Tablets, diloxanide furoate 500 mg, net price 30-tab pack = £93.50. Label: 9
METRONIDAZOLE
Indications see under Dose below; anaerobic infections, section 5.1.11
Cautions section 5.1.11
Hepatic impairment section 5.1.11
Pregnancy section 5.1.11
Breast-feeding section 5.1.11
Side-effects section 5.1.11
Dose
By mouth, invasive intestinal amoebiasis, extra-intestinal amoebiasis (including liver abscess), 800 mg every 8 hours for 5 days in intestinal infection (for 5–10 days in extra-intestinal infection); CHILD 1–3 years 200 mg every 8 hours; 3–7 years 200 mg every 6 hours; 7–10 years 400 mg every 8 hours
Urogenital trichomoniasis, 200 mg every 8 hours for 7 days or 400–500 mg every 12 hours for 5–7 days, or 2 g as a single dose; CHILD 1–3 years 50 mg every 8 hours for 7 days; 3–7 years 100 mg every 12 hours; 7–10 years 100 mg every 8 hours
Giardiasis, 2 g daily for 3 days or 400 mg 3 times daily for 5 days or 500 mg twice daily for 7–10 days; CHILD 1–3 years 500 mg daily for 3 days; 3–7 years 600–800 mg daily; 7–10 years 1 g daily
TINIDAZOLE
Indications see under Dose below; anaerobic infections, section 5.1.11
Cautions section 5.1.11
Pregnancy section 5.1.11
Breast-feeding section 5.1.11
Side-effects section 5.1.11
Dose
Intestinal amoebiasis, 2 g daily for 2–3 days; CHILD 50–60 mg/kg daily for 3 days
Amoebic involvement of liver, 1.5–2 g daily for 3–6 days; CHILD 50–60 mg/kg daily for 5 days
Urogenital trichomoniasis and giardiasis, single 2 g dose; CHILD single dose of 50–75 mg/kg (repeated once if necessary)
5.4.3 Trichomonacides
Metronidazole (section 5.4.2) is the treatment of choice for Trichomonas vaginalis infection. Contact tracing is recommended and sexual contacts should be treated simultaneously. If metronidazole is ineffective, tinidazole (section 5.4.2) may be tried.
5.4.4 Antigiardial drugs
Metronidazole (section 5.4.2) is the treatment of choice for Giardia lamblia infections. Alternative treatments are tinidazole (section 5.4.2) or mepacrine hydrochloride.
MEPACRINE HYDROCHLORIDE
Indications giardiasis; discoid lupus erythematosus (Antimalarials, section 10.1.3)
Cautions hepatic impairment, elderly, history of psychosis; avoid in psoriasis; interactions: Appendix 1 (mepacrine)
Side-effects gastro-intestinal disturbances; dizziness, headache; with large doses nausea, vomiting and occasionally transient acute toxic psychosis and CNS stimulation; on prolonged treatment yellow discoloration of skin and urine, chronic dermatoses (including severe exfoliative dermatitis), hepatitis, aplastic anaemia; also reported blue/black discoloration of palate and nails and corneal deposits with visual disturbances
Dose
Giardiasis [unlicensed], 100 mg every 8 hours for 5–7 days
Mepacrine Hydrochloride
Tablets, mepacrine hydrochloride 100 mg. Label: 4, 9, 14, 21
Available from ‘special-order’ manufacturers or specialist importing companies
5.4.5 Leishmaniacides
Cutaneous leishmaniasis frequently heals spontaneously but if skin lesions are extensive or unsightly, treatment is indicated, as it is in visceral leishmaniasis (kala-azar). Leishmaniasis should be treated under specialist supervision.
Sodium stibogluconate, an organic pentavalent antimony compound, is used for visceral leishmaniasis. The dose is 20 mg/kg daily by intramuscular or intravenous injection for 28 days in visceral leishmaniasis and for 20 days in cutaneous infection; the dosage varies with different geographical regions and expert advice should be obtained. Some early non-inflamed lesions of cutaneous leishmaniasis can be treated with intralesional injections of sodium stibogluconate under specialist supervision.
Amphotericin is used with or after an antimony compound for visceral leishmaniasis unresponsive to the antimonial alone; side-effects may be reduced by using liposomal amphotericin (AmBisome® — section 5.2.3) at a dose of 1–3 mg/kg daily for 10–21 days to a cumulative dose of 21–30 mg/kg or at a dose of 3 mg/kg for 5 consecutive days followed by a single dose of 3 mg/kg 6 days later. Abelcet®, a lipid formulation of amphotericin is also likely to be effective but less information is available.
Pentamidine isetionate (pentamidine isethionate) (section 5.4.8) has been used in antimony-resistant visceral leishmaniasis, but although the initial response is often good, the relapse rate is high; it is associated with serious side-effects. Other treatments include paromomycin [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies).
SODIUM STIBOGLUCONATE
Indications leishmaniasis
Cautions intravenous injections must be given slowly over 5 minutes (to reduce risk of local thrombosis) and stopped if coughing or substernal pain; mucocutaneous disease (see below); treat intercurrent infection (e.g. pneumonia); monitor ECG before and during treatment; heart disease (withdraw if conduction disturbances occur); predisposition to QT interval prolongation (including concomitant use with drugs that prolong QT interval); interactions: Appendix 1 (sodium stibogluconate)
Mucocutaneous disease Successful treatment of mucocutaneous leishmaniasis may induce severe inflammation around the lesions (may be life-threatening if pharyngeal or tracheal involvement) — may require corticosteroid
Hepatic impairment use with caution
Renal impairment avoid in significant impairment
Pregnancy manufacturer advises use only if potential benefit outweighs risk
Breast-feeding amount probably too small to be harmful
Side-effects anorexia, nausea, vomiting, abdominal pain, diarrhoea; ECG changes; coughing (see Cautions); headache, lethargy; arthralgia, myalgia; rarely jaundice, flushing, bleeding from nose or gum, substernal pain (see Cautions), vertigo, fever, sweating, and rash; also reported pancreatitis and anaphylaxis; pain and thrombosis on intravenous administration, intramuscular injection also painful
Dose
See notes above
5.4.6 Trypanocides
The prophylaxis and treatment of trypanosomiasis is difficult and differs according to the strain of organism. Expert advice should therefore be obtained.
5.4.7 Drugs for toxoplasmosis
Most infections caused by Toxoplasma gondii are self-limiting, and treatment is not necessary. Exceptions are patients with eye involvement (toxoplasma choroidoretinitis), and those who are immunosuppressed. Toxoplasmic encephalitis is a common complication of AIDS. The treatment of choice is a combination of pyrimethamine and sulfadiazine, given for several weeks (expert advice essential). Pyrimethamine is a folate antagonist, and adverse reactions to this combination are relatively common (folinic acid supplements and weekly blood counts needed). Alternative regimens use combinations of pyrimethamine with clindamycin or clarithromycin or azithromycin. Long-term secondary prophylaxis is required after treatment of toxoplasmosis in immunocompromised patients; prophylaxis should continue until immunity recovers.
If toxoplasmosis is acquired in pregnancy, transplacental infection may lead to severe disease in the fetus. Spiramycin [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies) may reduce the risk of transmission of maternal infection to the fetus.
5.4.8 Drugs for pneumocystis pneumonia
Pneumonia caused by Pneumocystis jirovecii (Pneumocystis carinii) occurs in immunosuppressed patients; it is a common cause of pneumonia in AIDS. Pneumocystis pneumonia should generally be treated by those experienced in its management. Blood gas measurement is used to assess disease severity.
Treatment
Mild to moderate disease Co-trimoxazole (section 5.1.8) in high dosage is the drug of choice for the treatment of mild to moderate pneumocystis pneumonia.
Atovaquone is licensed for the treatment of mild to moderate pneumocystis infection in patients who cannot tolerate co-trimoxazole. A combination of dapsone 100 mg daily (section 5.1.10) with trimethoprim 5 mg/kg every 6–8 hours (section 5.1.8) is given by mouth for the treatment of mild to moderate disease [unlicensed indication].
A combination of clindamycin 600 mg by mouth every 8 hours (section 5.1.6) and primaquine 30 mg daily by mouth (section 5.4.1) is used in the treatment of mild to moderate disease [unlicensed indication]; this combination is associated with considerable toxicity.
Severe disease Co-trimoxazole (section 5.1.8) in high dosage, given by mouth or by intravenous infusion, is the drug of choice for the treatment of severe pneumocystis pneumonia. Pentamidine isetionate given by intravenous infusion is an alternative for patients who cannot tolerate co-trimoxazole, or who have not responded to it. Pentamidine isetionate is a potentially toxic drug that can cause severe hypotension during or immediately after infusion.
Corticosteroid treatment can be lifesaving in those with severe pneumocystis pneumonia (see Adjunctive Therapy below).
Adjunctive therapy In moderate to severe infections associated with HIV infection, prednisolone 50–80 mg daily is given by mouth for 5 days (alternatively, hydrocortisone may be given parenterally); the dose is then reduced to complete 21 days of treatment. Corticosteroid treatment should ideally be started at the same time as the anti-pneumocystis therapy and certainly no later than 24–72 hours afterwards. The corticosteroid should be withdrawn before anti-pneumocystis treatment is complete.
Prophylaxis
Prophylaxis against pneumocystis pneumonia should be given to all patients with a history of the infection. Prophylaxis against pneumocystis pneumonia should also be considered for severely immunocompromised patients. Prophylaxis should continue until immunity recovers sufficiently. It should not be discontinued if the patient has oral candidiasis, continues to lose weight, or is receiving cytotoxic therapy or long-term immunosuppressant therapy.
Co-trimoxazole by mouth is the drug of choice for prophylaxis against pneumocystis pneumonia. It is given in a dose of 960 mg daily or 960 mg on alternate days (3 times a week); the dose may be reduced to co-trimoxazole 480 mg daily to improve tolerance.
Inhaled pentamidine isetionate is better tolerated than parenteral pentamidine. Intermittent inhalation of pentamidine isetionate is used for prophylaxis against pneumocystis pneumonia in patients unable to tolerate co-trimoxazole. It is effective but patients may be prone to extrapulmonary infection. Alternatively, dapsone 100 mg daily (section 5.1.10) can be used. Atovaquone 750 mg twice daily has also been used for prophylaxis [unlicensed indication].
ATOVAQUONE
Indications treatment of mild to moderate Pneumocystis jirovecii (Pneumocystis carinii) pneumonia in patients intolerant of co-trimoxazole
Cautions initial diarrhoea and difficulty in taking with food may reduce absorption (and require alternative therapy); other causes of pulmonary disease should be sought and treated; elderly; interactions: Appendix 1 (atovaquone)
Hepatic impairment manufacturer advises caution — monitor more closely
Renal impairment manufacturer advises caution — monitor more closely
Pregnancy manufacturer advises avoid unless potential benefit outweighs risk — no information available
Breast-feeding manufacturer advises avoid
Side-effects nausea, diarrhoea, vomiting; headache, insomnia; fever; anaemia, neutropenia, hyponatraemia; rash, pruritus; also reported, Stevens-Johnson syndrome
Dose
750 mg twice daily with food (particularly high fat) for 21 days; CHILD not recommended
Wellvone® (GSK) 
Suspension, sugar-free, atovaquone 750 mg/5 mL, net price 226 mL (tutti-frutti-flavoured) = £486.37. Label: 21
PENTAMIDINE ISETIONATE
Indications see under Dose (should only be given by specialists)
Cautions risk of severe hypotension following administration (monitor blood pressure before starting treatment, during administration, and at regular intervals, until treatment concluded; patient should be lying down when receiving drug parenterally); hypokalaemia, hypomagnesaemia, coronary heart disease, bradycardia, history of ventricular arrhythmias, concomitant use with other drugs which prolong QT-interval; hypertension or hypotension; hyperglycaemia or hypoglycaemia; leucopenia, thrombocytopenia, or anaemia; carry out laboratory monitoring according to product literature; care required to protect personnel during handling and administration; interactions: Appendix 1 (pentamidine isetionate)
Hepatic impairment manufacturer advises caution
Renal impairment reduce intravenous dose for pneumocystis pneumonia if creatinine clearance less than 10 mL/minute: in life-threatening infection, use 4 mg/kg once daily for 7–10 days, then 4 mg/kg on alternate days to complete course of at least 14 doses; in less severe infection, use 4 mg/kg on alternate days for at least 14 doses
Pregnancy manufacturer advises avoid unless essential
Breast-feeding manufacturer advises avoid unless essential — no information available
Side-effects severe reactions, sometimes fatal, due to hypotension, hypoglycaemia, pancreatitis, and arrhythmias; also leucopenia, thrombocytopenia, acute renal failure, hypocalcaemia; also reported: azotaemia, abnormal liver-function tests, anaemia, hyperkalaemia, nausea and vomiting, dizziness, syncope, flushing, hyperglycaemia, rash, and taste disturbances; Stevens-Johnson syndrome reported; on inhalation, bronchoconstriction (may be prevented by prior use of bronchodilators), cough, and shortness of breath; discomfort, pain, induration, abscess formation, and muscle necrosis at injection site
Dose
Treatment of Pneumocystis jirovecii (Pneumocystis carinii) pneumonia, by intravenous infusion, 4 mg/kg once daily for at least 14 days
Prophylaxis of Pneumocystis jirovecii (Pneumocystis carinii) pneumonia, by inhalation of nebulised solution (using suitable equipment — consult product literature), 300 mg every 4 weeks or 150 mg every 2 weeks [unlicensed for primary prevention]
Visceral leishmaniasis (kala-azar, section 5.4.5), by deep intramuscular injection, 3–4 mg/kg on alternate days to max. total of 10 injections; course may be repeated if necessary
Cutaneous leishmaniasis, by deep intramuscular injection, 3–4 mg/kg once or twice weekly until condition resolves (but see also section 5.4.5)
Trypanosomiasis, by deep intramuscular injection or intravenous infusion, 4 mg/kg daily or on alternate days to total of 7–10 injections
Note Direct intravenous injection should be avoided whenever possible and never given rapidly; intramuscular injections should be deep and preferably given into the buttock
Pentacarinat® (Sanofi-Aventis) 
Injection, powder for reconstitution, pentamidine isetionate, net price 300-mg vial = £31.77
Caution in handling Pentamidine isetionate is toxic and personnel should be adequately protected during handling and administration — consult product literature
Note Pentacarinat® Injection (dissolved in water for injection) may be used for nebulisation
5.5 Anthelmintics
Advice on prophylaxis and treatment of helminth infections is available from:
| Birmingham | (0121) 424 0357 |
| Scottish Centre for Infection and Environmental Health (registered users of Travax only) | (0141) 300 1100 (weekdays 12–5 p.m. only) |
| Liverpool | (0151) 705 3100 |
| London | 0845 155 5000 (treatment) |
5.5.1 Drugs for threadworms
(pinworms, Enterobius vermicularis)
Anthelmintics are effective in threadworm infections, but their use needs to be combined with hygienic measures to break the cycle of auto-infection. All members of the family require treatment.
Adult threadworms do not live for longer than 6 weeks and for development of fresh worms, ova must be swallowed and exposed to the action of digestive juices in the upper intestinal tract. Direct multiplication of worms does not take place in the large bowel. Adult female worms lay ova on the perianal skin which causes pruritus; scratching the area then leads to ova being transmitted on fingers to the mouth, often via food eaten with unwashed hands. Washing hands and scrubbing nails before each meal and after each visit to the toilet is essential. A bath taken immediately after rising will remove ova laid during the night.
Mebendazole is the drug of choice for treating threadworm infection in patients of all ages over 2 years. It is given as a single dose; as reinfection is very common, a second dose may be given after 2 weeks.
MEBENDAZOLE
Indications threadworm, roundworm, whipworm, and hookworm infections
Cautions interactions: Appendix 1 (mebendazole)
Note The package insert in the Vermox® pack includes the statement that it is not suitable for women known to be pregnant or children under 2 years
Pregnancy manufacturer advises toxicity in animal studies
Breast-feeding amount too small to be harmful but manufacturer advises avoid
Side-effects abdominal pain; less commonly diarrhoea, flatulence; rarely hepatitis, convulsions, dizziness, neutropenia, urticaria, alopecia, rash (including Stevens-Johnson syndrome and toxic epidermal necrolysis)
Dose
Threadworms, ADULT and CHILD over 2 years, 100 mg as a single dose; if reinfection occurs second dose may be needed after 2 weeks; CHILD under 2 years, see BNF for Children
Whipworms, ADULT and CHILD over 2 years, 100 mg twice daily for 3 days; CHILD under 2 years, see BNF for Children
Roundworms — section 5.5.2
Hookworms — section 5.5.4
5.5.2 Ascaricides
(common roundworm infections)
Mebendazole (section 5.5.1) is effective against Ascaris lumbricoides and is generally considered to be the drug of choice; the usual dose is 100 mg twice daily for 3 days or 500 mg as a single dose [unlicensed single dose].
Levamisole [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies) is an alternative when mebendazole cannot be used. It is very well tolerated; mild nausea or vomiting has been reported in about 1% of treated patients; it is given as a single dose of 120–150 mg in adults.
5.5.3 Drugs for tapeworm infections
Taenicides
Niclosamide [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies) is the most widely used drug for tapeworm infections and side-effects are limited to occasional gastro-intestinal upset, lightheadedness, and pruritus; it is not effective against larval worms. Fears of developing cysticercosis in Taenia solium infections have proved unfounded. All the same, an antiemetic can be given before treatment and a laxative can be given 2 hours after niclosamide.
Praziquantel [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies) is as effective as niclosamide and is given as a single dose of 5–10 mg/kg after a light breakfast (a single dose of 25 mg/kg for Hymenolepis nana).
Hydatid disease
Cysts caused by Echinococcus granulosus grow slowly and asymptomatic patients do not always require treatment. Surgical treatment remains the method of choice in many situations. Albendazole [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies) is used in conjunction with surgery to reduce the risk of recurrence or as primary treatment in inoperable cases. Alveolar echinococcosis due to E. multilocularis is usually fatal if untreated. Surgical removal with albendazole cover is the treatment of choice, but where effective surgery is impossible, repeated cycles of albendazole (for a year or more) may help. Careful monitoring of liver function is particularly important during drug treatment.
5.5.4 Drugs for hookworms
(ancylostomiasis, necatoriasis)
Hookworms live in the upper small intestine and draw blood from the point of their attachment to their host. An iron-deficiency anaemia may occur and, if present, effective treatment of the infection requires not only expulsion of the worms but treatment of the anaemia.
Mebendazole (section 5.5.1) has a useful broad-spectrum activity, and is effective against hookworms; the usual dose is 100 mg twice daily for 3 days. Albendazole [unlicensed] (available from ‘special-order’ manufacturers or specialist importing companies) given as a single dose of 400 mg, is an alternative.
5.5.5 Schistosomicides
(bilharziasis)
Adult Schistosoma haematobium worms live in the genito-urinary veins and adult S. mansoni in those of the colon and mesentery. S. japonicum is more widely distributed in veins of the alimentary tract and portal system.
Praziquantel [unlicensed] is available from Merck Serono (Cysticide®) and is effective against all human schistosomes. The dose is 20 mg/kg followed after 4–6 hours by one further dose of 20 mg/kg (20 mg/kg given 3 times on one day for S. japonicum infections). No serious adverse effects have been reported. Of all the available schistosomicides, it has the most attractive combination of effectiveness, broad-spectrum activity, and low toxicity.
Hycanthone, lucanthone, niridazole, oxamniquine, and sodium stibocaptate have now been superseded.
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