Novadom C

Novadom C is a synthetic anticoagulant and an indanedione derivative. It prevents the formation of active procoagulation factors II, VII, IX, and X, as well as the anticoagulant proteins C and S, in the liver by inhibiting the vitamin K mediated gamma-carboxylation of precursor proteins.

Dyspeptic symptom complex often associated with delayed gastric emptying, gastroesophageal reflux disease (GERD) or esophagitis: Epigastric sense of fullness, feeling of abdominal distention, upper abdominal pain, flatulence (gassiness), eructation (belching), and heartburn.

Short-term treatment of nausea and vomiting of various origins including functional, organic, infectious, diabetic origin, or induced by radiotherapy or medicine therapy. (It is not considered suitable for chronic nausea and vomiting, nor for the routine prophylaxis of postoperative vomiting.)

Treatment of nausea and vomiting induced by dopamine agonists ie, L-dopa and bromocriptine used in Parkinson's disease.

Novadom C may also be given as needed, together with paracetamol for the symptomatic treatment of nausea and vomiting associated with migraine.

Novadom C is a medicine that increases the movements or contractions of the stomach and bowel. Novadom C is also used to treat nausea and vomiting caused by other drugs used to treat Parkinson's Disease.

Novadom C is to be given only by or under the immediate supervision of your doctor.

Novadom C is injected submucosally in the urinary bladder in close proximity to the ureteral orifice. The injection of Novadom C creates increased tissue bulk thereby providing coaptation of the distal ureter during filling and contraction of the bladder. The dextranomer microspheres are gradually surrounded by host connective tissue.

Directions For Use

Novadom C is to be administered only by qualified surgeons experienced in the use of a cystoscope and trained in the technique of subureteric and/or intraureteric injections injections (with Novadom C or other materials).

It is recommended to use the Novadom C metal needle (3.7F x 23G tip x 350 mm) for safe and accurate administration of Novadom C. To assist the physician in positioning the needle, the Novadom C metal needle has a circular mark 6 mm from the needle tip. To show the position of the needle bevel, there is a square mark 8 mm from the needle tip. The marks are for reference only.

Novadom C can be injected with any common pediatric cystoscope with a minimum 4 French working channel. A type of cystoscope witha straight working channel is also well adapted for this type of procedure. The child is placed in a lithotomy position under general anesthesia and cystoscopy is performed to localize the ureteral orifices.

Before injecting Novadom C the following is recommended:

• Flush physiological saline solution through the needle.
• Fasten the needle tightly to the syringe.
• Remove the air from the needle by injecting the gel into the needle up to a point where a droplet is visible at the tip.

Please note that the luer lock adapter is snapped onto the syringe and held in place with friction only. It can rotate freely or be pulled off should enough force be applied. Because of this, it is recommended that the thumb and forefinger are held firmly around both the glass syringe barrel and the luer lock adapter when assembling the needle and syringe. To facilitate proper threading/fastening of needle hub and luer lock adapter, please both push and rotate them firmly together.

To avoid any interruption in patient treatment or the need to repeat a procedure because of leakage or breakage of a syringe, it is recommended that extra syringes be kept in inventory.

Novadom C is easily injected by finger pressure on a normal syringe with any commonly used pediatric cystoscope. Due to its viscoelastic properties, Novadom C can be injected through a fine needle – no special injection device is necessary.

Injection Techniques

Several techniques have been described for the endoscopic treatment of VUR including a subureteric injection (STING procedure), a single intra-ureteric injection (HIT procedure) and a double (proximal and distal) intra-ureteric injection (Double-HIT procedure). The Double-HIT procedure is a refinement of the original STING and HIT procedures and has been reported to result in greater clinical success rates.

In general, the bladder is semi-filled to allow for good visualization of the ureteral orifice(s) and to avoid tension within the submucosal layer of the ureter secondary to overdistension. For the HIT procedure, hydrodistention of the ureteral orifice is initiated to define the site of injection within the submucosa of the intramural ureter. The needle is inserted approximately 4 mm in the submucosa of the mid- to distal ureteral tunnel at the 6 o

Hypersensitivity to Novadom C or any ingredient of Novadom C.

If patients are taking oral ketoconazole, fluconazole, voriconazole, erythromycin, clarithromycin, telithromycin, amiodarone, selective serotonin reuptake inhibitors, HIV protease inhibitors, calcium antagonists which can increase plasma concentrations of Novadom C, leading to a prolonged QTc interval. These medicines can increase plasma concentrations of Novadom C leading to a prolonged QTc interval. Patients with long QT syndrome develop a very fast heart rhythm disturbance leading to a sudden loss of consciousness.

Gastrointestinal hemorrhage (bleeding), obstruction, perforation or conditions where gastrointestinal stimulation or movements may be dangerous.

Prolactin-releasing pituitary tumor (prolactinoma).

Novadom C is used to treat vomiting or nausea caused due to indigestion, diseases or drugs. It is also used to relieve fullness of stomach, belching and heavy bloating, gas and heartburn for a longer period up to 2 weeks.

Concomitant administration of anticholinergic drugs may antagonise the antidyspeptic effect of Novadom C.

Antacids and antisecretory drugs should not be given simultaneously with oral formulations of Novadom C as they lower its oral bioavailability.

The main metabolic pathway of Novadom C is through CYP3A4. In vitro and human data show that the concomitant use of drugs that significantly inhibit this enzyme may result in increased plasma levels of Novadom C. Examples of potent CYP3A4 inhibitors include: Azole antifungals eg, fluconazole*, itraconazole, ketoconazole* and voriconazole*; macrolide antibiotics eg, clarithromycin* and erythromycin*; HIV protease inhibitors eg, amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir and saquinavir; calcium antagonists eg, diltiazem and verapamil; amiodarone*; aprepitant; nefazodone; telithromycin*.

(*Also prolong the QTc interval; see Contraindications.)

Separate pharmacokinetic/pharmacodynamic interaction studies with oral ketoconazole or oral erythromycin in healthy subjects confirmed a marked inhibition of Novadom C's CYP3A4 mediated first-pass metabolism by these drugs.

With the combination of Novadom C 10 mg 4 times daily and ketoconazole 200 mg twice daily, a mean QTc prolongation of 9.8 msec was seen over the observation period, with changes at individual time points ranging from 1.2-17.5 msec. With the combination of Novadom C 10 mg 4 times daily and erythromycin 500 mg 3 times daily, mean QTc over the observation period was prolonged by 9.9 msec, with changes at individual time points ranging from 1.6-14.3 msec. Both the C_max and AUC of Novadom C at steady-state were increased approximately 3-fold in each of these interaction studies.

The contribution of increased plasma concentrations of Novadom C to the observed effect on QTc is not known.

In these studies, Novadom C monotherapy at 10 mg 4 times daily resulted in increases in mean QTc of 1.6 msec (ketoconazole study) and 2.5 msec (erythromycin study), while ketoconazole monotherapy (200 mg twice daily) and erythromycin monotherapy (500 mg 3 times daily) led to increases in mean QTc of 3.8 and 4.9 msec, respectively, over the observation period.

In another multiple-dose study in healthy subjects, no significant increases in QTc were noted during steady-state treatment with Novadom C monotherapy at 40 mg 4 times daily (total daily dose of 160 mg, which is double the maximum daily dose) at plasma concentrations of Novadom C that were at least similar to those found in the combination arms of the interaction studies.

Theoretically, since Novadom C has gastrokinetic effects, it could influence the absorption of concomitantly orally administered drugs, particularly those with sustained release or enteric-coated formulations. However, in patients already stabilised on digoxin or paracetamol, concomitant administration of Novadom C did not influence the blood levels of these drugs.

Novadom C may also be given with neuroleptics, the action of which it does not potentiate; dopaminergic agonists (bromocriptine, L-dopa), whose unwanted peripheral effects eg, digestive disorders, nausea and vomiting, it suppresses without counteracting their central properties.

See also:
What are the possible side effects of Novadom C?

Adverse Events

The safety of Novadom C in the treatment of VUR is based on a pivotal randomized study in which 39 children were treated with Novadom C, two nonrandomized supportive studies in which 170 children were treated with Novadom C, and a nonrandomized post-approval study in which 165 children were treated with Novadom C. Follow-up for the pivotal and supportive studies was 12 months; follow-up for the post-approval study was 5 years (5-year data available for 31 of the 165 enrolled subjects (18.8%) ). No patients died during the course of these studies.

A list of the treatment -related adverse events occurring in > 1% of patients in all four studies is presented in Table 1.

Table 1: List of Treatment-Related Adverse Events Occurring in > 1% of Patients in the Pivitol, Supportive and Post-Approval Studies

The following adverse events were associated with the use of Novadom C from spontaneous post-marketing surveillance reporting or from clinical studies (occurring ≤ 1%) and include but are not limited to: ureteral obstruction with or without hydronephrosis (some cases requiring temporary placement of a ureteric stent, and rare cases of ureteral re-implant procedures), hematuria, urgency, frequency, pyelonephritis, foreign body reaction, calcification, pyrexia, hypertonic bladder, bladder irritation, and Henoch-Schonlein purpura.

Adverse events should be reported to:

Salix Product Information Call Center, Phone: 1-800-508-0024, Fax: 1-510-595-8183, E-mail: Salix@medcomsol.com