Contraindications: Severe liver disease; Chronic alcoholism
Special Precautions: May impair ability to drive and operate machinery. Angle-closure glaucoma, urinary retention, prostatic hypertrophy or pyloroduodenal obstruction; epilepsy; hepatic impairment, in elderly & lactation. Because of potential drowsiness, Doxinate should be prescribed with caution to patients who drive automobiles or operate machinery.
Adverse Drug Reactions: Acute dystonic reactions and long-lasting impaired consciousness in child. CNS depression including slight drowsiness to deep sleep, lassitude, dizziness, in coordination. Headache, psychomotor impairment and antimuscarinic effects.
Rarely rashes and hypersensitivity reactions, blood disorders, convulsions, sweating, myalgia, extrapyramidal effects, tremor, confusion, tinnitus, hypotension, hair loss. Severe peripheral neuropathies with long-term admin of large doses of Pyridoxine.
Other possible side effects of doxylamine succinate include a dry mouth, throat or nose, decreased coordination and blurred vision. In most cases, these side effects are not too bothersome to the patients.
Drug Interactions: Doxylamine enhances effects of CNS depressants e.g. alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytic sedatives and antipsychotics. Atropine, tricyclic antidepressants (TCAs), MAOIs. It can mask signs of ototoxicity caused by amino glycosides. INH, penicillamine and OC require greater pyridoxine dose. Pyridoxine reduces the effects of levodopa, phenobarb and phenytoin.
Pharmacodynamics: Doxylamine Succinate is one of the many sedating antihistamines used by itself as a short-term sedative, in combination with other drugs as a night-time cold and allergy relief drug, in combination with the analgesics paracetamol (acetaminophen) and codeine as an analgesic/calmative preparation, and is prescribed in combination with vitamin B6 (pyridoxine) to prevent morning sickness in pregnant women.
Pharmacokinetics Doxylamine is an antihistamine derived from monoethanolamine possessing antimuscarinic and pronounced sedative effects. Pyridoxine is a precursor of pyridoxal, which functions in the metabolism of carbohydrates, proteins and fats. It is essential in Hb formation and GABA synthesis within the CNS. It also aids in the release of glycogen stored in the liver and muscles.
Absorption, Distribution, Metabolism and Excretion: Randomized study in a two-way, open window, on the relative bioavailability and performed with 22 healthy women, the pharmacokinetics after ingestion of dose of two (2 x [10 mg + 10 mg]) Doxinate® (Doxylamine + Pyridoxine [10 mg + 10 mg]) tablets.
Among the non-fasting and fasting in patients was compared ingestion of food delayed the absorption of doxylamine and pyridoxine for about 5 hours. However, this delay did not affect the peak concentration or extent of absorption of doxylamine, since the Cmax and AUC were not discernible between treatments. But the peak concentration and extent of absorption of pyridoxine were significantly reduced in non-fasting. The effect of food on pyridoxine is more complex, since pyridoxine, pyridoxal and pyridoxal 5'-phosphate also contribute to the biological activity.
Even if the peak concentration of Pyridoxal is somewhat reduced, peak concentrations of pyridoxal 5'-phosphate are slightly raised, and the AUC values for pyridoxal and pyridoxal 5'-phosphate is not affected in subjects not fasting. The average peak concentrations of total pyridoxine is slightly reduced, absorption measured by AUC is not affected by the treatment
Doxylamine Succinate: Doxylamine is metabolized in the liver by N-dealkylation to its major metabolites. Doxylamine N-desmethyl and N, N-didesméthyldoxylamine, which are excreted by the kidneys.
Mechanism of Action: Doxylamine is an antihistamine derived from monoethanolamine possessing antimuscarinic and pronounced sedative effects. Pyridoxine is a precursor of pyridoxal, which functions in the metabolism of carbohydrates, proteins and fats. It is essential in Hb formation and GABA synthesis within the CNS. It also aids in the release of glycogen stored in the liver and muscles.
Pyridoxine hydrochloride: Pyridoxine is readily absorbed in the gastrointestinal tract, mainly in the jejunum. Pyridoxine is metabolized primarily in the liver after phosphorylation, the active metabolite. Main, pyridoxal 5'-phosphate is released into the circulation (which is at least 60% of the Vitamin B6 outstanding) and is highly protein bound, mainly to albumin.
The metabolic pathway of pyridoxine is complex and involves the formation of primary and secondary metabolites and Interconversion to pyridoxine.
All metabolites, including pyridoxal, have biological activity. The 4-pyridoxic acid, the major metabolite is inactive and is excreted in urine.
Dosage The dosage safety of Doxinate – Doses ranging from 0.1 to 2 mg/Kg body weight can be prescribed (Upto 12 tablets a day of Doxinate can be taken safely by a normal weight patient).