P02 ANTHELMINTICS
P02B Antitrematodals
P02BA Quinoline derivatives
P02BB Organophosphorous compounds
P02C Antinematodal agents
P02CA Benzimidazole derivatives
P02CB Piperazine and derivatives
P02CC Tetrahydropyrimidine derivatives
P02D Anticestodals
P02DA Salicylic acid derivatives
Clinical notes:
Common intestinal nematode infestations
Table: Agents used in common helminthic infestations.
There is a high prevalence of schistosomiasis (bilharzia) in the tropical and subtropical areas of southern Africa. Urinary schistosomiasis is caused by S.haematobium. Adult worms live in the bladder, prostatic and uterine plexuses of veins where they lay eggs and produce haematuria and other clinical features of urinary schistosomiasis. S.mansoni adult worms inhabit the inferior mesenteric veins and cause intestinal schistosomiasis.
Praziquantel is the agent of choice in the treatment of schistosomiasis. It is highly effective against both species of schistosome, has low toxicity and may be used as a single dose.
Oxamniquine is specific against S.mansoni for acute or chronic infections and may be used in patients with advanced splenohepatic involvement. It is not effective against S.haematobium. It is not readily available in South Africa.
Metrifonate is ideal for mass therapy against S.haematobium and may be effective for prophylaxis. It is not effective against S.mansoni. Its low cost and high efficacy has made it an important agent in developing countries, but it is not readily available in SA.
Praziquantel
(WHO essential agent)
Praziquantel produces contraction and paralysis of helminths by affecting membrane permeability to calcium. It also leads to vacuolisation and disintegration of the integument of susceptible parasites.
Indications: Schistosomiasis (agent of choice); intestinal tapeworm infestations (T.solium, T.saginata, D.latum and H.nana); cysticercosis caused by T.solium.
Pharmacokinetics: Readily absorbed.
* T½ = 1-1.5 hours due to rapid hepatic metabolism. T½ of metabolites = 4-6 hours.
* About 80% of the dose, mainly as inactive metabolites, is eliminated in urine in about 4 days, more than 90% of this in the first 24 hours.
Precautions:
Contraindications: Ocular cysticercosis - irreparable ocular lesions may result from local destruction of parasites.
Drug interactions: None documented.
Pregnancy: Safety has not been established; avoid in the first trimester, and use thereafter only if the benefits outweigh the possible risk to the fetus. Category B.
Lactation: Excreted in breast milk to reach 25% of maternal serum levels; discontinue breast- feeding on the day of therapy and for 72 hours thereafter.
Porphyria: Insufficient data available.
Geriatrics: No specific precautions required.
Paediatrics: Has been used in children over 2 years of age without evidence of adverse age- related reactions.
Adverse effects: These are usually mild and transient. Frequent - malaise, non-specific gastrointestinal disturbances, headache, drowsiness and dizziness.
Less frequent - urticaria, eosinophilia and arthralgia.
* Inflammatory responses to dead and dying parasites in neurocysticercosis may cause fever, brain oedema, raised intracranial pressure and convulsions.
Special Prescriber's Points
* Patients with cerebral cysticercosis are at risk of developing reactive cerebral oedema and are best treated in hospital with expert advice and supervision. Concomitant steroid therapy, e.g. dexamethasone or prednisolone, is often indicated. There is recent evidence that concomitant corticosteroids lower plasma levels of praziquantel.
* Calcified cysts do not respond to treatment.
* Hospital treatment is recommended when treating schistosomiasis or adult tapeworms in patients with concomitant cysticercosis.
* Patients should be warned that the drug may cause temporary drowsiness and dizziness, affecting the ability to drive or perform other tasks requiring mental alertness. Alcohol may aggravate these effects.
* Dose reduction may be required in patients with severely impaired hepatic function.
Adult dose: (taken unchewed with some liquid after a meal).
S.haematobium and S.mansoni: 40 mg/kg in a single dose.
T.solium, T.saginata and D.latum: 10-20 mg/kg as a single dose.
Cysticercosis: 50 mg/kg/day in 3 divided doses for 15 days.
Paediatric dose: Children over 2 years may receive doses according to body weight as for adults.
Preparations include:
Praziquantel [INN] [P02BA01]
Biltricide® Bayer [S4]
tablets, 600 mg
Cysticide® Merck [S4]
tablets, 500 mg
Oxamniquine
(WHO essential agent)
Oxamniquine is active against mature as well as early developmental stages of S.mansoni. Adult male worms are thought to be more susceptible than females. Mode of action is not clear; worms migrate from the mesenteric veins to the liver where they are destroyed. It is ineffective against S.haematobium.
Pharmacokinetics: Well absorbed orally, but absorption is delayed by food.
* T½ = 1-2.5 hours. Most drug is cleared from the serum within 12 hours; it is extensively metabolised to inactive products and excreted mainly in urine.
Contraindications: Relative - epilepsy, history of epilepsy or seizures. Use with caution under close supervision.
Pregnancy: Embryotoxic in animals. Potential effects on the human fetus are not known; avoid during the first 16 weeks of pregnancy.
Lactation: Problems have not been reported. Use with caution only if essential; abstain from nursing for 72 hours.
Adverse effects: Frequent - transient dizziness, drowsiness, headache, nausea, vomiting and diarrhoea.
Rare - skin rashes, fever, hallucinations and convulsions (usually in patients with a history of epilepsy).
Eosinophilia has developed 2-3 days after therapy.
Special Prescriber's Points
* Gastrointestinal intolerance may be markedly improved by taking the drug with food.
* May cause a non-significant orange or red discoloration of urine.
* As patients may become drowsy or dizzy, they should be warned not to drive or operate machinery.
Adult dose: Oral, 15 mg/kg twice daily for 2 days. Dosage range and duration depends on the geographical location and the strain of S.mansoni.
Paediatric dose: As for adults.
Preparations include:
Oxamniquine [INN] [P02BA02]
Vansil® Pfizer [S4]
* Not available in South Africa; contact the pharmaceutical company if required.
P02BB Organophosphorous compounds
Metrifonate
(syn. metriphonate)
(WHO essential agent)
Indications: Treatment and prophylaxis of schistosomiasis caused by S.haematobium.
Pharmacokinetics: Well absorbed orally and converted to dichlorvos, the active metabolite. Plasma cholinesterase levels are rapidly depressed and may need 4-6 weeks to return to normal.
Contraindications: Recent exposure to insecticides; severe liver disease.
Drug interactions: Use of depolarising neuromuscular blocking agents should be avoided for at least 48 hours after therapy.
Pregnancy and Lactation: Contraindicated.
Adverse effects: Nausea, colic, weakness, bronchospasm, tremor, sweating, fainting, headache and vertigo; usually mild and subside spontaneously.
Adult dose: Therapy: Oral, 7.5-10 mg/kg in a single dose, repeated 3 times at intervals of 2-weeks.
Prophylaxis: Oral, 7.5 mg/kg once every 4 weeks.
Paediatric dose: Oral, 7.5-10 mg/kg in a single dose, repeated every 2 weeks for 3 doses.
Preparations include:
Metrifonate [INN] [P02BB01]
Bilarcil® Bayer
* May be used in South Africa only with special permission from the MCC.
The following agents are included in the WHO essential drug list.
Mebendazole, a benzimidazole derivative, is a useful broad spectrum anthelmintic and a drug of choice for mixed worm infestations.
Albendazole, a new member of the benzimidazole group, has the broadest spectrum of activity in the single dose oral treatment of intestinal helminth infestation. It is challenging the position of mebendazole as the drug of choice in mixed worm infestation.
Piperazine is used in ascariasis and enterobiasis; it is relatively inexpensive.
Pyrantel may be used in the treatment of round-, thread- and hookworm infestations; it is not effective against whipworm.
Tiabendazole (syn. thiabendazole), another benzimidazole, is the drug of choice against strongyloidiasis, cutaneous larva migrans and may be of some value in therapy of visceral larva migrans.
Diethylcarbamazine, a piperazine derivative, is mainly indicated for the treatment of filariasis due to W.bancrofti, B.malayi and L.loa.
Ivermectin has a broad spectrum of activity and is now considered the drug of choice in onchocerciasis. It is given as a single dose according to body weight and produces a prolonged reduction in microfilarial levels. Retreatment is required at intervals of 6-12 months, depending on symptoms, until adult worms have died out. It is associated with fewer and less severe systemic and ocular reactions than diethylcarbamazine.
It is not registered in South Africa, but can be obtained from the pharmaceutical company (Logos) after MCC approval.
Levamisole, an imidazothiazole derivative, is not registered for use as an anthelmintic in South Africa.
Common intestinal nematode infestations
Roundworm infestation (ascariasis) is the most common helminthic disease in man, occurring most frequently in children playing in soil contaminated with infected faeces. During the intestinal phase most people are asymptomatic or may have vague abdominal pain. However, complications of light or severe infestations include malnourishment, intestinal obstruction and appendicitis and treatment is always indicated. Helminth infestation of one family member may indicate infestation of others. Treatment of all family members and pets is generally recommended; stools should be checked after 2 weeks and therapy repeated if necessary.
Agents of choice are pyrantel, mebendazole, albendazole. Piperazine is an alternative. Recommendations vary regarding the safety of the available agents in children under 2 years. While in practice they have all been used, for infants the usual risk/benefit assessment is required.
Pinworm (syn. threadworm) infestation (enterobiasis), though cosmopolitan, is more common in temperate climates with a high incidence in urbanised areas. It seldom causes serious clinical problems, but pruritus in the perianal and perineal areas can be severe and scratching may lead to secondary infection. Worms do not multiply in the gut; the female worm lays her eggs in the perianal area, usually at night and ova must be swallowed for the development of fresh parasites. As it spreads easily in those infested, as well as from person to person, attention should be paid to hygiene, including: daily changing of pyjamas and underwear; proper cleansing of the perianal area; protection of children against anal-finger- mouth transmission; regular vacuum cleaning of bedrooms if possible, as airborne eggs can be inhaled and swallowed.
Agents of choice are albendazole, mebendazole, pyrantel. Piperazine is also effective if taken regularly for 7 consecutive days. All members of a family should generally be treated. As reinfection is very common, treatment may be repeated after 2 weeks.
Whipworm (trichiuriasis) is most prevalent in warm, humid geographical areas. Infestation is usually not intensive and seldom causes serious clinical problems, except in children in whom severe infestion (with large amounts of worms lodging in the large intestine) may cause abdominal cramps, anaemia and rectal prolapse.
Agent of choice is mebendazole. Albendazole is also effective.
Hookworms (A.duodenale and N.americanus) invade humans by skin penetration during contact with contaminated soil. Wearing shoes (in addition to improving sanitation) may help to prevent infestation. Anaemia is a common complication and iron supplementation, together with a proper diet, is usually indicated.
Agents of choice are albendazole, mebendazole, pyrantel.
Strongyloidiasis is acquired through larvae penetrating the skin and is most prevalent in warm, humid geographical areas. Most people infested are asymptomatic but they should always be treated since cyclic autoinfection may develop which may lead to hyperinfection with a massive worm burden. Hyperinfection is particularly dangerous in immunosuppressed patients, e.g. those with neoplastic diseases, or receiving corticosteroid or immunosuppressive therapy, and also during pregnancy and in the puerperium. Anaemia and hypoproteinaemia should be corrected when therapy is started.
Agents of choice: As larval stages migrate through the tissues in cases of autoinfection, curative agents must be active in the bowel lumen and in the tissues. Tiabendazole is considered the agent of choice but produces significant adverse effects. High doses of albendazole or mebendazole eliminate the worm from the bowel in more than 80% of cases; albendazole is preferred as higher serum concentrations of active metabolites are obtained.
Cutaneous larva migrans is usually caused by Ancylostoma braziliense. The drug of choice is tiabendazole. Oral albendazole has been shown to be effective and well tolerated.
Visceral larva migrans is caused by Toxocara canis or Toxocara cati. Diethylcarbamazine or tiabendazole, or alternatively mebendazole, together with corticosteroids, has been used. A recent study has shown albendazole to be as effective as tiabendazole with fewer adverse reactions.
Filarial infections include lymphatic filariasis caused by Wuchereria bancrofti and Brugia malayi, loiasis caused by Loa loa and onchocerciasis caused by Onchocerca volvulus.
Diethylcarbamazine is effective against the microfilariae and adult worms of W.bancrofti, B.malayi and L.loa.
In onchocerciasis, diethylcarbamazine causes such serious systemic and ocular reactions that its use is no longer recommended. Ivermectin is now considered the agent of choice.
Guineaworm (dracunculosis): The agents used exhibit anti-inflammatory rather than anthelmintic action, facilitating removal of parasites from the tissue. Extraction of the parasite should be performed under sterile conditions and sterile dressings applied wherever needed.
Metronidazole may decrease the host's response to the infection making it easier to remove the emerging worms. (Adult dose, 250 mg three times daily for 10 days.) Tiabendazole has also been used.
P02CA BENZIMIDAZOLE DERIVATIVES
Albendazole
(WHO essential agent)
Albendazole blocks glucose uptake in susceptible helminths, depleting the energy level until it becomes inadequate for survival.
Indications: Single or mixed intestinal parasite infestations - effective against roundworm, pinworm (threadworm), whipworm, hookworm, Strongyloides stercoralis and Taenia spp.(tapeworm). Hydatid disease - chemotherapeutic agent of choice in inoperable cases and prophylactically before and after surgery. Also effective in neurocysticercosis, cutaneous larva migrans, and visceral larva migrans (one study).
Pharmacokinetics: Absorbed, but almost undetectable in plasma due to rapid conversion to an active sulphoxide metabolite with T½ = 8.5 hours; this is excreted in the urine together with other metabolites. Systemic availability is increased when taken with a fatty meal.
Precautions:
Drug interactions: None reported.
Pregnancy: Teratogenicity and embryotoxicity have been demonstrated in animals; should not be taken at any stage of pregnancy nor by women likely to become pregnant during or shortly after the course of therapy.
Lactation: No data available on excretion in breast milk; not recommended.
Porphyria: Use with caution.
Geriatrics: May be used.
Paediatrics: Has not been fully evaluated in children under 2 years of age, but use in 1-2 year-olds in intestinal nematode infestations has been reported.
Adverse effects: The dose recommended for intestinal worms is very well tolerated. Epigastric pain, diarrhoea, headache, nausea, dizziness, vomiting, constipation, pruritus ani and dry mouth have been reported in a small percentage of patients.
Leucopenia has occurred with large doses and/or long periods of therapy.
Abnormalities in liver function, gastrointestinal symptoms, allergic reactions and alopecia have been reported with the higher doses used in hydatid disease and neurocysticercosis.
Special Prescriber's Points
* Frequent white cell counts should be done when given in large doses or for long periods.
* In neurocysticercosis supervision is recommended as there may be inflammatory reactions in response to the death of the parasite, which if severe may require steroids.
* Tablets may be chewed, swallowed or crushed and mixed with food.
* No fasting or purging is necessary; however, since food increases systemic availability, it would seem preferable to take the medicine on an empty stomach when a high intraluminal concentration is desirable for treating intestinal worms.
Adult dose: Oral, 400 mg as a single dose.
Strongyloidiasis, taeniasis and heavy mixed infestations involving trichuris: Efficacy is improved by giving 400 mg daily for 3 consecutive days. If a cure is not achieved the same dose can be given after 3 weeks.
Hydatid disease: Oral, 10-15 mg/kg/day. The regimen most frequently used has been 400 mg twice daily for three 28- day cycles with 14 days' rest between cycles. Long- standing cysts or those in biologically less accessible sites such as bone and brain may require more prolonged therapy.
Neurocysticercosis: 15 mg/kg/day in 3 divided doses for one month has been used in most studies. Recently shorter courses (8 days or 3 days) have also been shown to be effective.
Cutaneous larva migrans: Oral, 400 mg/day either once or for 3 consecutive days has been reported to be effective and well tolerated.
Visceral larva migrans: 5 mg/kg twice daily for 5 days has been used in one study.
Paediatric dose: Children over 2 years of age see adult dose above. Children 1-2 years (or less than 10 kg): 200 mg as a single dose has been used safely and effectively in single and mixed intestinal nematode infestation.
Preparations include:
Albendazole [INN] [P02CA03]
Zentel® SK Beecham [S4]
tablets, 200 mg
suspension, 20 mg/mL
Mebendazole
(WHO essential therapeutic group)
Mebendazole causes selective inhibition of glucose uptake in susceptible helminths.
Indications: Roundworm, hookworm, pinworm (threadworm), whipworm and Strongyloides stercoralis infestations.
Pharmacokinetics: About 5-10% absorbed orally, increased by fatty food; bioavailability is further decreased by first-pass effect in the liver.
* T½ = 2-9 hours; up to 35 hours in impaired hepatic function.
* Excreted mainly in faeces as unchanged drug and metabolites; 2-5% eliminated in urine.
Precautions:
Contraindications: Relative - Crohn's disease, ulcerative colitis and other ulceration of GI tract (increased absorption and possible toxicity); impaired hepatic function.
Drug interactions:
Carbamazepine: Lowers plasma concentrations of mebendazole by induction of hepatic microsomal enzymes.
Pregnancy: Crosses the placenta; teratogenicity has been demonstrated in animals; should not be used during the first trimester, and only if essential during the later trimesters. Category C.
Lactation: Not known if excreted in breast milk; no problems recorded.
Porphyria: May prove unsafe: use with extreme caution.
Geriatrics: No specific information available; is used.
Paediatrics: Some authorities recommend that it should not be given to children under 2 years old. However, in practice it is used and the manufacturers do not contraindicate it in this age group. One report of serious toxicity in an 8-week, 5.1 kg infant.
Adverse effects: Uncommon with doses
recommended for intestinal worms.
Occasionally - gastrointestinal discomfort; abdominal
pain, nausea and diarrhoea are usually associated with
severe infestations and upward migration of worms.
Rarely - itching, pyrexia, dizziness, drowsiness and headache.
High doses used for hydatid disease have been associated with bone marrow depression and hepatotoxicity; allergic reactions and alopecia may also occur.
Special Prescriber's Points
* Leucocyte counts should be done at regular intervals if used in high doses for hydatid disease; it has been superseded by albendazole.
* Caution should be exercised where hepatic metabolising capacity is impaired as high plasma mebendazole concentrations may develop with potential drug toxicity.
* Upward migration of round worms may occur, with parasites being expelled through the nose and mouth of heavily infested persons.
* No fasting or purging is required.
Adult dose: Oral, 100 mg twice daily for 3 days.
Pinworm (Enterobius): 100 mg as a single dose, repeated after 2 weeks, is also effective.
Strongyloidiasis: 200 mg twice daily for 3 days.
Hookworm: 200 mg twice daily for 4 days has been used.
Tapeworm (Taenia spp.): 100 mg twice daily for 6 days. There are reports of high success rates with higher doses for shorter periods such as 200 mg twice daily for 4 days or 300 mg twice daily for 3 days.
* Treatment may be repeated after 2 weeks if necessary.
Hydatid disease: 40-50 mg/kg/day in divided doses (up to 200 mg/kg/day) has been used. Treatment may be needed for 3 months or longer.
Paediatric dose: Oral, 100 mg twice daily for 3 days.
Pinworm (Enterobius): 100 mg as a single dose, repeated after 2 weeks, is also effective.
Tapeworm (Taenia spp.): 100 mg twice daily for 6 days.
Preparations include:
Mebendazole [INN] [P02CA01]
Vermox® Janssen [S2]
tablets, 100 mg
suspension, 100 mg/5 mL
Also: Anthex® Rolab; Vermazide® Lennon.
Tiabendazole
(syn. thiabendazole)
The action of tiabendazole is uncertain but may involve interference with the source of energy of susceptible helminths.
Indications: Strongyloidiasis, visceral and cutaneous larva migrans, guinea-worm and porkworm (T.spiralis).
Pharmacokinetics: Rapidly and almost completely absorbed orally; may be absorbed from preparations applied to the skin.
* T½ = 1-2 hours.
* Metabolised in the liver. About 90% is eliminated in urine within 48 hours, mainly as metabolites; 5% is excreted in faeces.
Precautions:
Contraindications: Absolute - history of hypersensitivity to tiabendazole.
Use with caution in hepatic and renal impairment.
Drug interactions:
Theophylline: Serum theophylline levels may be increased.
Pregnancy: Teratogenicity has been reported in animals and safety in humans has not been established; best avoided. Category C.
Lactation: No data available on excretion into breast milk; potential for adverse effects in the nursing infant.
Porphyria: No data available.
Geriatrics: No specific data available.
Paediatrics: Clinical experience in children weighing less than 15 kg is limited.
Adverse effects: Frequent - anorexia, nausea, vomiting and dizziness.
Less frequent - pruritus, skin rashes, headache, drowsiness, tinnitus, disturbances of vision, effects on the liver, leucopenia, crystalluria, malodour of urine, hyperglycaemia, bradycardia, hypotension and collapse.
Erythema multiforme, including fatal Stevens-Johnson syndrome, toxic epidermal necrolysis, convulsions and effects on mental state have also been recorded.
Fever, chills, angioedema and lymphadenopathy have occurred, but may represent allergic response to dead parasites rather than to the drug.
Special Prescriber's Points
* Therapy should be discontinued at the first sign of hypersensitivity.
* As drowsiness may occur, patients should be warned not to drive or operate machinery.
* Despite the frequent and unpleasant side-effects it remains the treatment of choice for strongyloidiasis.
* Not suitable for mixed infestation with Ascaris as it may cause these worms to migrate.
* Tablets should be taken after meals and chewed before swallowing.
Adult dose: Oral, 25 mg/kg twice daily (maximum 3 g/day).
Strongyloidiasis: The above dose is given for 2 successive days, and for at least 5 days if the infestation is disseminated.
Cutaneous larva migrans: Two consecutive days of treatment are recommended; may be repeated 2 days later if active lesions are still present.
Topical application (approximately 17%) four times daily has been reported to successfully eliminate the larvae in about a week.
Visceral larva migrans: 25 mg/kg may be given twice daily for 7 days.
Guineaworm: 25 mg/kg twice daily for 2-3 days.
Paediatric dose: Children and adolescents weighing more than 15 kg as for adults above.
Preparations include:
Tiabendazole [INN] [P02CA02]
Mintezol® Logos [S4]
tablets, 500 mg
* Not readily available but can be obtained from the pharmaceutical company.
P02CB PIPERAZINE AND DERIVATIVES
Piperazine
(WHO essential agent)
Piperazine causes paralysis of roundworms by blocking the action of acetylcholine at the neuromuscular junction. Its mechanism in enterobiasis is not clear.
Indications: Roundworm and pinworm (threadworm) infestations.
Pharmacokinetics: Piperazine salts are readily absorbed. The excretion rate of unchanged drug and metabolites varies widely in individuals. Despite systemic absorption it appears to have little or no effect on larvae in the tissues.
Precautions:
Contraindications: Absolute - patients with a history of epilepsy or other neurological disorders, severe malnutrition or anaemia.
Relative - impaired renal or hepatic function.
Drug interactions:
Phenothiazines: Increased risk of extrapyramidal reactions.
Pyrantel: Mutual antagonism of the anthelmintic effect; concurrent use is contraindicated.
Pregnancy: After a long history of use without reported adverse effect, there have been two recent reports of fetal abnormalities. Avoid use during the first trimester and preferably delay treatment until after parturition.
Lactation: Excreted in breast milk; use with caution if essential during lactation. Manufacturers advise that the infant be fed immediately before maternal dosing, then milk expressed and discarded during the next 8 hours.
Porphyria: Insufficient data available.
Geriatrics: No specific problems documented.
Paediatrics: Has been widely used in children of all ages. Manufacturers' recommended dosages are from 9 months old.
Adverse effects: These are generally rare and dose-related. Mild nausea and abdominal pain may develop. Neurotoxicity with vertigo, ataxia, nystagmus and hyporeflexia are seen mostly in children and in patients with neurological or renal disease. Hypersensitivity reactions have been reported.
Special Prescriber's Points
* Roundworm infestation: If constipation is a problem, an effective purgative should be taken on the morning after the dose of piperazine to expel the worms before the effect of the drug wears off.
* Efficacy is improved by giving a second dose 24 hours after the first.
* Piperazine citrate 125 mg is equivalent to 100 mg piperazine hydrate.
Adult dose: Doses are for piperazine hydrate.
Roundworm: Oral, 4 g as a single dose with the evening meal.
Pinworm (threadworm): Oral, 2 g daily for 7 days.
Paediatric dose: Roundworm: Oral, 120 mg/kg (maximum 4 g ) as a single dose.
Pinworm: Oral, over 12 years, 2 g daily in 2-3 divided doses; 6-12 years, 1.5 g daily; 1-5 years, 250 mg/day per year of age. Treatment should be continued for 7 days. A second course after a 1-week interval may be required.
Preparations include:
Piperazine [P02CB01]
Pipralen® Lennon
syrup, piperazine hydrate 750 mg/5 mL (as citrate)
Also: Ascarient® Propan-Vernleigh; Pip-A-Ray® Vernleigh; Wormelix® Pharmalab; Padax® AI Self Med; Piprine® Be-Tabs.
* All preparations contain tartrazine.
Diethylcarbamazine
(WHO essential agent)
Indications: Filariasis due to W.bancrofti, B.malayi, L.loa; visceral larva migrans.
Pharmacokinetics: Well absorbed and widely distributed.
* T½ = 5-13 hours.
* Excreted in the urine, approximately half unchanged and half as metabolites.
Precautions:
Contraindications: Relative - impaired renal function, hypertension, tuberculosis or malnutrition; onchocerciasis.
Drug interactions: None documented.
Pregnancy: Treatment is best deferred until after delivery.
Porphyria: No data available.
Geriatrics: No specific information available; is used.
Paediatrics: No adequate, well-controlled studies done; no specific problems documented.
Adverse effects: Minor effects include headache, weakness and anorexia. Sleepiness, nausea and vomiting sometimes occur. Prolonged use may lead to ocular damage.
* Allergic responses to killed organisms vary with the infecting species:
W.bancrofti and B.malayi: Headache, fever, skin rashes, weakness, arthralgia, malaise and gastrointestinal symptoms and precipitation of asthma.
Loiasis: Risk of encephalitis.
Onchocerciasis: Potentially fatal `Mazotti' reaction, generally occurring within 24 hours after beginning therapy and usually subsiding after 3-7 days, with intense skin reactions, tachycardia, hypotension and fever. Lymph glands draining affected areas may become painful and enlarged.
Special Prescriber's Points
* Ivermectin is preferred in onchocerciasis.
* To diminish adverse reactions due to the destruction of microfilariae, particularly those of L.loa, it is advisable to use a small initial dose. Corticosteroids may be needed in cases of severe reaction. Close medical supervision is necessary, particularly in loiasis where in rare instances there may be severe cerebral reactions.
* Swelling and itching of the eyes, or any other sign of an allergic reaction should be reported to the prescriber.
* Ocular damage may require corticosteroid therapy.
* Dosage should be adjusted in impaired renal function.
Adult dose: W.bancrofti, B.malayi and L.loa (recommended regimen): Day 1, single dose of 50 mg; Day 2, 50 mg for 3 doses; Day 3, 100 mg for 3 doses ; thereafter 2 mg/kg 3 times daily for total 21 days. In loiasis, some authorities recommend 3 mg/kg 3 times daily from day 4 to day 21 in all age groups.
Visceral larva migrans (Toxocara): Initially 1 mg/kg 3 times daily, increased if well tolerated to 2-3 mg/kg three times daily for 21 days.
Paediatric dose: W.bancrofti, L.loa and B.malayi: Day 1, 25-50 mg; Day 2, 25-50 mg 3 times; Day 3, 50-100 mg 3 times; from Day 4 through to Day 21, 2 mg/kg 3 times daily.
Visceral larva migrans: Day 1, 1 mg/kg; Day 2, 1 mg/kg 3 times daily; Day 3, 2 mg/kg 3 times daily; then 3 mg/kg 3 times daily for 21 days.
Preparations include:
Diethylcarbamazine [INN] [P02CB02]
Hetrazan® Lederle [S4]
tablets, 50 mg
* Not readily available but can be obtained from the pharmaceutical company.
P02CC TETRAHYDROPYRIMIDINE DERIVATIVES
Pyrantel
(WHO essential agent)
Pyrantel produces depolarising neuromuscular blockade in the helminths that leads to spastic paralysis. The paralysed worms are dislodged and expelled by peristaltic activity.
Indications: Roundworm, pinworm (threadworm) and hookworm infestations.
Pharmacokinetics: Over 50% is not absorbed and is excreted unchanged in faeces; less than 15% is excreted in urine as unchanged drug and metabolites.
Precautions:
Contraindications: Relative - impaired liver function, severe anaemia or malnutrition.
Drug interactions:
Piperazine: Mutual antagonism of the anthelmintic effect; concurrent use is contraindicated.
Pregnancy: Teratogenicity has not been shown in animals, but safety to the human fetus has not been established; use not recommended unless essential.
Lactation: Poor absorption and low maternal serum concentrations mean that significant amounts are unlikely to appear in breast milk; use with caution.
Porphyria: Insufficient data available.
Geriatrics: No specific information documented; is used.
Paediatrics: No adequate, well-controlled studies done in children under 2 years old; however some authorities indicate that paediatric doses are for children over 6 months.
Adverse effects: Usually mild and transient - nausea and vomiting, anorexia, abdominal pain, diarrhoea, headache, dizziness and skin rash.
Occasionally - a transient elevation of serum transaminases.
Special Prescriber's Points
* Use of a purgative is not necessary.
* May be taken with milk or other fluid.
Adult dose: Oral, 10 mg/kg as a single dose (maximum 1 g).
Hookworm: 10 mg/kg once daily for 3 days for more severe infestations of N.americanus.
Paediatric dose: 10 mg/kg as a single dose.
Preparations include:
Pyrantel [INN] [P02CC01]
Combantrin® Pfizer
suspension, 50 mg/mL (as pamoate)
tablets, 125 mg
Adult tapeworms which inhabit the human intestine include T.solium and T.saginata, D.latum and H.nana.
T.solium (pork tapeworm) and T.saginata (beef tapeworm) may be contracted by eating undercooked pork and beef which contain viable cysticerci. In the human intestine the cysticercus develops into an adult worm. Infestations are usually asymptomatic, and the worms are often discovered incidentally as segments in stool, clothing or bedding. Infestation with T.solium places the host and others (if faecal contamination of food or water occurs) at risk of developing cysticercosis, and since this may have grave consequences, elimination of adult tapeworms is usually recommended without delay.
Hydatid disease is caused by the larval stage of the dog tape worms, E.granulosus and E.multilocularis.
Agents used: Niclosamide and praziquantel are effective against T.solium and T.saginata (affecting the adult worms in the intestine). Albendazole and mebendazole are alternatives. The theoretical risk of developing cysticercosis from treating T.solium worms with niclosamide should not be a clinical problem, provided dosage instructions are followed.
Niclosamide and praziquantel are effective against D.latum (fish tapeworm) and H.nana (dwarf tapeworm).
Praziquantel is used in the treatment of cerebral cysticercosis, but is not recommended in ocular cysticercosis. In parenchymal brain cysticercosis, albendazole is as effective as (and in some recent studies reported to be more effective than) praziquantel.
In hydatid disease, while surgery remains standard management, albendazole is the most effective chemotherapeutic agent available for inoperable cases, and pre- and post-operatively to reduce the risk of metastatic spread. It has greater systemic bioavailability and has superseded mebendazole in this area.
P02DA SALICYLIC ACID DERIVATIVES
Niclosamide
(WHO essential agent)
Niclosamide inhibits metabolic processes in helminths, resulting in the death of scolices and proximal proglottids (but not of the ova). Scolices are detached from the intestinal wall and the worms may be partly digested before they are excreted.
Indications: Eradication of beef (T.saginata), pork (T.solium), dwarf (H.nana), and fish (D.latum) tapeworm.
Pharmacokinetics: 10-20% absorbed from the GI tract; excreted, mostly unchanged, in faeces.
Precautions:
Contraindications: No absolute contraindications.
Drug interactions: None documented.
Pregnancy: Poorly absorbed; adverse effects on the fetus are unlikely but it is recommended that treatment be deferred until after delivery, or until the second or third trimester, if therapy is essential. Category B.
Lactation: Since little is absorbed, significant amounts are unlikely to appear in breast milk.
Porphyria: Insufficient data available.
Geriatrics: No specific information available; has been used.
Paediatrics: No adequate, well-controlled studies done in children under 2 years of age; has been used for all ages.
Adverse effects: Occasional - gastrointestinal disturbances, lightheadedness, pruritus ani.
Rare - urticaria and skin rashes, possibly due to absorption of disintegrated parasite material.
Special Prescriber's Points
* Patients with chronic constipation should receive a purgative the night before treatment.
* An antiemetic may be given on wakening as a precaution against the possible development of cysticercosis.
* Given as a single dose, after a light breakfast.
* Tablets must be chewed thoroughly or crushed finely and swallowed with a small amount of water.
* For T.solium, an effective purge (e.g. magnesium sulphate) should be given 2 hours afterwards to eliminate all mature segments before the viable ova can be released into the gut.
* It is recommended that no alcohol be taken during treatment.
Adult dose: Beef, pork and fish tapeworm: 2 g as a single dose.
H.nana: 2 g on the first day followed by 1 g for the following 6 days.
Paediatric dose: Children over 6 years, as adult dose; 2-6 years, half the adult dose; under 2 years, one-quarter the adult dose.
Preparations include:
Niclosamide [INN] [P02DA01]
Yomesan® Bayer
tablets, 500 mg