Pyrinate

Uses

For prophylaxis and symptomatic relief of nausea, vomiting, dizziness, motion sickness, radiation sickness and vertigo associated with diseases of vestibular motion sickness, radiation sickness and vertigo associated with diseases of vestibular system, morning sickness during pregnancy, drug induced nausea, vomiting induced by oral contraceptives or Estrogen preparations.

Pyrinate is also used to associated treatment for these conditions: Dizziness, Motion SicknessBackache, Dizziness, Fever, Headache, Hepatic; Functional Disturbance, Hepatitis, Iron Deficiency Anemia (IDA), Ketosis, Macrocytic anemia, Menière's Disease, Menstrual Distress (Dysmenorrhea), Metabolic Acidosis, Motion Sickness, Nausea and vomiting, Neuralgia, Sciatic, Neuritis, Neurological Conditions caused by B Vitamin Deficiency, Secondary anemia, Soreness, Muscle, Toothache, Toxinfectious state, Trigeminal Neuralgia (TN), Vitamin B1 deficiency, Vitamin B12 Deficiency, Vitamin B6 Deficiency, Vitamin Deficiency, Minor aches and pains, Minor pain, Nutritional supplementation, Supplementation, Vitamin supplementation, Wellness of the Liver

How Pyrinate works

Vomiting is a centrally regulated reflex mechanism that initiates from the vomiting center and the chemoreceptor trigger zone (CTZ) located in the medulla. Motion sickness is also regulated by CTZ. The blood-brain barrier near the CTZ is relatively permeable to circulating mediators and CTZ can transmit impulses to vomiting center located in the brainstem. Different receptors responding to different factors, including histamine, 5-HT, enkephalins, substance P, and dopamine, are expressed along the brainstem to activate respective pathways and contribute to the control of vomiting. Histamine H1 receptors are expressed on the vestibular nuclei and nucleus of the solitary tract (NTS) that are activated by motion sickness and stimuli from the pharynx and stomach. When activated, H1 receptor signaling from these nuclei is transmitted to the CTZ and vomiting centre.

Through its antagonistic action on the H1 receptors, meclizine primarily works by inhibiting signaling pathway transduction through histaminergic neurotransmission from the vestibular nuclei and NTS to the CTZ and medullary vomiting center. Meclizine may also decrease the labyrinth excitability and vestibular stimulation.

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

Dosage

Pyrinate dosage

The fixed-dose combination is recommended for oral administration-

Nausea & vomiting (including morning sickness in pregnancy): One tablet 1-2 times daily.

Motion sickness: One or two tablets one hour prior to journey. The dose may be repeated every 24 hours as indicated for the duration of journey.

Vertigo: One tablet 2 times daily or as directed by physician.

Labyrinthine and vestibular disturbances: The optimal dose of Meclizine Hydrochloride is usually 25 to 100 mg daily in divided doses, depending on the clinical response.

Radiation sickness: 50 mg (Meclizine Hydrochloride) administered 2 to 12 hours prior to radiation treatment. Pyridoxine Hydrochloride (vitamin B6) has been shown to be safe and effective in dosages of 50 to 200 mg per day.

contraceptive pill (ECP) : 25-50 mg, 1 hour before first ECP dose; repeat if needed in 24 hours.

Side Effects

Drowsiness, dry mouth, urinary retention in rare occasions, blurred vision has been reported. Sensory neuropathy reported with high dosage of Pyridoxine Hydrochloride given for extended periods.

Toxicity

The oral and intraperitoneal LD₅₀ in mouse are 1600 mg/kg and 625 mg/kg, respectively. The lowest published toxic dose (TDLo) in rats via the oral route is 800 mg/kg.

Symptoms of overdose mainly involve CNS depression with drowsiness, coma, and convulsions. Hypotension may also occur, particularly in the elderly. In children, anticholinergic effects and CNS stimulation, characterized by hallucinations, seizures, trouble sleeping, are more likely to occur. In case of overdose, symptomatic and supportive treatment is recommended. In case of recent ingestion, induction of emesis or gastric lavage should be initiated to limit further drug absorption. Although there is no known antidote to meclizine, physostigmine may be useful to counteract the CNS anticholinergic effects of meclizine.

Oral Rat LD50 = 4 gm/kg. Toxic effects include convulsions, dyspnea, hypermotility, diarrhea, ataxia and muscle weakness.

Precaution

Due to its potential anticholinergic action, patient with asthma, bronchitis, emphysema, enlarged prostate, glaucoma or urinary tract blockade should take Meclizine HCl (like other antiemetics) with caution.

Interaction

The CNS depressant effects of Meclizine can be potentiated by concurrent use of Ethanol or other CNS depressant agents such as Benzodiazepines, Barbiturates, Tricyclic antidepressants, opiate agonists, skeletal muscle relaxants and antihistamines. Concurrent use of other anticholinergics can potentiate the anticholinergic effects of Meclizine. Meclizine can increase the absorption of digoxin by decreasing gastrointestinal motility.

Volume of Distribution

The volume of distribution of meclizine in humans has not been fully studied. It is proposed that meclizine may be excreted into breast milk.

Pyridoxine main active metabolite, pyridoxal 5’-phosphate, is released into the circulation (accounting for at least 60% of circulating vitamin B6) and is highly protein bound, primarily to albumin.

Elimination Route

Most histamine H1 antagonists are reported to be readily absorbed following oral administration. Upon oral administration, the time to reach peak plasma concentrations (Cmax) of meclizine is about 3 hours post-dose, with the value ranging from 1.5 to 6 hours.

The B vitamins are readily absorbed from the gastrointestinal tract, except in malabsorption syndromes. Pyridoxine is absorbed mainly in the jejunum. The Cmax of pyridoxine is achieved within 5.5 hours.

Half Life

Meclizine has a plasma elimination half-life of about 5-6 hours in humans.

The total adult body pool consists of 16 to 25 mg of pyridoxine. Its half-life appears to be 15 to 20 days.

Clearance

There is limited data on the clearance of meclizine.

Elimination Route

Meclizine is excreted in the urine as metabolites and in the feces as unchanged drug.

The major metabolite of pyridoxine, 4-pyridoxic acid, is inactive and is excreted in urine

Pregnancy & Breastfeeding use

Use in pregnancy: Meclizine is pregnancy Category B drug. Large-scale human studies have not demonstrated adverse fetal effects. It has been suggested that, based on available data, Meclizine presents the lowest risk of teratogenicity and is the drug of first choice in treating nausea and vomiting during pregnancy. On the other hand, Pyridoxine is pregnancy category A drug. Pyridoxine itself is considered as safe during pregnancy and has been used in pregnant women without any evidence of fetal harm.

Use in lactation: Meclizine may be distributed into breast milk. However problem in human have not been documented. On the other hand, Pyridoxine has no adverse effects during lactation.

Contraindication

Meclizine Hydrochloride and Pyridoxine Hydrochloride is contraindicated in patients who are hypersensitive to these ingredients.

Special Warning

Use in children: Safety and efficacy have not been established in children below 2 years of age.

Acute Overdose

Symptoms: Extreme excitability, seizures, drowsiness and hallucinations.

Treatment: Appropriate supportive and symptomatic treatment. Consider dialysis.

Storage Condition

Store in a cool, dry place, away from light. Keep out of reach of children.

Innovators Monograph

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