CoTrimoxazole

CoTrimoxazole is a rational combination of two antifolate drugs,

1. Pyrimidine Analogue : Trimethoprim.
2. Sulfonamide: Sulfamethoxazole.

used in treatment of various diseases where alone drug fails.

• CoTrimoxazole name itself indicates “ COmbination of TRIMethoprim and SulfamethOXAZOLE”.
• This combinations offers “Synergistic Effect” hence the benefit is more than used alone.

Mechanism of Action:

• These drugs attack the bacterial folic acid synthesis pathway at different steps and prevent bacterial folic acid synthesis leading to a “Bactericidal Effect”.
• Sulfamethoxazole inhibits bacterial enzyme “Folate Synthtase”  and prevents formation of “Dihydrofolic acid from PABA (Para Amino Benzoic Acid).
• Trimethoprim inhibits bacterial enzyme “Dihydrofolate Reductase” and prevents conversion of “Dihydrofolic acid to Tetrahydrofolic acid.”.

Dose Combination:

• This is a fixed dose combination that comes in 1:5 ratio of Trimethoprim and Sulfamethoxazole i.e. 80 mg of Trimethoprim is combined with 400 mg of Sulfamethoxazole.
• Double dose DS combination combines 160 mg of Trimethoprim and 800 mg of Sulfamethoxazole.
• Lower dose or half dose combines 40 mg of Trimethoprim and 200 mg of Sulfamethoxazole.

Benefits of CoTrimoxazole:

• Produces synergistic effect “Two drugs acting at different sites to produce similar response.”
• Spectrum of antimicrobial activity is greater than that of sulfonamide alone
• Development of resistance is slow.

Why CoTrimoxazole is a rational combination?

• Both drugs have similar activity i.e Antibacterial.
• Half lives of both drugs are almost similar i.e. Sulfamethoxazole 10 Hrs and Trimethoprim 8 Hrs.
• They have different mechanism of action but similar pharmacokinetic profiles.

Pharmacokinetics of CoTrimoxazole

Component	Tmax (h)	Vd (L)	Protein binding	t1/2 (h)	Excretion
Sulfamethoxazole	1-4	20	66%	8-10	Renal
Trimethoprim	1-4	130	42-45%	10	Renal

Uses:

1. Urinary tract infection
2. Respiratory tract infection
3. Bacterial dysentery
4. Skin infections & burns.
5. Malaria
6. Travelers diarrhea.

Adverse Effects:

1. Crystaluria – causing kidney damage
2. Kernicterus(Bilirubin induced brain dysfunction) in foetus & neonates
3. Hypersensitivity reaction and skin rashes
4. Aplastic anaemia
5. Steven Johnson’s syndrome (SJS)

Contraindications:

1. Known hypersensitivity.
2. Pregnancy.
3. Neonates bellow 6 weeks.
4. Hepatic failure.
5. Renal Failure.

Market Brands:

1. Bactrim.
2. Septran.

Note:

• Combination of Trimethoprim and Sulfadiazine is called as “CoTrimazine”