Inj. Loovi
Levocarnitine Injection IV
1g/5ml
DESCRIPTION:
Loovi (levocarnitine) is a carrier molecule in the transport of long-chain fatty acids
across the inner mitochondrial membrane.
INDICATIONS AND USAGE:
For the acute and chronic treatment of patients with an inborn error of metabolism which results
in secondary carnitine deficiency.
For the prevention and treatment of carnitine deficiency in patients with end stage renal disease
who are undergoing dialysis.
CONTRAINDICATIONS:
None known.
WARNINGS
Hypersensitivity Reactions:
Serious hypersensitivity reactions, including anaphylaxis, laryngeal edema, and bronchospasm
have been reported following LOOVI administration, mostly in patients with end stage
renal disease who are undergoing dialysis. Some reactions occurred within minutes after
intravenous administration of LOOVI.
If a severe hypersensitivity reaction occurs, discontinue LOOVI treatment and initiate
appropriate medical treatment. Consider the risks and benefits of re-administering LOOVI
to individual patients following a severe reaction. If the decision is made to re-administer the
product, monitor patients for a reoccurrence of signs and symptoms of a severe hypersensitivity
reaction.
PRECAUTIONS:
General:
The safety and efficacy of oral levocarnitine has not been evaluated in patients with renal
insufficiency. Chronic administration of high doses of oral levocarnitine in patients with
severely compromised renal function or in ESRD patients on dialysis may result in accumulation
of the potentially toxic metabolites, trimethylamine (TMA) and trimethylamine-N-oxide
(TMAO), since these metabolites are normally excreted in the urine.
Drug Interactions:
Reports of INR increase with the use of warfarin have been observed. It is recommended that
INR levels be monitored in patients on warfarin therapy after the initiation of treatment with
levocarnitine or after dose adjustments.
Pregnancy:
Reproductive studies have been performed in rats and rabbits at doses up to 3.8 times the human
dose on the basis of surface area and have revealed no evidence of impaired fertility or harm to
the fetus due to LOOVI. There are, however, no adequate and well controlled studies in
pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug
should be used during pregnancy only if clearly needed.
Nursing Mothers:
Levocarnitine supplementation in nursing mothers has not been specifically studied.
Studies in dairy cows indicate that the concentration of levocarnitine in milk is increased
following exogenous administration of levocarnitine. In nursing mothers receiving levocarnitine,
any risks to the child of excess carnitine intake need to be weighed against the benefits of
levocarnitine supplementation to the mother. Consideration may be given to discontinuation of
nursing or of levocarnitine treatment.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Mutagenicity tests performed in Salmonella typhimurium, Saccharomyces cerevisiae, and
Schizosaccharomyces pombe indicate that levocarnitine is not mutagenic. No long-term animal
studies have been performed to evaluate the carcinogenic potential of levocarnitine.
OVERDOSAGE:
There have been no reports of toxicity from levocarnitine overdosage. Levocarnitine is easily
removed from plasma by dialysis. The intravenous LD50 of levocarnitine in rats is 5.4 g/kg and
the oral LD50 of levocarnitine in mice is 19.2 g/kg. Large doses of levocarnitine may cause
diarrhea.
DOSAGE AND ADMINISTRATION:
LOOVI Injection is administered intravenously.
Metabolic Disorders:
The recommended dose is 50 mg/kg given as a slow 2-3 minute bolus injection or by infusion.
Often a loading dose is given in patients with severe metabolic crisis, followed by an equivalent
dose over the following 24 hours. It should be administered q3h or q4h, and never less than q6h
either by infusion or by intravenous injection. All subsequent daily doses are recommended to
be in the range of 50 mg/kg or as therapy may require. The highest dose administered has been
300 mg/kg.
It is recommended that a plasma carnitine concentration be obtained prior to beginning this
parenteral therapy. Weekly and monthly monitoring is recommended as well. This monitoring
should include blood chemistries, vital signs, plasma carnitine concentrations (the plasma free
carnitine concentration should be between 35 and 60 µmol/L) and overall clinical condition.
ESRD Patients on Hemodialysis:
The recommended starting dose is 10-20 mg/kg dry body weight as a slow 2-3 minute bolus
injection into the venous return line after each dialysis session. Initiation of therapy may be
prompted by trough (pre-dialysis) plasma levocarnitine concentrations that are below normal
(40-50 µmol/L). Dose adjustments should be guided by trough (pre-dialysis) levocarnitine
concentrations, and downward dose adjustments (e.g. to 5 mg/kg after dialysis) may be made as
early as the third or fourth week of therapy.
Parenteral drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit.
COMPATIBILITY AND STABILITY:
LOOVI Injection is compatible and stable when mixed in parenteral solutions of Sodium
Chloride 0.9% or Lactated Ringer’s in concentrations ranging from 250 mg/500 mL (0.5 mg/mL)
to 4200 mg/500 mL (8.0 mg/mL) and stored at room temperature (25°C) for up to 24 hours in
PVC plastic bags.
HOW SUPPLIED:
LOOVI (levocarnitine) Injection is available in 1 g per 5 mL single dose ampule packaged
1 ampule per pack.
Store ampule at controlled room temperature (25°C).