Uprima

Uprima - General Information

A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [PubChem]

 

Pharmacology of Uprima

Uprima is a type of dopaminergic agonist, a morphine derivative which primarily affects the hypothalamic region of the brain. Drugs containing this substance are sometimes used in the treatment of Parkinson's disease or erectile dysfunction. In higher doses it is a highly effective emetic.

 

Uprima for patients

APOKYN is intended only for subcutaneous injection and must not be given intravenously. Patients and caregivers should be urged to read the attached Patient Package Insert and Directions for Use of the ampule and dosing pen. Patients should be instructed to use APOKYN only as prescribed. Patients and/or caregivers who are advised to administer APOKYN in medically unsupervised situations should receive instruction on the proper use of the product from the physician or other suitably qualified health care professional and then observed during the initial dosing.

In particular, patients and caregivers must receive detailed instruction in the use of the dosing pen, with particular attention paid to two issues: 1) Patients need to be aware that the drug is dosed in milliliters, not milligrams. Patients should be particularly cautioned that a dose of 1 mg is represented on the dosing pen as 0.1 mL, and not as 1.0 (the latter representing a dose of 10 mg). It is critical that patients and caregivers be made to understand this distinction to prevent potentially life-threatening overdose if a dose of 1 mg is prescribed. 2) Patients and caregivers must be informed that it is possible to dial in their usual dose of apomorphine even though the cartridge may contain less than that amount of drug. In this case, they will receive only a partial dose with the injection, and the amount left to inject will appear in the dosing window. To complete the correct dose, patients/caregivers will need to "re-arm" the device and dial in the correct amount of the remaining dose. If at all possible, this situation should be avoided, and patients and caregivers should be alerted to the fact that there may be insufficient drug left in the cartridge to deliver a complete dose (for example, patients and caregivers should be urged to keep records of how many doses they have delivered for each cartridge, so that they can replace any cartridge that has an inadequate amount of drug remaining).

Patients should be instructed to rotate the injection site and to observe proper aseptic technique.

Patients should be informed that hallucinations can occur.

Patients should be advised that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sometimes sweating. Hypotension and/or orthostatic symptoms may occur more frequently during initial therapy or with an increase in dose at any time (cases have been seen after months of treatment). Accordingly, patients should be cautioned against rising rapidly after sitting or lying down, especially if they have been sitting or lying for prolonged periods, and especially at the initiation of treatment with APOKYN. Alcohol, antihyper-tensive medications, and vasodilating medications may potentiate the hypotensive effect of apomorphine.

Patients should be alerted to the potential sedating effects of APOKYN, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse event with potentially serious consequences, patients should neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient experience with APOKYN to gauge whether or not it affects their mental and/or motor performance adversely. Patients should be advised that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., watching television, passenger in a car, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their physician. Because of possible additive effects, caution should be advised when patients are taking other sedating medications or alcohol in combination with APOKYN.

Because apomorphine has not been evaluated for effects on reproduction and embryo-fetal development, patients should be advised to notify their physicians if they become pregnant or intend to become pregnant.

Because of the possibility that apomorphine may be excreted in breast milk, patients should be advised to notify their physicians if they intend to breast-feed.

Rare cases of abuse (use of apomorphine significantly in excess of prescribed frequency) have been reported. Apomorphine abuse may be associated with inappropriate sexual behavior.

 

Uprima Interactions

5HT₃ Antagonists

Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT³ antagonist class (including, for example, ondansetron, granisetron, dolasetron, palonosetron, and alosetron) is contraindicated.

Antihypertensive Medications and Vasodilators

The following adverse events were experienced more commonly in patients receiving concomitant antihypertensive medications or vasodilators (n = 94) compared to patients not receiving these concomitant drugs (n = 456): hypotension 10% vs 4%, myocardial infarction 3% vs 1%, serious pneumonia 5% vs 3%, serious falls 9% vs 3%, and bone and joint injuries 6% vs 2%. The mechanism underlying many of these events is unknown, but may represent increased hypotension . Dopamine Antagonists

Since apomorphine is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenoth-iazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of APOKYN. Patients with major psychotic disorders, treated with neuroleptics, should be treated with dopamine agonists only if the potential benefits outweigh the risks.

Drugs Prolonging the QT/QTc Interval

Caution should be exercised when prescribing apomorphine concomitantly with drugs that prolong the QT/QTc interval.

Drug/Laboratory Test Interactions

There are no known interactions between APOKYN and laboratory tests.

 

Uprima Contraindications

Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with ondansetron, the concomitant use of apomorphine with drugs of the 5HT₃ antagonist class (including, for example, ondansetron, granisetron, dolasetron, palonosetron, and alosetron) is contraindicated.

APOKYN is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients (notably sodium metabisulfite).

 

Additional information about Uprima

Uprima Indication: For the acute, intermittent treatment of hypomobility, off episodes (end-of-dose wearing off and unpredictable on/off episodes) associated with advanced Parkinson's disease.
Mechanism Of Action: The precise mechanism of action of apomorphine as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of post-synaptic dopamine D2-type receptors within the brain. Uprima has been shown to improve motor function in an animal model of Parkinson's disease. In particular, apomorphine attenuates the motor deficits induced by lesions in the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in primates.
Drug Interactions: Not Available
Food Interactions: Not Available
Generic Name: Apomorphine
Synonyms: Apomorfin; Apomorphine Hydrochloride Hemihydrate; Apomorphinium Chloride Hemihydrate; Apormorphine; L-Apomorphine
Drug Category: Antiparkinson Agents; Dopamine Agonists; Antidyskinetics
Drug Type: Small Molecule; Approved; Investigational

Other Brand Names containing Apomorphine: Uprima;
Absorption: 100% following subcutaneous administration
Toxicity (Overdose): LD₅₀=0.6 mmoles/kg (mice, intraperitoneal)
Protein Binding: ~50%-albumin
Biotransformation: Hepatic
Half Life: 40 minutes (range 30 - 60 minutes)
Dosage Forms of Uprima: Solution Subcutaneous
Chemical IUPAC Name: Not Available
Chemical Formula: C17H17NO2
Apomorphine on Wikipedia: https://en.wikipedia.org/wiki/Apomorphine
Organisms Affected: Humans and other mammals