Background

Trimethoprim-sulfamethoxazole (TMP-SMX), also known as Septra, Bactrim, and

cotrimoxazole, is a key antibiotic for prophylaxis and treatment of several HIV-related
illnesses. It is the most effective prophylaxis and the first-line treatment for Pneumocystis
jiroveci pneumonia (PCP). In addition, it is effective in preventing toxoplasmosis encephalitis
in severely immunocompromised patients who have evidence of previous infection, and it is
effective against certain bacterial infections. TMP-SMX also is quite inexpensive, which is a
rarity in the world of HIV treatment. Because of its effectiveness and availability, it is used
widely throughout the world. However, adverse reactions to TMP-SMX and other sulfa drugs
occur in a high proportion of HIV-infected patients (roughly 25%), and such reactions may
limit treatment.

Desensitization to TMP-SMX should be considered when there are no reasonable or available

alternatives and the patient has not experienced severe reactions (eg, Stevens-Johnson
syndrome) to sulfa drugs. Several methods of desensitizing patients with previous reactions
to TMP-SMX have been tried. These methods vary in starting dosage and length of dosage
escalation, but success rates are around 80% in most cases and may be higher in those
patients with <200 CD4 cells/µL.

S: Subjective
The patient reports a previous adverse reaction to sulfa drugs, such as erythema, pruritus, or
rash. The patient has no history of anaphylaxis, Stevens-Johnson syndrome, or toxic
epidermal necrolysis, and no reaction involving vesiculation, desquamation, ulceration,
exfoliative dermatitis, etc.

O: Objective
CD4 count <200 cells/µL, or other important indication for TMP-SMX.

A: Assessment
Reaction to sulfa, possibly reversible with desensitization protocol.

P: Plan
Begin 9- to 13-day desensitization protocol, starting with pediatric oral suspension, which
contains 40 mg of TMP and 200 mg of SMX per 5 mL (1 teaspoon). Gradually increase the
dosage according to the protocol.

If there is any question about the severity of a previous reaction, have the patient take the
initial morning dose in the clinic so that the patient may be monitored for 3-4 hours before
going home. (This assumes that emergency treatment, including IV access materials and IV
fluids, antihistamines, and steroids, are readily available.)

Treat with an antihistamine medication 1 day before starting the desensitization regimen and
continue daily until the dose escalation is completed.
More rapid desensitization protocols are available (see " References " below) for patients
urgently needing treatment with TMP-SMX.

Desensitization Regimen
Use commercially available pediatric suspension (containing TMP 8 mg and SMX 40 mg per
mL), followed by double-strength tablets, as follows:

Table 1. Sulfa Desensitization Regimen

Dosage
Days Volume or Tablet
(TMP/SMX)

1-3 8 mg/40 mg 1 mL
3-6 16 mg/80 mg 2 mL
5-9 40 mg/200 5 mL
mg
7-12 80 mg/400 1/2 double-strength tablet (or 1 single-
mg strength tablet)
9-10 and 160 mg/800 1 double-strength tablet
thereafter mg

In the event of mild reaction: If the patient experiences a mild reaction or itching, the same
dosage should be given for an additional day. If the reaction diminishes, the patient may
advance to the next dosage; if the reaction worsens, the TMP-SMX should be discontinued.
Antihistamines or antipyretics may be used to treat symptoms of mild reactions.

In case of severe reaction: the desensitization regimen should be discontinued.

Patient Education
For home desensitization regimen
Explain the benefits of using TMP-SMX. Be sure the patient understands and is able to follow
instructions.

• Measure your dose carefully and take it each morning, followed by a glass (6-8 oz) of
water. (The patient should do a demonstration, if possible, using the syringe that will
be used for the actual measuring at home.)
• TMP-SMX can make you very ill unless you pay attention to any problems you have.
It is extremely important that you check your temperature each afternoon. If your
temperature is more than 100.5° F by mouth, stop taking the drug and contact your
clinician. Note: If you have shaking chills, check your temperature as soon as the
shaking stops, and contact the clinic. If you continue the medication despite a red
rash and/or fever, serious illness or a life-threatening reaction may occur. Report any
adverse event immediately.
• Stop the regimen and return to the clinic or emergency room immediately if you
develop a red rash, blisters on your skin or in your mouth, or vomiting. Check your
skin each evening, and any time you notice itching.
If you have mild itching or a faint rash, you can take diphenhydramine (Benadryl) 25-50 mg.
every 4 hours as needed. If this persists, stay with the same dosage for an additional day;
and call or go to the clinic if you have questions or concerns.

• Call or go to the clinic for alternate dosage instructions in the event of persistent
itching without rash.

For all desensitized patients

• After desensitization is complete, continue to take the daily dosage. If the drug is
stopped, the entire regimen may have to be repeated.

Sulfa Desensitization
Long Protocol

For the first 5 days dilute the

standard TMP40/SMX200/5ml
suspension and use as follows.

Solution preparation:

One (1) ml TMP40/SMX200 +

9ml saline in 10ml syringe =
4mg/ml SMX.

Dosing

Day 1, take 0.25ml = 1mg SMX

Day 2, take 0.5ml = 2mg SMX
Day 3, take 1ml = 4mg SMX
Day 4, take 2ml = 8mg SMX
Day 5, take 4ml =16mg SMX

Then switch to standard susp

and use full strength:

Day 6, take 0.5ml = 20mg SMX

Day 7, take 1ml = 40mg SMX
Day 8, take 2ml = 80mg SMX
Day 9, take 4ml =160mg SMX

Then switch to tabs as follows:

Day 10, take 1 SS tab (adults) or

1/2 SS tab (<12 y/o)

If no rash, begin 1 SS tab (adults)

or 1/2 SS tab or 5ml standard
susp (<12 y/o) BID for 30 days.

After 30 days continuous therapy

w/o rash, may give full dose.

Source: Purdy, Ann Int Med,

1984:100; 512-14
© 2000-2006 Pharmacy OneSource, Inc.

การแพ้ยาแบบ type IV Hypersensitivity Reaction หรือ Delayed type

Hypersensitivity เป็นปฏิกิริยาที่เกิดจากการเกิด inflammatory reaction โดยผ่าน
perivascular lymphocytes และ macrophages 1
แนวทางการรักษาการแพ้ยาแบบ Deleyed type Hypersensitivity อย่างหนึ่งคือ การทำา
desensitization
หลักการ desensitization เป็นการเพิ่มขนาดยาให้กับผู้ป่วยทีละน้อย จนผู้ป่วยสามารถทนยาได้ แม้ไม่ทราบกลไกที่
เกี่ยวกับระบบคุ้มกันของ Desensitization แต่เชื่อว่าวิธีดังกล่าวทำาให้ mast cells ไม่ตอบสนองต่อแอนติเจน
จำาเพาะ
การทำา desensitization ควรทำาในโรงพยาบาลที่มีความพร้อมในการช่วยชีวิตผู้ป่วย การให้ยา
premedication ด้วย antihistamine หรือ corticosteroid ไม่มีประโยชน์เพราะจะไปบดบัง
อาการแพ้ยาจาก IgE2
ในการทำา Rapid desensitization มีความจำาเป็นอย่างยิ่งต่อผู้ป่วยที่มีประวัติการแพ้ยา หรือมีผล positive
skin test และไม่มีทางเลือกอื่นในการรักษา จำาเป็นที่ต้องใช้ยาตัวนั้นในการรักษา เช่น การทำา desensitization
ของยา penicillin และ foreign serum1
Cotrimoxazole desensitization
Cotrimaxazole เป็นยาที่ใช้ในการจัดการผู้ป่วยที่มีภาวะภูมิคุ้มกันบกพร่อง โดยใช้ในการป้องกันการติดเชื้อ
Pneumocistis carinii, toxoplasmosis and diarrhea ( Isospora belli ) โดยมี
การศึกษาการทำา desensitization
ยา Cotrimoxazole ในผู้ป่วยที่มีภาวะภูมิคุ้มกันบกพร่อง ตั้งแต่ปี ค.ศ. 1988 จึงทำาให้มีหลากหลาย protocol
ซึ่งขอยกตัวอย่างดังนี้
1. การทำา desensitization ประมาณ 9 - 13 วัน 3

Days TMP/SMX (mg) Volume or tablet

1 – 3 80/40 1 ml.
3 – 6 16/80 2 ml.
5 – 9 40/200 5 ml.
7 – 12 80/400 ½ double-strenge tablet (or 1 single-strength tablet)
9 – 10 and thereafter 160/800 1 double-strength tablet

2. การทำา desensitization ประมาณ 2 วัน 4

DAY TIME SMZ (mg) TMP (mg)

1 9 AM. 4 0.8
11 AM 8 1.6
1 PM 20 4
5 PM. 40 8
2 9 AM. 80 16
3 PM. 160 32
9 PM. 200 40
3 9 PM. 400 80
Every day 400 80

3. การทำา desensitization ประมาณ 4 ชม. 5

hour Dose of TMP - 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.

คำาถามที่เกี่ยวข้องกับ desensitization ต่อยา cotrimoxazole ใน web site นี้ คือ คำาถามข้อที่

1025, 3321, 4337, 5594

เอกสารอ้างอิง
1. http://www.merck.com, accessed 24 พ.ย. 48
2. สมเกียรติ วัฒนศิรชิ ัยกุล. Antimicrobial Therapy. ภาวะติดเชื้อ. เม็ดทรายพริ้นติ้ง. กรุงเทพมหานคร.
เล่มที1
่ ; 892 –
893.
3. http://www.hiv.va.gov, accessed 21 พ.ย. 48
4. Dipiro J, et al. Desensitization. Pharmacotherapy A
Pathophysiologic Approach. Fifth edition. 1999; 1594 – 1595
5. Glukstein D , Ruskin J. Rapid Oral Desensitization to
Trimaetroprim-Sulfamethoxazole (TMP-SMZ): Use in Prophylaxis for
Pneumocystis carinii Pneumonia in Patients with AIDS Who were
Previously Intolerant to TMP-SMZ. Clinical Infectious Diseases. 1995;
20: 849 – 853.

ระยะเวลาในการสืบค้น : 2 ชัว่ โมง

Keywords : desensitization , cotrimoxazole, AIDS