Zid Kid

Uses

Tuberculosis

Zid Kid is also used to associated treatment for these conditions: Active Tuberculosis, Mycobacterium kansasii infection, Late phase TuberculosisCholestatic pruritus, MRSA Infection, Prosthetic Joint Infection, Asymptomatic Neisseria meningitidis carrier of the nasopharynx, Initial phase Tuberculosis, Late phase Tuberculosis, Antibacterial therapy

How Zid Kid works

Isoniazid is a prodrug and must be activated by bacterial catalase. Specficially, activation is associated with reduction of the mycobacterial ferric KatG catalase-peroxidase by hydrazine and reaction with oxygen to form an oxyferrous enzyme complex. Once activated, isoniazid inhibits the synthesis of mycoloic acids, an essential component of the bacterial cell wall. At therapeutic levels isoniazid is bacteriocidal against actively growing intracellular and extracellular Mycobacterium tuberculosis organisms. Specifically isoniazid inhibits InhA, the enoyl reductase from Mycobacterium tuberculosis, by forming a covalent adduct with the NAD cofactor. It is the INH-NAD adduct that acts as a slow, tight-binding competitive inhibitor of InhA.

Rifampin acts via the inhibition of DNA-dependent RNA polymerase, leading to a suppression of RNA synthesis and cell death.

Dosage

Zid Kid dosage

Body weight <50 kg: 3 tab of 150/100 once daily or 1 tab of 450/300 once daily

Body weight >50 kg: 2 tab of 300/150 once daily.

Hepatic impairment: Max: 8 mg/kg daily.

Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals.

Preparation Of Solution For IV Infusion: Reconstitute the lyophilized powder by transferring 10 mL of sterile water for injection to a vial containing 600 mg of rifampin for injection. Swirl vial gently to completely dissolve the antibiotic. The reconstituted solution contains 60 mg rifampin per mL and is stable at room temperature for up to 30 hours. Prior to administration, withdraw from the reconstituted solution a volume equivalent to the amount of rifampin calculated to be administered and add to 500 mL of infusion medium. Mix well and infuse at a rate allowing for complete infusion within 3 hours. Alternatively, the amount of rifampin calculated to be administered may be added to 100 mL of infusion medium and infused in 30 minutes.

Dilutions in dextrose 5% for injection (D5W) are stable at room temperature for up to 8 hours and should be prepared and used within this time. Precipitation of rifampin from the infusion solution may occur beyond this time. Dilutions in normal saline are stable at room temperature for up to 6 hours and should be prepared and used within this time. Other infusion solutions are not recommended.

Side Effects

Unwanted effects which may occur during continuous daily or intermittent therapy: Rifampicin: Rifampicin may cause reddish discolouration of body fluids and occasionally other body secretions eg, urine, sputum, lacrimal fluid, faeces, saliva and sweat. It may permanently discolour soft contact lenses.

Hepatic Effects: Very common (>10%) is an asymptomatic increase in liver enzymes; severe life-threatening hepatic reactions eg, hepatic failure and acute fulminant hepatitis are uncommon (>0.1% and <1%). In isolated cases (<0.01 %), a fatal outcome was observed.

Renal Effects: Elevations of BUN and serum uric acid, haemolysis, haematuria, interstitial nephritis, renal insufficiency. Gastrointestinal Effects: Nausea, abdominal pains, vomiting or diarrhoea, pseudomembranous colitis.

Central and Peripheral Nervous System Effects: Tiredness, drowsiness, headache, dizziness, ataxia, mental confusion, muscular weakness, visual disturbances. Haematological Changes: Leucopenia, eosinophilia, thrombocytopenia and thrombocytopenic purpura. Effects on Skin and Appendages: Flushing, itching with or without skin rash, urticaria, reddening of the eyes, exudative conjunctivitis or generalised hypersensitivity reactions involving the skin eg, exfoliative dermatitis, Lyell's syndrome and pemphigoid reactions. Endocrine Effects: Disturbances in the menstrual cycle, induction of crisis in Addison patients. Unwanted effects chiefly occurring during intermittent therapy or upon resumption of treatment after temporary interruption

Toxicity

LD₅₀ 100 mg/kg (Human, oral). Adverse reactions include rash, abnormal liver function tests, hepatitis, peripheral neuropathy, mild central nervous system (CNS) effects. In vivo, Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate; high doses interfere with the coenzyme function of the latter.

LD₅₀=1570 mg/kg (rat), chronic exposure may cause nausea and vomiting and unconsciousness

Precaution

Use of isoniazid should be carefully monitored in the following:

• Daily users of alcohol. Daily ingestion of alcohol may be associated with a higher incidence of isoniazid hepatitis.
• Patients with active chronic liver disease or severe renal dysfunction.
• Age > 35.
• Concurrent use of any chronically administered medication.
• History of previous discontinuation of isoniazid.
• Existence of peripheral neuropathy or conditions predisposing to neuropathy. Pregnancy.
• Injection drug use.
• Women belonging to minority groups, particularly in the post-partum period.
• HIV seropositive patients.

Interaction

May reduce effectivity of hormonal contraceptives. Reduced absorption with antacids. May decrease plasma concentrations of antivirals (e.g. atazanavir, darunavir, fosamprenavir), atovaquone with rifampicin. Rifampicin may reduce serum levels of anticonvulsants (e.g. phenytoin), antiarrhythmics (e.g. disopyramide), oral anticoagulants, antifungals (e.g. ketoconazole), barbiturates, ?-blockers, Ca channel blockers (e.g. diltiazem), chloramphenicol, clarithromycin, corticosteroids, ciclosporin, cardiac glycosides, clofibrate, dapsone, diazepam, doxycycline, fluoroquinolones (e.g. ciprofloxacin), haloperidol, oral hypoglycemic agents (sulfonylureas), levothyroxine, methadone, narcotic analgesics, progestins, quinine, tacrolimus, theophylline, TCAs (e.g. amitriptyline, nortriptyline) and zidovudine. Increased risk of hepatotoxicity with halothane.

Isoniazid may inhibit the metabolism of anticonvulsants (e.g. carbamazepine, phenytoin), benzodiazepines (e.g. diazepam), haloperidol, ketoconazole, theophylline, and warfarin. May enhance the CNS effects of meperidine, cycloserine, and disulfiram with isoniazid. Loss of glucose control in patients on oral hypoglycaemics with isoniazid.

Elimination Route

Readily absorbed following oral administration; however, may undergo significant first pass metabolism. Absorption and bioavailability are reduced when isoniazid is administered with food.

Well absorbed from gastrointestinal tract.

Half Life

Fast acetylators: 0.5 to 1.6 hours. Slow acetylators: 2 to 5 hours.

3.35 (+/- 0.66) hours

Clearance

• 0.19 +/- 0.06 L/hr/kg [300 mg IV]
• 0.14 +/- 0.03 L/hr/kg [600 mg IV]

Elimination Route

From 50 to 70 percent of a dose of isoniazid is excreted in the urine within 24 hours.

Less than 30% of the dose is excreted in the urine as rifampin or metabolites.

Pregnancy & Breastfeeding use

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks

Contraindication

Known or suspected hypersensitivity to rifamycins and/or to INH, and/or to any of the excipients including a history of drug-induced hepatitis; acute liver diseases, regardless of their origin; peripheral neuritis.

Special Warning

Geriatric Use: Clinical studies of Rifampicin did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Caution should therefore be observed in using rifampin in elderly patients.

Acute Overdose

Nausea, vomiting, abdominal pain, pruritus, headache, and increasing lethargy will probably occur within a short time after ingestion; unconsciousness may occur when there is severe hepatic disease. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange discoloration of the skin, urine, sweat, saliva, tears, and feces will occur, and its intensity is proportional to the amount ingested.

Liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage; bilirubin levels may increase and jaundice may develop rapidly. Hepatic involvement may be more marked in patients with prior impairment of hepatic function. Other physical findings remain essentially normal. A direct effect upon the hematopoietic system, electrolyte levels, or acid-base balance is unlikely.

Facial or periorbital edema has also been reported in pediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.

Storage Condition

Should be stored in cool and dry place

Innovators Monograph

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