Actions of Odrinil in details
Odrinil stimulates medullary, vagal, vasomotor, and respiratory centers, promoting bradycardia, vasoconstriction, and increased respiratory rate. This action was previously believed to be due primarily to increased intracellular cyclic 3′,5′-adenosine monophosphate (cyclic AMP) following inhibition of phosphodiesterase, the enzyme that degrades cyclic AMP. It is now thought that xanthines such as Odrinil act as antagonists at adenosine-receptors within the plasma membrane of virtually every cell. As adenosine acts as an autocoid, inhibiting the release of neurotransmitters from presynaptic sites but augmenting the actions of norepinephrine or angiotensin, antagonism of adenosine receptors promotes neurotransmitter release. This explains the stimulatory effects of Odrinil. Blockade of the adenosine A1 receptor in the heart leads to the accelerated, pronounced "pounding" of the heart upon Odrinil intake.
How should I take Odrinil?
Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your child's dose. Use the medicine exactly as directed.
Odrinil citrate is for short-term use only. Do not use Odrinil citrate for longer than 12 days without the advice of your child's doctor.
Odrinil citrate oral solution is given by mouth.
Odrinil citrate injection is given as an infusion into a vein. A healthcare provider will give your child this injection.
Measure oral solution carefully. Use the dosing syringe provided, or use a medicine dose-measuring device (not a kitchen spoon).
Do not use the medicine if it looks cloudy, has changed colors, or has particles in it. Call your pharmacist for new medication.
Your child will need frequent medical tests.
Odrinil citrate contains no preservative. Do not open a bottle of this medicine until you are ready to give the dose.
Each bottle of Odrinil citrate oral solution is for one use only. Throw it away after one use, even if there is still medicine left inside.
Store at room temperature away from moisture and heat.
Odrinil administration
Use this medication exactly as it was prescribed for your child. Do not use the medication in larger amounts, or use it for longer than recommended by your doctor. Follow the instructions on the prescription label.
Odrinil citrate is for short-term use only. Do not use the medication for longer than 12 days without the advice of your child's doctor.
Measure Odrinil citrate with a special dose-measuring spoon or cup, not a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one.
Each bottle of Odrinil citrate is for one use only, even if your child does not use the entire bottle for a single dose. Throw away any medication left over in the bottle after measuring your child's dose.
Do not use the medication if the liquid has changed colors or has particles in it. Call your doctor for a new prescription.
Call your doctor if the child's breathing symptoms do not improve after using Odrinil citrate.
To be sure Odrinil citrate is helping your child's condition, the child's blood will need to be tested on a regular basis. Do not miss any scheduled appointments.
Store the medication at room temperature away from heat and moisture. Do not open a bottle of Odrinil citrate until you are ready to give the dose. This medication contains no preservatives.
Odrinil pharmacology
Mechanism of Action
Odrinil is structurally related to other methylxanthines, theophylline, and theobromine. It is a bronchial smooth muscle relaxant, a CNS stimulant, a cardiac muscle stimulant, and a diuretic.
Although the mechanism of action of Odrinil in apnea of prematurity is not known, several mechanisms have been hypothesized. These include: (1) stimulation of the respiratory center, (2) increased minute ventilation, (3) decreased threshold to hypercapnia, (4) increased response to hypercapnia, (5) increased skeletal muscle tone, (6) decreased diaphragmatic fatigue, (7) increased metabolic rate, and (8) increased oxygen consumption.
Most of these effects have been attributed to antagonism of adenosine receptors, both A1 and A2 subtypes, by Odrinil, which has been demonstrated in receptor binding assays and observed at concentrations approximating those achieved therapeutically.
Pharmacokinetics
Absorption
After oral administration of 10 mg Odrinil base/kg to preterm neonates, the peak plasma level (Cmax) for Odrinil ranged from 6 to 10 mg/L and the mean time to reach peak concentration (Tmax) ranged from 30 minutes to 2 hours. The Tmax was not affected by formula feeding. The absolute bioavailability, however, was not fully examined in preterm neonates.
Distribution
Odrinil is rapidly distributed into the brain. Odrinil levels in the cerebrospinal fluid of preterm neonates approximate their plasma levels. The mean volume of distribution of Odrinil in infants (0.8 to 0.9 L/kg) is slightly higher than that in adults (0.6 L/kg). Plasma protein binding data are not available for neonates or infants. In adults, the mean plasma protein binding in vitro is reported to be approximately 36%.
Metabolism
Hepatic cytochrome P4501A2 (CYP1A2) is involved in Odrinil biotransformation. Odrinil metabolism in preterm neonates is limited due to their immature hepatic enzyme systems.
Interconversion between Odrinil and theophylline has been reported in preterm neonates; Odrinil levels are approximately 25% of theophylline levels after theophylline administration and approximately 3 to 8% of Odrinil administered would be expected to convert to theophylline.
Elimination
In young infants, the elimination of Odrinil is much slower than that in adults due to immature hepatic and/or renal function. Mean half-life (T1/2) and fraction excreted unchanged in urine (Ae) of Odrinil in infants have been shown to be inversely related to gestational/postconceptual age. In neonates, the T1/2 is approximately 3 to 4 days and the Ae is approximately 86% (within 6 days). By 9 months of age, the metabolism of Odrinil approximates that seen in adults (T1/2 = 5 hours and Ae = 1%).
Special Populations
Studies examining the pharmacokinetics of Odrinil in neonates with hepatic or renal insufficiency have not been conducted. Odrinil Citrate should be administered with caution in preterm neonates with impaired renal or hepatic function. Serum concentrations of Odrinil should be monitored and dose administration of Odrinil Citrate should be adjusted to avoid toxicity in this population.
Clinical Studies
One multicenter, randomized, double-blind trial compared Odrinil Citrate to placebo in eighty five (85) preterm infants (gestational age 28 to <33 weeks) with apnea of prematurity. Apnea of prematurity was defined as having at least 6 apnea episodes of greater than 20 seconds duration in a 24-hour period with no other identifiable cause of apnea. A 1 mL/kg (20 mg/kg Odrinil Citrate providing 10 mg/kg as Odrinil base) loading dose of Odrinil Citrate was administered intravenously, followed by a 0.25 mL/kg (5 mg/kg Odrinil Citrate providing 2.5 mg/kg of Odrinil base) daily maintenance dose administered either intravenously or orally (generally through a feeding tube). The duration of treatment in this study was limited to 10 to 12 days. The protocol allowed infants to be “rescued” with open-label Odrinil Citrate treatment if their apnea remained uncontrolled during the double-blind phase of the trial.
The percentage of patients without apnea on day 2 of treatment (24 to 48 hours after the loading dose) was significantly greater with Odrinil Citrate than placebo. The following table summarizes the clinically relevant endpoints evaluated in this study:
| Odrinil Citrate | Placebo | p-value | |
| Number of patients evaluated1 | 45 | 37 | |
| % of patients with zero apnea events on day 2 | 26.7 | 8.1 | 0.03 |
| Apnea rate on day 2 (per 24 h) | 4.9 | 7.2 | 0.134 |
| % of patients with 50% reduction in apnea events from baseline on day 2 | 76 | 57 | 0.07
|
1 Of 85 patients who received drug, 3 were not included in the efficacy analysis because they had <6 apnea episodes/24 hours at baseline.
In this 10 to 12 day trial, the mean number of days with zero apnea events was 3 in the Odrinil Citrate group and 1.2 in the placebo group. The mean number of days with a 50% reduction from baseline in apnea events was 6.8 in the Odrinil Citrate group and 4.6 in the placebo group.
References
- DailyMed. "CAFFEINE; ERGOTAMINE TARTRATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- NCIt. "Caffeine: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
- EPA DSStox. "Caffeine: DSSTox provides a high quality public chemistry resource for supporting improved predictive toxicology.". https://comptox.epa.gov/dashboard/ds... (accessed September 17, 2018).
Reviews
The results of a survey conducted on ndrugs.com for Odrinil are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Odrinil. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.User reports
Consumer reported administration
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Information checked by Dr. Sachin Kumar, MD Pharmacology
