Triomune (Lamivudine, Stavudine and Nevirapine Tablets)

Triomune (Lamivudine, Stavudine and Nevirapine Tablets)
© The Swiss Pharmacy

Triomune (Lamivudine, Stavudine and Nevirapine Tablets) is used
for the treatment of HIV-1 infection. The following points should
be considered when initiating therapy with Lamivudine,
Stavudine and Nevirapine Tablets: Based on serious and life-
threatening hepatotoxicity observed in controlled and
uncontrolled studies, Nevirapine should not be initiated in
adult females with CD4+ cell counts greater than 250
cells/mm3 or in adult males with CD4+ cell counts greater
than 400 cells/mm3 unless the benefit outweighs the risk. The 14-
day lead-in period with Nevirapine 200 mg daily dosing has been
demonstrated to reduce the frequency of rash.

Triomune Tablets are manufactured
by Cipla Limited, India in the
strength of 380 mg (Lamivudine
150mg, Stavudine 30mg and
Nevirapine 200mg) and 390 mg
(Lamivudine 150mg, Stavudine
40mg and Nevirapine 200mg).

Chemical Structure - Lamivudine

Chemical Structure - Stavudine

Chemical Structure - Nevirapine

The active ingredients contained in
Triomune tablets are Lamivudine, Stavudine
and Nevirapine.
Each film-coated Triomune tablet contains
150 mg of Lamivudine, 30 mg of Stavudine
and 200 mg of Nevirapine or 150 mg of
Lamivudine, 40 mg of Stavudine and 200
mg of Nevirapine.

Uses of Triomune 380mg and 390mgTablets:
Triomune (Lamivudine, Stavudine and Nevirapine Tablets) is used to
treat HIV (human immunodeficiency virus) infection is used in the
treatment of HIV infection in adult patients once the patient is stabilized
on the maintenance regimen of Nevirapine 200 mg twice a day.
Triomune tablets contain three active ingredients that are used to treat
HIV infection: Lamivudine, Stavudine and Nevirapine. Lamivudine and
Stavudine belongs to a group of anti-retroviral medicines called
nucleoside analogue reverse transcriptase inhibitors (NRTIs). Both drugs
act by terminating the growth of the DNA chain and inhibiting the reverse
transcriptase of HIV-1.
Nevirapine belongs to a group called non-nucleoside analogue reverse
transcriptase inhibitor. It acts by directly inhibiting reverse transcriptase.

Uses of Triomune 380mg and 390mgTablets:
Triomune tablets do not completely cure HIV infection. They reduce the
amount of virus in your body, and keeps it at a low level.
Triomune also increases the CD4 cell count in your blood. CD4 cells are
a type of white blood cells that are important in helping your body to
fight infection.
The decision to use Triomune (Lamivudine, Stavudine and Nevirapine
Tablets) should take into account liver and skin toxicity, potentially
fatal, especially in patients with higher CD4 counts and in women, due to
the Nevirapine component.

Recommended Dosage
The recommended dosage of
Triomune (Lamivudine, Stavudine and Nevirapine Tablets) for
treatment of HIV-1 infected patients is given below: A 14 day
lead-in period with once daily Nevirapine has been associated
with lower risks of rash. Therefore, the following regimen is
recommended for the initial 14 days of dosing: For adult
patients 60 kg or more: One Lamivudine, Stavudine and
Nevirapine Tablet, 150 mg/40 mg/200 mg (Triomune-40)
taken once per day followed by a daily oral dose of Lamivudine
150 mg and Stavudine 40 mg 12 hours later using an alternate
formulation of these drugs.

Recommended Dosage
For patients less than 60 kg: One Lamivudine, Stavudine and
Nevirapine Tablet, 150mg / 30mg /200mg (Triomune-30)
taken once per day followed by a daily oral dose of Lamivudine
150 mg and Stavudine 30 mg 12 hours later.
Maintenance: If the initial 14 days of Nevirapine is tolerated
without any hypersensitivity reactions (e.g. rash, liver function
test abnormalities;),
The recommended maintenance oral dose is as follows: For patients
60 kg or more: One Lamivudine, Stavudine and Nevirapine
Tablet, 150mg/40 mg /200 mg (Triomune-40) taken twice daily
(at 12 hour intervals).

Recommended Dosage
The recommended maintenance oral dose is as follows: For patients
less than 60 kg: One Lamivudine, Stavudine and Nevirapine
Tablet, 150mg/30 mg/200 mg (Triomune-30) taken twice daily
(at 12 hour intervals).
Lamivudine, Stavudine and Nevirapine Tablets should be
taken at intervals of 12 hours under fasted conditions.
Because Lamivudine, Stavudine and Nevirapine Tablets are a
fixed dose combination tablet, it should not be prescribed
for patients requiring dosage adjustment or those
experiencing dose-limiting adverse events.

Recommended Dosage
Pediatrics: Lamivudine, Stavudine and Nevirapine Tablets 150
mg/30 mg/200mg are recommended for pediatric patients
greater than 12 years of age and and weighing 50 kg or more.
Lamivudine, Stavudine and Nevirapine Tablets 150 mg/40
mg/200 mg are recommended for pediatric patients greater than
12 years of age and weighing 60 kg or more.
Geriatrics: Although no specific dosage alterations are
recommended, caution should be exercised when Lamivudine,
Stavudine and Nevirapine Tablets are administered to
geriatric patients (greater than 65 years of age).

Recommended Adult Dosage
The 14-day lead-in period with Nevirapine 200 mg once daily must be
strictly followed; it has been demonstrated to reduce the frequency of
rash. If any patient experiences rash during the 14-day lead-in period, do
not dose escalate to 200 mg twice daily until the rash has resolved. Do not
continue the lead-in dosing regimen beyond 28 days.
If dosing is interrupted for greater than 7 days, restart 14-day Nevirapine
lead-in period. Because Lamivudine, Zidovudine and Nevirapine tablets is
a fixed dose combination and cannot be dose adjusted, Lamivudine,
Zidovudine and Nevirapine tablets is not recommended in pediatric
patients weighing less than 35 kg, patients with creatinine clearance less
than 50 mL per minute, patients with hepatic impairment or
experiencing dose-limiting adverse reactions.

Contraindications
➔
Triomune is contraindicated in patients with a known hypersensitivity
(eg, anaphylaxis, Stevens-Johnson Syndrome) to Lamivudine,
Stavudine, Nevirapine or any other component of this medication.
➔
Co-administration with Didanosine due to the potential for serious
and/or life-threatening events notably lactic acidosis, liver function
abnormalities, pancreatitis and peripheral neuropathy
➔
Triomune is contraindicated in patients with moderate or severe
(Child-Pugh Class B or C, respectively) hepatic impairment.

Contraindications
➔
Use of this medicine as part of occupational and non-occupational post-
exposure prophylaxis (PEP) regimens, an unapproved use.
➔
Triomune is contraindicated in patients who have been discontinued for severe
rash, rash accompanied by constitutional symptoms, hypersensitivity reactions,
or clinical hepatitis due to Nevirapine.
➔
Triomune is contraindicated in patients who previously had AST or ALT greater
than 5X Upper Limit of Normality (ULN) during Nevirapine therapy.
➔
Coadministration of Triomune with herbal preparations containing St John’s
wort (Hypericum perforatum) is contraindicated due to the risk of potentially
significant decreases of plasma concentrations and reduced clinical effects of
Nevirapine.

Storage Instructions
Triomune-30 and Triomune-40 (Lamivudine,
Stavudine and Nevirapine Tablets) has to be stored
at controlled room temperature i.e. from 20°C to
25°C (68°F to 77°F) with excursions permitted
between 15° to 30°C (59° to 86°F).
Keep this as well as all other medicines away from
children and pets.

Warnings
Triomune Tablets (Lamivudine, Stavudine and Nevirapine Tablets) should not
be administered concomitantly with formulations containing any of the
three drugs. The complete prescribing information for all agents being
considered for use with Lamivudine, Stavudine and Nevirapine Tablets
should be consulted before therapy with Triomune Tablets is initiated. Lactic
acidosis and severe hepatomegaly with steatosis, including fatal cases, have been
reported with the use of nucleoside analogues.
Severe acute exacerbations of hepatitis B have been reported in patients who are
co-infected with hepatitis B virus (HBV) and human immunodeficiency virus (HIV-
1) and have discontinued Lamivudine, a component of Triomune.
Monitor hepatic function closely in these patients and, if appropriate, initiate anti-
hepatitis B treatment.

Warnings
Triomune should not be administered with other Lamivudine- Stavudine- or
Nevirapine- containing products or Emtricitabine-containing products.
Hepatic decompensation, some fatal, has occurred in HIV-1/HCV co-infected
patients receiving combination antiretroviral therapy and interferon alfa
with/without Ribavirin.
Discontinue Triomune as medically appropriate and consider dose reduction or
discontinuation of interferon Alfa, Ribavirin, or both.
In pediatric patients with a history of prior antiretroviral nucleoside
exposure, a history of pancreatitis, or other significant risk factors for the
development of pancreatitis, Lamivudine should be used with caution. Treatment
with Lamivudine should be stopped immediately if clinical signs,
symptoms, or laboratory abnormalities suggestive of pancreatitis occur.

Warnings
Pancreatitis: Use with caution in patients with a history of pancreatitis or other
significant risk factors for pancreatitis. Discontinue treatment as clinically appropriate.
Immune reconstitution syndrome and redistribution/accumulation of body fat have
been reported in patients treated with combination antiretroviral therapy.
Opportunistic infections: Patients receiving Lamivudine and Zidovudine or any other
antiretroviral therapy can continue to develop opportunistic infections and other
complications of HIV infection. Therefore patients must remain under close clinical
observation by physicians experienced in the treatment of HIV infection.
Motor weakness has been reported rarely in patients receiving combination
antiretroviral therapy including stavudine. Most of these cases occurred in the setting
of lactic acidosis. The evolution of motor weakness may mimic the clinical
presentation of Guillain-Barré syndrome (including respiratory failure).
Symptoms may continue or worsen following discontinuation of therapy.

Effects On Ability To Drive And Use Machines
There have been no studies to investigate the effect of Lamivudine or
Stavudine on driving performance or the ability to operate machinery.
Further, a detrimental effect on such activities cannot be predicted
from the pharmacology of the active substances.
Nevertheless, the clinical status of the patient and the adverse event
profile of Lamivudine, Stavudine and Nevirapine Tablets (Triomune)
should be borne in mind when considering the patient's ability to drive
or operate machinery.

Possible Side Effects
Side effects reported with a frequency of 5% or more in four controlled clinical
trials for Lamivudine include Headache, Malaise and fatigue, Fever or chills,
Nausea, Diarrhea, Nausea and vomiting, Anorexia and/or decreased appetite,
Abdominal pain, Abdominal cramps, Dyspepsia, Neuropathy, Insomnia and other
sleep disorders, Dizziness, Depressive disorders, Nasal signs and symptoms, Cough,
Skin rashes, Musculoskeletal pain, Myalgia and Arthralgia
Treatment-related side effects of moderate or severe intensity observed in greater
than 2% of subjects receiving Nevirapine in placebo-controlled trials include Rash,
Nausea, Granulocytopenia, Headache, Fatigue, Diarrhea, Abdominal pain and
Myalgia.
Selected side effects that occurred in adult patients receiving Stavudine in a
controlled monotherapy study include Headache, Diarrhea, Peripheral neurologic
symptoms/Neuropathy, Rash, Nausea and vomiting

In addition to the side effects identified during clinical trials, the following adverse
reactions have been identified during post-approval use of Nevirapine. Because
these reactions are reported voluntarily from a population of uncertain size, it is not
always possible to reliably estimate their frequency or establish a causal
relationship to drug exposure.
Body as a whole: fever, somnolence, drug withdrawal, redistribution/accumulation
of body fat.
Gastrointestinal: vomiting.
Liver and Biliary: jaundice, fulminant and cholestatic hepatitis, hepatic necrosis,
hepatic failure.
Hematology: anemia, eosinophilia, neutropenia.
Investigations: decreased serum phosphorous
Musculoskeletal: arthralgia, rhabdomyolysis associated with skin and/or liver
reactions.

In addition to the side effects identified during clinical trials, the following side
effects have been identified during post-approval use of Nevirapine.
Neurologic: paresthesia.
Skin and Appendages: allergic reactions, including anaphylaxis, angioedema,
bullous eruptions, ulcerative stomatitis and urticaria, have all been reported. In
addition, hypersensitivity syndrome and hypersensitivity reactions with rash
associated with constitutional findings such as fever, blistering, oral lesions,
conjunctivitis, facial edema, muscle or joint aches, general malaise, fatigue, or
significant hepatic abnormalities, drug reaction with eosinophilia and systemic
symptoms (DRESS) plus one or more of the following: hepatitis, eosinophilia,
granulocytopenia, lymphadenopathy, and/or renal dysfunction, have been
reported.

Triomune Tablets Overdosage
There is limited experience of overdosage with Lamivudine, Stavudine
and Nevirapine combination tablets (Triomune-30 and Triomune-40 ).
Lamivudine: Because a negligible amount of Lamivudine was removed via
(4-hour) hemodialysis, continuous ambulatory peritoneal dialysis, and
automated peritoneal dialysis, it is not known if continuous hemodialysis
would provide clinical benefit in a Lamivudine overdose event.
Stavudine: Experience with adults treated with 12 to 24 times the
recommended daily dosage revealed no acute toxicity. Complications of
chronic overdosage include peripheral neuropathy and hepatic toxicity.
Stavudine can be removed by hemodialysis; the mean ± SD hemodialysis
clearance of stavudine is 120 ± 18 ml/min. Whether Stavudine is
eliminated by peritoneal dialysis has not been studied.

Triomune Tablets Overdosage
Nevirapine: There is no known antidote for Nevirapine overdosage.
Cases of Nevirapine overdose at doses ranging from 800 to 1,800
mg per day for up to 15 days have been reported. Patients have
experienced adverse events, including edema, erythema nodosum,
fatigue, fever, headache, insomnia, nausea, pulmonary infiltrates,
rash, vertigo, vomiting, and weight decrease. All events subsided
following discontinuation of Nevirapine.

Triomune Tablets During Pregnancy
Lamivudine, Stavudine and Nevirapine (Triomune Tablets) has been
classified by the US FDA as Pregnancy Category C.
There are no adequate and well-controlled studies of Lamivudine,
Stavudine and Nevirapine Tablets (Triomune-30 and Triomune-40) in
pregnant women. Triomune tablets should be used during pregnancy
only if the potential benefit justifies the potential risk to the fetus.
Reproduction studies have been performed in rats and rabbits at
orally administered doses up to 4,000 mg/kg/day and 1,000 mg/kg/day,
respectively, producing plasma levels up to approximately 35 times that for
the adult HIV dose. No evidence of teratogenicity due to Lamivudine
was observed. Lamivudine should be used during pregnancy only if
the potential benefits outweigh the risks.

Triomune Tablets During Pregnancy
Stavudine: Reproduction studies have been performed in rats and rabbits with exposures
(based on Cmax) up to 399 and 183 times, respectively, of that seen at a clinical dosage of 1
mg/kg/day and have revealed no evidence of teratogenicity. The incidence in fetuses of a
common skeletal variation, unossified or incomplete ossification of sternebra, was
increased in rats at 399 times human exposure, while no effect was observed at 216 times
human exposure. There are no adequate and well-controlled studies of Stavudine in
pregnant women. Stavudine should be used during pregnancy only if the potential
benefit justifies the potential risk.
Nevirapine: No observable teratogenicity was detected in reproductive studies
performed in pregnant rats and rabbits. In rats, a significant decrease in fetal body weight
occurred at doses providing systemic exposure approximately 50% higher, based on
AUC, than that seen at the recommended human clinical dose. Severe hepatic events,
including fatalities, have been reported in pregnant women receiving chronic Nevirapine
therapy as part of combination treatment of HIV-1 infection. It is unclear if pregnancy
augments the already increased risk observed in non-pregnant women.

Triomune Tablets are manufactured by
Cipla Limited, India.
For More details Click Here

Triomune (Lamivudine, Stavudine and Nevirapine Tablets)

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