GENERIC NAME OF THE MEDICINAL PRODUCT:

a) Amphotericin B Lipid Complex Injection 50mg/10ml Taj Pharma
b) Amphotericin B Lipid Complex Injection 100mg/20ml Taj Pharma

QUALITATIVE AND QUANTITATIVE COMPOSITION:

a) Each 1ml Amphotericin B Lipid Complex Injection 50mg/10ml Taj Pharma contains:
Amphotericin B    5mg
Excipients       q.s.
b) Each 1ml Amphotericin B Lipid Complex Injection 100mg/20ml Taj Pharma contains:
Amphotericin B     5mg
Excipients        q.s.

THERAPEUTIC INDICATIONS:

Amphotericin B Lipid Complex is indicated for the treatment of severe invasive candidiasis. Amphotericin B Lipid Complex is also indicated as second line therapy for the treatment of severe systemic fungal infections in patients who have not responded to conventional amphotericin B or other systemic antifungal agents, in those who have renal impairment or other contra-indications to conventional amphotericin B, or in patients who have developed amphotericin B nephrotoxicity. Amphotericin B Lipid Complex treatment is indicated as second line treatment for invasive aspergillosis, cryptococcal meningitis and disseminated cryptococcosis in HIV patients, fusariosis, coccidiomycosis, zygomycosis and blastomycosis.

Amphotericin B Lipid Complex Injection 50mg/10ml

  1. NAME OF THE MEDICINAL PRODUCT

a) Amphotericin B Lipid Complex Injection 50mg/10ml Taj Pharma
b) Amphotericin B Lipid Complex Injection 100mg/20ml Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

a) Each 1ml Amphotericin B Lipid Complex Injection 50mg/10ml Taj Pharma contains:
Amphotericin B 5mg
Sodium Chloride 9mg
Lipids:
Dimyristoylphosphatidylcholine (DMPC) 3.4mg
Dimyristoylphosphatidyl Glycerol 1.5mg
(DMPG as Sodium salt)

b) Each 1ml Amphotericin B Lipid Complex Injection 100mg/20ml Taj Pharma contains:
Amphotericin B 5mg
Sodium Chloride 9mg
Lipids:
Dimyristoylphosphatidylcholine (DMPC) 3.4mg
Dimyristoylphosphatidyl Glycerol 1.5mg
(DMPG as Sodium salt)

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Liquid Injection.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Amphotericin B Lipid Complex is indicated for the treatment of severe invasive candidiasis.

Amphotericin B Lipid Complex is also indicated as second line therapy for the treatment of severe systemic fungal infections in patients who have not responded to conventional amphotericin B or other systemic antifungal agents, in those who have renal impairment or other contra-indications to conventional amphotericin B, or in patients who have developed amphotericin B nephrotoxicity. Amphotericin B Lipid Complex treatment is indicated as second line treatment for invasive aspergillosis, cryptococcal meningitis and disseminated cryptococcosis in HIV patients, fusariosis, coccidiomycosis, zygomycosis and blastomycosis.

4.2 Posology and method of administration

Non-equivalence of amphotericin products

Different amphotericin products (sodium deoxycholate, liposomal, lipid complex) are not equivalent in terms of pharmacodynamics, pharmacokinetics and dosing and so the products should not be used interchangeably without accounting for these differences. Both the trade name, common name and dose should be verified pre-administration.

There is a risk of under-dose if Amphotericin B Lipid Complex is administered at a dose recommended for amphotericin B deoxycholate.

Amphotericin B Lipid Complex is a sterile, pyrogen-free suspension which must be diluted for intravenous infusion only.

Posology

Amphotericin B Lipid Complex should be administered by intravenous infusion at 5 mg/kg at a rate of 2.5 mg/kg/hr.

Elderly

Systemic fungal infections in elderly patients have been treated successfully with Amphotericin B Lipid Complex at doses comparable to the recommended dose on a bodyweight basis.

Patients with diabetes insipidus

Amphotericin B Lipid Complex may be administered to patients with diabetes insipidus.

Patients with neutropenia

Amphotericin B Lipid Complex has been used successfully to treat systemic fungal infections in patients who are severely neutropenic as a consequence of haematological malignancy or the use of cytotoxic or immunosuppressive drugs.

Renal or hepatic impairment

Systemic fungal infections in patients with renal or liver disease have been treated successfully with Amphotericin B Lipid Complex at doses comparable to the recommended dose on a body weight basis (see section 4.4).

Paediatric population

Use in children and adolescents

Systemic fungal infections in children (ranging from 1 month to 16 years of age) have been treated successfully with Amphotericin B Lipid Complex at doses comparable to the recommended adult dose on a bodyweight basis.

There are no sufficient data on efficacy and safety available in children less that one month.

No data on the efficacy and safety of Amphotericin B Lipid Complex in preterm newborn infants suffering from fungal infections due to aspergillus species are available.

Method of administration

When commencing treatment with Amphotericin B Lipid Complex for the first time it is recommended to administer a test dose immediately prior to the first infusion. The first infusion should be prepared according to the instructions (see section 6.6), then, over a period of approximately 15 minutes, 1 mg of the infusion should be administered to the patient. After this amount has been administered the infusion should be stopped and the patient observed carefully for 30 minutes. If the patient shows no signs of hypersensitivity the infusion may be continued. As for use with all amphotericin B products, facilities for cardiopulmonary resuscitation should be readily at hand when administering Amphotericin B Lipid Complex for the first time, due to the possible occurrence of anaphylactoid reactions.

For severe systemic infections treatment is generally recommended for at least 14 days.

Amphotericin B Lipid Complex has been administered for as long as 28 months, and cumulative doses have been as high as 73.6 g without significant toxicity.

An in-line filter may be used for intravenous infusion of Amphotericin B Lipid Complex. The mean pore diameter of the filter should be no less than 15 microns.

For instructions on preparation of the suspension for infusion before administration, see section 6.6.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1, unless in the opinion of the physician the advantages of using Amphotericin B Lipid Complex outweigh the risks of hypersensitivity.

4.4 Special warnings and precautions for use

In patients for whom sodium intake is of medical concern (e.g. patients with congestive heart failure, renal failure, nephrotic syndrome), the sodium content of this product should be taken into account (see section 2).

Infusion hypersensitivity reactions

Infusion related reactions (such as chills and pyrexia) recorded following the administration of Amphotericin B Lipid Complex have generally been mild or moderate, and have mainly be recorded during the first 2 days of administration (see section 4.8).

Premedication (e.g. paracetamol) may be administered for the prevention of infusion related adverse reactions.

Systemic fungal infections

Amphotericin B Lipid Complex should not be used for treating common or superficial, clinically inapparent fungal infections that are detectable only by positive skin or serologic tests.

Renal impairment

Since Amphotericin B Lipid Complex is a potentially nephrotoxic drug, monitoring of renal function should be performed before initiating treatment in patients with pre-existing renal disease or who have already experienced renal failure, and at least once weekly during therapy. Amphotericin B Lipid Complex can be administered to patients during renal dialysis or haemofiltration. Serum potassium and magnesium levels should be monitored regularly.

Hepatic impairment

Patients with concurrent hepatic impairment due to infection, graft-versus-host disease, other liver disease or administration of hepatotoxic drugs have been successfully treated with Amphotericin B Lipid Complex. In cases where serum bilirubin, alkaline phosphatase or serum transaminases increased, factors other than Amphotericin B Lipid Complex were present and possibly accounted for the abnormalities. These factors included infection, hyperalimentation, concomitant hepatotoxic drugs and graft-versus-host disease.

4.5 Interaction with other medicinal products and other forms of interaction

Nephrotoxic drugs

Amphotericin B Lipid Complex is a potentially nephrotoxic drug, and particularly close monitoring of renal function is required in patients receiving nephrotoxic drugs concomitantly.

Zidovudine

In dogs, exacerbated myelotoxicity and nephrotoxicity were observed when Amphotericin B Lipid Complex was administered concomitantly with zidovudine. If concomitant treatment with zidovudine is required, renal and haematologic function should be closely monitored.

Cyclosporin

Interaction data with amphotericin B containing products indicate that patients receiving amphotericin B concomitantly with high dose cyclosporine experience an increase in serum creatinine caused by simultaneous administration of these two compounds. However, Amphotericin B Lipid Complex has been shown to be less nephrotoxic than conventional amphotericin B.

Other drugs

The interaction of Amphotericin B Lipid Complex with other drugs has not been studied to date. Conventional amphotericin B has been reported to interact with the following drugs, and caution should be exercised during concomitant use with Amphotericin B Lipid Complex: antineoplastic agents, corticosteroids and corticotrophin (ACTH), digitalis glycosides, flucytosine, and skeletal muscle relaxants.

Leukocyte transfusions

Acute pulmonary toxicity has been reported in patients receiving intravenous conventional amphotericin B and leukocyte transfusions. It is not recommended to administer Amphotericin B Lipid Complex with leukocyte transfusions.

4.6 Fertility, pregnancy and lactation

Pregnancy

Conventional amphotericin B has been used successfully to treat systemic fungal infections in pregnant women with no obvious effects on the foetus, but only a small number of cases have been reported. Reproductive toxicity studies of Amphotericin B Lipid Complex in rats and rabbits showed no evidence of embryotoxicity, foetotoxicity or teratogenicity. However, safety for use in pregnant women has not been established for Amphotericin B Lipid Complex. Amphotericin B Lipid Complex should only be administered to pregnant women when the likely benefit exceeds the risk to the mother and foetus.

Breast-feeding

It is unknown whether Amphotericin B Lipid Complex passes into breast milk. A decision on whether to continue/discontinue nursing or whether to continue/discontinue Amphotericin B Lipid Complex should be made taking into account the benefit of breast-feeding to the child and the benefit of Amphotericin B Lipid Complex to the woman.

4.7 Effects on ability to drive and use machines

The effects of Amphotericin B Lipid Complex on the ability to drive and /or use machines have not been investigated. Some of the undesirable effects of Amphotericin B Lipid Complex presented below may impact the ability to drive and use machines. However, the clinical condition of patients who require Amphotericin B Lipid Complex generally precludes driving or operating machinery.

4.8 Undesirable effects

The most common clinical adverse reactions in randomised controlled and open label clinical trials have been chills (16%), increased creatinine (13%), pyrexia (10%), hypokalaemia (9%), nausea (7%) and vomiting (6%).

The incidence is based on analysis from pooled clinical trials of 709 Amphotericin B Lipid Complex treated patients.

There were 556 cases in emergency use studies (open-label, non-comparative studies) and 153 in a randomised controlled trial in invasive candidiasis (38% ≥ 65 years). In the emergency use studies, patients had either shown intolerance to conventional amphotericin B treatment, had renal impairment as a result of previous conventional amphotericin B treatment, had pre-existing renal disease or were treatment failures.

The following adverse reactions have been reported with Amphotericin B Lipid Complex during clinical trials and/or post-marketing use.

Adverse reactions are listed below as MedDRA preferred term by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), not known (cannot be estimated from the available data).

System organ classVery commonCommonUncommonNot known
Blood and lymphatic system disordersThrombocytopenia
Immune system disordersAnaphylactic response
Metabolism and nutrition disordersHyperbilirubinaemia, Hypokalaemia, Electrolyte imbalance including blood potassium increased, blood magnesium decreased
Nervous system disordersHeadache, TremorConvulsion, NeuropathyEncephalopathy
Cardiac disordersTachycardia, Cardiac ArrhythmiasCardiac arrest
Vascular disordersHypertension, HypotensionShock
Respiratory, thoracic and mediastinal disordersDyspnoea, AsthmaRespiratory failureBronchospasm
Gastrointestinal disordersNausea, Vomiting, Abdominal pain
Hepatobiliary disordersLiver function tests abnormal
Skin and subcutaneous tissue disordersRashPruritusDermatitis exfoliative
Musculoskeletal and connective tissue disordersMyalgia
Renal and urinary disordersRenal impairment including renal failureHyposthenuria, Renal tubular acidosis, Nephrogenic diabetes insipidus
General disorders and administration site conditionsChills, PyrexiaInjection site reaction
InvestigationsBlood creatinine increasedBlood alkaline phosphatase increased, blood urea increased

The undesirable effects listed with frequency “not known” (encephalopathy, bronchospasm, dermatitis exfoliative, hyposthenuria, renal tubular acidosis, nephrogenic diabetes insipidus) have been observed during post-marketing use.

Adverse reactions that have been reported to occur with conventional amphotericin B may occur with Amphotericin B Lipid Complex. In general, the physician should monitor the patient for any type of adverse event associated with conventional amphotericin B.

Infusion hypersensitivity reactions have been associated with abdominal pain, nausea, vomiting, myalgia, pruritus, maculopapular rash, fever, hypotension, shock, bronchospasm, respiratory failure, chest pain and in certain patients a decrease in oxygen saturation and cyanosis (see section 4.4).

Patients in whom significant renal toxicity was observed following conventional amphotericin B frequently did not experience similar effects when Amphotericin B Lipid Complex was substituted.

Declines in renal function, shown by increased serum creatinine and hypokalaemia, have not typically required discontinuation of treatment.

Renal tubular acidosis has been reported including hyposthenuria and electrolyte imbalance such as increased potassium and decreased magnesium.

Abnormal liver function tests have been reported with Amphotericin B Lipid Complex and other amphotericin B products. Although other factors such as infection, hyperalimentation, concomitant hepatotoxic drugs and graft-versus-host disease may be contributory, a causal relationship with Amphotericin B Lipid Complex cannot be excluded. Patients with abnormal liver function tests should be carefully monitored and cessation of treatment considered if liver function deteriorates.

Paediatric population

Undesirable effects observed in children and adolescents are similar to those observed in adults

Elderly population

In elderly patients, the adverse reaction profile was similar to that seen in adults less than 65 years. Important exceptions were increases in serum creatinine and dyspnoea which were reported in elderly patients for both Amphotericin B Lipid Complex and conventional amphotericin B with a greater frequency in this age group.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms

Dosages up to 10 mg/kg/day have been administered in clinical studies with no apparent dose-dependent toxicity.

Instances of overdose reported with Amphotericin B Lipid Complex have been consistent with those reported in clinical trials with treatment at standard doses (see section 4.8). In addition, seizures and bradycardia were experienced by one paediatric patient who received a dose of 25 mg/kg.

Management

In case of overdose, the status of the patient (in particular the cardio-pulmonary, renal and hepatic function as well as the blood count and serum electrolytes) should be monitored and supportive measures initiated. No specific antidote to amphotericin B is known.

  1. PHARMACOLOGICAL PROPERTIES

Amphotericin B Lipid Complex consists of the antifungal agent, amphotericin B, complexed to two phospholipids. Amphotericin B is a macrocyclic, polyene, broad-spectrum antifungal antibiotic produced by Streptomyces nodosus. The lipophilic moiety of amphotericin B allows molecules of the drug to be complexed in a ribbon-like structure with the phospholipids.

5.1 Pharmacodynamic properties

Mechanism of action

Amphotericin B, the active antifungal agent in Amphotericin B Lipid Complex, may be fungistatic or fungicidal, depending on its concentration and on fungal susceptibility. The drug probably acts by binding to ergosterol in the fungal cell membrane causing subsequent membrane damage. As a result, cell contents leak from the fungal cell, and, ultimately, cell death occurs. Binding of the drug to sterols in human cell membranes may result in toxicity, although amphotericin B has greater affinity for fungal ergosterol than for the cholesterol of human cells.

Microbiological activity

EUCAST breakpoints for amphotericin B lipid complex have not yet been established.

Amphotericin B is active against many fungal pathogens in vitro, including Candida spp., Cryptococcus neoformans, Aspergillus spp., Mucor spp., Sporothrix schenckii, Blastomyces dermatitidis, Coccidioides immitis and Histoplasma capsulatum. Most strains are inhibited by amphotericin B concentrations of 0.03-1.0 μg/ml. Amphotericin B has little or no activity against bacteria or viruses. The activity of Amphotericin B Lipid Complex against fungal pathogens in vitro is comparable to that of amphotericin B. However, activity of Amphotericin B Lipid Complex in vitro may not predict activity in the infected host.

5.2 Pharmacokinetic properties

Amphotericin B is complexed to phospholipids in Amphotericin B Lipid Complex. The pharmacokinetic properties of Amphotericin B Lipid Complex and conventional amphotericin B are different. Pharmacokinetic studies in animals showed that, after administration of Amphotericin B Lipid Complex, amphotericin B levels were highest in the liver, spleen and lung. Amphotericin B in Amphotericin B Lipid Complex was rapidly distributed to tissues. The ratio of drug concentrations in tissues to those in blood increased disproportionately with increasing dose, suggesting that elimination of the drug from the tissues was delayed. Peak blood levels of amphotericin B were lower after administration of Amphotericin B Lipid Complex than after administration of equivalent amounts of conventional drug. Administration of conventional amphotericin B resulted in much lower tissue levels than did dosing with Amphotericin B Lipid Complex. However, in dogs, conventional amphotericin B produced 20-fold higher kidney concentrations than did Amphotericin B Lipid Complex given at comparable doses.

The pharmacokinetics of Amphotericin B Lipid Complex in whole blood were determined in patients with mucocutaneous leishmaniasis. Results for mean pharmacokinetic parameters at 5.0 mg/kg/day were as follows:

Amphotericin B Lipid Complex
Dose: (mg/kg/day)5.0
Peak blood level Cmax: (μg/ml)1.7
Area under time-concentration curve AUC0-24: (μg.hr/ml)9.5
Clearance: (ml/hr.kg)211.0
Volume of distribution Vd: (l/kg)2286.0
Half-life T½: (hr)173.4

The rapid clearance and large volume of distribution of Amphotericin B Lipid Complex result in a relatively low AUC and are consistent with preclinical data showing high tissue concentrations. The kinetics of Amphotericin B Lipid Complex are linear, the AUC increases proportionately with dose.

Details of the tissue distribution and metabolism of Amphotericin B Lipid Complex in humans, and the mechanisms responsible for reduced toxicity, are not well understood. The following data are available from necropsy in a heart transplant patient who received Amphotericin B Lipid Complex at a dose of 5.3 mg/kg for 3 consecutive days immediately before death:

OrganAmphotericin B Lipid Complex tissue concentration expressed as amphotericin B content (mg/kg)
Spleen290.0
Lung222.0
Liver196.0
Kidney6.9
Lymph node7.6
Heart5.0
Brain1.6

5.3 Preclinical safety data

Acute toxicity studies in rodents showed that Amphotericin B Lipid Complex was 10-fold to 20-fold less toxic than conventional amphotericin B. Multiple-dose toxicity studies in dogs lasting 2-4 weeks showed that on a mg/kg basis, Amphotericin B Lipid Complex was 8-fold to 10-fold less nephrotoxic than conventional amphotericin B. This decreased nephrotoxicity was presumably a result of lower drug concentrations in the kidney.

Since conventional amphotericin B first became available, there have been no reports of drug-related carcinogenicity, mutagenicity, teratogenicity or adverse effect on fertility. Amphotericin B Lipid Complex has been shown not to be mutagenic by the in vivo mouse micronucleus assay, in vitro bacterial and lymphoma mutation assays, and an in vivo cytogenetic assay. It has been shown not to be teratogenic in mice and rabbits.

Phospholipids are essential constituents of human cell membranes. The average diet provides several grams of phospholipids each day. There is no evidence that phospholipids, including DMPC and DMPG, are carcinogenic, mutagenic or teratogenic.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

L-α-dimyristoylphosphatidylcholine (DMPC), L-α-dimyristoylphosphatidylglycerol (sodium and ammonium salts) (DMPG), Sodium Chloride & Water for Injection.

6.2 Incompatibilities

Amphotericin B Lipid Complex should not be mixed with other drugs or electrolytes.

6.3 Shelf life

24 months.

6.4 Special precautions for storage

Store at 2 °C – 8 °C. Do not freeze. Keep vial in the outer carton.

6.5 Nature and contents of container

Amphotericin B Lipid Complex is a sterile, pyrogen-free yellow suspension in a type I glass single use vial containing 10 or 20 ml (50 mg or 100 mg amphotericin B). The vial is sealed with a rubber stopper and aluminium seal. Vials are packaged in cartons of 10 vials. Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Amphotericin B Lipid Complex is a sterile, pyrogen-free suspension to be diluted for intravenous infusion only.

Preparation of the suspension for infusion

ASEPTIC TECHNIQUE MUST BE STRICTLY OBSERVED THROUGHOUT HANDLING OF Amphotericin B Lipid Complex, SINCE NO BACTERIOSTATIC AGENT OR PRESERVATIVE IS PRESENT.

Allow the suspension to come to room temperature. Shake gently until there is no evidence of any yellow settlement at the bottom of the vial. Withdraw the appropriate dose of Amphotericin B Lipid Complex from the required number of vials into one or more sterile 20 ml syringes using a 17 to 19 gauge needle. Remove the needle from each syringe filled with Amphotericin B Lipid Complex and replace with the 5 micron high flow filter needle (supplied by B. Braun Medical, Inc.) provided with each vial. Insert the filter needle of the syringe into an IV bag containing 5.0% Dextrose for Injection and empty the contents of the syringe into the bag using either manual pressure or an infusion pump. The final infusion concentration should be 1 mg/ml. For paediatric patients and patients with cardiovascular disease the drug may be diluted with 5.0% Dextrose for Injection to a final infusion concentration of 2 mg/ml. Do not use the agent after dilution with 5.0% Dextrose for Injection if there is any evidence of foreign matter. Vials are single use. Unused material should be discarded. The infusion is best administered by means of an infusion pump.

DO NOT DILUTE WITH SALINE SOLUTIONS OR MIX WITH OTHER DRUGS OR ELECTROLYTES. The compatibility of Amphotericin B Lipid Complex with these materials has not been established. An existing intravenous line should be flushed with 5.0% Dextrose for Injection before infusion of Amphotericin B Lipid Complex or a separate infusion line should be used.

The diluted ready for use suspension may be stored at 2 °C – 8 °C for up to 24 hours prior to use. Shake vigorously before use. Do not store for later use.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
Survey No. 506, At: Palli,
Sachana- Kalyanpura Road,
TAL-KADI, DIST- MEHSANA,
Palli, 382165, GUJARAT

Amphotericin B Lipid Complex Injection 50mg/10ml

(Amphotericin B Lipid Complex)

Package leaflet: Information for the user

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or nurse.
  • This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
  • If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet:

  1. What Amphotericin B Lipid Complex is and what it is used for
    2. What you need to know before you use Amphotericin B Lipid Complex
    3. How to use Amphotericin B Lipid Complex
    4. Possible side effects
    5. How to store Amphotericin B Lipid Complex
    6. Contents of the pack and other information
  2. WHAT AMPHOTERICIN B LIPID COMPLEX IS AND WHAT IT IS USED FOR

Amphotericin B Lipid Complex is a medicine to treat severe fungal infections such as blood infection with candida, aspergillus, cryptococcus, fusarium, zygomycetes, blastomycetes or coccidiodes, or cryptococcal meningitis (inflammation of the brain). Fungi are common and are found throughout nature but do not normally cause infections. However, under certain circumstances, for instance, when the body’s immune system is not working properly, a few types of fungi can infect humans.

Abelcet is used to treat fungal infections in children aged 1 month to 16 years of age.

  1. WHAT YOU NEED TO KNOW BEFORE YOU USE AMPHOTERICIN B LIPID COMPLEX

Do not use Amphotericin B Lipid Complex

If you are allergic to amphotericin B or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

Talk to your doctor or nurse before using Amphotericin B Lipid Complex.

  • Your doctor may need to monitor you carefully and do some extra tests while you are being treated with Amphotericin B Lipid Complex, particularly if you have had previous problems with your kidneys or liver.
  • If you have a kidney problem, your doctor will perform a blood test at least once a week to check how your kidneys are working while you are receiving Amphotericin B Lipid Complex.

Children

Do not give this medicine to children less than 1 month of age because there are no data to support its use.

Other medicines and Amphotericin B Lipid Complex

Tell your doctor if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription.

Amphotericin B Lipid Complex may interact with

  • drugs which can affect your kidney function
  • other drugs such as zidovudine (used to treat HIV infection) or ciclosporin (a drug to suppress your immune system).

Amphotericin B has been reported to interact with the following drugs:

  • drugs to treat cancer
  • corticosteroids and corticotrophin (ACTH) (drugs given to treat a variety of conditions such as allergies and hormone imbalances)
  • digitalis glycosides (used to treat heart conditions)
  • flucytosine (used to treat fungal infections)
  • muscle relaxants.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor for advice before taking this medicine.

Driving and using machines

You should avoid driving a vehicle or operating machinery after treatment with Amphotericin B Lipid Complex as the side effects of Amphotericin B Lipid Complex could affect your ability to drive safely.

Important information about some of the ingredients of Amphotericin B Lipid Complex

This medicinal product contains 0.156 mmol (or 3.6 mg) sodium per mL. This represents 3.12 mmol (or 71.8 mg) sodium per 20 mL vial. To be taken into consideration by patients on a controlled sodium diet.

  1. HOW TO USE AMPHOTERICIN B LIPID COMPLEX

Method and route of administration

Amphotericin B Lipid Complex must be diluted with a dextrose (sugar) solution before use.

Amphotericin B Lipid Complex must be administered as an infusion to the vein. This will be given by a drip into a vein in your arm over about 2 hours.

Dosage and frequency of administration

Amphotericin B Lipid Complex will normally be given to you by your doctor or by a nurse.

The recommended daily dose is 5.0 mg of Amphotericin B Lipid Complex for every kg of your body weight, given as a single infusion. A test dose of 1 mg is given initially to see if you are sensitive to any of the ingredients. The number of days over which you will be treated depends on many factors, but will probably be at least 14 days.

No change in dose is required for children, elderly people and those suffering from kidney or liver disease.

If you stop using Amphotericin B Lipid Complex

It is important that you follow your doctor’s instructions and receive all the medication prescribed for you even if you feel better.

If you use more Amphotericin B Lipid Complex than you should

You should tell your doctor immediately if you think you received too much Amphotericin B Lipid Complex.

You may experience side effects as listed in section 4 “Possible side effects”. You doctor may need to check your heart and breathing rates, your kidney and liver function, your blood cell counts or the level of potassium in your body.

If you forget to use Amphotericin B Lipid Complex

Do not take a double dose to make up for a forgotten dose. You should tell your doctor immediately, he will decide when you should be given your next dose of Amphotericin B Lipid Complex.

If you have any further questions on the use of this medicine, ask your doctor or nurse

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Uncommon allergic reactions (may affect 1 to 10 people in 1000)

Seek medical help immediately if you have any of the following symptoms of a serious allergic reaction:

  • difficulty breathing and/or feeling dizzy or faint
  • severe itching of the skin or raised lumps on the skin
  • swelling of the face, lips, tongue and/or throat, which may cause difficulty in swallowing

You should also seek urgent medical help if you have any of the following serious side effects:

  • severe chest pain (heart attack) or difficulty breathing
  • encephalopathy (a disease of the brain, which may cause you to become confused or behave strangely, and/or feel drowsy).

You may experience chills, fever, nausea (feeling sick), vomiting (being sick), rash, itching, muscle pain, abdominal pain, convulsions (fits), chest pain, or low blood oxygen levels and blue lips and skin, although this will probably only occur during the infusion or in the first 2 days of treatment. Your nurse or doctor may be able to arrange some simple treatment to help control these side effects.

Amphotericin B Lipid Complex may affect your kidney, liver or blood. Your doctor will check for these and other unwanted effects by carrying out appropriate tests, for example checking the level of potassium in your body.

Very common side effects (may affect more than 1 in 10 people)

Chills, fever, increased levels of a substance called creatinine in the blood.

Common side effects (may affect up to 1 in 10 people)

Increased heart rate, irregular heartbeat, low or high blood pressure, low blood platelets (which can lead to an increased risk of bleeding), breathing problems, asthma, nausea (feeling sick), vomiting (being sick), headache, shaking, kidney problems (signs include tiredness and passing less urine), kidney function tests abnormal, increased or decreased blood potassium levels (which can make you feel tired, confused, and have muscle weakness or cramps or make your heart beat abnormally), decreased blood magnesium levels (which can give you “pins and needles”, muscular pains, weakness or spasms), liver function tests abnormal, rash

Uncommon side effects (may affect up to 1 in 100 people)

Injection site reactions, convulsions (fits), neuropathy (nerve disease)

The following side effects have also been reported with the use of Amphotericin B Lipid Complex but it is not known how often they occur: Widespread flaking or scaling of the skin, excessive thirst and the production of large amounts of weak (watery) urine

Side effects in children and adolescents are similar to those observed in adults.

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet.

  1. HOW TO STORE AMPHOTERICIN B LIPID COMPLEX

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the label after EXP.

Store in a refrigerator (2°C – 8°C).

Do not freeze.

Keep vial in the outer carton.

  1. CONTENTS OF THE PACK AND OTHER INFORMATION

What Amphotericin B Lipid Complex contains

The active substance is Amphotericin B.

The other ingredients are L-α-dimyristoylphosphatidylcholine (DMPC), L-α-dimyristoylphosphatidylglycerol (sodium and ammonium salts) (DMPG), sodium chloride (common salt) and water for injection.

What Amphotericin B Lipid Complex looks like and contents of the pack

Amphotericin B Lipid Complex is supplied as a yellow concentrate for suspension for infusion.

Each vial contains 5 mg Amphotericin B per ml. Vials of 10 ml contain 50 mg amphotericin B. Vials of 20 ml contain 100 mg amphotericin B. Vials are packaged in cartons of 10 vials. Not all pack sizes may be marketed.

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
Survey No. 506, At: Palli,
Sachana- Kalyanpura Road,
TAL-KADI, DIST- MEHSANA,
Palli, 382165, GUJARAT