Domperidone Bioavailabilty of Domperidone is decreased by pretreatment with cimetidine or alkali

Domperifdone may reduce the hypoprolactinemic effect of Bromocriptine

The GIT actions of Domperidone may be antagonised by antimuscarinics an opoid analgesics.

Domperidone produces a rise in thyroid hormone in hypothyroid women.

Domperidone partially inhibits apomorphine stimulated growth hormone rises.

Chronic alcoholics are at particular risk of liver damage following overdose.

Paracetamol Alcohol markedly reduces the metaboic activation of Paracetamol.

Anticholinergic may delay the onset of Paracetamol without effecting their pharmacoligical action.

Betablockers such as Propranolol appears to inhibit the enzyme systems responsible for the glucordination of paracetamol resulting in increased pharmacological effects.

Oral contraceptives appear to increase the glucoordinatin of Paracetamol resulting in increased plasma clearance and decreased half life.

Probenecid may increase the therapeutic effectiveness of paracetamol slightly

Effects of diuretics may be decreased because paracetamol may decrease renal prostagladin excretion and decrease plasma renin activity.

Migraine

Paracetamol

Hemolytic anemia, neutropenia, pancytopenia, agranuocytosis, thrombocytopenia, skin eruptions, urticarial and erythematous skin reactions, fever, hypoglycemic coma, jaundice.

Domperidone

Hypoprolactinemia, galactorrhea, breast enlargement and soreness, reduced libido, drymouth, headache, nervousness, drowsiness, diarrhea, skin rash, and itch, increased serum prolactin, (more in females than males). Rarely, sedation, extapyrimidal dystonic reactions, parkinsonisms and tardive dyskinesia.

Hypersensitivity to paracetamol, domperidone or any of the constituents.

Special precautions:

Paracetamol -To be used with caution in patients with severe acute and decompensated liver disease because the half-life of paracetamol will be prolonged in such cases.

Patients with chronic renal failure,

Paracetamol conjugates gets accumulated.

Regular use to be avoided in patients with analgesic neuropathy

Not recomended for use during pregnancy.

Domperidone -Not recomended for use in neonates

Not recommended for use during pregnancy

Domperidone may precipitate galatorrhea and improve postnatal lactation

Indication-

Migraine 

Dosage:

Adults- 1-2 tablets , 4 hourly .Max 8 tablets per day.

Children: not recommended.

Pharmacology:

Paracetamol

Paracetamol has been used in the treatment of migraine and is often effective for mild to moderate attacks. Its mechanism of action is not clearly understood, but it may work by inhibiting the prostaglandin production centrally, as opposed to peripheral action of salicylates

Domperidone

Domperidone has been tried to abort attacks in migraine. but there are no comparitive studies to this effect.. However a combination of domperidone with paracetamol has proved effective in shortening the duration of migraine headache.

Pharmacokinetics:

Paracetamol

Paaracetamol is absorbed rapidly from the GIT and is distributed through out most body tissues. The absolute bioavailability is about 80% and is independent of dose in the range of 5-20mg/kg.The mean plasma life is 1.25- 3 hrs, but may be increased by liver damage and following overdose.

Approximately 85% of the oral dose appear in the urine within 24 hrs. of administration of therapeutic dose of paracetramol and is excreted inchanged in the urine.

Domperidone

About 93% of the domperidone is rapidly absorbed following oral administration. The peak plasma concentration is reached within 30 minutes of oral administration and is in the range of 15-19ng/ml.

Administering the drug 90 minutes after meals may increase the bioavailability. In healthy volunteers given 40mg of domperidone orally , 31-66% of the activity were recovered in urine and feces respy over a period of 4 days.

Administering drug before meals increases bioavilability.

Not recomended for use during pregnancy