Drugs List

Therapeutic Indications

Uses

Malaria - prophylaxis
Malaria - suppression

For up to date advice on geographical resistance patterns and appropriate prophylaxis, current guidelines should be consulted.
Guidelines for Malaria Prevention from the Health Protection Agency specifically developed for travellers from the United Kingdom may be obtained on the HPA website:https://www.hpa.org.uk/webw

Contraindications

Children under 1 year
Within 3 days of oral typhoid vaccine

Precautions and Warnings

Elderly
Breastfeeding
Diabetes mellitus
Epileptic disorder
G6PD deficiency
Hepatic cirrhosis
Hepatic impairment
History of neurological disorder
History of seizures
Myasthenia gravis
Neurological disorder
Porphyria
Pregnancy
Psoriasis
Renal impairment - creatinine clearance < 60ml/minute/1.73m sq
Severe gastrointestinal disorder

May exacerbate myasthenia gravis
Reduce dose in patients with renal impairment
Advice available from specialist unit for the use of this drug
Advise ability to drive/operate machinery may be affected by side effects
Consider prevalence of resistance when prescribing
Drugs for malaria prophylaxis are not prescribable on the NHS
Perform ophthalmological examination before therapy and 3-6 monthly
Monitor cardiac function during prolonged treatment
Monitor the elderly for optimum dosing
Perform blood counts on prolonged use of this treatment
Advise patient to report new visual problems and symptoms
May exacerbate psoriasis
May induce severe hypoglycaemia
Avoid antacids within 4 hours of dose
Advise of importance of avoiding mosquito bites
Advise patients of the warning signs of hypoglycaemia
Advise patients on the importance of taking treatment regularly
Consult Dr. if illness occurs within 1 year of return from malarious area

Warn travellers about importance of avoiding mosquito bites, importance of taking prophylaxis regularly, and importance of immediate visit to doctor if ill within 1 year and especially within 3 months of return.

Irreversible retinal damage and corneal changes may develop during long term therapy with chloroquine, or after the drug has been discontinued. Ophthalmic examination prior to treatment and at 3 to 6 monthly intervals is therefore recommended in patients taking chloroquine at continuous high doses for longer than 12 months, as a weekly treatment for longer than 3 years, or when total consumption exceeds 1.6 g/kg (cumulative dose 100 g).

A small number of cases of diffuse parenchymal lung disease have been identified in patients taking chloroquine. A small number of cases responded to steroid therapy.

Caution is necessary when treating patients with porphyria as chloroquine may cause severe constitutional symptoms and an increase in the amount of porphyrins excreted in the urine. This effect is more likely to occur in patients with a high alcohol intake.

Pregnancy and Lactation

Pregnancy

Use with caution. Chloroquine and proguanil should not be used during pregnancy unless the potential benefit outweighs the risks.

Chloroquine
Chloroquine is believed to cross the placenta and the use of chloroquine during pregnancy is contraindicated by the manufacturer. However, human studies regarding the use of chloroquine during pregnancy have shown that when used in the usual dosage for malaria prophylaxis or for the treatment of malarial infection in a three day course, chloroquine is neither embryotoxic nor foetotoxic. Chloroquine is one of the drugs of choice for travellers to malaria-endemic areas, and for treatment of malarial infection (if the parasite is sensitive).

When used in high doses or on a long term basis, chloroquine therapy has been linked to foetal retina and inner ear damage.

Animal studies have shown chloroquine to be highly embryotoxic and teratogenic. Studies in monkeys showed that chloroquine rapidly crosses the placenta and accumulates in the foetal adrenal cortex and retina. Studies in mice showed selective accumulation in melanin structures of the foetal eye. Accumulated chloroquine persisted for 5 months after it was eliminated from the rest of the body.

Proguanil
Proguanil has been widely used during human pregnancy for over 40 years and a causal connection to any adverse effect on the mother or foetus has not been established.

Guidelines recommend that folate supplements, 5 mg folic acid daily, should be given if proguanil is used during pregnancy.

Non-treatment of malaria can produce severe complications for mother and foetus including: anaemia, abortion, stillbirth, prematurity, low birth weight, foetal distress. The choice of drug for malaria prophylaxis and treatment during pregnancy depends upon the local pattern of drug resistance, severity of malaria and the degree of pre-existing malaria immunity.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chloroquine and proguanil are excreted into milk at levels too low to harm the infant. The levels excreted are insufficient to provide the infant with protection against malaria. If appropriate, chemoprophylaxis should be administered to the infant.

Note that in cases of long term chloroquine therapy for rheumatoid disease, breastfeeding is not recommended.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal cramps
Abnormal liver function tests
Aggravation of porphyria
Agranulocytosis
Allergic reaction
Anaphylactic reaction
Angioedema
Anxiety
Aplastic anaemia
Blindness
Blood disorders
Blurred vision
Bone marrow depression
Cardiomyopathy
Cholestasis
Constipation
Convulsions
Corneal opacities
Delirium
Depigmentation of hair
Diarrhoea
Diplopia
Discolouration of nails (temporary)
Disturbances in accommodation
Drug fever
Drug rash with eosinophilia and systemic symptoms (DRESS)
ECG changes
Emotional lability
Erythema multiforme
Exacerbation of myasthenia gravis
Exacerbation of psoriasis
Exfoliative dermatitis
Gastro-intestinal disturbances
Haematological changes in renal impairment
Haemolysis
Hair loss
Hallucinations
Headache
Hearing disturbances
Hepatic damage
Hepatitis
Hypoglycaemia
Hypotension
Interstitial lung disease
Lichen-planus type reaction
Liver function disturbances
Macular degeneration of colour vision
Maculopapular rash
Mouth ulcers
Myopathy
Nausea
Nerve deafness
Neuromyopathy
Neutropenia
Optic atrophy scotomas
Ototoxicity
Personality change
Photosensitivity
Pigmentation (ophthalmic)
Pigmentation of mucous membranes
Pigmented deposits in the eye
Pruritus
Psychotic reactions
Purpura
Rash
Retinal damage (irreversible)
Retinopathy
Skin pigmentation changes
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vasculitis (allergic)
Visual field defects
Vomiting

Presentation

Travel pack with tablets containing chloroquine phosphate and tablets containing proguanil hydrochloride

Drugs List

Therapeutic Indications

Uses

Malaria - prophylaxis
Malaria - suppression

For up to date advice on geographical resistance patterns and appropriate prophylaxis, current guidelines should be consulted.
Guidelines for Malaria Prevention from the Health Protection Agency specifically developed for travellers from the United Kingdom may be obtained on the HPA website:https://www.hpa.org.uk/webw

Dosage

Chloroquine is no longer recommended for the treatment of falciparum malaria due to widespread resistance, nor is it recommended if the infective species is unknown or if the infection is mixed.

Non-immune subjects entering a malarious area should begin daily treatment with proguanil one week (or at least 48 hours) before arrival. The daily dose should be continued throughout exposure to risk and for 4 weeks after leaving the malarious area.

A single dose of chloroquine should be taken each week on the same day of the week. Start one week before exposure to risk and continue until 4 weeks after leaving the malarious area.

Adults

Elderly

Children

Adolescents

Patients with Renal Impairment

Contraindications

Children under 1 year
Within 3 days of oral typhoid vaccine

Precautions and Warnings

Elderly
Breastfeeding
Diabetes mellitus
Epileptic disorder
G6PD deficiency
Hepatic cirrhosis
Hepatic impairment
History of neurological disorder
History of seizures
Myasthenia gravis
Neurological disorder
Porphyria
Pregnancy
Psoriasis
Renal impairment - creatinine clearance < 60ml/minute/1.73m sq
Severe gastrointestinal disorder

May exacerbate myasthenia gravis
Reduce dose in patients with renal impairment
Advice available from specialist unit for the use of this drug
Advise ability to drive/operate machinery may be affected by side effects
Consider prevalence of resistance when prescribing
Drugs for malaria prophylaxis are not prescribable on the NHS
Perform ophthalmological examination before therapy and 3-6 monthly
Monitor cardiac function during prolonged treatment
Monitor the elderly for optimum dosing
Perform blood counts on prolonged use of this treatment
Advise patient to report new visual problems and symptoms
May exacerbate psoriasis
May induce severe hypoglycaemia
Avoid antacids within 4 hours of dose
Advise of importance of avoiding mosquito bites
Advise patients of the warning signs of hypoglycaemia
Advise patients on the importance of taking treatment regularly
Consult Dr. if illness occurs within 1 year of return from malarious area

Warn travellers about importance of avoiding mosquito bites, importance of taking prophylaxis regularly, and importance of immediate visit to doctor if ill within 1 year and especially within 3 months of return.

Irreversible retinal damage and corneal changes may develop during long term therapy with chloroquine, or after the drug has been discontinued. Ophthalmic examination prior to treatment and at 3 to 6 monthly intervals is therefore recommended in patients taking chloroquine at continuous high doses for longer than 12 months, as a weekly treatment for longer than 3 years, or when total consumption exceeds 1.6 g/kg (cumulative dose 100 g).

A small number of cases of diffuse parenchymal lung disease have been identified in patients taking chloroquine. A small number of cases responded to steroid therapy.

Caution is necessary when treating patients with porphyria as chloroquine may cause severe constitutional symptoms and an increase in the amount of porphyrins excreted in the urine. This effect is more likely to occur in patients with a high alcohol intake.

Pregnancy and Lactation

Pregnancy

Use with caution. Chloroquine and proguanil should not be used during pregnancy unless the potential benefit outweighs the risks.

Chloroquine
Chloroquine is believed to cross the placenta and the use of chloroquine during pregnancy is contraindicated by the manufacturer. However, human studies regarding the use of chloroquine during pregnancy have shown that when used in the usual dosage for malaria prophylaxis or for the treatment of malarial infection in a three day course, chloroquine is neither embryotoxic nor foetotoxic. Chloroquine is one of the drugs of choice for travellers to malaria-endemic areas, and for treatment of malarial infection (if the parasite is sensitive).

When used in high doses or on a long term basis, chloroquine therapy has been linked to foetal retina and inner ear damage.

Animal studies have shown chloroquine to be highly embryotoxic and teratogenic. Studies in monkeys showed that chloroquine rapidly crosses the placenta and accumulates in the foetal adrenal cortex and retina. Studies in mice showed selective accumulation in melanin structures of the foetal eye. Accumulated chloroquine persisted for 5 months after it was eliminated from the rest of the body.

Proguanil
Proguanil has been widely used during human pregnancy for over 40 years and a causal connection to any adverse effect on the mother or foetus has not been established.

Guidelines recommend that folate supplements, 5 mg folic acid daily, should be given if proguanil is used during pregnancy.

Non-treatment of malaria can produce severe complications for mother and foetus including: anaemia, abortion, stillbirth, prematurity, low birth weight, foetal distress. The choice of drug for malaria prophylaxis and treatment during pregnancy depends upon the local pattern of drug resistance, severity of malaria and the degree of pre-existing malaria immunity.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Chloroquine and proguanil are excreted into milk at levels too low to harm the infant. The levels excreted are insufficient to provide the infant with protection against malaria. If appropriate, chemoprophylaxis should be administered to the infant.

Note that in cases of long term chloroquine therapy for rheumatoid disease, breastfeeding is not recommended.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Counselling

When chloroquine sulfate is used for malaria prophylaxis warn travellers about the importance of avoiding mosquito bites, the importance of taking prophylaxis regularly, and the importance of an immediate visit to a doctor if they fall ill within 1 year and especially within 3 months of return.

Antacids may impair absorption, therefore antacids should be taken at least 4 hours before or 4 hours after administration with chloroquine.

The tablets may be crushed and mixed with milk, honey, or jam for administration to young children.

Patients should be advised to discontinue the medication and seek immediate medical advice if they notice any deterioration in their vision which persists for more than 48 hours.

Ability to drive and operate machinery may be affected by side effects.

Side Effects

Abdominal cramps
Abnormal liver function tests
Aggravation of porphyria
Agranulocytosis
Allergic reaction
Anaphylactic reaction
Angioedema
Anxiety
Aplastic anaemia
Blindness
Blood disorders
Blurred vision
Bone marrow depression
Cardiomyopathy
Cholestasis
Constipation
Convulsions
Corneal opacities
Delirium
Depigmentation of hair
Diarrhoea
Diplopia
Discolouration of nails (temporary)
Disturbances in accommodation
Drug fever
Drug rash with eosinophilia and systemic symptoms (DRESS)
ECG changes
Emotional lability
Erythema multiforme
Exacerbation of myasthenia gravis
Exacerbation of psoriasis
Exfoliative dermatitis
Gastro-intestinal disturbances
Haematological changes in renal impairment
Haemolysis
Hair loss
Hallucinations
Headache
Hearing disturbances
Hepatic damage
Hepatitis
Hypoglycaemia
Hypotension
Interstitial lung disease
Lichen-planus type reaction
Liver function disturbances
Macular degeneration of colour vision
Maculopapular rash
Mouth ulcers
Myopathy
Nausea
Nerve deafness
Neuromyopathy
Neutropenia
Optic atrophy scotomas
Ototoxicity
Personality change
Photosensitivity
Pigmentation (ophthalmic)
Pigmentation of mucous membranes
Pigmented deposits in the eye
Pruritus
Psychotic reactions
Purpura
Rash
Retinal damage (irreversible)
Retinopathy
Skin pigmentation changes
Skin reactions
Stevens-Johnson syndrome
Stomatitis
Thrombocytopenia
Tinnitus
Toxic epidermal necrolysis
Urticaria
Vasculitis (allergic)
Visual field defects
Vomiting

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: November 2013

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Joint Formulary Committee. British National Formulary. 66th ed. London: BMJ Group and Pharmaceutical Press; 2013. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press [Accessed on November 20 2013].

Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

Paediatric Formulary Committee. BNF for Children 2013-2014. London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2013. Paediatric Formulary Committee. BNF for Children (online) London: BMJ Group, Pharmaceutical Press, and RCPCH Publications [Accessed on November 20 2013].

Summary of Product Characteristics: Paludrine/Avloclor Anti-Malarial Travel pack tablets. Alliance UK Ltd. Revised February 2013.

The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.