WHO Model Prescribing Information: Drugs Used in HIV-Related Infections
(1999; 58 pages) View the PDF document
Table of Contents
View the documentPreface
Open this folder and view contentsOpportunistic infections
Close this folderRespiratory disease
View the documentPneumonia due to Pneumocystis carinii (PCP)
View the documentPulmonary tuberculosis
View the documentHistoplasmosis and coccidioidomycosis
View the documentAspergillosis
Open this folder and view contentsNeurological disorders
Open this folder and view contentsOpthalmological complications
Open this folder and view contentsFebrile illness
Open this folder and view contentsGastrointestinal tract/diarrhoeal disease
Open this folder and view contentsMucocutaneous and cutaneous eruptions
Open this folder and view contentsDrugs
View the documentBack Cover
 

Pneumonia due to Pneumocystis carinii (PCP)

The frequency of PCP varies world-wide, ranging from 64% in the US to <5% in reports from some areas in Africa, although some African studies suggest higher rates. The reason for this variability is uncertain, but may in part be due to under-reporting and under-diagnosis in developing countries or perhaps geographic variability. The most typical presenting symptoms of PCP in HIV-positive patients are a non-productive cough, dyspnoea on exertion and fever. The onset of illness is often subtle and many of these symptoms can develop slowly over a number of weeks. Chest X-rays may reveal extensive interstitial infiltration, a mild peri-hilar haze or may be normal. Whenever practicable, attempts should be made to identify the organism using induced sputum or broncho-alveolar washings. Mortality has been reduced significantly due to early recognition of disease, use of the most effective drug regimes and the inclusion of primary and secondary prophylaxis.

Treatment of PCP

Sulfamethoxazole (SMZ)/trimethoprim (TMP) has been shown to be the best regimen for both the treatment and prevention of PCP.

 

drug

dose

1st choice

sulfamethoxazole/trimethoprim oral
or
sulfamethoxazole/trimethoprim IV

SMZ 75 mg/kg
TMP 15 mg/kg
divided doses
daily for 2-3 weeks

2nd choice

clindamycin IV/oral
and primaquine oral
or
dapsone (oral) and
trimethoprim (IV/oral)

600 mg 4 x day
15 mg OD

100 mg OD
20 mg/kg OD (divided doses)
daily for 2-3 weeks

If the patient is unable to tolerate these regimens, pentamidine given intravenously can be used.

Signs of improvement may not be evident for 4-8 days, and treatment should be maintained for 2-3 weeks. For mild to moderate disease oral drugs can be used throughout the treatment (2 week course); in severe disease, treatment is normally administered intravenously during the first 7-10 days (total 3 weeks course). However, if the patient is receiving second line treatment, components that are not available in the intravenous formulation are administered orally.

When no improvement is evident after 7-10 days, clinicians often resort to switching to one of the other regimens. The severe toxicity of pentamidine compared to the other regimens has limited its use. This drug is now used only as a last resort. If switching to pentamidine is being considered, an overlap of two to three days should occur to allow pentamidine to accumulate in the body.

The first few days of antimicrobial treatment are critical since the decomposition of many dead parasites exacerbates the pre-existing inflammatory process and aggravates hypoxia. However, the risk of death at this stage can be substantially reduced especially in patients whose arterial oxygen tension (pO2) is less than 70 mmHg (9.33 kPa) if a corticosteroid - oral prednisolone or, when necessary intravenous methylprednisolone -is administered as soon as antimicrobial therapy is started. Prednisolone given orally at a dose of 40 mg twice daily for 5 days, followed by 40 mg daily for 5 days, and then 20 mg daily for 10 days is a regimen that has been used. It has not demonstrably increased the vulnerability of patients to other opportunistic infections, with the possible exception of candidiasis, herpes virus disease and cytomegalovirus disease.

Prophylaxis

In industrialised countries, every patient who has a CD4+ lymphocyte count of less than 200/mm3, or symptomatic disease (oral Candida, fevers, weight loss etc.) or another ADDS-defining illness such as Kaposi’s sarcoma, or has been successfully treated for pneumonia due to Pneumocystis carinii, should receive continuous prophylaxis. Various estimates place the 3-month relapse rate among patients not receiving prophylaxis following a course of treatment for PCP at 10% - 40%; about one in five such episodes is fatal. In developing countries, where PCP is much less common, there have been no efficacy trials for the use of sulfamethoxazole/trimethoprim as PCP prophylaxis, though early results indicate it may be of benefit in reducing other HIV-associated infections.

Prophylaxis for PCP

 

drug

dose

1st choice

sulfamethoxazole/trimethoprim oral

SMZ 800 mg
TMP 160 mg
OD

2nd choice

dapsone oral
or
dapsone oral
and pyrimethamine** oral2

50-100 mg OD*

100 mg 3 x week
25 mg 3 x week

3rd choice

sulfadoxine/pyrimethamine (Fansidar)

1-2 tablets weekly

4th choice

pentamidine (nebulised)

300 mg every 2-4 weeks

* the higher dose should be used if the patient is taking concurrent enzyme inducers e.g. rifampacin and/or drags which increase gastric pH e.g. antacids, didanosine (ddI)

** When pyrimethamine is used if the patient is borderline neutropenic i.e. neutrophil count <1.0 x 109/L folinic acid 15 mg orally should be given in conjunction

2 Dapsone and pyrimethamine should be used in patients that cannot tolerate sulfamethoxazole/trimethoprim with a CD4 count less than 100/mm3 and Toxoplasma gondii antibody positive.

Sulfamethoxazole/trimethoprim has been shown to be the best form of PCP prophylaxis and also provides protection against Toxoplasma encephalitis; therefore, every effort should be made to ensure that where possible patients receive it. A recent trial showed that patients were more likely to tolerate sulfamethoxazole/trimethoprim if a low dose was used (800 mg/160 mg) three times a week), and it was as effective as the higher doses, although a higher dose daily may be preferable if the patient has a CD4+ count less than 100/mm3 and is Toxoplasma gondii antibody positive. In patients that have experienced reactions to sulfamethoxazole/trimethoprim that are not considered serious (i.e. rash, fever, or mild elevations of liver function tests), either rechallenge or desensitisation should be attempted. It has been shown that in about 50% of patients this will allow continuation of sulfamethoxazole/trimethoprim.

Desensitisation schedule for sulfamethoxazole/trimethoprim

Sulfamethoxazole/trimethoprim has been shown to be the best agent for both the treatment and prophylaxis of PCP. It is therefore important that, where indicated, as many patients as possible receive sulfamethoxazole/trimethoprim and not other less effective medications. Desensitisation has been used as a method of increasing the number of patients able to tolerate sulfamethoxazole/trimethoprim.

Indications:

Patients who have a documented allergy, e.g. rash or itching due to sulfamethoxazole/trimethoprim and have failed rechallenge

Contraindications:

Patients who have had a serious reaction to sulfamethoxazole/ trimethoprim e.g. Stevens-Johnsons, anaphylaxis, hepatitis or pancreatitis.

Desensitisation of sulfamethoxazole/trimethoprim carried be done over a day as an inpatient or over 10 days an outpatient.

In patient desensitisation of sulfamethoxazole/trimethoprim

Time (hours)

dose sulfamethoxazole (TMP)/trimethoprim (SMZ)

0

0.004/0.02 mg*

1

0.04/0.2 mg*

2

0.4/2 mg*

3

4/20 mg*

4

40/200 mg*

5

160/800 mg*

* Dilute a solution containing 40 mg of TMP and 200 mg of SMZ per 5 ml.

Out patient desensitisation of sulfamethoxazole/trimethoprim

Day

mg

composition

1

2.4

1 ml 1 in 20 paediatric suspension

2

4.8

2 ml 1 in 20 paediatric suspension

3

9.6

4 ml 1 in 20 paediatric suspension

4

19.2

8 ml 1 in 20 paediatric suspension

5

28.8

0.6 ml paediatric suspension

6

60

1.25 ml paediatric suspension

7

120

2.5 ml paediatric suspension

8

240

5 ml paediatric suspension

9

480

10 ml paediatric suspension

10

480

One 480 mg tablet or half a 960 mg tablet

11

960

One 480 mg tablet or half a 960 mg tablet twice a day

Then continue with the regimen or Pneumocystis carinii pneumonia prophylaxis. If the regimen, to be used is sulfamethoxazole/trimethoprim (cotrimoxazole) 480 mg daily, stop at day 10 and continue at this dose.

If sulfamethoxazole/trimethoprim cannot be continued due to intolerance or severe side effects dapsone may be given although a small percentage of patients may show cross intolerance.

Nebulized pentamidine at the dosage of 300 mg every two weeks should be used in patients with a CD4+ count less than 100/mm3 if systemic therapy cannot be tolerated. Sulfadoxine/pyrimethamine (Fansidar), one tablet given once or twice a week, is useful in patients in whom compliance is considered to be a problem. However, it has been associated with hepatotoxicity, Stevens-Johnson syndrome and toxic epidermal necrolysis.

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