Romisan Uses

• Romisan indications
• Uses of Romisan in details
• Romisan description
• Romisan dosage
• Romisan interactions
• Romisan side effects
• Romisan contraindications

What is Romisan?

Romisan (Romisan) is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Romisan is used to treat cancers of the colon and rectum. It is usually given with other cancer medicines in a combination chemotherapy.

Romisan may also be used for purposes not listed in this medication guide.

Romisan indications

As a single-agent or combination treatment of patients with: Metastatic carcinoma of the colon or rectum that has recurred or progressed following 5-fluorouracil (5-FU)-based therapy; previously untreated metastatic carcinoma of the colon or rectum; non-small-cell lung cancer (NSCLC); small-cell lung cancer; cervical and ovarian cancer; inoperable or recurrent gastric cancer; esophageal cancer.

Romisan in combination with cetuximab is indicated for the treatment of patients with EGFR-expressing metastatic colorectal cancer after failure of Romisan-including cytotoxic therapy.

Romisan in combination with 5-FU, folinic acid (FA) and bevacizumab is indicated for 1st-line treatment of patients with metastatic carcinoma of the colon or rectum.

As a single-agent treatment of patients with glioma.

How should I use Romisan?

Use Romisan as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Romisan is usually given as an injection at your doctor's office, hospital, or clinic. If you will be using Romisan at home, a health care provider will teach you how to use it. Be sure you understand how to use Romisan. Follow the procedures you are taught when you use a dose. Contact your health care provider if you have any questions.
• Do not use Romisan if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Drink plenty of water and other clear liquids while using Romisan.
• If you spill Romisan on your skin, wash it off right away with soap and water.
• Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• If you miss a dose of Romisan, contact your doctor right away.

Ask your health care provider any questions you may have about how to use Romisan.

Uses of Romisan in details

This medication is used to treat cancer of the colon and rectum.

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

This drug may also be used to treat other types of cancer (such as lung, bone cancer).

How to use Romisan intravenous

This medication is given by injection into a vein by a health care professional. The dosage is based on your medical condition, body size, and response to treatment.

If this medication comes into contact with your skin, wash the skin right away and completely with soap and water. If this medication gets into your eyes, mouth, or nose, flush completely with plenty of water. Consult your doctor for more details.

Romisan description

DBL Romisan Injection Concentrate is an antineoplastic agent of the topoisomerase I inhibitor class.

Romisan hydrochloride is a semisynthetic derivative of camptothecin, an alkaloid extract from plants such as Camptotheca acuminata. It is a pale yellow to yellow crystalline powder, with the empirical formula C₃₃H₃₈N₄O₆·HCl·3H₂O and a molecular weight of 677.19.

Its chemical name is (4S)-4,11-diethyl-4-hydroxy-9-[(4-piperidinopiperidino)carbonyloxy]-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)dione hydrochloride trihydrate.

DBL Romisan Injection Concentrate is supplied as a sterile, aqueous solution of pH 3.5. It is intended for dilution with 5% Glucose Injection or 0.9% Sodium Chloride Injection prior to infusion. The 2 mL and 5 mL injections contain 40 mg and 100 mg of Romisan hydrochloride trihydrate, respectively. In addition to Romisan hydrochloride trihydrate, the ingredients are sorbitol and lactic acid. Sodium hydroxide and hydrochloric acid are used for pH adjustment.

Romisan dosage

Adults: Monotherapy (for previously treated patients): Recommended Dose: 350 mg/m² administered as an IV infusion over a 30- to 90- min period every 3 weeks.

Combination Therapy (for previously untreated patients): Safety and efficacy of Romisan in combination with 5-fluorouracil (5-FU) and folinic acid (FA) has been assessed in the following schedule: Romisan Plus 5-FU/FA in a 2-Weekly Schedule: Recommended Dose: 180 mg/m² administered once every 2 weeks as an IV infusion over a 30 to 90- minutes period, followed by infusion with folinic acid and 5-fluorouracil.

Dose Adjustments: Romisan should be administered after appropriate recovery of all adverse events to grade 0 to 1 NCI-CTC grading (National Cancer Institute Common Toxicity Criteria) and when treatment-related diarrhoea is fully resolved.

At the start of a subsequent infusion of therapy, the dose of Romisan and 5-FU when applicable, should be decreased according to the worst grade of adverse events observed in the prior infusion. Treatment should be delayed by 1-2 weeks to allow recovery from treatment-related adverse events.

With the following adverse events, a dose reduction of 15-20% should be applied for Romisan and/or 5-FU when applicable: Haematological toxicity [neutropenia grade 4, febrile neutropenia (neutropenia grade 3-4 and fever grade 2-4), thrombocytopenia and leucopenia (grade 4)] and nonhaematological toxicity (grade 3-4).

Treatment Duration: Treatment with Romisan should be continued until there is objective progression of the disease or unacceptable toxicity.

Special Populations: Patients with Impaired Hepatic Function: In patients with bilirubin up to 1.5 times the upper limit of the normal range (ULN), the recommended dosage of Romisan is 350 mg/m². In patients with bilirubin ranging from 1.5 to 3 times ULN the recommended dosage is 200 mg/m². PATIENTS WITH BILIRUBIN BEYOND 3 TIMES THE ULN SHOULD NOT BE TREATED WITH Romisan.

Patients with Impaired Renal Function: Romisan is not recommended for use in patients with impaired renal function as studies in this population have not been conducted.

Elderly: No specific pharmacokinetic studies have been performed in the elderly. However, the dose should be chosen carefully in this population due to their greater frequency of decreased biological functions. This population therefore requires more intensive surveillance.

Administration: Preparation for IV Infusion: As with any other injectable drugs, the Romisan solution must be prepared aseptically.

Aseptically withdraw the required amount of Romisan solution from the vial with a calibrated syringe and inject into a 250-mL infusion bag or bottle containing either 0.9% sodium chloride or a 5% dextrose solution. The infusion should then be thoroughly mixed by manual rotation.

Romisan infusion solution should be infused into a peripheral or central vein.

Romisan should not be delivered as an IV bolus or an IV infusion <30 min or >90 minutes.

Romisan interactions

See also:
What other drugs will affect Romisan?

5-Fluorouracil (5-FU) And Leucovorin (LV)

In a phase 1 clinical study involving Romisan, 5-fluorouracil (5-FU), and leucovorin (LV) in 26 patients with solid tumors, the disposition of Romisan was not substantially altered when the drugs were co-administered. Although the Cmax and AUC0-24 of SN-38, the active metabolite, were reduced (by 14% and 8%, respectively) when Romisan was followed by 5-FU and LV administration compared with when Romisan was given alone, this sequence of administration was used in the combination trials and is recommended. Formal in vivo or in vitro drug interaction studies to evaluate the influence of Romisan on the disposition of 5-FU and LV have not been conducted.

Strong CYP3A4 Inducers

Exposure to Romisan or its active metabolite SN-38 is substantially reduced in adult and pediatric patients concomitantly receiving the CYP3A4 enzyme-inducing anticonvulsants phenytoin, phenobarbital, carbamazepine, or St. John's wort. The appropriate starting dose for patients taking these or other strong inducers such as rifampin and rifabutin has not been defined. Consider substituting non-enzyme inducing therapies at least 2 weeks prior to initiation of Romisan therapy. Do not administer strong CYP3A4 inducers with Romisan unless there are no therapeutic alternatives.

Strong CYP3A4 Or UGT1A1 Inhibitors

Romisan and its active metabolite, SN-38, are metabolized via the human cytochrome P450 3A4 isoenzyme (CYP3A4) and uridine diphosphate-glucuronosyl transferase 1A1 (UGT1A1), respectively,. Patients receiving concomitant ketoconazole, a CYP3A4 and UGT1A1 inhibitor, have increased exposure to Romisan hydrochloride and its active metabolite SN-38. Coadministration of Romisan with other inhibitors of CYP3A4 (e.g., clarithromycin, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telaprevir, voriconazole) or UGT1A1 (e.g., atazanavir, gemfibrozil, indinavir) may increase systemic exposure to Romisan or SN-38. Discontinue strong CYP3A4 inhibitors at least 1 week prior to starting Romisan therapy. Do not administer strong CYP3A4 or UGT1A1 inhibitors with Romisan unless there are no therapeutic alternatives.

Romisan side effects

See also:
What are the possible side effects of Romisan?

Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Common adverse reactions ( ≥ 30%) observed in combination therapy clinical studies are: nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, mucositis, neutropenia, leucopenia (including lymphocytopenia), anemia, thrombocytopenia, asthenia, pain, fever, infection, abnormal bilirubin, and alopecia.

Common adverse reactions ( ≥ 30%) observed in single agent therapy clinical studies are: nausea, vomiting, abdominal pain, diarrhea, constipation, anorexia, neutropenia, leukopenia (including lymphocytopenia), anemia, asthenia, fever, body weight decreasing, and alopecia.

Serious opportunistic infections have not been observed, and no complications have specifically been attributed to lymphocytopenia.

First-Line Combination Therapy

A total of 955 patients with metastatic colorectal cancer received the recommended regimens of Romisan in combination with 5-FU/LV, 5-FU/LV alone, or Romisan alone. In the two phase 3 studies, 370 patients received Romisan in combination with 5-FU/LV, 362 patients received 5-FU/LV alone, and 223 patients received Romisan alone.

In Study 1, 49 (7.3%) patients died within 30 days of last study treatment: 21 (9.3%) received Romisan in combination with 5-FU/LV, 15 (6.8%) received 5-FU/LV alone, and 13 (5.8%) received Romisan alone. Deaths potentially related to treatment occurred in 2 (0.9%) patients who received Romisan in combination with 5-FU/LV (2 neutropenic fever/sepsis), 3 (1.4%) patients who received 5-FU/LV alone (1 neutropenic fever/sepsis, 1 CNS bleeding during thrombocytopenia, 1 unknown) and 2 (0.9%) patients who received Romisan alone (2 neutropenic fever). Deaths from any cause within 60 days of first study treatment were reported for 15 (6.7%) patients who received Romisan in combination with 5-FU/LV, 16 (7.3%) patients who received 5-FU/LV alone, and 15 (6.7%) patients who received Romisan alone. Discontinuations due to adverse events were reported for 17 (7.6%) patients who received Romisan in combination with 5FU/LV, 14 (6.4%) patients who received 5-FU/LV alone, and 26 (11.7%) patients who received Romisan alone.

In Study 2, 10 (3.5%) patients died within 30 days of last study treatment: 6 (4.1%) received Romisan in combination with 5-FU/LV and 4 (2.8%) received 5-FU/LV alone. There was one potentially treatment-related death, which occurred in a patient who received Romisan in combination with 5-FU/LV (0.7%, neutropenic sepsis). Deaths from any cause within 60 days of first study treatment were reported for 3 (2.1%) patients who received Romisan in combination with 5-FU/LV and 2 (1.4%) patients who received 5-FU/LV alone. Discontinuations due to adverse events were reported for 9 (6.2%) patients who received Romisan in combination with 5FU/LV and 1 (0.7%) patient who received 5-FU/LV alone.

The most clinically significant adverse events for patients receiving Romisan-based therapy were diarrhea, nausea, vomiting, neutropenia, and alopecia. The most clinically significant adverse events for patients receiving 5-FU/LV therapy were diarrhea, neutropenia, neutropenic fever, and mucositis. In Study 1, grade 4 neutropenia, neutropenic fever (defined as grade 2 fever and grade 4 neutropenia), and mucositis were observed less often with weekly Romisan/5-FU/LV than with monthly administration of 5-FU/LV.

Tables 5 and 6 list the clinically relevant adverse events reported in Studies 1 and 2, respectively.

Table 5: Study 1: Percent (%) of Patients Experiencing Clinically Relevant Adverse Events in Combination Therapies Other includes events such as accidental injury, hepatomegaly, syncope, vertigo, and weight loss

The incidence of akathisia in clinical trials of the weekly dosage schedule was greater (8.5%, 4/47 patients) when prochlorperazine was administered on the same day as Romisan than when these drugs were given on separate days (1.3%, 1/80 patients). The 8.5% incidence of akathisia, however, is within the range reported for use of prochlorperazine when given as a premedication for other chemotherapies.

Postmarketing Experience