg/kg intravenously.

DOSAGE AND ADMINISTRATION (SEE INDICATIONS AND USAGE)

The recommended regimen of Ismo tablets is 20 mg (one tablet) twice daily, with the two doses given 7 hours apart. For most patients, this can be accomplished by taking the first dose on awakening and the second dose 7 hours later. Dosage adjustments are not necessary for elderly patients or patients with altered renal or hepatic function. As noted above (CLINICAL PHARMACOLOGY), multiple studies of organic nitrates have shown that maintenance of continuous 24-hour plasma levels results in refractory tolerance. The dosing regimen for Ismo tablets provides a daily nitrate-free interval to avoid the development of this tolerance.

As also noted under CLINICAL PHARMACOLOGY, well-controlled studies have shown that tolerance to Ismo tablets is avoided when using the twice-daily regimen in which the two doses are given 7 hours apart. This regimen has been shown to have antianginal efficacy beginning 1 hour after the first dose and lasting at least 5 hours after the second dose. The duration (if any) of antianginal activity beyond 12 hours has not been studied; large controlled studies with other nitrates suggest that no dosing regimen should be expected to provide more than about 12 hours of continuous antianginal efficacy per day.

In clinical trials, Ismo tablets have been administered in a variety of regimens. Single doses less than 20 mg have not been adequately studied, while single doses greater than 20 mg have demonstrated no greater efficacy than doses of 20 mg.

How is Ismo Supplied

Ismo® (isosorbide mononitrate) tablets, 20 mg, are available in bottles of 100 (NDC 67857-702-01). Each orange, round, film-coated tablet is engraved “Ismo 20” on one side and scored on the reverse side.

Store at 20 - 25° C (68 -77° F) [See USP Controlled Room Temperature].

Dispense in tight container.

Manufactured by:

West-ward Pharmaceutical Corp.

Eatontown, NJ 07724

Manufactured for:

Reddy Pharmaceuticals, LLC

Bridgewater, NJ 08807

Ismo  isosorbide mononitrate  tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 67857-702 Route of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength isosorbide mononitrate (isosorbide mononitrate) Active 20 MILLIGRAM  In 1 TABLET colloidal silicon dioxide Inactive   D&C Yellow 10 Aluminum Lake Inactive   FD&C Yellow 6 Aluminum Lake Inactive   hydroxypropyl methylcellulose Inactive   lactose Inactive   magnesium stearate Inactive   microcrystalline cellulose Inactive   polyethylene glycol Inactive   polysorbate 20 Inactive   povidone Inactive   sodium starch glycolate Inactive   titanium dioxide Inactive   hydroxypropyl cellulose Inactive

Product Characteristics Color ORANGE (orange) Score 2 pieces Shape ROUND (round) Size 8mm Flavor Imprint Code Ismo;20 Contains          Coating true Symbol false

Packaging # NDC Package Description Multilevel Packaging 1 67857-702-01 100 TABLET In 1 BOTTLE, PLASTIC None

Revised: 03/2007Reddy Pharmaceuticals, LLC

More Ismo resources

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

• Ismo Advanced Consumer (Micromedex) - Includes Dosage Information


• Isosorbide Mononitrate Professional Patient Advice (Wolters Kluwer)


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• Angina Pectoris Prophylaxis
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